AGA Clinical Practice Guideline on Endoscopic Eradication Therapy of Barrett's Esophagus and Related Neoplasia.

BACKGROUND & AIMS: Barrett's esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC). Endoscopic eradication therapy (EET) can be effective in eradicating BE and related neoplasia and has greater risk of harms and resource use than surveillance endoscopy. This clinical practice guideline aims to inform clinicians and patients by providing evidence-based practice recommendations for the use of EET in BE and related neoplasia. METHODS: The Grading of Recommendations Assessment, Development and Evaluation framework was used to assess evidence and make recommendations. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients, conducted an evidence review, and used the Evidence-to-Decision Framework to develop recommendations regarding the use of EET in patients with BE under the following scenarios: presence of (1) high-grade dysplasia, (2) low-grade dysplasia, (3) no dysplasia, and (4) choice of stepwise endoscopic mucosal resection (EMR) or focal EMR plus ablation, and (5) endoscopic submucosal dissection vs EMR. Clinical recommendations were based on the balance between desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 5 recommendations for the use of EET in BE and related neoplasia. Based on the available evidence, the panel made a strong recommendation in favor of EET in patients with BE high-grade dysplasia and conditional recommendation against EET in BE without dysplasia. The panel made a conditional recommendation in favor of EET in BE low-grade dysplasia; patients with BE low-grade dysplasia who place a higher value on the potential harms and lower value on the benefits (which are uncertain) regarding reduction of esophageal cancer mortality could reasonably select surveillance endoscopy. In patients with visible lesions, a conditional recommendation was made in favor of focal EMR plus ablation over stepwise EMR. In patients with visible neoplastic lesions undergoing resection, the use of either endoscopic mucosal resection or endoscopic submucosal dissection was suggested based on lesion characteristics. CONCLUSIONS: This document provides a comprehensive outline of the indications for EET in the management of BE and related neoplasia. Guidance is also provided regarding the considerations surrounding implementation of EET. Providers should engage in shared decision making based on patient preferences. Limitations and gaps in the evidence are highlighted to guide future research opportunities.

Serum biomarker signature is predictive of the risk of hepatocellular cancer in patients with cirrhosis.

BACKGROUND: Inflammatory and metabolic biomarkers have been associated with hepatocellular cancer (HCC) risk in phases I and II biomarker studies. We developed and internally validated a robust metabolic biomarker panel predictive of HCC in a longitudinal phase III study. METHODS: We used data and banked serum from a prospective cohort of 2266 adult patients with cirrhosis who were followed until the development of HCC (n=126). We custom designed a FirePlex immunoassay to measure baseline serum levels of 39 biomarkers and established a set of biomarkers with the highest discriminatory ability for HCC. We performed bootstrapping to evaluate the predictive performance using C-index and time-dependent area under the receiver operating characteristic curve (AUROC). We quantified the incremental predictive value of the biomarker panel when added to previously validated clinical models. RESULTS: We identified a nine-biomarker panel (P9) with a C-index of 0.67 (95% CI 0.66 to 0.67), including insulin growth factor-1, interleukin-10, transforming growth factor ß1, adipsin, fetuin-A, interleukin-1 ß, macrophage stimulating protein α chain, serum amyloid A and TNF-α. Adding P9 to our clinical model with 10 factors including AFP improved AUROC at 1 and 2 years by 4.8% and 2.7%, respectively. Adding P9 to aMAP score improved AUROC at 1 and 2 years by 14.2% and 7.6%, respectively. Adding AFP L-3 or DCP did not change the predictive ability of the P9 model. CONCLUSIONS: We identified a panel of nine serum biomarkers that is independently associated with developing HCC in cirrhosis and that improved the predictive ability of risk stratification models containing clinical factors.

PNPLA3, Obesity, and Heavy Alcohol Use in Cirrhosis Patients May Exert a Synergistic Increase Hepatocellular Carcinoma Risk.

