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.

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

BACKGROUND: Gastric 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. METHODS: We 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. RESULTS: GHIPs 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. CONCLUSIONS: GHIPs 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.

Four cases of non-Helicobacter pylori Helicobacter-infected gastritis with duodenal spiral bacilli.

BACKGROUND: Non-Helicobacter pylori Helicobacter (NHPH) is rarely detected in duodenal mucosa due to its preference for slightly acidic environments. Here, we report four cases of NHPH-infected gastritis with duodenal spiral bacilli, potentially NHPH, indicating the possibility of duodenal mucosal infection. CASE PRESENTATION: In every case, gastric mucosa showed endoscopic findings characteristic of NHPH-infected gastritis, and a mucosal biopsy was taken from the duodenal bulb; spiral bacilli were identified under microscopy using Giemsa staining. Case 1, a 46-year-old man, had diffuse spotty redness, mucosal edema, and multiple tiny erosions in the duodenal bulb, along with larger erosions in the second portion of the duodenum upon endoscopic examination. Histopathologically, moderate infiltration of mononuclear cells and neutrophils in the lamina propria and gastric epithelial metaplasia were observed. Case 2, a 54-year-old man, showed an elevated lesion, 1 cm in diameter, with multiple red spots and a few tiny erosions in the duodenal bulb. Histopathologically, mild inflammatory cell infiltration and gastric epithelial metaplasia were observed. In Case 3, a 52-year-old man, endoscopy revealed a flat elevated lesion, 7 mm in diameter, with multiple red spots and a few tiny erosions in the anterior wall of the duodenal bulb. Histopathologically, we observed moderate inflammatory cell infiltration in the gastric antrum and gastric epithelial metaplasia in the duodenal bulb. Case 4, a 40-year-old man, showed mild spotty redness in the duodenal bulb. Histopathologically, mild mononucleocyte infiltration and gastric epithelial metaplasia were observed. A single spiral bacillus was observed in Case 4 by microscopy. In all but Case 2, Helicobacter suis was identified in the gastric juice by polymerase chain reaction analysis. CONCLUSIONS: Spiral bacilli resembling NHPH may infect the duodenal mucosa, particularly the bulb, causing inflammation. Gastric contents entering the duodenum may reduce the intraduodenal pH, promoting NHPH survival and proliferation.

Histopathology Features of H. pylori Gastritis Associated With Altered Lipid Profile: An Observational Study from a Tertiary Healthcare Center in North West Romania.

BACKGROUND/AIM: H. pylori infection can promote a systemic inflammatory syndrome, eventually leading to intestinal metaplasia and gastric cancer. The aim of our study was to investigate the possible association between dyslipidemia and histopathological features of H. pylori gastritis. PATIENTS AND METHODS: An observational, retrospective study was conducted over the period 2017-2022 on symptomatic patients with a positive rapid urease test. A total of 121 patients who underwent upper gastrointestinal endoscopy with stomach biopsy were enrolled in this study. Based on the updated Sydney System, we investigated the association between neutrophils, mononuclear cells, intestinal metaplasia, or gastric atrophy and altered lipid profiles. RESULTS: A high prevalence of H. pylori infection was noticed in the studied group upon the application of the rapid urease test, being associated with dyslipidemia regardless of patient sex. All the endoscopic diagnoses (acute, chronic, or atrophic chronic gastritis, metaplasia) correlated with the histopathological features. Mononuclear cells and metaplasia were more likely to be found in H. pylori-positive patients with dyslipidemia, which is consistent with acute and chronic inflammation caused by H. pylori in the gastric mucosa. CONCLUSION: Although our study was conducted on a small scale, it offers new insights and details regarding H. pylori infection and histopathological features. Mononuclear cells and metaplasia were associated with an altered lipid profile in H. pylori-positive patients. These findings warrant future investigation, such as the evolution of gastric biopsies and lipid profiles before and after eradication.

Clinical characteristics of ulcerative colitis patients with different types of Helicobacter pylori infection.

