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Joshua Demb,1,2 Tomi Akinyemiju,3 Isabel Allen,1 Tracy Onega,4 Robert A Hiatt,1 Dejana Braithwaite2 1Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA; 2Department of Oncology, Georgetown University School of Medicine, Washington, DC, USA; 3Department of Epidemiology, University of Kentucky, Lexington, KY, USA; 4Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Hanover, NH, USA Background: The extent to which screening mammography (SM) recommendations in older women incorporate life expectancy factors is not well established. Objective: The objective of this review was to evaluate evidence on SM utilization in older women by life expectancy factors. Data sources: We searched Medline, Embase and Web of Science from January 1991 to March 2016. Study selection: We included studies examining SM utilization in women ages ≥65 years that measured life expectancy using comorbidity, functional limitations or health or prognostic status. Data extraction and synthesis: ORs and 95% CIs were extracted and grouped by life expectancy category. Findings were aggregated into pooled ORs and 95% CIs and meta-analyzed by life expectancy category. Main outcomes and measures: The primary outcome was SM utilization within the last 5 years. Life expectancy factors included number of comorbidities, Charlson Comorbidity Index (CCI), activities of daily living, instrumental activities of daily living, self-reported health status and 5-year prognostic indices. Results: Of 2,606 potential titles, we identified 25 meeting the inclusion criteria (comorbidity: eight studies, functional status: 11 studies and health/prognostic status: 13 studies). Women with higher CCI scores had decreased SM utilization (pooled OR: 0.75, 95% CI: 0.67–0.85), but increased absolute number of comorbidities were weakly associated with increased SM utilization (pooled OR: 1.17, 95% CI: 1.00–1.36). Women with more functional limitations had lower SM use odds than women with no limitations (pooled OR: 0.72, 95% CI: 0.62–0.83). Screening utilization odds were lower among women with poor vs excellent health (pooled OR: 0.85, 95% CI: 0.74–0.96). Conclusion: Greater CCI score, functional limitations and lower perceived health were associated with decreased SM use, whereas higher absolute number of comorbidities was associated with increased SM use. SM guidelines should consider these factors to improve assessments of potential benefits and harms in older women. Keywords: screening mammography, comorbidity, functional limitations, health status, meta-analysis

Dejana Braithwaite,1 Joshua Demb,1 Louise M Henderson2 1Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, 2Department of Radiology, University of North Carolina, Chapel Hill, NC, USA Abstract: Breast cancer is a major cause of cancer-related deaths among older women, aged 65 years or older. Screening mammography has been shown to be effective in reducing breast cancer mortality in women aged 50–74 years but not among those aged 75 years or older. Given the large heterogeneity in comorbidity status and life expectancy among older women, controversy remains over screening mammography in this population. Diminished life expectancy with aging may decrease the potential screening benefit and increase the risk of harms. In this review, we summarize the evidence on screening mammography utilization, performance, and outcomes and highlight evidence gaps. Optimizing the screening strategy will involve separating older women who will benefit from screening from those who will not benefit by using information on comorbidity status and life expectancy. This review has identified areas related to screening mammography in older women that warrant additional research, including the need to evaluate emerging screening technologies, such as tomosynthesis among older women and precision cancer screening. In the absence of randomized controlled trials, the benefits and harms of continued screening mammography in older women need to be estimated using both population-based cohort data and simulation models. Keywords: aging, breast cancer, precision cancer screening

Our aim was to examine the association between fatal colorectal cancer (CRC) and time to colonoscopy among individuals who underwent diagnostic colonoscopy after abnormal stool blood test (SBT) in a cohort of United States Veterans. Methods: We performed a cohort study of Veterans aged 50-75 years, with an abnormal SBT using the Veterans Health Administration's (VA) national electronic health record data during the years 1999 and 2010. Colonoscopy receipt was ascertained using current procedural terminology codes after abnormal SBT. The study outcome, CRC death, was defined through National Death Index cause-specific mortality data. We followed patients through CRC-related death, other death, or until December 31, 2015. Multivariable Cox proportional hazards modeling was used to generate CRC-specific mortality hazard ratios (HRs) and 95% confidence intervals (CI) for 3-month colonoscopy intervals, with 3-6 months as the reference. Models were adjusted for age, sex, race/ethnicity, smoking, diabetes, body mass index, and Charlson Comorbidity Index. Results: We included 222,004 patients with abnormal SBTs; the average age was 63 with a standard deviation of 7.2 years, 97% were male, 72% were Non-Hispanic White and 20% were Black. Of the 222,004 patients, 69% completed diagnostic colonoscopy within 12 months of abnormal SBT, 4% were diagnosed with CRC, and 1% died of CRC specific death. Compared to patients with a colonoscopy at 3-6 months (standard of care), CRC-related mortality risk was significantly higher for patients with colonoscopies at 0-3 months (HR = 1.29; 95% CI, 1.14-1.47), 18-21 months (HR = 1.57; 95% CI, 1.19-2.06), and 21-24 months (HR = 1.46; 95% CI, 1.07-1.97). No significant increase in mortality risk was shown for 6-9 month, 9-12 month, 12-15 month, 15-18 months, and 24+ month intervals. Conclusion: Time to colonoscopy plays a significant role in CRC death after abnormal SBT. Compared to a colonoscopy performed during a 3-6-month window, a colonoscopy performed outside of the 15-month window had a higher risk for mortality. Given the impact of timely diagnostic colonoscopy on CRC mortality, development of interventions to increase timely diagnostic follow-up after abnormal SBT are essential to CRC outcome improvement. [ABSTRACT FROM AUTHOR]

Obesity, a growing pandemic in Western societies, significantly impacts metabolic health and contributes to visual disorders. While the systemic consequences of obesity, such as chronic inflammation and insulin resistance, are well-studied in adults, its early-life effects on retinal health remain underexplored. Using a maternal Western Diet (WD) exposure model, we investigated the developmental impact of early-life metabolic disturbances on retinal and cognitive function. Our findings reveal that WD exposure from gestation to early adulthood accelerates the onset of features resembling diabetic retinopathy, including increased retinal vascularization, inflammation, and compromised blood-retina barrier integrity, observed within just four months. Females exhibited heightened vulnerability, showing pronounced ocular defects such as anophthalmia, microphthalmia, and congenital cataracts. These results underscore a critical developmental window during which metabolic disruptions predispose to sex-specific retinal and neurovascular pathologies. This work bridges the link between pediatric and adult obesity, highlighting the urgent need for early interventions to mitigate long-term visual impairments that could further impair recognition memory.

