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Current guidelines consider endoscopic resection appropriate treatment for malignant colon polyps with negative margins, low-grade histology, and no lymphovascular invasion. While increasing literature demonstrates a worse prognosis for advanced stage right- versus left-sided colon cancers after curative treatment, there is paucity of data regarding prognostic effect of location in patients undergoing endoscopic resection of T1 polyps. We hypothesized the more aggressive biologic behavior observed in advanced right-sided cancers would be similarly represented in malignant polyps, and this location would be associated with lower overall survival.The National Cancer Database was queried for adults with T1NxMx tumors who underwent endoscopic polypectomy (2004-2017). Patients with positive margins or without follow-up information were excluded.A total of 2,337 patients met inclusion criteria; 22% had right-sided polyps. Endoscopically excised proximal tumors were more common in elderly, and those with public insurance and more comorbidities (all P.01). Among patients with complete pathologic data, there were no statistical differences between right- and left-sided polyps with 1 cm median size,92% without lymphovascular invasion, and 100% without tumor deposits. Univariate analysis showed 73% vs 86% 5-year overall survival for right versus left polyps (P.01). After adjustment for available confounders, right-sided location remained significantly associated with worse overall survival (hazard ratio 1.49, 95% confidence interval 1.21-1.83).In this national cohort of patients with endoscopically excised malignant polyps, we identified right colon location as an independent prognostic factor associated with increased risk of mortality. Our data suggest polyp location should be taken into consideration when making clinical decisions regarding treatment and/or surveillance.

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality among patients with inflammatory bowel disease (IBD). However, data on national trends remain limited.To assess national trends in VTE-associated hospitalisations among patients with IBD as well as risk factors for, and mortality associated with, these events METHODS: Using the U.S. Nationwide Inpatient Sample from 2000-2018, temporal trends in VTE were assessed using the National Cancer Institute's Joinpoint Regression Program with estimates presented as the average annual percent change (AAPC) with 95% confidence intervals (CIs).Between 2000 and 2018, there were 4,859,728 hospitalisations among patients with IBD, with 128,236 (2.6%) having a VTE, and 6352 associated deaths. The rate of VTE among hospitalised patients with IBD increased from 192 to 295 cases per 10,000 hospitalisations (AAPC 2.4%, 95%CI 1.4%, 3.4%, p 0.001), and remained significant when stratified by ulcerative colitis (UC) and Crohn's disease as well as by deep vein thrombosis and pulmonary embolism. On multivariable analysis, increasing age, male sex, UC (aOR: 1.30, 95%CI 1.26, 1.33), identifying as non-Hispanic Black, and chronic corticosteroid use (aOR: 1.22, 95%CI 1.16, 1.29) were associated with an increased risk of a VTE-associated hospitalisation.Rates of VTE-associated hospitalisations are increasing among patients with IBD. Continued efforts need to be placed on education and risk reduction.

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Perspective on this Article from Effects of Vitamin D and Calcium Supplementation on Markers of Apoptosis in Normal Colon Mucosa: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Supplementary Appendix 1 from Effects of Vitamin D and Calcium Supplementation on Markers of Apoptosis in Normal Colon Mucosa: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Supplementary Table 2. Odds ratios and 95% confidence intervals for individual-level factors controlled for in the original and sensitivity-adjusted multivariate regression models for the 60-day and 6-month follow-up outcomes.