BACKGROUND & AIMS: In patients with cirrhosis, continued heavy alcohol consumption and obesity may increase risk of hepatocellular carcinoma (HCC). We examined whether germline susceptibility to hepatic steatosis not only independently predisposes to HCC but may also act synergistically with other risk factors. METHODS: We analyzed data from 1911 patients in 2 multicenter prospective cohort studies in the United States. We classified patients according to alcohol consumption (current heavy vs not current heavy), obesity (body mass index ≥30 vs <30 kg/m2), and PNPLA3 I148M variant status (carrier of at least one G risk allele vs noncarrier). We examined the independent and joint effects of these risk factors on risk of developing HCC using Cox regression with competing risks. RESULTS: Mean age was 59.6 years, 64.3% were male, 28.7% were Hispanic, 18.3% were non-Hispanic Black, 50.9% were obese, 6.2% had current heavy alcohol consumption, and 58.4% harbored at least 1 PNPLA3 G-allele. One hundred sixteen patients developed HCC. Compared with PNPLA3 noncarriers without heavy alcohol consumption, HCC risk was 2.65-fold higher (hazard ratio [HR], 2.65; 95% confidence interval [CI], 1.20-5.86) for carriers who had current heavy alcohol consumption. Compared with noncarrier patients without obesity, HCC risk was higher (HR, 2.40; 95% CI, 1.33-4.31) for carrier patients who were obese. PNPLA3 and alcohol consumption effect was stronger among patients with viral etiology of cirrhosis (HR, 3.42; 95% CI, 1.31-8.90). PNPLA3 improved 1-year risk prediction for HCC when added to a clinical risk model. CONCLUSIONS: The PNPLA3 variant may help refine risk stratification for HCC in patients with cirrhosis with heavy alcohol consumption or obesity who may need specific preventive measures.

Risk factors for HCC in contemporary cohorts of patients with cirrhosis.

BACKGROUND AND AIMS: Etiological risk factors for cirrhosis have changed in the last decade. It remains unclear to what extent these trends in cirrhosis risk factors have changed HCC risk. APPROACH AND RESULTS: We used data from two contemporary, prospective multiethnic cohorts of patients with cirrhosis: the Texas Hepatocellular Carcinoma Consortium Cohort and the Houston Veterans Administration Cirrhosis Surveillance Cohort. Patients with cirrhosis were enrolled from seven US centers and followed until HCC diagnosis, transplant, death, or June 30, 2021. We calculated the annual incidence rates for HCC and examined the effects of etiology, demographic, clinical, and lifestyle factors on the risk of HCC. We included 2733 patients with cirrhosis (mean age 60.1 years, 31.3% women). At enrollment, 19.0% had active HCV, 23.3% had cured HCV, 16.1% had alcoholic liver disease, and 30.1% had NAFLD. During 7406 person-years of follow-up, 135 patients developed HCC at an annual incidence rate of 1.82% (95% CI, 1.51-2.13). The annual HCC incidence rate was 1.71% in patients with cured HCV, 1.32% in patients with alcoholic liver disease, and 1.24% in patients with NAFLD cirrhosis. Compared to patients with NAFLD, the risk of progression to HCC was 2-fold higher in patients with cured HCV (HR, 2.04; 95% CI, 1.24-3.35). Current smoking (HR, 1.63; 95% CI, 1.01-2.63) and overweight/obesity (HR, 1.79; 95% CI, 1.08-2.95) were also associated with HCC risk. CONCLUSIONS: HCC incidence among patients with cirrhosis was lower than previously reported. HCC risk was variable across etiologies, with higher risk in patients with HCV cirrhosis and lower risk in those with NAFLD cirrhosis. Current smoking and overweight/obesity increased HCC risk across etiologies.

Patient- and system-level factors associated with racial/ethnic disparities in the delivery of guideline-concordant therapy among US patients with gastric cancer.

BACKGROUND: Disparities in gastric cancer (GC) outcomes show a higher disease burden among minorities. We aimed to evaluate the associations between sociodemographic and system-level factors and guideline-concordant treatment among GC patients. METHODS: Cohort study with GC patients in the National Cancer Data Base (2006-2018) treated with upfront resection or neoadjuvant therapy (NAT). We used logistic regression to identify associations between deviations from guideline-concordant therapy and patient- and system-level factors, and Cox regression models to assess risk of death. RESULTS: The cohort included 43 597 GC patients treated with endoscopic resection (8.9%), surgery only (47.1%), surgery and adjuvant therapy (20.6%), or NAT followed by surgery (23.5%). A total of 31 470 patients (72.2%) received guideline-concordant therapy. Relative to Non-Hispanic Whites (NHWs), Non-Hispanic Blacks (NHBs) (odds ratio [OR] 1.19, [95% confidence intervals 1.10-1.28]) and Asian/Pacific Islanders (APIs) (OR 1.12 [1.03-1.23]) had an increased risk of deviations from treatment guidelines. Medicare/Medicaid increased the risk of deviations while treatment at high-volume facilities decreased its risk for all races/ethnicities. Deviations from guidelines were associated with an increased risk of death (hazard ratio 1.56 [1.50-1.63]. CONCLUSIONS: Racial disparities in the delivery of guideline-concordant therapy among GC patients are affected by several sociodemographic factors at the patient- and system-level.

