Evolving Concepts in Helicobacter pylori Management.

Helicobacter pylori is the most common chronic bacterial infection worldwide and the most significant risk factor for gastric cancer, which remains a leading cause of cancer-related death globally. H pylori and gastric cancer continue to disproportionately impact racial and ethnic minority and immigrant groups in the United States. The approach to H pylori case-finding thus far has relied on opportunistic testing based on symptoms or high-risk indicators, such as racial or ethnic background and family history. However, this approach misses a substantial proportion of individuals infected with H pylori who remain at risk for gastric cancer because most infections remain clinically silent. Moreover, individuals with chronic H pylori infection are at risk for gastric preneoplastic lesions, which are also asymptomatic and only reliably diagnosed using endoscopy and biopsy. Thus, to make a significant impact in gastric cancer prevention, a systematic approach is needed to better identify individuals at highest risk of both H pylori infection and its complications, including gastric preneoplasia and cancer. The approach to H pylori eradication must also be optimized given sharply decreasing rates of successful eradication with commonly used therapies and increasing antimicrobial resistance. With growing acceptance that H pylori should be managed as an infectious disease and the increasing availability of susceptibility testing, we now have the momentum to abandon empirical therapies demonstrated to have inadequate eradication rates. Molecular-based susceptibility profiling facilitates selection of a personalized eradication regimen without necessitating an invasive procedure. An improved approach to H pylori eradication coupled with population-level programs for screening and treatment could be an effective and efficient strategy to prevent gastric cancer, especially in minority and potentially marginalized populations that bear the heaviest burden of H pylori infection and its complications.

The road to a world-unified approach to the management of patients with gastric intestinal metaplasia: a review of current guidelines.

OBJECTIVE: During the last decade, the management of gastric intestinal metaplasia (GIM) has been addressed by several distinct international evidence-based guidelines. In this review, we aimed to synthesise these guidelines and provide clinicians with a global perspective of the current recommendations for managing patients with GIM, as well as highlight evidence gaps that need to be addressed with future research. DESIGN: We conducted a systematic review of the literature for guidelines and consensus statements published between January 2010 and February 2023 that address the diagnosis and management of GIM. RESULTS: From 426 manuscripts identified, 16 guidelines were assessed. There was consistency across guidelines regarding the purpose of endoscopic surveillance of GIM, which is to identify prevalent neoplastic lesions and stage gastric preneoplastic conditions. The guidelines also agreed that only patients with high-risk GIM phenotypes (eg, corpus-extended GIM, OLGIM stages III/IV, incomplete GIM subtype), persistent refractory Helicobacter pylori infection or first-degree family history of gastric cancer should undergo regular-interval endoscopic surveillance. In contrast, low-risk phenotypes, which comprise most patients with GIM, do not require surveillance. Not all guidelines are aligned on histological staging systems. If surveillance is indicated, most guidelines recommend a 3-year interval, but there is some variability. All guidelines recommend H. pylori eradication as the only non-endoscopic intervention for gastric cancer prevention, while some offer additional recommendations regarding lifestyle modifications. While most guidelines allude to the importance of high-quality endoscopy for endoscopic surveillance, few detail important metrics apart from stating that a systematic gastric biopsy protocol should be followed. Notably, most guidelines comment on the role of endoscopy for gastric cancer screening and detection of gastric precancerous conditions, but with high heterogeneity, limited guidance regarding implementation, and lack of robust evidence. CONCLUSION: Despite heterogeneous populations and practices, international guidelines are generally aligned on the importance of GIM as a precancerous condition and the need for a risk-stratified approach to endoscopic surveillance, as well as H. pylori eradication when present. There is room for harmonisation of guidelines regarding (1) which populations merit index endoscopic screening for gastric cancer and GIM detection/staging; (2) objective metrics for high-quality endoscopy; (3) consensus on the need for histological staging and (4) non-endoscopic interventions for gastric cancer prevention apart from H. pylori eradication alone. Robust studies, ideally in the form of randomised trials, are needed to bridge the ample evidence gaps that exist.

AGA Clinical Practice Update on High-Quality Upper Endoscopy: Expert Review.

