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BACKGROUND: A major health priority is to increase colorectal cancer screening, and colonoscopy has become an increasingly important method of screening. The Medicare program began coverage for colonoscopy for average risk individuals in 2001. OBJECTIVES: We sought to examine whether overall colorectal cancer screening increased over time and whether these increases were a result of increased utilization of all methods or a result of greater use of colonoscopy but reduced use of other methods, whether the enactment of Medicare coverage was associated with an increase in colonoscopy among Medicare enrollees, and whether these trends equally affected subpopulations. METHODS: We used nationally representative data from the 2000 and 2003 National Health Interview Surveys and analyzed data using used chi, difference-in-differences tests, and logistic regression analyses to examine whether screening rates differed between 2000 and 2003. RESULTS: The percentage of individuals being screened for colorectal cancer using any method increased modestly from 2000 to 2003 (3%), with increases a result of increased use of colonoscopy and a reduction in the use of other methods. Increases in colonoscopy use were significant among all populations except the insured, non-Medicare population with low incomes. Among Medicare enrollees with high/middle incomes, colonoscopy use increased 14% from 2000 to 2003 compared with an increase of only 7% among low-income groups, which was a significant difference (P < 0.01). Similarly, among insured, non-Medicare enrollees with high/middle incomes, colonoscopy use increased 11% from 2000 to 2003 compared with an increase of only 4% among low-income groups, which also was a significant difference (P < 0.01). CONCLUSIONS: Colorectal cancer screening utilization increased modestly from 2000 to 2003, with the increases that primarily were the result of increased colonoscopy use. Increases in colonoscopy use, however, were primarily among high/middle income groups. Although Medicare coverage may have indirectly facilitated the increase in colonoscopy, we could not determine that coverage directly increased screening rates. Screening rates remain modest and lower income individuals continue to be screened less. Topics for future research include approaches to facilitating screening among low-income individuals and evaluating the impact of policy coverage decisions. [ABSTRACT FROM AUTHOR]

Li-Fraumeni syndrome (LFS) is a rare autosomal dominant inherited genetic disorder that greatly increases the risk of developing several types of cancer, including young children and young adults. LFS is primarily caused by specific mutations in the tumor suppressor gene TP53. In this study, we successfully generated two human induced pluripotent stem cell (iPSC) lines derived from patients diagnosed with LFS, each carrying a distinct heterozygous mutation in the TP53 gene. These LFS patient-derived iPSC lines exhibited robust expression of key pluripotency markers, demonstrated the capacity to differentiate into all three germ layers (endoderm, mesoderm, and ectoderm), and maintained a normal karyotype. The establishment of these iPSC lines provides a valuable tool for modeling LFS in vitro, enabling researchers to investigate the underlying pathological mechanisms associated with the disease across various cell types and tissues., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JCW is a co-founder and scientific advisory board member of Greenstone Biosciences. The other authors confirm that they do not possess any known competing financial interests or personal relationships that could have influenced the work presented in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Colorectal cancer (CRC) is the third leading cause of cancer mortality in the United States. Familial adenomatous polyposis (FAP) is a hereditary syndrome that raises the risk of developing CRC, with total colectomy as the only effective prevention. Even though FAP is rare (0.5% of all CRC cases), this disease model is well suited for studying the early stages of malignant transformation as patients form many polyps reflective of pre-cancer states. In order to spatially profile and analyze the pre-cancer and tumor microenvironment, we have performed single-cell multiplexed imaging for 52 samples: 12 normal mucosa,16 FAP mucosa,18 FAP polyps, 2 FAP adenocarcinoma, and 4 sporadic colorectal cancer (CRCs) using Co-detection by Indexing (CODEX) imaging platform. The data revealed significant changes in cell type composition