Recent Trends in the Incidence of Gastric Cancer in the United States.

BACKGROUND: Gastric cancer (GC) incidence rates overall in the United States have declined over recent decades and are predicted to continue declining. However, there have been mixed recent findings regarding the potential stabilization of rates and potential divergent trends by age group. We used the most recent cancer data for the United States and examined trends in GC between 1992 and 2019, overall and in important subgroups of the population. METHODS: Age-adjusted GC incidence rates and trends in adults 20 years or older were calculated using data from the Surveillance, Epidemiology, and End Results (SEER) 12 program. Secular trends were examined overall and by age group, sex, race/ethnicity, SEER registry, and tumor location. We used joinpoint regression to compute annual percent changes, average annual percent changes, and associated 95% CI. RESULTS: GC rates decreased by 1.23% annually from 1992 to 2019. Despite overall decreases, GC incidence rates increased for age groups below 50 years, predominately driven by noncardia GC (74.3% of all GCs). Cardia GC (26.7% of GC) rates decreased in all age groups except for 80 to 84 years. Overall GC rates decreased for both sexes, all races, and for all SEER registry regions, with the largest decreases occurring in males, Asians and Pacific Islanders, and in Hawaii. Age-period-cohort analysis revealed that birth cohorts before 1940 and after 1980 both had increased rates of GC compared with the reference birth cohort of 1955. CONCLUSION: GC rates overall have continued to decline through 2019, despite increases in the rate of noncardia GC for younger age groups.

An Electronic Health Record Model for Predicting Risk of Hepatic Fibrosis in Primary Care Patients.

BACKGROUND: One challenge for primary care providers caring for patients with nonalcoholic fatty liver disease is to identify those at the highest risk for clinically significant liver disease. AIM: To derive a risk stratification tool using variables from structured electronic health record (EHR) data for use in populations which are disproportionately affected with obesity and diabetes. METHODS: We used data from 344 participants who underwent Fibroscan examination to measure liver fat and liver stiffness measurement [LSM]. Using two approaches, multivariable logistic regression and random forest classification, we assessed risk factors for any hepatic fibrosis (LSM > 7 kPa) and significant hepatic fibrosis (> 8 kPa). Possible predictors included data from the EHR for age, gender, diabetes, hypertension, FIB-4, body mass index (BMI), LDL, HDL, and triglycerides. RESULTS: Of 344 patients (56.4% women), 34 had any hepatic fibrosis, and 15 significant hepatic fibrosis. Three variables (BMI, FIB-4, diabetes) were identified from both approaches. When we used variable cut-offs defined by Youden's index, the final model predicting any hepatic fibrosis had an AUC of 0.75 (95% CI 0.67-0.84), NPV of 91.5% and PPV of 40.0%. The final model with variable categories based on standard clinical thresholds (i.e., BMI ≥ 30 kg/m2; FIB-4 ≥ 1.45) had lower discriminatory ability (AUC 0.65), but higher PPV (50.0%) and similar NPV (91.3%). We observed similar findings for predicting significant hepatic fibrosis. CONCLUSIONS: Our results demonstrate that standard thresholds for clinical risk factors/biomarkers may need to be modified for greater discriminatory ability among populations with high prevalence of obesity and diabetes.

Neighborhood-Level Factors Contribute to Disparities in Hepatocellular Carcinoma Incidence in Texas.