Importance: Rates of early-onset (before 50 years of age) colorectal cancer (EOCRC) are increasing, with notable differences across racial and ethnic groups. Limited data are available on EOCRC-related mortality differences when disaggregating racial and ethnic groups., Objective: To investigate racial and ethnic differences in EOCRC mortality, including disaggregation of Asian American populations separately, including Native Hawaiian or Other Pacific Islander populations and specific Asian American groups, and to quantify the contribution of clinical and sociodemographic factors accounting for these differences., Design, Setting, and Participants: This population-based cohort study included California Cancer Registry data for individuals aged 18 to 49 years with EOCRC between January 1, 2000, to December 31, 2019. Median follow-up was 4.2 (IQR, 1.6-10.0) years. The data analysis was conducted between July 1, 2021, and September 30, 2024., Exposure: Race and ethnicity defined as Asian American (and 7 disaggregated subgroups), Hispanic, Native Hawaiian or Other Pacific Islander, non-Hispanic American Indian or Alaska Native, non-Hispanic Black, and non-Hispanic White., Main Outcomes and Measures: Cox proportional hazards regression models were used to measure association between race and ethnicity and CRC mortality risk, yielding adjusted hazard ratios (AHRs) and 95% CIs. Associations of sociodemographic, health system, and clinical factors with differences in mortality by racial and ethnic minority group were assessed using sequential modeling., Results: There were 22 834 individuals diagnosed with EOCRC between 2000 and 2019 (12 215 [53.5%] male; median age, 44 [IQR, 39-47] years). Racial and ethnic identity included 3544 (15.5%) Asian American, 6889 (30.2%) Hispanic, 135 (0.6%) Native Hawaiian or Other Pacific Islander, 125 (0.5%) non-Hispanic American Indian or Alaska Native, 1668 (7.3%) non-Hispanic Black, and 10 473 (45.9%) non-Hispanic White individuals. Compared with non-Hispanic White individuals, higher EOCRC mortality was found for Native Hawaiian or Other Pacific Islander (AHR, 1.34; 95% CI, 1.01-1.76) and non-Hispanic Black (AHR, 1.18; 95% CI, 1.07-1.29) individuals. Disaggregation of Asian American ethnic groups revealed notable heterogeneity, but no single group had increased EOCRC mortality risk after full adjustment for covariates. For Hispanic individuals, there was higher EOCRC mortality (AHR, 1.15 [95% CI, 1.08-1.22]) with the base model (adjustment for age, sex, and tumor characteristics), but the association disappeared once neighborhood socioeconomic status was added to the base model (AHR, 1.00 [95% CI, 0.94-1.06]). Similarly, there was higher EOCRC mortality among Southeast Asian individuals with the base model (AHR, 1.17 [95% CI, 1.03-1.34], but that association disappeared with the addition of insurance status to the model (AHR, 1.10 [95% CI, 0.96-1.25])., Conclusions and Relevance: In this cohort study, racial and ethnic disparities in EOCRC mortality were evident, with the highest burden among Native Hawaiian or Other Pacific Islander and non-Hispanic Black individuals. These results provide evidence of the role of social determinants of health in explaining these differences.

Introduction: Non-Hispanic Black (NHB) Americans have a higher incidence of colorectal cancer (CRC) and worse survival than non-Hispanic white (NHW) Americans, but the relative contributions of biological versus access to care remain poorly characterized. This study used two nationwide cohorts in different healthcare contexts to study health system effects on this disparity., Methods: We used data from the Surveillance, Epidemiology, and End Results (SEER) registry as well as the United States Veterans Health Administration (VA) to identify adults diagnosed with colorectal cancer between 2010 and 2020 who identified as non-Hispanic Black (NHB) or non-Hispanic white (NHW). Stratified survival analyses were performed using a primary endpoint of overall survival, and sensitivity analyses were performed using cancer-specific survival., Results: We identified 263,893 CRC patients in the SEER registry (36,662 (14%) NHB; 226,271 (86%) NHW) and 24,375 VA patients (4,860 (20%) NHB; 19,515 (80%) NHW). In the SEER registry, NHB patients had worse OS than NHW patients: median OS of 57 months (95% confidence interval (CI) 55-58) versus 72 months (95% CI 71-73) (hazard ratio (HR) 1.14, 95% CI 1.12-1.15, p  = 0.001). In contrast, VA NHB median OS was 65 months (95% CI 62-69) versus NHW 69 months (95% CI 97-71) (HR 1.02, 95% CI 0.98-1.07, p  = 0.375). There was significant interaction in the SEER registry between race and Medicare age eligibility ( p  < 0.001); NHB race had more effect in patients <65 years old (HR 1.44, 95% CI 1.39-1.49, p < 0.001) than in those ≥65 (HR 1.13, 95% CI 1.11-1.15, p < 0.001). In the VA, age stratification was not significant ( p  = 0.21)., Discussion: Racial disparities in CRC survival in the general US population are significantly attenuated in Medicare-aged patients. This pattern is not present in the VA, suggesting that access to care may be an important component of racial disparities in this disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Riviere, Morgan, Deshler, Demb, Mehtsun, Martinez, Gupta, Banegas, Murphy and Rose.)