There has been a suggestion of a potential protective effect of Helicobacter pylori (H. pylori) in the development of ulcerative colitis (UC). Virulence factor is an important factor in H. pylori, but little is known about the clinical characteristics of ulcerative colitis. In this retrospective study, a total of 322 patients with UC were analyzed. They were divided into three groups based on H. pylori antibody typing classification: type I H. pylori infection group, type II H. pylori infection group, and H. pylori-negative group. The study aimed to analyze the clinical characteristics of different types of H. pylori infection groups. The proportions of disease course, nationality, clinical type, and disease severity among UC patients in different types of H. pylori infection groups exhibited statistically significant differences (P < 0.05). However, no significant differences were observed in terms of sex, age, smoking status, alcohol consumption, body mass index (BMI), or lesion range (P > 0.05). Among the extraintestinal manifestations, the incidence of joint lesions in the type I H. pylori infection group was significantly lower compared with H. pylori-negative group (P < 0.05). The levels of red blood cell, hemoglobin, packed cell volume, albumin, A/G, and alanine aminotransferase were significantly higher in the type I H. pylori infection group compared with both the type II H. pylori infection group and H. pylori-negative group in the hematology index. Conversely, the levels of D-Dimer, C-reactive protein, and erythrocyte sedimentation rate were significantly lower in the type II H. pylori infection group (P < 0.05). In patients with UC, infections with the highly virulent type I H. pylori exhibit a negative correlation with both the severity of the disease and extraintestinal manifestations. While infections with the less virulent type II H. pylori are negatively correlated only with the disease severity. Therefore, the virulence factors of H. pylori play an important role in the regulation of UC. IMPORTANCE: The number of patients with ulcerative colitis (UC) has increased dramatically worldwide, posing a global public health challenge, There has been a suggestion of a potential protective effect of Helicobacter pylori in the development of UC. Virulence factor is an important factor in H. pylori, but high-quality clinical evidence is lacking. This study comprehensively analyzed the clinical characteristics of UC patients with different types of H. pylori infection. Infections with the highly virulent type I H. pylori are found to be negatively correlated with the severity of the disease as well as extraintestinal manifestations, whereas infections with the less virulent type II H. pylori demonstrate a negative correlation solely with disease severity. These results suggest that the virulence factors of H. pylori play a pivotal role in UC. Consequently, virulence factors should be taken into consideration when targeting H. pylori eradication in clinical practice, particularly in UC patients. It is crucial to evaluate the individual benefits to optimize personalized eradication therapies.

Helicobacter pylori enhances HLA-C expression in the human gastric adenocarcinoma cells AGS and can protect them from the cytotoxicity of natural killer cells.

Helicobacter pylori (H. pylori) seems to play causative roles in gastric cancers. H. pylori has also been detected in established gastric cancers. How the presence of H. pylori modulates immune response to the cancer is unclear. The cytotoxicity of natural killer (NK) cells, toward infected or malignant cells, is controlled by the repertoire of activating and inhibitory receptors expressed on their surface. Here, we studied H. pylori-induced changes in the expression of ligands, of activating and inhibitory receptors of NK cells, in the gastric adenocarcinoma AGS cells, and their impacts on NK cell responses. AGS cells lacked or had low surface expression of the class I major histocompatibility complex (MHC-I) molecules HLA-E and HLA-C-ligands of the major NK cell inhibitory receptors NKG2A and killer-cell Ig-like receptor (KIR), respectively. However, AGS cells had high surface expression of ligands of activating receptors DNAM-1 and CD2, and of the adhesion molecules LFA-1. Consistently, AGS cells were sensitive to killing by NK cells despite the expression of inhibitory KIR on NK cells. Furthermore, H. pylori enhanced HLA-C surface expression on AGS cells. H. pylori infection enhanced HLA-C protein synthesis, which could explain H. pylori-induced HLA-C surface expression. H. pylori infection enhanced HLA-C surface expression also in the hepatoma Huh7 and HepG2 cells. Furthermore, H. pylori-induced HLA-C surface expression on AGS cells promoted inhibition of NK cells by KIR, and thereby protected AGS cells from NK cell cytotoxicity. These results suggest that H. pylori enhances HLA-C expression in host cells and protects them from the cytotoxic attack of NK cells expressing HLA-C-specific inhibitory receptors.

Antagonizing roles of SHP1 in the pathogenesis of Helicobacter pylori infection.

