Chronic active and atrophic gastritis as significant contributing factor to the development of gastric cystica profunda

Gastric cystica profunda(GCP)is an uncommon but underestimated gastric lesion.Its precancerous potential determines its significance.In addition to previous mucosa injury due to operations,biopsy or polypectomy,chronic active and atrophic gastritis may also lead to the development of GCPs.By carefully examining the stomach and taking biopsy samples from the susceptible regions,the stage of atrophy can be determined.Chronic atrophic gastritis is a risk factor for cancer evolvement and it can also contribute to GCPs formation.GCPs frequently occur close to early gastric cancers(EGCs)or EGC can arise from the cystic glands.Endoscopic resection is an effective and minimally invasive treat-ment in GCP.

Update understanding on diagnosis and histopathological examination of atrophic gastritis:A review

Chronic atrophic gastritis(CAG)is a complex syndrome in which long-term chronic inflammatory stimulation causes gland atrophy in the gastric mucosa,reducing the stomach's ability to secrete gastric juice and pepsin,and interfering with its normal physiological function.Multiple pathogenic factors contribute to CAG incidence,the most common being Helicobacter pylori infection and the immune reactions resulting from gastric autoimmunity.Furthermore,CAG has a broad spectrum of clinical manifestations,including gastroenterology and extraintestinal symptoms and signs,such as hematology,neurology,and oncology.Therefore,the initial CAG evaluation should involve the examination of clinical and serological indicators,as well as diagnosis confirmation via gastroscopy and histopathology if necessary.Depending on the severity and scope of atrophy affecting the gastric mucosa,a histologic staging system(Operative Link for Gastritis Assessment or Operative Link on Gastritis intestinal metaplasia)could also be employed.Moreover,chronic gastritis has a higher risk of progressing to gastric cancer(GC).In this regard,early diagnosis,treatment,and regular testing could reduce the risk of GC in CAG patients.However,the optimal interval for endoscopic monitoring in CAG patients remains uncertain,and it should ideally be tailored based on individual risk evaluations and shared decision-making processes.Although there have been many reports on CAG,the precise etiology and histopathological features of the disease,as well as the diagnosis of CAG patients,are yet to be fully elucidated.Consequently,this review offers a detailed account of CAG,including its key clinical aspects,aiming to enhance the overall understanding of the disease.

Yiwei Xiaoyu granules for treatment of chronic atrophic gastritis with deficiency syndrome of the spleen and stomach

BACKGROUND The Correa sequence,initiated by Helicobacter pylori(H.pylori),commonly progresses to gastric cancer through the stage of chronic atrophic gastritis(CAG).Although eradication of H.pylori only reduces the risk of gastric cancer,it does not eliminate the risk for neoplastic progression.Yiwei Xiaoyu granules(YWXY)are a commonly used composite preparation in Chinese clinics.However,the pursuit of excellence in clinical trials and the establishment of standardized animal experiments are still needed to contribute to full understanding and application of traditional Chinese medicine in the treatment of CAG.AIM To demonstrate the effectiveness of YWXY in patients with CAG and spleenstomach deficiency syndrome(DSSS),by alleviating histological scores,improving response rates for pathological lesions,and achieving clinical efficacy in relieving DSSS symptoms.METHODS We designed a double-blind,randomized,controlled trial.The study enrolled seventy-two H.pylori-negative patients(mean age,52.3 years;38 men)who were randomly allocated to either the treatment group or control group in a 1:1 ratio,and treated with 15 g YWXY or 0.36 g Weifuchun(WFC)tablet combined with the respective dummy for 24 wk.The pre-randomization phase resulted in the exclusion of 72 patients:50 participants did not meet the inclusion criteria,12 participants declined to participate,and 10 participants were excluded for various other reasons.Seven visits were conducted during the study,and histopathological examination with target endoscopic biopsy of narrow-band imaging was requested before the first and seventh visits.We also evaluated endoscopic performance scores,total symptom scores,serum pepsinogen and gastrin-17.RESULTS Six patients did not complete the trial procedures.Treatment with YWXY improved the Operative Link on Gastric Intestinal Metaplasia Assessment(OLGIM)stage,compared with WFC(P<0.05).YWXY provided better relief from symptoms of DSSS and better improvement in serum gastric function,compared with WFC(P<0.05).CONCLUSION YWXY compared with WFC significantly reduced the risk of mild or moderate atrophic disease,according to OLGIM stage,significantly relieved symptoms of DSSS,and improved serum gastric function.

