Atrophic Gastritis Research Articles

Association between fish and shellfish consumption, n-3 polyunsaturated fatty acids, and gastric cancer risk: the Japan Public Health Center-based Prospective Study

PurposeFish and shellfish consumption is suggested to be a cancer-protective factor. However, studies investigating this association for gastric cancer, especially considering Helicobacter pylori (H. pylori) and atrophic gastritis (AG), are limited. We investigated gastric cancer risk associated with fish, shellfish, and n-3 polyunsaturated fatty acids (n-3 PUFAs) consumption among Japanese adults.Methods90,504 subjects enrolled in the Japan Public Health Center-based Prospective Study (JPHC Study) were followed until December 2013. Dietary intake data were collected using a food frequency questionnaire. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for gastric cancer risk associated with fish and shellfish consumption and marine n-3 PUFAs (sum of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA)) using Cox proportional hazards models. Among those with avaliable data, we conducted a subgroup analysis taking H. pylori infection and AG status into consideration.ResultsThere were 2,701 gastric cancer cases during an average of 15 years of follow-up. We observed an increased gastric cancer risk for salted fish consumption for men [HR for fifth quintile versus first quintile 1.43 (95% CI 1.18–1.75)] and for women [HR 1.33 (95% CI 1.00–1.77)]. We observed a weak risk reduction trend for women as the intake of marine n-3 PUFAs increased (p-trend:0.07). When we included H. pylori infection and atrophic gastritis status in the analysis, the associations diminished.ConclusionOur results suggest that salted fish increases gastric cancer risk for men and women, while marine n-3 PUFAs marginally decreases this risk among women in Japan.

Diagnostic value of combined detection of three gastric functions and Helicobacter pylori typing in chronic gastritis and gastric cancer

This research attempted to clarify the clinical diagnostic value of combined detection of gastric function and Helicobacter pylori (Hp) serotyping in chronic gastritis and gastric cancer (GC). The 80 chronic non atrophic gastritis (CNAG) patients treated in our hospital from October 2021 to October 2022 received selection as the CNAG group. The 96 chronic atrophic gastritis (CAG) patients diagnosed by gastroscopy and pathology in the same period received selection as CAG group. During the same period, 50 patients diagnosed with GC received inclusion in GC group. Pepsin I (PG I), PG II (PG II), gastrin-17 (G-17) and Hp serotyping received detection and comparison in three groups. The diagnostic efficacy of PG Ⅰ, PG Ⅱ, G-17, the ratio of serum PG I to PG II (PGR), and Hp serotyping in chronic gastritis and GC received evaluation by receiver operating characteristic (ROC). Relative to in the CNAG group, PG I and PGR levels in the other two groups exhibited depletion (P < 0.05); no statistical significance was observed in the PG II level among the three groups (P > 0.05); relative to the CNAG group, the G-17 level in the other two groups exhibited elevation (P < 0.05). Total Hp positive rate was 61.06 %, among which GC group exhibited the highest positive rate (72.00 %), and type I Hp positive rate also exhibited the highest in GC group (60.00 %). The type II Hp positive rate exhibited the highest in CNAG group (15.00 %). The PG I and PGR levels in type I Hp positive patients exhibited depletion relative to those in type II Hp positive patients, whereas PG II and G-17 levels exhibited elevation. When testing each indicator alone, the area under the curve (AUC) of PG I exhibited the highest in CNAG group, which was 0.874. When testing each indicator alone, AUC of Hp typing exhibited the highest in CAG group, which was 0.515. When testing each indicator alone, AUC of G-17 exhibited the highest in GC group, which was 0.787. The performance of combined detection was better than that of individual detection, with AUCs greater than 0.9 in three groups. In conclusion, changes in PG I, PG II, PGR and G-17 levels and Hp serotyping can receive application as screening indicators for chronic gastritis and GC, which can reflect relevant status of gastric mucosa to varying degrees. Combined detection of indicators has higher diagnostic performance and can receive application as an auxiliary diagnostic indicator in addition to gastroscopy biopsy, providing a reference basis for the formulation of clinical diagnosis and treatment plans.

Integrated Approaches Revealed the Therapeutic Mechanisms of Zuojin Pill Against Gastric Mucosa Injury in a Rat Model with Chronic Atrophic Gastritis.