occurring in early stage polyps and during the malignant transformation of polyps to CRC. We observe a decrease in CD4+/CD8+ T cell ratio and M1/M2 macrophage ratio along the FAP disease continuum. Advanced dysplastic polyps show a higher population of cancer associated fibroblasts (CAFs), which likely alter the pre-cancer microenvironment. Within polyps and CRCs, we observe strong nuclear expression of beta-catenin and higher number neo-angiogenesis events, unlike FAP mucosa and normal colon counterparts. We identify an increase in cancer stem cells (CSCs) within the glandular crypts of the FAP polyps and also detect Tregs, tumor associated macrophages (TAMs) and vascular endothelial cells supporting CSC survival and proliferation. We detect a potential immunosuppressive microenvironment within the tumor 'nest' of FAP adenocarcinoma samples, where tumor cells tend to segregate and remain distant from the invading immune cells. TAMs were found to infiltrate the tumor area, along with angiogenesis and tumor proliferation. CAFs were found to be enriched near the inflammatory region within polyps and CRCs and may have several roles in supporting tumor growth. Neighborhood analyses between adjacent FAP mucosa and FAP polyps show significant differences in spatial location of cells based on functionality. For example, in FAP mucosa, naive CD4+ T cells alone tend to localize near the fibroblast within the stromal compartment. However, in FAP polyp, CD4+T cells colocalize with the macrophages for T cell activation. Our data are expected to serve as a useful resource for understanding the early stages of neogenesis and the pre-cancer microenvironment, which may benefit early detection, therapeutic intervention and future prevention., Competing Interests: Competing interests MPS is a cofounder and scientific advisor of Crosshair Therapeutics, Exposomics, Filtricine, Fodsel, iollo, InVu Health, January AI, Marble Therapeutics, Mirvie, Next Thought AI, Orange Street Ventures, Personalis, Protos Biologics, Qbio, RTHM, SensOmics. MPS is a scientific advisor of Abbratech, Applied Cognition, Enovone, Jupiter Therapeutics, M3 Helium, Mitrix, Neuvivo, Onza, Sigil Biosciences, TranscribeGlass, WndrHLTH, Yuvan Research. MPS is a cofounder of NiMo Therapeutics. MPS is an investor and scientific advisor of R42 and Swaza. MPS is an investor in Repair Biotechnologies. W.J.G. is a consultant and equity holder for 10x Genomics, Guardant Health, Quantapore and Ultima Genomics, and cofounder of Protillion Biosciences, and is named on patents describing ATAC-seq. EDE is an employee and stockholder of Labcorp Genetics and an advisor and stockholder of Taproot Health, Exir Bio, and ROMTech. The remaining authors declare no competing interests.

Background & Aims: Whether gastric cancer (GC) precursor lesions progress to invasive cancer at similar rates globally remains unknown. We conducted a systematic review and meta-analysis to determine the progression of precursor lesions to GC in countries with low versus medium/high incidence., Methods: We searched relevant databases for studies reporting the progression of endoscopically confirmed precursor lesions to GC. Studies were stratified by low (<6 per 100,000) or medium/high (≥6 per 100,000) GC incidence countries. Random-effects models were used to estimate the progression rates of atrophic gastritis (AG), intestinal metaplasia (IM), and dysplasia to GC per 1000 person-years., Results: Among the 5829 studies identified, 44 met our inclusion criteria. The global pooled estimates of the progression rate per 1000 person-years were 2.09 (95% confidence interval, 1.46-2.99), 2.89 (2.03-4.11), and 10.09 (5.23-19.49) for AG, IM, and dysplasia, respectively. The estimated progression rates per 1000 person-years for low versus medium/high GC incidence countries, respectively, were 0.97 (0.86-1.10) versus 2.47 (1.70-2.99) for AG (P < .01), 2.37 (1.43-3.92) versus 3.47 (2.13-5.65) for IM (P = .29), and 5.51 (2.92-10.39) versus 14.80 (5.87-37.28) for dysplasia (P = .08). There were no differences for progression of AG between groups when high-quality studies were compared., Conclusions: Similar progression rates of IM and dysplasia were observed among low and medium/high GC incidence countries. This suggests that the potential benefits of surveillance for these lesions in low-risk regions may be comparable with those of population-wide interventions in high-risk regions. Further prospective studies are needed to confirm these findings and inform global screening and surveillance guidelines., (Copyright © 2024 AGA Institute. All rights reserved.)