Yangyin Huowei mixture alleviates chronic atrophic gastritis by inhibiting the IL-10/JAK1/STAT3 pathway

BACKGROUND The Chinese medicine Yangyin Huowei mixture(YYHWM)exhibits good clinical efficacy in the treatment of chronic atrophic gastritis(CAG),but the mechanisms underlying its activity remain unclear.AIM To investigate the therapeutic effects of YYHWM and its underlying mechanisms in a CAG rat model.METHODS Sprague-Dawley rats were allocated into control,model,vitacoenzyme,and low,medium,and high-dose YYHWM groups.CAG was induced in rats using Nmethyl-N′-nitro-N-nitrosoguanidine,ranitidine hydrochloride,hunger and satiety perturbation,and ethanol gavage.Following an 8-wk intervention period,stomach samples were taken,stained,and examined for histopathological changes.ELISA was utilized to quantify serum levels of PG-I,PG-II,G-17,IL-1β,IL-6,and TNF-α.Western blot analysis was performed to evaluate protein expression of IL-10,JAK1,and STAT3.RESULTS The model group showed gastric mucosal layer disruption and inflammatory cell infiltration.Compared with the blank control group,serum levels of PGI,PGII,and G-17 in the model group were significantly reduced(82.41±3.53 vs 38.52±1.71,23.06±0.96 vs 11.06±0.70,and 493.09±12.17 vs 225.52±17.44,P<0.01 for all),whereas those of IL-1β,IL-6,and TNF-αwere significantly increased(30.15±3.07 vs 80.98±4.47,69.05±12.72 vs 110.85±6.68,and 209.24±11.62 vs 313.37±36.77,P<0.01 for all),and the protein levels of IL-10,JAK1,and STAT3 were higher in gastric mucosal tissues(0.47±0.10 vs 1.11±0.09,0.49±0.05 vs 0.99±0.07,and 0.24±0.05 vs 1.04±0.14,P<0.01 for all).Compared with the model group,high-dose YYHWM treatment significantly improved the gastric mucosal tissue damage,increased the levels of PGI,PGII,and G-17(38.52±1.71 vs 50.41±3.53,11.06±0.70 vs 15.33±1.24,and 225.52±17.44 vs 329.22±29.11,P<0.01 for all),decreased the levels of IL-1β,IL-6,and TNF-α(80.98±4.47 vs 61.56±4.02,110.85±6.68 vs 89.20±8.48,and 313.37±36.77 vs 267.30±9.31,P<0.01 for all),and evidently decreased the protein levels of IL-10 and STAT3 in gastric mucosal tissues(1.11±0.09 vs 0.19±0.07 and 1.04±0.14 vs 0.55±0.09,P<0.01 for both).CONCLUSION YYHWM reduces the release of inflammatory factors by inhibiting the IL-10/JAK1/STAT3 pathway,alleviating gastric mucosal damage,and enhancing gastric secretory function,thereby ameliorating CAG development and cancer transformation.

Postprandial gastrin-17 level is a useful dynamic marker for atrophic gastritis

Atrophic gastritis and intestinal metaplasia may progress to gastric malignancy.Non-invasive serum biomarkers have been extensively studied and proven to be useful as a screening tool to stratify risk and identify patients for endoscopy to detect early gastric cancer.These non-invasive biomarkers have been endorsed and recommended by many international consensus guidelines.In this letter,we reviewed the literature and evidence supporting the use of serum biomarkers as a dynamic test to monitor the status of atrophic gastritis.

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

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

Mucosal patterns change after Helicobacter pylori eradication:Evaluation using blue laser imaging in patients with atrophic gastritis

BACKGROUND Mucosal patterns(MPs)observed on blue laser imaging in patients with atrophic gastritis can be classified as spotty,cracked,and mottled.Furthermore,we hypothesized that the spotty pattern may change to the cracked pattern after Helicobacter pylori(H.pylori)eradication.AIM To further substantiate and comprehensively investigate MP changes after H.pylori eradication in a larger number of patients.METHODS We included 768 patients who were diagnosed with atrophic gastritis with evaluable MP using upper gastrointestinal endoscopy at the Nishikawa Gastrointestinal Clinic,Japan.Among them,325 patients were H.pylori-positive,and of them,101 patients who underwent upper gastrointestinal endoscopy before and after H.pylori eradication were evaluated for post-eradication MP changes.The patients’MPs were interpreted by three experienced endoscopists who were blinded to their clinical features.RESULTS Among 76 patients with the spotty pattern before or after H.pylori eradication,the pattern disappeared or decreased in 67 patients[88.2%,95%confidence interval(CI):79.0%-93.6%),appeared or increased in 8 patients(10.5%,95%CI:5.4%-19.4%),and showed no change in 1 patient(1.3%,95%CI:0.2%-7.1%).In 90 patients with the cracked pattern before or after H.pylori eradication,the pattern disappeared or decreased in 7 patients(7.8%,95%CI:3.8%-15.2%),appeared or increased in 79 patients(87.8%,95%CI:79.4%-93.0%),and showed no change in 4 patients(4.4%,95%CI:1.7%-10.9%).In 70 patients with the mottled pattern before or after H.pylori eradication,the pattern disappeared or decreased in 28 patients(40.0%,95%CI:29.3%-51.7%),appeared or increased in 35 patients(50.0%,95%CI:38.6%-61.4%),and showed no change in 7 patients(10.0%,95%CI:4.9%-19.2%).CONCLUSION After H.pylori eradication,MPs changed from spotty to cracked in most patients,which may help endoscopists easily and precisely evaluate H.pylori-related gastritis status.

