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PURPOSE Noncardia gastric cancer (NCGC) is a leading cause of global cancer mortality, and is often diagnosed at advanced stages. Development of NCGC risk models within electronic health records (EHR) may allow for improved cancer prevention. There has been much recent interest in use of machine learning (ML) for cancer prediction, but few studies comparing ML with classical statistical models for NCGC risk prediction. METHODS We trained models using logistic regression (LR) and four commonly used ML algorithms to predict NCGC from age-/sex-matched controls in two EHR systems: Stanford University and the University of Washington (UW). The LR model contained well-established NCGC risk factors (intestinal metaplasia histology, prior Helicobacter pylori infection, race, ethnicity, nativity status, smoking history, anemia), whereas ML models agnostically selected variables from the EHR. Models were developed and internally validated in the Stanford data, and externally validated in the UW data. Hyperparameter tuning of models was achieved using cross-validation. Model performance was compared by accuracy, sensitivity, and specificity. RESULTS In internal validation, LR performed with comparable accuracy (0.732; 95% CI, 0.698 to 0.764), sensitivity (0.697; 95% CI, 0.647 to 0.744), and specificity (0.767; 95% CI, 0.720 to 0.809) to penalized lasso, support vector machine, K-nearest neighbor, and random forest models. In external validation, LR continued to demonstrate high accuracy, sensitivity, and specificity. Although K-nearest neighbor demonstrated higher accuracy and specificity, this was offset by significantly lower sensitivity. No ML model consistently outperformed LR across evaluation criteria. CONCLUSION Drawing data from two independent EHRs, we find LR on the basis of established risk factors demonstrated comparable performance to optimized ML algorithms. This study demonstrates that classical models built on robust, hand-chosen predictor variables may not be inferior to data-driven models for NCGC risk prediction.

Background: Gastric cancer is a leading cause of cancer morbidity and mortality. Developing information systems which integrate clinical and genomic data may accelerate discoveries to improve cancer prevention, detection, and treatment. To support translational research in gastric cancer, we developed the Gastric Cancer Registry (GCR), a North American repository of clinical and cancer genomics data. Methods: Participants self-enrolled online. Entry criteria into the GCR included the following: (i) diagnosis of gastric cancer, (ii) history of gastric cancer in a first- or second-degree relative, or (iii) known germline mutation in the gene CDH1. Participants provided demographic and clinical information through a detailed survey. Some participants provided specimens of saliva and tumor samples. Tumor samples underwent exome sequencing, whole-genome sequencing, and transcriptome sequencing. Results: From 2011 to 2021, 567 individuals registered and returned the clinical questionnaire. For this cohort 65% had a personal history of gastric cancer, 36% reported a family history of gastric cancer, and 14% had a germline CDH1 mutation. 89 patients with gastric cancer provided tumor samples. For the initial study, 41 tumors were sequenced using next-generation sequencing. The data was analyzed for cancer mutations, copy-number variations, gene expression, microbiome, neoantigens, immune infiltrates, and other features. We developed a searchable, web-based interface (the GCR Genome Explorer) to enable researchers’ access to these datasets. Conclusions: The GCR is a unique, North American gastric cancer registry which integrates clinical and genomic annotation. Impact: Available for researchers through an open access, web-based explorer, the GCR Genome Explorer will accelerate collaborative gastric cancer research across the United States and world.

Purpose:The tumor microenvironment (TME) consists of a heterogenous cellular milieu that can influence cancer cell behavior. Its characteristics have an impact on treatments such as immunotherapy. These features can be revealed with single-cell RNA sequencing (scRNA-seq). We hypothesized that scRNA-seq analysis of gastric cancer together with paired normal tissue and peripheral blood mononuclear cells (PBMC) would identify critical elements of cellular deregulation not apparent with other approaches.Experimental Design:scRNA-seq was conducted on seven patients with gastric cancer and one patient with intestinal metaplasia. We sequenced 56,167 cells comprising gastric cancer (32,407 cells), paired normal tissue (18,657 cells), and PBMCs (5,103 cells). Protein expression was validated by multiplex immunofluorescence.Results:Tumor epithelium had copy number alterations, a distinct gene expression program from normal, with intratumor heterogeneity. Gastric cancer TME was significantly enriched for stromal cells, macrophages, dendritic cells (DC), and Tregs. TME-exclusive stromal cells expressed distinct extracellular matrix components than normal. Macrophages were transcriptionally heterogenous and did not conform to a binary M1/M2 paradigm. Tumor DCs had a unique gene expression program compared to PBMC DCs. TME-specific cytotoxic T cells were exhausted with two heterogenous subsets. Helper, cytotoxic T, Treg, and NK cells expressed multiple immune checkpoint or co-stimulatory molecules. Receptor–ligand analysis revealed TME-exclusive intercellular communication.Conclusions:Single-cell gene expression studies revealed widespread reprogramming across multiple cellular elements in the gastric cancer TME. Cellular remodeling was delineated by changes in cell numbers, transcriptional states, and intercellular interactions. This characterization facilitates understanding of tumor biology and enables identification of novel targets including for immunotherapy.

