Risk Of Gastric Adenocarcinoma Research Articles

Gastric Carcinoma in Autoimmune Gastritis: A Histopathologic and Molecular Study

Patients with autoimmune gastritis (AIG) have a 13-fold risk of developing type-1 neuroendocrine tumors, whereas the risk for gastric adenocarcinoma is still uncertain. Here we describe the clinicopathologic and molecular features of a series of gastric carcinomas (GC) arising in the context of AIG. A total of 26 AIG-associated GC specimens were collected from 4 Italian Institutions. Immunohistochemistry for MUC1, MUC2, MUC5AC, MUC6, CDX2, HER2, PD-L1, CLDN18, mismatch repair (MMR) proteins, and p53 and EBV-encoded RNA (EBER) in situ hybridization were performed. Histologic and immunohistochemical features were jointly reviewed by 5 expert gastrointestinal pathologists. Next-generation sequencing analysis (TrueSight Oncology 500, Illumina) of 523 cancer-related genes was performed on 19 cases. Most tumors were diagnosed as pT1 (52%) and they were located in the corpus/fundus (58%) and associated with operative link for gastritis assessment stage II gastritis (80.8%), absence of parietal cells, complete intestinal metaplasia, and enterochromaffin-like-cell micronodular hyperplasia. Only 4 (15.4%) GCs were diagnosed during follow-up for AIG. The following histotypes were identified: 20 (77%) adenocarcinomas; 3 (11%) mixed neuroendocrine–non-neuroendocrine neoplasms, and 2 (8%) high-grade solid adenocarcinomas with focal neuroendocrine component, 1 (4%) adenocarcinoma with an amphicrine component. Overall, 7 cases (27%) showed MMR deficiency, 3 (12%) were positive (score 3+) for HER2, 6 (23%) were CLDN18 positive, and 11 (42%) had PD-L1 combined positive score ≥ 10. EBER was negative in all cases. Molecular analysis revealed 5/19 (26%) microsatellite instability (MSI) cases and 7 (37%) tumor mutational burden (TMB) high. The most frequently altered genes were TP53 (8/19, 42%), RNF43 (7/19, 37%), ERBB2 (7/19, 37% [2 amplified and 5 mutated cases]), ARID1A (6/19, 32%), and PIK3CA (4/19, 21%). In summary, AIG-associated GCs are often diagnosed at low stage in patients with longstanding misrecognized severe AIG; they often display a neuroendocrine component or differentiation, have relatively higher rates of MMR deficiency, and TMB high.

Autoimmune gastritis

Diagnosis of autoimmune gastritis (AIG) is often challenging because of the absence of typical symptoms. Clinical guidelines are lacking, which results in inadequate treatment and poor cancer screening. This work presents an overview of current management options and aims at raising awareness for this disease. The paper also describes a clinical case of the full-scale course of AIG with all its complications. Autoimmune gastritis is mostly considered as a disease of elderly with vitamin B12 deficiency and pernicious anaemia. Today it is recognized that AIG is found with a similar prevalence in all age groups, with iron deficiency being a frequent symptom. Conventional therapy consists of adequate iron and vitamin B12 supplementation, as well as symptomatic approaches. The associated risk for gastric adenocarcinoma and gastric neuroendocrine tumours requires regular endoscopic follow-up. New treatments aiming to reduce gastric atrophy and cancer risk are currently under development. Thus, treatment of autoimmune gastritis should focus on optimizing supplementation of vitamin and macronutrient deficiencies, symptomatic therapy that improves quality of life, and include cancer prevention measures. Clinical studies should address the possibility to arrest the inflammation process and to prevent progression of AIG. The author of the article suggests that itopride hydrochloride and rebamipide will be used for symptomatic and pathogenetic therapy. The problem facing gastroenterologists today is to develop domestic guidelines for the management and screening endoscopic intervals of patients with AIG.

Risk of Gastric Adenocarcinoma in a Multiethnic Population Undergoing Routine Care: An Electronic Health Records Cohort Study.