Efficacy and safety of Huangqi Jianzhong decoction in the treatment of chronic atrophic gastritis:A meta-analysis

BACKGROUND Chronic atrophic gastritis is a persistent disorder of the digestive system where the gastric mucosa epithelium and glands undergo atrophy,leading to a decrease in their number and thinning of the gastric mucosa.It is worth noting that the prevalence of chronic atrophic gastritis is higher in China compared to the global average,and it is also considered a precancerous condition for gastric cancer.AIM To evaluate the efficacy of Huangqi Jianzhong decoction in treating chronic atrophic gastritis.Chronic atrophic gastritis is a persistent illness characterized by the progressive disappearance of healthy gastric glands due to repeated injury.Huangqi Jianzhong decoctions are widely used in China to treat chronic atrophic gastritis.However,there is limited scientific evidence regarding their efficacy in treating this illness.METHODS The present meta-analysis adhered to the PRISMA guidelines and used the Cochrane Collaboration methodology.We performed a comprehensive search for clinical trials investigating the use of Huangqi Jianzhong decoction in treating chronic atrophic gastritis published until January 2023.The risk of bias and the quality of the included studies were evaluated using the Cochrane Handbook guidelines.Finally,a meta-analysis was conducted using the RevMan 5.4 softRESULTS This study included a total of 13 articles,comprising 1269 samples.The meta-analysis was conducted on these 13 articles,yielding the following results:I2=0%,P=0.60,[RR=1.24,95%CI:1.18 to 1.30,P<0.00001].The forest plot analysis of the Helicobacter pylori clearance rate revealed I2=0%,P=0.36,[RR=1.20,95%CI:1.05 to 1.38,P=0.009].The forest plot of PG-I level showed I2=99%,P<0.00001,[MD=4.99,95%CI:-1.59 to 11.58,P=0.14].The forest plot of stomach pain demonstrated I2=54%,P=0.04,[MD=-0.63,95%CI:-0.68 to-0.58,P<0.00001].The forest plot of reflux indicated I2=82%,P=0.0009,[MD=-0.48,95%CI:-0.63 to-0.33,P<0.00001].The forest plot of recurrence rate exhibited I2=0%,P=0.92,[RR=0.15,95%CI:0.04 to 0.66,P=0.01].The forest plot of adverse reactions showed no heterogeneity in outcome data,[RR=1.07,95%CI:0.53 to 2.17,P=0.86].CONCLUSION This study demonstrated that Huangqi Jianzhong decoction improved various factors in adults with chronic atrophic gastritis.These factors included the total effective rate,Helicobacter pylori clearance rate,symptoms such as stomachache and acid reflux alleviation,and recurrence rates.

Risk for gastric neoplasias in patients with chronic atrophic gastritis:A critical reappraisal

Chronic atrophic gastritis （CAG） is an inflammatory condition characterized by the loss of gastric glandular structures which are replaced by connective tissue （non-metaplastic atrophy） or by glandular structures inappropriate for location （metaplastic atrophy）. Epidemiological data suggest that CAG is associated with two different types of tumors： Intestinal-type gastric cancer （GC） and type I gastric carcinoid （T I GC）. The pathophysiological mechanisms which lead to the development of these gastric tumors are different, It is accepted that a multistep process initiating from Helico- bacterpylori-related chronic inflammation of the gastric mucosa progresses to CAG, intestinal metaplasia, dysplasia and, finally, leads to the development of GC. The T I GC is a gastrin-dependent tumor and the chronic elevation of gastrin, which is associated with CAG, stimulates the growth of enterochromaffin-like cells with their hyperplasia leading to the development of T I GC. Thus, several events occur in the gastric mucosa before the development of intestinatype GC and/ or T I GC and these take several years. Knowledge ofCAG incidence from superficial gastritis, its prevalence in different clinical settings and possible risk factors as- sociated with the progression of this condition to gastric neoplasias are important issues. This editorial intends to provide a brief review of the main studies regarding incidence and prevalence of CAG and risk factors for the development of gastric neoplasias.