PURPOSE: Gastric cancers are classified as diffuse-type (DTGC) or intestinal-type (ITGC). DTGCs have distinct clinical and histopathologic features, and carry a worse overall prognosis compared to ITGCs. Atrophic gastritis (AG) and intestinal metaplasia (IM) are known precursors to ITGC. It is unknown if AG and IM increase risk for DTGC. METHODS: We performed a systematic review to identify studies reporting on the association of AG/IM and DTGC. We extracted the odds ratio (OR) of the association from studies, and performed pool analysis. Subgroup analysis was performed on studies reporting histologic severity (using operative link systems) to assess if histologic severity of AG/IM was associated with higher risk. RESULTS: We identified six case-control and eight cohort studies for inclusion. Both AG (pooled OR=1.9, 95% CI 1.5 to 2.4, p

There exists no coherent national strategy for the early detection or prevention of gastric cancer in the United States (US), even among identified high-risk groups such as Asian Americans, African Americans, Hispanic Americans, and Alaska Native/American Indian peoples. As a result, patients with gastric cancer in the US are diagnosed at later stages and demonstrate worse overall survival compared to nations of East Asia with established screening programs (Table 1). The under-recognition of gastric cancer risk within minority communities is a significant unaddressed healthcare disparity.

Background The Affordable Care Act (ACA) with Medicaid expansion implemented in 2014, extended health insurance to >20-million previously uninsured individuals. However, it is unclear whether enhanced primary care access with Medicaid expansion decreased emergency department (ED) visits and hospitalizations for gastrointestinal (GI)/pancreatic/liver diseases. Methods We evaluated trends in GI/pancreatic/liver diagnosis-specific ED/hospital utilization over a 5-year period leading up to Medicaid expansion and a year following expansion, in California (a state that implemented Medicaid expansion) and compare these with Florida (a state that did not). Results From 2009 to 2013, GI/pancreatic/liver disease ED visits increased by 15.0% in California and 20.2% in Florida and hospitalizations for these conditions decreased by 2.6% in California and increased by 7.9% in Florida. Following Medicaid expansion, a shift from self-pay/uninsured to Medicaid insurance was seen California; in addition, a new decrease in ED visits for nausea/vomiting and GI infections, was evident, without associated change in overall ED/hospital utilization trends. Total hospitalization charges for abdominal pain, nausea/vomiting, constipation, and GI infection diagnoses decreased in California following Medicaid expansion, but increased over the same time-period in Florida. Conclusions We observed a striking payer shift for GI/pancreatic/liver disease ED visits/hospitalizations after Medicaid expansion in California, indicating a shift in the reimbursement burden in self-pay/uninsured patients, from patients and hospitals to the government. ED visits and hospitalization charges decreased for some primary care-treatable GI diagnoses in California, but not for Florida, suggesting a trend toward lower cost of gastroenterology care, perhaps because of decreased hospital utilization for conditions amenable to outpatient management.

Background & Aims Gastric cancer (GC) remains a leading cause of mortality among certain racial, ethnic, and immigrant groups in the United States (US). The majority of GCs are diagnosed at advanced stages, and overall survival remains poor. There exist no structured national strategies for GC prevention in the US. Methods On March 5–6, 2020 a summit of researchers, policy makers, public funders, and advocacy leaders was convened at Stanford University to address this critical healthcare disparity. After this summit, a writing group was formed to critically evaluate the effectiveness, potential benefits, and potential harms of methods of primary and secondary prevention through structured literature review. This article represents a consensus statement prepared by the writing group. Results The burden of GC is highly inequitably distributed in the US and disproportionately falls on Asian, African American, Hispanic, and American Indian/Alaskan Native populations. In randomized controlled trials, strategies of Helicobacter pylori testing and treatment have been demonstrated to reduce GC-specific mortality. In well-conducted observational and ecologic studies, strategies of endoscopic screening have been associated with reduced GC-specific mortality. Notably however, all randomized controlled trial data (for primary prevention) and the majority of observational data (for secondary prevention) are derived from non-US sources. Conclusions There exist substantial, high-quality data supporting GC prevention derived from international studies. There is an urgent need for cancer prevention trials focused on high-risk immigrant and minority populations in the US. The authors offer recommendations on how strategies of primary and secondary prevention can be applied to the heterogeneous US population.

Gastric intestinal metaplasia (GIM) is a known premalignant condition of the human stomach along the pathway to gastric cancer (GC). Histologically, GIM represents the replacement of normal gastric mucosa by mucin-secreting intestinal mucosa. Helicobacter pylori infection is the most common etiologic agent of GIM development worldwide. The prevalence of GIM is heterogeneous among different regions of the world and correlates with the population endemicity of H. pylori carriage, among other environmental factors. GC remains the third leading cause of cancer-related mortality globally. GIM is usually diagnosed by upper endoscopy with biopsy, and histologic scoring systems have been developed to risk-stratify patients at highest risk for progression to GC. Several recent endoscopic imaging modalities may improve the optical detection of GIM and early GC. Appropriate surveillance of GIM may be cost effective and represents an opportunity for the early diagnosis and therapy of GC. Certain East Asian nations have established population-level programs for the screening and surveillance of GIM; guidelines regarding GIM surveillance have also recently been published in Europe. By contrast, few data exist regarding the appropriateness of surveillance of GIM in the United States. In this review, we discuss the pathogenesis, epidemiology, diagnosis, and management of GIM with an emphasis on the role of appropriate endoscopic surveillance.