Background: Colorectal cancers (CRCs) arise from adenomas, which can produce fecal occult blood and can be detected endoscopically, or sessile serrated lesions (SSLs), which rarely bleed and may be more challenging to detect. Models informing CRC screening policy should reflect both pathways, accounting for uncertainty., Methods: Novel decision-analytic model of the adenoma and serrated pathways for CRC (ANSER) to compare current and emerging screening strategies, accounting for differential test sensitivities for adenomas and SSLs, and uncertainty. Strategies included colonoscopy every 10 years, stool-DNA/FIT (sDNA-FIT) every 1-3 years, or fecal immunochemical testing (FIT) every year from age 45 to 75 years. Outcomes included CRC cases and deaths, cost-effectiveness (cost/quality-adjusted life-year [QALY] gained), and burden-benefit (colonoscopies/life-year gained), with 95% uncertainty intervals (UIs)., Results: ANSER predicted 62.5 (95% UI = 58.8-66.3) lifetime CRC cases and 24.1 (95% UI = 22.5-25.7) CRC deaths/1000 45-year-olds without screening, and 78%-87% CRC mortality reductions with screening. The tests' outcome distributions overlapped for QALYs gained but separated for required colonoscopies and costs. All strategies cost less than $100 000/QALY gained vs no screening. Colonoscopy was the most effective and cost-effective, costing $9300/life-year gained (95% UI = $500-$21 900) vs FIT. sDNA-FIT cost more than $500 000/QALY gained vs FIT. As more CRCs arose from SSLs, colonoscopy remained preferred based on clinical benefit and cost-effectiveness, but cost-effectiveness improved for a next-generation sDNA-FIT., Conclusion: When the serrated pathway is considered, modeling suggests that colonoscopy is cost-effective vs FIT. In contrast, modeling suggests that sDNA-FIT is not cost-effective vs FIT despite its greater sensitivity for SSLs, even if a substantial minority of CRCs arise from SSLs., (© The Author(s) 2024. Published by Oxford University Press.)

Background & Aims: The prevalence of precursor lesions for gastric cancer (GC) and the differential burden between countries of varying GC risk is not well-understood. We conducted a systematic review and meta-analysis to estimate the global prevalence of precursor lesions., Methods: We estimated the prevalence of atrophic gastritis (AG), gastric intestinal metaplasia (IM), and dysplasia in regions with low, medium, and high GC incidence. Because IM is an advanced manifestation of AG, we assessed the prevalence of less advanced precursors, regardless of the presence of more advanced lesions. Prevalence was sub-stratified by Helicobacter pylori infection, symptomatology, and period (<2000, 2000-2010, and >2010)., Results: Among the 582 articles that underwent full-text review, 166 studies met inclusion criteria. The global prevalence estimates of AG, IM, and dysplasia were 25.4%, 16.2%, and 2.0%, respectively, on the basis of 126 studies that reported the prevalence of less advanced precursors, regardless of the presence of more advanced lesions. The prevalence of all precursor lesions was higher in high and medium compared with low GC incidence countries (P < .01). Prevalence of AG and IM was significantly higher among H pylori-infected individuals (P < .01) but not statistically different between symptomatic and asymptomatic individuals (P > .17). All precursors demonstrated a secular decrease in prevalence over time., Conclusions: Gastric precursor lesions have differences in prevalence in regions with differential GC incidence and are associated with H pylori infection. Because of the substantial prevalence of precursor lesions in both symptomatic and asymptomatic individuals, symptomatic evaluation may not be sufficient to identify individuals at risk. These estimates provide important insights for tailoring GC prevention strategies., (Copyright © 2024 AGA Institute. All rights reserved.)

Introduction: Artificial intelligence (AI) could minimize the operator-dependent variation in colonoscopy quality. Computer-aided detection (CADe) has improved adenoma detection rate (ADR) and adenomas per colonoscopy (APC) in randomized controlled trials. There is a need to assess the impact of CADe in real-world settings., Methods: We searched MEDLINE, EMBASE, and Web of Science for nonrandomized real-world studies of CADe in colonoscopy. Random-effects meta-analyses were performed to examine the effect of CADe on ADR and APC. The study is registered under PROSPERO (CRD42023424037). There was no funding for this study., Results: Twelve of 1,314 studies met inclusion criteria. Overall, ADR was statistically significantly higher with vs without CADe (36.3% vs 35.8%, risk ratio [RR] 1.13, 95% confidence interval [CI] 1.01-1.28). This difference remained significant in subgroup analyses evaluating 6 prospective (37.3% vs 35.2%, RR 1.15, 95% CI 1.01-1.32) but not 6 retrospective (35.7% vs 36.2%, RR 1.12, 95% CI 0.92-1.36) studies. Among 6 studies with APC data, APC rate ratio with vs without CADe was 1.12 (95% CI 0.95-1.33). In 4 studies with GI Genius (Medtronic), there was no difference in ADR with vs without CADe (RR 0.96, 95% CI 