DESCRIPTION: The purpose of this Clinical Practice Update (CPU) Expert Review is to provide clinicians with guidance on best practices for performing a high-quality upper endoscopic exam. METHODS: The best practice advice statements presented herein were developed from a combination of available evidence from published literature, guidelines, and consensus-based expert opinion. No formal rating of the strength or quality of the evidence was carried out, which aligns with standard processes for American Gastroenterological Association (AGA) Institute CPUs. These statements are meant to provide practical, timely advice to clinicians practicing in the United States. This Expert Review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates (CPU) Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPU Committee and external peer review through standard procedures of Clinical Gastroenterology & Hepatology. BEST PRACTICE ADVICE 1: Endoscopists should ensure that upper endoscopy is being performed for an appropriate indication and that informed consent clearly explaining the risks, benefits, alternatives, sedation plan, and potential diagnostic and therapeutic interventions is obtained. These elements should be documented by the endoscopist before the procedure. BEST PRACTICE ADVICE 2: Endoscopists should ensure that adequate visualization of the upper gastrointestinal mucosa, using mucosal cleansing and insufflation as necessary, is achieved and documented. BEST PRACTICE ADVICE 3: A high-definition white-light endoscopy system should be used for upper endoscopy instead of a standard-definition white-light endoscopy system whenever possible. The endoscope used for the procedure should be documented in the procedure note. BEST PRACTICE ADVICE 4: Image enhancement technologies should be used during the upper endoscopic examination to improve the diagnostic yield for preneoplasia and neoplasia. Suspicious areas should be clearly described, photodocumented, and biopsied separately. BEST PRACTICE ADVICE 5: Endoscopists should spend sufficient time carefully inspecting the foregut mucosa in an anterograde and retroflexed view to improve the detection and characterization of abnormalities. BEST PRACTICE ADVICE 6: Endoscopists should document any abnormalities noted on upper endoscopy using established classifications and standard terminology whenever possible. BEST PRACTICE ADVICE 7: Endoscopists should perform biopsies for the evaluation and management of foregut conditions using standardized biopsy protocols. BEST PRACTICE ADVICE 8: Endoscopists should provide patients with management recommendations based on the specific endoscopic findings (eg, peptic ulcer disease, erosive esophagitis), and this should be documented in the medical record. If recommendations are contingent upon histopathology results (eg, H pylori infection, Barrett's esophagus), then endoscopists should document that appropriate guidance will be provided after results are available. BEST PRACTICE ADVICE 9: Endoscopists should document whether subsequent surveillance endoscopy is indicated and, if so, provide appropriate surveillance intervals. If the determination of surveillance is contingent on histopathology results, then endoscopists should document that surveillance intervals will be suggested after results are available.

Effect of Helicobacter pylori Eradication Therapy on the Incidence of Noncardia Gastric Adenocarcinoma in a Large Diverse Population in the United States.

BACKGROUND & AIMS: High-quality data regarding the effect of Helicobacter pylori eradication on the risk of noncardia gastric adenocarcinoma (NCGA) remain limited in the United States. We investigated the incidence of NCGA after H pylori eradication therapy in a large, community-based US population. METHODS: We performed a retrospective cohort study of Kaiser Permanente Northern California members who underwent testing and/or treatment for H pylori between 1997 and 2015 and were followed through December 31, 2018. The risk of NCGA was evaluated using the Fine-Gray subdistribution hazard model and standardized incidence ratios. RESULTS: Among 716,567 individuals with a history of H pylori testing and/or treatment, the adjusted subdistribution hazard ratios and 95% confidence intervals of NCGA for H pylori-positive/untreated and H pylori-positive/treated individuals were 6.07 (4.20-8.76) and 2.68 (1.86-3.86), respectively, compared with H pylori-negative individuals. When compared directly with H pylori-positive/untreated individuals, subdistribution hazard ratios for NCGA in H pylori-positive/treated were 0.95 (0.47-1.92) at <8 years and 0.37 (0.14-0.97) ≥8 years of follow-up. Compared with the Kaiser Permanente Northern California general population, standardized incidence ratios (95% confidence interval) of NCGA steadily decreased after H pylori treatment: 2.00 (1.79-2.24) ≥1 year, 1.01 (0.85-1.19) ≥4 years, 0.68 (0.54-0.85) ≥7 years, and 0.51 (0.38-0.68) ≥10 years. CONCLUSION: In a large, diverse, community-based population, H pylori eradication therapy was associated with a significantly reduced incidence of NCGA after 8 years compared with no treatment. The risk among treated individuals became lower than the general population after 7 to 10 years of follow-up. The findings support the potential for substantial gastric cancer prevention in the United States through H pylori eradication.

