Intestinal metaplasia (IM) is a significant gastric mucosal change that warrants attention due to its potential role in the pathogenesis of gastric cancer. IM is often triggered by Helicobacter pylori (H. pylori) infection and some risk factors.

This study examined H. pylori infection and related risk factors in 7,096 participants, identifying 2,200 cases of IM linked to H. pylori and 4,896 controls without the infection in Wuwei, Gansu Province, China. The Operative Link on Gastritis/Intestinal Metaplasia (OLGIM) and (Operative Link on Gastritis Assessment (OLGA) classifications tools were used for identifying participants at high risk for gastric cancer by evaluating the severity and extent of H. pylori infection and IM.

The study found that IM and H. pylori prevalence were gender-related, with males representing 41.09 % of cases compared to 33.92 % of controls, a significant difference (P < 0.0001). Conversely, females were more prevalent in the control group (66.07 %) compared to the case group (58.91 %). Age analysis showed higher proportions of IM cases in the 40-49 years group (46.95 %) compared to controls (43.40 %), with significant differences across age groups (P < 0.0001). IM showed significant positive correlations with smoking , alcohol consumption , and drinking water sources . H. pylori infection was detected in 238 (10.81 %) of the case group and 542 (11.07 %) of the control group. Using the OLGIM classification, which incorporates IM into gastric cancer risk assessment, stage 0 (no IM) was observed in 1,189 (24.28 %) of the control group and 530 (24.09 %) of the case group. Stage 1 (mild IM) was found in 3,165 (64.62 %) of the controls and 1,432 (65.09 %) of the cases. Stage 2 (moderate IM) was present in 520 (10.62 %) of the controls and 220 (10 %) of the cases, while stage 3 (severe IM) was observed in 24 (0.49 %) of the controls and 18 (0.82 %) of the cases. For OLGA staging, the case group had a higher percentage of individuals in higher stages (III and IV) compared to the control group. Specifically, 50.84 % of the cases were classified as stage 0, 19.75 % , stage I, 14.71 %, stage II, 8.40 %, stage III, and IV, 6.30 %. In the control group, 54.43 % were classified as stage 0, 24.17 %, stage I, 18.45 %, stage II, 1.66 %, stage III, and IV, 1.29 % respectively.

These findings suggest that older individuals, males, smokers, drinkers, and those using certain drinking water sources are more likely to develop IM. The study highlights the combined impact of H. pylori and risk factors on IM development, emphasizing the need for comprehensive public health strategies to address these risks. The higher proportion of advanced OLGA stages in the case group suggests more severe gastric atrophy, potentially indicating a higher risk for gastric cancer development.