BACKGROUND AND AIMS: Texas has the highest hepatocellular carcinoma (HCC) incidence rates in the continental United States, but these rates vary by race-ethnicity. We examined racial-ethnic disparities through a geospatial analysis of the social determinants of health. METHODS: Using data from the Texas Cancer Registry, we assembled 11,547 HCC cases diagnosed between 2011 and 2015 into Texas's census tracts geographic units. Twenty-nine neighborhood measures representing demographics and socioeconomic, and employment domains were retrieved from the U.S. Census Bureau. We performed a series of aspatial and spatially weighted regression models to identify neighborhood-level characteristics associated with HCC risk. RESULTS: We found positive associations between HCC and proportion of population in census tracts that are Black or African American, Hispanic, over 60 years of age, in the construction industry, and in the service occupation but an inverse association with the proportion of population employed in the agricultural industry. The magnitude of these associations varied across Texas census tracts. CONCLUSIONS: We found evidence that neighborhood-level factors are differentially associated with variations in HCC incidence across Texas. Our findings reinforce existing knowledge about HCC risk factors and expose others, including neighborhood-level employment status.

Inverse Association Between Gluteofemoral Obesity and Risk of Non-Cardia Gastric Intestinal Metaplasia.

BACKGROUND & AIMS: It is unclear whether obesity confers increased risk of non-cardia gastric adenocarcinoma and its precursor, gastric intestinal metaplasia. Here, we examined whether various dimensions of adiposity independently predispose to the development of non-cardia gastric intestinal metaplasia. METHODS: We compared data from 409 non-cardia gastric intestinal metaplasia cases and 1748 controls without any gastric intestinal metaplasia from a cross-sectional study at the VA Medical Center in Houston, Texas. Participants completed standardized questionnaires, underwent anthropometric measurements, and underwent a study endoscopy with gastric mapping biopsies. Non-cardia gastric intestinal metaplasia cases included participants with intestinal metaplasia on any non-cardia gastric biopsy. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) using logistic regression models. RESULTS: Increasing body mass index (BMI) was not associated with risk of non-cardia gastric intestinal metaplasia (per unit BMI adjusted OR, 0.98; 95% CI, 0.96-1.00). Similarly, we found no associations with increase in waist circumference (per 10-cm increase adjusted OR, 0.94; 95% CI, 0.87-1.03) and waist-to-hip ratio (WHR) (per unit WHR adjusted OR, 2.34; 95% CI, 0.37-14.7). However, there was a significant inverse association with gastric intestinal metaplasia and increasing hip circumference, reflecting gluteofemoral obesity (per 10-cm increase adjusted OR, 0.89; 95% CI, 0.80-0.98). The inverse association was observed for both extensive and focal gastric intestinal metaplasia. CONCLUSIONS: The independent dimensions of adiposity (BMI, waist circumference) are not associated with increased risk of non-cardia gastric intestinal metaplasia. The inverse association between gluteofemoral obesity and risk of gastric intestinal metaplasia warrants additional study.

The Global Landscape of Esophageal Squamous Cell Carcinoma and Esophageal Adenocarcinoma Incidence and Mortality in 2020 and Projections to 2040: New Estimates From GLOBOCAN 2020.

BACKGROUND & AIMS: The aim of this study was to provide an overview of the burden of esophageal cancer in 185 countries in 2020 and projections for the year 2040. METHODS: Estimates of esophageal cancer cases and deaths were extracted from the GLOBOCAN database for 2020. Age-standardized incidence and mortality rates were calculated overall, by sex, histologic subtype (adenocarcinoma [AC] and squamous cell carcinoma [SCC]), country, and level of human development for 185 countries. The predicted burden of incidence and mortality in 2040 was calculated based on global demographic projections. RESULTS: Globally, there were an estimated 604,100 new cases of, and 544,100 deaths from, esophageal cancer in 2020, corresponding to age-standardized incidence and mortality rates of 6.3 and 5.6 per 100,000, respectively. Most cases were SCCs (85% [512,500 cases]) and 14% (85,700 cases) were ACs. Incidence and mortality rates were 2- to 3-fold higher in male (9.3 and 8.2, respectively) compared with female (3.6 and 3.2, respectively) individuals. Global variations in incidence and mortality were observed across countries and world regions; the highest rates occurred in Eastern Asia and Southern and Eastern Africa and the lowest occurred in Western Africa and Central America regions. If rates remain stable, 957,000 new cases (141,300 AC cases and 806,000 SCC cases) and 880,000 deaths from esophageal cancer are expected in 2040. CONCLUSIONS: These updated estimates of the global burden of esophageal cancer represent an important baseline for setting priorities in policy making and developing and accelerating cancer control initiatives to reduce the current and projected burden. Although primary prevention remains key, screening and early detection represent important components of esophageal cancer control in high-risk populations.

The Prevalence and Determinants of NAFLD and MAFLD and Their Severity in the VA Primary Care Setting.