Purpose: Helicobacter pylori is the most common cause of infection-associated cancer worldwide. We aimed to evaluate the impact of H. pylori infection and treatment on colorectal cancer (CRC) incidence and mortality., Patients: US Veterans who completed H. pylori testing between 1999 and 2018., Methods: We conducted a retrospective cohort analysis among adults within the Veterans Health Administration who completed testing for H. pylori. The primary exposures were (1) H. pylori test result (positive/negative) and (2) H. pylori treatment (untreated/treated) among H. pylori-positive individuals. The primary outcomes were CRC incidence and mortality. Follow-up started at the first H. pylori testing and continued until the earliest of incident or fatal CRC, non-CRC death, or December 31, 2019., Results: Among 812,736 individuals tested for H. pylori, 205,178 (25.2%) tested positive. Being H. pylori-positive versus H. pylori-negative was associated with higher CRC incidence and mortality. H. pylori treatment versus no treatment was associated with lower CRC incidence and mortality (absolute risk reduction 0.23%-0.35%) through 15-year follow-up. Being H. pylori-positive versus H. pylori-negative was associated with an 18% (adjusted hazard ratio [adjusted HR], 1.18 [95% CI, 1.12 to 1.24]) and 12% (adjusted HR, 1.12 [95% CI, 1.03 to 1.21]) higher incident and fatal CRC risk, respectively. Individuals with untreated versus treated H. pylori infection had 23% (adjusted HR, 1.23 [95% CI, 1.13 to 1.34]) and 40% (adjusted HR, 1.40 [95% CI, 1.24 to 1.58]) higher incident and fatal CRC risk, respectively. The results were more pronounced in the analysis restricted to individuals with nonserologic testing., Conclusion: H. pylori positivity may be associated with small but statistically significant higher CRC incidence and mortality; untreated individuals, especially those with confirmed active infection, appear to be most at risk.

Importance: Early-onset colorectal cancer (EOCRC), defined as a diagnosis at younger than age 50 years, is increasing, and so-called red flag signs and symptoms among these individuals are often missed, leading to diagnostic delays. Improved recognition of presenting signs and symptoms associated with EOCRC could facilitate more timely diagnosis and impact clinical outcomes., Objective: To report the frequency of presenting red flag signs and symptoms among individuals with EOCRC, to examine their association with EOCRC risk, and to measure variation in time to diagnosis from sign or symptom presentation., Data Sources: PubMed/MEDLINE, Embase, CINAHL, and Web of Science were searched from database inception through May 2023., Study Selection: Studies that reported on sign and symptom presentation or time from sign and symptom presentation to diagnosis for patients younger than age 50 years diagnosed with nonhereditary CRC were included., Data Extraction and Synthesis: Data extraction and quality assessment were performed independently in duplicate for all included studies using Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines. Joanna Briggs Institute Critical Appraisal tools were used to measure risk of bias. Data on frequency of signs and symptoms were pooled using a random-effects model., Main Outcomes and Measures: Outcomes of interest were pooled proportions of signs and symptoms in patients with EOCRC, estimates for association of signs and symptoms with EOCRC risk, and time from sign or symptom presentation to EOCRC diagnosis., Results: Of the 12 859 unique articles initially retrieved, 81 studies with 24 908 126 patients younger than 50 years were included. The most common presenting signs and symptoms, reported by 78 included studies, were hematochezia (pooled prevalence, 45% [95% CI, 40%-50%]), abdominal pain (pooled prevalence, 40% [95% CI, 35%-45%]), and altered bowel habits (pooled prevalence, 27% [95% CI, 22%-33%]). Hematochezia (estimate range, 5.2-54.0), abdominal pain (estimate range, 1.3-6.0), and anemia (estimate range, 2.1-10.8) were associated with higher EOCRC likelihood. Time from signs and symptoms presentation to EOCRC diagnosis was a mean (range) of 6.4 (1.8-13.7) months (23 studies) and a median (range) of 4 (2.0-8.7) months (16 studies)., Conclusions and Relevance: In this systematic review and meta-analysis of patients with EOCRC, nearly half of individuals presented with hematochezia and abdominal pain and one-quarter with altered bowel habits. Hematochezia was associated with at least 5-fold increased EOCRC risk. Delays in diagnosis of 4 to 6 months were common. These findings highlight the need to identify concerning EOCRC signs and symptoms and complete timely diagnostic workup, particularly for individuals without an alternative diagnosis or sign or symptom resolution.

Introduction: Achalasia is a postulated risk factor of esophageal cancer (EC); however, EC-associated risk in achalasia is understudied. We aimed to evaluate EC risk among individuals within the nationwide Veterans Affairs Achalasia Cohort., Methods: We conducted a matched cohort study among US veterans aged 18 years or older from 1999 to 2019. Individuals with achalasia were age matched and sex matched 1:4 to individuals without achalasia. Follow-up continued from study entry until diagnosis with incident/fatal EC (primary outcome), death from non-EC-related causes, or end of the study follow-up (December 31, 2019). Association between achalasia and EC risk was examined using Cox regression models., Results: We included 9,315 individuals in the analytic cohort (median age 55 years; 92% male): 1,863 with achalasia matched to 7,452 without achalasia. During a median 5.5 years of follow-up, 17 EC occurred (3 esophageal adenocarcinoma, 12 squamous cell carcinoma, and 2 unknown type) among individuals with achalasia, compared with 15 EC (11 esophageal adenocarcinoma, 1 squamous cell carcinoma, and 3 unknown type) among those without achalasia. EC incidence for those with achalasia was 1.4 per 1,000 person-years, and the median time from achalasia diagnosis to EC development was 3.0 years (Q1-Q3: 1.3-9.1). Individuals with achalasia had higher cumulative EC incidence at 5, 10, and 15 years of follow-up compared with individuals without achalasia, and EC risk was 5-fold higher (hazard ratio 4.6, 95% confidence interval: 2.3-9.2)., Discussion: Based on substantial EC risk, individuals with achalasia may benefit from a high index of suspicion and endoscopic surveillance for EC., (Copyright © 2023 by The American College of Gastroenterology.)

