Patient Decisions Regarding Rescheduling Colonoscopies Postponed Due to the COVID-19 Pandemic.

BACKGROUND: Due to the COVID-19 pandemic, elective colonoscopies were postponed in Ohio from 3/17/2020 to 5/1/2020. When the ban was lifted, canceled patients determined whether to reschedule their colonoscopy in the midst of the ongoing pandemic. AIMS: We aim to determine whether demographic, colorectal cancer (CRC) risk, and COVID-19 morbidity and mortality risk factors are associated with rescheduling of colonoscopies canceled by the COVID-19 pandemic. METHODS: A medical record review of 420 participants ages 40-74 at a midwestern academic health system with elective colonoscopies canceled from 3/17/2020 to 5/1/2020 due to the COVID-19 pandemic was performed. RESULTS: More than half of participants (71.0%) rescheduled their colonoscopy within the next 8 months. Indication for colonoscopy being 'surveillance following adenoma', colonoscopy ordered by primary care provider rather than gastroenterologist, and dyslipidemia were independently associated with rescheduling colonoscopy. Higher body mass index, indication for colonoscopy being simply 'screening for CRC,' and stool testing were associated with not rescheduling. Diagnoses associated with colorectal cancer risk such as adenomas, personal or family history of colorectal cancer, and inflammatory bowel disease were not associated with rescheduling, nor were other comorbidities associated with increased COVID-19 severity. 4.5% (19/420) opted for stool fecal immunochemical test or Cologuard testing. CONCLUSIONS: Most patients rescheduled their colonoscopy despite the risk of virus exposure, suggesting that concern of missed colorectal cancer diagnosis outweighed coronavirus concerns. Patient trust in referring providers may be important for rescheduling, and colonoscopy indications were independently associated with rescheduling status.

Potential role of fructose on human colon DNA methylation in racial disparities observed for colorectal cancer risk.

Background and aims: An increasing body of observational studies has linked fructose intake to colorectal cancer (CRC). African Americans (AAs) are significantly more likely than European Americans to consume greater quantities of fructose and to develop right-side colon cancer. Yet, a mechanistic link between these two associations remains poorly defined. We aimed to identify differentially methylated regions (DMRs) associated with dietary fructose consumption measures obtained from food frequency questionnaires in a cohort of normal colon biopsies derived from AA men and women (n=79). Methods: DNA methylation data from this study was obtained using the Illumina Infinium MethylationEPIC kit and is housed under accession GSE151732. DMR analysis was carried out using DMRcate in right and matched left colon, separately. Secondary analysis of CRC tumors was carried out using data derived from TCGA-COAD, GSE101764 and GSE193535. Differential expression analysis was carried out on CRC tumors from TCGA-COAD using DESeq2 . Results: We identified 4,263 right-side fructose-DMRs. In contrast, only 24 DMRs survived multiple testing corrections (FDR<0.05) in matched, left colon. To identify targets by which dietary fructose drives CRC risk, we overlaid these findings with data from three CRC tumor datasets. Remarkably, almost 50% of right-side fructose-DMRs overlapped regions associated with CRC in at least one of three datasets. TNXB and CDX2 ranked among the most significant fructose risk DMRs in right and left colon respectively that also displayed altered gene expression in CRC tumors. Conclusions: Our mechanistic data support the notion that fructose has a greater CRC-related effect in right than left AA colon, alluding to a potential role for fructose in contributing to racial disparities in CRC.

Cancer burden in women with HIV on Medicaid: A nationwide analysis.

BACKGROUND: Cancer is the leading cause of death in people living with HIV. In the United States, nearly 1 in 4 people living with HIV are women, more than half of whom rely on Medicaid for healthcare coverage. OBJECTIVE: The objective of this study is to evaluate the cancer burden of women living with HIV on Medicaid. DESIGN: We conducted a cross-sectional study of women 18-64 years of age enrolled in Medicaid during 2012, using data from Medicaid Analytic eXtract files. METHODS: Using International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes, we identified women living with HIV (n = 72,508) and women without HIV (n = 17,353,963), flagging the presence of 15 types of cancer and differentiating between AIDS-defining cancers and non-AIDS-defining cancers. We obtained adjusted prevalence ratios and 95% confidence intervals for each cancer and for all cancers combined, using multivariable log-binomial models, and additionally stratifying by age and race/ethnicity. RESULTS: The highest adjusted prevalence ratios were observed for Kaposi's sarcoma (81.79 (95% confidence interval: 57.11-117.22)) and non-Hodgkin's lymphoma (27.69 (21.67-35.39)). The adjusted prevalence ratios for anal and cervical cancer, both of which were human papillomavirus-associated cancers, were 19.31 (17.33-21.51) and 4.20 (3.90-4.52), respectively. Among women living with HIV, the adjusted prevalence ratio for all cancer types combined was about two-fold higher (1.99 (1.86-2.14)) in women 45-64 years of age than in women 18-44 years of age. For non-AIDS-defining cancers but not for AIDS-defining cancers, the adjusted prevalence ratios were higher in older than in younger women. There was no significant difference in the adjusted prevalence ratios for all cancer types combined in the race/ethnicity-stratified analyses of the women living with HIV cohort. However, in cancer type-specific sub-analyses, differences in adjusted prevalence ratios between Hispanic versus non-Hispanic women were observed. For example, the adjusted prevalence ratio for Hispanic women for non-Hodgkin's lymphoma was 2.00 (1.30-3.07) and 0.73 (0.58-0.92), respectively, for breast cancer. CONCLUSION: Compared to their counterparts without HIV, women living with HIV on Medicaid have excess prevalence of cervical and anal cancers, both of which are human papillomavirus related, as well as Kaposi's sarcoma and lymphoma. Older age is also associated with increased burden of non-AIDS-defining cancers in women living with HIV. Our findings emphasize the need for not only cancer screening among women living with HIV but also for efforts to increase human papillomavirus vaccination among all eligible individuals.