BACKGROUND & AIMS: A recent panel of international experts proposed the disease acronym metabolic (dysfunction)-associated fatty liver disease (MAFLD) in lieu of nonalcoholic fatty liver disease (NAFLD). We aimed to estimate the burden of and risk factors for NAFLD and MAFLD, and to examine the concordance between definitions in a Veterans population. METHODS: We conducted a cross-sectional study among randomly selected patients within primary care at the Houston Veterans Affairs (VA) facility. Participants completed a survey, provided blood, and underwent Fibroscan. In the absence of heavy alcohol, hepatitis C virus and hepatitis B virus, a controlled attenuation parameter median ≥290 dB/m was used to define NAFLD, whereas MAFLD was defined as controlled attenuation parameter median ≥290 dB/m and either body mass index ≥25 kg/m2 or diabetes, or 2 or more of the following: hypertension, high triglycerides, low high-density lipoprotein cholesterol, and high low-density lipoprotein cholesterol. RESULTS: The mean age of participants was 50.9 years, 55.4% were women, 42.8% were white, and 43.8% were Black. The prevalence of NAFLD was 40.6% (82/202). All 82 patients with NAFLD had a body mass index ≥25 kg/m2, and therefore met our criteria for MAFLD (ie, 100% concordance). Compared with patients with no metabolic trait, patients with ≥3 traits had a 48-fold (adjusted odds ratio, 47.6; 95% confidence interval, 11.3-200) higher risk of NAFLD/MAFLD. Overall, 19 participants (9.4% of the total, 15.9% of those with NAFLD) had at least moderate fibrosis. CONCLUSIONS: NAFLD was present in 40% of Veterans registered in primary care; 9.4% of veterans had at least moderate hepatic fibrosis, with most having concurrent NAFLD. There was perfect concordance between NAFLD and the alternative MAFLD definition.

Admixture Mapping in African Americans Identifies New Risk Loci for HCV-Related Cirrhosis.

BACKGROUND & AIMS: Cirrhosis is the main predisposing condition for hepatocellular carcinoma. Host genetic risk factors have been reported for cirrhosis; however, whether there is a genetic contribution to racial disparities in cirrhosis requires further investigation. METHODS: We used an affected-only mapping by admixture linkage disequilibrium analysis to characterize the genetic risk of cirrhosis in 227 African American patients with cirrhosis genotyped at 19,804 ancestry-informative marker single nucleotide polymorphisms. We additionally performed analyses stratified by hepatitis C virus (HCV) infection status. To replicate our findings, we conducted a case-control analysis in an external study population (452 cases and 196 controls). RESULTS: The mean age of patients was 63.3 years and 98.2% were male. Risk factors for cirrhosis included HCV infection (83.7%) and alcohol abuse (56.4%). In the admixture mapping analysis, we found that European ancestry on chromosome 2q21.1 and African ancestry on chromosome 6p21.2 were associated with increased risk of cirrhosis in African Americans. In the fine-mapping analysis, we identified regions near POTEKP on 2q21.1 (P = .0001) and DNAH8 on 6p21.2 (P = .0017) that were associated with cirrhosis. As the admixture peaks in the HCV-positive patients were the same as those in the overall group, findings in the analysis are reflective of the HCV-positive group. In the replication analysis, the results on chromosome 2 were not significant after adjusting for multiple comparisons, and we could not replicate the results on chromosome 6. CONCLUSIONS: We used admixture mapping to identify novel genomic regions on 2q21.1 and 6p21.2 that may be associated with HCV-related cirrhosis risk in African Americans.

Using Natural Language Processing to Automatically Identify Dysplasia in Pathology Reports for Patients With Barrett's Esophagus.