Supplementary Material 2. Organizational structure and process survey details

Background: This study assessed the contribution of organizational structures and processes identified from facility surveys to follow-up for positive fecal occult blood tests [FOBT-positive (FOBT+)].Methods: We identified 74,104 patients with FOBT+ results from 98 Veterans Health Administration (VHA) facilities between August 16, 2009 and March 20, 2011, and followed them until September 30, 2011, for completion of colonoscopy. We identified patient characteristics from VHA administrative records, and organizational factors from facility surveys completed by primary care and gastroenterology chiefs. We estimated predictors of colonoscopy completion within 60 days and six months using hierarchical logistic regression models.Results: Thirty percent of patients with FOBT+ results received colonoscopy within 60 days and 49% within six months. Having gastroenterology or laboratory staff notify gastroenterology providers directly about FOBT+ cases was a significant predictor of 60-day [odds ratio (OR), 1.85; P = 0.01] and six-month follow-up (OR, 1.25; P = 0.008). Additional predictors of 60-day follow-up included adequacy of colonoscopy appointment availability (OR, 1.43; P = 0.01) and frequent individual feedback to primary care providers about FOBT+ referral timeliness (OR, 1.79; P = 0.04). Additional predictors of six-month follow-up included using guideline-concordant surveillance intervals for low-risk adenomas (OR, 1.57; P = 0.01) and using group appointments and combined verbal–written methods for colonoscopy preparation instruction (OR, 1.48; P = 0.0001).Conclusion: Directly notifying gastroenterology providers about FOBT+ results, using guideline-concordant adenoma surveillance intervals, and using colonoscopy preparations instruction methods that provide both verbal and written information may increase overall follow-up rates. Enhancing follow-up within 60 days may require increased colonoscopy capacity and feedback to primary care providers.Impact: These findings may inform organizational-level interventions to improve FOBT+ follow-up. Cancer Epidemiol Biomarkers Prev; 24(2); 422–34. ©2014 AACR.

Supplementary Material 3. Codes used to identify colonoscopy procedures

Supplementary Material 4. Methods used to identify and adjust for reasons for not completing a colonoscopy.

Supplementary Material 1. Codes used to identify FOBT procedures

Supplementary Table 1. Bivariate odds ratios and follow-up percentage estimates used for model building

Supplementary Figures 1-4 from A Randomized Clinical Trial of the Effects of Supplemental Calcium and Vitamin D3 on Markers of Their Metabolism in Normal Mucosa of Colorectal Adenoma Patients

Supplementary References from A Randomized Clinical Trial of the Effects of Supplemental Calcium and Vitamin D3 on Markers of Their Metabolism in Normal Mucosa of Colorectal Adenoma Patients

In cancer cell lines and rodent models, calcium and vitamin D favorably modulate cell proliferation, differentiation, and apoptosis in colonic epithelia. These effects may be modulated by local expression of the calcium receptor (CaR), the vitamin D receptor (VDR), and the P450 cytochromes, CYP27B1 and CYP24A1; however, they have yet to be investigated in humans. To address this gap, we conducted a randomized, double-blinded, placebo-controlled 2 × 2 factorial clinical trial. Patients with at least one pathology-confirmed colorectal adenoma were treated with 2 g/d elemental calcium and/or 800 IU/d vitamin D3 versus placebo over 6 months (n = 92; 23 per group). CaR, VDR, CYP27B1, and CYP24A1 expression and distribution in biopsies of normal appearing rectal mucosa were detected by standardized, automated immunohistochemistry and quantified by image analysis. In the calcium-supplemented group, CaR expression increased 27% (P = 0.03) and CYP24A1 expression decreased 21% (P = 0.79). In the vitamin D3-supplemented group, CaR expression increased 39% (P = 0.01) and CYP27B1 expression increased 159% (P = 0.06). In patients supplemented with both calcium and vitamin D3, VDR expression increased 19% (P = 0.13) and CaR expression increased 24% (P = 0.05). These results provide mechanistic support for further investigation of calcium and vitamin D3 as chemopreventive agents against colorectal neoplasms, and CaR, VDR, CYP27B1, and CYP24A1 as modifiable, preneoplastic risk biomarkers for colorectal neoplasms. Cancer Res; 71(2); 413–23. ©2010 AACR.

Supplementary Figure Legends 1-4 from A Randomized Clinical Trial of the Effects of Supplemental Calcium and Vitamin D3 on Markers of Their Metabolism in Normal Mucosa of Colorectal Adenoma Patients

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

This document is a focused update to the 2017 colorectal cancer (CRC) screening recommendations from the U.S. Multi-Society Task Force on Colorectal Cancer, which represents the American College of Gastroenterology, the American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy. This update is restricted to addressing the age to start and stop CRC screening in average-risk individuals and the recommended screening modalities. Although there is no literature demonstrating that CRC screening in individuals under age 50 improves health outcomes such as CRC incidence or CRC-related mortality, sufficient data support the U.S. Multi-Society Task Force to suggest average-risk CRC screening begin at age 45. This recommendation is based on the increasing disease burden among individuals under age 50, emerging data that the prevalence of advanced colorectal neoplasia in individuals ages 45 to 49 approaches rates in individuals 50 to 59, and modeling studies that demonstrate the benefits of screening outweigh the potential harms and costs. For individuals ages 76 to 85, the decision to start or continue screening should be individualized and based on prior screening history, life expectancy, CRC risk, and personal preference. Screening is not recommended after age 85.