Chronic atrophic gastritis detection with a convolutional neural network considering stomach regions

BACKGROUND The risk of gastric cancer increases in patients with Helicobacter pylori-associated chronic atrophic gastritis(CAG).X-ray examination can evaluate the condition of the stomach,and it can be used for gastric cancer mass screening.However,skilled doctors for interpretation of X-ray examination are decreasing due to the diverse of inspections.AIM To evaluate the effectiveness of stomach regions that are automatically estimated by a deep learning-based model for CAG detection.METHODS We used 815 gastric X-ray images(GXIs)obtained from 815 subjects.The ground truth of this study was the diagnostic results in X-ray and endoscopic examinations.For a part of GXIs for training,the stomach regions are manually annotated.A model for automatic estimation of the stomach regions is trained with the GXIs.For the rest of them,the stomach regions are automatically estimated.Finally,a model for automatic CAG detection is trained with all GXIs for training.RESULTS In the case that the stomach regions were manually annotated for only 10 GXIs and 30 GXIs,the harmonic mean of sensitivity and specificity of CAG detection were 0.955±0.002 and 0.963±0.004,respectively.CONCLUSION By estimating stomach regions automatically,our method contributes to the reduction of the workload of manual annotation and the accurate detection of the CAG.

Effects of Helicobacter pylori eradication on atrophic gastritis and intestinal metaplasia: A 3-year follow-up study

AIM: To investigate the effect of H pylori eradication on atrophic gastritis and intestinal metaplasia (IM).METHODS: Two hundred and fifty-nine patients with atrophic gastritis in the antrum were included in the study, 154 patients were selected for H pylori eradication therapy and the remaining 105 patients served as untreated group. Gastroscopy and biopsies were performed both at the beginning and at the end of a 3-year follow-up study. Gastritis was graded according to the updated Sydney system.RESULTS: One hundred and seventy-nine patients completed the follow-up, 92 of them received H pylori eradication therapy and the remaining 87 H pyloriinfected patients were in the untreated group. Chronic gastritis, active gastritis and the grade of atrophy significantly decreased in H pylori eradication group (P＜0.01). However, the grade of IM increased in H pylori -infected group (P＜0.05).CONCLUSION: H pylori eradication may improve gastric mucosal inflammation, atrophy and prevent the progression of IM.

Inflammatory cytokine gene polymorphisms increase the risk of atrophic gastritis and intestinal metaplasia

AIM: To investigate the effects of interleukin-8 (IL-8 ), macrophage migration inhibitory factor (MIF ) gene polymorphisms, Helicobacter pylori (H. pylori ) infection, on the risk of developing severe chronic atrophic gastritis (SCAG) and intestinal metaplasia (IM). METHODS: A total of 372 cases were selected from a cohort study in Linqu County, a high risk area for gastric cancer (GC) in northern China. To obtain a sufficient group size, patients with normal or superficial gastritis were included. Based on an average follow-up period of 56 mo, the 372 cases were divided into no progres-sion group (no histological progression from normal or superficial gastritis, n = 137), group Ⅰ (progressed from normal or superficial gastritis to SCAG, n = 134) and group Ⅱ (progressed from normal or superficial gastritis to IM, n = 101). IL-8 , MIF gene polymorphisms were detected by polymerase chain reaction-based denaturing high-performance liquid chromatography analysis and DNA sequencing. RESULTS: An increased risk of SCAG was found in subjects with IL-8-251 AA genotype [odds ratio (OR) = 2.62, 95% CI: 1.23-5.72] or IL-8-251 A allele carriers (AA + AT) (OR = 1.81, 95% CI: 1.06-3.09). An elevated risk of IM was found in subjects with IL-8-251 AT genotype (OR = 2.27, 95% CI: 1.25-4.14) or IL-8-251 A allele carriers (OR = 2.07, 95% CI: 1.16-3.69). An increased risk of SCAG was found in subjects with MIF-173 GC genotype (OR = 2.36, 95% CI: 1.38-4.02) or MIF-173 C allele carriers (GC + CC) (OR = 2.07, 95% CI: 1.21-3.55). An elevated risk of IM was found in subjects with MIF-173 CC genotype (OR = 2.27, 95% CI: 1.16-4.46) or MIF-173 C allele carriers (OR = 3.84, 95% CI: 1.58-9.34). The risk of SCAG and IM was more evident in subjects carrying IL-8-251 A allele (OR = 6.70, 95% CI: 1.29-9.78) or MIF-173 C allele (OR = 6.54, 95% CI: 2.97-14.20) and positive for H. pylori infection. CONCLUSION: IL-8-251 and MIF-173 gene polymorphisms are significantly associated with the risk of SCAG and IM in a population with a high risk of GC in Linqu County, Shandong Province, China.