The Zuojin Pill (ZJP) is widely used for treating chronic atrophic gastritis (CAG) in clinical practice, effectively ameliorating symptoms such as vomiting, pain, and abdominal distension in patients. However, the underlying mechanisms of ZJP in treating CAG has not been fully elucidated. This study aimed to clarify the characteristic function of ZJP in the treatment of CAG and its potential mechanism. The CAG model was established by alternant administrations of ammonia solution and sodium deoxycholate, as well as an irregular diet. Therapeutic effects of ZJP on body weight, serum biochemical indexes and general condition were analyzed. HE staining and AB-PAS staining were analyzed to characterize the mucosal injury and the thickness of gastric mucosa. Furthermore, network pharmacology and molecular docking were used to predict the regulatory mechanism and main active components of ZJP in CAG treatment. RT-PCR, immunohistochemistry, immunofluorescence and Western blotting were used to measure the expression levels of apoptosis-related proteins, gastric mucosal barrier-associated proteins and PI3K/Akt signaling pathway proteins. The results demonstrated that ZJP significantly improved the general state of CAG rats, alleviated weight loss and gastric histological damage and reduced the serum biochemical indicators. Network pharmacology and molecular docking found that ZJP in treating CAG by inhibiting inflammation, suppressing apoptosis, and protecting the gastric mucosal barrier via the PI3K/Akt signaling pathway. Further experiments confirmed that ZJP obviously modulated the expression of key proteins involved in gastric mucosal cell apoptosis, such as Bax, Bad, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, Cytochrome C, Bcl-2, and Bcl-xl. Moreover, ZJP significantly reversed the protein expression of Occludin, ZO-1, Claudin-4 and E-cadherin. Our study revealed that ZJP treats CAG by inhibiting the PI3K/Akt signaling pathway. This research provided a scientific basis for the rational use of ZJP in clinical practice.

An Exploration of Professor Shen Shuwen's Experience in Chronic Atrophic Gastritis

An Exploration of Professor Shen Shuwen's Experience in Chronic Atrophic Gastritis

Survey on the Knowledge and the Management of Helicobacter pylori Infection by Italian General Practitioners and Doctors in General Practice Training

The management of gastric Helicobacter pylori (H. pylori) infection represents a significant concern in primary healthcare. This survey evaluates the approaches, attitudes, and knowledge regarding gastric H. pylori infection among Italian general practitioners (GPs) and young doctors undergoing general practice training (ITGPs). The survey enrolled 466 GPs and 70 ITGPs. Among GPs, specialist recommendations and the Maastricht–Florence guidelines were frequently referenced sources, while ITGPs relied more on the Maastricht–Florence guidelines and internet resources. ITGPs demonstrated more proactive approaches than GPs in investigating and treating conditions such as gastric ulcers, atrophic gastritis, and iron-deficiency anemia. However, there was limited attention given to the role of H. pylori treatment in first-degree relatives of gastric cancer patients. The most used diagnostic methods were the urea breath test and fecal test. Triple therapy was the most frequently chosen initial treatment regimen, with quadruple bismuth therapy becoming the primary option after initial treatment failure, followed by quinolone therapy and concomitant therapy. This survey underscores a disparity between real-world practices and the recommendations outlined in current guidelines, indicating a need for improved understanding of H. pylori guidelines among both GPs and ITGPs.

Research Progress of Traditional Chinese Medicine in the Treatment of Chronic Atrophic Gastritis

Research Progress of Traditional Chinese Medicine in the Treatment of Chronic Atrophic Gastritis

Meta-analysis of modified Sijunzi decoction for the treatment of chronic atrophic gastritis.