Importance: To date, the diagnostic test completion rate and the time to diagnostic endoscopy or colonoscopy among adults with iron-deficiency anemia (IDA) and/or hematochezia have not been well characterized., Objective: To evaluate the diagnostic test completion rate and the time to diagnostic testing among veterans younger than 50 years with IDA and/or hematochezia., Design, Setting, and Participants: This cohort study was conducted within the Veterans Health Administration between October 1, 1999, and December 31, 2019, among US veterans aged 18 to 49 years from 2 separate cohorts: those with a diagnosis of IDA (n = 59 169) and those with a diagnosis of hematochezia (n = 189 185). Statistical analysis was conducted from August 2021 to August 2023., Exposures: Diagnostic testing factors included age, sex, race and ethnicity, Veterans Health Administration geographic region, and hemoglobin test value (IDA cohort only)., Main Outcomes and Measures: Primary outcomes of diagnostic testing were (1) bidirectional endoscopy after diagnosis of IDA and (2) colonoscopy or sigmoidoscopy after diagnosis of hematochezia. The association between diagnostic testing factors and diagnostic test completion was examined using Poisson models., Results: There were 59 169 veterans with a diagnosis of IDA (mean [SD] age, 40.7 [7.1] years; 30 502 men [51.6%]), 189 185 veterans with a diagnosis of hematochezia (mean [SD] age, 39.4 [7.6] years; 163 690 men [86.5%]), and 2287 veterans with IDA and hematochezia (mean [SD] age, 41.6 [6.9] years; 1856 men [81.2%]). The cumulative 2-year diagnostic workup completion rate was 22% (95% CI, 22%-22%) among veterans with IDA and 40% (95% CI, 40%-40%) among veterans with hematochezia. Veterans with IDA were mostly aged 40 to 49 years (37 719 [63.7%]) and disproportionately Black (24 480 [41.4%]). Women with IDA (rate ratio [RR], 0.42; 95% CI, 0.40-0.43) had a lower likelihood of diagnostic test completion compared with men with IDA. Black (RR, 0.65; 95% CI, 0.62-0.68) and Hispanic (RR, 0.88; 95% CI, 0.82-0.94) veterans with IDA were less likely to receive diagnostic testing compared with White veterans with IDA. Veterans with hematochezia were mostly White (105 341 [55.7%]). Among veterans with hematochezia, those aged 30 to 49 years were more likely to receive diagnostic testing than adults younger than 30 years of age (age 30-39 years: RR, 1.15; 95% CI, 1.12-1.18; age 40-49 years: RR, 1.36; 95% CI, 1.33-1.40). Hispanic veterans with hematochezia were less likely to receive diagnostic testing compared with White veterans with hematochezia (RR, 0.96; 95% CI, 0.93-0.98)., Conclusions and Relevance: In the cohorts of veterans younger than 50 years with IDA and/or hematochezia, the diagnostic test completion rate was low. Follow-up was less likely among female, Black, and Hispanic veterans with IDA and Hispanic veterans with hematochezia. Optimizing timely follow-up across social and demographic groups may contribute to improving colorectal cancer outcomes and mitigate disparities.

Background and Aims: There are limited contemporary population-based data on Helicobacter pylori epidemiology and outcomes in the United States. Our primary aim was to create a validated cohort of veterans with H pylori testing or treatment using Veterans Health Administration data., Methods: Using Veterans Health Administration structured and unstructured data, we developed and validated 4 algorithms for H pylori infection (3 algorithms) and treatment status (1 algorithm). During the development phase, we iteratively modified each algorithm based on a manual review of random sets of electronic health records (reference standard). The a priori validation goal was to achieve a one-sided 95% confidence lower bound (LB) for positive predictive value (PPV) and/or negative predictive value (NPV) >90%. We applied the Bonferroni correction when both PPV and NPV were relevant., Results: For H pylori infection, we achieved 99.0% PPV (LB = 94.6%) and 100% NPV (LB = 96.4%) for discriminating H pylori positive vs negative status using structured (ie, laboratory tests) and 95% PPV (LB = 90.3%) and 97.9% NPV (LB = 93.9%) using unstructured (ie, histopathology reports) data. Diagnostic codes achieved 98% PPV (LB = 93.0%) for H pylori diagnosis. The treatment algorithm was composed of multiple antimicrobial combinations and overall achieved ≥98% PPV (LB = 93.0%) for H pylori treatment, except for amoxicillin/levofloxacin (PPV<60%). Application of these algorithms yielded nearly 1.2 million veterans with H pylori testing and/or treatment between 1999 and 2018., Conclusion: We assembled a validated national cohort of veterans who were tested or treated for H pylori infection. This cohort can be used for evaluating H pylori epidemiology and treatment patterns, as well as complications of chronic infection.