BACKGROUND: SHP1 has been documented as a tumor suppressor and it was thought to play an antagonistic role in the pathogenesis of Helicobacter pylori infection. In this study, the exact mechanism of this antagonistic action was studied. MATERIALS AND METHODS: AGS, MGC803, and GES-1 cells were infected with H. pylori, intracellular distribution changes of SHP1 were first detected by immunofluorescence. SHP1 overexpression and knockdown were then constructed in these cells to investigate its antagonistic roles in H. pylori infection. Migration and invasion of infected cells were detected by transwell assay, secretion of IL-8 was examined via ELISA, the cells with hummingbird-like alteration were determined by microexamination, and activation of JAK2/STAT3, PI3K/Akt, and ERK pathways were detected by immunoblotting. Mice infection model was established and gastric pathological changes were evaluated. Finally, the SHP1 activator sorafenib was used to analyze the attenuating effect of SHP1 activation on H. pylori pathogenesis in vitro and in vivo. RESULTS: The sub-localization of SHP1 changed after H. pylori infection, specifically that the majority of the cytoplasmic SHP1 was transferred to the cell membrane. SHP1 inhibited H. pylori-induced activation of JAK2/STAT3 pathway, PI3K/Akt pathway, nuclear translocation of NF-κB, and then reduced EMT, migration, invasion, and IL-8 secretion. In addition, SHP1 inhibited the formation of CagA-SHP2 complex by dephosphorylating phosphorylated CagA, reduced ERK phosphorylation and the formation of CagA-dependent hummingbird-like cells. In the mice infection model, gastric pathological changes were observed and increased IL-8 secretion, indicators of cell proliferation and EMT progression were also detected. By activating SHP1 with sorafenib, a significant curative effect against H. pylori infection was obtained in vitro and in vivo. CONCLUSIONS: SHP1 plays an antagonistic role in H. pylori pathogenesis by inhibiting JAK2/STAT3 and PI3K/Akt pathways, NF-κB nuclear translocation, and CagA phosphorylation, thereby reducing cell EMT, migration, invasion, IL-8 secretion, and hummingbird-like changes.

Role and research progress of spasmolytic polypeptide­expressing metaplasia in gastric cancer (Review).

Gastric cancer ranks as one of the most prevalent cancers worldwide. While the incidence of gastric cancer in Western countries has notably diminished over the past century, it continues to be a leading cause of cancer­related mortality on a global scale. The majority of gastric cancers in humans are attributed to chronic Helicobacter pylori infection and the progression of gastric cancer is often preceded by gastritis, atrophy, metaplasia and dysplasia. However, the precise mechanisms underlying the development of gastric cancer remain ambiguous, including the formation of gastric polyps and precancerous lesions. In humans, two types of precancerous metaplasia have been identified in relation to gastric malignancies: Intestinal metaplasia and spasmolytic polypeptide­expressing metaplasia (SPEM). The role of SPEM in the induction of gastric cancer has gained recent attention and its link with early­stage human gastric cancer is increasingly evident. To gain insight into SPEM, the present study reviewed the role and research progress of SPEM in gastric cancer.

Helicobacter pylori CagA protein induces gastric cancer stem cell-like properties through the Akt/FOXO3a axis.

The presence of Helicobacter pylori (H. pylori) infection poses a substantial risk for the development of gastric adenocarcinoma. The primary mechanism through which H. pylori exerts its bacterial virulence is the cytotoxin CagA. This cytotoxin has the potential to induce inter-epithelial mesenchymal transition, proliferation, metastasis, and the acquisition of stem cell-like properties in gastric cancer (GC) cells infected with CagA-positive H. pylori. Cancer stem cells (CSCs) represent a distinct population of cells capable of self-renewal and generating heterogeneous tumor cells. Despite evidence showing that CagA can induce CSCs-like characteristics in GC cells, the precise mechanism through which CagA triggers the development of GC stem cells (GCSCs) remains uncertain. This study reveals that CagA-positive GC cells infected with H. pylori exhibit CSCs-like properties, such as heightened expression of CD44, a specific surface marker for CSCs, and increased ability to form tumor spheroids. Furthermore, we have observed that H. pylori activates the PI3K/Akt signaling pathway in a CagA-dependent manner, and our findings suggest that this activation is associated with the CSCs-like characteristics induced by H. pylori. The cytotoxin CagA, which is released during H. pylori infection, triggers the activation of the PI3K/Akt signaling pathway in a CagA-dependent manner. Additionally, CagA inhibits the transcription of FOXO3a and relocates it from the nucleus to the cytoplasm by activating the PI3K/Akt pathway. Furthermore, the regulatory function of the Akt/FOXO3a axis in the transformation of GC cells into a stemness state was successfully demonstrated.

IL-6 facilitates cross-talk between epithelial cells and tumor- associated macrophages in Helicobacter pylori-linked gastric carcinogenesis.