At a population level, the European Society of Gastrointestinal Endoscopy (ESGE), the European Helicobacter and Microbiota Study Group (EHMSG), and the European Society of Pathology (ESP) suggest endoscopic screening for gastric cancer (and precancerous conditions) in high-risk regions (age-standardized rate [ASR] > 20 per 100 000 person-years) every 2 to 3 years or, if cost-effectiveness has been proven, in intermediate risk regions (ASR 10-20 per 100 000 person-years) every 5 years, but not in low-risk regions (ASR < 10).ESGE/EHMSG/ESP recommend that irrespective of country of origin, individual gastric risk assessment and stratification of precancerous conditions is recommended for first-time gastroscopy. ESGE/EHMSG/ESP suggest that gastric cancer screening or surveillance in asymptomatic individuals over 80 should be discontinued or not started, and that patients' comorbidities should be considered when treatment of superficial lesions is planned.ESGE/EHMSG/ESP recommend that a high quality endoscopy including the use of virtual chromoendoscopy (VCE), after proper training, is performed for screening, diagnosis, and staging of precancerous conditions (atrophy and intestinal metaplasia) and lesions (dysplasia or cancer), as well as after endoscopic therapy. VCE should be used to guide the sampling site for biopsies in the case of suspected neoplastic lesions as well as to guide biopsies for diagnosis and staging of gastric precancerous conditions, with random biopsies to be taken in the absence of endoscopically suspected changes. When there is a suspected early gastric neoplastic lesion, it should be properly described (location, size, Paris classification, vascular and mucosal pattern), photodocumented, and two targeted biopsies taken.ESGE/EHMSG/ESP do not recommend routine performance of endoscopic ultrasonography (EUS), computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET)-CT prior to endoscopic resection unless there are signs of deep submucosal invasion or if the lesion is not considered suitable for endoscopic resection.ESGE/EHMSG/ESP recommend endoscopic submucosal dissection (ESD) for differentiated gastric lesions clinically staged as dysplastic (low grade and high grade) or as intramucosal carcinoma (of any size if not ulcerated or ≤ 30 mm if ulcerated), with EMR being an alternative for Paris 0-IIa lesions of size ≤ 10 mm with low likelihood of malignancy.ESGE/EHMSG/ESP suggest that a decision about ESD can be considered for malignant lesions clinically staged as having minimal submucosal invasion if differentiated and ≤ 30 mm; or for malignant lesions clinically staged as intramucosal, undifferentiated and ≤ 20 mm; and in both cases with no ulcerative findings.ESGE/EHMSG/ESP recommends patient management based on the following histological risk after endoscopic resection: Curative/very low-risk resection (lymph node metastasis [LNM] risk < 0.5 %-1 %): en bloc R0 resection; dysplastic/pT1a, differentiated lesion, no lymphovascular invasion, independent of size if no ulceration and ≤ 30 mm if ulcerated. No further staging procedure or treatment is recommended.Curative/low-risk resection (LNM risk < 3 %): en bloc R0 resection; lesion with no lymphovascular invasion and: a) pT1b, invasion ≤ 500 µm, differentiated, size ≤ 30 mm; or b) pT1a, undifferentiated, size ≤ 20 mm and no ulceration. Staging should be completed, and further treatment is generally not necessary, but a multidisciplinary discussion is required. Local-risk resection (very low risk of LNM but increased risk of local persistence/recurrence): Piecemeal resection or tumor-positive horizontal margin of a lesion otherwise meeting curative/very low-risk criteria (or meeting low-risk criteria provided that there is no submucosal invasive tumor at the resection margin in the case of piecemeal resection or tumor-positive horizontal margin for pT1b lesions [invasion ≤ 500 µm; well-differentiated; size ≤ 30 mm, and VM0]). Endoscopic surveillance/re-treatment is recommended rather than other additional treatment. High-risk resection (noncurative): Any lesion with any of the following: (a) a positive vertical margin (if carcinoma) or lymphovascular invasion or deep submucosal invasion (> 500 µm from the muscularis mucosae); (b) poorly differentiated lesions if ulceration or size > 20 mm; (c) pT1b differentiated lesions with submucosal invasion ≤ 500 µm with size > 30 mm; or (d) intramucosal ulcerative lesion with size > 30 mm. Complete staging and strong consideration for additional treatments (surgery) in multidisciplinary discussion.ESGE/EHMSG/ESP suggest the use of validated endoscopic classifications of atrophy (e. g. Kimura-Takemoto) or intestinal metaplasia (e. g. endoscopic grading of gastric intestinal metaplasia [EGGIM]) to endoscopically stage precancerous conditions and stratify the risk for gastric cancer.ESGE/EHMSG/ESP recommend that biopsies should be taken from at least two topographic sites (2 biopsies from the antrum/incisura and 2 from the corpus, guided by VCE) in two separate, clearly labeled vials. Additional biopsy from the incisura is optional.ESGE/EHMSG/ESP recommend that patients with extensive endoscopic changes (Kimura C3 + or EGGIM 5 +) or advanced histological stages of atrophic gastritis (severe atrophic changes or intestinal metaplasia, or changes in both antrum and corpus, operative link on gastritis assessment/operative link on gastric intestinal metaplasia [OLGA/OLGIM] III/IV) should be followed up with high quality endoscopy every 3 years, irrespective of the individual's country of origin.ESGE/EHMSG/ESP recommend that no surveillance is proposed for patients with mild to moderate atrophy or intestinal metaplasia restricted to the antrum, in the absence of endoscopic signs of extensive lesions or other risk factors (family history, incomplete intestinal metaplasia, persistent H. pylori infection). This group constitutes most individuals found in clinical practice.ESGE/EHMSG/ESP recommend H. pylori eradication for patients with precancerous conditions and after endoscopic or surgical therapy.ESGE/EHMSG/ESP recommend that patients should be advised to stop smoking and low-dose daily aspirin use may be considered for the prevention of gastric cancer in selected individuals with high risk for cardiovascular events.

Helicobacter pylori eradication reduces but cannot eliminate the risk of gastric cancer (GC). The prevalence of post-eradication GC has been rising. Characterization of the endoscopic findings of post-eradication GC may facilitate its early detection. We performed a meta-analysis and systematic review to clarify endoscopic risk factors to accelerate the early diagnosis of post-eradication GC.

Medline and PubMed were searched for randomized controlled trials, cohort studies, and case-control studies published in the English-language medical literature between January 1997 and July 2023. The included articles assessed the correlation between post-eradication GC and pre- and post-eradication endoscopic findings, and associated post-eradication GC with gastric atrophy, intestinal metaplasia (IM), map-like redness, and xanthoma.

A total of 963 articles were retrieved. In these articles, 66 papers were finally included, comprising randomized controlled trials, cohort studies, and case-control studies. The included articles addressed gastric atrophy (16 studies), IM (eight studies), map-like redness (six studies), and xanthoma (two studies). Risk ratio (RR) of incident post-eradication GC was 3.40 (95%confidence interval [95%CI]: 1.98-5.84; p < 0.001) in cases of severe atrophy, 5.38 (95%CI: 3.62-8.00) in cases of severe IM, 2.34 (95%CI: 1.16-4.68) in cases with post-eradication map-like redness, and 2.75 (95% CI: 1.78-4.26) in cases with xanthoma.

Endoscopic atrophy, IM, and xanthoma observed at pre- and post-eradication time points and post-eradication map-like redness were suggested as endoscopic risk factors for post-eradication GC. Further studies are needed to clarify the risk of post-eradication GC based on these risk factors.

Although Helicobacter pylori (H. pylori) eradication therapy is important for preventing gastric cancer (GC), the occurrence of GC after H. pylori eradication remains a problem. In this study, the aim was to identify risk factors for GC after H. pylori eradication by comparing long-term histological, endoscopic, and serological evaluations of patients with and without GC.

Patients who underwent H. pylori eradication therapy at Oita University Hospital between June 1997 and August 2013 and were followed for at least 3 years with long-term endoscopy, histology, and serum biochemical tests were included, and the GC (215 cases) and non-GC (11 cases) groups were compared.

The GC group was older than the non-GC group at the time of eradication, had lower serum pepsinogen I/II levels, had severe endoscopic atrophic changes, had higher activity at the antrum, and inflammation and intestinal metaplasia (IM) at the corpus on updated Sydney system scoring. On long-term follow-up after eradication, the GC group had a wider range of endoscopic mucosal atrophy and a lower serum pepsinogen I/II ratio at any time point.