Introduction: Colorectal cancer (CRC) incidence and mortality rates are increasing in adults aged <50 years. Young-onset adenoma (YOA)-adenoma detected in adults younger than 50 years-may signify increased CRC risk, but this association has not been widely studied. Our aim was to compare the risk of incident and fatal CRC in adults aged <50 years with YOA diagnosis compared with those with a normal colonoscopy., Methods: We conducted a cohort study of US Veterans aged 18-49 years who received colonoscopy between 2005 and 2016. The primary exposure of interest was YOA. Primary outcomes included incident and fatal CRC. We used Kaplan-Meier curves to calculate cumulative incident and fatal CRC risk and Cox models to examine relative CRC risk., Results: The study cohort included 54,284 Veterans aged <50 years exposed to colonoscopy, among whom 13% (n = 7,233) had YOA at start of follow-up. Cumulative 10-year CRC incidence was 0.11% (95% confidence interval [CI]: 0.00%-0.27%) after any adenoma diagnosis, 0.18% (95% CI: 0.02%-0.53%) after advanced YOA diagnosis, 0.10% (95% CI: 0.00%-0.28%) after nonadvanced adenoma diagnosis, and 0.06% (95% CI: 0.02%-0.09%) after normal colonoscopy. Veterans with advanced adenoma had 8-fold greater incident CRC risk than those with normal colonoscopy (hazard ratio: 8.0; 95% CI: 1.8-35.6). Across groups, no differences in fatal CRC risk were observed., Discussion: Young-onset advanced adenoma diagnosis was associated with 8-fold increased incident CRC risk compared with normal colonoscopy. However, cumulative CRC incidence and mortality at 10 years among individuals with either young onset non-advanced or advanced adenoma diagnosis were both relatively low., (Copyright © 2023 by The American College of Gastroenterology.)

Background: Prompt detection of colorectal cancer (CRC) among individuals younger than age 50 years (early-onset CRC) is a clinical priority because of its alarming rise., Methods: We conducted a matched case-control study of 5075 incident early-onset CRC among US commercial insurance beneficiaries (113 million adults aged 18-64 years) with 2 or more years of continuous enrollment (2006-2015) to identify red-flag signs and symptoms between 3 months to 2 years before the index date among 17 prespecified signs and symptoms. We assessed diagnostic intervals according to the presence of these signs and symptoms before and within 3 months of diagnosis., Results: Between 3 months and 2 years before the index date, 4 red-flag signs and symptoms (abdominal pain, rectal bleeding, diarrhea, and iron deficiency anemia) were associated with an increased risk of early-onset CRC, with odds ratios (ORs) ranging from 1.34 to 5.13. Having 1, 2, or at least 3 of these signs and symptoms were associated with a 1.94-fold (95% confidence interval [CI] = 1.76 to 2.14), 3.59-fold (95% CI = 2.89 to 4.44), and 6.52-fold (95% CI = 3.78 to 11.23) risk (Ptrend < .001), respectively, with stronger associations for younger ages (Pinteraction < .001) and rectal cancer (Pheterogenity = .012). The number of different signs and symptoms was predictive of early-onset CRC beginning 18 months before diagnosis. Approximately 19.3% of patients had their first sign or symptom occur between 3 months and 2 years before diagnosis (median diagnostic interval = 8.7 months), and approximately 49.3% had the first sign or symptom within 3 months of diagnosis (median diagnostic interval = 0.53 month)., Conclusions: Early recognition of red-flag signs and symptoms (abdominal pain, rectal bleeding, diarrhea, and iron-deficiency anemia) may improve early detection and timely diagnosis of early-onset CRC., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: 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., Methods: 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., Results: 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 (ADR <19.7%-39.3%) vs the highest quintile (ADR >47.0%). 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)., Conclusions: 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., (Published by Elsevier Inc.)

Background and Aims: 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., Methods: We conducted a retrospective cohort study of U.S. Veterans ≥18 years of age with ≥1 TSA between 1999 and 2018. 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)., Results: 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)., Conclusion: 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., (Published by Elsevier Inc.)

Background: Delays in colonoscopy work-up for red flag signs or symptoms of colorectal cancer (CRC) during the COVID-19 pandemic are not well characterized., Aims: To examine colonoscopy uptake and time to colonoscopy after red flag diagnosis, before and during the COVID-19 pandemic., Methods: 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)., Results: 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. 42 days), but longer for individuals with IDA (60 vs. 49 days). There was no association between time period and colonoscopy completion (aHR: 0.99, 95% CI 0.95-1.03)., Conclusions: 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., (© 2022. The Author(s).)

Background Context: Postoperative recovery after adult spinal deformity (ASD) operations is arduous, fraught with complications, and often requires extended hospital stays. A need exists for a method to rapidly predict patients at risk for extended length of stay (eLOS) in the preoperative setting., Purpose: To develop a machine learning model to preoperatively estimate the likelihood of eLOS following elective multi-level lumbar/thoracolumbar spinal instrumented fusions (≥3 segments) for ASD., Study Design/setting: Retrospectively from a state-level inpatient database hosted by the Health care cost and Utilization Project., Patient Sample: Of 8,866 patients of age ≥50 with ASD undergoing elective lumbar or thoracolumbar multilevel instrumented fusions., Outcome Measures: The primary outcome was eLOS (>7 days)., Methods: Predictive variables consisted of demographics, comorbidities, and operative information. Significant variables from univariate and multivariate analyses were used to develop a logistic regression-based predictive model that use six predictors. Model accuracy was assessed through area under the curve (AUC), sensitivity, and specificity., Results: Of 8,866 patients met inclusion criteria. A saturated logistic model with all significant variables from multivariate analysis was developed (AUC=0.77), followed by generation of a simplified logistic model through stepwise logistic regression (AUC=0.76). Peak AUC was reached with inclusion of six selected predictors (combined anterior and posterior approach, surgery to both lumbar and thoracic regions, ≥8 level fusion, malnutrition, congestive heart failure, and academic institution). A cutoff of 0.18 for eLOS yielded a sensitivity of 77% and specificity of 68%., Conclusions: This predictive model can facilitate identification of adults at risk for eLOS following elective multilevel lumbar/thoracolumbar spinal instrumented fusions for ASD. With a fair diagnostic accuracy, the predictive calculator will ideally enable clinicians to improve preoperative planning, guide patient expectations, enable optimization of modifiable risk factors, facilitate appropriate discharge planning, stratify financial risk, and accurately identify patients who may represent high-cost outliers. Future prospective studies that validate this risk assessment tool on external datasets would be valuable., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To develop a model for factors predictive of Post-Acute Care Facility (PACF) discharge in adult patients undergoing elective multi-level (≥ 3 segments) lumbar/thoracolumbar spinal instrumented fusions., Methods: The State Inpatient Databases acquired from the Healthcare Cost and Utilization Project from 2005 to 2013 were queried for adult patients who underwent elective multi-level thoracolumbar fusions for spinal deformity. Outcome variables were classified as discharge to home or PACF. Predictive variables included demographic, pre-operative, and operative factors. Univariate and multivariate logistic regression analyses informed development of a logistic regression-based predictive model using seven selected variables. Performance metrics included area under the curve (AUC), sensitivity, and specificity., Results: Included for analysis were 8866 patients. The logistic model including significant variables from multivariate analysis yielded an AUC of 0.75. Stepwise logistic regression was used to simplify the model and assess number of variables needed to reach peak AUC, which included seven selected predictors (insurance, interspaces fused, gender, age, surgical region, CCI, and revision surgery) and had an AUC of 0.74. Model cut-off for predictive PACF discharge was 0.41, yielding a sensitivity of 75% and specificity of 59%., Conclusions: The seven variables associated significantly with PACF discharge (age > 60, female gender, non-private insurance, primary operations, instrumented fusion involving 8+ interspaces, thoracolumbar region, and higher CCI scores) may aid in identification of adults at risk for discharge to a PACF following elective multi-level lumbar/thoracolumbar spinal fusions for spinal deformity. This may in turn inform discharge planning and expectation management., (© 2022. The Author(s).)