Gastric adenocarcinoma (GAC) is often diagnosed at advanced stages and portends a poor prognosis. We hypothesized that electronic health records (EHR) could be leveraged to identify individuals at highest risk for GAC from the population seeking routine care. This was a retrospective cohort study, with endpoint of GAC incidence as ascertained through linkage to an institutional tumor registry. We utilized 2010 to 2020 data from the Palo Alto Medical Foundation, a large multispecialty practice serving Northern California. The analytic cohort comprised individuals ages 40-75 receiving regular ambulatory care. Variables collected included demographic, medical, pharmaceutical, social, and familial data. Electronic phenotyping was based on rule-based methods. The cohort comprised 316,044 individuals and approximately 2 million person-years (p-y) of observation. 157 incident GACs occurred (incidence 7.9 per 100,000 p-y), of which 102 were non-cardia GACs (incidence 5.1 per 100,000 p-y). In multivariable analysis, male sex [HR: 2.2, 95% confidence interval (CI): 1.6-3.1], older age, Asian race (HR: 2.5, 95% CI: 1.7-3.7), Hispanic ethnicity (HR: 1.9, 95% CI: 1.1-3.3), atrophic gastritis (HR: 4.6, 95% CI: 2.2-9.3), and anemia (HR: 1.9, 95% CI: 1.3-2.6) were associated with GAC risk; use of NSAID was inversely associated (HR: 0.3, 95% CI: 0.2-0.5). Older age, Asian race, Hispanic ethnicity, atrophic gastritis, and anemia were associated with non-cardia GAC. Routine EHR data can stratify the general population for GAC risk. Such methods may help triage populations for targeted screening efforts, such as upper endoscopy.

Li Fraumeni Syndrome predisposes to gastro-esophageal junction tumours

Li-Fraumeni Syndrome (LFS), caused by germline pathogenic variants in TP53, predisposes to a wide range of young-onset malignancies, particularly sarcoma, breast and brain cancer. More recently, an increased risk of gastric adenocarcinoma has been recognised, although uptake of surveillance upper endoscopy is unclear. Our retrospective review of 65 patients with LFS, of whom 53.8% had undergone endoscopy, identified four patients (6.2%) with gastro-esophageal junction (GEJ) adenocarcinomas. Two cases were found on asymptomatic screening and were early stage. No cases had family history of gastrointestinal malignancy. Reviewing genomic data from The Cancer Genome Atlas Program, 76.4% of sporadic esophageal adenocarcinomas harboured somatic TP53 pathogenic variants, compared with 39.9% of non-cardia gastric cancers. This similar pattern observed in germline and sporadic cases warrants further investigation. We propose that upper endoscopy be recommended to all patients with LFS, with a focus on appropriate surveillance of the GEJ.

Long-Term Natural History of Autoimmune Gastritis: Results From a Prospective Monocentric Series.

The natural history of autoimmune gastritis (AIG) has been poorly described. In this study, we report the long-term natural history and clinical clustering of the full spectrum of AIG, from the potential to the complicated stage. Prospective single-center study conducted in a tertiary referral center. Patients with AIG at any stage (0 = potential; 1 = early; 2 = florid; 3 = severe; and 4 = complicated) were enrolled (January 2000-December 2022). The histopathological evolution, the clinical presentation, and the correlates of evolution of potential AIG were assessed. Four hundred ninety-eight patients with AIG (mean age 56.7 ± 15.2 years, F:M ratio 2.5:1) were included, of whom 93 experienced potential AIG. The maximum disease duration was 27 years (median 18, interquartile range 14-23), while the overall median follow-up was 52 months (interquartile range 12-95). Age was significantly lower in stage 0 compared with that in the other stages. Accidental histologic evidence and hematologic findings were the most common clusters of diagnosis. The overall median rate of progression was 7.29 per 100 persons/yr (95% confidence interval [CI] 6.19-8.59), while the stage-specific rates of progression were 10.85 (stage 0; 95% CI 7.75-15.18), 14.83 (stages 1-2; 95% CI 11.89-18.49), and 2.68 (stage 3; 95% CI 1.88-3.84). Newly onset neoplastic complications at follow-up occurred in 41/483 patients (8.5%; 23 neuroendocrine tumors and 18 epithelial dysplasia). No cases of adenocarcinoma were noticed. Male sex was associated with a greater likelihood of evolving from potential AIG to overt AIG. AIG is a progressive disorder, with a virtually absent risk of gastric adenocarcinoma. Patients with potential AIG should be monitored because they carry a high risk of evolving into overt AIG.