Endoscopic mucosal atrophy and the serum pepsinogen I/II ratio are useful predictors of GC in patients post H. pylori eradication at any time point.

Helicobacter pylori (H. pylori), one of the most prevalent pathogenic bacteria worldwide, is the leading cause of gastritis, gastric intestinal metaplasia, and gastric cancer. Antibiotics, the conventional treatment for eliminating H. pylori, often lead to severe bacterial resistance, gut dysbiosis, and hepatic insufficiency and fail to address the inflammatory response or gastric mucosal damage caused by H. pylori infection. In this study, based on 10-week animal experiments, two models of L. salivarius NCUH062003 for the prophylaxis and therapy of H. pylori infection in C57BL/6 mice were established; a comprehensive comparative analysis was performed to investigate the anti-H. pylori effect of probiotics, the reduction in inflammation, and repair of gastric mucosal damage. ELISA, immunohistochemistry, and pathology analyses showed that NCUH062003 decreased the expression of pro-inflammatory cytokine interleukins (IL-1β, IL-6) and myeloperoxidase (MPO) and reduced neutrophil infiltration in the gastric mucosa lamina propria. Immunofluorescence and biochemical analysis showed that NCUH062003 resisted gastric epithelial cell apoptosis, increased the level of superoxide dismutase (SOD) in gastric mucosa, and promoted the expression of tight junction protein ZO1 and Occludin. In addition, through high-throughput sequencing, in the probiotic therapy and prophylactic mode, the diversity and composition of the gut microbiota of HP-infected mice were clarified, the potential functions of the gut microbiota were analyzed, the levels of short-chain fatty acids (SCFAs) were measured, and the effects of L. salivarius NCUH062003 on the gut microbiota and its metabolites in HP-infected mice treated with amoxicillin/metronidazole were revealed. This study provides functional strain resources for the development and application of microbial agents seeking to antagonize H. pylori beyond antibiotics.

One of the reasons for the decrease of Helicobacter pylori eradication effectiveness is its resistance to antibiotics.

To examine the prevalence of H. pylori point mutations responsible for clarithromycin and levofloxacin resistance among the patients with upper gastrointestinal (GI) tract disorders in Kazan.

The study included 203 patients with symptoms of dyspepsia who underwent upper GI endoscopy at the University Hospital of Kazan Federal University (Kazan, Russia) in 2019-2021. DNA isolation from gastric antrum mucosal biopsies was performed using PureLink Genomic DNA Mini Kits (Thermo Fisher Scientific, USA). Polymerase chain reaction was performed using primers specific for the V-region of the 23S gene and the A subunit DNA gyrase encoding gyrA gene region. The sequencing of obtained DNA fragments was performed on 3730 DNA Analyzer. The sequences were searched for point mutations responsible for H. pylori resistance to clarithromycin (A2143G, A2142G and A2142C193 mutations) and levofloxacin (mutations of the gyrA gene).

H. pylori was detected in 47.78% of biopsy specimens using polymerase chain reaction. The proportion of H. pylori strains with mutations leading to clarithromycin resistance was 17.53%. Amino acid substitutions in the gyrA gene were found in 12.37% of samples. In case of two H. pylori strains (2.06%), dual resistance to clarithromycin and levofloxacin was found.

So high incidence of mutations underlying the development of H. pylori resistance to clarithromycin and levofloxacin was observed among examined patients in Kazan.

Autoimmune gastritis (AIG) is a rare chronic inflammatory disorder with potential long-term sequelae including gastric neoplasia. There is limited data on the natural history of pediatric AIG. We aimed to characterize the clinical course and outcomes of children with AIG.

This was a multicenter retrospective study that included pediatric patients diagnosed with AIG between January 1, 2000 and December 31, 2021. Diagnosis of AIG was based on the demonstration of histological corpus-predominant atrophic gastritis, with or without positive antiparietal cell (APCA) or anti-intrinsic factor (IF) antibodies. Demographic, clinical, laboratory, endoscopic, and histologic data were retrieved, along with follow-up data.

Thirty-three patients, (23 females [69.7%], median age 12.0 [interquartile range 7.0-15.0] years at diagnosis) were identified. Twenty-two patients (66.7%) had positive APCA and/or anti-IF serology. The most common presenting manifestation was iron deficiency anemia (75%), and accompanying autoimmune disorders were significantly more common in patients with positive serology (62% vs. 18%, p < 0.05). Pseudo-pyloric or intestinal-type metaplasia was present at diagnosis in eight patients (24%), and 11 additional patients (33%) developed metaplasia during a median follow-up time of 27 (17.5-48.3) months. One patient developed a type 1 gastric neuroendocrine tumor. Helicobacter pylori was identified in only one patient, while two patients had prior eradication. Endoscopic and histologic improvements weren't identified in any patients.

AIG should be considered in patients with autoimmunity and resistant iron-deficiency anemia. H. pylori infection may not be associated with pediatric AIG. The development of neuroendocrine tumor in one patient, and the high rates of metaplasia, highlight the importance of surveillance.