Receipt of Targeted Therapy and Survival Outcomes in Patients With Metastatic Colorectal Cancer.

Importance: Professional society guidelines recommend treating patients with metastatic colorectal cancer with targeted therapies, including epithelial growth factor receptor (EGFR) inhibitors and vascular endothelial growth factor (VEGF) inhibitors, depending on the presence or absence of certain mutations. Since most studies of first-line targeted therapies have been limited by sample size, there is a need for larger studies using data from routine clinical care. Objectives: To identify factors associated with receipt of first-line targeted therapies among patients with metastatic colorectal cancer for whom RAS or BRAF mutation data in the tumor were available and investigate whether targeted therapy is associated with survival. Design, Setting, and Participants: This cohort study used deidentified data from an electronic health record-derived database to include patients from 800 sites of patient care across the US who were diagnosed with de novo metastatic colorectal cancer between January 1, 2013, and March 31, 2020 (n = 9134). Main Outcomes and Measures: Receipt of first-line targeted therapy, categorized as ever having received EGFR inhibitors, VEGF inhibitors, or neither. The secondary outcome was overall survival. Results: The study population included 9134 patients. The median age at diagnosis was 62 years (IQR, 53-71 years), 5019 (54.9%) were male, and 5692 (62.3%) were White. The median follow-up period was 15 months. Overall, 713 patients (7.8%) received EGFR inhibitors and 5081 patients (55.6%) received VEGF inhibitors as part of their first-line treatment. Among patients with RAS wild-type (RAS-WT) tumors, 625 patients (15.5%) received EGFR inhibitors and 2053 patients (50.9%) received VEGF inhibitors. In patients with RAS mutant (RAS-Mut) tumors, 50 patients (1.1%) received EGFR inhibitors and 2682 patients (59.7%) received VEGF inhibitors; among those with BRAF-mutant (BRAF-Mut) tumors, 38 patients (6.3%) received EGFR inhibitors and 346 patients (57.2%) received VEGF inhibitors. More than one-third of the patients (36.6%) received neither EGFR inhibitors nor VEGF inhibitors. Compared with patients younger than age 40 years, those aged 80 years or older had significantly lower odds to receive targeted therapies (EGFR or VEGF inhibitors in patients with RAS-WT tumors: adjusted odds ratio [aOR], 0.53; 95% CI, 0.36-0.79; and VEGF inhibitors in patients with RAS-Mut tumors: aOR, 0.62; 95% CI, 0.42-0.90). Improved survival was associated with EGFR inhibitor therapy in patients with RAS-WT tumors (adjusted hazard ratio [aHR], 0.85; 95% CI, 0.74-0.98). Unlike in clinical trials, however, no survival benefit was noted with use of VEGF inhibitors among patients with RAS-WT (aHR, 1.00; 95% CI, 0.91-1.11) or RAS-Mut (aHR, 1.01; 95% CI, 0.93-1.10) tumors. Conclusions and Relevance: The findings of this study showed mixed results on survival benefits associated with targeted therapy. In addition, given that some of the results differed from those of randomized clinical trials, this study highlights the importance of using data originating from routine clinical care.

Fecal Microbiome Associated with Both Colon Adenomas and Lifetime Colorectal Cancer Risk.