0.85-1.07)., Discussion: ADR, but not APC, was slightly higher with vs without CADe among all available real-world studies. This difference was attributed to the results of prospective but not retrospective studies. The discrepancies between these findings and those of randomized controlled trials call for future research on the true impact of current AI technology on colonoscopy quality and the subtleties of human-AI interactions., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Purpose: The aim of this study was to describe the clinical impact of commercial laboratories issuing conflicting classifications of genetic variants., Methods: Results from 2000 patients undergoing a multigene hereditary cancer panel by a single laboratory were analyzed. Clinically significant discrepancies between the laboratory-provided test reports and other major commercial laboratories were identified, including differences between pathogenic/likely pathogenic and variant of uncertain significance (VUS) classifications, via review of ClinVar archives. For patients carrying a VUS, clinical documentation was assessed for evidence of provider awareness of the conflict., Results: Fifty of 975 (5.1%) patients with non-negative results carried a variant with a clinically significant conflict, 19 with a pathogenic/likely pathogenic variant reported in APC or MUTYH, and 31 with a VUS reported in CDKN2A, CHEK2, MLH1, MSH2, MUTYH, RAD51C, or TP53. Only 10 of 28 (36%) patients with a VUS with a clinically significant conflict had a documented discussion by a provider about the conflict. Discrepant counseling strategies were used for different patients with the same variant. Among patients with a CDKN2A variant or a monoallelic MUTYH variant, providers were significantly more likely to make recommendations based on the laboratory-reported classification., Conclusion: Our findings highlight the frequency of variant interpretation discrepancies and importance of clinician awareness. Guidance is needed on managing patients with discrepant variants to support accurate risk assessment., Competing Interests: Conflict of Interest Gregory E. Idos reports research funding from Myriad Genetics (Inst). Jason A. Zell serves in a consulting role for Tempus. Charité N. Ricker reports research funding from Myriad Genetics (Inst). Kevin J. McDonnell has served in a consulting or advisory role for Brogent International and reports research funding from Myriad Genetics. Uri Ladabaum serves as an advisor for Universal Dx, Lean Medical, Kohler Ventures, Vivante, and a consultant for Freenome, Guardant, Medtronic, Neptune Medical, Medial EarlySign. Stephen B. Gruber reports that he is co-founder with equity with Brogent International. Giovanni Parimigiani reports that he holds equity as a co-founder in Phaeno Biotechnologies, is on the SAB of Realm Idx (which owns Ambry Genetics) and currently consults for Delphi Diagnostics and (pro bono) for Martingale Labs. He also co-leads the BayesMendel laboratory, which licenses the BayesMendel package which include several ML tools for the computation of carrier probability of cancer susceptibility genes and future cancer risk. He does not derive any personal income from these licenses. Danielle Braun co-leads the BayesMendel lab, which develops and maintains the BayesMendel software package. This includes a variety of risk assessment tools, including BRCAPRO, PancPRO, MelaPRO, MMRpro and is licensed for commercial use. All other authors declare no conflicts of interest., (Copyright © 2023 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Among the characteristics of high-risk adenomas (HRAs), some may predict a higher risk of metachronous advanced lesions. Our aim was to assess which HRA characteristics are associated with high risk of metachronous colorectal cancer (CRC) or advanced adenomas (AAs)., Methods: We systematically searched Pubmed, EMBASE, and Cochrane for cohort studies and clinical trials of CRC or AA incidence at surveillance stratified by baseline lesion size, histology, and multiplicity. We calculated pooled relative risks (RRs) using a random-effects model. Heterogeneity was assessed with the I 2 statistic., Results: Fifty-five studies were included, with 936,540 patients with mean follow-up 5.4 ± 2.9 years. CRC incidence per 1000 person-years was 2.6 (2.1-3.0) for adenomas ≥20 mm, 2.7 (2.2-3.2) for high-grade dysplasia (HGD), 2.0 (1.8-2.3) for villous component, 0.8 (0.1-1.4) for ≥5 adenomas, 1.0 (0.7-1.2) for ≥3 adenomas. Metachronous CRC risk was higher in adenomas ≥20 mm vs 10 to 19 mm (RR, 2.08; 95% confidence interval [CI], 1.20-3.61), HGD vs low-grade dysplasia (RR, 2.89; 95% CI, 1.88-4.44), villous vs tubular (RR, 1.75; 95% CI, 1.33-2.31). No significant differences in CRC risk were found in ≥3 adenomas vs 1 to 2 (RR, 1.24; 95% CI, 0.84-1.83), nor in ≥5 adenomas vs 3 to 4 (RR, 0.79; 95% CI, 0.30-2.11). Compared with normal colonoscopy, RR for CRC risk was 2.61 (95% CI, 2.06-3.32) for ≥10mm, 6.62 (95% CI, 4.60-9.52) for HGD, 3.58 (95% CI, 2.24-5.73) for villous component, and 2.03 (95% CI, 1.40-2.94) for ≥3 adenomas. Similar trends were seen for metachronous AAs., Conclusion: Metachronous CRC risk is highest in patients with baseline adenomas with ≥20 mm or HGD. Multiplicity does not seem to be associated with substantially higher CRC risk in the near term., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Overweight and obese persons have not only elevated rates of colorectal cancer (CRC), but also higher competing mortality and healthcare spending. We examined the cost-effectiveness of intensified CRC screening in overweight and obese persons., Methods: We adapted our validated decision analytic model of CRC screening to compare screening starting at 45 or 40 years of age instead of at 50 years of age, or shortening screening intervals, in women and men with body mass index (BMI) ranging from normal to grade III obesity. Strategies included colonoscopy every 10 years (Colo10) or every 5 years (Colo5), or annual fecal immunochemical test., Results: Without screening, sex-specific total CRC deaths were similar for persons with overweight or obesity I-III, reflecting the counterbalancing of higher CRC risk by lower life expectancy as BMI rises. For all BMI and sex groups, Colo10 starting at 45 years of age or FIT starting at 40 years of age were cost-effective at a threshold of $100,000 per quality-adjusted life year gained. Colo10 starting at 40 years of age was cost-effective only for men with obesity II-III, at $93,300 and $80,400 per quality-adjusted life year gained, respectively. Shifting Colo10 to earlier starting ages was always preferred over Colo5 starting at later ages. Results were robust in sensitivity analysis, including varying all-cause mortality, complication, and BMI-specific CRC risks., Conclusions: CRC screening starting at 45 years of age with colonoscopy, or at 40 years of age with FIT, appears cost-effective for women and men across the range of BMI. In men with obesity II-III, who have the highest CRC but also all-cause mortality risks, colonoscopy starting at 40 years of age appears cost-effective. It remains to be decided whether BMI should be used as a single predictor or incorporated into a multivariable tool to tailor CRC screening., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background and Aims: All major U.S. guidelines now endorse average-risk colorectal cancer (CRC) screening at 45-49 years of age. Concerns exist that endoscopic capacity may be strained, that low-risk persons may self-select for screening, and that calculations of the adenoma detection rate may be diluted. We analyzed age-specific screening colonoscopy volumes and lesion detection rates before vs after the endorsement of CRC screening at 45-49 years of age., Methods: We compared colonoscopy volumes and lesion detection rates in our healthcare system during period 1 (October 2017 to December 2018), before the first change in guidelines, vs period 2 (January 2019 to August 2021), the era of new guidelines., Results: The proportion of first-time screening colonoscopies performed in 45- to 49-year-olds increased from 3.5% to 11.6% (relative risk, 3.36; 95% CI, 2.45-4.61). The period 2 detection rates for adenoma, advanced adenoma, sessile serrated lesion, advanced sessile serrated lesion, adenomas per colonoscopy, and lesions per colonoscopy were very similar for 45- to 49-year-olds (34.3%, 6.3%, 8.6%, 2.9%, 0.58, and 0.69, respectively) and 50- to 54-year-olds (38.2%, 5.8%, 9.4%, 3.0%, 0.63, and 0.76, respectively) at first-time screening, and for 60- to 64-year-olds at rescreening (33.4%, 6.1%, 7.2%, 2.3%, 0.61, and 0.70, respectively). All detection rates, adenomas per colonoscopy, and lesions per colonoscopy increased from period 1 to period 2 (eg, overall adenoma detection rate 35.1% vs 42.6%; P < .0001), without any decreases among 45- to 49-year-olds., Conclusions: In our healthcare system, a lower CRC screening initiation age has modestly affected colonoscopy volume by age without compromising screening yield. Lesion detection rates, including for advanced adenomas, in average-risk 45- to 49-year-olds approximate those in 50- to 54-year-olds at first-time screening and 60- to 64-year-olds at rescreening. National monitoring is needed to assess fully the impact of lowering the CRC screening initiation age., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

In 2018, the American Gastroenterological Association's Center for GI Innovation and Technology convened a consensus conference, entitled "Colorectal Cancer Screening and Surveillance: Role of Emerging Technology and Innovation to Improve Outcomes." The conference participants, which included more than 60 experts in colorectal cancer, considered recent improvements in colorectal cancer screening rates and polyp detection, persistent barriers to colonoscopy uptake, and opportunities for performance improvement and innovation. This white paper originates from that conference. It aims to summarize current patient- and physician-centered gaps and challenges in colonoscopy, diagnostic and therapeutic challenges affecting colonoscopy uptake, and the potential use of emerging technologies and quality metrics to improve patient outcomes., (Copyright © 2022 AGA Institute. All rights reserved.)