Helicobacter pylori eradication therapy reduces the risk of gastric cancer. However, it is unclear whether the severity of risk factors for gastric cancer such as atrophy and intestinal metaplasia are reduced after eradication in the long term. We aimed to study long-term changes in endoscopic risk factors for gastric cancer up to 20 years post-eradication. The endoscopic severity of gastritis according to the Kyoto Classification of Gastritis in 167 patients was retrospectively evaluated over an average follow-up 15.7 years. A significant improvement in mean total gastric cancer risk score (4.36 ± 1.66 to 2.69 ± 1.07, p < 0.001), atrophy (1.73 ± 0.44 to 1.61 ± 0.49, p = 0.004), and diffuse redness (1.22 ± 0.79 to 0.02 ± 0.13, p < 0.001) was observed compared to baseline in the Eradication group. However, there was no change in the never infection and current infection groups. The frequency of map-like redness increased over time until 15 years (3.6% to 18.7%, p = 0.03). The Cancer group had significantly higher risk scores at all time points. Endoscopic atrophy significantly improved in eradicated patients over long-term, suggested that eradication is one of the key elements in gastric cancer prevention. Individualized surveillance strategies based on endoscopic gastritis severity before eradication may be important for those at risk of gastric cancer.

Due to the emergence and spread of multidrug resistance in Helicobacter pylori (H. pylori), its eradication has become difficult. Sodium sulfite (SS), a widely used food additive for ensuring food safety and storage, has been recognized as an effective nonbactericidal agent for H. pylori eradication. However, the mechanism by which H. pylori adapts and eventually succumbs under low- or no-oxygen conditions remains unknown. In this study, we aimed to evaluate the anti-H. pylori effect of SS and investigated the multiomics mechanism by which SS kills H. pylori. The results demonstrated that SS effectively eradicated H. pylori both in vitro and in vivo. H. pylori responds to the oxygen changes regulated by SS, downregulates the HcpE gene, which is responsible for redox homeostasis in bacteria, decreases the activities of enzymes related to oxidative stress, and disrupts the outer membrane structure, increasing susceptibility to oxidative stress. Furthermore, SS downregulates the content of cytochrome C in the microaerobic respiratory chain, leading to a sharp decrease in ATP synthesis. Consequently, the accumulation of triglycerides (TGs) in bacteria due to oxidative stress supports anaerobic respiration, meeting their energy requirements. The multifaceted death of H. pylori caused by SS does not result in drug resistance. Thus, screening of the redox homeostasis of HcpE as a new target for H. pylori infection treatment could lead to the development of a novel approach for H. pylori eradication therapy.

A 61-year-old female patient underwent upper gastrointestinal endoscopy, which confirmed the presence of Helicobacter pylori (H. pylori)-positive nodular gastritis (NG). Routine upper gastrointestinal endoscopy after H. pylori eradication revealed atrophic changes of the corpus, having gradually progressed over the 10 years after successful eradication. Serological and biopsy specimen examination showed hypergastrinemia (1200 pg/mL), positive anti-parietal cell antibody (with a titer of more 160), and endocrine cell micronests after 11 years of H. pylori eradication. The patient was diagnosed with autoimmune gastritis (AIG) based on endoscopic, serological, and histological findings. This is the first report of AIG diagnosed in a patient with NG over a long period of time after H. pylori eradication.

It's still controversial whether Helicobacter pylori (H. pylori) eradication can reverse atrophic gastritis (AG) and intestinal metaplasia (IM). Therefore, we performed a meta-analysis to estimate the effect of H. pylori eradication on AG and IM.

We searched the PubMed, Web of Science and EMBASE datasets through April 2023 for epidemiological studies, which provided mean glandular atrophy (GA) or IM score before and after H. pylori eradication, or provided ORs, RRs or HRs and 95% CIs for the association of AG or IM with H. pylori eradication. Weighted mean difference (WMD) and pooled ORs and 95%CIs were used to estimate the effect of H. pylori eradication on AG and IM.

Twenty articles with a total of 5242 participants were included in this meta-analysis. H. pylori eradication significantly decreased GA score in the antrum (WMD -0.36; 95% CI: -0.52, -0.19, p < 0.01), GA score in the corpus (WMD -0.35; 95% CI: -0.52, -0.19, p < 0.01), IM score in the antrum (WMD -0.16; 95% CI: -0.26, -0.07, p < 0.01) and IM score in the corpus (WMD -0.20; 95% CI: -0.37, -0.04, p = 0.01). H. pylori eradication significantly improved AG (pooled OR 2.96; 95% CI: 1.70, 5.14, p < 0.01) and IM (pooled OR 2.41; 95% CI: 1.24, 4.70, p < 0.01). The association remained significant in the subgroup analyses by study design, sites of lesions, regions and follow-up time. Although Publication bias was observed for AG, the association remained significant after trim-and-fill adjustment.

H. pylori eradication could significantly improve AG and IM at early stage.

The question of whether eradication of Helicobacter pylori (Hp) can reverse gastric precancerous lesions, including intestinal metaplasia, remains uncertain, leading to ongoing debate. Therefore, a meta-analysis was performed to evaluate the effect of Hp eradication on gastric precancerous lesions.

PubMed, Embase, Cochrane Library, Web of Science, Scopus database, and ClinicalTrials.gov were systematically searched from inception to April 2023 for studies that explored the impact of Hp eradication on gastric precancerous lesions. Risk ratios (RRs) and their 95% confidence intervals (95% CIs) were selected as the effect size. We used the random-effects model to assess pooled data. We also performed quality assessments, subgroup analyses, and sensitivity analyses.

Fifteen studies were included. Compared with placebo, Hp eradication could significantly prevent the progression of gastric precancerous lesions (RR = 0.87, 95% CI: 0.81-0.94, p < 0.01) and reverse them (RR = 1.32, 95% CI: 1.17-1.50, p < 0.01). Then, specific precancerous lesions were further explored. The progression of intestinal metaplasia was significantly prevented by Hp eradication compared to placebo or no treatment (RR = 0.80, 95% CI: 0.69-0.94, p < 0.01). Moreover, compared with placebo or no treatment, Hp eradication also improved chronic atrophic gastritis (RR = 1.84, 95% CI: 1.30-2.61, p < 0.01) and intestinal metaplasia (RR = 1.41, 95% CI: 1.15-1.73, p < 0.01). However, in terms of preventing dysplasia progression (RR = 0.86, 95% CI: 0.37-2.00) and improving dysplasia (RR = 0.89, 95% CI: 0.47-1.70), Hp eradication had no advantage compared to placebo or no treatment.