Purpose of review Diverticulosis leads to significant morbidity and mortality and is increasing in prevalence worldwide. In this paper, we review the clinical features, diagnosis, and management of diverticular disorders, followed by a discussion of recent updates and changes in the clinical approach to diverticular disease. Recent findings Recent literature suggests that antibiotics are likely not necessary for low-risk patients with acute uncomplicated diverticulitis, and not all patients with recurrent diverticulitis require colectomy. Dietary restrictions do not prevent recurrent diverticulitis. Visceral hypersensitivity is increasingly being recognized as a cause of persistent abdominal pain after acute diverticulitis and should be considered along with chronic smoldering diverticulitis, segmental colitis associated with diverticula, and symptomatic uncomplicated diverticular disease. Summary Clinicians should be aware that traditionally held assumptions regarding the prevention and management of diverticular disorders have recently been called into question and should adjust their clinical practice accordingly.

Recent randomized controlled trials (RCTs) and meta-analysis have demonstrated improved adenoma detection rate (ADR) for colonoscopy with artificial intelligence (AI) compared with high-definition (HD) colonoscopy without AI. We aimed to perform a systematic review and network meta-analysis of all RCTs to assess the impact of AI compared with other endoscopic interventions aimed at increasing ADR such as distal attachment devices, dye-based/virtual chromoendoscopy, water-based techniques, and balloon-assisted devices.A comprehensive literature search of PubMed/Medline, Embase, and Cochrane was performed through May 6, 2022, to include RCTs comparing ADR for any endoscopic intervention mentioned above. Network meta-analysis was conducted using a frequentist approach and random effects model. Relative risk (RR) and 95% CI were calculated for proportional outcome.A total of 94 RCTs with 61,172 patients (mean age 59.1±5.2 y, females 45.8%) and 20 discrete study interventions were included. Network meta-analysis demonstrated significantly improved ADR for AI compared with autofluorescence imaging (RR: 1.33, CI: 1.06 to 1.66), dye-based chromoendoscopy (RR: 1.22, CI: 1.06 to 1.40), endocap (RR: 1.32, CI: 1.17 to 1.50), endocuff (RR: 1.19, CI: 1.04 to 1.35), endocuff vision (RR: 1.26, CI: 1.13 to 1.41), endoring (RR: 1.30, CI: 1.10 to 1.52), flexible spectral imaging color enhancement (RR: 1.26, CI: 1.09 to 1.46), full-spectrum endoscopy (RR: 1.40, CI: 1.19 to 1.65), HD (RR: 1.41, CI: 1.28 to 1.54), linked color imaging (RR: 1.21, CI: 1.08 to 1.36), narrow band imaging (RR: 1.33, CI: 1.18 to 1.48), water exchange (RR: 1.22, CI: 1.06 to 1.42), and water immersion (RR: 1.47, CI: 1.19 to 1.82).AI demonstrated significantly improved ADR when compared with most endoscopic interventions. Future RCTs directly assessing these associations are encouraged.

Summary Esophageal adenocarcinoma (EAC) develops in a step-wise manner, from low-grade dysplasia (LGD) to high-grade dysplasia (HGD), and ultimately to invasive EAC. However, there remains diagnostic uncertainty about LGD and its risk of progression to HGD/EAC. The aim is to investigate the role of Ki-67, immune-histochemical marker of proliferation, surface expression in patients with confirmed LGD, and risk stratify progression to HGD/EAC. A retrospective cohort study was conducted. Patients with confirmed LGD and indefinite for dysplasia (IND), with a mean follow-up of ≥1 year, were included. Pathology specimens were stained for Ki-67 and analyzed for evidence of surface expression. Our results reveal that 29% of patients with confirmed LGD who stained positive with Ki-67 progressed to HGD/EAC as opposed to none (0%) of the patients who stained negative, a statistically significant result (P = 0.003). Similarly, specimens from patients with IND were stained and analyzed revealing a nonsignificant trend toward a higher rate of progression for Ki-67 positive cases versus Ki-67 negative, 30% versus 21%, respectively. Ki-67 expression by itself can identify patients with LGD at a high risk of progression.