Background: Early onset colorectal cancer (CRC) incidence is rising under age 50, with a birth cohort effect for increasing incidence among individuals born 1950 and later. It is unclear whether increasing incidence trends will confer increased risk beyond age 50, the previously most commonly recommended age to initiate screening, when screening availability might modify incidence trends., Aim: Evaluate US trends in colorectal cancer (CRC) for ages 40-59 years., Methods: We analyzed counts and incidence rates for CRC, including by anatomic subsite, using the US Cancer Statistics dataset covering 100% of the population 2003-2017. Joinpoint regression was used to quantify Average Annual Percent Change (AAPC) in cancer incidence by age subgroup., Results: 470,458 CRC cases were observed age 40-59, with absolute numbers of rectal (n = 4173) and distal cases (n = 3327) per year for age 50-54 approaching age 55-59 cases for rectal (n = 4566) and distal (n = 3682) cancer by 2017. Increasing early onset rectal cancer incidence per 100,000 occuring under age 50 was observed to extend to age 50-54, from 4.9 to 6.3 for age 40-44 (AAPC 2.1; 95% CI 1.5-2.7), 9.3 to 12.0 for age 45-49 (AAPC 1.5; 95% CI 1.1-1.4), and from 16.7 to 19.5 for age 50-54 (AAPC 1.0; 95% CI 0.7-1.3)., Conclusions: CRC trends suggest observed increased risks under age 50 are also present after age 50, despite prior availability of screening for this group. Recent CRC trends support initiation of screening earlier than age 50, and promotion of "on-time" screening initiation., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Introduction: Limited evidence exists on the impact of age and comorbidity on biopsy rates and findings among older women., Materials and Methods: We used data from 170,657 women ages 66-94 enrolled in the United States Breast Cancer Surveillance Consortium (BCSC). We estimated one-year rates of biopsy by type (any, fine-needle aspiration (FNA), core or surgical) and yield of the most invasive biopsy finding (benign, ductal carcinoma in situ (DCIS) and invasive breast cancer) by age and comorbidity. Statistical significance was assessed using Wald statistics comparing coefficients estimated from logistic regression models adjusted for age, comorbidity, BCSC registry, and interaction between age and comorbidity., Results: Of 524,860 screening mammograms, 9830 biopsies were performed following 7930 exams (1.5%) within one year, specifically 5589 core biopsies (1.1%), 3422 (0.7%) surgical biopsies and 819 FNAs (0.2%). Biopsy rates per 1000 screens decreased with age (66-74:15.7, 95%CI:14.8-16.8), 75-84:14.5(13.5-15.6), 85-94:13.2(11.3,15.4), p trend  < 0.001) and increased with Charlson Comorbidity Score (CCS = 0:14.4 (13.5-15.3), CCS = 1:16.6 (15.2-18.1), CCS ≥2:19.0 (16.9-21.5), p trend  < 0.001).Biopsy rates increased with CCS at ages 66-74 and 75-84 but not 85-94. Core and surgical biopsy rates increased with CCS at ages 66-74 only. For each biopsy type, the yield of invasive breast cancer increased with age irrespective of comorbidity., Discussion: Women aged 66-84 with significant comorbidity in a breast cancer screening population had higher breast biopsy rates and similar rates of invasive breast cancer diagnosis than their counterparts with lower comorbidity. A considerable proportion of these diagnoses may represent overdiagnoses, given the high competing risk of death from non-breast-cancer causes among older women., Competing Interests: Declaration of Competing Interest Dr. Braithwaite reports grants from National Cancer Institute (NCI) during the conduct of the study. Dr. Lee reports grants from NCI during the conduct of the study. Dr. Lee also reports grants from GE Healthcare to his institution, research consulting fees from GRAIL, Inc., personal fees for editorial board work from American College of Radiology, and textbook royalties from McGraw Hill, Inc., Oxford University Press, and UpToDate, Inc.; all outside the submitted work. Ms. Abraham reports grants from NCI during the conduct of the study. Dr. Buist reports grants from NCI during the conduct of the study. Dr. Miglioretti reports grants from NIH/NCI during the conduct of the study. Dr. O'Meara reports grants from NIH/NCI, during the conduct of the study. Dr. Sprague reports grants from NIH during the conduct of the study., (Published by Elsevier Ltd.)