Effects of He-Ne laser irradiation on chronic atrophic gastritis in rats

AIM: To study the effects of He-Ne laser irradiation on experimental chronic atrophic gastritis (CAG) in rats.METHODS: Sixty-three male adult Wistar rats were randomly divided into five groups including normal control group, model control group and three different dosages He-Ne laser groups. The chronic atrophic gastritis (CAG)model in rats was made by pouring medicine which was a kind of mixed liquor including 2% sodium salicylate and 30% alcohol down the throat for 8 wk to stimulate rat gastric mucosa, combining with irregular fasting and compulsive sporting as pathogenic factors; 3.36, 4.80, and 6.24J/cm2doses of He-Ne laser were used, respectively for three different treatment groups, once a day for 20 d. The pH value of diluted gastric acid was determined by acidimeter,the histopathological changes such as the inflammatory degrees in gastric mucosa, the morphology and structure of parietal cells were observed, and the thickness of mucosa was measured by micrometer under optical microscope.RESULTS: In model control group, the secretion of gastric acid was little, pathologic morphological changes in gastric mucosa such as thinner mucous, atrophic glands, notable inflammatory infiltration were found. After 3.36 J/cm2 dose of He-Ne laser treatment for 20 d, the secretion of gastric acid was increased (P＜0.05), the thickness of gastric mucosa was significantly thicker than that in model control group (P＜0.01), the gastric mucosal inflammation cells were decreased (P＜0.05). Morphology, structure and volume of the parietal cells all recuperated or were closed to normal.CONCLUSION: 3.36J/cm2 dose of He-Ne laser has a significant effect on CAG in rats.

Histopathological classification and follow-up analysis of chronic atrophic gastritis

BACKGROUND The pathological diagnosis and follow-up analysis of gastric mucosal biopsy have been paid much attention,and some scholars have proposed the pathological diagnosis of 12 kinds of lesions and accompanying pathological diagnosis,which is of great significance for the treatment of precision gastric diseases,the improvement of the early diagnosis rate of gastric cancer,and the reduction of missed diagnosis rate and misdiagnosis rate.AIM To perform a histopathological classification and follow-up analysis of chronic atrophic gastritis(CAG).METHODS A total of 2248 CAG tissue samples were collected,and data of their clinical characteristics were also gathered.Based on these samples,the expression levels of Mucin 1(MUC1),MUC2,MUC5AC,and MUC6 in CAG tissue were tested by immunohistochemical assay.Moreover,we followed these patients for up to four years.The difference between different stages of gastroscopic biopsy was observed.RESULTS Through observation,it is believed that CAG should be divided into four types,simple type,hyperplasia type,intestinal metaplasia(IM)type,and intraepithelial neoplasia(IEN)type.Simple CAG accounted for 9.1%(205/2248),which was more common in elderly people over 60 years old.The main change was that the lamina propria glands were reduced in size and number.Hyperplastic CAG accounted for 29.1%(654/2248),mostly occurring between 40 and 60 years old.The main change was that the lamina propria glands were atrophy accompanied by glandular hyperplasia and slight expansion of the glands.IM CAG accounted for 50.4%(1132/2248),most of which increased with age,and were more common in those over 50 years.The atrophy of the lamina propria glands was accompanied by significant IM,and the mucus containing sialic acid or sulfate was distinguished according to the nature of the mucus.The IEN type CAG accounted for 11.4%(257/2248),which developed from the previous types,with severe gland atrophy and reduced mucus secretion,and is an important precancerous lesion.CONCLUSION The histological typing of CAG is convenient to understand the property of lesion,determine the follow-up time,and guide the clinical treatment.