Clinical Management of Patients with Gastric MALT Lymphoma: A Gastroenterologist's Point of View.

Gastric mucosa-associated lymphoid tissue (MALT) lymphomas (GML) are non-Hodgkin lymphomas arising from the marginal zone of the lymphoid tissue of the stomach. They are usually induced by chronic infection with Helicobacter pylori (H. pylori); however, H. pylori-negative GML is of increasing incidence. The diagnosis of GML is based on histological examination of gastric biopsies, but the role of upper endoscopy is crucial since it is the first step in the diagnostic process and, with currently available novel endoscopic techniques, may even allow an in vivo diagnosis of GML per se. The treatment of GML, which is usually localized, always includes the eradication of H. pylori, which should be performed even in H. pylori-negative GML. In the case of GML persistence after eradication of the bacteria, low-dose radiotherapy may be proposed, while systemic treatments (immunochemotherapy) should be reserved for very rare disseminated cases. In GML patients, at diagnosis but even after complete remission, special attention must be paid to an increased risk of gastric adenocarcinoma, especially in the presence of associated gastric precancerous lesions (gastric atrophy and gastric intestinal metaplasia), which requires adequate endoscopic surveillance of these patients.

H. Pylori Gastritis and Gastric Carcinoma: Uncovering Histological Links and Risk Factors

Objective: Aim was to determine the risk of gastric carcinoma among patients of Helicobacter pylori gastritics and its risk factors. Study Design: Retrospective study Place and Duration: Department of gastroenterology, DHQ Teaching Hospital and Ghazi Khan Medical College DG Khan, Punjab in the duration from November, 2022 to April, 2023. Methods: Total 131 patients who had gastric carcinoma were included. Stored serum samples collected, were tested for IgG antibodies to H. pylori by enzyme-linked immunosorbent assay. Data on cigarette use, blood group, ulcer disease, and gastric surgery were obtained from questionnaires administered at enrollment. Tissue sections and pathology reports were reviewed to confirm the histologic results. SPSS 23.0 was used to analyze data. Results: In our study, male patients were higher in numbers 86 (65.6%) as compared to females 45 (34.4%). The patients mean age was 51.17±6.20 years and had mean BMI 24.16 ±7.46 kg/m2. 73 (55.7%) patients had smoking history. 97 (74.04%) patients had gastric ulcer. Average time from serum collection to stomach gastric carcinoma was 12.7±3.26 years. Among all, 74 (56.5%) patients had adenocarcinoma, gastroesophageal junction was found in 20 (15.3) cases, gastric lymphoma in 11 (8.4%) cases and 26 (19.4%) cases had undetermined or other cancers. We found that 83 (63.4%) patients had history of H.pylori infection. There was a significant negative association between a history of peptic ulcer disease and eventual gastric carcinoma (P = 0.003) and an independent association between a history of gastric surgery and the development of cancer (p = 0.004). Conclusion: The results of this research led us to the conclusion that an infection with H. pylori is linked to an elevated risk of gastric adenocarcinoma and may play a role as a cofactor in the process that leads to the development of this malignant condition. Keywords: H.pylori infection, Gastric Carcinoma, Risk Factors

Gastric Adenocarcinoma of the Remnant Stomach After Roux-en-Y Diagnosed by Endoscopic Ultrasound-Directed Transgastric Endoscopic Retrograde Cholangiopancreatography (EDGE)

It can be difficult to evaluate for pathology with traditional endoscopic modalities following a Roux-en-Y gastric bypass. This is due to the truncated gastrointestinal tract and excluded distal stomach formed during a Roux-en-Y procedure. In these circumstances, a modified endoscopic procedure, known as endoscopic ultrasound (EUS)-directed transgastric endoscopic retrograde cholangiopancreatography (ERCP) (EDGE) is used. Although the Roux-en-Y procedure slightly increases the risk of gastric adenocarcinoma in the general population, the occurrence of gastric adenocarcinoma in the excluded stomach, specifically, is uncommon. Herein, we present a case of gastric adenocarcinoma of the excluded stomach, diagnosed 20 years after a Roux-en-Y procedure. This case is unique because after an extensive five-year workup for melena and iron deficiency anemia, the malignancy was ultimately diagnosed utilizing the innovative EDGE procedure.