BACKGROUND & AIMS: Identifying dysplasia of Barrett's esophagus (BE) in the electronic medical record (EMR) requires manual abstraction of unstructured data. Natural language processing (NLP) creates structure to unstructured free text. We aimed to develop and validate an NLP algorithm to identify dysplasia in BE patients on histopathology reports with varying report formats in a large integrated EMR system. METHODS: We randomly selected 600 pathology reports for NLP development and 400 reports for validation from patients with suspected BE in the national Veterans Affairs databases. BE and dysplasia were verified by manual review of the pathology reports. We used NLP software (Clinical Language Annotation, Modeling, and Processing Toolkit; Melax Tech, Houston, TX) to develop an algorithm to identify dysplasia using findings. The algorithm performance characteristics were calculated as recall, precision, accuracy, and F-measure. RESULTS: In the development set of 600 patients, 457 patients had confirmed BE (60 with dysplasia). The NLP identified dysplasia with 98.0% accuracy, 91.7% recall, and 93.2% precision, with an F-measure of 92.4%. All 7 patients with confirmed high-grade dysplasia were classified by the algorithm as having dysplasia. Among the 400 patients in the validation cohort, 230 had confirmed BE (39 with dysplasia). Compared with manual review, the NLP algorithm identified dysplasia with 98.7% accuracy, 92.3% recall, and 100.0% precision, with an F-measure of 96.0%. CONCLUSIONS: NLP yielded a high degree of sensitivity and accuracy for identifying dysplasia from diverse types of pathology reports for patients with BE. The application of this algorithm would facilitate research and clinical care in an EMR system with text reports in large data repositories.

Prevention of Hepatocellular Carcinoma (HCC). White Paper of the Texas Collaborative Center for Hepatocellular Cancer (TeCH) Multi-stakeholder Conference.

BACKGROUND & AIMS: Texas has the highest age-adjusted incidence rate of hepatocellular carcinoma (HCC) in the United States. The Cancer Prevention and Research Institute of Texas has funded the Texas Collaborative Center for Hepatocellular Cancer (TeCH) to facilitate HCC research, education, and advocacy activities with the overall goal of reducing HCC mortality in Texas through coordination, collaboration, and advocacy. METHODS: On September 17, 2022, TeCH co-sponsored a multi-stakeholder conference on HCC with the Baker Institute Center for Health and Biosciences. This conference was attended by HCC researchers, policy makers, payers, members from pharmaceutical industry and patient advocacy groups in and outside of Texas. This report summarizes the results of the conference. RESULTS: The goal of this meeting was to identify different strategies for preventing HCC and evaluate their readiness for implementation. CONCLUSIONS: We call for a statewide (1) viral hepatitis elimination program; (2) program to increase nonalcoholic steatohepatitis and obesity awareness; (3) research program to develop health care models that integrate alcohol associated liver disease treatment and treatment for alcohol use disorder; and (4) demonstration projects to evaluate the effectiveness of identifying and linking patient with advanced fibrosis and cirrhosis to clinical care.

Risk Stratification Model for Hepatocellular Cancer in Patients With Cirrhosis.

BACKGROUND & AIMS: The available risk stratification indices for hepatocellular cancer (HCC) have limited applicability. We developed and externally validated an HCC risk stratification index in U.S. cohorts of patients with cirrhosis. METHODS: We used data from 2 prospective U.S. cohorts to develop the risk index. Patients with cirrhosis were enrolled from 8 centers and followed until development of HCC, death, or December 31, 2021. We identified an optimal set of predictors with the highest discriminatory ability (C-index) for HCC. The predictors were refit using competing risk regression and its predictive performance was evaluated using the area under the receiver-operating characteristic curve (AUROC). External validation was performed in a cohort of 21,550 patients with cirrhosis seen in the U.S Veterans Affairs system between 2018 and 2019 with follow-up through 2021. RESULTS: We developed the model in 2431 patients (mean age 60 years, 31% women, 24% cured hepatitis C, 16% alcoholic liver disease, and 29% nonalcoholic fatty liver disease). The selected model had a C-index of 0.77 (95% confidence interval [CI], 0.73-0.81), and the predictors were age, sex, smoking, alcohol use, body mass index, etiology, α-fetoprotein, albumin, alanine aminotransferase, and platelet levels. The AUROCs were 0.75 (95% CI, 0.65-0.85) at 1 year and 0.77 (95% CI, 0.71-0.83) at 2 years, and the model was well calibrated. In the external validation cohort, the AUROC at 2 years was 0.70 with excellent calibration. CONCLUSION: The risk index, including objective and routinely available risk factors, can differentiate patients with cirrhosis who will develop HCC and help guide discussions regarding HCC surveillance and prevention. Future studies are needed for additional external validation and refinement of risk stratification.

A Study of Dietary Patterns Derived by Cluster Analysis and Their Association With Metabolic Dysfunction-Associated Steatotic Liver Disease Severity Among Hispanic Patients.