Helicobacter pylori Burden in the United States According to Individual Demographics and Geography: A Nationwide Analysis of the Veterans Healthcare System.

BACKGROUND & AIMS: There are no contemporary large-scale studies evaluating the burden of Helicobacter pylori in the United States according to detailed demographics. The primary objective was to evaluate H pylori positivity in a large national healthcare system according to individual demographics and geography. METHODS: We conducted a nationwide retrospective analysis of adults in the Veterans Health Administration who completed H pylori testing between 1999 and 2018. The primary outcome was H pylori positivity overall, as well as according to zip code-level geography, race, ethnicity, age, sex, and time period. RESULTS: Among 913,328 individuals (mean, 58.1 years; 90.2% male) included between 1999 and 2018, H pylori was diagnosed in 25.8%. Positivity was highest in non-Hispanic black (median, 40.2%; 95% confidence interval [CI], 40.0%-40.5%) and Hispanic (36.7%; 95% CI, 36.4%-37.1%) individuals and lowest in non-Hispanic white individuals (20.1%; 95% CI, 20.0%-20.2%). Although H pylori positivity declined in all racial and ethnic groups over the timeframe, the disproportionate burden of H pylori in non-Hispanic black and Hispanic compared with non-Hispanic white individuals persisted. Approximately 4.7% of the variation in H pylori positivity was explained by demographics, with race and ethnicity accounting for the vast majority. CONCLUSIONS: The burden of H pylori is substantial in the United States among veterans. These data should (1) motivate research aimed at better understanding why marked demographic differences in H pylori burden persist so that mitigating interventions may be implemented and (2) guide resource allocation to optimize H pylori testing and eradication in high-risk groups.

The Clinical Impact and Cost-Effectiveness of Surveillance of Incidentally Detected Gastric Intestinal Metaplasia: A Microsimulation Analysis.

BACKGROUND & AIMS: Gastric intestinal metaplasia (GIM) is associated with a higher risk of noncardia intestinal gastric adenocarcinoma (GA). The aim of this study was to estimate lifetime benefits, complications, and cost-effectiveness of GIM surveillance using esophagogastroduodenoscopy (EGD). METHODS: We developed a semi-Markov microsimulation model of patients with incidentally detected GIM, to compare the effectiveness of EGD surveillance with no surveillance at 10-year, 5-year, 3-year, 2-year, and 1-year intervals. We modeled a simulated cohort of 1,000,000 US individuals aged 50 with incidental GIM. Outcome measures were lifetime GA incidence, mortality, number of EGDs, complications, undiscounted life-years gained, and incremental cost-effectiveness ratio with a willingness-to-pay threshold of $100,000/quality-adjusted life-year (QALY). RESULTS: In the absence of surveillance, the model simulated 32.0 lifetime GA cases and 23.0 lifetime GA deaths per 1000 individuals with GIM, respectively. Among surveilled individuals, simulated lifetime GA incidence (per 1000) decreased with shorter surveillance intervals (10-year to 1-year, 11.2-6.1) as did GA mortality (7.4-3.6). Compared with no surveillance, all modeled surveillance intervals yielded greater life expectancy (87-190 undiscounted life-years gained per 1000); 5-year surveillance provided the greatest number of life-years gained per EGD performed and was the cost-effective strategy ($40,706/QALY). In individuals with risk factors of family history of GA or anatomically extensive, incomplete-type GIM intensified 3-year surveillance was cost-effective (incremental cost-effectiveness ratio $28,156/QALY and $87,020/QALY, respectively). CONCLUSIONS: Using microsimulation modeling, surveillance of incidentally detected GIM every 5 years is associated with reduced GA incidence/mortality and is cost-effective from a health care sector perspective. Real-world studies evaluating the impact of GIM surveillance on GA incidence and mortality in the United States are needed.

Dynamic Prediction of Advanced Colorectal Neoplasia in Inflammatory Bowel Disease.

