Search

Traditional serrated adenomas (TSAs) may confer increased risk for colorectal cancer (CRC). Our objective with this study was to examine clinical characteristics and long-term outcomes associated with TSA diagnosis.We conducted a retrospective cohort study of U.S. Veterans ≥18 years of age with ≥1 TSA between 1999 and 2016. Baseline characteristics, colonoscopy findings, and diagnosis of incident and fatal CRC were abstracted. Advanced neoplasia was defined by CRC or adenoma with high-grade dysplasia, villous histology, or size ≥1 cm. Follow-up was through CRC diagnosis, death, or end of study (December 31, 2018).A total of 853 Veterans with a baseline TSA were identified; 74% were ≥60 years of age, 96% were men, 14% were Black, and 73% were non-Hispanic White. About 64% were current or former smokers. Over 2044 total person-years at follow-up, there were 11 incident CRC cases and 1 CRC death. Cumulative CRC incidence was 1.34% (95% confidence interval [CI], 0.67%-2.68%), and cumulative CRC death was 0.12% (95% CI, 0.00%-0.35%). Among the subset of 378 TSA patients with ≥1 surveillance colonoscopy, 65.1% had high-risk neoplasia on follow-up. CRC incidence among TSA patients was significantly higher than in a comparison cohort of patients with normal baseline colonoscopy at baseline (hazard ratio, 3.70; 95% CI, 1.63-8.41) and similar to a comparison cohort with baseline conventional advanced adenoma (hazard ratio, 0.86; 95% CI, 0.45-1.64).Individuals with TSA have substantial risk for CRC, based on their cumulative CRC incidence, as well as significant risk of developing other high-risk neoplasia at follow-up surveillance colonoscopy. These data underscore importance of current recommendations for close colonoscopy surveillance after TSA diagnosis.

Delays in colonoscopy work-up for red flag signs or symptoms of colorectal cancer (CRC) during the COVID-19 pandemic are not well characterized. To examine colonoscopy uptake and time to colonoscopy after red flag diagnosis, before and during the COVID-19 pandemic. Cohort study of adults ages 50-75 with iron deficiency anemia (IDA), hematochezia, or abnormal stool blood test receiving Veterans Health Administration (VHA) care from April 2019 to December 2020. Index date was first red flag diagnosis date, categorized into "pre" (April-December 2019) and "intra" (April-December 2020) policy implementation prioritizing diagnostic procedures, allowing for a 3-month "washout" (January-March 2020) period. Outcomes were colonoscopy completion and time to colonoscopy pre- vs. intra-COVID-19, examined using multivariable Cox models with hazard ratios (aHRs) and 95% confidence intervals (CIs). There were 52,539 adults with red flag signs or symptoms (pre-COVID: 25,154; washout: 7527; intra-COVID: 19,858). Proportion completing colonoscopy was similar pre- vs. intra-COVID-19 (27.0% vs. 26.5%; p = 0.24). Median time to colonoscopy among colonoscopy completers was similar for pre- vs. intra-COVID-19 (46 vs. 42days), but longer for individuals with IDA (60 vs. 49days). There was no association between time period and colonoscopy completion (aHR: 0.99, 95% CI 0.95-1.03). Colonoscopy work-up of CRC red flag signs and symptoms was not delayed within VHA during the COVID-19 pandemic, possibly due to VHA policies supporting prioritization and completion. Further work is needed to understand how COVID-19 policies on screening and surveillance impact CRC-related outcomes, and how to optimize colonoscopy completion after a red flag diagnosis.