Diet quality and risk of gastric adenocarcinoma: The Multiethnic Cohort

BackgroundCertain dietary patterns (i.e., low intake of fruit/vegetables and high intake of salt and processed meats) have been associated with the risk of gastric cancer. However, it is unclear whether overall diet quality assessed by predefined indices that consider the complexity of dietary intake is associated with gastric cardia and distal adenocarcinoma. ObjectivesTo examine the association of a variety of diet indices with the risk of gastric cardia and distal adenocarcinoma and assess whether there are any subgroups that may benefit from better diets to reduce the risk of gastric adenocarcinoma. MethodsDietary indices of interest included the Alternative Healthy Index (AHEI)-2010, Healthy Eating Index (HEI)-2015, the Dietary Approach to Stop Hypertension, alternate Mediterranean diet (aMED), and the energy-adjusted Dietary Inflammatory Index. ResultsAfter an average follow-up time of 19.2 years, there were 836 incident cases of gastric distal adenocarcinoma and 207 cases of gastric cardia adenocarcinoma. We did not observe any significant associations between the dietary indices and gastric cancer for either anatomic site. Among former aspirin users, we observed an inverse association between aMED with distal cancer (HRQ5 vs. Q1: 0.64; 95% CI: 0.33, 1.23; P-trend = 0.03). Never smokers, who showed high-quality diet according to AHEI-2010, exhibited a 40% decreased risk of gastric distal cancer compared with those with the poorest-quality AHEI-2010 diet (HRQ5 vs. Q1: 0.60; 95% CI: 0.41, 0.88; P-trend = 0.08). ConclusionsIn a multiethnic population, we did not observe overall significant associations between these dietary quality indices and risk of gastric cancer. However, among former aspirin users and never smokers, there could be a reduction of gastric distal adenocarcinoma risk with a higher adherence to a Mediterranean diet.

Penetrance of Gastric Adenocarcinoma Susceptibility Genes: A Systematic Review.

Gastric adenocarcinoma (GAC) is the fifth most common cancer in the world, and the presence of germline pathogenic variants has been linked with approximately 5% of gastric cancer diagnoses. Multiple GAC susceptibility genes have been identified, but information regarding the risk associated with pathogenic variants in these genes remains obscure. We conducted a systematic review of existing studies reporting the penetrance of GAC susceptibility genes. A structured search query was devised to identify GAC-related papers indexed in MEDLINE/PubMed. A semi-automated natural language processing algorithm was applied to identify penetrance papers for inclusion. Original studies reporting the penetrance of GAC were included and the full-text articles were independently reviewed. Summary statistics, effect estimates, and precision parameters from these studies were compiled into a table using a predetermined format to ensure consistency. Forty-five studies were identified reporting the penetrance of GAC among patients harboring mutations in 13 different genes: APC, ATM, BRCA1, BRCA2, CDH1, CHEK2, MLH1, MSH2, MSH6, PMS2, MUTYH-Monoallelic, NBN, and STK11. Our systematic review highlights the importance of testing for germline pathogenic variants in patients before the development of GAC. Management of patients who harbor a pathogenic mutation is multifactorial, and clinicians should consider cancer risk for each applicable gene-cancer association throughout the screening and management process. The scarcity of studies we found investigating the risk of GAC among patients with pathogenic variants in GAC susceptibility genes highlights the need for more investigations that focus on producing robust risk estimates for gene-cancer associations.

Meat Intake, Cooking Methods, Doneness Preferences and Risk of Gastric Adenocarcinoma in the MCC-Spain Study.