BACKGROUND & AIMS: Colonoscopic surveillance is recommended in patients with colonic inflammatory bowel disease (IBD) given their increased risk of colorectal cancer (CRC). We aimed to develop and validate a dynamic prediction model for the occurrence of advanced colorectal neoplasia (aCRN, including high-grade dysplasia and CRC) in IBD. METHODS: We pooled data from 6 existing cohort studies from Canada, The Netherlands, the United Kingdom, and the United States. Patients with IBD and an indication for CRC surveillance were included if they underwent at least 1 follow-up procedure. Exclusion criteria included prior aCRN, prior colectomy, or an unclear indication for surveillance. Predictor variables were selected based on the literature. A dynamic prediction model was developed using a landmarking approach based on Cox proportional hazard modeling. Model performance was assessed with Harrell's concordance-statistic (discrimination) and by calibration curves. Generalizability across surveillance cohorts was evaluated by internal-external cross-validation. RESULTS: The surveillance cohorts comprised 3731 patients, enrolled and followed-up in the time period from 1973 to 2021, with a median follow-up period of 5.7 years (26,336 patient-years of follow-up evaluation); 146 individuals were diagnosed with aCRN. The model contained 8 predictors, with a cross-validation median concordance statistic of 0.74 and 0.75 for a 5- and 10-year prediction window, respectively. Calibration plots showed good calibration. Internal-external cross-validation results showed medium discrimination and reasonable to good calibration. CONCLUSIONS: The new prediction model showed good discrimination and calibration, however, generalizability results varied. Future research should focus on formal external validation and relate predicted aCRN risks to surveillance intervals before clinical application.

Risk of Esophageal Cancer in Achalasia: A Matched Cohort Study Using the Nationwide Veterans Affairs Achalasia Cohort.

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

Endoscopic Surveillance of Intestinal Metaplasia of the Esophagogastric Junction: A Decision Modeling Analysis.

INTRODUCTION: The incidence of esophagogastric junction adenocarcinoma (EGJAC) has been rising. Intestinal metaplasia of the esophagogastric junction (EGJIM) is a common finding in gastroesophageal reflux (irregular Z-line) and may represent an early step in the development of EGJAC in the West. Worldwide, EGJIM may represent progression along the Correa cascade triggered by Helicobacter pylori . We sought to evaluate the cost-effectiveness of endoscopic surveillance of EGJIM. METHODS: We developed a decision analytic model to compare endoscopic surveillance strategies for 50-year-old patients after diagnosis of non-dysplastic EGJIM: (i) no surveillance (standard of care), (ii) endoscopy every 3 years, (iii) endoscopy every 5 years, or (iv) 1-time endoscopy at 3 years. We modeled 4 progression scenarios to reflect uncertainty: A (0.01% annual cancer incidence), B (0.05%), C (0.12%), and D (0.22%). RESULTS: Cost-effectiveness of endoscopic surveillance depended on the progression rate of EGJIM to cancer. At the lowest progression rate (scenario A, 0.01%), no surveillance strategies were cost-effective. In moderate progression scenarios, 1-time surveillance at 3 years was cost-effective, at $30,989 and $16,526 per quality-adjusted life year for scenarios B (0.05%) and C (0.12%), respectively. For scenario D (0.22%), surveillance every 5 years was cost-effective at $77,695 per quality-adjusted life year. DISCUSSION: Endoscopic surveillance is costly and can cause harm; however, low-intensity longitudinal surveillance (every 5 years) is cost-effective in populations with higher EGJAC incidence. No surveillance or 1-time endoscopic surveillance of patients with EGJIM was cost-effective in low-incidence populations. Future studies to better understand the natural history of EGJIM, identify risk factors of progression, and inform appropriate surveillance strategies are required.

Practice Trends among US Gastroenterologists following the 2020 American Gastroenterological Association Guidelines on Gastric Intestinal Metaplasia: Data from a Tertiary Care Center.