BACKGROUND: Increasing data indicates the gut flora including bacteria and fungi combined with environmental factors are important in the pathogenesis of colorectal cancer (CRC). Understanding differences in the microbiome in patients with colon neoplasia will foster the development of biomarkers for early detection. AIMS: Determine the association of microbiome with presence of adenomas and predicted CRC risk. METHODS: In subjects referred for colonoscopy, the NCI CRC risk assessment tool was completed and stool for microbiome analysis as well as fecal immunochemical test (FIT) were collected. We calculated the microbiome alpha diversity using the Shannon index as well as individual bacterial and fungal species. RESULTS: Among 34 patients, we identified 10 with one or more adenomas. Only 2 patients were FIT positive. The median predicted lifetime CRC risk was 2.75% and the prevalence of adenoma was higher in the fourth quartile (P < 0.001). The measured alpha diversity was somewhat higher in patients with adenomas (P = 0.07). We identified 4 bacterial species with an increased relative abundance among patients with adenomas [P < 0.5]. Lifetime CRC risk was associated with 2 specific bacterial species, P. distasonis & E. hermannii [P = 0.05 & 0.09, respectively]. No associations were seen with fungal species and adenoma prevalence or lifetime CRC risk. CONCLUSIONS: In addition to a strong correlation of predicted CRC risk and adenoma prevalence, we also found important differences in specific bacterial species and both adenoma prevalence and CRC risk. Larger trials are needed to potentially implement further data in the clinical setting.

Post-Affordable Care Act Improvements in Cancer Stage Among Ohio Medicaid Beneficiaries Resulted From an Increase in Stable Coverage.

BACKGROUND: The mechanisms underlying improvements in early-stage cancer at diagnosis following Medicaid expansion remain unknown. We hypothesized that Medicaid expansion allowed for low-income adults to enroll in Medicaid before cancer diagnosis, thus increasing the number of stably-enrolled relative to those who enroll in Medicaid only after diagnosis (emergently-enrolled). METHODS: Using data from the 2011-2017 Ohio Cancer Incidence Surveillance System and Medicaid enrollment files, we identified individuals diagnosed with incident invasive breast (n=4850), cervical (n=1023), and colorectal (n=3363) cancer. We conducted causal mediation analysis to estimate the direct effect of pre- (vs. post-) expansion on being diagnosed with early-stage (-vs. regional-stage and distant-stage) disease, and indirect (mediation) effect through being in the stably- (vs. emergently-) enrolled group, controlling for individual-level and area-level characteristics. RESULTS: The percentage of stably-enrolled patients increased from 63.3% to 73.9% post-expansion, while that of the emergently-enrolled decreased from 36.7% to 26.1%. The percentage of patients with early-stage diagnosis remained 1.3-2.9 times higher among the stably-than the emergently-enrolled group, both pre-expansion and post-expansion. Results from the causal mediation analysis showed that there was an indirect effect of Medicaid expansion through being in the stably- (vs. emergently-) enrolled group [risk ratios with 95% confidence interval: 1.018 (1.010-1.027) for breast cancer, 1.115 (1.064-1.167) for cervical cancer, and 1.090 (1.062-1.118) for colorectal cancer. CONCLUSION: We provide the first evidence that post-expansion improvements in cancer stage were caused by an increased reliance on Medicaid as a source of stable insurance coverage.

Medicaid Expansion Associated With Reduction in Geospatial Breast Cancer Stage at Diagnosis Disparities.

CONTEXT: Prior studies demonstrate that Medicaid expansion has been associated with earlier-stage breast cancer diagnosis among women with low income, likely through increased access to cancer screening services. However, how this policy change has impacted geospatial disparities in breast cancer stage at diagnosis is unclear. OBJECTIVE: To examine whether there were reductions in geospatial disparities in advanced stage breast cancer at diagnosis in Ohio after Medicaid expansion. DESIGN: The study included 33 537 women aged 40 to 64 years diagnosed with invasive breast cancer from the Ohio Cancer Incidence Surveillance System between 2010 and 2017. The space-time scan statistic was used to detect clusters of advanced stage at diagnosis before and after Medicaid expansion. Block group variables from the Census were used to describe the contextual characteristics of detected clusters. RESULTS: The percentage of local stage diagnosis among women with breast cancer increased from 60.2% in the pre-expansion period (2010-2013) to 62.6% in the post-expansion period (2014-2017), while the uninsured rate among those women decreased from 13.7% to 7.5% during the same period. Two statistically significant ( P < .05) and 6 nonsignificant spatial clusters ( P > .05) of advanced stage breast cancer cases were found in the pre-expansion period, while none were found in the post-expansion period. These clusters were in the 4 largest metropolitan areas in Ohio, and individuals inside the clusters were more likely to be disadvantaged along numerous socioeconomic factors. CONCLUSIONS: Medicaid expansion has played an important role in reducing geospatial disparities in breast cancer stage at diagnosis, likely through the reduction of advanced stage disease among women living in socioeconomically disadvantaged communities.

Excess cancer prevalence in men with HIV: A nationwide analysis of Medicaid data.