Background and Aims: The 2012 and 2020 US Multi-Society Task Force postpolypectomy guidelines have recommended progressively longer surveillance intervals for patients with low-risk adenomas (LRAs). These guidelines require data from past colonoscopies. We examined the impact of the 2012 guidelines for second surveillance on clinical practice, including the availability of prior colonoscopy data, with the aim of informing the implementation of the 2020 guidelines., Methods: We identified surveillance colonoscopies at Stanford Health Care and the Palo Alto Veterans Affairs Health Care System in 3 periods: preguideline (March-August 2012), postguideline (January-June 2013), and delayed postguideline (July-September 2017). We collected data on the most recent previous colonoscopy, findings at the study entry surveillance colonoscopy, and recommendations for subsequent surveillance., Results: Among 977 patients, the most recent prior colonoscopy data were available in 78% of preguideline, 78% of postguideline, and 61% of delayed postguideline cases ( P < .001). The fraction of surveillance colonoscopy reports that deferred recommendations awaiting pathology increased from 6% to 11% in preguideline and postguideline to 59% in delayed postguideline cases ( P < .001). Overall adherence to guidelines for subsequent surveillance was similar in all 3 periods (54%-67%; P  = .089). In the postguideline and delayed postguideline periods combined, a 10-year subsequent surveillance interval was recommended in 0 of 29 cases with LRA followed by normal surveillance colonoscopy., Conclusion: In patients undergoing surveillance, prior colonoscopy data were not always available and recommendations were often deferred awaiting pathology. Adherence to subsequent surveillance guidelines was suboptimal, especially for LRA followed by normal colonoscopy. Strategies addressing these gaps are needed to optimize implementation of the updated 2020 postpolypectomy guidelines., (© 2023 The Authors.)

The landmark Centers for Medicare & Medicaid Services (CMS) decision memo on blood-based biomarkers to screen for colorectal cancer (CRC) sets thresholds of 74% or higher for sensitivity and 90% or higher for specificity for CRC. This approach does not consider detection of advanced precancerous lesions as true positives. We contrasted the impact of counting advanced precancerous lesions as true vs false positives and projected CRC outcomes under contrasting tests in a validated model. A test with the threshold performance set by CMS decreased CRC incidence by 30% and CRC mortality by 48% in individuals aged 45 years. If this test also detected advanced precancerous lesions with 30% sensitivity, CRC incidence decreased by 45% and mortality by 58%, but the CRC specificity of the test of only 88% would not satisfy the CMS threshold. CMS should reconsider its definition of threshold specificity for CRC screening biomarkers. Future coverage determinations on biomarkers to screen for cancer should consider detection of relevant precursor lesions and projected outcomes., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background & Aims: Reports of mailed fecal immunochemical test (FIT) outreach effectiveness over time are minimal. We aimed to better evaluate a mailed FIT program with longitudinal metrics., Methods: A total of 10,771 patients aged 50 to 75 years not up-to-date with colorectal cancer screening were randomized to intervention or usual care. The intervention arm received an advanced notification call and informational postcard prior to a mailed FIT. Usual care was at the discretion of the primary care provider. Patients were followed for up to 2.5 years. The primary outcome was the difference in cumulative proportion of completed FIT screening between arms. Screening was further examined with the proportion of time up-to-date, consistency of adherence, and frequency of abnormal FIT., Results: The cumulative proportion of FIT completion was higher in the outreach intervention (73.2% vs 55.1%; P < .001). The proportion of time covered by screening was higher in the intervention group (46.8% vs 27.3%; Δ19.6%; 95% confidence interval, 18.2%-20.9%). Patients assigned to FIT outreach were more likely to consistently complete FITs (2 completed of 2 offered) (50.1% vs 21.8%; P < .001). However, for patients who did not complete the FIT during the first cycle, only 17.1% completed a FIT during the second outreach cycle. The number and overall proportion of abnormal FIT was significantly higher in the outreach intervention (6.9% Outreach vs 4.1% Usual Care; P < .01)., Conclusions: Organized mailed FIT outreach significantly increased colorectal cancer screening over multiple years in this safety-net health system. Although mailing was overall effective, the effect was modest in patients