Qi deficiency in the spleen and stomach is considered to be the fundamental pathogenesis of chronic atrophic gastritis (CAG) in Traditional Chinese medicine. Spleen strengthening and Qi replenishment are the basic treatment principles. Sijunzi Decoction serves as the fundamental remedy for spleen notification and Qi replenishment. The Cochrane Library, China National Knowledge Infrastructure China Biology Medicine disc, VIP, Wanfang Database, Web of Science, PubMed, and Embase were retrieved for related randomized controlled trials published from the inception of the databases to June 3, 2023. Literature screening and data extraction were executed by 2 independent investigators. The Cochrane Collaboration tool was leveraged to appraise the quality of included studies. Meta-analysis was implemented utilizing Stata 15. This analysis incorporated 32 studies with 2780 patients. The analysis results unveiled that compared to Western medicine treatment, modified Sijunzi Decoction significantly enhanced the clinical efficacy (relative risk [RR] = 1.241, 95% confidence interval [95% CI] = 1.199-1.285, P < .0001), lowered symptom scores (standardized mean difference [SMD] = -1.846, 95% CI = -2.160 to -1.532, P < .00001) and gastroscopic pathological scores (SMD = -1.122, 95% CI = -1.492 to -0.752, P < .00001), ameliorated quality of life (SMD = 4.294, 95% CI = 2.982-5.606, P < .00001), increased the Helicobacter pylori eradication rate (RR = 1.297, 95% CI = 1.035-1.625, P < .001), pepsinogen I levels (SMD = 2.615, 95% CI = 2.344-2.886, P < .00001), pepsinogen I/II ratio (SMD = 3.107, 95% CI = 2.811-3.403, P < .00001), and gastrin-17 levels (SMD = 1.004, 95% CI = 0.794-1.215, P < .00001), and reduced the incidence of adverse reactions (RR = 0.361, 95% CI = 0.235-0.556, P < .01) in individuals with CAG, with statistically significant discrepancies. Modified Sijunzi Decoction exhibited superior efficacy to conventional Western medicine in treating CAG. It was shown to improve the Helicobacter pylori eradication rate, reduce symptom scores, enhance quality of life, and improve pepsinogen-related indicators with a high safety profile.

Detection Rate of Helicobacter Pylori Infection and Atrophic Gastritis Using Serological Markers “GastroPanel®” Among Employees of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation

Aim: to evaluate, using the “GastroPanel®”, the frequency of detection of H. pylori infection and associated gastric diseases among doctors and medical staff of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, Moscow.Materials and methods. Employees of three branches of the National Medical Research Radiological Centre (n = 434, mean age — 48.5 ± 0.6 years) were examined using laboratory tests “GastroPanel®” (Biohit Oyj, Finland). The test results make it possible to identify infection of the stomach with H. pylori, hypo- and hyperacid conditions, as well as atrophic gastritis of the antrum and body of the stomach, as its precancerous conditions. Esophagogastroduodenoscopy (EGDS) for suspected atrophic gastritis was performed with an Olympus GIF-HQ190 video endoscope (Japan) in a narrow-spectrum mode with close focus (NBI Dual Focus).Results. The absence of pathological signs detected by “GastroPanel®” was established in 23.3 % of cases, hyperacid state — in 18.4 %, and hypoacid state — in 5.2 %. These disorders are classified as functional. Consequently, the conditional norm in total was identified in 46.9 % of observations. An increased level of antibodies to H. pylori was found in 43.3 % of those examined. Atrophic gastritis in the body of the stomach according to the results of the “GastroPanel®” was detected in 4.8 % of cases (median age — 59 years), in the antrum (or increased secretion of hydrochloric acid) — also in 4.8 % of cases (median age — 52 years). Within two months after laboratory diagnostics, EGDS was performed for 10 out of 15 patients examined at the P. Hertsen Moscow Oncology Research Institute in whom, based on the results of the “GastroPanel®”, the presence of atrophic gastritis in the antrum (or increased secretion of hydrochloric acid) was suspected. In 6 out of 10 cases, atrophic gastritis of the antrum was confirmed (in two of them, the atrophy extended to the body of the stomach and was assessed as severe). Of the 11 people with the “GastroPanel®” conclusion “Atrophic gastritis of the body of the stomach,” an endoscopic examination was carried out in 7 persons, and in all these cases the diagnosis was confirmed, and in two people the conclusion was made of severe atrophic pangastritis.Conclusion. “GastroPanel®” confirmed its high significance in identifying H. pylori infection and precancerous atrophic changes in the gastric mucosa. Regarding the occupational risks of infection among medical workers, we consider it advisable to conduct such screening without selecting an asymptomatic population.

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.