BACKGROUND: Cancer is one of the most common comorbidities in men living with HIV (MLWH). However, little is known about the MLWH subgroups with the highest cancer burden to which cancer prevention efforts should be targeted. Because Medicaid is the most important source of insurance for MLWH, we evaluated the excess cancer prevalence in MLWH on Medicaid relative to their non-HIV counterparts. METHODS: In this cross-sectional study using 2012 Medicaid Analytic eXtract data nationwide, we flagged the presence of HIV, 13 types of cancer, symptomatic HIV, and viral coinfections using codes from the International Classification of Diseases, Ninth Revision, Clinical Modification. The study population included individuals administratively noted to be of male sex (men), aged 18 to 64 years, with (n = 82,495) or without (n = 7,302,523) HIV. We developed log-binomial models with cancer as the outcome stratified by symptomatic status, age, and race/ethnicity. RESULTS: Cancer prevalence was higher in MLWH than in men without HIV (adjusted prevalence ratio [APR], 1.84; 95% confidence interval [CI], 1.78-1.90) and was higher among those with symptomatic HIV (APR, 2.74; 95% CI, 2.52-2.97) than among those with asymptomatic HIV (APR, 1.73; 95% CI, 1.67-1.79). The highest APRs were observed for anal cancer in younger men, both in the symptomatic and asymptomatic groups: APR, 312.97; 95% CI, 210.27-465.84, and APR, 482.26; 95% CI, 390.67-595.32, respectively. In race/ethnicity strata, the highest APRs were among Hispanic men for anal cancer (APR, 198.53; 95% CI, 144.54-272.68) and for lymphoma (APR, 9.10; 95% CI, 7.80-10.63). CONCLUSIONS: Given the Medicaid program's role in insuring MLWH, the current findings highlight the importance of the program's efforts to promote healthy behaviors and vaccination against human papillomavirus in all children and adolescents and to provide individualized cancer screening for MLWH.

Rates of Intestinal Resection and Colectomy in Inflammatory Bowel Disease Patients After Initiation of Biologics: A Cohort Study.

BACKGROUND & AIMS: 50% to 80% Crohn's disease (CD) and 10% to 30% ulcerative colitis (UC) patients require surgery over their lifetime. Biologic therapies may alter this natural history, but data on the effect of biologics on surgery rates in this patient population are mixed. We sought to investigate the influence of biologics on surgery prevalence in CD and UC. METHODS: We used a commercial database (Explorys Inc, Cleveland, OH), which includes electronic health record data from 26 major integrated US healthcare systems. We identified all patients who were diagnosed with CD or UC that were treated with any biologics between 2015 and 2020. The primary outcome was to examine the association between biologics therapy and the prevalence of bowel resection. Also, we identified the factors associated with surgery in IBD patients on biologics. RESULTS: Of 32,904,480 patients in the database, we identified 140,540 patients with CD and 115,260 patients with UC, of whom 25,840 (18%) and 9,050 (7.8%) patients received biologics, respectively. The prevalence of intestinal resection was significantly lower in biologics-treated CD patients (9.3%) compared to those who did not receive biologics (12.1%) (p < .001). Similarly, biologic-treated UC patients were significantly less likely to undergo colectomy (7.3%) compared to UC patients who did not receive biologic therapy (11.0%) (p < .001). Tobacco use, Clostridium difficile infection, and perianal disease were associated with intestinal resection in CD. Colon neoplasm and Clostridium difficile infection were associated with colectomy in UC. CONCLUSIONS: In this study of a large healthcare administrative database, inflammatory bowel disease (IBD) patients treated with biologics were significantly less likely to undergo bowel resection when compared to those who never received biologics. This data suggests that biologics may impact surgical rates in IBD.

Receipt of Serial Endoscopy Procedures Prior to Esophageal Adenocarcinoma Diagnosis Is Associated with Better Survival.

BACKGROUND: The poor prognosis of esophageal adenocarcinoma (EAC) has focused efforts on early detection by serial endoscopic surveillance of Barrett's esophagus (BE). Previously, we reported that receipt of endoscopy before EAC diagnosis was associated with improved survival. AIM: We aimed to refine our previous analysis, assessing surveillance as measured by performance of serial endoscopy before EAC diagnosis and evaluating its association with stage and survival. METHODS: A retrospective cohort study was performed using the Surveillance, Epidemiology and End Results-Medicare database. Patients aged ≥ 70 years with EAC diagnosed during 1998-2009 were identified. Diagnosis with BE and receipt of ≥ 2 upper endoscopic procedures within 5 years before cancer diagnosis were identified. We compared a reference group not receiving serial endoscopy to 3 patterns based on ≥ 2 endoscopy dates relative to a timepoint 2 years before cancer diagnosis: "remote," "recent," and "sustained." RESULTS: Among 5532 patients, 28% (n = 1,575) had localized stage. Thirteen percent (n = 703) received ≥ 2 endoscopic procedures before cancer diagnosis: 224, 298, and 181 in the "recent," "remote," and "sustained" groups. Serial endoscopy and prior BE were associated with localized stage ("sustained" group OR 2.95, 95% confidence interval [CI] 2.07, 4.19; prior BE OR 2.68, 95% CI 2.03, 3.56). Serial endoscopy was associated with improved survival even with adjustment for lead time bias ("sustained" group HR 0.45, 95% CI 0.37, 0.55) and length time bias. CONCLUSIONS: Sustained endoscopy was associated with earlier stage and improved survival. These results support the role of sustained surveillance in early detection of EAC.

