[Therapeutic efficacy analysis of endoscopic combined with serological diagnosis strategy and endoscopic in G1 and G2 gastric neuroendocrine neoplasms].

Objective: To investigate the endoscopic combined serological diagnosis strategy for G1 and G2 gastric neuroendocrine neoplasms (G-NENs), and to evaluate the safety, short-term, and long-term efficacy of two endoscopic treatment procedures: endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). Methods: This study retrospectively analyzed the clinical data of 100 consecutive patients with G-NENs who were hospitalized at the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2011 to October 2023. These patients underwent endoscopic treatment, and propensity score matching (PSM) was used to compare clinicopathological characteristics, as well as short-term and long-term efficacy of lesions in the EMR group and ESD group before and after treatment. Results: Among the 100 patients with G-NENs, the median age was 54 years old. Before surgery, 29 cases underwent endoscopic combined serological examination, and 24 of them (82.2%) had abnormally elevated plasma chromogranin A. The combined diagnostic strategy for autoimmune atrophic gastritis (AIG) achieved a diagnostic accuracy of 100%(22/22). A total of 235 G-NEN lesions were included, with 84 in the ESD group and 151 in the EMR group. The median size of the lesions in the ESD group (5.0 mm) was significantly larger than that in the EMR group (2.0 mm, P＜0.001). Additionally, the ESD group had significantly more lesions with pathological grade G2[23.8%(20/84) vs. 1.3%(2/151), P＜0.001], infiltration depth reaching the submucosal layer [78.6%(66/84) vs. 51.0%(77/151), P＜0.001], and more T2 stage compared to the EMR group[15.5%(13/84) vs. 0.7%(1/151), P＜0.001]. After PSM, 49 pairs of lesions were successfully matched between the two groups. Following PSM, there were no significant differences in the en bloc resection rate [100.0%(49/49) vs. 100.0%(49/49)], complete resection rate [93.9%(46/49) vs. 100.0%(49/49)], and complication rate [0(0/49) vs. 4.1%(2/49)] between the two groups. During the follow-up period, no recurrence or distant metastasis was observed in any of the lesions in both groups. Conclusions: The combination of endoscopy and serology diagnostic strategy has the potential to enhance the accuracy of diagnosing G1 and G2 stage G-NENs and their background mucosa. Endoscopic resection surgery (EMR, ESD) is a proven and safe treatment approach for G1 and G2 stage G-NENs.

Clinical manifestation, lifestyle, and treatment patterns of chronic erosive gastritis: A multicenter real-world study in China.

BACKGROUND: Although chronic erosive gastritis (CEG) is common, its clinical characteristics have not been fully elucidated. The lack of consensus regarding its treatment has resulted in varied treatment regimens. AIM: To explore the clinical characteristics, treatment patterns, and short-term outcomes in CEG patients in China. METHODS: We recruited patients with chronic non-atrophic or mild-to-moderate atrophic gastritis with erosion based on endoscopy and pathology. Patients and treating physicians completed a questionnaire regarding history, endoscopic findings, and treatment plans as well as a follow-up questionnaire to investigate changes in symptoms after 4 wk of treatment. RESULTS: Three thousand five hundred sixty-three patients from 42 centers across 24 cities in China were included. Epigastric pain (68.0%), abdominal distension (62.6%), and postprandial fullness (47.5%) were the most common presenting symptoms. Gastritis was classified as chronic non-atrophic in 69.9% of patients. Among those with erosive lesions, 72.1% of patients had lesions in the antrum, 51.0% had multiple lesions, and 67.3% had superficial flat lesions. In patients with epigastric pain, the combination of a mucosal protective agent (MPA) and proton pump inhibitor was more effective. For those with postprandial fullness, acid regurgitation, early satiety, or nausea, a MPA appeared more promising. CONCLUSION: CEG is a multifactorial disease which is common in Asian patients and has non-specific symptoms. Gastroscopy may play a major role in its detection and diagnosis. Treatment should be individualized based on symptom profile.

Chronological Trend of Opportunistic Endoscopic Screening for Gastric Cancer and Atrophic Gastritis.