The association of meat intake with gastric adenocarcinoma is controversial. We examined the relation between white, red, and processed meat intake and gastric adenocarcinoma, considering doneness preference and cooking methods, by histological subtype and anatomical subsite. MCC-Spain is a multicase-control study that included 286 incident gastric adenocarcinoma cases and 2993 controls who answered a food-frequency questionnaire. The association of gastric adenocarcinoma with meat intake, doneness preference and cooking methods was assessed using binary multivariate logistic regression mixed models and a possible interaction with sex was considered. Multinomial logistic regression models were used to estimate risk by tumor subsite (cardia vs. non-cardia) and subtype (intestinal vs. diffuse). Sensitivity analyses were conducted comparing models with and without data on Helicobacter pylori infection. The intake of red and processed meat increased gastric adenocarcinoma risk (OR for one serving/week increase (95% CI) = 1.11 (1.02;1.20) and 1.04 (1.00;1.08), respectively), specifically among men and for non-cardia and intestinal gastric adenocarcinoma. Those who consume well done white or red meat showed higher risk of non-cardia (white: RRR = 1.57 (1.14;2.16); red: RRR = 1.42 (1.00;2.02)) and intestinal tumors (white: RRR = 1.69 (1.10;2.59); red: RRR = 1.61 (1.02;2.53)) than those with a preference for rare/medium doneness. Stewing and griddling/barbequing red and white meat, and oven baking white meat, seemed to be the cooking methods with the greatest effect over gastric adenocarcinoma. The reported associations remained similar after considering Helicobacter pylori seropositivity. Reducing red and processed meat intake could decrease gastric adenocarcinoma risk, especially for intestinal and non-cardia tumors. Meat cooking practices could modify the risk of some gastric cancer subtypes.

Risk of gastric and oesophageal adenocarcinoma following discontinuation of long-term proton-pump inhibitor therapy

BackgroundThere is uncertainty whether long-term use of proton-pump inhibitors can cause gastric adenocarcinoma (GAC) and oesophageal adenocarcinoma (OAC). This study aimed to determine how discontinuation of long-term PPI therapy influences the risk of GAC and OAC.MethodsThis population-based cohort study included all long-term users of PPI therapy in Sweden in 2005–2018 was based on Swedish nationwide health registry data. The exposure was discontinuation of long-term PPI therapy, defined as no dispensation of PPI following inclusion and used as a time-varying variable, compared to remaining on PPI. Main outcomes were GAC and OAC, while oesophageal squamous cell carcinoma (OSCC) was included as a comparison outcome. Incidence rate ratios (IRR) with 95% CI adjusted for age, sex, comorbidity, obesity, diabetes, hyperlipidaemia, NSAIDs/aspirin, and statins were calculated with Poisson regression.ResultsAmong 730,176 long-term PPI users (mean age 65.6 years, 58.4% females) with 4,210,925 person-years at risk (median 5.5 person-years), 439,390 (60.2%) discontinued PPIs. In total, 495 developed GAC, 598 OAC, and 188 developed OSCC. PPI discontinuation was associated with decreased risk of GAC (IRR 0.81, 95% CI 0.67–0.98) and OAC (IRR 0.80, 95% CI 0.68–0.96), but not OSCC (IRR 1.10, 95% CI 0.82–1.49) compared to continued PPI use. Stratified analyses showed decreased point estimates across most age categories and both sexes for GAC and OAC risk among participants discontinuing PPI therapy.ConclusionDiscontinuation of long-term PPI therapy may decrease the risk of GAC and OAC, suggesting that physicians should consider ceasing prescribing long-term PPI in patients without continued indication for its use.

Improving the Endoscopic Detection and Management of Gastric Intestinal Metaplasia Through Training: A Practical Guide

Improving the Endoscopic Detection and Management of Gastric Intestinal Metaplasia Through Training: A Practical Guide

Клинический случай эндоскопической диагностики аутоиммунного атрофического гастрита