Morphological and pathologic changes of experimental chronic atrophic gastritis (CAG)and the regulating mechanism of protein expression in rats

Objective： To study the pathologic change and molecular regulation in cell proliferation and apoptosis of gastric mucosa in rats with chronic atrophic gastritis （CAG）, and evaluate the possible mechanisms. Methods： Rats were administered with 60% alcohol or 2% salicylate sodium, 20 mmol/L deoxycholate sodium and 0.1% ammonia water to establish chronic atrophic gastritis （CAG） models. The gastric specimens were prepared for microscopic view with hematoxylin and eosin （H-E） and alcian blue （A-B） stain. The number of infiltrated inflammatory cells, the thickness of the mucosa gland layer （μm） and the number of gastric glands were calculated. The damage of barrier in mucosa with erosion or ulceration, and the thickness of mucin were examined by scanned electron microscope （SEM）. The levels of PGE2, EGF （epiderminal growth factor） and gastrin in the serum were measured with radioimmunoassay or ELISA method. The immunohistochemistry method was used to observe the number of G cells, the expression of protein of EGFR （EGF receptor）, C-erbB-2, p53, p6 and bcl-2 in gastric tissue. Results： Under SEM observation, the gastric mucosa was diffused erosion or ulceration and the thickness of mucin was decreased. Compared with normal rats, the grade of inflammatory cell infltration in CAG rats was elevated, whereas the thickness and number of gastric gland were significantly lower （P〈0.05）. Compared with normal level of （0.61±0.28） μg/L, EGF in CAG （2.24±0.83） μg/L was significantly higher （P〈0.05）. The levels of PGEz and gastrin in serum were significantly lower in CAG rats than that in normal rats （P〈0.05）. Immunohistochemistry detection showed that the number of G cell in antrum was lower in CAG group （P〈0.05）. Imrauno-stain showed EGFR protein expression in the basal and bilateral membrane, and the cytoplasma in atrophic gastric gland, while negative expression was observed in normal gastric epithelial cells. Positive staining of p53 and p 16 protein was localized in the nucleus of epithelial cells. The former was higher positively expressed in atrophic gland, while the later was higher positively stained in normal gastric tissue, bcl-2 protein was positively stained in the cytoplasma in atrophic gastric gland, while very weakly stained in normal gastric tissue. Conclusion： The pathological findings in gastric gland accorded with the Houston diagnostic criteria of antrum-predominant CAG. CAG in rats was related with the damage of barrier in gastric mucosa and the misbalance of cell proliferation and apoptosis. There was high protein expression of oncogene, while inhibitor of suppressor gene in CAG rats indicated high trend of carcinogenesis.

Updated Kimura-Takemoto classification of atrophic gastritis

BACKGROUND The Updated Sydney system for visual evaluation of gastric mucosal atrophy viaendoscopic observation is subject to sampling error and interobserver variability.The Kimura-Takemoto classification system was developed to overcome theselimitations.AIMTo compare the morphological classification of atrophic gastritis between theKimura-Takemoto system and the Updated Sydney system.METHODSA total of 169 patients with atrophic gastritis were selected according to diagnosisby the visual endoscopic Kimura-Takemoto method. Following the UpdatedKimura-Takemoto classification system, one antrum biopsy and five gastriccorpus biopsies were taken according to the visual stages of the Kimura-Takemoto system. The Updated Kimura-Takemoto classification system was thenapplied to each and showed 165 to have histological mucosal atrophy;theremaining 4 patients had no histological evidence of atrophy in any biopsy. The Updated Kimura-Takemoto classification was verified as a referencemorphological method and applied for the diagnosis of atrophic gastritis. Addingone more biopsy from the antrum to the six biopsies according to the Updated Kimura-Takemoto classification, constitutes the updated combined Kimura-Takemoto classification and Sydney system.RESULTSThe sensitivity for degree of mucosal atrophy assessed by the Updated Sydneysystem was 25% for mild, 36% for moderate, and 42% for severe, when comparedwith the Updated Kimura-Takemoto classification of atrophic gastritis formorphological diagnosis. Four types of multifocal atrophic gastritis wereidentified: sequential uniform (type 1;in 28%), sequential non-uniform (type 2;in7%), diffuse uniform (type 3;in 23%), diffuse non-uniform (type 4;in 24%), and"alternating atrophic – non-atrophic" (type 5;in 18%). The pattern of the spread ofatrophy, sequentially from the antrum to the cardiac segment of the stomach,which was described by the Updated Kimura-Takemoto system, washistologically confirmed in 82% of cases evaluated.CONCLUSIONThe Updated Sydney system is significantly inferior to the Updated Kimura-Takemoto classification for morphological verification of atrophic gastritis.