BACKGROUND: Opportunistic endoscopic screening for gastric cancer was initiated in 2004 at our institute. We investigated chronological trends in gastric cancer detection rates based on individual characteristics and atrophic gastritis prevalence. METHODS: Overall, 15,081 asymptomatic individuals aged ≥40 years without a medical history of gastric cancer underwent first-time esophagogastroduodenoscopy in our institute between February 2004 and December 2017. We retrospectively investigated individual characteristics and endoscopic diagnoses by period (early period: 2004-2007, middle period: 2008-2012, and late period: 2013-2017), clarified the long-term detection rate and the characteristics of endoscopic screening-detected gastric cancer, and evaluated the relationship between gastric cancer and atrophic gastritis. RESULTS: Gastric cancer detection rates in the early, middle, and late periods were 1.01% (76/7,503, men/women: 4,360/3,143, average age: 59.4 years, prevalence of atrophic gastritis: 72%), 0.69% (40/5,820, men/women: 3,668/2,152, average age: 56.8 years, prevalence of atrophic gastritis: 48%), and 0.46% (8/1,758, men/women: 1,083/675, average age: 58.7 years, prevalence of atrophic gastritis: 37%), respectively. Multivariate analysis revealed that male sex (odds ratio 1.92, 95% confidence interval 1.28-2.95), age ≥75 years (2.73, 95% CI 1.32-5.05), and atrophic gastritis (C1-C3: 2.21, 1.36-3.73, O1-O3: 5.36, 3.17-9.30) were significantly associated with the incidence of gastric cancer. CONCLUSIONS: The gastric cancer detection rate and atrophic gastritis prevalence have decreased over time. However, continuing endoscopic screening is important, especially for those at a high risk of developing gastric cancer complicated by severe atrophic gastritis.

Creating a Framework for Treating Autoimmune Gastritis-The Case for Replacing Lost Acid.

Autoimmune gastritis (AIG) is characterized by the destruction of gastric parietal cells, resulting in hypochlorhydria and eventual achlorhydria, as oxyntic glands in the corpus are destroyed and become atrophic. The permanent loss of gastric acid has many impacts-both theoretical and documented. The most concerning of these are hypergastrinemia and increased N-nitroso compounds, both of which increase the risk of gastric cancers. While known deficiencies of B12 and iron are often replaced in AIG, acid is not. Moreover, patients with AIG are often prescribed acid suppression for a stomach that is decidedly no longer acidic, worsening the sequelae of gastric atrophy. Betaine hydrochloride (BHCL) is a short-acting acidifying agent, available over the counter in capsule form. Mealtime acid supplementation has an historic basis and could ameliorate many AIG-related gastrointestinal symptoms. Theoretically, acidification could also reduce the potential for hypergastrinemia and the production of N-nitroso compounds, consequently reducing the risk of gastric cancers. Supplemental vitamin C may also help in preventing gastric N-nitroso formation, regardless of the gastric pH. This narrative review describes the functions of gastric acid in gastrointestinal and immune health, documents the effects of hypochlorhydria in AIG, and proposes potential options for safely re-establishing the acid milieu of the stomach for patients with AIG.

Autoimmune gastritis serological biomarkers in gastric cancer patients.

The role of autoimmunity in the pathogenesis of gastric cancer remains controversial. We studied antiparietal cell antibody (anti-PCA) and anti-intrinsic factor antibody (anti-IFA) levels and their associations with pepsinogen I/pepsinogen II levels in patients with gastric adenocarcinoma compared to a control group with mild or no atrophy of the stomach mucosa. Plasma levels of anti-PCA and anti-IFA were measured by ELISA (Inova Diagnostics Inc, San Diego, California, USA). The cutoff value for anti-PCA and anti-IFA positivity was ≥25 units. Altogether 214 patients (126 men, 88 women, median age 64.46, range: 35-86) with confirmed gastric adenocarcinoma and 214 control cases paired for age and sex were included in the study. Positive anti-PCA was present in 22 (10.3%) gastric cancer patients and controls (P ≥ 0.999); positive anti-IFA in 6 (2.8%) and 4 (1.9.%), P < 0.232, respectively. We did not find significant differences in anti-PCA and anti-IFA positivity between gastric cancer patients and the control group; further investigation is required to better understand the potential involvement of autoimmune gastritis in the development of gastric cancer.