Exploration of lncRNA/circRNA-miRNA-mRNA network in patients with chronic atrophic gastritis in Tibetan plateau areas based on DNBSEQ-G99 RNA sequencing

A higher incidence of chronic atrophic gastritis (CAG) is generally considered as a precancerous lesion in gastric cancer (GC). The aim of this study was to identify potential molecules involved in the pathogenesis of CAG in the Tibetan plateau, hoping to help the diagnosis and management of the disease. Atrophic and non-atrophic gastric mucosal tissue samples were collected from seven patients with chronic gastritis (CG). Differentially expressed lncRNAs, circRNAs, miRNAs, and mRNAs between CAG and chronic non-atrophic gastritis (CNAG) groups were identified based on DNBSEQ-G99 RNA sequencing. Subsequently, competitive endogenous RNA (ceRNA) regulatory networks (lncRNA/circRNA-miRNA-mRNA networks) were constructed. Two datasets (GSE153224 and GSE163416), involving data from non-Tibetan plateau areas, were used to further screen out Tibetan plateau key mRNAs, followed by the common genes of Tibetan plateau key and ferroptosis-related mRNAs were also identified. Functional enrichment analyses were performed to investigate the biological functions of Tibetan plateau mRNAs in the CAG. A total of seven lncRNA-miRNA-mRNA relationship pairs and 424 circRNA-miRNA-mRNA relationship pairs were identified in this study. The relationship pairs of hsa_circ_0082984-hsa-miR-204-5p-CACNG8, lncRNA DRAIC/has_circ_0008561-hsa-miR-34a-5p-AR/GXYLT2, lncRNA GAS1RR/RGMB-AS1/hsa_circ_0008561-hsa-miR-3614-5p-TMEM216/SUSD5, and LINC00941/hsa_circ_0082984-hsa-miR-873-3p-TMC5 can be involved in the pathogenesis of CAG. Additionally, eight common genes of Tibetan plateau key and ferroptosis-related differentially expressed mRNAs (DEmRNAs) (CBS, SLC2A4, STAT3, ALOX15B, ATF3, IDO1, NOX4, and SOCS1) were identified in CAG. The common genes of Tibetan plateau key and ferroptosis-related DEmRNAs can play a role in the JAK-STAT signaling pathway. This study identified important molecular biomarkers that may be involved in regulating the pathological mechanisms of CAG in the Tibetan plateau, which provides potential research directions for future research.

Clinicopathologic and endoscopic characteristics of ten patients with gastric hamartomatous inverted polyp: a single center case series

BackgroundGastric hamartomatous inverted polyps (GHIPs) are not well characterized and remain diagnostically challenging due to rarity. Therefore, this study aims to investigate the clinicopathologic and endoscopic characteristics of patients with GHIP.MethodsWe retrospectively reviewed clinicopathologic and endoscopic features of ten patients with GHIP who were admitted to Beijing Friendship Hospital from March 2013 to July 2022. All patients were treated successfully by endoscopic resection.ResultsGHIPs were usually asymptomatic and found incidentally during gastroscopic examination. They may be sessile or pedunculated, with diffuse or local surface redness or erosion. On endoscopic ultrasonography, the sessile submucosal tumor-type GHIP demonstrated a heterogeneous lesion with cystic areas in the third layer of the gastric wall. Histologically, GHIPs were characterized by a submucosal inverted proliferation of cystically dilated hyperplastic gastric glands accompanied by a branching proliferation of smooth muscle bundles. Inflammatory cells infiltration was observed in the stroma, whereas only one patient was complicated with glandular low-grade dysplasia. Assessment of the surrounding mucosa demonstrated that six patients (60%) had atrophic gastritis or Helicobacter pylori–associated gastritis, and four patients (40%) had non-specific gastritis. Endoscopic resection was safe and effective.ConclusionsGHIPs often arise from the background of abnormal mucosa, such as atrophic or H.pylori-associated gastritis. We make the hypothesis that acquired inflammation might lead to the development of GHIPs. We recommend to make a full assessment of the background mucosa and H. pylori infection status for evaluation of underlying gastric mucosal abnormalities, which may be the preneoplastic condition of the stomach.

Pathogenesis and potential reversibility of intestinal metaplasia - a milestone in gastric carcinogenesis.