Hp eradication therapy could prevent the progression of gastric precancerous lesions and reverse them. Notably, intestinal metaplasia can be reversed, but this may only be appropriate for patients with epigenetic alterations and milder lesions.

Corpus-restricted atrophic gastritis is a chronic inflammatory disorder leading to possible development of type 1 neuroendocrine tumors (T1gNET), intraepithelial neoplasia (IEN), and gastric cancer (GC). We aimed to assess occurrence and predictors of gastric neoplastic lesions in patients with corpus-restricted atrophic gastritis at long-term follow-up.

A prospective single-center cohort of patients with corpus-restricted atrophic gastritis adhering to endoscopic-histological surveillance was considered. Follow-up gastroscopies were scheduled according to the management of epithelial precancerous conditions and lesions of the stomach guidelines. In case of new/worsening of known symptoms, gastroscopy was anticipated. Cox regression analyses and Kaplan-Meier survival curves were obtained.

Two hundred seventy-five patients with corpus-restricted atrophic gastritis (72.0% female, median age 61 [23-84] years) were included. At a median follow-up of 5 (1-17) years, the annual incidence rate person-year was 0.5%, 0.6%, 2.8%, and 3.9% for GC/high-grade IEN, low-grade IEN, T1gNET, and all gastric neoplastic lesions, respectively. All patients showed at baseline operative link for gastritis assessment (OLGA)-2, except 2 low-grade (LG) IEN patients and 1 T1gNET patient with OLGA-1. Age older than 60 years (hazard ratio [HR] 4.7), intestinal metaplasia without pseudopyloric metaplasia (HR 4.3), and pernicious anemia (HR 4.3) were associated with higher risk for GC/HG-IEN or LG-IEN development and shorter mean survival time for progression (13.4, 13.2, and 11.1, respectively, vs 14.7 years, P = 0.01). Pernicious anemia was an independent risk factor for T1gNET (HR 2.2) and associated with a shorter mean survival time for progression (11.7 vs 13.6 years, P = 0.04) as well as severe corpus atrophy (12.8 vs 13.6 years, P = 0.03).

Patients with corpus-restricted atrophic gastritis are at increased risk for GC and T1gNET despite low-risk OLGA scores, and those aged older than 60 years with corpus intestinal metaplasia or pernicious anemia seem to display a high-risk scenario.

CAG is a burdensome and progressive disease. Numerous studies have shown the effectiveness of RUT in digestive system diseases. The therapeutic effects of RUT on MNNG-induced CAG and the potential mechanisms were probed. MNNG administration was employed to establish a CAG model. The HE and ELISA methods were applied to detect the treatment effects. WB, qRT-PCR, immunohistochemistry, TUNEL, and GES-1 cell flow cytometry approaches were employed to probe the mechanisms. The CAG model was successfully established. The ELISA and HE staining data showed that the RUT treatment effects on CAG rats were reflected by the amelioration of histological damage. The qRT-PCR and WB analyses indicated that the protective effect of RUT is related to the upregulation of the SHH pathway and downregulation of the downstream of apoptosis to improve gastric cellular survival. Our data suggest that RUT induces a gastroprotective effect by upregulating the SHH signaling pathway and stimulating anti-apoptosis downstream.

Helicobacter pylori ( H. pylori ) can persistently colonize on the gastric mucosa after infection and cause gastritis, atrophy, metaplasia, and even gastric cancer (GC).

Therefore, the detection and eradication of H. pylori are the prerequisite.

Clinically, there are some controversial issues, such as why H. pylori infection is persistent, why it translocases along with the lesser curvature of the stomach, why there is oxyntic antralization, what the immunological characteristic of gastric chronic inflammation caused by H. pylori is, whether H. pylori infection is associated with extra-gastric diseases, whether chronic atrophic gastritis (CAG) is reversible, and what the potential problems are after H. pylori eradication. What are the possible answers?

In the review, we will discuss these issues from the attachment to eradication in detail.

Aging may affect the efficacy of Helicobacter pylori eradication. The aim of our study was to assess the efficacy and safety of 7-day non-bismuth concomitant quadruple therapy as a first-line H. pylori infection eradication regimen in elderly individuals.

We retrospectively analyzed a cohort with prospectively collected data from January 2013 to December 2019 at Chang Gung Memorial Hospital in Kaohsiung. There were 408 naive infected subjects aged 20 years or older who were treated with 7 days of concomitant therapy as a first-line H. pylori eradication regimen. We divided the patients into an elderly group (aged ≥ 65 years) and a control group (aged < 65 years). Two patients were lost during follow-up in the elderly group and 29 patients were lost in the control group, resulting in 56 in the ≥ 65-year age group and 321 in the control group. The patients were asked to perform urea breath tests 8 weeks later.

The eradication rates for the elderly and control groups were 93.1% (95% confidence interval (CI): 83.3-98.1) and 84.0% (95% CI 79.7-87.7) (p = 0.070), respectively, in the intention-to-treat analysis, and 96.4% (95% CI 87.6-99.6) and 91.6% (95% CI 88.0-94.4) (p = 0.210), respectively, in the per-protocol (PP) analysis. The adverse event rates were 8.9% in the elderly group and 12.8% in the control group (p = 0.417). The compliance was 100% in both groups. No significant difference was seen in antibiotic resistance in either group. Multivariate analysis revealed that metronidazole resistance (odds ratio (OR) 6.870, 95% CI 1.182-39.919, p = 0.032) and dual-therapy resistance (OR 7.188, 95% CI 1.326-38.952, p = 0.022) were independent factors for eradication failure.