BACKGROUND AND AIMS: Studies from our group and others demonstrate residual fluid in 42% to 95% of endoscope working channels despite high-level disinfection and drying. Additionally, persistent simethicone has been reported in endoscope channels despite reprocessing. METHODS: Endoscopy was performed by using water or varied simethicone concentrations (0.5%, 1%, 3%) for flushing. After high-level disinfection/drying, we inspected endoscope working channels for retained fluid by using the SteriCam borescope. Working channel rinsates were evaluated for adenosine triphosphate (ATP) bioluminescence. Fourier transform infrared spectroscopy was performed on fluid droplets gathered from a colonoscope in which low-concentration simethicone was used. RESULTS: Use of medium/high concentrations of simethicone resulted in a higher mean number of fluid droplets (13.5/17.3 droplets, respectively) and ATP bioluminescence values (20.6/23 relative light units [RLUs], respectively) compared with that of procedures using only water (6.3 droplets/10.9 RLUs; P < .001). Two automated endoscope reprocessing cycles resulted in return of a fluid droplet and ATP bioluminescence values to ranges similar to that of procedures that used only water (P = .56). Low-concentration simethicone did not increase the mean residual fluid or ATP bioluminescence values compared with procedures that used only water (5.8 droplets/15.6 RLUs). Fourier transform infrared analysis revealed simethicone in the endoscope working channel after use of low-concentration simethicone. CONCLUSIONS: Use of medium/high concentrations of simethicone is associated with retention of increased fluid droplets and higher ATP bioluminescence values in endoscope working channels, compared with endoscopes in which water or low concentration simethicone was used. However, simethicone is detectable in endoscopes despite reprocessing, even when it is utilized in low concentrations. Our data suggest that when simethicone is used, it should be used in the lowest concentration possible. Facilities may consider 2 automated endoscope reprocessor cycles for reprocessing of endoscopes when simethicone has been used. (Gastrointest Endosc 2019;89:115–23.)

Gastric cancer (GC) remains a leading cause of cancer morbidity and mortality worldwide. Outcomes from GC remain poor, especially in Western nations where cancer diagnosis is usually at advanced stages where curative resection is not possible. By contrast, nations of East Asia have adopted methods of population-level screening with improvements in stage of diagnosis and survival. In this review, the authors discuss the epidemiology of GC in Western populations, highlight at-risk populations who may benefit from screening, overview screening modalities, and discuss promising approaches to early GC detection.

PurposeBreast cancer is the second leading cause of female cancer mortality in the United States and breast cancer mortality in Asian Americans (AA) is rising by 1.5% per year. However, aggregated AA breast cancer death rates may mask important mortality differences in major AA groups.Population & Setting11,388 AA and 473,927 non-Hispanic White (NHW) females based on the United States Centers for Disease Control and Prevention National Vital Statistics System database 2003-2017.MethodsAge-adjusted mortality rates (AAMR) were used to estimate trends in breast cancer mortality in Asian Indians, Chinese, Filipinas, Japanese, Koreans, Vietnamese, and non-Hispanic Whites from 2003–2017, with attention to annual percentage change (APC) and proportional mortality rates (PMR).ResultsFrom 2003-2017, breast cancer deaths comprised 14.4% in NHWs, 13.7% in aggregate AAs, 19.8% in Asian Indians, and 18.6% of all cancer deaths in Filipinas. While NHW breast cancer mortality rate significantly decreased (APC -2.1; CI -2.6, -1.6; p < 0.001) from 2003 to 2017, aggregate AA mortality rates were unchanged (APC 3.07; CI -0.37, 7.8; p = 0.071). However, when disaggregated, breast cancer mortality in Filipina (APC 1.9; CI 0.8, 3.0; p < 0.002), Chinese (APC 2.1; CI 1.3, 3.0; p < 0.001), and Korean (APC 2.6; CI 1.0, 4.1; p = 0.004) women significantly increased. Breast cancer mortality rates in Japanese women decreased (APC -1.9; CI -5.9, 2.1; p = 0.3).ConclusionWhile the proportion of women dying from breast cancer were similar in NHWs and aggregate Asians, when disaggregated, Filipina, Korean, and Chinese women had increased mortality rates over the past 15 years. During this time, breast cancer mortality in NHW and Japanese women decreased. Understanding disaggregated breast cancer mortality rates in Asians may improve culturally-tailored outreach, prevention, and treatment strategies to reduce cancer deaths from this critical disease.

Objective Asian Indians are among the fastest growing United States (US) ethnic subgroups. We characterized mortality trends for leading causes of death among foreign-born and US-born Asian Indians in the US between 2005–2017. Study design and setting Using US standardized death certificate data, we examined leading causes of death in 73,470 Asian Indians and 20,496,189 non-Hispanic whites (NHWs) across age, gender, and nativity. For each cause, we report age-standardized mortality rates (AMR), longitudinal trends, and absolute percent change (APC). Results We found that Asian Indians’ leading causes of death were heart disease (28% mortality males; 24% females) and cancer (18% males; 22% females). Foreign-born Asian Indians had higher all-cause AMR compared to US-born (AMR 271 foreign-born, CI 263–280; 175.8 US-born, CI 140–221; p Conclusions Foreign-born Asian Indians were 2.2 times more likely to die of heart disease and 1.6 times more likely to die of cancer. Asian Indian male AMR was 49% greater than female on average, although AMR was consistently lower for Asian Indians when compared to NHWs.