who did not complete FIT in first cycle of intervention. (ClincialTrials.gov, NCT02613260)., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Gastric cancer is inherited as an autosomal dominant condition in hereditary diffuse gastric cancer (HDGC). The gene associated with HDGC is an E-cadherin gene CDH1. At the time of initiation of this study, it was estimated that 70% of patients who inherited the CDH1 gene mutation would develop gastric cancer. We hypothesized that the rate of signet ring cell cancer in asymptomatic patients with CDH1 mutations may be higher than anticipated and that the surgery could be conducted with acceptable short-term and long-term complications suggesting that the quality of life with the surgery is acceptable., Methods: We prospectively studied the role of total gastrectomy in symptomatic and asymptomatic patients with CDH1 mutations. A total of 43 patients with mutations of the CDH1 gene were studied prospectively, including 8 with symptoms and 35 without symptoms. Total gastrectomy was recommended to each. Quality of life was assessed in patients who underwent prophylactic gastrectomy. Proportions are compared with Fisher's exact test., Results: In total, 13 (30%) asymptomatic patients declined surgery. Total gastrectomy was performed in 8 symptomatic patients and 22 asymptomatic patients of whom only 3 asymptomatic patients (14%) had endoscopically proven signet ring cell cancer preoperatively, while 21 of 22 (95%) had it on final pathology ( p = 0.05). Each asymptomatic patient was T1, N0, while seven out of eight symptomatic patients had T3-T4 tumors and six had positive lymph nodes. None had operative complications or operative death. The median follow-up was 7 years. Five (63%) symptomatic patients died, while only one (95%) prophylactic patient died of a non-gastric cancer- or surgery-related issue ( p = 0.05). A total of 15 prophylactic patients had long-term follow-up. Each had significant weight loss (mean 23%) but all had a normal body mass index. In total, 40% had bile reflux gastritis controlled with sucralfate. Each returned to work and, if given the choice, said that they would undergo the surgery again., Conclusions: Total gastrectomy is indicated for patients who have an inherented CDH1 mutation. Endoscopic screening is not reliable for diagnosing signet ring cell stomach cancer. If patients wait for symptoms, they will have a more advanced disease and significantly reduced survival. Operative complications of prophylactic gastrectomy are minimal, and long-term quality of life is acceptable.

Background: The adenoma detection rate at screening (ADR) predicts interval colorectal cancer. Monitoring other lesion detection rates and colonoscopy indications has been proposed. We developed a comprehensive, automated colonoscopy audit program based on standardized clinical documentation, explored detection rates across indications, and developed the Adenoma Detection Rate - Extended to all Screening / Surveillance (ADR-ESS) score., Methods: In a prospective cohort study, we calculated overall and advanced adenoma and sessile serrated lesion (SSL) detection rates among 15,253 colonoscopies by 35 endoscopists from 4 endoscopy units across all colonoscopy indications. We explored correlations between detection rates, and the precision and stability of ADR-ESS versus ADR., Results: The overall "screening, first" ADR was 36.3% (95% confidence interval [CI], 34.5%-38.1%). The adenoma detection rate was lower for "screening, not first" (relative rate [RR], 0.80; 95% CI, 0.74-0.87) and "family history" (RR, 0.84; 95% CI, 0.74-0.96), and higher for "surveillance" (RR, 1.22; 95% CI, 1.15-1.31) and "follow-up, FIT" (RR, 1.21; 95% CI, 1.07-1.37). For "screening, first," the detection rates for advanced adenoma, SSL, and advanced SSL were 6.7% (95% CI, 5.7%-7.7%), 7.2% (95% CI, 6.2%-8.2%), and 2.6% (95% CI, 2.0%-3.2%), respectively. Adenoma and SSL detection were correlated (r = 0.44; P = .008). ADR-ESS had substantially narrower confidence intervals and less period-to-period variability than ADR, and was not improved by weighting for indication volume and correction for detection by indication., Conclusions: Comprehensive, automated colonoscopy audit based on standardized clinical documentation is feasible. Adenoma detection is a fair but imperfect proxy for SSL detection. ADR-ESS increases the precision of adenoma detection assessments and emphasizes quality across colonoscopy indications., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Colorectal cancer (CRC) incidence at ages younger than 50 years is increasing, leading to proposals to lower the CRC screening initiation age to 45 years. Data on the effectiveness of CRC screening at ages 45-49 years are lacking., Methods: We studied the association between undergoing