Autoimmune atrophic gastritis (AIG) is a chronic progressive inflammatory disease that results in damage to the gastric parietal cells and replacement of these cells by atrophic and metaplastic mucosa. In the course of the disease autoantibodies gradually destroy parietal cells, causing hypochlorhydria followed by achlorhydria; vitamin B12 absorption is also impaired. The resulting cobalamin deficiency is manifested by megaloblastic anemia and neurological disorders, the combination referred to as pernicious anemia. AIG is also associated with the increased risk of gastric adenocarcinoma and gastric neuroendocrine tumors, that is why patients diagnosed with AIG should be followed-up. Since metaplastic changes in the mucous membrane are the major histological feature found in patients with autoimmune atrophic gastritis, English sources recommend to use the term “autoimmune metaplastic atrophic gastritis”. It is believed that to date AIG has been found in all populations and ethnic groups, however, there is no reliable data on the prevalence due to complexity of the diagnosis. Endoscopic diagnosis is one of the key tests for the diagnosis of AIG. The paper provides the clinical case of the endoscopic diagnosis of AIG and discusses typical endoscopic features of the disease.

Abstract 737: Diet quality and risk of gastric adenocarcinoma: The Multiethnic Cohort

Abstract Background: Certain diet components (i.e. low intake of fruit/vegetables and high intake of salt and processed meats) have been associated with risk of gastric cancer. However, it is unclear whether overall diet quality assessed by pre-defined indices, that take into account the complexity of dietary intake, is associated with gastric cardia and distal adenocarcinoma particularly in a racially and ethnically diverse population. Our objectives are to 1) examine the association of a variety of diet quality indices with risk of gastric cardia and distal adenocarcinoma and 2) assess if there are any subgroups that may benefit from better diets to reduce risk of gastric adenocarcinoma. Methods: The analysis included 176,752 men and women aged 45-75 from the Multiethnic Cohort (MEC), who were African American, Japanese American, Latino, Native Hawaiian, or White, and completed a quantitative food frequency questionnaire (QFFQ) at cohort entry. Incident cases of gastric cancer (cardia ICD-O-3 C16.0 and non-cardia adenocarcinoma C16.1-C16.6) were identified by linkages with the Surveillance, Epidemiology, and End Results (SEER) cancer registries. Dietary indices, Alternative Healthy Index-2010 (AHEI-2010), Healthy Eating Index-2015 (HEI-2015), Dietary Approach to Stop Hypertension (DASH) score, alternate Mediterranean Diet (aMED) score, and Dietary Inflammatory Index (DII®), were calculated from the QFFQ and categorized into quintiles. Multivariable Cox models were used to estimate the association between dietary indices and gastric cancer risk by anatomic site. Effect modification was assessed for distal cancer by sex, smoking status, and aspirin use. Results: A total of 207 incident cases of gastric cardia and 836 incident cases of gastric non-cardia were identified during an average follow up of 19.2 years. We did not observe any significant associations between any of the dietary indices and gastric cancer for both cardia and non-cardia tumors. However, we observed effect modification by aspirin use for aMED (P for heterogeneity = 0.01) as well as for DII (P for heterogeneity = 0.02). Among ever aspirin users, we observed an inverse association between aMED (HRQ5 vs Q1: 0.82, 95% CI: 0.53-1.26, Ptrend = 0.03) with non-cardia cancer, and the association with DII® was borderline statistically significant for the trend test (HRQ5 vs Q1: 0.86, 95% CI: 0.57-1.29, Ptrend = 0.07). Conclusion: In a multiethnic population, we did not observe overall significant associations between these dietary quality indices and risk of gastric cancer. However, among ever aspirin users there could be a reduction of gastric non-cardia adenocarcinoma risk with a higher adherence to a Mediterranean diet. Citation Format: Nicholas Acuna, Song-Yi Park, Anna H. Wu, Lynne R. Wilkens, V. Wendy Setiawan. Diet quality and risk of gastric adenocarcinoma: The Multiethnic Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 737.