Early identification of gastric precancerous lesions, including atrophic gastritis (AG) and intestinal metaplasia (IM), may improve gastric cancer detection and prevention. Because AG and IM are generally asymptomatic, many of the estimated 15 million Americans who carry these lesions remain undiagnosed.1 AG and IM are associated with either active or prior Helicobacter pylori (Hp) infection. Hp infection leads to perturbations in the serum concentration of gastric hormones pepsinogen I (PGI), pepsinogen II, the pepsinogen I/II ratio (PGR), gastrin-17 (G-17), and Hp IgG.2,3 In East Asia and other regions with high burden of Hp infection and gastric cancer, these biomarkers have been used as screening tools for AG and IM.4 However, there exists limited data on the sensitivity and discrimination of these serologic markers in low-Hp-prevalence populations, such as the United States.

Background and study aims Patients with cirrhosis demonstrate alterations in physiology, hemodynamics, and immunity which may increase procedural risk. There exist sparse data regarding the safety of performing ambulatory colonoscopy in patients with cirrhosis. Patients and methods From a population-based sample of three North American states (California, Florida, and New York), we collected data on 3,590 patients with cirrhosis who underwent ambulatory colonoscopy from 2009 to 2014. We created a control cohort propensity score-matched for cirrhotic severity who did not undergo colonoscopy (N = 3,590) in order to calculate the attributable risk for adverse events. The primary endpoint was the rate of unplanned hospital encounters (UHEs) within 14 days of colonoscopy (or from a synthetic index date for the control cohort). Predictors for UHE were assessed in multivariable regression. Results The attributable risk for any UHE following colonoscopy was 3.1 % (confidence interval [CI] 2.1–4.1 %, P Conclusions There is a moderate though detectable increase in risk for adverse event following ambulatory colonoscopy in patients with cirrhosis. The presence of ascites in particular portends higher risk. These data may guide clinicians when counseling patients with cirrhosis on the choice of colorectal cancer screening modality.

Biliary strictures after orthotopic liver transplantation (OLT) are typically managed by sequential ERCP procedures, with incremental dilation of the stricture and stent exchange (IDSE) and placement of new stents. This approach resolves80% of strictures after 12 months but requires costly, lengthy ERCPs with significant patient radiation exposure. Increasing awareness of the harmful effects of radiation, escalating healthcare costs, and decreasing reimbursement for procedures mandate maximal efficiency in performing ERCP. We compared the traditional IDSE protocol with a sequential stent addition (SSA) protocol, in which additional stents are placed across the stricture during sequential ERCPs, without stent removal/exchange or stricture dilation.Patients undergoing ERCP for OLT-related anastomotic strictures from 2010 to 2016 were identified from a prospectively maintained endoscopy database. Procedure duration, fluoroscopy time, stricture resolution rates, adverse events, materials fees, and facility fees were analyzed for IDSE and SSA procedures.Seventy-seven patients underwent 277 IDSE and 132 SSA procedures. Mean fluoroscopy time was 64.5% shorter (P .0001) and mean procedure duration 41.5% lower (P .0001) with SSA compared with IDSE. SSA procedures required fewer accessory devices, resulting in significantly lower material (63.8%, P .0001) and facility costs (42.8%, P .0001) compared with IDSE. Stricture resolution was95%, and low adverse event rates did not significantly differ.SSA results in shorter, cost-effective procedures requiring fewer accessory devices and exposing patients to less radiation. Stricture resolution rates are equivalent to IDSE, and adverse events do not differ significantly, even in this immunocompromised population.

Following a period of uncertainty and disorganization, the gastroenterology (GI) national leadership decided to reinstitute the fellowship match (the Match) under the auspices of the National Residency Matching Program (NRMP) in 2006. Although it has now been a decade since the rebirth of the Match, there have been limited data published regarding progress made. In this piece, we discuss reasons for the original collapse of the GI Match, including most notably a perceived oversupply of GI physicians and a poor job market. We discuss the negative impacts the absence of the Match had on programs and on applicants, as well as the impetus to re-organize the Match under the NRMP. We then utilize data published annually by the NRMP to demonstrate that in the decade since its rebirth, the GI Match has been remarkably successful in terms of attracting the participation of applicants and programs. We show that previous misguided concerns of an oversupply of GI physicians were not realized, and that GI fellowship positions remain highly competitive for internal medicine applicants. Finally, we discuss possible implications of recent changes in the healthcare landscape on the GI Match.

Background: Asian Americans are at higher risk for noncardia gastric cancers (NCGC) relative to non-Hispanic Whites (NHW). Asian Americans are genetically, linguistically, and culturally heterogeneous, yet have mostly been treated as a single population in prior studies. This aggregation may obscure important subgroup-specific cancer patterns. Methods: We utilized data from 13 regional United States cancer registries from 1990 to 2014 to determine secular trends in incidence and survivorship from NCGC. Data were analyzed for NHWs and the six largest Asian American subgroups: Chinese, Japanese, Filipino, Korean, Vietnamese, and South Asian (Indian/Pakistani). Results: There exists substantial heterogeneity in NCGC incidence between Asian subgroups, with Koreans (48.6 per 100,000 person-years) having seven-fold higher age-adjusted incidence than South Asians (7.4 per 100,000 person-years). Asians had generally earlier stages of diagnosis and higher rates of surgical resection compared with NHWs. All Asian subgroups also demonstrated higher 5-year observed survival compared with NHWs, with Koreans (41.3%) and South Asians (42.8%) having survival double that of NHWs (20.1%, P < 0.001). In multivariable regression, differences in stage of diagnosis and rates of resection partially explained the difference in survivorship between Asian subgroups. Conclusions: We find substantial differences in incidence, staging, histology, treatment, and survivorship from NCGC between Asian subgroups, data which challenge our traditional perceptions about gastric cancer in Asians. Both biological heterogeneity and cultural/environmental differences may underlie these findings. Impact: These data are relevant to the national discourse regarding the appropriate role of gastric cancer screening, and identifies high-risk racial/ethnic subgroups who many benefit from customized risk attenuation programs.