Postpolypectomy risk stratification for subsequent metachronous advanced neoplasia (MAN) is imprecise and does not account for colonoscopist adenoma detection rate (ADR). Our aim was to assess association of ADR with MAN and create a prediction model for postpolypectomy risk stratification incorporating ADR and other factors.We conducted a retrospective cohort study of individuals with baseline polypectomy and subsequent surveillance colonoscopy from 2004 to 2016 within the U.S. Department of Veterans Affairs (VA). Clinical factors, polyp findings, and baseline colonoscopist ADR were considered for the model. Model performance (sensitivity, specificity, and area under the curve) for identifying individuals with MAN was compared with 2020 U.S. Multi-Society Task Force on Colorectal Cancer (USMSTF) surveillance recommendations.A total of 30,897 individuals were randomly assigned 2:1 into independent model training and validation sets. Increasing age, male sex, diabetes, current smoking, adenoma number, polyp location, adenoma ≥10 mm or with tubulovillous/villous features, and decreasing colonoscopist ADR were independently associated with MAN. A range of 1.48- to 1.66-fold increased risk for MAN was observed for ADR in the lowest 3 quintiles (ADR19.7%-39.3%) vs the highest quintile (ADR47.0%). When the final model selected based on the training set was applied to the validation set, improved sensitivity and specificity over 2020 USMSTF risk stratification were achieved (P = .001), with an area under the curve of 0.62 (95% confidence interval, 0.60-0.64).Colonoscopist ADR is associated with MAN. Combining clinical factors and ADR for risk stratification has potential to improve postpolypectomy risk stratification. Improving ADR is likely to improve postpolypectomy outcomes.

Supplemental Digital Content is available in the text., Background: Aspirin impacts risk for important outcomes such as cancer, cardiovascular disease, and gastrointestinal bleeding. However, ascertaining exposure to medications available both by prescription and over-the-counter such as aspirin for research and quality improvement purposes is a challenge. Objectives: Develop and validate a strategy for ascertaining aspirin exposure, utilizing a combination of structured and unstructured data. Research Design: This is a retrospective cohort study. Subjects: In total, 1,869,439 Veterans who underwent usual care colonoscopy 1999–2014 within the Department of Veterans Affairs. Measures: Aspirin exposure and dose were obtained from an ascertainment strategy combining query of structured medication records available in electronic health record databases and unstructured data extracted from free-text progress notes. Prevalence of any aspirin exposure and dose-specific exposure were estimated. Positive predictive value and negative predictive value were used to assess strategy performance, using manual chart review as the reference standard. Results: Our combined strategy for ascertaining aspirin exposure using structured and unstructured data reached a positive predictive value and negative predictive value of 99.2% and 97.5% for any exposure, and 92.6% and 98.3% for dose-specific exposure. Estimated prevalence of any aspirin exposure was 36.3% (95% confidence interval: 36.2%–36.4%) and dose-specific exposure was 35.4% (95% confidence interval: 35.3%–35.5%). Conclusions: A readily accessible approach utilizing a combination of structured medication records and query of unstructured data can be used to ascertain aspirin exposure when manual chart review is impractical.

Purpose Cancer ascertainment using large-scale electronic health records is a challenge. Our aim was to propose and apply a structured approach for evaluating multiple candidate approaches for cancer ascertainment using colorectal cancer (CRC) ascertainment within the US Department of Veterans Affairs (VA) as a use case. Methods The proposed approach for evaluating cancer ascertainment strategies includes assessment of individual strategy performance, comparison of agreement across strategies, and review of discordant diagnoses. We applied this approach to compare three strategies for CRC ascertainment within the VA: administrative claims data consisting of International Classification of Diseases, Ninth Revision (ICD9) diagnosis codes; the VA Central Cancer Registry (VACCR); and the newly accessible Oncology Domain, consisting of cases abstracted by local cancer registrars. The study sample consisted of 1,839,043 veterans with index colonoscopy performed from 1999 to 2014. Strategy-specific performance was estimated based on manual record review of 100 candidate CRC cases and 100 colonoscopy controls. Strategies were further compared using Cohen’s κ and focused review of discordant CRC diagnoses. Results A total of 92,197 individuals met at least one CRC definition. All three strategies had high sensitivity and specificity for incident CRC. However, the ICD9-based strategy demonstrated poor positive predictive value (58%). VACCR and Oncology Domain had almost perfect agreement with each other (κ, 0.87) but only moderate agreement with ICD9-based diagnoses (κ, 0.51 and 0.57, respectively). Among discordant cases reviewed, 15% of ICD9-positive but VACCR- or Oncology Domain–negative cases had incident CRC. Conclusion Evaluating novel strategies for identifying cancer requires a structured approach, including validation against manual record review, agreement among candidate strategies, and focused review of discordant findings. Without careful assessment of ascertainment methods, analyses may be subject to bias and limited in clinical impact.