The efficacy of non-bismuth concomitant quadruple therapy in the elderly cohort was comparable with that in the non-elderly cohort for first-line H. pylori eradication with acceptable adverse effects.

Chronic atrophic gastritis is a significant premalignant lesion of gastric carcinoma. There is a great need to prevent the progression to gastric carcinoma through early intervention and treatment for chronic atrophic gastritis. Weifuchun, a famous Chinese patent drug, has been widely used for chronic atrophic gastritis in China. However, it remains unclear whether Weifuchun is effective for atrophic gastritis.

To determine the effectiveness and safety of Weifuchun for chronic atrophic gastritis.

We systematically retrieved seven databases (Cochrane Library, EMBASE, PubMed, China National Knowledge Infrastructure, Wanfang database, Chinese Scientific Journals Database, and Chinese Biological Medical Database) from their inception to October 5, 2022. Methodological quality was examined using the Cochrane Risk of bias tool. We also used RevMan 5.4 software for statistical analysis to examine the effectiveness and safety of Weifuchun.

Fifteen studies with 1,488 patients were enrolled in this meta-analysis. The study indicated that Weifuchun was more effective (RR 1.52; 95% CI 1.41, 1.63; p<0.00001) than Western medicine and other Chinese patent medicine. In addition, Weifuchun was more effective in improving gastric mucosal under gastroscopy, improving histopathologic changes of gastric mucosal, and inhibiting Helicobacter pylori. However, no significant difference in safety was examined between Weifuchun and the control group (RR 2.83; 95% CI 0.85, 9.38; P = 0.09).

The meta-analysis revealed a significant statistical difference with Weifuchun in effectiveness compared to the control group. However, there was no significant difference in safety. Thus, more high-quality clinical studies are needed in the future.

Registration number CRD42022365703.

Helicobacter pylori (H pylori) eradication treatment can reduce the risk of gastric cancer. However, early gastric cancer (EGC) can still be detected after eradication. Meanwhile, EGC after eradication is challenging to diagnose by an endoscopist in some cases due to the lack of apparent characteristics and the complex mucosal status. This review aims to summarize the endoscopic and histological characteristics and the mucosal risk factors for gastric cancer after H pylori eradication. The literature was searched for possible reported gastric cancer after eradication in "PubMed." These included related clinical studies and reviews, and unrelated or non-English articles were excluded. Endoscopically, EGC displays a small, reddish and depressed lesion, indistinct border, "gastritis-like" appearance and submucosal invasion. Histologically, it is divided into surface differentiation, nontumorous epithelium, and intestinal type. The risk factors include severe gastric atrophy, intestinal metaplasia in the corpus, and map-like redness. In conclusion, these studies on the characteristics and risk mucosal factors of patients with gastric cancer after H pylori eradication will drive the establishment of a novel endoscopic surveillance and diagnosis system for H pylori-eradicated patients.

This study aimed to assess the efficacy and safety of probiotics for Helicobacter pylori (H. pylori) eradication therapy as well as their effects on gastric microbiota.

Patients who had failed H. pylori eradication therapy for at least twice were prospectively enrolled during March 2019 and March 2021. A 2-week administration of compound Lactobacillus acidophilus probiotic (1 g thrice daily) followed by a 10-day quadruple bismuth-containing H. pylori eradication therapy was administrated. Endoscopy was performed, and gastric biopsy samples were obtained for drug sensitivity testing and 16S rRNA gene sequencing before and after probiotic treatment. Eradication was evaluated by the ¹³ C-urea breath test at least 4 weeks after treatment completion. Adverse events (AEs) were recorded.

Thirty-seven patients were included. Probiotic supplementation had no effects on the diversity, community structure, and composition of gastric microbiota and no inhibition on H. pylori activity. However, it increased some of the beneficial bacteria such as Blautia, Dorea, and Roseburia (P < 0.05). The overall eradication rate was 97.3% (95% confidence interval [CI] 91.8%-100%). AEs, mainly dizziness, nausea, diarrhea, and chest distress, were detected in six individuals, all of which were resolved upon cessation of antibiotic administration. Dyspeptic symptoms were improved after probiotic supplementation and at treatment completion (both P < 0.001).

H. pylori-infected individuals might benefit from probiotics followed by a quadruple bismuth-containing eradication therapy. Further studies with large sample sizes are warranted.

Helicobacter pylori eradication may prevent the recurrence of gastric epithelial neoplasia after endoscopic treatment. However, H. pylori eradication therapy is unlikely to prevent gastric cancer. This study determined the longterm results and clinical outcomes of patients with gastric epithelial neoplasia based on H. pylori infection status and microsatellite stability (MSS).

Patients diagnosed with gastric epithelial neoplasia who underwent an endoscopic mucosal resection or submucosal dissection between 2004 and 2010 were included in this retrospective study. During the follow-up period (range, 4 to 14 years), disease recurrence was monitored, and tissue examinations were conducted for seven sets of microsatellite loci initially linked to the tumour suppressor gene locus. When H. pylori infection was identified, patients underwent eradication therapy.