Non-cardia gastric cancer remains a major cause of cancer-related mortality worldwide, despite declining incidence rates in many industrialized countries. The development of intestinal-type gastric cancer occurs through a multistep process in which normal mucosa is sequentially transformed into hyperproliferative epithelium, followed by metaplastic processes leading to carcinogenesis. Chronic infection with Helicobacter pylori is the primary etiological agent that causes chronic inflammation of the gastric mucosa, induces atrophic gastritis, and can lead to intestinal metaplasia and dysplasia. Both intestinal metaplasia and dysplasia are precancerous lesions, in which gastric cancer is more likely to occur. Atrophic gastritis often improves after eradication of Helicobacter pylori; however, the occurrence of intestinal metaplasia has been traditionally regarded as "the point of no return" in the carcinogenesis sequence. Helicobacter pylori eradication heals non-atrophic chronic gastritis, may lead to regression of atrophic gastritis, and reduces the risk of gastric cancer in patients with these conditions. In this article, we discuss the pathogenesis, epigenomics, and reversibility of intestinal metaplasia and briefly touch upon potential treatment strategy. Gastric intestinal metaplasia no longer appears to be an irreversible precancerous lesion. However, there are still many controversies regarding the improvement of intestinal metaplasia after Helicobacter pylori eradication.

CD20 + T lymphocytes in isolated Hashimoto’s thyroiditis and type 3 autoimmune polyendocrine syndrome: a pilot study

BackgroundCD20+ T cells represent up to 5% of circulating T lymphocytes. These cells have been shown to produce higher levels of IL-17A and IFN-γ than those of CD20− T lymphocytes. Some reports described the role of CD20+ T cells in autoimmune disorders such as multiple sclerosis and rheumatoid arthritis possibly due to their ability to produce these inflammatory cytokines. This study is aimed at describing the behavior of CD20+ T lymphocytes in the most frequent autoimmune disorder, i.e., Hashimoto’s thyroiditis (HT), presenting isolated or associated to further autoaggressive disorders in a frame of poly-autoimmunity.MethodsThe study group encompasses 65 HT patients: 23 presenting in isolated form (IT) and 42 with an associated non-endocrine autoimmune disorder [16 with chronic atrophic gastritis (CAG), 15 with nonsegmental vitiligo (VIT), and 11 with celiac disease (CD)]. Twenty healthy donors act as control group (HD). Chronic use of interfering drugs, severe or chronic disorders, and pregnancy and lactation were used as exclusion criteria. Whole blood samples (100 µl) were stained with fluorescent-labeled antibodies (anti-CD45, anti-CD3, anti-CD19, anti-CD16, anti-CD56, anti-CD4, anti-CD8, anti-CD20). Red blood cells were then lysed by adding 1 ml of hypotonic buffer, and samples were acquired on a Flow Cytometer.ResultsCD3+CD8+CD20+ T lymphocytes’ percentages, were significantly higher in the whole group of autoimmune patients compared to healthy donors (p = 0.0145). Dividing HT patients based on the type of presentation of autoimmune thyroiditis, CAG group showed the highest percentage of these cells as compared to HD and CD (p = 0.0058). IT patients showed higher percentages of CD3+ CD8+CD20+ cells than those of HD patients although not reaching statistical significance. However, dividing IT group based on thyroid function, hypothyroid patients showed higher CD8+CD20+ cell percentages than those of HD and euthyroid patients (p = 0.0111). Moreover, in IT patients, these cells were negatively correlated with FT4 levels (p = 0.0171; r = −0.4921).ConclusionsThese preliminary findings indicate that CD8+CD20+ T cells are activated in patients with autoimmune thyroiditis and may behave differently according to the presence of poly-autoimmunity and hypothyroidism.

Exploring the pathogenesis of chronic atrophic gastritis with atherosclerosis via microarray data analysis.