PURPOSE: Helicobacter pylori (H. pylori) is a significant risk factor for development of gastric cancer (GC), one of the deadliest malignancies in the world. However, the mechanism by which H. pylori induces gastric oncogenesis remains unclear. Here, we investigated the function of IL-6 in gastric oncogenesis and macrophage-epithelial cell interactions. METHODS: We analyzed publicly available datasets to investigate the expression of IL-6 and infiltration of M2 macrophages in GC tissues, and determine the inter-cellular communication in the context of IL-6. Human gastric epithelial and macrophage cell lines (GES-1 and THP-1-derived macrophages, respectively) were used in mono- and co-culture experiments to investigate autocrine-and paracrine induction of IL-6 expression in response to H. pylori or IL-6 stimulation. RESULTS: We found that IL-6 is highly expressed in GC and modulates survival. M2 macrophage infiltration is predominant in GC and drives an IL-6 mediated communication with gastric epithelium cells. In vitro, IL-6 triggers its own expression in GES-1 and THP-1-derived macrophages cells. In addition, these cell lines are able to upregulate each other's IL-6 levels in an autocrine fashion, which is enhanced by H. pylori stimulation. CONCLUSION: This study indicates that IL-6 in the tumor microenvironment is essential for intercellular communication. We show that H. pylori enhances an IL-6-driven autocrine and paracrine positive feedback loop between macrophages and gastric epithelial cells, which may contribute to gastric carcinogenesis.

RE.GA.IN.: the Real-world Gastritis Initiative-updating the updates.

At the end of the last century, a far-sighted 'working party' held in Sydney, Australia addressed the clinicopathological issues related to gastric inflammatory diseases. A few years later, an international conference held in Houston, Texas, USA critically updated the seminal Sydney classification. In line with these initiatives, Kyoto Global Consensus Report, flanked by the Maastricht-Florence conferences, added new clinical evidence to the gastritis clinicopathological puzzle.The most relevant topics related to the gastric inflammatory diseases have been addressed by the Real-world Gastritis Initiative (RE.GA.IN.), from disease definitions to the clinical diagnosis and prognosis. This paper reports the conclusions of the RE.GA.IN. consensus process, which culminated in Venice in November 2022 after more than 8 months of intense global scientific deliberations. A forum of gastritis scholars from five continents participated in the multidisciplinary RE.GA.IN. consensus. After lively debates on the most controversial aspects of the gastritis spectrum, the RE.GA.IN. Faculty amalgamated complementary knowledge to distil patient-centred, evidence-based statements to assist health professionals in their real-world clinical practice. The sections of this report focus on: the epidemiology of gastritis; Helicobacter pylori as dominant aetiology of environmental gastritis and as the most important determinant of the gastric oncogenetic field; the evolving knowledge on gastric autoimmunity; the clinicopathological relevance of gastric microbiota; the new diagnostic horizons of endoscopy; and the clinical priority of histologically reporting gastritis in terms of staging. The ultimate goal of RE.GA.IN. was and remains the promotion of further improvement in the clinical management of patients with gastritis.

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.

Low prevalence of gastric intestinal metaplasia and Helicobacter pylori on surveillance upper endoscopy in Lynch syndrome.

Lynch syndrome (LS) increases the risk of numerous different cancers including gastric cancer. While some current guidelines recommend empiric gastric biopsies be performed during upper gastrointestinal cancer surveillance in Lynch syndrome (LS), the yield of these biopsies and the prevalence of gastric intestinal metaplasia (GIM) and Helicobacter pylori (HP) in LS remains unknown. Herein we analyze 165 consecutive individuals with LS who underwent upper endoscopic surveillance with biopsies of the gastric antrum and body being performed universally in all individuals. Of the study cohort, 6.7% of universally biopsied individuals with LS had GIM and/or HP (5.5% GIM, 3.6% HP). Biopsies of the gastric body did not increase rates of GIM/HP identification compared to antral biopsies alone. GIM was detected on subsequent surveillance in 2.2% of individuals without prior GIM, which may represent either newly developed GIM or GIM that was missed on a prior upper endoscopy due to sampling error. These findings support inclusion of at least baseline gastric antrum biopsies as a routine component of all standard surveillance upper endoscopies performed in LS.

Endoscopic Kyoto and Kimura-Takemoto Classifications Are Comparable in Predicting High-Risk Gastric Precancerous Lesions.