A136 A RARE CAUSE OF AUTOIMMUNE ATROPHIC PANGASTRITIS COMPLICATED WITH GASTRIC OUTLET OBSTRUCTION

BackgroundChronic gastritis comes in two well recognized forms: environmental, which is most commonly antral or multifocal in distribution and is typically caused by Helicobacter Pylori (HP) infection, and autoimmune gastritis(AIG), which affects the corpus and fundus. Presented here is a case of autoimmune atrophic pangastritis(AIAP).AimsTo increase awareness of a rare condition with limited data on available treatment modalities.MethodsCase ReportResultsA 68-year old female with autoimmune hypothyroidism, presented with weight loss and elevated anti-TTG serology. Index esophagogastroduodenoscopy (EGD) biopsies demonstrated chronic non-specific gastritis limited to the antrum. Strict gluten free diet adherence was initiated. Testing for HLA revealed HLADq2 and HLADq8 negativity but HLADq2.5 positivity. Subsequent EGD showed a markedly atrophic appearing gastric body. The corresponding biopsies demonstrated persistent moderately chronic active gastritis with severe atrophy now involving the body, fundus and antrum. The biopsies were negative for HP. Notably, there was a lack of ECL-cell hyperplasia and the number of antral G cells appeared decreased. Anti-parietal cell antibody serology was positive with a titre of 1:80. Despite combination therapy with budesonide and mesalamine and treatment for HP given persistent symptoms, the patient’s course was further complicated by gastric-outlet obstruction (GOO). Urgent EGD biopsies showed pyloric stenosis requiring dilation. Endoscopic Ultrasound (EUS) guided biopsies were negative for malignancy. The patient was started on corticosteroids and azathioprine(AZA). Most recently, an EGD on AZA, continued to demonstrate severe chronic active pangastritis now with intestinal metaplasia involving the body. Corticosteroid therapy was reinitiated with a plan to start mycophenolate mofetil (MMF).ConclusionsAIAP is a rarely described entity, not well documented in the literature. An eight patient case series reported a distinctive form of atrophic gastritis that was independent of HP infection with the absence of neuroendocrine hyperplasia that involved the body and antrum. Thyroid disease, specifically Hashimoto thyroiditis is present in about 40% of patients with AIG. Additionally, AIG progression to atrophic gastritis with intestinal metaplasia confers an increased risk for gastric adenocarcinoma in more than 10% of patients.Limited literature exists regarding the management of AIAP. Pediatric data suggests the use of prednisone and/or azathioprine for AIAP. Furthermore, a recent case report of AIAP demonstrated clinical and endoscopic remission with MMF. Currently, no guidelines exist for the treatment, screening and monitoring of patients with AIAP. This case report presents a rare case of AIAP refractory to AZA complicated with GOO and adds to the little literature that exists.Funding AgenciesNone

A Predictive Model of Noncardia Gastric Adenocarcinoma Risk Using Antibody Response to Helicobacter pylori Proteins and Pepsinogen.

Blood-based biomarkers for gastric cancer risk stratification could facilitate targeting screening to people who will benefit from it most. The ABC Method, which stratifies individuals by their Helicobacter pylori infection and serum-diagnosed chronic atrophic gastritis status, is currently used in Japan for this purpose. Most gastric cancers are caused by chronic H. pylori infection, but few studies have explored the capability of antibody response to H. pylori proteins to predict gastric cancer risk in addition to established predictors. We used the least absolute shrinkage and selection operator (Lasso) to build a predictive model of noncardia gastric adenocarcinoma risk from serum data on pepsinogen and antibody response to 13 H. pylori antigens as well as demographic and lifestyle factors from a large international study in East Asia. Our best model had a significantly (P < 0.001) higher AUC of 73.79% [95% confidence interval (CI), 70.86%-76.73%] than the ABC Method (68.75%; 95% CI, 65.91%-71.58%). At 75% specificity, the new model had greater sensitivity than the ABC Method (58.67% vs. 52.68%) as well as NPV (68.24% vs. 66.29%). Along with serologically defined chronic atrophic gastritis, antibody response to the H. pylori proteins HP 0305, HP 1564, and UreA can improve the prediction of gastric cancer risk. The new risk stratification model could help target more invasive gastric screening resources to individuals at high risk.