Although several studies have reported a link between chronic atrophic gastritis (CAG) and atherosclerosis, the underlying mechanisms have not been elucidated. The present study aimed to investigate the molecular mechanisms common to both diseases from a bioinformatics perspective. Gene expression profiles were obtained from the Gene Expression Omnibus database. Data on atherosclerosis and CAG were downloaded from the GSE28829 and GSE60662 datasets, respectively. We identified the differentially expressed genes co-expressed in CAG and atherosclerosis before subsequent analyses. We constructed and identified the hub genes and performed functional annotation. Finally, the transcription factor (TF)-target genes regulatory network was constructed. In addition, we validated core genes and certain TFs. We identified 116 common differentially expressed genes after analyzing the 2 datasets (GSE60662 and GSE28829). Functional analysis highlighted the significant contribution of immune responses and the positive regulation of tumor necrosis factor production and T cells. In addition, phagosomes, leukocyte transendothelial migration, and cell adhesion molecules strongly correlated with both diseases. Furthermore, 16 essential hub genes were selected with cytoHubba, including PTPRC, TYROBP, ITGB2, LCP2, ITGAM, FCGR3A, CSF1R, IRF8, C1QB, TLR2, IL10RA, ITGAX, CYBB, LAPTM5, CD53, CCL4, and LY86. Finally, we searched for key gene-related TFs, especially SPI1. Our findings reveal a shared pathogenesis between CAG and atherosclerosis. Such joint pathways and hub genes provide new insights for further studies.

Prevalence of H. pylori and Gastric Intestinal Metaplasia in BRCA1 and BRCA2 Carriers.

BRCA1 and BRCA2 carriers may be at increased risk for gastric cancer; however, the mechanisms of gastric carcinogenesis remain poorly understood. We sought to determine the prevalence of gastric cancer risk factors Helicobacter pylori (H. pylori) infection and gastric intestinal metaplasia (GIM) among BRCA1/2 carriers to gain insight into the pathogenesis of gastric cancer in this population. A total of 100 unselected BRCA1/2 carriers who underwent endoscopic ultrasound from March 2022 to March 2023 underwent concomitant upper endoscopy with nontargeted gastric antrum and body biopsies. The study population (70% women; mean age 60.1 years) included 66% BRCA2 carriers. H. pylori was detected in one (1%) individual, 7 (7%) had GIM, 2 (2%) had autoimmune atrophic gastritis, and no gastric cancers were diagnosed. Among BRCA1/2 carriers, H. pylori prevalence was low and GIM prevalence was similar to that in the general population; however, identification of H. pylori or GIM may help inform future gastric cancer risk management strategies in BRCA1/2 carriers. Prevention Relevance: Evaluating the burden of H. pylori infection and GIM among BRCA1/2 carriers is warranted to better understand the mechanisms of gastric carcinogenesis and to help inform risk management strategies for gastric cancer among this at-risk population.

Vitamins D and B&lt;sub&gt;12&lt;/sub&gt;, homocysteine and laboratory markers of chronic atrophic gastritis in Chernobyl liquidators with metabolic syndrome

Vitamins D and B&lt;sub&gt;12&lt;/sub&gt;, homocysteine and laboratory markers of chronic atrophic gastritis in Chernobyl liquidators with metabolic syndrome

Characteristics of early gastric tumors with different differentiation and predictors of long-term outcomes after endoscopic submucosal dissection

BACKGROUND Gastric cancer is a common malignant tumor of the digestive tract, and endoscopic submucosal dissection (ESD) is the preferred treatment for early-stage gastric cancer. The analysis of the epidemiological characteristics of gastric mucosal tumors with different differentiation degrees and the influencing factors of long-term ESD efficacy may have certain significance for revealing the development of gastric cancer and ESD. AIM To analyze the features of gastric mucosal tumors at different differentiation levels, and to explore the prognostic factors of ESD. METHODS We retrospectively studied 301 lesions in 285 patients at The Second Affiliated Hospital of Xi'an Jiaotong University from 2014 to 2021, according to the latest Japanese guidelines (sixth edition), and divided them into low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and differentiated and undifferentiated early carcinoma. They are followed up by endoscopy, chest and abdominal computed tomography at 3, 6 and 12 months after ESD. We compared clinicopathologic characteristics, ESD efficacy, and complications with different degrees of differentiation, and analyzed the related factors associated with ESD. RESULTS HGIN and differentiated carcinoma patients were significantly older compared with LGIN patients (P &lt; 0.001) and accounted for more 0-IIc (P &lt; 0.001), atrophic gastritis was common (P &lt; 0.001), and irregular microvascular patterns (IMVPs) and demarcation lines (DLs) were more obvious (P &lt; 0.001). There was more infiltration in the undifferentiated carcinoma tissue (P &lt; 0.001), more abnormal folds and poorer mucosal peristalsis (P &lt; 0.001), and more obvious IMVPs, irregular microsurface patterns and DLs (P &lt; 0.05) than in the LGIN and HGIN tissues. The disease-free survival rates at 2, 5, and 8 years after ESD were 95.0%, 90.1%, and 86.9%, respectively. Undifferentiated lesions (HR 5.066), white moss (HR 7.187), incomplete resection (HR 3.658), and multiple primary cancers (HR 2.462) were significantly associated with poor prognosis. CONCLUSION Differentiations of gastric mucosal tumors have different epidemiological and endoscopic characteristics, which are closely related to the safety and efficacy of ESD.