Prior studies of screening mammography patterns by functional status in older women show inconsistent results. We used Breast Cancer Surveillance Consortium-Medicare linked data (1999-2014) to investigate the association of functional limitations with adherence to screening mammography in 145,478 women aged 66-74 years. Functional limitation was represented by a claims-based function-related indicator (FRI) score which incorporated 16 items reflecting functional status. Baseline adherence was defined as mammography utilization 9-30 months after the index screening mammography. Longitudinal adherence was examined among women adherent at baseline and defined as time from the index mammography to end of the first 30-month gap in mammography. Multivariable logistic regression and Cox proportional hazards models were used to investigate baseline and longitudinal adherence, respectively. Subgroup analyses were conducted by age (66-70 vs. 71-74 years). Overall, 69.6% of participants had no substantial functional limitation (FRI score 0), 23.5% had some substantial limitations (FRI score 1), and 6.8% had serious limitations (FRI score ≥ 2). Mean age at baseline was 68.5 years (SD = 2.6), 85.3% of participants were white, and 77.1% were adherent to screening mammography at baseline. Women with a higher FRI score were more likely to be non-adherent at baseline (FRI ≥ 2 vs. 0: aOR = 1.13, 95% CI = 1.06, 1.20, p-trend < 0.01). Similarly, a higher FRI score was associated with longitudinal non-adherence (FRI ≥ 2 vs. 0: aHR = 1.16, 95% CI = 1.11, 1.22, p-trend < 0.01). Effect measures of FRI did not differ substantially by age categories. Older women with a higher burden of functional limitations are less likely to be adherent to screening mammography recommendations., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: Although screening decreases incidence of and mortality from colorectal cancer (CRC), screening rates are low. Health-promoting financial incentives may increase uptake of cancer screening., Objective: To evaluate the relative and absolute benefit associated with adding financial incentives to the uptake of CRC screening., Data Sources: PubMed, Cochrane Central Register of Controlled Trials, and Web of Science were searched from inception to July 31, 2020. Keywords and Medical Subject Headings terms were used to identify published studies on the topic. The search strategy identified 835 studies., Study Selection: Randomized clinical trials (RCTs) were selected that involved adults older than 50 years who were eligible for CRC screening, who received either various forms of financial incentives along with mailed outreach or no financial incentives but mailed outreach and reminders alone, and who reported screening completion by using recommended tests at different time points. Observational or nonrandomized studies and a few RCTs were excluded., Data Extraction and Synthesis: The review was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). Data were abstracted and risk of bias was assessed by 2 independent reviewers. Random-effects meta-analysis was conducted, heterogeneity was examined through subgroup analysis and metaregression, and quality of evidence was appraised., Main Outcomes and Measures: The primary outcome was CRC screening completion within 12 months of receiving the intervention., Results: A total of 8 RCTs that were conducted in the United States and reported between January 1, 2014, and December 31, 2020, were included. The trials involved 110 644 participants, of whom 53 444 (48.3%) were randomized to the intervention group (received financial incentives) and 57 200 (51.7%) were randomized to the control group (received no financial incentives). Participants were predominantly male, with 59 113 men (53.4%). Low-quality evidence (rated down for risk of bias and heterogeneity) suggested that adding financial incentives may be associated with a small benefit of increasing CRC screening vs no financial incentives (odds ratio [OR], 1.25; 95% CI, 1.05-1.49). With mailed outreach having a 30% estimated CRC screening completion rate, adding financial incentives may increase the rate to 33.5% (95% CI, 30.8%-36.2%). On metaregression, the magnitude of benefit decreased as the proportion of participants with low income and/or from racial/ethnic minority groups increased. No significant differences were observed by type of behavioral economic intervention (fixed amount: OR, 1.26 [95% CI, 1.05-1.52] vs lottery: OR, 1.06 [95% CI, 0.80-1.40]; P = .32), amount of incentive (≤$5: OR, 1.09 [95% CI, 1.01-1.18] vs >$5: OR, 1.25 [95% CI, 1.02-1.54]; P = .22), or screening modality (stool-based test: OR, 1.14 [95% CI, 0.92-1.41] vs colonoscopy: OR, 1.63 [95% CI, 1.01-2.64]; P = .18)., Conclusions and Relevance: Adding financial incentives appeared to be associated with a small benefit of increasing CRC screening uptake, with marginal benefits in underserved populations with adverse social determinants of health. Alternative approaches to enhancing CRC screening uptake are warranted.