Correlation of chronic atrophic gastritis with gastric-specific circulating biomarkers.

BACKGROUND AND STUDY AIMS: It has been suggested that the combined detection of multiple serum biomarkers can effectively screen out the high-risk population of chronic atrophic gastritis in the general population. Therefore, it is necessary to establish an effective predictive model of chronic atrophic gastritis. PATIENTS AND METHODS: Serum biopsies were assessed using five stomach-specific circulating biomarkers pepsinogen I (PGI), PGII, PGI/II ratio, anti- H. pylori antibody, and gastrin-17 (G-17) to identify high-risk individuals and evaluate the risk of developing chronic atrophic gastritis. RESULTS: In the cross-sectional analysis, PGII, the PG ratio, G17, anti- H. pylori IgG were positively associated with the presence of chronic atrophic gastritis, and combined prediction of the five biomarkers was more accurate than single-factor prediction ((0.692 vs 0.54(PG1), 0.604 (PGⅡ), 0.616(PGI/II ratio), 0.629(G-17)). CONCLUSION: The combination of PGI, PGII, the PGI/II ratio, G17, and anti-H. pylori antibodies for serological analysis are helpful to screen chronic atrophic gastritis high-risk subjects from the general population and recommend that these people carry out further endoscopy and biopsy.

Diagnosing and grading gastric atrophy and intestinal metaplasia using semi-supervised deep learning on pathological images: development and validation study.

OBJECTIVE: Patients with gastric atrophy and intestinal metaplasia (IM) were at risk for gastric cancer, necessitating an accurate risk assessment. We aimed to establish and validate a diagnostic approach for gastric biopsy specimens using deep learning and OLGA/OLGIM for individual gastric cancer risk classification. METHODS: In this study, we prospectively enrolled 545 patients suspected of atrophic gastritis during endoscopy from 13 tertiary hospitals between December 22, 2017, to September 25, 2020, with a total of 2725 whole-slide images (WSIs). Patients were randomly divided into a training set (n = 349), an internal validation set (n = 87), and an external validation set (n = 109). Sixty patients from the external validation set were randomly selected and divided into two groups for an observer study, one with the assistance of algorithm results and the other without. We proposed a semi-supervised deep learning algorithm to diagnose and grade IM and atrophy, and we compared it with the assessments of 10 pathologists. The model's performance was evaluated based on the area under the curve (AUC), sensitivity, specificity, and weighted kappa value. RESULTS: The algorithm, named GasMIL, was established and demonstrated encouraging performance in diagnosing IM (AUC 0.884, 95% CI 0.862-0.902) and atrophy (AUC 0.877, 95% CI 0.855-0.897) in the external test set. In the observer study, GasMIL achieved an 80% sensitivity, 85% specificity, a weighted kappa value of 0.61, and an AUC of 0.953, surpassing the performance of all ten pathologists in diagnosing atrophy. Among the 10 pathologists, GasMIL's AUC ranked second in OLGA (0.729, 95% CI 0.625-0.833) and fifth in OLGIM (0.792, 95% CI 0.688-0.896). With the assistance of GasMIL, pathologists demonstrated improved AUC (p = 0.013), sensitivity (p = 0.014), and weighted kappa (p = 0.016) in diagnosing IM, and improved specificity (p = 0.007) in diagnosing atrophy compared to pathologists working alone. CONCLUSION: GasMIL shows the best overall performance in diagnosing IM and atrophy when compared to pathologists, significantly enhancing their diagnostic capabilities.

[Endoscopic and morphometric analysis of the reduction of acute inflammatory process in the gastric mucosa after therapy with Regasthym Gastro].