INTRODUCTION: Diet is a modifiable metabolic dysfunction-associated steatotic liver disease (MASLD) risk factor, but few studies have been conducted among Hispanic patients, despite the fact that MASLD prevalence and severity are highest among this ethnic subgroup. We aimed to identify prevalent dietary patterns among Hispanic patients using cluster analysis and to investigate associations with MASLD severity. METHODS: This cross-sectional analysis included 421 Harris County MASLD Cohort participants who self-reported Hispanic ethnicity and completed baseline food frequency questionnaires. All included patients had MASLD, diagnosed per standard clinical criteria. K-means analysis was used to identify clusters of patients sharing similar dietary habits. Multivariable adjusted logistic regression was used to estimate associations of dietary clusters with aminotransferases among the overall sample and with histologic steatosis, metabolic dysfunction-associated steatohepatitis, and fibrosis among a subsample of patients who underwent liver biopsy within 6 months of their baseline food frequency questionnaire (n = 186). RESULTS: We identified 2 clusters: a plant-food/prudent and a fast-food/meat pattern. The fast-food/meat pattern was associated with 2.47-fold increased odds (95% confidence interval 1.31-4.65) of more severe steatosis than the plant-food/prudent pattern after adjusting for demographics, metabolic score, physical activity, and alcohol ( q = 0.0159). No significant association was observed between diet and aminotransferases, metabolic dysfunction-associated steatohepatitis, or fibrosis. DISCUSSION: Given the importance of sociocultural influences on diet, it is important to understand dietary patterns prevalent among Hispanic patients with MASLD. Using cluster analysis, we identified 1 plant-based pattern vs 1 distinct fast-food/meat-based pattern associated with detrimental effects among our population. This information is an important starting point for tailoring dietary interventions for Hispanic patients with MASLD.

Validation of a pre-endoscopy risk score for predicting the presence of gastric intestinal metaplasia in a U.S. population.

BACKGROUND AND AIMS: Surveillance of gastric intestinal metaplasia (GIM) may lead to early gastric cancer detection. Our purpose was to externally validate a predictive model for endoscopic GIM previously developed in a veteran population in a second U.S. METHODS: We previously developed a pre-endoscopy risk model for detection of GIM using 423 GIM cases and 1796 control subjects from the Houston Veterans Affairs Hospital. The model included sex, age, race/ethnicity, smoking, and Helicobacter pylori infection with an area under the receiver-operating characteristic curve (AUROC) of .73 for GIM and .82 for extensive GIM. We validated this model in a second cohort of patients from 6 Catholic Health Initiative (CHI)-St Luke's hospitals (Houston, Tex, USA) from January to December 2017. Cases were defined as having GIM on any gastric biopsy sample and extensive GIM as involving both the antrum and corpus. We further optimized the model by pooling both cohorts and assessing discrimination using AUROC. RESULTS: The risk model was validated in 215 GIM cases (55 with extensive GIM) and 2469 control subjects. Cases were older than control subjects (59.8 vs 54.7 years) with more nonwhites (59.1% vs 42.0%) and H pylori infections (23.7% vs 10.9%). The model applied to the CHI-St Luke's cohort had an AUROC of .62 (95% confidence interval [CI], .57-.66) for predicting GIM and of .71 (95% CI, .63-.79) for predicting extensive GIM. When the Veterans Affairs and CHI-St Luke's cohorts were pooled, discrimination of both models improved (GIM vs extensive GIM AUROC: .74 vs .82). CONCLUSIONS: A pre-endoscopy risk prediction model was validated and updated using a second U.S. cohort with robust discrimination for endoscopic GIM. This model should be evaluated in other U.S. populations to risk-stratify patients for endoscopic GIM screening.

Trends and Variations in Pancreatic Cancer Mortality Among US Metro and Nonmetro Adults, 1999-2020.