Pancreatic cancer incidence and mortality among patients with pancreas cysts are unclear. The aims of this study are to evaluate incidence of pancreatic cancer and cause-specific mortality among patients with pancreatic cysts using a large national cohort over a long follow-up period. We conducted a retrospective cohort study of US Veterans diagnosed with a pancreatic cyst 1999–2013, based on International Classification of Diseases, 9th edition (ICD9) coding within national Department of Veterans Affairs (VA) data. Pancreatic cancer incidence was ascertained using VA cancer registry data, ICD-9 codes, and the National Death Index, a national centralized database of death records, including cause-specific mortality. Among 7211 Veterans with pancreatic cysts contributing 31,501 person-years of follow-up (median follow-up 4.4 years), 79 (1.1%) developed pancreatic cancer. A total of 1982 patients (27.5%) died during the study follow-up period. Sixty-three patients (3.2% of deaths; 0.9% of pancreas cyst cohort) died from pancreatic cancer, but the leading causes of death in the cohort were non-pancreatic cancer (n = 498, 25% of deaths) and cardiovascular disease (n = 398, 20% of deaths). Pancreas cancer incidence and pancreatic cancer-associated mortality are very low in a large national cohort of VA pancreatic cyst patients with long-term follow-up. Most deaths were from non-pancreas cancers and cardiovascular causes, and only a minority (3.2%) were attributable to pancreas cancer. Given death from pancreas cancer is rare, future research should focus on identifying criteria for selecting individuals at high risk for death from pancreatic cancer for pancreatic cyst surveillance.

Background & Aims The incidence and mortality of early-onset colorectal cancer (CRC) are increasing. Adenoma detection, removal, and subsequent endoscopic surveillance might modify risk of CRC diagnosed before age 50 years (early-onset CRC). We conducted a systematic review of young-onset adenoma (YOA) prevalence, associated risk factors, and rate of metachronous advanced neoplasia after YOA diagnosis. Methods We performed a systematic search of multiple electronic databases through February 12, 2019 and identified studies of individuals 18 to 49 years old that reported prevalence of adenoma, risk factors for adenoma, and/or risk for metachronous advanced neoplasia. Summary estimates were derived using random effects meta-analysis, when feasible. Results The pooled overall prevalence of YOA was 9.0% (95% CI, 7.1%–11.4%), based on 24 studies comprising 23,142 individuals. On subgroup analysis, the pooled prevalence of YOA from autopsy studies was 3.9% (95% CI, 1.9%–7.6%), whereas the prevalence from colonoscopy studies was 10.7% (95% CI, 8.5%–13.5). Only advancing age was identified as a consistent risk factor for YOA, based on 4 studies comprising 78,880 individuals. Pooled rate of metachronous advanced neoplasia after baseline YOA diagnosis was 6.0% (95% CI, 4.1%–8.6%), based on 3 studies comprising 1493 individuals undergoing follow-up colonoscopy, with only 1 CRC case reported. Overall, few studies reported metachronous advanced neoplasia and no studies evaluated whether routine surveillance colonoscopy decreases risk of CRC. Conclusions In a systematic review, we estimated the prevalence of YOA to be 9% and to increase with age. Risk for metachronous advanced neoplasia after YOA diagnosis is estimated to be 6%. More research is needed to understand the prevalence, risk factors, and risk of CRC associated with YOA.

Purpose Standardized approaches for rigorous validation of phenotyping from large-scale electronic health record (EHR) data have not been widely reported. We proposed a methodologically rigorous and efficient approach to guide such validation, including strategies for sampling cases and controls, determining sample sizes, estimating algorithm performance, and terminating the validation process, hereafter referred to as the San Diego Approach to Variable Validation (SDAVV). Methods We propose sample size formulae which should be used prior to chart review, based on pre-specified critical lower bounds for positive predictive value (PPV) and negative predictive value (NPV). We also propose a stepwise strategy for iterative algorithm development/validation cycles, updating sample sizes for data abstraction until both PPV and NPV achieve target performance. Results We applied the SDAVV to a Department of Veterans Affairs study in which we created two phenotyping algorithms, one for distinguishing normal colonoscopy cases from abnormal colonoscopy controls and one for identifying aspirin exposure. Estimated PPV and NPV both reached 0.970 with a 95% confidence lower bound of 0.915, estimated sensitivity was 0.963 and specificity was 0.975 for identifying normal colonoscopy cases. The phenotyping algorithm for identifying aspirin exposure reached a PPV of 0.990 (a 95% lower bound of 0.950), an NPV of 0.980 (a 95% lower bound of 0.930), and sensitivity and specificity were 0.960 and 1.000. Conclusions A structured approach for prospectively developing and validating phenotyping algorithms from large-scale EHR data can be successfully implemented, and should be considered to improve the quality of “big data” research.