Purpose: The tumor microenvironment (TME) consists of a heterogenous cellular milieu that can influence cancer cell behavior. Its characteristics have an impact on treatments such as immunotherapy. These features can be revealed with single-cell RNA sequencing (scRNA-seq). We hypothesized that scRNA-seq analysis of gastric cancer together with paired normal tissue and peripheral blood mononuclear cells (PBMC) would identify critical elements of cellular deregulation not apparent with other approaches. Experimental Design: scRNA-seq was conducted on seven patients with gastric cancer and one patient with intestinal metaplasia. We sequenced 56,167 cells comprising gastric cancer (32,407 cells), paired normal tissue (18,657 cells), and PBMCs (5,103 cells). Protein expression was validated by multiplex immunofluorescence. Results: Tumor epithelium had copy number alterations, a distinct gene expression program from normal, with intratumor heterogeneity. Gastric cancer TME was significantly enriched for stromal cells, macrophages, dendritic cells (DC), and Tregs. TME-exclusive stromal cells expressed distinct extracellular matrix components than normal. Macrophages were transcriptionally heterogenous and did not conform to a binary M1/M2 paradigm. Tumor DCs had a unique gene expression program compared to PBMC DCs. TME-specific cytotoxic T cells were exhausted with two heterogenous subsets. Helper, cytotoxic T, Treg, and NK cells expressed multiple immune checkpoint or co-stimulatory molecules. Receptor–ligand analysis revealed TME-exclusive intercellular communication. Conclusions: Single-cell gene expression studies revealed widespread reprogramming across multiple cellular elements in the gastric cancer TME. Cellular remodeling was delineated by changes in cell numbers, transcriptional states, and intercellular interactions. This characterization facilitates understanding of tumor biology and enables identification of novel targets including for immunotherapy.

PurposeThe tumor microenvironment (TME) consists of a heterogenous cellular milieu that can influence cancer cell behavior. The characteristics of the cellular TME have a dramatic impact on treatments such as immunotherapy. These features can be revealed with single-cell RNA sequencing (scRNA-seq). We hypothesized that single cell gene expression studies of gastric cancer (GC) together with paired normal tissue and peripheral blood mononuclear cells (PBMCs) would identify critical elements of cellular dysregulation not apparent with other approaches.MethodsSingle cell gene expression studies were conducted on seven patients with GC and one patient with intestinal metaplasia. We sequenced 56,167 cells comprising GC (32,407 cells), paired normal tissue (18,657 cells) and PBMCs (5,103 cells). Protein expression of genes of interest was validated by multiplex immunofluorescence.ResultsTumor epithelium had copy number alterations and a distinct gene expression program compared to normal with intra-tumor heterogeneity. The GC TME was significantly enriched for stromal cells, macrophages, dendritic cells (DCs) and Tregs. TME-exclusive stromal cells expressed extracellular matrix components distinct from normal tissue. Macrophages were transcriptionally heterogenous and did not conform to a binary M1/M2 paradigm. Gene expression program of tumor DCs was unique from PBMC DCs. TME-specific cytotoxic T cells comprised of two exhausted heterogenous subsets. Helper, cytotoxic T, Treg and NK cells expressed multiple immune checkpoint or costimulatory molecules. Receptor-ligand analysis revealed TME-exclusive inter-cellular communication.ConclusionsSingle cell gene expression studies revealed widespread reprogramming across multiple cellular elements in the milieu of the GC TME. Cellular remodeling was delineated by changes in cell numbers, transcriptional states and inter-cellular interactions. This characterization facilitates understanding of tumor biology and enables the identification of novel molecular targets including for cancer immunotherapy.STATEMENT OF TRANSLATIONAL RELEVANCEWe leveraged the power of single-cell genomics to characterize the heterogenous cell types and states in the tumor microenvironment (TME). By profiling thousands of single cells from surgical resections of gastric cancer together with paired normal mucosa and peripheral blood mononuclear cells (PBMCs), we determined the deviations in the TME from physiological conditions. Our analysis revealed a cellular reprogramming of the TME compared to normal mucosa in immune and stromal lineages. We detected transcriptional heterogeneity within macrophages and a TME-specific gene expression program in dendritic cells. Cytotoxic T cells in the TME had heterogenous profiles of exhaustion and expression of multiple immune checkpoint and costimulatory molecules. We constructed a receptor-ligand based inter-cellular communications network that was exclusive to tumor tissue. These discoveries provide information at a highly granular cellular resolution enabling advances in cancer biology, biomarker discovery and identification of treatment targets such as for immunotherapy.