BACKGROUND AND AIMS: Studies show variability in gastroenterologists' management of gastric intestinal metaplasia (GIM) in the United States. In 2020, the American Gastroenterological Association published GIM guidelines, recommending physician-patient shared decision-making on GIM surveillance based on risk factors. We compared gastroenterologists' communication trends of a GIM finding and surveillance recommendations before and after 2020 and evaluated patient and provider factors associated with a surveillance recommendation. METHODS: A sample of patients diagnosed with GIM on biopsies from upper endoscopies performed in 2018 (cohort A) and 2021 (cohort B) were included. Logistic regression analysis assessed the association between patient/provider characteristics and surveillance recommendations in the overall cohort and over time. MATERIALS: In all, 347 patients were included: 175 in cohort A and 172 in B. Median age was 65.7 (56.0, 73.4), and 54.5% were females. Communication to patients about GIM findings and surveillance recommendations increased from 24.6% <2020 to 50% >2020 (P<0.001) and 20% <2020 to 41.3% >2020 (P<0.001), respectively. Overall, endoscopy >2020, family history of gastric cancer, autoimmune gastritis, female providers, and gastroenterologists with 10 to 20 years of experience were associated with a surveillance recommendation. The effect of family history of gastric cancer and the effect of the patient's female sex on surveillance was significantly different between both cohorts [Odds ratio (OR): 0.13, 95% (Confidence interval) CI: 0.02, 0.97 and OR 3.39, 95% CI: 1.12, 10.2, respectively). CONCLUSIONS: Despite a 2-fold increase in surveillance recommendations after 2020, there was no meaningful effect of any of the patients' factors on a recommendation for surveillance over time, which raises the question as to whether surveillance is being offered to both average and high-risk patients without thorough risk stratification.

Endoscopic Surveillance of Gastric Intestinal Metaplasia: A Retrospective Cohort Study.

BACKGROUND: Gastric intestinal metaplasia (GIM) is a precancerous condition. Limited data exist on real-world clinical practice relative to guidelines. AIM: The aim of this study was to evaluate adherence to GIM risk stratification and identify factors associated with follow-up endoscopy. MATERIALS AND METHODS: We conducted manual chart review of patients with histologically confirmed GIM at an urban, tertiary medical center were identified retrospectively and details of their demographics, Helicobacter pylori, biopsy protocol, endoscopic/histologic findings, and postendoscopy follow-up were recorded. Multivariable logistic regression was used to identify factors independently associated with follow-up endoscopy. RESULTS: Among 253 patients, 59% were female, 37% non-Hispanic White (NHW), 26% Hispanic, 16% non-Hispanic Black (NHB). The median age at index endoscopy was 63.4 years (IQR: 55.9 to 70.0), with median follow-up of 65.1 months (IQR: 44.0 to 72.3). H. pylori was detected in 21.6% patients at index EGD. GIM extent and subtype data were frequently missing (22.9% and 32.8%, respectively). Based on available data, 26% had corpus-extended GIM and 28% had incomplete/mixed-type GIM. Compared with NHW, Hispanic patients had higher odds of follow-up EGD (OR=2.48, 95% CI: 1.23-5.01), while NHB patients had 59% lower odds of follow-up EGD (OR=0.41, 95% CI: 0.18-0.96). Corpus-extended GIM versus limited GIM (OR=2.27, 95% CI: 1.13-4.59) was associated with follow-up EGD, but GIM subtype and family history of gastric cancer were not. CONCLUSIONS: We observed suboptimal risk stratification among patients with GIM and notable race and ethnic disparities with respect to endoscopic surveillance. Targeted interventions are needed to improve practice patterns and mitigate observed disparities.

The association between dietary fiber intake and gastric cancer: a pooled analysis of 11 case-control studies.

PURPOSE: Gastric cancer (GC) is among the leading causes of cancer mortality worldwide. The objective of this study was to investigate the association between dietary fiber intake and GC. METHODS: We pooled data from 11 population or hospital-based case-control studies included in the Stomach Cancer Pooling (StoP) Project, for a total of 4865 histologically confirmed cases and 10,626 controls. Intake of dietary fibers and other dietary factors was collected using food frequency questionnaires. We calculated the odds ratios (OR) and 95% confidence intervals (CI) of the association between dietary fiber intake and GC by using a multivariable logistic regression model adjusted for study site, sex, age, caloric intake, smoking, fruit and vegetable intake, and socioeconomic status. We conducted stratified analyses by these factors, as well as GC anatomical site and histological type. RESULTS: The OR of GC for an increase of one quartile of fiber intake was 0.91 (95% CI: 0.85, 0.97), that for the highest compared to the lowest quartile of dietary fiber intake was 0.72 (95% CI: 0.59, 0.88). Results were similar irrespective of anatomical site and histological type. CONCLUSION: Our analysis supports the hypothesis that dietary fiber intake may exert a protective effect on GC.