10-Year Trend of Abdominal Magnetic Resonance Imaging Compared With Abdominal Computed Tomography Scans in Inflammatory Bowel Disease.

BACKGROUND: Patients with inflammatory bowel disease (IBD) frequently undergo multiple computed tomography (CT) examinations. With the widespread availability of magnetic resonance imaging (MRI), it is unclear whether the use of CTs in IBD has declined. We aimed to analyze the trends of CT and MRI use in a large cohort of IBD patients in a 10-year period. METHODS: We retrospectively analyzed adults ≥18 years of age using a de-identified database, IBM Explorys. Patients with ≥1 CT of the abdomen (± pelvis) or MRI of the abdomen (± pelvis) at least 30 days after the diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) were included. We examined the factors associated with patients undergoing multiple CTs (≥5 CTs of the abdomen) and performed a trend analysis from 2010 to 2019. RESULTS: Among 176 110 CD and 143 460 UC patients, those with ≥1 CT of the abdomen annually increased from 2010 to 2019 with mean annual percentage change of +3.6% for CD and +4.9% for UC. Similarly, annual percentage change for patients with ≥1 MRI (CD: +15.6%; UC: +22.8%) showed a rising trend. There was a 3.8% increase in CD patients receiving ≥5 CTs of the abdomen annually compared with a 2.4% increase among UC patients in the 10-year period. Age ≥50 years, men, African Americans, public insurance payors, body mass index ≥30kg/m2, and smoking history were associated with ≥5 CTs. CONCLUSIONS: There is a considerable increase in the number of CT scans performed in IBD patients. Further studies can explore factors influencing the use of CT and MRI of the abdomen in IBD patients.

The proportion of inflammatory bowel disease patients with ≥5 computed tomographies of the abdomen annually has increased by 2.4%-3.8% from 2010 to 2019. Age ≥50 years, men, African Americans, public insurance payors, body mass index ≥30kg/m2, and smoking history were associated with ≥5 computed tomographies of the abdomen annually.

A Race-Specific, DNA Methylation Analysis of Aging in Normal Rectum: Implications for the Biology of Aging and Its Relationship to Rectal Cancer.

Approximately 90% of colorectal cancer (CRC) develop over the age of 50, highlighting the important role of aging in CRC risk. African Americans (AAs) shoulder a greater CRC burden than European Americans (EA) and are more likely to develop CRC at a younger age. The effects of aging in AA and EA normal rectal tissue have yet to be defined. Here, we performed epigenome-wide DNA methylation analysis in the first, large-scale biracial cohort of normal rectum (n = 140 samples). We identified increased epigenetic age acceleration in EA than AA rectum (p = 3.91 × 10-4) using linear regression. We also identified differentially methylated regions (DMRs) associated with chronological aging in AA and EA, separately using DMRcate. Next, a consensus set of regions associated with cancer was identified through DMR analysis of two rectal cancer cohorts. The vast majority of AA DMRs were present in our analysis of aging in rectum of EA subjects, though rates of epigenetic drift were significantly greater in AA (p = 1.94 × 10-45). However, 3.66-fold more DMRs were associated with aging in rectum of EA subjects, many of which were also associated with rectal cancer. Our findings reveal a novel relationship between race, age, DNA methylation and rectal cancer risk that warrants further investigation.

Dietary inflammatory index and risk of colorectal adenoma: effect measure modification by race, nonsteroidal anti-inflammatory drugs, cigarette smoking and body mass index?