Gastric neuroendocrine neoplasms.

Gastric neuroendocrine neoplasms (gNENs) display peculiar site-specific features among all NENs. Their incidence and prevalence have been rising in the past few decades. gNENscomprise gastric neuroendocrine carcinomas (gNECs) and gastricneuroendocrine tumours (gNETs), the latter further classified into three types. Type I anatype II gNETs are gastrin-dependent and develop in chronic atrophic gastritis and as part of Zollinger-Ellison syndrome within a multiple endocrine neoplasia type 1 syndrome (MEN1), respectively. Type III or sporadic gNETs develop in the absence of hypergastrinaemia and in the context of a near-normal or inflamed gastric mucosa. gNECs can also develop in the context of variable atrophic, relatively normal or inflamed gastric mucosa. Each gNEN type has different clinical characteristics and requires a different multidisciplinary approach in expert dedicated centres. Type I gNETs are managed mainly by endoscopy or surgery, whereas the treatment of typeII gNETs largely depends on the management of the concomitant MEN1. Type III gNETs may require both locoregional approaches and systemic treatments; NECs are often metastatic and therefore require systemic treatment. Specific data regarding the systemic treatment of gNENs are lacking and are derived from the treatment of intestinal NETs and NECs. An enhanced understanding of molecular and clinical pathophysiology is needed to improve the management and outcomes of patients' gNETs.

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.

Costunolide ameliorates MNNG-induced chronic atrophic gastritis through inhibiting oxidative stress and DNA damage via activation of Nrf2

BackgroundChronic atrophic gastritis (CAG) is a chronic digestive disease. Modern research has revealed substantial evidence indicating that the progression of CAG is closely linked to the occurrence of oxidative stress-induced DNA damage and apoptosis in the gastric mucosa. Additionally, research has indicated that Costunolide (COS), the primary active compound found in Aucklandiae Radix, a traditional herb, exhibits antioxidant properties. Nevertheless, the therapeutic potential of COS in treating CAG and its molecular targets have not yet been determined. PurposeThe objective of this research was to explore the potential gastric mucosal protective effects and mechanisms of COS against N-Methyl-N´-nitro-N-nitrosoguanidine (MNNG)-induced CAG. MethodsFirstly, the MNNG-induced rat CAG model was established in vivo. Occurrence of CAG was detected through macroscopic examination of the stomachs and H&E staining. Additionally, we assessed oxidative stress, DNA damage, and apoptosis using biochemical detection, Western blot, immunohistochemistry and immunofluorescence. Then, an in vitro model was developed to induce MNNG-induced damage in GES-1 cells, and the occurrence of cell damage was determined by Hoechst 33,342 staining and flow cytometry. Finally, the key targets of COS for the treatment of CAG were identified through molecular docking, cellular thermal shift assay (CETSA), and inhibitor ML385. ResultsIn vivo studies demonstrated that COS promotes the expression of Nrf2 in gastric tissues. This led to an increased expression of SOD, GSH, HO-1, while reducing the production of MDA. Furthermore, COS inhibited DNA damage and apoptosis by suppressing the expression of γH2AX and PARP1 in gastric tissues. In vitro studies showed that COS effectively reversed apoptosis induced by MNNG in GES-1 cells. Additionally, COS interacted with Nrf2 to promote its expression. Furthermore, the expression levels of SOD, GSH, and HO-1 were augmented, while the generation of ROS and MDA was diminished. ConclusionsOur results indicate that COS exhibits therapeutic effects on CAG through the promotion of Nrf2 expression and inhibition of oxidative stress and DNA damage. Therefore, COS has the potential to provide new drugs for the treatment of CAG.