Genetic Inhibition of APOL1 Pore-Forming Function Prevents APOL1-Mediated Kidney Disease.

SIGNIFICANCE STATEMENT: African Americans are at increased risk of CKD in part due to high-risk (HR) variants in the apolipoprotein L1 ( APOL1 ) gene, termed G1/G2. A different APOL1 variant, p.N264K , reduced the risk of CKD and ESKD among carriers of APOL1 HR variants to levels comparable with individuals with APOL1 low-risk variants in an analysis of 121,492 participants of African ancestry from the Million Veteran Program (MVP). Functional genetic studies in cell models showed that APOL1 p.N264K blocked APOL1 pore-forming function and ion channel conduction and reduced toxicity of APOL1 HR mutations. Pharmacologic inhibitors that mimic this mutation blocking APOL1 -mediated pore formation may be able to prevent and/or treat APOL1 -associated kidney disease. BACKGROUND: African Americans are at increased risk for nondiabetic CKD in part due to HR variants in the APOL1 gene. METHODS: We tested whether a different APOL1 variant, p.N264K , modified the association between APOL1 HR genotypes (two copies of G1/G2) and CKD in a cross-sectional analysis of 121,492 participants of African ancestry from the MVP. We replicated our findings in the Vanderbilt University Biobank ( n =14,386) and National Institutes of Health All of Us ( n =14,704). Primary outcome was CKD and secondary outcome was ESKD among nondiabetic patients. Primary analysis compared APOL1 HR genotypes with and without p.N264K . Secondary analyses included APOL1 low-risk genotypes and tested for interaction. In MVP, we performed sequential logistic regression models adjusting for demographics, comorbidities, medications, and ten principal components of ancestry. Functional genomic studies expressed APOL1 HR variants with and without APOL1 p.N264K in cell models. RESULTS: In the MVP cohort, 15,604 (12.8%) had two APOL1 HR variants, of which 582 (0.5%) also had APOL1 p.N264K . In MVP, 18,831 (15%) had CKD, 4177 (3%) had ESKD, and 34% had diabetes. MVP APOL1 HR, without p.N264K , was associated with increased odds of CKD (odds ratio [OR], 1.72; 95% confidence interval [CI], 1.60 to 1.85) and ESKD (OR, 3.94; 95% CI, 3.52 to 4.41). In MVP, APOL1 p.N264K mitigated the renal risk of APOL1 HR, in CKD (OR, 0.43; 95% CI, 0.28 to 0.65) and ESKD (OR, 0.19; CI 0.07 to 0.51). In the replication cohorts meta-analysis, APOL1 p.N264K mitigated the renal risk of APOL1 HR in CKD (OR, 0.40; 95% CI, 0.18 to 0.92) and ESKD (OR, 0.19; 95% CI, 0.05 to 0.79). In the mechanistic studies, APOL1 p.N264K blocked APOL1 pore-forming function and ion channel conduction and reduced toxicity of APOL1 HR variants. CONCLUSIONS: APOL1 p.N264K is associated with reduced risk of CKD and ESKD among carriers of APOL1 HR to levels comparable with individuals with APOL1 low-risk genotypes.

Colorectal Cancer in Inflammatory Bowel Disease: Mechanisms and Management.

Patients with inflammatory bowel disease (IBD) are at increased risk of developing colorectal cancer (CRC), despite decreases in CRC incidence in recent years. Chronic inflammation is the driver of neoplastic progression, resulting in dysplastic precursor lesions that may arise in multiple areas of the colon through a process of field cancerization. Colitis-associated CRC shares many molecular similarities with sporadic CRC, and preclinical investigations have demonstrated a potential role for the microbiome in concert with the host immune system in the development of colitis-associated colorectal cancer (CAC). Some unique molecular differences occur in CAC, but their role in the pathogenesis and behavior of inflammation-associated cancers remains to be elucidated. Nonconventional types of dysplasia have been increasingly recognized, but their natural history is not well defined, and they have not been incorporated into surveillance algorithms. The concept of cumulative inflammatory burden highlights the importance of considering histologic inflammation over time as an important risk factor for CAC. Dysplasia is arguably the most important risk factor for developing CAC, and advances have been made in the endoscopic detection and removal of precancerous lesions, thereby deferring or avoiding surgical resection. Some of the agents used to treat IBD are chemopreventive. It is hoped that by gaining better control of the underlying inflammation with newer medications and better endoscopic detection and management, a more sophisticated appreciation of clinicopathologic risk factors, and growing awareness of the genetic, immunologic, and environmental causes of colitis- associated neoplasia, that colitis-associated colorectal neoplasia will become even more predictable and manageable in the coming years.