Introduction Metformin may be associated with reduced colorectal cancer (CRC) risk, but findings from previous studies have been inconsistent and had insufficient sample sizes to examine whether the association differs by anatomic site. This study examined whether metformin was associated with reduced CRC risk, both overall and stratified by anatomic site, in a large sample of persons with diabetes who underwent colonoscopy. Methods We performed a case-control study of US Veterans with prevalent diabetes who underwent colonoscopy between 1999 and 2014 using Department of Veterans Affairs electronic health record data. Cases were defined by presence of CRC at colonoscopy, while controls had normal colonoscopy. The primary exposure was metformin use at time of colonoscopy (yes/no). Association of metformin exposure with CRC (further stratified by proximal, distal, or rectal subsite) was examined using multivariable and multinomial logistic regression and summarized by odds ratios (ORs) with 95% confidence intervals (CIs). Results We included 6,650 CRC patients and 454,507 normal colonoscopy patients. CRC cases were older and had lower metformin exposure. Metformin was associated with 8% relative reduction in CRC odds (OR: 0.92, 95% CI: 0.87-0.96). By subsite, metformin was associated with a 14% statistically significant reduced rectal cancer odds (OR: 0.86, 95% CI: 0.78-0.94) but no reduced distal or proximal cancer odds. Discussion Metformin was associated with reduced CRC odds-particularly rectal cancer-in a large sample of persons with diabetes undergoing colonoscopy.

ObjectiveTo conduct an anatomic site-specific case–control study of candidate colorectal cancer (CRC) risk factors.DesignCase–control study of US veterans with >1 colonoscopy during 1999–2011. Cases had cancer registry-identified CRC at colonoscopy, while controls were CRC free at colonoscopy and within 3 years of colonoscopy. Primary outcome was CRC, stratified by anatomic site: proximal, distal, or rectal. Candidate risk factors included age, sex, race/ethnicity, body mass index, height, diabetes, smoking status, and aspirin exposure summarised by adjusted ORs and 95% CIs.Results21 744 CRC cases (n=7017 rectal; n=7039 distal; n=7688 proximal) and 612 646 controls were included. Males had significantly higher odds relative to females for rectal cancer (OR=2.84, 95% CI 2.25 to 3.58) than distal cancer (OR=1.84, 95% CI 1.50 to 2.24). Relative to whites, blacks had significantly lower rectal cancer odds (OR=0.88, 95% CI 0.82 to 0.95), but increased distal (OR=1.27, 95% CI 1.19 to 1.37) and proximal odds (OR=1.62, 95% CI 1.52 to 1.72). Diabetes prevalence was more strongly associated with proximal (OR=1.29, 95% CI 1.22 to 1.36) than distal (OR=1.15, 95% CI 1.08 to 1.22) or rectal cancer (OR=1.12, 95% CI 1.06 to 1.19). Current smoking was more strongly associated with rectal cancer (OR=1.81, 95% CI 1.68 to 1.95) than proximal cancer (OR=1.53, 95% CI 1.43 to 1.65) or distal cancer (OR=1.46, 95% CI 1.35 to 1.57) compared with never smoking. Aspirin use was significantly more strongly associated with reduced rectal cancer odds (OR=0.71, 95% CI 0.67 to 0.76) than distal (OR=0.85, 95% CI 0.81 to 0.90) or proximal (OR=0.91, 95% CI 0.86 to 0.95).ConclusionCandidate CRC risk factor associations vary significantly by anatomic site. Accounting for site may enable better insights into CRC pathogenesis and cancer control strategies.