Introduction: Within the United States (US), Asian/Pacific Islanders (APIs) are at increased risk for non-cardia gastric adenocarcinoma (NCGA) compared to non-Hispanic whites (NHWs). Previous epidemiologic research has treated APIs as an aggregated group for analysis; however, substantial genetic and environmental differences may exist within subgroups. Very limited data exist regarding gastric cancer epidemiology as stratified by API subgroup. Methods: All incident cases of NCGA diagnosed in the years 2000-2014 were identified from the Surveillance, Epidemiology, and End Results Program registries incorporating California, Connecticut, Detroit, Hawaii, Iowa, New Mexico, Seattle, Atlanta, and New Jersey. API subgroup of patients was identified: Korean, Japanese, Chinese, Vietnamese, Filipino, and Indian. API subgroup population estimates were obtained from the American Community Survey. The age-adjusted incidence rates per 100,000 population and 95% confidence intervals (CIs) were generated for each subgroup, and among non-Hispanic whites (NHWs) for reference. The stages of diagnosis (as defined by National Cancer Institute summary stage) were compared between subgroups. Differences between subgroups in all-cause mortality following diagnosis were evaluated utilizing proportional hazards (PH) regression, adjusting for differences in tumor stage, age, and gender. Results: There exist substantial differences in age-adjusted incidences of NCGA between subgroups: Koreans (34.8 per 100K), Japanese (17.0 per 100K), Vietnamese (14.6 per 100K), Chinese (11.2 per 100K), Indian (5.4 per 100K), and Filipino (5.3 per 100K). The incidence among NHWs was 3.8 per 100K. All API subgroups as well as NHWs demonstrated a decrease in age-standardized incidence over the study period. There exist differences in the proportion of cancers diagnosed at local stage: Koreans (37.8%), Japanese (28.1%), Chinese (25.7%), Vietnamese (24.4%), Indian (21.6%), Filipino (18.9%), and NHWs (23.7%). API subgroups had better overall survival from NCGA compared to NHWs (reference) in PH regression: Korean (HR 0.50, CI 0.47-0.54, p Discussion: Substantial heterogeneity in risk for NCGA exist between API subgroups. Korean Americans are at highest risk, with incidence nearly seven-fold higher than Filipinos and Indians (whose risk is similar to NHW). This suggests that the higher NCGA-risk in APIs in aggregate are driven by certain subgroups. Interestingly, Koreans, Japanese, Vietnamese, Chinese, and Indians all had better survival following NCGA diagnosis than NHWs, even after adjustment for stage of diagnosis. These epidemiologic data may hold important implications for gastric cancer screening or surveillance programs. This abstract is also being presented as Poster B104. Citation Format: Robert J. Huang, Joo Ha Hwang, Ann Hsing, Latha Palaniappan. Disaggregation of gastric cancer risk Between Asian American subgroups [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr PR03.

Introduction Gastric intestinal metaplasia (GIM) is a precursor to gastric cancer (GC). It is not cost effective to survey the general American population for progression from GIM onto GC; however, development of risk-stratification models may allow for targeted surveillance. There exist very limited data regarding GIM epidemiology or risk derived from North American populations. The Stanford Gastric Precancerous Conditions Study (GAPS) is an ongoing, prospective study incorporating both 1) a cross-sectional, case-control study of subjects with GIM compared to controls, and 2) a longitudinal evaluation of subjects with GIM to evaluate risk factors for progression. The purpose of GAPS is to both improve the detection of GIM, and to predict risk for progression of GIM onto dysplasia or GC. Methods At time of enrollment in GAPS, all patients complete a standardized questionnaire inquiring about medical, family, dietary, and exposure history. Biopsies are performed from both antrum and body, and bio-specimens from the gastric mucosa, blood, and saliva are collected. Subjects are assigned an operative link for GIM (OLGIM) score based on adjudication by an expert pathologist. Demographic, clinical, and environmental covariates are compared between cases of GIM and controls. Subgroup analysis is performed to compare cases of advanced GIM (defined as OLGIM >=2) and controls. Continuous variables are analyzed using Student’s T-test, and categorical variables are analyzed using the Chi-squared test. Results As of July 2019, 44 cases and 49 controls have undergone questionnaire administration, endoscopy, and bio-specimen collection. Of cases, 23 demonstrate advanced GIM. Subjects with GIM were older (65 vs 56 years, p Citation Format: Robert J Huang, Sungho Park, Tanvi Chitre, Jeanne Shen, Teri Longacre, Joo Ha Hwang. A case-control study of risk factors for advanced gastric intestinal metaplasia in a multiethnic United States population (The Stanford GAPS Study) [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C059.