Geographic Variation in Colorectal Cancer Incidence Among Asian Americans: A Population-Based Analysis 2006-2016.

Among Asian Americans, cancer is the leading cause of death and colorectal cancer (CRC) is the second most common cancer.1 The uptake of CRC screening influences incidence and mortality trends; however, the most recent American Cancer Society CRC statistics reveals ongoing disparities in screening based on race and ethnicity, with people of Asian descent demonstrating the lowest CRC screening rates despite being the fastest growing racial or ethnic group in the United States.2,3.

Development and Validation of the Veterans Affairs Eosinophilic Esophagitis Cohort.

BACKGROUND & AIMS: Gaps remain in understanding the epidemiology of eosinophilic esophagitis (EoE). Our aim was to identify and validate a national cohort of individuals with EoE using Veterans Health Administration (VHA) data. METHODS: We used 2 validation strategies to develop algorithms that identified adults with EoE between 1999 and 2020. The first validation strategy applied International Classification of Diseases (ICD) code algorithms to a base cohort of individuals who underwent esophagogastroduodenoscopy with esophageal biopsy specimens. The second applied ICD code algorithms to a base cohort of all individuals in the VHA. For each ICD algorithm applied, a random sample of candidate EoE cases and non-EoE controls were selected and the charts were reviewed manually by a blinded reviewer. Each algorithm was modified iteratively until the prespecified diagnostic accuracy end point (95% confidence lower bound for a positive predictive value [PPV], >88%) was achieved. We compiled individuals from each strategy's maximum performance algorithm to construct the Veterans Affairs Eosinophilic Esophagitis Cohort. RESULTS: The maximum performance algorithm from the first validation strategy included 2 or more ICD code encounters for EoE separated by more than 30 days and achieved a 93.3% PPV (lower bound, 88.1%) for identifying true EoE cases. The maximum performance algorithm from the second validation strategy included 4 or more ICD code encounters for EoE in which 2 codes were separated by at least 30 days, and similarly achieved a 93.3% PPV (lower bound, 88.1%). Combining both strategies yielded 6637 individuals, which comprised the Veterans Affairs Eosinophilic Esophagitis Cohort. CONCLUSIONS: We developed and validated 2 highly accurate coding algorithms for EoE and established a nationwide VHA cohort of adults with EoE for future studies.

Up-Front Endoscopy Maximizes Cost-Effectiveness and Cost-Satisfaction in Uninvestigated Dyspepsia.

BACKGROUND & AIMS: Practice guidelines promote a routine noninvasive, non-endoscopic initial approach to investigating dyspepsia without alarm features in young patients, yet many patients undergo prompt upper endoscopy. We aimed to assess tradeoffs among costs, patient satisfaction, and clinical outcomes to inform discrepancy between guidelines and practice. METHODS: We constructed a decision-analytic model and performed cost-effectiveness/cost-satisfaction analysis over a 1-year time horizon on patients with uninvestigated dyspepsia without alarm features referred to gastroenterology. A RAND/UCLA expert panel informed model design. Four competing diagnostic/management strategies were evaluated: prompt endoscopy, testing for Helicobacter pylori and eradicating if present (test-and-treat), testing for H pylori and performing endoscopy if present (test-and-scope), and empiric acid suppression. Outcomes were derived from systematic reviews of clinical trials. Costs were informed by prospective observational cohort studies and national commercial/federal cost databases. Health gains were represented using quality-adjusted life years. RESULTS: From the patient perspective, costs and outcomes were similar for all strategies (maximum out-of-pocket difference of $30 and <0.01 quality-adjusted life years gained/year regardless of strategy). Prompt endoscopy maximized cost-satisfaction and health system reimbursement. Test-and-scope maximized cost-effectiveness from insurer and patient perspectives. Results remained robust on multiple one-way sensitivity analyses on model inputs and across most willingness-to-pay thresholds. CONCLUSIONS: Noninvasive management strategies appear to result in inferior cost-effectiveness and patient satisfaction outcomes compared with strategies promoting up-front endoscopy. Therefore, additional studies are needed to evaluate the drivers of patient satisfaction to facilitate inclusion in value-based healthcare transformation efforts.