AIM: To analyze the anti-inflammatory efficacy of Regasthym Gastro (alpha-glutamyl-tryptophan) in the treatment of patients with chronic atrophic gastritis according to endoscopic and morphometric studies. MATERIALS AND METHODS: As part of a double-blind placebo-controlled study, the results of gastroscopy and histological (morphometric) studies were retrospective analyzed in 80 patients diagnosed with chronic atrophic gastritis associated with Helicobacter pylori in exacerbation: 43 patients took Regasthym Gastro, 37 patients - placebo. The conclusions of the gastroscopy were structured in the form of a standardized scale, which included an assessment of criteria in points (from 0 to 3): thickness of folds, hyperemia, edema of the gastric mucosa, the signs of atrophy, metaplasia; the severity of the erosive process. The sum of points according to all criteria was used to assess the dynamics of the inflammatory process: positive dynamics; lack of dynamics; the pathological process is progressing. The results of the endoscopic examination were compared with morphometry data (the number of inflammation pool cells per 1 mm2 of gastric mucosa). Statistical processing of the results was carried out using the Statistica 12 application software package. RESULTS: According to the gastroscopy, before therapy, hyperemia of the gastric mucosa was present in 82.5%, edema - in 53.8%, erosion - in 17.5%, signs of metaplasia - in 12.5% of patients. After therapy with the investigated drug a statistically significant decrease in the severity of edema of the gastric mucosa (p=0.008), the total set of signs of acute inflammatory process (p=0.006), a decrease in the proportion of outcomes with negative dynamics of the inflammatory process (p=0.038) was revealed. Statistically significant (p<0.05) correlations were found between gastroscopy data of inflammation and the number of neutrophil, eosinophil granulocytes, macrophages and lymphocytes per 1 mm2. CONCLUSION: Regasthym Gastro contributes to a significant decrease in the severity of the inflammatory process according to the evaluation of the results of gastroscopy and morphometry. It is possible to recommend the inclusion of this drug in the complex therapy of chronic gastritis to increase the effectiveness and reduce the risks of progression of inflammation.

Update on Serum Biomarkers in Autoimmune Atrophic Gastritis.

BACKGROUND: Autoimmune atrophic gastritis (AAG) is a persistent, corpus-restricted immune-mediated destruction of the gastric corpus oxyntic mucosa with reduced gastric acid and intrinsic factor secretion, leading to iron deficiency and pernicious anemia as a consequence of iron and cobalamin malabsorption. Positivity toward parietal cell (PCA) and intrinsic factor (IFA) autoantibodies is very common. AAG may remain asymptomatic for many years, thus making its diagnosis complex and often delayed. Due to the increased risk of gastric neoplasms, a timely diagnosis of AAG is clinically important. CONTENT: The gold standard for AAG diagnosis is histopathological assessment of gastric biopsies obtained during gastroscopy, but noninvasive, preendoscopic serological screening may be useful in some clinical scenarios. Serum biomarkers for AAG may be divided into 2 groups: gastric autoimmunity-related biomarkers, such as PCA and IFA, and gastric corpus atrophy/reduced gastric acid secretion-related biomarkers, such as serum gastrin and pepsinogens. The present review focuses on the clinical significance and pitfalls of serum biomarkers related to gastric autoimmunity and gastric corpus atrophy, including some discussion of analytical methods. SUMMARY: Serum assays for PCA, IFA, gastrin, and pepsinogen I show good diagnostic accuracy for noninvasive diagnostic work-up of AAG. Diagnostic performance may increase by combining >1 of these tests, overcoming the problem of seronegative AAG. However, appropriately designed, comparative studies with well-characterized patient cohorts are needed to better define the reliability of these biomarkers in the diagnosis of patients with AAG. Currently, positive serum tests should always be followed by the state-of-art diagnostic test, that is, histopathological assessment of gastric biopsies obtained during gastroscopy to definitively confirm or rule out AAG and eventually neoplastic complications.

Paradoxical association between dyspepsia and autoimmune chronic atrophic gastritis: Insights into mechanisms, pathophysiology, and treatment options.