The patients (n = 120) were divided into three groups: H. pylori-negative with MSS, H. pylori-positive with MSS, and microsatellite instability (MSI). After H. pylori eradication, the rate of metachronous recurrence was significantly different in the MSI (28.2%) and MSS groups (3.7%, p < 0.01). The mean duration of recurrence was 77 months (range, 24 to 139) in the MSI group. There was no recurrence after eradication therapy in patients who were positive for H. pylori in the MSS group.

H. pylori eradication could help prevent gastric cancer recurrence in patients with stable microsatellite loci. Careful, long-term monitoring is required in patients with unstable microsatellite loci.

Gram-negative bacterium Helicobacter pylori (H. pylori) infection is lifelong and usually acquired in childhood, which is etiologically linked to gastric cancer (GC). H. pylori gastritis is defined as an infectious disease with varying severity in virtually all infected subjects. Chronic atrophic gastritis (CAG) is the precancerous condition with the decrease or the loss of gastric glands, which can further be replaced by metaplasia or fibrosis. Patients with advanced stages of CAG are at higher risk of GC and should be followed up with a high-quality endoscopy every 3 years. H. pylori infection is the most common cause and its eradication is recommended, which may contribute to the regression of CAG. However, it is controversial whether CAG is reversible after eradication therapy. In the review, we discuss recent studies which provide important insights into whether CAG is 'reversibility' and when it may progress into GC after eradicating H. pylori.

To systematically review the current evidence on Helicobacter pylori-negative chronic gastritis including natural history, available therapies and outcomes.

Articles providing data on the prevalence, treatment or outcomes of Helicobacter pylori-negative gastritis were identified through a systematic search in the MEDLINE and EMBASE databases. All original research articles from human studies until October 31, 2021, were included.

A total of 54 studies were included consisted of eosinophilic gastritis (n = 9), autoimmune gastritis (n = 11), collagenous gastritis (n = 16), focally enhanced gastritis (n = 6), lymphocytic gastritis (n = 5) and other causes including idiopathic gastritis and chronic renal failure related (n = 7). Most of the included studies were either cross-sectional or longitudinal cohorts except for collagenous gastritis, which mainly included case reports and case series. The prevalence of paediatric eosinophilic gastritis ranges between 5 and 7/100,000 and patients have generally favourable outcome with 50% to 70% clinical and histological response to either corticosteroids or elimination diets. Autoimmune gastritis and collagenous gastritis are extremely rare entities, commonly present with refractory iron deficiency anaemia, while lymphocytic gastritis is relatively common (10%-45%) in children with coeliac disease. Data on treatments and outcomes of autoimmune, collagenous, and focally enhanced gastritis are lacking with limited data implying poor response to therapy in the former 2 diagnoses.

Helicobacter pylori-negative gastritis is uncommonly reported, mainly in small cohorts, mixed adult-paediatric cohorts or as sporadic case reports. As common symptoms are not specific, thus not always result in an endoscopic evaluation, the true prevalence of these distinct disorders may be underestimated, and thus under reported.

The current international consensus report indicated that all Helicobacter pylori (H. pylori)-positive patients should be treated. This study aimed to evaluate the long-term effects and benefits of H. pylori eradication on the gastric mucosa in the elderly population.

We performed a retrospective cohort study with 311 individuals aged ≥60 years, including 83 with persistent H. pylori infection (persistent group), 128 with successful H. pylori eradication (eradicated group), and 100 without H. pylori infection (control group). The results of endoscopy and mucosal histology were investigated at baseline and followed up for 5 and 10 years.

In the 5 to 10-year follow-up, there was a significant difference in the atrophy score among the three groups (P < 0.001); however, no significant difference was observed in the intestinal metaplasia (IM) score (P > 0.05). There was no significant difference in the cumulative incidence of gastric neoplastic lesion (GNL) between the eradicated and persistent groups during the 5 to 10-year follow-up period (P > 0.05). The baseline IM score of patients with GNL was significantly higher than that of those without GNL in the eradicated and control groups (P < 0.05). In all patients with GNL, the mean interval time between baseline and diagnosis of GLN was more than 6 years. The severity of baseline mucosal IM (odds ratio: OR 3.092, 95% confidence interval [CI]: 1.690-5.655, P < 0.001) and H. pylori infection (OR: 2.413, 95%CI: 1.019-5.712, P = 0.045) significantly increased the risk for GNL.

Older patients with a life expectancy of less than 5 to 10 years, especially those with moderate to severe gastric mucosal IM, may not benefit from the eradication of H. pylori to prevent gastric cancer.

Intestinal metaplasia (IM) is the inevitable precancerous stage to develop intestinal-type gastric cancer (GC). Deoxycholic acid (DCA) is the main bile acid (BA) component of duodenogastric reflux and has shown an increased concentration during the transition from chronic gastritis to IM associated with continued STAT3 activation. However, the mechanisms underlying how DCA facilitates IM in the gastric epithelium need exploration. We evaluated IM and bile reflux in corpus tissues from 161 subjects undergoing GC screening. Cell survival and proliferation, proinflammatory cytokine expression and TGR5/STAT3/KLF5 axis activity were measured in normal human gastric cells, cancer cells, and organoid lines derived from C57BL/6, FVB/N and insulin-gastrin (INS-GAS) mice treated with DCA. The effects of DCA on IM development were determined in INS-GAS mice with long-term DCA supplementation, after which the gastric bacterial and BA metabolic profiles were measured by 16S rRNA gene sequencing and LC-MS. We revealed a BA-triggered TGR5/STAT3/KLF5 pathway in human gastric IM tissues. In gastric epithelial cells, DCA promoted proliferation and apoptotic resistance, upregulated proinflammatory cytokines and IM markers, and facilitated STAT3 phosphorylation, nuclear accumulation and DNA binding to the KLF5 promoter. DCA triggered STAT3 signaling and the downstream IM marker KLF5 in mouse gastric organoids in vitro and in vivo. In INS-GAS mice, DCA promoted the accumulation of serum total BAs and accelerated the stepwise development of gastric IM and dysplasia. DCA induced gastric environmental alterations involving abnormal BA metabolism and microbial dysbiosis, in which the Gemmobacter and Lactobacillus genera were specifically enriched. Lactobacillus genus enrichment was positively correlated with increased levels of GCA, CA, T-α-MCA, TCA and β-MCA in DCA-administrated INS-GAS mice. DCA promotes nuclear STAT3 phosphorylation, which mediates KLF5 upregulation associated with gastric inflammation and IM development. DCA disturbs the gastric microbiome and BA metabolism homeostasis during IM induction.