Background & aimsColorectal cancer (CRC) incidence and mortality are increasing among persons younger than 50 years old in the United States, but risk factors associated with early-onset CRC (EOCRC) have not been widely studied.MethodsWe conducted a case-control study of US veterans 18 to 49 years old who underwent colonoscopy examinations from 1999 through 2014. EOCRC cases were identified from a national cancer registry; veterans who were free of CRC at their baseline colonoscopy through 3 years of follow-up were identified as controls. We collected data on age, sex, race/ethnicity, body weight, body mass index (BMI), diabetes, smoking status, and aspirin use. Multivariate-adjusted EOCRC odds were estimated for each factor, with corresponding 95% confidence interval (CI) values.ResultsOur final analysis included 651 EOCRC cases and 67,416 controls. Median age was 45.3 years, and 82.3% were male. Higher proportions of cases were older, male, current smokers, nonaspirin users, and had lower BMIs, compared with controls (P < .05). In adjusted analyses, increasing age and male sex were significantly associated with increased risk of EOCRC, whereas aspirin use and being overweight or obese (relative to normal BMI) were significantly associated with decreased odds of EOCRC. In post hoc analyses, weight loss of 5 kg or more within the 5-year period preceding colonoscopy was associated with higher odds of EOCRC (odds ratio 2.23; 95% CI 1.76-2.83).ConclusionsIn a case-control study of veterans, we found increasing age and male sex to be significantly associated with increased risk of EOCRC, and aspirin use to be significantly associated with decreased risk; these factors also affect risk for CRC onset after age 50. Weight loss may be an early clinical sign of EOCRC. More intense efforts are required to identify the factors that cause EOCRC and signs that can be used to identify individuals at highest risk.

Objective: To describe a framework for leveraging big data for research and quality improvement purposes and demonstrate implementation of the framework for design of the Department of Veterans Affairs (VA) Colonoscopy Collaborative.Methods: We propose that research utilizing large-scale electronic health records (EHRs) can be approached in a 4 step framework: 1) Identify data sources required to answer research question; 2) Determine whether variables are available as structured or free-text data; 3) Utilize a rigorous approach to refine variables and assess data quality; 4) Create the analytic dataset and perform analyses. We describe implementation of the framework as part of the VA Colonoscopy Collaborative, which aims to leverage big data to 1) prospectively measure and report colonoscopy quality and 2) develop and validate a risk prediction model for colorectal cancer (CRC) and high-risk polyps.Results: Examples of implementation of the 4 step framework are provided. To date, we have identified 2,337,171 Veterans who have undergone colonoscopy between 1999 and 2014. Median age was 62 years, and 4.6 percent (n = 106,860) were female. We estimated that 2.6 percent (n = 60,517) had CRC diagnosed at baseline. An additional 1 percent (n = 24,483) had a new ICD-9 code-based diagnosis of CRC on follow up.Conclusion: We hope our framework may contribute to the dialogue on best practices to ensure high quality epidemiologic and quality improvement work. As a result of implementation of the framework, the VA Colonoscopy Collaborative holds great promise for 1) quantifying and providing novel understandings of colonoscopy outcomes, and 2) building a robust approach for nationwide VA colonoscopy quality reporting.

The most commonly used noninvasive test for colorectal cancer (CRC) screening has been the guaiac fecal occult blood test (gFOBT). The fecal immunochemical test (FIT) detects CRC and colorectal polyps with higher levels of sensitivity than the gFOBT, and may be more acceptable to patients. However, the FIT has not replaced the gFOBT in many clinical settings. We analyzed data from a large healthcare system that replaced the gFOBT with the FIT to determine the effects on CRC screening.We conducted a retrospective observational study of 7898 patients at the Veterans' Administration San Diego Healthcare System, 50-75 years old, who were offered stool-based CRC screening as part of primary care March 2014 through January 2015. Test orders and results were extracted from electronic health records; we performed manual reviews of colonoscopy and pathology reports for Veterans with positive results from the tests. Our primary outcome was test completion within 1 year of order; secondary outcomes were positive results and detection of advanced neoplasia by diagnostic colonoscopy. The primary analysis used an intention-to-screen approach, which included all patients with test orders; as-screened analyses were also performed.Among 7898 patients, 3236 had gFOBT and 4662 FIT orders. In the intention to screen analysis, a significantly higher proportion of subjects completed a FIT (42.6%) than a gFOBT (33.4%) (P .001); advanced neoplasia was detected in a significantly higher proportion of subjects offered a FIT (0.79%) than a gFOBT (0.28%) (P = .003). The numbers needed to invite to achieve 1 additional completed test and identify 1 additional patient with advanced neoplasia were 11 and 196, respectively.In a retrospective study of patients at a Veterans' administration healthcare system, replacing the gFOBT with the FIT increased the proportion of patients who completed CRC screening. Replacement of the gFOBT with the FIT should be strongly considered by all healthcare systems.