INTRODUCTION: Severe and extensive gastric atrophy, extensive or incomplete gastric intestinal metaplasia, and gastric dysplasia are considered high-risk gastric precancerous lesions (HGPLs). Endoscopic findings based on the endoscopic Kyoto classification (EKC) and the Kimura-Takemoto classification (KTC) have been reported to be significantly associated with HGPLs. This study aimed to compare these two classifications in predicting active Helicobacter pylori (H. pylori) infection and HGPLs. METHODS: This is a cross-sectional study conducted on naïve dyspeptic patients who underwent upper gastrointestinal endoscopy at a tertiary hospital. Endoscopic findings were scored according to the EKC and KTC. Mapping biopsies were taken, and H. pylori infection was determined using a locally validated rapid urease test and histology. The performance of EKC was compared with that of KTC using the area under the receiver operating characteristic curve (AUC) in predicting active H. pylori infection and HGPLs. RESULTS: There were 292 patients with a median age of 46 and a male-to-female ratio of 1:1. The rates of active H. pylori infection and HGPLs were 61.3% and 14.0%, respectively. The EKC was better than the KTC in predicting active H. pylori infection (AUC: 0.771 vs. 0.658, respectively; p < 0.001). However, these two classifications had comparable performance in predicting HGPLs (AUC: 0.792 vs. 0.791, respectively; p = 0.956). CONCLUSION: Compared to EKC, KTC is inferior in predicting active H. pylori infection but has comparable performance in predicting HGPLs.

Prevalence and temporal trend of gastric preneoplastic lesions in Asia: A systematic review with meta-analysis.

BACKGROUND: Gastric cancer is the fifth most common cancer globally, with about 75% of cases occurring in Asia. While chronic atrophic gastritis (CAG) and intestinal metaplasia (IM) are well-recognized preneoplastic gastric lesions, we determined the prevalence and temporal trend of CAG and IM in Asia over the past 50 years. METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, MEDLINE, Scopus, and Web of Science for studies reporting the prevalence of CAG and IM in Asia (according to the United Nations geoscheme) published between 1970 and 2022. Heterogeneity was assessed by the I2 index and Cochran Q test. We adopted the random effects model to estimate the pooled prevalence and 95% confidence interval (CI). The slope of prevalence was estimated as a function of time in simple linear regression and weighted meta-regression models to demonstrate the temporal trend. Studies that reported the odds ratio (OR) of Helicobacter pylori infection and CAG/IM were analyzed separately to compile a pooled OR with a 95% CI. This study was registered in INPLASY2022120028. RESULTS: Of the 81 studies from 19 Asian countries identified, the pooled prevalence for CAG and IM in Asia was 26.1% (95%CI: 22.7-30.0) and 22.9% (95%CI: 19.7-26.6), respectively. Over the past 5 decades, there was a significant decline in the prevalence of IM (slope in adjusted meta-regression models: -0.79 [95%CI: -1.28 to -0.26], P = 0.003), but there was no significant change in the pooled prevalence of CAG. Within Asia, the prevalence varied significantly among different regions. Southern Asia reported the highest pooled prevalence of CAG (42.9%, 95%CI: 27.5%-67.1%), while Western Asia reported the lowest level (12.7%, 95%CI: 5.0%-32.3%). For IM, Eastern Asia reported the highest prevalence (27.1%, 95%CI: 21.1-34.9), with the lowest prevalence reported in Western Asia (3.1%; 95% CI 1.2%-8.0%). H. pylori infection was linked to CAG and IM with OR of 2.16 (95%CI: 2.09-2.22) and 1.64 (95%CI: 1.57-1.72), respectively. CONCLUSION: This updated meta-analysis showed that up to 26% of study individuals in Asia harbored preneoplastic gastric lesions. There was a declining temporal trend in the prevalence of IM, but not for CAG, in Asia.

Gastric coinfection with thiopeptide-positive Cutibacterium acnes decreases FOXM1 and pro-inflammatory biomarker expression in a murine model of Helicobacter pylori-induced gastric cancer.

IMPORTANCE: H. pylori infects half of the world population and is the leading cause of gastric cancer. We previously demonstrated that gastric cancer risk is associated with gastric microbiota. Specifically, gastric urease-positive Staphylococcus epidermidis and Streptococcus salivarius had contrasting effects on H. pylori-associated gastric pathology and immune responses in germ-free INS-GAS mice. As gastritis progresses to gastric cancer, the oncogenic transcription factor Foxm1 becomes increasingly expressed. In this study, we evaluated the gastric commensal C. acnes, certain strains of which produce thiopeptides that directly inhibit FOXM1. Thiopeptide-positive C. acnes was isolated from Nicaraguan patient gastric biopsies and inoculated into germ-free INS-GAS mice with H. pylori. We, therefore, asked whether coinfection with C. acnes expressing thiopeptide and H. pylori would decrease gastric Foxm1 expression and pro-inflammatory cytokine mRNA and protein levels. Our study supports the growing literature that specific non-H. pylori gastric bacteria affect inflammatory and cancer biomarkers in H. pylori pathogenesis.