BACKGROUND: Pancreatic cancer is the third leading cause of cancer deaths in the United States. Despite decreasing cancer mortality rates as a whole, pancreatic cancer death rates in the United States remain steady and demonstrate racial/ethnic disparities. Divergent cancer mortality trends have also been observed between metro and nonmetro populations. We therefore aimed to compare metro and nonmetro trends in pancreatic cancer mortality rates in the United States from 1999 to 2020 and investigate potential sex and racial/ethnic differences. METHODS: We analyzed National Center for Health Statistics data for all pancreatic cancer deaths among individuals aged 25 years or older in the United States. We estimated the average annual percent change (AAPC) in age-standardized pancreatic cancer mortality rates in metro versus nonmetro areas by sex and race/ethnicity. RESULTS: Of the total 810,425 pancreatic cancer-related deaths identified from 1999 to 2020, 668,547 occurred in metro areas and 141,878 in nonmetro areas. Non-Hispanic Black individuals had the highest rates of pancreatic cancer mortality regardless of metropolitan status. In both metro and nonmetro areas, pancreatic cancer mortality rates among non-Hispanic White individuals increased over the study period (AAPC: metro, males, 0.32%; females, 0.27%; nonmetro, males, 0.77%; females, 0.62%). Non-Hispanic Black individuals in metro areas had a decrease in pancreatic cancer mortality (AAPC: males, -0.25%; females, -0.29%), but rates among non-Hispanic Black women in nonmetro areas increased (AAPC, 0.49%). CONCLUSIONS: There are variations not only in pancreatic cancer mortality by metro and nonmetro status but also by sex and race/ethnicity within these areas. Individuals who live in nonmetro areas have higher pancreatic cancer mortality rates and increasing death rates compared with their metro counterparts. These findings highlight the need for targeted cancer prevention strategies that are specific to metro or nonmetro populations.

Evolution of endoscopic mucosal resection (EMR) technique and the reduced recurrence of large colonic polyps from 2012 to 2020.

BACKGROUND: Endoscopic mucosal resection (EMR) is an effective method for removing non-pedunculated polyps ≥ 20 mm. We aimed to examine changes in EMR techniques over a 9-year period and evaluate frequency of histologic-confirmed recurrence. METHODS: We identified patients who underwent EMR of non-pedunculated polyps ≥ 20 mm at a safety net and the Veteran's Affairs (VA) hospital in Houston, Texas between 2012 and 2020. Odds ratios (ORs) and 95% confidence intervals (CI) for associations with recurrence risk were estimated using multivariable logistic regression. RESULTS: 461 unique patients were included. The histologic-confirmed recurrence was 29.0% at 15.6 months median follow up (IQR 12.3 - 17.4). Polyps removed between 2018 and 2020 had a 0.43 decreased odds of recurrence vs. polyps removed between 2012 and 2014. The use of viscous lifting agents increased over time (from 0 to 54%), and the use of saline was associated with increased risk of recurrence (OR 2.28 [CI 1.33 - 3.31]). CONCLUSIONS: Histologic-confirmed recurrence after EMR for non-pedunculated polyps ≥ 20 mm decreased over the seven year-period. Saline was associated with a higher risk of recurrence and the use of more viscous agents increased over time.

Gastric Cancer Risk in Patients with Long-Term Use of Proton Pump Inhibitors: A Systematic Review and Meta-Analysis of Observational and Interventional Studies.

BACKGROUND: A growing number of studies that differ in design, quality, and results report an association between the use of proton pump inhibitors (PPIs) and the risk of gastric cancer (GC). We conducted a systematic review and meta-analysis, when possible, of observational and interventional studies examining PPI use and risk of GC. METHODS: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We identified studies fully published in English through January 2023 using MeSH and non-MeSH keywords. We used random effects models to calculate pooled risk estimates with 95% confidence interval (CI) between PPI use and overall GC, cardia GC, and non-cardia GC. We estimated heterogeneity (I2) among studies. We examined the effect of study design and quality, GC site, H. pylori infection, and PPI duration. We assessed quality using the Newcastle-Ottawa Quality Assessment Scale and Risk Of Bias In Non-randomized Studies of Interventions. RESULTS: We identified 15 observational studies, of which 13 were included in the meta-analysis (six cohort and seven case-control). There was a modest 1.67-fold increase in overall GC risk (95% CI 1.39, 2.00) and no increase in cardia GC risk [odds ratio (OR) 1.12; 95% CI 0.80, 1.56] with PPI use. However, there was high heterogeneity (I2 = 61.3%, p = 0.004) among studies. All but one study had at least moderate risk of bias. In the six studies accounting for H. pylori, GC risk associated with PPI use increased slightly (OR 1.78; 95% CI 1.25, 2.52). Duration response was not reported consistently to allow pooled estimates. We identified only one interventional randomized controlled study that included GC as an outcome of interest, and it did not show increased GC risk. CONCLUSIONS: The overall available evidence is not supportive of a meaningful change in GC risk, either cardia or non-cardia, with PPI use.