PURPOSE: To investigate if the association between dietary inflammatory potential and colorectal adenoma (CRA) is modified by race and factors known to modulate inflammation. METHODS: We examined effect measure modification of race, nonsteroidal anti-inflammatory drugs (NSAIDs), cigarette smoking and body mass index (BMI) on the diet-CRA association by employing energy-adjusted dietary inflammatory index (E-DII™) to characterize dietary inflammatory potential among 587 cases and 1,313 controls participating in a colonoscopy screening-based cross-sectional study of CRA. Participants completed a food frequency questionnaire from which E-DII score was derived. E-DII score was calculated from 34 food parameters (constituents), utilizing an energy-adjusted global comparative database to compute z scores from which centered proportions were summed to create the score. CRA cases were defined as individuals whose colonoscopy detected at least one pathologically confirmed adenomatous polyp. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A pro-inflammatory diet was not statistically significantly associated with elevated CRA risk (OR 1.07; 95% CI 0.97-1.19; p value = 0.18) in the multivariate regression model. NSAIDs use (ORnever-users 1.19; 95% CI 1.03-1.38; ORever-users 0.96; 95% CI 0.83-1.12; Pinteraction = 0.04) and race (ORAfrican Americans 1.22; 95% CI 1.03-1.44; OREuropean Americans 0.99; 95% CI 0.86-1.14; Pinteraction = 0.14) appeared to modify the association, whereas cigarette smoking and BMI did not (Pinteraction = 0.40 and 0.78, respectively). CONCLUSION: NSAIDs use and race may modify the diet-CRA association. Further investigation in prospective cohort studies is warranted to confirm these findings.

Barriers to Follow-Up Colonoscopy After Positive FIT or Multitarget Stool DNA Testing.

BACKGROUND: Fecal immunochemical testing (FIT) and multi-target stool DNA testing (mt-sDNA) are recommended colorectal cancer screening options but require follow-up with colonoscopy to determine the source of a positive result. We performed a retrospective analysis in an academic health system to determine adherence to colonoscopy in these patients. METHODS: We identified all patients aged 40 years and older with at least 1 primary care visit who had a positive FIT or mt-sDNA between January 2016 and June 2018. We identified receipt of colonoscopy within 6 months of the positive test and reviewed medical records to determine reasons for lack of colonoscopy. RESULTS: We identified 308 eligible patients with positive FIT and 323 with positive mt-sDNA. Some patients with positive FIT (46.7%) and patients with positive mt-sDNA (71.5%) underwent colonoscopy within 6 months, and time to colonoscopy was also shorter with mt-sDNA (hazard ratio, 1.83; 95% CI, 1.48-2.25). These differences remained in a multivariable model adjusting for patient characteristics. Among patients without colonoscopy after positive FIT, 1 or more system, provider, and patient-related barriers were identified in 32.1%, 57.6%, and 36.3%, respectively. Among patients without colonoscopy after positive mt-sDNA, corresponding frequencies were 30.4%, 43.5%, and 57.6%, respectively. CONCLUSIONS: Follow-up colonoscopy was higher for mt-sDNA than FIT, which could be due in part to preselection by clinicians and/or patients. Among patients who did not follow-up, provider and system factors were as frequently encountered as patient factors. These findings reinforce the need for multi-level interventions to improve follow-up.

Racial Disparities in Epigenetic Aging of the Right vs Left Colon.

There are well-documented racial differences in age-of-onset and laterality of colorectal cancer. Epigenetic age acceleration is postulated to be an underlying factor. However, comparative studies of side-specific colonic tissue epigenetic aging are lacking. Here, we performed DNA methylation analysis of matched right and left biopsies of normal colon from 128 individuals. Among African Americans (n = 88), the right colon showed accelerated epigenetic aging as compared with individual-matched left colon (1.51 years; 95% confidence interval [CI] = 0.62 to 2.40 years; 2-sided P = .001). In contrast, among European Americans (n = 40), the right colon shows remarkable age deceleration (1.93 years; 95% CI = 0.65 to 3.21 years; 2-sided P = .004). Further, epigenome-wide analysis of DNA methylation identifies a unique pattern of hypermethylation in African American right colon. Our study is the first to report such race and side-specific differences in epigenetic aging of normal colon, providing novel insight into the observed younger age-of-onset and relative preponderance of right-side colon neoplasia in African Americans.

Colorectal Cancer, Age, and Obesity-Related Comorbidities: A Large Database Study.

BACKGROUND AND AIMS: The association between obesity and colorectal cancer (CRC) is well established in older individuals, but evidence is limited in the younger population. The study aims to analyze the relationship of obesity and its related comorbidities in early-onset CRC (E-CRC) and compare it to late-onset CRC (L-CRC). METHODS: A retrospective, cross-sectional study was performed on average-risk individuals ≥ 20 years who were active patients in the commercial database, IBM Watson Health Explorys in the last 5 years. Individuals with CRC were compared to those without CRC across different age groups (20-39, 40-49, and 50-74 years). Individuals with CRC diagnosed < 50 years (E-CRC) were compared to those with CRC between 50 and 74 years (L-CRC). Variables included sex, smoking, obese BMI, diabetes mellitus type 2 (DM2), hypertension (HTN), and hyperlipidemia (HLD). Since Explorys aggregates population-level, de-identified data, approval from institutional review board was not required. RESULTS: Among 37,483,140 individuals, 162,150 cases of sporadic CRC were identified. Compared to the general population, obesity and HLD were independent risk factors for CRC across all age groups; DM2, HTN, and smoking were independent risk factors for CRC in men of all age groups and women with L-CRC. Compared to L-CRC, individuals with E-CRC had lower percentages of obesity-related comorbidities. CONCLUSION: In E-CRC, obesity, DM2, HTN, HLD, and smoking are independent risk factors for CRC among men; obesity and HLD are independent risk factors for CRC in women. These subgroups may benefit from a personalized screening approach to detect early-onset CRC.