Epidemiology of Gastric Malignancies 2000-2018 According to Histology: A Population-Based Analysis of Incidence and Temporal Trends.

BACKGROUND & AIMS: Gastric cancer (GC) remains a leading cause of cancer and cancer-related mortality. Recent reports suggest noncardia GC is increasing in certain U.S. POPULATIONS: However, whether these trends are driven by gastric adenocarcinoma (GA) or other histologies, including neuroendocrine tumors (NETs), lymphoma, or gastrointestinal stromal tumors (GISTs), is unclear. METHODS: We analyzed the Surveillance, Epidemiology and End Results-18 cancer registry (2000-2018) to determine age-standardized incidence rates (ASIR) and annual percentage change (APC) trends for histologically-confirmed GCs, stratified by anatomic location (noncardia vs cardia), age group (20-49 vs 50+ years), sex, race, and ethnicity. Joinpoint regression modeling estimated the statistical significance of trend comparisons. RESULTS: Of 74,520 individuals with noncardia GC, most (66.2%) were GA, with the next largest categories being non-mucosa-associated lymphoid tissue (non-MALT) lymphomas (6.9%), GIST (6.7%), NET (6.4%), and MALT lymphoma (5.6%). Noncardia GA ASIR was significantly higher than other histologies and demonstrated the greatest differences by race and ethnicity. APCs for GA and MALT, both Helicobacter pylori-associated cancers, declined significantly over time, which was driven primarily by trends among individuals ≥50 years-old. NET and GIST APCs significantly increased irrespective of age group, with the highest APCs observed among non-Hispanic white individuals. Cardia GC was rarer than noncardia GC and comprised primarily by GA (87.9%). Cardia GC incidence fell during the study period, which was primarily driven by decline in cardia GA. CONCLUSIONS: GA was the most common histology. On the basis of our findings, the rise in noncardia GC among certain U.S. populations appears predominantly driven by NET and GIST, not GA. Further studies are needed to clarify underlying etiologies for these findings.

Adenoma Detection Rate and Clinical Characteristics Influence Advanced Neoplasia Risk After Colorectal Polypectomy.

BACKGROUND AND AIMS: Postpolypectomy risk stratification for subsequent metachronous advanced neoplasia (MAN) is imprecise and does not account for colonoscopist adenoma detection rate (ADR). Our aim was to assess association of ADR with MAN and create a prediction model for postpolypectomy risk stratification incorporating ADR and other factors. METHODS: We conducted a retrospective cohort study of individuals with baseline polypectomy and subsequent surveillance colonoscopy from 2004 to 2016 within the U.S. Department of Veterans Affairs (VA). Clinical factors, polyp findings, and baseline colonoscopist ADR were considered for the model. Model performance (sensitivity, specificity, and area under the curve) for identifying individuals with MAN was compared with 2020 U.S. Multi-Society Task Force on Colorectal Cancer (USMSTF) surveillance recommendations. RESULTS: A total of 30,897 individuals were randomly assigned 2:1 into independent model training and validation sets. Increasing age, male sex, diabetes, current smoking, adenoma number, polyp location, adenoma ≥10 mm or with tubulovillous/villous features, and decreasing colonoscopist ADR were independently associated with MAN. A range of 1.48- to 1.66-fold increased risk for MAN was observed for ADR in the lowest 3 quintiles (ADR <19.7%-39.3%) vs the highest quintile (ADR >47.0%). When the final model selected based on the training set was applied to the validation set, improved sensitivity and specificity over 2020 USMSTF risk stratification were achieved (P = .001), with an area under the curve of 0.62 (95% confidence interval, 0.60-0.64). CONCLUSIONS: Colonoscopist ADR is associated with MAN. Combining clinical factors and ADR for risk stratification has potential to improve postpolypectomy risk stratification. Improving ADR is likely to improve postpolypectomy outcomes.

Risk of Incident and Fatal Colorectal Cancer After Young-Onset Adenoma Diagnosis: A National Cohort Study.

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