BACKGROUND Antibiotic resistance is a major cause of Helicobacter pylori (H. pylori ) treatment failures. The increased resistance to clarithromycin and metronidazole has reduced the ability of this therapeutic regimen and prompted researchers to look for other drugs. One of the antibiotics of interest in this regard is furazolidone because of its low drug resistance. The aim of this study is compare two-drug regimens including low-dose and high-dose furazolidone in the treatment of H. pylori. METHODS This study is a clinical trial in which the studied subjects were categorized into two groups. The first group underwent treatment with amoxicillin 1000 mg-BD, furazolidone 100 mg-BD, omeprazole 20 mg-BD, and bismuth subcitrate 240 mg-BD for two weeks (low-dose OFAB). The second group received furazolidone 200 mg-BD (high-dose OFAB). Then eight weeks after completion of the treatment, they were examined in terms of eradication via the UBT test. RESULTS 85 participants completed the study in each group. The response to treatment was 76% and 83% in the low and high-dose groups, respectively, based on intention to treat analysis. Based on per protocol analysis the response to treatment was 78% and 84%, respectively, if excluded patients had completed their protocol and had response to treatment, and 72% and 79%, respectively, if excluded patients had completed their protocol and did not have response to treatment (p = 0.298). In the low-dose and high-dose groups, 16.5% and 24.7% of the participants suffered the complications of treatment with furazolidone (p = 0.18), respectively. Three patients in the high-dose group and one in the low-dose group did not complete the treatment because of the medication's bad taste (p = 0.03). CONCLUSION Low doses of furazolidone had a comparable therapeutic effect compared with high doses, but patients experienced significantly lower levels of bad taste, which was a major cause of reluctance to continue treatment. Therefore, we think four-drug low-dose furazolidone treatment is a good choice in eradicating H. pylori.

Gastric cancer (GC) is the fifth leading cause of cancer-related death worldwide. GC is usually preceded by a cascade of well-defined precursor lesions, set in place by an environmental trigger (H. pylori) including intestinal metaplasia (GIM) and dysplasia.

To investigate the rates of progression of GIM to dysplasia and GC in a region of low gastric cancer incidence.

We identified all patients diagnosed with GIM between January 1, 2008, and June 30, 2012. Any repeat upper endoscopy more than 1 year after index diagnosis and before December 31, 2018, was considered follow-up. Carcinomas the bulk of which were macroscopically located below the OGJ were considered primary gastric cancer.

Progression to more advanced lesions was observed in six patients (0.6%). Four patients (three male) developed GC at median age 74 years (SD 6). Two patients progressed to dysplasia (one male) at median age 71 years (SD 4). Patients with GIM in both gastric antrum and body were significantly more likely to progress than those with GIM in only one location (3.1% vs. 0.4%) (p value 0.017). Fifty-eight patients who had H. pylori eradicated were followed up. No progression to dysplasia or GC was noted in this group, with 28 patients having persistent GIM at follow-up.

Patients with GIM in both antrum and body had a significantly increased risk of progression and warrant close attention. This is comparable to routinely followed premalignant conditions such as Barrett's esophagus and Colonic Polyps, and appropriate surveillance protocols should be followed in this group.

Helicobacter pylori (H. pylori) eradication reduces gastric cancer risk. Since 2013, a population-wide H. pylori eradication strategy for patients with chronic gastritis has begun to prevent gastric cancer in Japan. The aim of this study was to evaluate the economic and health effects of H. pylori eradication strategy in national gastric cancer prevention program.

We developed a cohort state-transition model for H. pylori eradication and no eradication over a lifetime horizon from a healthcare payer perspective, and performed one-way and probabilistic sensitivity analyses. We targeted a hypothetical cohort of H. pylori-positive patients aged 20, 30, 40, 50, 60, 70, and 80. The main outcomes were costs, quality-adjusted life-years (QALYs), life expectancy life-years (LYs), incremental cost-effectiveness ratios, gastric cancer cases, and deaths from gastric cancer.

H. pylori eradication was more effective and cost-saving for all age groups than no eradication. Sensitivity analyses showed strong robustness of the results. From 2013-2019 for 8.50 million patients, H. pylori eradication saved US$3.75 billion, increased 11.11 million QALYs and 0.45 million LYs, and prevented 284,188 cases and 65,060 deaths. For 35.59 million patients without eradication, H. pylori eradication has the potential to save US$14.82 billion, increase 43.10 million QALYs and 1.66 million LYs, and prevent 1,084,532 cases and 250,256 deaths.

National policy using population-wide H. pylori eradication to prevent gastric cancer has significant cost savings and health impacts for young-, middle-, and old-aged individuals in Japan. The findings strongly support the promotion of H. pylori eradication strategy for all age groups in high-incidence countries.