BACKGROUND: Autoimmune gastritis (AIG) is a progressive, chronic, immune-mediated inflammatory disease characterized by the destruction of gastric parietal cells leading to hypo/anacidity and loss of intrinsic factor. Gastrointestinal symptoms such as dyspepsia and early satiety are very common, being second in terms of frequency only to anemia, which is the most typical feature of AIG. AIM: To address both well-established and more innovative information and knowledge about this challenging disorder. METHODS: An extensive bibliographical search was performed in PubMed to identify guidelines and primary literature (retrospective and prospective studies, systematic reviews, case series) published in the last 10 years. RESULTS: A total of 125 records were reviewed and 80 were defined as fulfilling the criteria. CONCLUSION: AIG can cause a range of clinical manifestations, including dyspepsia. The pathophysiology of dyspepsia in AIG is complex and involves changes in acid secretion, gastric motility, hormone signaling, and gut microbiota, among other factors. Managing dyspeptic symptoms of AIG is challenging and there are no specific therapies targeting dyspepsia in AIG. While proton pump inhibitors are commonly used to treat dyspepsia and gastroesophageal reflux disease, they may not be appropriate for AIG. Prokinetic agents, antidepressant drugs, and non-pharmacological treatments may be of help, even if not adequately evidence-based supported. A multidisciplinary approach for the management of dyspepsia in AIG is recommended, and further research is needed to develop and validate more effective therapies for dyspepsia.

Endoscopic grading of gastric atrophy and histological gastritis staging on risk assessment for early gastric cancer: A case-control study.

OBJECTIVES: To assess the predictive value of endoscopic grading of gastric atrophy using Kimura-Takemoto classification, histological grading systems of operative link on gastritis assessment (OLGA) and operative link on gastric intestinal metaplasia (OLGIM) on risk stratification for early gastric cancer (EGC) and other potential risk factors of EGC. METHODS: A single-center, case-control study was retrospectively conducted including 68 patients with EGC treated with endoscopic submucosal dissection and 68 age- and sex-matched control subjects. Kimura-Takemoto classification, OLGA and OLGIM systems, and other potential risk factors were evaluated between the two groups. RESULTS: Of the 68 EGC lesions, 22 (32.4%) were well differentiated, 38 (55.9%) were moderately differentiated, and 8 (11.8%) were poorly differentiated, respectively. Multivariate analysis revealed O-type Kimura-Takemoto classification (adjusted odds ratio [AOR] 3.282, 95% confidence interval [CI] 1.106-9.744, P = 0.032) and OLGIM stage III/IV (AOR 17.939, 95% CI 1.874-171.722, P = 0.012) were significantly related to a higher risk of EGC. Especially, O-type Kimura-Takemoto classification within 6-12 months before EGC diagnosis (AOR 4.780, 95% CI 1.650-13.845, P = 0.004) was independently associated with EGC risk. Areas under the receiver operating characteristic curve of the three systems for EGC were comparable. CONCLUSIONS: Endoscopic Kimura-Takemoto classification and histological OLGIM stage III/IV are independent risk factors for EGC, which may reduce the need for biopsies in risk stratification of EGC. Further multicenter prospective studies of large sizes are needed.

Chronic atrophic gastritis - An overlooked association with severe vitamin B12 deficiency: A case report and rapid review of literature.

Current guidelines recommend surveillance for gastric adenocarcinoma in patients with extensive chronic atrophic gastritis (CAG), which is considered a premalignant condition. Although the association between vitamin B12 deficiency and CAG is well described, the indication for endoscopic investigation is only advised in patients with pernicious anaemia. Our case did not have evidence of autoimmune or H. pylori infection but despite this she had CAG. We suggest considering gastroscopy for severe, unexplained vitamin B12 deficiency, particularly in this patient group.

The Efficacy of Morodan in Combination with Rabeprazole for the Treatment of Chronic Gastritis and its Impact on Gastric Mucosal Repair.