Endoscopic Features of Undifferentiated-Type Early Gastric Cancer in Patients with Helicobacter pylori-Uninfected or -Eradicated Stomachs: A Comprehensive Review.

Since the indications for endoscopic submucosal dissection have been expanded to include undifferentiated-type early gastric cancers, improvements in preoperative diagnostic ability have been an area of research. There are also concerns about the impact on the diagnosis of Helicobacter pylori infection. Based on our previous studies, in undifferentiated-type early gastric cancers, magnifying endoscopy with narrow-band imaging is useful for delineating the demarcation regardless of the tumor size. Additionally, inflammatory cell infiltration appears to be a cause of misdiagnosis, suggesting that the resolution of inflammation could contribute to the accurate diagnosis of demarcations. As such, the accuracy of demarcation in eradicated and uninfected cases is higher than that in non-eradicated cases. The common features of the endoscopic findings were discoloration under white-light imaging and a predominance of sites in the lower and middle regions. The uninfected group was characterized by smaller tumor size, flat type, more extended intervening parts in magnifying endoscopy with narrow-band imaging, and pure signet ring cell carcinoma. In contrast, the eradication and non-eradication groups were characterized by larger tumor size, depressed type, and wavy microvessels in magnifying endoscopy with narrow-band imaging. In this comprehensive review, as described above, we discuss the diagnosis of demarcation of undifferentiated-type early gastric cancers, undifferentiated-type early gastric cancers that developed following H. pylori eradication, and H. pylori-uninfected undifferentiated-type early gastric cancers, with a focus on studies with self-examination and endoscopic findings and describe the future direction.

A noninvasive multianalytical approach establishment for risk assessment and gastric cancer screening.

Effective screening and early detection are critical to improve the prognosis of gastric cancer (GC). Our study aims to explore noninvasive multianalytical biomarkers and construct integrative models for preliminary risk assessment and GC detection. Whole genomewide methylation marker discovery was conducted with CpG tandems target amplification (CTTA) in cfDNA from large asymptomatic screening participants in a high-risk area of GC. The methylation and mutation candidates were validated simultaneously using one plasma from patients at various gastric lesion stages by multiplex profiling with Mutation Capsule Plus (MCP). Helicobacter pylori specific antibodies were detected with a recomLine assay. Integrated models were constructed and validated by the combination of multianalytical biomarkers. A total of 146 and 120 novel methylation markers were found in CpG islands and promoter regions across the genome with CTTA. The methylation markers together with the candidate mutations were validated with MCP and used to establish a 133-methylation-marker panel for risk assessment of suspicious precancerous lesions and GC cases and a 49-methylation-marker panel as well as a 144-amplicon-mutation panel for GC detection. An integrated model comprising both methylation and specific antibody panels performed better for risk assessment than a traditional model (AUC, 0.83 and 0.63, P < .001). A second model for GC detection integrating methylation and mutation panels also outperformed the traditional model (AUC, 0.82 and 0.68, P = .005). Our study established methylation, mutation and H. pylori-specific antibody panels and constructed two integrated models for risk assessment and GC screening. Our findings provide new insights for a more precise GC screening strategy in the future.

Autophagy induced by Helicobacter Pylori infection can lead to gastric cancer dormancy, metastasis, and recurrence: new insights.

According to the findings of recent research, Helicobacter Pylori (H. pylori) infection is not only the primary cause of gastric cancer (GC), but it is also linked to the spread and invasion of GC through a number of processes and factors that contribute to virulence. In this study, we discussed that H. pylori infection can increase autophagy in GC tumor cells, leading to poor prognosis in such patients. Until now, the main concerns have been focused on H. pylori's role in GC development. According to our hypothesis, however, H. pylori infection may also lead to GC dormancy, metastasis, and recurrence by stimulating autophagy. Therefore, understanding how H. pylori possess these processes through its virulence factors and various microRNAs can open new windows for providing new prevention and/or therapeutic approaches to combat GC dormancy, metastasis, and recurrence which can occur in GC patients with H. pylori infection with targeting autophagy and eradicating H. pylori infection.