Background/Aims: Within the United States (U.S.) regional disparities in overall mortality exist at both the state and county levels. The epidemiology and outcomes of non-cardia gastric cancer (NCGA) based on geographic region is incompletely studied. Such knowledge would inform resource allocation and targeting of cancer prevention/early detection programs. The aims of this study were to define NCGA-specific mortality in the U.S. according to population-based county-level data, and to analyze the association between county-level attributes (ruralness, educational attainment, poverty, unemployment) and survival. Methods: All NCGAs reported to the Surveillance Epidemiology and End Results Program (SEER) between 2004-2016 were identified; tumor stage, performance of surgical resection, patient-level demographic covariates, survival time, and mortality were captured. Diagnoses were linked to county-level attributes of ruralness, educational attainment, poverty, and unemployment derived from the American Community Survey. Cox proportional hazards regression, adjusted for relevant confounders and effect modifiers, was utilized to identify county-level attributes which impacted survival. Analysis was performed stratified by stage of diagnosis. Results: 48,284 NCGAs from 614 (260 Urban, 354 Rural) counties were included for analysis. Rural counties had significantly worse NCGA-specific survival compared to Urban counties (HR 1.18, CI 1.12-1.23, p Citation Format: Robert Jeffrey Huang, Ann Hsing, Latha Palaniappan, Joo Ha Hwang. Regional disparities in gastric cancer survival in the United States: An observational cohort study of the Surveillance Epidemiology and End Results Program, 2004-2016 [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C058.

BACKGROUND AND AIMS: Pancreatic intraepithelial neoplasia is associated with chronic pancreatitis (CP) changes on EUS. The objective of this study was to determine whether CP changes were more common in high-risk individuals (HRIs) than in control subjects and whether these changes differed among higher-risk subsets of HRIs. METHODS: HRIs and control subjects were identified from an endoscopy database. HRIs were defined as having predisposing mutations or a family history (FH) of pancreatic ductal adenocarcinoma. HRIs were classified as vHRIs who met Cancer of the Pancreas Screening (CAPS) criteria for high risk and mHRIs who did not. Multivariable logistic regression was used to adjust for confounders and CP risk factors. RESULTS: Sixty-five HRIs (44 vHRIs, 21 mHRIs) and 118 control subjects were included. HRIs were included for FH (25), Lynch syndrome (5), Peutz-Jeghers syndrome (2), and mutations in BRCA1/2 (26), PALB2 (3), ATM (3), and CDKN2A (1). After adjustment for relevant variables, HRIs were 16 times more likely to exhibit 3 or more CP changes than control subjects (95% confidence interval, 2.6–97.0; P = .003). HRIs were also more likely to have hypoechoic foci (odds ratio, 8.0; 95% confidence interval, 1.9–32.9; P = .004). vHRIs and mHRIs did not differ in frequency of 3 or more CP changes on EUS. CONCLUSIONS: HRIs were more likely to exhibit CP changes and hypoechoic foci on EUS compared with control subjects. HRIs with these findings may require closer surveillance. HRIs who did or did not meet CAPS criteria did not differ with regard to CP findings, supporting a more inclusive approach to screening. (Gastrointest Endosc 2019;89:842–51.)

Cholecystectomy (CCY) after an episode of choledocholithiasis requiring endoscopic retrograde cholangiopancreatography (ERCP) with stone extraction reduces recurrent biliary events compared to expectant management. We studied practice patterns for performance of CCY after ERCP for choledocholithiasis using data from 3 large states and evaluated the effects of delaying CCY.We conducted a retrospective cohort study using the ambulatory surgery, inpatient, and emergency department databases from the states of California (years 2009-2011), New York (2011-2013), and Florida (2012-2014). We collected data from 4516 patients hospitalized with choledocholithiasis who underwent ERCP. We compared outcomes of patients who underwent CCY at index admission (early CCY), elective CCY within 60 days of discharge (delayed CCY), or did not undergo CCY (no CCY), calculating rate of recurrent biliary events (defined as an emergency department visit or unplanned hospitalization due to symptomatic cholelithiasis, cholecystitis, choledocholithiasis, cholangitis, or biliary pancreatitis), mortality, and cost by CCY cohort. We also evaluated risk factors for not undergoing CCY. The primary outcome measure was the rate of recurrent biliary events in the 365 days after discharge from index admission.Of the patients who underwent ERCP for choledocholithiasis, 41.2% underwent early CCY, 10.9% underwent delayed CCY, and 48.0% underwent no CCY. Early CCY reduced relative risk of recurrent biliary events within 60 days by 92%, compared with delayed or no CCY (P.001). After 60 days following discharge from index admission, patients with early CCY had an 87% lower risk of recurrent biliary events than patients with no CCY (P.001) and patients with delayed CCY had an 88% lower risk of recurrent biliary events than patients with no CCY (P.001). A strategy of delayed CCY performed on an outpatient basis was least costly. Performance of early CCY was inversely associated with low facility volume. Hispanic race, Asian race, Medicaid insurance, and no insurance associated inversely with performance of delayed CCY.In a retrospective analysis of4500 patients hospitalized with choledocholithiasis, we found that CCY was not performed after ERCP for almost half of the cases. Although early and delayed CCY equally reduce the risk of subsequent recurrent biliary events, patients are at 10-fold higher risk of recurrent biliary event while waiting for a delayed CCY compared with patients who underwent early CCY. Delayed CCY is a cost-effective strategy that must be balanced against the risk of loss to follow-up, particularly among patients who are ethnic minorities or have little or no health insurance.