Objective: This study aimed to investigate the application and effectiveness of Morodan combined with rabeprazole in patients with chronic gastritis, focusing on its impact on gastric mucosa repair. Methods: A cohort of 109 patients diagnosed with chronic gastritis, who received treatment at our hospital between January 2020 and January 2021, were included in this study. Among them, 56 patients were assigned to the control group and received treatment with rabeprazole alone, while 53 were assigned to the research group and received a combination therapy of Morodan and rabeprazole. A comparative analysis was conducted between the two groups, assessing clinical efficacy, gastric mucosa repair effects, serum-related factors, and the incidence of adverse reactions. Results: The research group exhibited a higher total effective rate of treatment (94.64%) compared to the control group (79.25%) (P < .05). Following treatment, the research group showed lower levels of pepsinogen II, serum transforming growth factor α, serum epidermal growth factor, tumor necrosis factor-α, interleukin 6, and C-reactive protein compared to the control group (P < .05). Additionally, the research group displayed higher levels of pepsinogen I compared to the control group (P < .05). There was no significant difference in the incidence of adverse reactions between the research group and the control group (P > .05). Conclusions: The combination therapy of Morodan and rabeprazole demonstrates efficacy in the treatment of chronic gastritis. It promotes gastric mucosa repair, reduces inflammatory damage, and exhibits a higher safety profile with no significant increase in adverse reactions. This treatment approach holds a higher clinical application value.

Adequacy of endoscopic recognition and surveillance of gastric intestinal metaplasia and atrophic gastritis: A multicentre retrospective study in low incidence countries.

BACKGROUND: Gastric atrophy (GA) and gastric intestinal metaplasia (GIM) are precursor conditions to gastric adenocarcinoma (GAC) and should be monitored endoscopically in selected individuals. However, little is known about adherence to recommendations in clinical practice in low-risk countries. OBJECTIVE: The aim of this study was to evaluate endoscopic recognition and adequacy of surveillance for GA and GIM in countries with low GAC prevalence. METHODS: We retrospectively analysed patients diagnosed with GIM or GA in three centers in The Netherlands and UK between 2012 and 2019. Cases with GIM and/or GA diagnosis at index endoscopy were retrieved through systematic search of pathology databases using 'gastric' and 'intestinal metaplasia' or 'atrophy' keywords. Endoscopy reports were analysed to ascertain accuracy of endoscopic diagnoses. Adequacy of surveillance was assessed following histological diagnosis at the index endoscopy based on ESGE guidelines published in 2012. RESULTS: We included 396 patients with a median follow-up of 57.2 months. Mean age was 66 years and the rates of antrum-predominant versus extensive GIM were comparable (37% vs 38%). Endoscopic recognition rates were 48.5% for GA and 16.3% for GIM. Surveillance was adequately carried out in 215 of 396 patients (54.3%). CONCLUSION: In countries with a low incidence of GAC, the rate of endoscopic recognition of gastric pre-cancerous lesions and adherence to surveillance recommendation are low. Substantial improvement is required in endoscopic training and awareness of guidelines recommendation in order to optimise detection and management of pre-malignant gastric conditions.

Diagnostic performance of the normal range of gastrin calculated using strict criteria based on a combination of serum markers and pathological evaluation for detecting gastritis: a retrospective study.

BACKGROUND: The ABC method, which combines the pepsinogen method and anti-Helicobacter pylori antibody titers, has been used for risk screening for gastric cancer in Japan. However, it has been reported that there are cases of gastritis and carcinogenesis risk even in group A, which is considered to be a low-risk group based on the ABC method. Currently, in group A, endoscopic examination is needed to strictly discriminate "patients without gastritis" (defined as true A patients) from those "with gastritis." A simple and minimally invasive diagnostic criterion for gastritis using serological markers is desirable. In this study, we aimed to identify the normal serum gastrin concentrations in normal stomach cases based on pathological diagnosis and investigate the usefulness of serum gastrin concentrations in diagnosing gastritis. METHODS: Patients who underwent endoscopy and blood tests at Hiroshima University Hospital were enrolled in the study and categorized into the "pathologically-evaluated group" and "endoscopically-evaluated group," according to the evaluation method of atrophic gastritis. Initially, we measured serum gastrin concentrations in the normal stomach cases in the pathologically-evaluated group and calculated the normal range of serum gastrin concentrations. We used the upper limit of this normal range of serum gastrin concentrations and performed a validation study to determine its usefulness as a diagnostic marker for distinguishing between cases of gastritis and true A in the endoscopically-evaluated group. RESULTS: The 95th percentile of serum gastrin concentrations in pathologically-evaluated normal stomach cases was 34.12-126.03 pg/mL. Using the upper limit of this normal range of serum gastrin concentrations, the sensitivity, specificity, positive predictive value, and negative predictive value for gastritis were 52.8%, 92.6%, 97.0%, and 31.0%, respectively. Additionally, the receiver operating characteristic (ROC) curve for the endoscopically-evaluated group showed an area under the ROC curve of 0.80. CONCLUSION: The gastrin cut-off value of 126 pg/mL has a good positive predictive value (97.0%) for detecting gastritis positing its use as a marker for cases requiring endoscopy. However, the identification of patients with gastritis having normal serum gastrin concentrations due to insufficient sensitivity remains a challenge for the future.