Epidemiology of Diverticulitis and Prevalence of First-Ever Colorectal Cancer Postdiverticulitis in Adults in the United States: A Population-Based National Study.

BACKGROUND: The incidence of acute diverticulitis is increasing, and previous studies showed a wide range of prevalence of colorectal cancer after diverticulitis. There is a lack of high-quality evidence to support performing colonoscopy after diverticulitis. OBJECTIVE: We aimed to describe the incidence of first-ever diverticulitis and prevalence of first-ever colorectal cancer postdiverticulitis in the United States. DESIGN: This is a retrospective cohort study. SETTINGS: We queried a national database that contains data from 26 major integrated healthcare systems in the United States. PATIENTS: We identified an aggregated patient cohort aged ≥18 years with a diagnosis of first-ever diverticulitis from February 2015 to February 2020, followed by first-ever colorectal cancer diagnosis, at least 1 day after and within 1 year of diverticulitis. MAIN OUTCOME MEASURES: The incidence of first-ever diverticulitis was calculated. The prevalence and OR of first-ever colorectal cancer after diverticulitis were analyzed. RESULTS: Among 31,778,290 individuals, we found the incidence of first-ever acute diverticulitis to be 2.9%. The prevalence of colorectal cancer within 1 year of first-ever acute diverticulitis was 0.57%, whereas the prevalence of colorectal cancer without a history of diverticulitis was 0.31% (OR = 1.8 (95% CI, 1.76-1.86)). The majority (92.3%) of the postdiverticulitis colorectal cancer were diagnosed within the first 6 months. The risk of colorectal cancer postdiverticulitis was higher in women (OR = 1.9), African Americans (OR = 2.0), and adults aged 18 to 65 years (OR = 2.3). LIMITATIONS: We are unable to validate the diagnostic code because patient information in our database is deidentified. CONCLUSIONS: Individuals are twice as likely to be diagnosed with colorectal cancer within 1 year of their first episode of acute diverticulitis compared with individuals without diverticulitis. We advocate for colonoscopy after the first occurrence of acute diverticulitis to screen for colorectal cancer, particularly for patients without a recent colonoscopy. See Video Abstract at http://links.lww.com/DCR/B412.

ANTECEDENTES: La incidencia de diverticulitis aguda está aumentando y los estudios anteriores mostraron una amplia gama de prevalencia de cáncer colorrectal después de diverticulitis. Hay una falta de evidencia de alta calidad para apoyar la realización de una colonoscopia después de la diverticulitis. OBJETIVOS: Nuestro objetivo fue describir la incidencia de la primera diverticulitis y la prevalencia del cáncer colorrectal posterior a la primera diverticulitis en los Estados Unidos.DISEÑO:Este es un estudio de cohorte retrospectivo. AJUSTES: Consultamos una base de datos nacional que contiene datos de 26 sistemas de salud integrados importantes en los Estados Unidos. PACIENTES: Identificamos una cohorte agregada de pacientes mayores de 18 años con un diagnóstico de diverticulitis por primera vez entre febrero de 2015 y febrero de 2020, seguido de un diagnóstico de cáncer colorrectal por primera vez, al menos 1 día después y dentro de 1 año de diverticulitis. PRINCIPALES MEDIDAS DE RESULTADO: Se calculó la incidencia de la primer diverticulitis. Se analizaron la prevalencia y el odds ratio del primer CCR después de la diverticulitis. RESULTADOS: Entre 31,778,290 individuos, encontramos que la incidencia de la primera diverticulitis aguda fue del 2.9%. La prevalencia de cáncer colorrectal dentro de 1 año de la primera diverticulitis aguda fue del 0,57%, mientras que la prevalencia del cáncer colorrectal sin antecedentes de diverticulitis fue del 0,31% (OR 1,8; IC del 95%: 1,76-1,86). La mayoría (92,3%) de los pacientes con cáncer colorrectal posterior a diverticulitis se diagnosticaron dentro de los primeros 6 meses. El riesgo de CCR después de diverticulitis fue mayor en mujeres (OR 1,9), afroamericanos (OR 2,0) y adultos de 18 a 65 años (OR 2,3). LIMITACIONES: No podemos validar el código de diagnóstico debido a que la información del paciente en nuestra base de datos no está identificada. CONCLUSIONES: Las personas tienen el doble de probabilidades de ser diagnosticadas con cáncer colorrectal dentro del primer año de su primer episodio de diverticulitis aguda en comparación con las personas sin diverticulitis. Abogamos por la colonoscopia después de la primera aparición de diverticulitis aguda para detectar cáncer colorrectal, particularmente en pacientes sin una colonoscopia reciente.