Importance: Breast density is associated with breast cancer risk in women aged 40 to 65 years, but there is limited evidence of its association with risk of breast cancer among women aged 65 years or older., Objective: To compare the association between breast density and risk of invasive breast cancer among women aged 65 to 74 years vs women aged 75 years or older and to evaluate whether the association is modified by body mass index (BMI)., Design, Setting, and Participants: This prospective cohort study used data from the Breast Cancer Surveillance Consortium from January 1, 1996, to December 31, 2012, for US women aged 65 years or older who underwent screening mammography. Data were analyzed from January 1, 2018, to December 31, 2020., Exposures: Breast Imaging Reporting and Data System breast density category, age, and BMI., Main Outcomes and Measures: The 5-year cumulative incidence of invasive breast cancer by level of breast density (almost entirely fat, scattered fibroglandular densities, or heterogeneous or extreme density) and age (65-74 vs ≥75 years) was calculated using weighted means. Cox proportional hazards models were fit to estimate the association of breast density with invasive breast cancer risk. The likelihood ratio test was used to test the interaction between BMI and breast density., Results: A total of 221 714 screening mammograms from 193 787 women were included in the study; a total of 38% of the study population was aged 75 years or older. Of the mammograms, most were from women aged 65 to 74 years (64.6%) and non-Hispanic White individuals (81.4%). The 5-year cumulative incidence of invasive breast cancer increased in association with increasing breast density among women aged 65 to 74 years (almost entirely fatty breasts: 11.3 per 1000 women [95% CI, 10.4-12.5 per 1000 women]; scattered fibroglandular densities: 17.2 per 1000 women [95% CI, 16.1-17.9 per 1000 women]; extremely or heterogeneously dense breasts: 23.7 per 1000 women [95% CI, 22.4-25.3 per 1000 women]) and among those aged 75 years or older (fatty breasts: 13.5 per 1000 women [95% CI, 11.6-15.5]; scattered fibroglandular densities: 18.4 per 1000 women [95% CI, 17.0-19.5 per 1000 women]; extremely or heterogeneously dense breasts: 22.5 per 1000 women [95% CI, 20.2-24.2 per 1000 women]). Extreme or heterogeneous breast density was associated with increased risk of breast cancer compared with scattered fibroglandular breast density in both age categories (65-74 years: hazard ratio [HR], 1.39 [95% CI, 1.28-1.50]; ≥75 years: HR, 1.23 [95% CI, 1.10-1.37]). Women with almost entirely fatty breasts had a decrease of approximately 30% (range, 27%-34%) in the risk of invasive breast cancer compared with women with scattered fibroglandular breast density (65-74 years: HR, 0.66 [95% CI, 0.58-0.75]; ≥75 years: HR, 0.73; 95% CI, 0.62-0.86). Associations between breast density and breast cancer risk were not significantly modified by BMI (for age 65-74 years: likelihood ratio test, 2.67; df, 2; P = .26; for age ≥75 years, 2.06; df, 2; P = .36)., Conclusions and Relevance: The findings suggest that breast density is associated with increased risk of invasive breast cancer among women aged 65 years or older. Breast density and life expectancy should be considered together when discussing the potential benefits vs harms of continued screening mammography in this population.

Background: Previous reports suggested risk of death and breast cancer varied by comorbidity and age in older women undergoing mammography. However, impacts of functional limitations remain unclear., Methods: We used data from 238,849 women in the Breast Cancer Surveillance Consortium-Medicare linked database (1999-2015) who had screening mammogram at ages 66-94 years. We estimated risk of breast cancer, breast cancer death, and non-breast cancer death by function-related indicator (FRI) which incorporated 16 claims-based items and was categorized as an ordinal variable (0, 1, and 2+). Fine and Gray proportional sub-distribution hazards models were applied with breast cancer and death treated as competing events. Risk estimates by FRI scores were adjusted by age and NCI comorbidity index separately and stratified by these factors., Results: Overall, 9,252 women were diagnosed with breast cancer, 406 died of breast cancer, and 41,640 died from non-breast cancer causes. The 10-year age-adjusted invasive breast cancer risk slightly decreased with FRI score [FRI = 0: 4.0%, 95% confidence interval (CI) = 3.8-4.1; FRI = 1: 3.9%, 95% CI = 3.7-4.2; FRI ≥ 2: 3.5%, 95% CI = 3.1-3.9). Risk of non-breast cancer death increased with FRI score (FRI = 0: 18.8%, 95% CI = 18.5-19.1; FRI = 1: 24.4%, 95% CI = 23.9-25.0; FRI ≥ 2: 39.8%, 95% CI = 38.8-40.9]. Risk of breast cancer death was low with minimal differences across FRI scores. NCI comorbidity index-adjusted models and stratified analyses yielded similar patterns., Conclusions: Risk of non-breast cancer death substantially increases with FRI score, whereas risk of breast cancer death is low regardless of functional status., Impact: Older women with functional limitations should be informed that they may not benefit from screening mammography., (©2021 American Association for Cancer Research.)

Background and Aims: The optimal time interval for diagnostic colonoscopy completion after an abnormal stool-based colorectal cancer (CRC) screening test is uncertain. We examined the association between time to colonoscopy and CRC outcomes among individuals who underwent diagnostic colonoscopy after abnormal stool-based screening., Methods: We performed a retrospective cohort study of veterans age 50 to 75 years with an abnormal fecal occult blood test (FOBT) or fecal immunochemical test (FIT) between 1999 and 2010. We used multivariable Cox proportional hazards to generate CRC-specific incidence and mortality hazard ratios (HRs) and 95% confidence intervals (CI) for 3-month colonoscopy intervals, with 1 to 3 months as the reference group. Association of time to colonoscopy with late-stage CRC diagnosis was also examined., Results: Our cohort included 204,733 patients. Mean age was 61 years (SD 6.9). Compared with patients who received a colonoscopy at 1 to 3 months, there was an increased CRC risk for patients who received a colonoscopy at 13 to 15 months (HR 1.13; 95% CI 1.00-1.27), 16 to 18 months (HR 1.25; 95% CI 1.10-1.43), 19 to 21 months (HR 1.28; 95% CI: 1.11-1.48), and 22 to 24 months (HR 1.26; 95% CI 1.07-1.47). Compared with patients who received a colonoscopy at 1 to 3 months, mortality risk was higher in groups who received a colonoscopy at 19 to 21 months (HR 1.52; 95% CI 1.51-1.99) and 22 to 24 months (HR 1.39; 95% CI 1.03-1.88). Odds for late-stage CRC increased at 16 months., Conclusions: Increased time to colonoscopy is associated with higher risk of CRC incidence, death, and late-stage CRC after abnormal FIT/FOBT. Interventions to improve CRC outcomes should emphasize diagnostic follow-up within 1 year of an abnormal FIT/FOBT result., (Published by Elsevier Inc.)

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., (Published by Elsevier Inc.)

Rising trends in the incidence and mortality of early-onset colorectal cancer (CRC) in those who are younger than 50 years have been well established. These trends have spurred intense investigation focused on elucidating the epidemiology and characteristics of early-onset CRC, as well as on identifying strategies for early detection and prevention. In this review, we provide a contemporary update on early-onset CRC with a particular focus on epidemiology, molecular characterization, red flag signs and symptoms, and screening for early-onset CRC., (Copyright © 2021 AGA Institute. All rights reserved.)