A Liquid Biopsy Signature for the Early Detection of Gastric Cancer in Patients.

BACKGROUND & AIMS: Diagnosing gastric cancer (GC) while the disease remains eligible for surgical resection is challenging. In view of this clinical challenge, novel and robust biomarkers for early detection thus improving prognosis of GC are necessary. The present study is to develop a blood-based long noncoding RNA (LR) signature for the early-detection of GC. METHODS: The present 3-step study incorporated data from 2141 patients, including 888 with GC, 158 with chronic atrophic gastritis, 193 with intestinal metaplasia, 501 healthy donors, and 401 with other gastrointestinal cancers. The LR profile of stage I GC tissue samples were analyzed using transcriptomic profiling in discovery phase. The extracellular vesicle (EV)-derived LR signature was identified with a training cohort (n = 554) and validated with 2 external cohorts (n = 429 and n = 504) and a supplemental cohort (n = 69). RESULTS: In discovery phase, one LR (GClnc1) was found to be up-regulated in both tissue and circulating EV samples with an area under the curve (AUC) of 0.9369 (95% confidence interval [CI], 0.9073-0.9664) for early-stage GC (stage I/II). The diagnostic performance of this biomarker was further confirmed in 2 external validation cohorts (Xi'an cohort, AUC: 0.8839; 95% CI: 0.8336-0.9342; Beijing cohort, AUC: 0.9018; 95% CI: 0.8597-0.9439). Moreover, EV-derived GClnc1 robustly distinguished early-stage GC from precancerous lesions (chronic atrophic gastritis and intestinal metaplasia) and GC with negative traditional gastrointestinal biomarkers (CEA, CA72-4, and CA19-9). The low levels of this biomarker in postsurgery and other gastrointestinal tumor plasma samples indicated its GC specificity. CONCLUSIONS: EV-derived GClnc1 serves as a circulating biomarker for the early detection of GC, thus providing opportunities for curative surgery and improved survival outcomes.

Determination of an Appropriate Endoscopic Monitoring Interval for Patients with Gastric Precancerous Conditions in China.

OBJECTIVE: Gastric precancerous conditions such as atrophic gastritis (AG) and intestinal metaplasia (IM) are considered independent risk factors for gastric cancer (GC). The suitable endoscopic monitoring interval is unclear when we attempt to prevent GC development. This study investigated the appropriate monitoring interval for AG/IM patients. METHODS: Totally, 957 AG/IM patients who satisfied the criteria for evaluation between 2010 and 2020 were included in the study. Univariate and multivariate analyses were used to determine the risk factors for progression to high-grade intraepithelial neoplasia (HGIN)/GC in AG/IM patients, and to determine an appropriate endoscopic monitoring scheme. RESULTS: During follow-up, 28 AG/IM patients developed gastric neoplasia lesions including gastric low-grade intraepithelial neoplasia (LGIN) (0.7%), HGIN (0.9%), and GC (1.3%). Multivariate analysis identified H. pylori infection (P=0.022) and extensive AG/IM lesions (P=0.002) as risk factors for HGIN/GC progression (P=0.025). CONCLUSION: In our study, HGIN/GC was present in 2.2% of AG/IM patients. In AG/IM patients with extensive lesions, a 1-2-year surveillance interval is recommended for early detection of HIGN/GC in AG/IM patients with extensive lesions.

Discrimination between Precancerous Gastric Lesions and Gastritis Using a Gastric Cancer Risk Stratification Model.