Description The purpose of this expert review is to describe the role of medications for the chemoprevention of colorectal neoplasia. Neoplasia is defined as precancerous lesions (e.g., adenoma and sessile serrated lesion) or cancer. The scope of this review excludes dietary factors and high-risk individuals with hereditary syndromes or inflammatory bowel disease. Methods The best practice advice statements are based on a review of the literature to provide practical advice. A formal systematic review and rating of the quality of evidence or strength of recommendation were not performed. Best Practice Advice 1 In individuals at average risk for CRC who are (1) younger than 70 years with a life expectancy of at least 10 years, (2) have a 10-year cardiovascular disease risk of at least 10%, and (3) not at high risk for bleeding, clinicians should use low-dose aspirin to reduce CRC incidence and mortality. Best Practice Advice 2 In individuals with a history of CRC, clinicians should consider using aspirin to prevent recurrent colorectal neoplasia. Best Practice Advice 3 In individuals at average risk for CRC, clinicians should not use non-aspirin NSAIDs to prevent colorectal neoplasia because of a substantial risk of cardiovascular and gastrointestinal adverse events. Best Practice Advice 4 In individuals with type 2 diabetes, clinicians may consider using metformin to prevent colorectal neoplasia. Best Practice Advice 5 In individuals with CRC and type 2 diabetes, clinicians may consider using metformin to reduce mortality. Best Practice Advice 6 Clinicians should not use calcium or vitamin D (alone or together) to prevent colorectal neoplasia. Best Practice Advice 7 Clinicians should not use folic acid to prevent colorectal neoplasia. Best Practice Advice 8 In individuals at average risk for CRC, clinicians should not use statins to prevent colorectal neoplasia. Best Practice Advice 9 In individuals with a history of CRC, clinicians should not use statins to reduce mortality.

Introduction: Clostridiodes difficile infection is the leading cause of infectious diarrhea in the United States, with substantial morbidity and mortality. Recurrent infection is especially challenging, with each recurrence increasing the likelihood of a successive recurrence, leading to cycles of prolonged symptoms, frequent antimicrobial use, and decreased quality of life. Fecal microbiota transplantation to prevent recurrent infection is a promising intervention with a large effect size in observational studies, but with conflicting results from randomized controlled trials. We are conducting a Veterans Affairs-wide randomized controlled trial utilizing centralized case identification, with enrollment and fecal microbiota transplant administration occurring at the participant’s home. This type of trial design significantly improves trial efficiency, greatly decreases trial cost, increases consistency of trial administration, and most importantly makes nationwide clinical trials in less-common diseases possible. Methods: This is a randomized comparison of capsule-delivered fecal microbiota transplant for the prevention of recurrent Clostridiodes difficile infection, administered after successful initial treatment of recurrent C. difficile infection with standard therapy. The primary endpoint is the incidence of recurrent C. difficile infection or death. Cases are identified by searching the Veterans Affairs Corporate Data Warehouse, with central study coordinators then reaching out to potential participants. Individuals meeting inclusion criteria and interested in participation are scheduled for in-home consent, randomization, and capsule administration, followed by telephone follow-up for 6 months. To mitigate risks of COVID-19, enrollment via video visits has been implemented. Results: A total of 102 participants have been enrolled through January 2021. Centralized case identification and in-home enrollment has facilitated enrollment from 34 unique states, with 38% being from rural or highly rural areas. Discussion: Centralized case identification and in-home enrollment is a feasible and innovative method of conducting randomized controlled trials in the Veterans Affairs system, improving access to clinical research for populations who may have difficulty engaging with the traditional model of clinical trials where enrollment is based at large hospitals in major metropolitan areas.