Comparison of operative link for gastritis assessment, operative link on gastric intestinal metaplasia assessment, and TAIM stagings among men with atrophic gastritis

BACKGROUND Gastric cancer is the world’s third most lethal malignancy. Most gastric cancers develop through precancerous states of atrophic gastritis and intestinal metaplasia. Two staging systems, operative link for gastritis assessment(OLGA)and operative link on gastric intestinal metaplasia assessment(OLGIM), have been developed to detect high gastric cancer risk. European guidelines recommend surveillance for high-risk OLGA/OLGIM patients(stages Ⅲ–Ⅳ),and for those with advanced stage of atrophic gastritis in the whole stomach mucosa. We hypothesize, that by combining atrophy and intestinal metaplasia into one staging named TAIM, more patients with increased gastric cancer risk could be detected.AIM To evaluate the clinical value of the OLGA, OLGIM, and novel TAIM stagings as prognostic indicators for gastric cancer.METHODS In the Helsinki Gastritis Study, 22346 elderly male smokers from southwestern Finland were screened for serum pepsinogen I(PGI). Between the years 1989 and1993, men with low PGI values(PGI < 25 μg/L), were invited to undergo an oesophagogastroduodenoscopy. In this retrospective cohort study, 1147 men that underwent gastroscopy were followed for gastric cancer for a median of 13.7 years, and a maximum of 27.3 years. We developed a new staging system, TAIM,by combining the topography with the severity of atrophy or intestinal metaplasia in gastric biopsies. In TAIM staging, the gastric cancer risk is classified as low or high.RESULTS Twenty-eight gastric cancers were diagnosed during the follow-up, and the incidence rate was 1.72 per 1000 patient-years. The cancer risk associated positively with TAIM [Hazard ratio(HR) 2.70, 95%CI: 1.09–6.69, P = 0.03]. The risk increased through OLGIM stages 0-Ⅳ(0 vs Ⅳ: HR 5.72, 95%CI: 1.03–31.77, P for trend = 0.004), but not through OLGA stages 0–Ⅳ(0 vs Ⅳ: HR 5.77, 95%CI:0.67–49.77, P for trend = 0.10). The sensitivities of OLGA and OLGIM stages Ⅲ–Ⅳ were low, 21% and 32%, respectively, whereas that of TAIM high-risk was good, 79%. On the contrary, OLGA and OLGIM had high specificity, 85% and81%, respectively, but TAIM showed low specificity, 42%. In all three staging systems, the high-risk men had three-to four-times higher gastric cancer risk compared to the general male population of the same age.CONCLUSION OLGIM and TAIM stagings show prognostic value in assessing gastric cancer risk in elderly male smokers with atrophic gastritis.

Atrophic gastritis and gastric cancer tissue miRNome analysis reveals hsa-miR-129-1 and hsa-miR-196a as potential early diagnostic biomarkers

BACKGROUND Gastric cancer(GC)is one of the most frequently diagnosed tumor globally.In most cases,GC develops in a stepwise manner from chronic gastritis or atrophic gastritis(AG)to cancer.One of the major issues in clinical settings of GC is diagnosis at advanced disease stages resulting in poor prognosis.Micro RNAs(mi RNAs)are small noncoding molecules that play an essential role in a variety of fundamental biological processes.However,clinical potential of mi RNA profiling in the gastric cancerogenesis,especially in premalignant GC cases,remains unclear.AIM To evaluate the AG and GC tissue mi RNomes and identify specific mi RNAs’potential for clinical applications(e.g.,non-invasive diagnostics).METHODS Study included a total of 125 subjects:Controls(CON),AG,and GC patients.All study subjects were recruited at the Departments of Surgery or Gastroenterology,Hospital of Lithuanian University of Health Sciences and divided into the profiling(n=60)and validation(n=65)cohorts.Total RNA isolated from tissue samples was used for preparation of small RNA sequencing libraries and profiled using next-generation sequencing(NGS).Based on NGS data,deregulated mi RNAs hsa-mi R-129-1-3 p and hsa-mi R-196 a-5 p were analyzed in plasma samples of independent cohort consisting of CON,AG,and GC patients.Expression level of hsa-mi R-129-1-3 p and hsa-mi R-196 a-5 p was determined using the quantitative real-time polymerase chain reaction and 2-ΔΔCt method.RESULTS Results of tissue analysis revealed 20 differentially expressed mi RNAs in AG group compared to CON group,129 deregulated mi RNAs in GC compared to CON,and 99 altered mi RNAs comparing GC and AG groups.Only 2 mi RNAs(hsa-mi R-129-1-3 p and hsa-mi R-196 a-5 p)were identified to be step-wise deregulated in healthy-premalignant-malignant sequence.Area under the curve(AUC)-receiver operating characteristic analysis revealed that expression level of hsa-mi R-196 a-5 p is significant for discrimination of CON vs AG,CON vs GC and AG vs GC and resulted in AUCs:88.0%,93.1%and 66.3%,respectively.Comparing results in tissue and plasma samples,hsa-mi R-129-1-3 p was significantly down-regulated in GC compared to AG(P=0.0021 and P=0.024,tissue and plasma,respectively).Moreover,analysis revealed that hsa-mi R-215-3 p/5 p and hsa-mi R-934 were significantly deregulated in GC based on Helicobacter pylori(H.pylori)infection status[log2 fold change(FC)=-4.52,P-adjusted=0.02;log2 FC=-4.00,P-adjusted=0.02;log2 FC=6.09,P-adjusted=0.02,respectively].CONCLUSION Comprehensive mi RNome study provides evidence for gradual deregulation of hsa-mi R-196 a-5 p and hsa-mi R-129-1-3 p in gastric carcinogenesis and found hsami R-215-3 p/5 p and hsa-mi R-934 to be significantly deregulated in H.pylori carrying GC patients.