BACKGROUND: Seropositivity to certain Helicobacter pylori proteins may affect development of gastric lesions that could become cancerous. Previously, we developed a model of gastric cancer risk including gender, age, HP0305 sero-positivity, HP1564 sero-positivity, UreA antibody titer and serologically defined chronic atrophic gastritis (termed: "Lasso model"). METHODS: We evaluated the Lasso model's ability to discriminate individuals with precancerous gastric lesions (n=320) from individuals with superficial or mild atrophic gastritis (n=226) in Linqu County, China, a population at high risk for gastric cancer. We also compared its performance to the ABC Method, a gastric cancer risk stratification tool currently used in East Asia. RESULTS: For distinguishing precancerous lesions from those with gastritis, the receiver operating characteristic curve had an area under the curve (AUC) of 73.41% (95% CI: 69.10%, 77.71%) and, at Youden's Index, a sensitivity of 78.44% (59.38%, 82.50%) and specificity of 64.72% (95% CI: 58.85%, 81.42%). Positive predictive value (PPV) was 75.38% (72.78%, 82.51%). Specificity, AUC and PPV were significantly greater (p < 0.05) than those of the ABC Method. When specificity was held constant, the Lasso model had greater sensitivity, PPV and negative predictive value (NPV) than the ABC Method. However, adjusting the ABC Method for age and gender negated the Lasso model's significant improvement in AUC. CONCLUSIONS: The Lasso model for gastric cancer risk prediction can classify precancerous lesions with significantly greater AUC than the ABC Method and, at constant specificity, with greater sensitivity, PPV and NPV. However, adding age and gender to the ABC Method, as included in the Lasso model, substantially improved its performance and negated the Lasso model's advantage.

The Morphologic Spectrum of Gastric Type 1 Enterochromaffin-Like Cell Neuroendocrine Tumors.

Although most well-differentiated gastric neuroendocrine tumors (gNETs) arise from enterochromaffin-like (ECL) cells in patients with autoimmune metaplastic atrophic gastritis (AMAG), the morphologic spectrum of these type 1 ECL-cell gNETs is not well defined. The extent of metaplastic progression in the background mucosa of AMAG patients with gNETs is likewise unclear. Here we report the histomorphology of 226 gNETs, including 214 type 1 gNETs (78 cases from 50 AMAG patients) pooled from a population with high AMAG prevalence. Most type 1 gNETs were ≤1.0 cm, of low grade, and multifocal, consistent with the results of previous reports. However, a high proportion (70/214, 33%) displayed unusual gNET morphologies not previously appreciated in AMAG patients. Unlike other type 1 gNETs with conventional neuroendocrine tumor morphologies, unconventional type 1 gNETs displayed cribriform networks of atrophic cells embedded within myxoid matrix (secretory-cribriform variant, 59%), sheets of deceptively bland discohesive cells resembling inflammatory infiltrates (lymphoplasmacytoid variant, 31%), or wreath-like arrangements of columnar cells wrapped around collagenous cores (pseudopapillary variant, 14%). Another unusual feature was that unconventional gNETs grew laterally within the mucosa (50/70, 71%) and were only rarely sampled from the submucosa (3/70, 4%). These features also differed from the conspicuous radial nodules (99/135, 73%) and frequent submucosal involvement (57/135, 42%) observed for conventional gNETs (P < .0001). Irrespective of morphology, type 1 gNETs were nearly always detected at first AMAG diagnosis (45/50, 90%) and tended to persist thereafter (34/43, 79%), despite similar clinical symptoms and laboratory values between AMAG patients with gNETs and those without. However, unlike AMAG patients without gNETs (n = 50), the background mucosa in patients with gNETs (n = 50) had already progressed to the morphologic equivalent of end-stage metaplasia (P < .0001). This included diffuse loss of parietal cells (92% vs 52%), complete intestinal metaplasia (82% vs 40%), and pancreatic metaplasia (56% vs 6%). Thus, type 1 ECL-cell gNETs are morphologically heterogeneous with a high prevalence of unconventional gNET morphologies. They tend to present silently at first AMAG diagnosis as multifocal lesions that persist within fields of mature metaplasia.