Background & Aims Fluoroscopy during endoscopic retrograde cholangiopancreatography (ERCP) is increasingly performed by therapeutic endoscopists, many of whom have not received formal training in modulating fluoroscopy use to minimize radiation exposure. Exposure to ionizing radiation has significant health consequences for patients and endoscopists. We aimed to evaluate whether a 20-minute educational intervention for endoscopists would improve use of fluoroscopy and decrease ERCP-associated exposure to radiation for patients. Methods We collected data from 583 ERCPs, performed in California from June 2010 through November 2012; 331 were performed at baseline and 252 following endoscopist education. The educational intervention comprised a 20-minute video explaining best practices for fluoroscopy, coupled with implementation of a formal fluoroscopy time-out protocol before the ERCP was performed. Our primary outcome was the effect of the educational intervention on direct and surrogate markers of patient radiation exposure associated with ERCPs performed by high-volume endoscopists (HVEs) (200 or more ERCPs/year) vs low-volume endoscopists (LVEs) (fewer than 200 ERCPs/year). Results At baseline, total radiation dose and dose area product were significantly higher for LVEs, but there was no significant difference between HVEs and LVEs following education. Education was associated with significant reductions in median fluoroscopy time (48% reduction for HVEs vs 30% reduction for LVEs), total radiation dose (28% reduction for HVEs vs 52% for LVEs) and dose area product (35% reduction for HVEs vs 48% reduction for LVEs). All endoscopists significantly increased their use of low magnification and collimation following education. Conclusions A 20-minute educational program with emphasis on ideal use of modifiable fluoroscopy machine settings results in an immediate and significant reduction in ERCP-associated patient radiation exposure for low-volume and high-volume endoscopists. Training programs should consider radiation education for advanced endoscopy fellows.

Importance The Affordable Care Act (ACA) has expanded access to health insurance for millions of Americans, but the impact of Medicaid expansion on healthcare delivery and utilization remains uncertain. Objective To determine the early impact of the Medicaid expansion component of ACA on hospital and ED utilization in California, a state that implemented the Medicaid expansion component of ACA and Florida, a state that did not. Design Analyze all ED encounters and hospitalizations in California and Florida from 2009 to 2014 and evaluate trends by payer and diagnostic category. Data were collected from State Inpatient Databases, State Emergency Department Databases and the California Office of Statewide Health Planning and Development. Setting Hospital and ED encounters. Participants Population-based study of California and Florida state residents. Exposure Implementation of Medicaid expansion component of ACA in California in 2014. Main outcomes or measures Changes in ED visits and hospitalizations by payer, percentage of patients hospitalized after an ED encounter, top diagnostic categories for ED and hospital encounters. Results In California, Medicaid ED visits increased 33% after Medicaid expansion implementation and self-pay visits decreased by 25% compared with a 5.7% increase in the rate of Medicaid patient ED visits and a 5.1% decrease in rate of self-pay patient visits in Florida. In addition, California experienced a 15.4% increase in Medicaid inpatient stays and a 25% decrease in self pay stays. Trends in the percentage of patients admitted to the hospital from the ED were notable; a 5.4% decrease in hospital admissions originating from the ED in California, and a 2.1% decrease in Florida from 2013 to 2014. Conclusions and relevance We observed a significant shift in payer for ED visits and hospitalizations after Medicaid expansion in California without a significant change in top diagnoses or overall rate of these ED visits and hospitalizations. There appears to be a shift in reimbursement burden from patients and hospitals to the government without a dramatic shift in patterns of ED or hospital utilization.

Background & Aims The risk of gastrointestinal (GI) bleeding (GIB) and thromboembolic events may increase with continuous-flow left ventricular assist devices (CF-LVADs). We aimed to characterize GIB and thromboembolic events that occurred in patients with CF-LVADs and compare them with patients receiving anticoagulation therapy. Methods We performed a retrospective analysis of 159 patients who underwent CF-LVAD placement at 2 large academic medical centers (mean age, 55 ± 13 y). We identified and characterized episodes of GIB and thromboembolic events through chart review; data were collected from a time period of 292 ± 281 days. We compared the rates of GIB and thromboembolic events between patients who underwent CF-LVAD placement and a control group of 159 patients (mean age, 64 ± 15 y) who received a cardiac valve replacement and were discharged with anticoagulation therapy. Results Bleeding events occurred in 29 patients on CF-LVAD support (18%; 45 events total). Sixteen rebleeding events were identified among 10 patients (range, 1–3 rebleeding episodes/patient). There were 34 thrombotic events among 27 patients (17%). The most common source of bleeding was GI angiodysplastic lesions (n = 20; 44%). GIB and thromboembolic events were more common in patients on CF-LVAD support than controls; these included initial GIB (18% vs 4%, P P = .001), and thromboembolic events (17% vs 8%, P = .01). Conclusions Patients with CF-LVADS receiving anticoagulants have a significantly higher risk of GIB and thromboembolic events than patients receiving anticoagulants after cardiac valve replacement surgery. GI angiodysplastic lesions are the most common source of bleeding.

Colonoscopy is the most commonly performed endoscopic procedure and overall is considered a low-risk procedure. However, adverse events (AEs) related to this routinely performed procedure for screening, diagnostic, or therapeutic purposes are an important clinical consideration. The purpose of this document from the American Society for Gastrointestinal Endoscopy's Standards of Practice Committee is to provide an update on estimates of AEs related to colonoscopy in an evidence-based fashion. A systematic review and meta-analysis of population-based studies was conducted for the 3 most common and important serious AEs (bleeding, perforation, and mortality). In addition, this document includes an updated systematic review and meta-analysis of serious AEs (bleeding and perforation) related to EMR and endoscopic submucosal dissection for large colon polyps. Finally, a narrative review of other colonoscopy-related serious AEs and those related to specific colonic interventions is included.