Background: Most studies of colorectal cancer (CRC) risk factors pool cases across anatomical sites, though tumor characteristics and embryologic origins differ. Our aim was to conduct a site-stratified (proximal, distal, rectal) case control study of candidate risk factors for CRC. Methods: Our study base was US Veterans with >1 colonoscopy 1999-2011. CRC cases at baseline colonoscopy were identified with the Veterans Affairs Central Cancer Registry. Controls had normal colonoscopy without biopsy, no history of CRC, and no CRC within 3 years of index colonoscopy. Age, sex, race/ethnicity, body mass index (BMI), diabetes, and smoking were considered candidate risk factors. Primary outcome was CRC, stratified by site. Site-specific odds ratios (OR) and 95% confidence intervals (CI) for each risk factor were computed with unadjusted and adjusted multinomial logistic regression models. Results: We identified 21,739 CRC cases and 616,323 normal colonoscopy controls. For cases combined vs. controls, median age was 68 vs. 61 years, 98% vs. 95% were male, median BMI was 27.8 vs. 28.8 kg/m2, 28% vs. 24% had diabetes, and 25% vs. 29% were non-smokers; race/ethnicity was similar. Presence and strength of associations differed by risk factor and CRC site (Table). Smoking was more closely associated with rectal (OR=1.84) than proximal (OR=1.59) or distal cancer (OR=1.50). Diabetes was more closely associated with proximal than distal or rectal cancer (OR=1.28, 1.17 and 1.12, respectively). Blacks had reduced odds for rectal (OR=0.89), but increased odds for distal (OR=1.27) and particularly proximal cancer (OR=1.60) when compared to non-Hispanic whites. For males vs. females, odds of rectal was higher than distal or proximal cancer (OR=2.64, 1.95 and 1.32, respectively). Conclusions: Presence and strength of association of cancer risk factors may differ by CRC site. Site should be a key consideration in future studies of CRC risk. Table 1.Site specific risk factors for 21,739 CRC cases compared to 616,323 normal colonoscopy controlsAnatomic Site of CRC*Proximal (n=7,686)Distal (n=7,036)Rectal (n=7,017)Candidate Risk FactorOR (CI)OR (CI)OR (CI)Age, years†1.100 (1.096-1.103)1.065 (1.062-1.069)‡1.055 (1.051- 1.059)‡§Gender, male vs. female1.318 (1.080-1.608)1.950 (1.538-2.471)‡2.636 (2.006-3.463)‡Race/ethnicityBlack vs. non-Hispanic white1.596 (1.480-1.720)1.270 (1.167-1.381)‡0.886 (0.808-0.971)‡§Hispanic vs. non-Hispanic white1.291 (1.123-1.485)1.531 (1.337-1.753)1.219 (1.053-1.411)§Asian vs. non-Hispanic white0.872 (0.634-1.201)0.917 (0.662-1.272)0.556 (0.371-0.832)BMI, kg/m2†0.994 (0.988-1.000)1.005 (0.999-1.012)‡0.963 (0.957-0.970)‡§Diabetes, yes vs. no1.278 (1.196-1.366)1.170 (1.089-1.257)1.119 (1.038-1.207)‡SmokingCurrent vs. never1.594 (1.476-1.722)1.500 (1.383-1.627)1.837 (1.695-1.992)‡§Former vs. never0.997 (0.926-1.073)1.082 (1.001-1.171)1.085 (0.998-1.119)* Multinomial analyses adjusted for other risk factors, as well as year of colonoscopy, 1999-2011† by one unit increment‡ p Citation Format: Samir Gupta, Ranier Bustamante, Ashley Earles, Maria E. Martinez, Karen Messer, Christina D. Williams, Andrew J. Gawron, Tonya Kaltenbach, Lin Liu. Site specific risk factors for colorectal cancer [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 281. doi:10.1158/1538-7445.AM2017-281