Disparities in Colorectal Cancer Screening Practices in a Midwest Urban Safety-Net Healthcare System.

AIMS: Although colorectal cancer screening (CRC) using stool-based test is well-studied, evidence on fecal immunochemical test (FIT) patterns in a safety-net healthcare system utilizing opportunistic screening is limited. We studied the FIT completion rates and adenoma detection rate (ADR) of positive FIT-colonoscopy (FIT-C) in an urban safety-net system. METHODS: We performed a retrospective cross-sectional chart review on individuals ≥ 50 years who underwent CRC screening using FIT or screening colonoscopy, 09/01/2017-08/30/2018. Demographic differences in FIT completion were studied; ADR of FIT-C was compared to that of screening colonoscopy. RESULTS: Among 13,427 individuals with FIT ordered, 7248 (54%) completed the stool test and 230 (48%) followed up a positive FIT with colonoscopy. Increasing age (OR 1.01, CI 1.01-1.02), non-Hispanic Blacks (OR 0.87, CI 0.80-0.95, p = 0.002), current smokers (OR 0.84, CI 0.77-0.92, p < 0.0001), those with Medicaid (OR 0.86, CI 0.77-0.96, p = 0.006), commercial insurance (OR 0.85, CI 0.78-0.94, p = 0.002), CCI score ≥ 3 (OR 0.82, CI 0.74-0.91, p < 0.0001), orders by family medicine providers (OR 0.87, CI 0.81-0.94, p < 0.0001) were associated with lower completion of stool test. Individuals from low median household income cities had lower follow-up of positive FIT, OR 0.43, CI 0.21-0.86, p = 0.017. ADR of FIT-C was higher than that of screening colonoscopy. CONCLUSION: Adherence to CRC screening is low in safety-net systems employing opportunistic screening. Understanding demographic differences may allow providers to formulate targeted strategies in high-risk vulnerable groups.

Epidemiology of Large Bowel Carcinoid Tumors in the USA: A Population-Based National Study.

BACKGROUND AND AIMS: Prior studies have shown that about 90% of all carcinoid tumors occur in the GI tract. However, epidemiological studies of these tumors have been limited by small sample size. Our aim was to obtain a more robust epidemiologic survey of large bowel carcinoids (LBC), using population-based data in order to more accurately identify risk factors for these tumors. METHODS: We used a commercial database (Explorys Inc, Cleveland, OH) which includes electronic health record data from 26 major integrated US healthcare systems. We identified all patients aged 18 and older who were diagnosed with LBC, excluding appendiceal carcinoids, between 1999 and 2018 based on Systematized Nomenclature Of Medicine-Clinical Terms (SNOMED-CT) and evaluated the prevalence of LBC. We also performed univariate analysis to describe age-, race-, and gender-based distributions and to identify potential risk factors. RESULTS: Of the 62,817,650 individuals in the database, 4530 were identified to have LBC with an overall prevalence of 7.21/100,000. Individuals with LBC were more likely to be elderly (age > 65) [OR 2.17, CI 2.05-2.31, p < 0.0001], smokers [OR 3.25; 95% CI 3.00-3.53, p < 0.0001], have a history of alcohol use [OR 3.75; 95% CI 3.52-3.99, p < 0.0001], diabetes mellitus (DM) [OR 4.42; 95% CI 4.14-4.72, p < 0.0001], obesity [OR 1.58; 95% CI 1.43-1.74, p < 0.0001], family history of cancer [OR 8.06; 95% CI 7.47-8.71, p < 0.0001], and personal history of ulcerative colitis [OR 6.93; 95% CI 5.55-8.64, p < 0.0001] or Crohn's disease [OR 6.45; 95% CI 5.24-7.95, p < 0.0001]. The prevalence of LBC was less among Caucasians compared to African-Americans [OR 0.57; 95% CI 0.53-0.61, p < 0.0001]. There was no statistically significant gender-based difference; men versus women [OR 1.02; 95% CI 0.96-1.08, p = 0.47]. The most common presenting symptoms included flushing, diarrhea, nausea, weight loss, and abdominal pain, while the most common GI associations included perforation, obstruction, hemorrhage, intussusception, and volvulus. CONCLUSION: This is the largest epidemiological study evaluating the prevalence of LBC. We estimated the prevalence rate of LBC to be 7.21/100,000. The presence of significant risk factors with the clinical picture suspicious for a LBC should warrant thorough evaluation as these tumors can lead to life-threatening complications. Further studies are needed to better understand the mechanism of association between these risk factors and LBC.