The continuing decline in the prevalence of Helicobacter pylori infection

The International Agency for Research on Cancer has classified Helicobacter pylori as a group 1 carcinogen. There is ample evidence that the risk of gastric adenocarcinoma is very low in the absence of H pylori infection. 1 Kawai S Wang C Lin Y Sasakabe T Okuda M Kikuchi S Lifetime incidence risk for gastric cancer in the Helicobacter pylori-infected and uninfected population in Japan: a Monte Carlo simulation study. Int J Cancer. 2022; 150: 18-27 Google Scholar Although several systematic reviews in recent years have described the changing prevalence of H pylori infection, most have shortcomings, such as being limited to adult populations, certain countries or geographical regions, time periods, or English language publications. 2 Zabala Torrres B Lucero Y Lagomarcino AJ et al. Review: prevalence and dynamics of Helicobacter pylori infection during childhood. Helicobacter. 2017; 22e12399 Google Scholar , 3 Hooi JKY Lai WY Ng WK et al. Global prevalence of Helicobacter pylori infection: systematic review and meta-analysis. Gastroenterology. 2017; 153: 420-429 Google Scholar , 4 Yuan C Adeloye D Luk TT et al. The global prevalence of and factors associated with Helicobacter pylori infection in children: a systematic review and meta-analysis. Lancet Child Adolesc Health. 2022; (published online Jan 24.)https://doi.org/10.1016/S2352-4642(21)00400-4 Google Scholar In The Lancet Child & Adolescent Health, Changzheng Yuan and colleagues 4 Yuan C Adeloye D Luk TT et al. The global prevalence of and factors associated with Helicobacter pylori infection in children: a systematic review and meta-analysis. Lancet Child Adolesc Health. 2022; (published online Jan 24.)https://doi.org/10.1016/S2352-4642(21)00400-4 Google Scholar are the first to provide a comprehensive analysis of the prevalence of H pylori infection in children (aged ≤18 years) over a 30-year period. Their estimated prevalence of H pylori infection is the most accurate to date because of the large number of studies from both high-income countries (HICs) and low-income and middle-income countries (LMICs) included in their analysis. Furthermore, the authors provide prevalence estimates stratified by the method used to diagnose H pylori infection, which is crucial in assessing prevalence in younger children. The global prevalence of and factors associated with Helicobacter pylori infection in children: a systematic review and meta-analysisH pylori infection is still highly prevalent in children and adolescents globally. Our findings can help to guide further research and the development and implementation of preventive and therapeutic measures to reduce H pylori infection in children. Full-Text PDF

Association Between Aspirin Use and Gastric Adenocarcinoma: A Prospective Cohort Study.

Novel prevention is urgently needed to reduce incidence and mortality of gastric cancer. We found that regular aspirin use was associated with lower risk of gastric adenocarcinoma among women, but not men. The benefit appeared after at least 10 years of use and was maximized at higher doses among women. See related Spotlight, p. 213.

Drug metabolism-related eight-gene signature can predict the prognosis of gastric adenocarcinoma.

BackgroundMetabolic abnormalities in patients with gastric adenocarcinoma lead to drug resistance and poor prognosis. Therefore, this study aimed to explore biomarkers that can predict the prognostic risk of gastric adenocarcinoma by analyzing drug metabolism‐related genes.MethodsThe RNA‐seq and clinical information on gastric adenocarcinoma were downloaded from the UCSC and gene expression omnibus databases. Univariate and least absolute shrinkage and selection operator regression analyses were used to identify the prognostic gene signature of gastric adenocarcinoma. The relationships between gastric adenocarcinoma prognostic risk and tumor microenvironment were assessed using CIBERSORT, EPIC, QUANTISEQ, MCPCounter, xCell, and TIMER algorithms. The potential drugs that could target the gene signatures were predicted in WebGestalt, and molecular docking analysis verified their binding stabilities.ResultsCombined with clinical information, an eight‐gene signature, including GPX3, ABCA1, NNMT, NOS3, SLCO4A1, ADH4, DHRS7, and TAP1, was identified from the drug metabolism‐related gene set. Based on their expressions, risk scores were calculated, and patients were divided into high‐ and low‐risk groups, which had significant differences in survival status and immune infiltrations. Risk group was also identified as an independent prognostic factor of gastric adenocarcinoma, and the established prognostic and nomogram models exhibited excellent capacities for predicting prognosis. Finally, miconazole and niacin were predicted as potential therapeutic drugs for gastric adenocarcinoma that bond stably with NOS3 and NNMT through hydrogen interactions.ConclusionsThis study proposed a drug metabolism‐related eight‐gene signature as a potential biomarker to predict the gastric adenocarcinoma prognosis risks.