Inverse correlation between gastroesophageal reflux disease and atrophic gastritis assessed by endoscopy and serology

BACKGROUND Helicobacter pylori(H.pylori)infection is known to prevent the occurrence of gastroesophageal reflux disease(GERD)by inducing gastric mucosal atrophy.However,little is known about the relationship between atrophic gastritis(AG)and GERD.AIM To confirm the inverse correlation between AG and the occurrence and severity of GERD.METHODS Individuals receiving health checkups who underwent upper gastrointestinal endoscopy at Seoul National University Healthcare System Gangnam Center were included.The grade of reflux esophagitis was evaluated according to the Los Angeles classification.Endoscopic AG(EAG)was categorized into six grades.Serologic AG(SAG)was defined as pepsinogen I≤70 ng/m L and pepsinogen I/II ratio≤3.0.The association between the extent of EAG and SAG and the occurrence and severity of GERD was evaluated using multivariate logistic regression analysis.RESULTS In total,4684 individuals with GERD were compared with 21901 healthy controls.In multivariate logistic regression analysis,advanced age,male sex,body mass index>23 kg/m2,presence of metabolic syndrome,current smoking,and alcohol consumption were associated with an increased risk of GERD.Seropositivity for H.pylori immunoglobulin G antibodies was associated with a decreased risk of GERD.There was an inverse correlation between the extent of EAG and occurrence of GERD:Odds ratio(OR),1.01[95%confidence interval(CI):0.90-1.14]in C1,0.87(0.78-0.97)in C2,0.71(0.62-0.80)in C3,0.52(0.44-0.61)in O1,0.37(0.29-0.48)in O2,and 0.28(0.18-0.43)in O3.Additionally,the extent of EAG showed an inverse correlation with the severity of GERD.The presence of SAG was correlated with a reduced risk of GERD(OR=0.49,95%CI:0.28-0.87,P=0.014).CONCLUSION The extent of EAG and SAG exhibited strong inverse relationships with the occurrence and severity of GERD.AG followed by H.pylori infection may be independently protect against GERD.

Effect of Hewei-Decoction on chronic atrophic gastritis and eradication of Helicobacter pylori

AIM: To demonstrate the effect of Hewei-Decoction (Decoction for regulating the stomach) on chronic atrophic gastritis (CAG) and eradication of Helicobacter pylori. METHODS: Ninety patients with CAG entering the investigation were divided into six differentiation syndromes, based on their major symptoms and signs. Hewei-Decoction was taken by all the patients orally for 4 or 8 wk. The efficacy was assessed by both the composite accumulation of reduced scores of major symptoms and the eradication of H pylori.X2 test was used to compare the efficacy between H pylori-positive and negative cases, and to disclose the relationship between efficacy and eradication of H pylori. RESULTS: In patients with six different syndrome types, the efficacy of Hewei-Decoction was 91.67% (11/12), 92.86% (13/14), 97.22% (35/36), 87.50% (14/16), 75.00% (6/8), 75.00% (3/4) respectively. The rate of highly efficacious was 58.33% (7/12), 50.00% (7/14), 77.78% (28/36), 62.50% (10/16), 12.50% (1/8) and 25.00% (1/4), respectively. The total efficacy was 91.11% (82/90), and the rate of highly efficacious was 60.00% (54/90). The eradication rate of H pylori was 67.86% (38/56). The therapeutic effect of Hewei-Decoction was better in H pylori positive cases than that in H pylori-negative cases with the total effect of 96.43% vs 82.35% (P<0.05). In 56 H pylori positive cases, the therapeutic effect was better in H pylori eradicated cases than that in H pylori-existent cases with the total effect of 97.37% vs 72.22% (P<0.01). CONCLUSION: Hewei-Decoction is effective in most cases of all the syndrome types. The results indicate that eradication of H pylori is one of the important mechanisms for alleviation of symptoms and signs. Also, the decoction is efficacious in H pylori-negative cases.