colonoscopy at ages 45-49 or 50-54 years and CRC incidence in a retrospective population-based cohort study using Florida's linked Healthcare Cost and Utilization Project databases with mandated reporting from 2005 to 2017 and Cox models extended for time-varying exposure., Results: Among 195,600 persons with and 2.6 million without exposure to colonoscopy at ages 45-49 years, 276 and 4844 developed CRC, resulting in CRC incidence rates of 20.8 (95% CI, 18.5-23.4) and 30.6 (95% CI, 29.8-31.5) per 100,000 person-years, respectively. Among 660,248 persons with and 2.4 million without exposure to colonoscopy at ages 50-54 years, 798 and 6757 developed CRC, resulting in CRC incidence rates of 19.0 (95% CI, 17.7-20.4) and 51.9 (95% CI, 50.7-53.1) per 100,000 person-years, respectively. The adjusted hazard ratios for incident CRC after undergoing compared with not undergoing colonoscopy were 0.50 (95% CI, 0.44-0.56) at ages 45-49 years and 0.32 (95% CI, 0.29-0.34) at ages 50-54 years. The results were similar for women and men (hazard ratio, 0.48; 95% CI, 0.40-0.57 and hazard ratio, 0.52; 95% CI, 0.43-0.62 at ages 45-49 years, and hazard ratio, 0.35; 95% CI, 0.31-0.39 and hazard ratio, 0.29; 95% CI, 0.26-0.32 at ages 50-54 years, respectively)., Conclusions: Colonoscopy at ages 45-49 or 50-54 years was associated with substantial decreases in subsequent CRC incidence. These findings can inform screening guidelines., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The American Gastroenterological Association's Center for Gastrointestinal Innovation and Technology convened a consensus conference in December 2018, entitled, "Colorectal Cancer Screening and Surveillance: Role of Emerging Technology and Innovation to Improve Outcomes." The goal of the conference, which attracted more than 60 experts in screening and related disciplines, including the authors, was to envision a future in which colorectal cancer (CRC) screening and surveillance are optimized, and to identify barriers to achieving that future. This White Paper originates from that meeting and delineates the priorities and steps needed to improve CRC outcomes, with the goal of minimizing CRC morbidity and mortality. A one-size-fits-all approach to CRC screening has not and is unlikely to result in increased screening uptake or desired outcomes owing to barriers stemming from behavioral, cultural, and socioeconomic causes, especially when combined with inefficiencies in deployment of screening technologies. Overcoming these barriers will require the following: efficient utilization of multiple screening modalities to achieve increased uptake; continued development of noninvasive screening tests, with iterative reassessments of how best to integrate new technologies; and improved personal risk assessment to better risk-stratify patients for appropriate screening testing paradigms., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Phone calls as part of multimodal fecal immunochemical test (FIT) outreach are effective but resource-intensive. Previous studies of advanced notification calls before FIT mailing have not differentiated patients' prior screening status., Objective: To determine the effectiveness of a phone call preceding mailing of a FIT kit on test completion rate for patients who have completed a prior FIT., Design: Randomized controlled trial nested within a larger study. All patients were assigned to receive organized mailed FIT outreach in the larger study., Participants: Patients in a safety-net health setting ages 50-75 years old with a previously negative FIT., Interventions: Patients were assigned to either receive an advanced notification phone call or no phone call preceding a mailed FIT kit. Both groups received an informational postcard prior to the mailed FIT., Main Measures: The primary outcome was FIT completion rate at 1 year. The secondary outcomes were FIT completion rates at 60, 90, and 180 days, rates stratified by demographic subgroups, and rates according to outcome of the phone call., Key Results: A total of 1645 patients were assigned to advanced notification calls and 1595 were assigned to no call preceding the FIT mailing. Although FIT completion rate was higher at day 60 (55.5% vs. 50.8%, p < 0.01), an advanced notification call did not significantly improve FIT completion at 1 year (70.9% vs. 69.9%, p = 0.52). Of the patients assigned to receive an advanced notification call, 90.5% were spoken with or left a voicemail; patients who were spoken with were more likely to complete a FIT at 1 year compared with patients who were only left a voicemail or could not be left a voicemail (79.9% vs. 69.2% vs. 49.6%, p < 0.01)., Conclusions: Advanced notification phone calls prior to FIT mailing did not improve rates at 1 year for patients with a previously negative FIT.