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.

History of chronic gastritis:How our perceptions have changed

Currently,the diagnostic strategy for chronic gastritis(CG)is aimed not just at fixing the presence of gastric mucosal inflammation,but also at gastric cancer(GC)risk stratification in a particular patient.Modern classification approach with the definition of the stage of gastritis determines the need,activities and frequency of dynamic monitoring of a patient.However,this attitude to the patient suffering from CG was far from always.The present publication is a literature review describing the key milestones in the history of CG research,from the description of the first observations of inflammation of the gastric mucosa,assessment of gastritis as a predominantly functional disease,to the advent of endoscopy of the upper digestive tract and diagnostic gastric biopsy,assessment of the role of Helicobacter pylori infection in progression of inflammatory changes to atrophy,intestinal metaplasia,dysplasia and GC.

Immune checkpoint inhibitor-associated gastritis:Patterns and management

Immune checkpoint inhibitors(ICIs)are widely used due to their effectiveness in treating various tumors.Immune-related adverse events(irAEs)are defined as adverse effects resulting from ICI treatment.Gastrointestinal irAEs are a common type of irAEs characterized by intestinal side effects,such as diarrhea and colitis,which may lead to the cessation of ICIs.Although irAE gastritis is rarely reported,it may lead to serious complications such as gastrorrhagia.Furthermore,irAE gastritis is often difficult to identify early due to its diverse symptoms.Although steroid hormones and immunosuppressants are commonly used to reverse irAEs,the best regimen and dosage for irAE gastritis remains uncertain.In addition,the risk of recurrence of irAE gastritis after the reuse of ICIs should be considered.In this editorial,strategies such as early identification,pathological diagnosis,mana-gement interventions,and immunotherapy rechallenge are discussed to enable clinicians to better manage irAE gastritis and improve the prognosis of these patients.

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.

Urinary metabolic profiles during Helicobacter pylori eradication in chronic gastritis

BACKGROUND Helicobacter pylori(H.pylori)infection is a major risk factor for chronic gastritis,affecting approximately half of the global population.H.pylori eradication is a popular treatment method for H.pylori-positive chronic gastritis,but its mecha-nism remains unclear.Urinary metabolomics has been used to elucidate the mechanisms of gastric disease treatment.However,no clinical study has been conducted on urinary metabolomics of chronic gastritis.AIM To elucidate the urinary metabolic profiles during H.pylori eradication in patients with chronic gastritis.METHODS We applied LC–MS-based metabolomics and network pharmacology to in-vestigate the relationships between urinary metabolites and H.pylori-positive chronic gastritis via a clinical follow-up study.RESULTS Our study revealed the different urinary metabolic profiles of H.pylori-positive chronic gastritis before and after H.pylori eradication.The metabolites regulated by H.pylori eradication therapy include cis-aconitic acid,isocitric acid,citric acid,L-tyrosine,L-phenylalanine,L-tryptophan,and hippuric acid,which were involved in four metabolic pathways:(1)Phenylalanine metabolism;(2)phenylalanine,tyrosine,and tryptophan biosynthesis;(3)citrate cycle;and(4)glyoxylate and dicarboxylate metabolism.Integrated metabolomics and network pharmacology revealed that MPO,COMT,TPO,TH,EPX,CMA1,DDC,TPH1,and LPO were the key proteins involved in the biological progress of H.pylori eradication in chronic gastritis.CONCLUSION Our research provides a new perspective for exploring the significance of urinary metabolites in evaluating the treatment and prognosis of H.pylori-positive chronic gastritis patients.

NLRP3-mediated autophagy dysfunction links gut microbiota dysbiosis to tau pathology in chronic sleep deprivation

Emerging evidence indicates that sleep deprivation(SD)can lead to Alzheimer’s disease(AD)-related pathological changes and cognitive decline.However,the underlying mechanisms remain obscure.In the present study,we identified the existence of a microbiota-gut-brain axis in cognitive deficits resulting from chronic SD and revealed a potential pathway by which gut microbiota affects cognitive functioning in chronic SD.Our findings demonstrated that chronic SD in mice not only led to cognitive decline but also induced gut microbiota dysbiosis,elevated NLRP3 inflammasome expression,GSK-3βactivation,autophagy dysfunction,and tau hyperphosphorylation in the hippocampus.Colonization with the“SD microbiota”replicated the pathological and behavioral abnormalities observed in chronic sleep-deprived mice.Remarkably,both the deletion of NLRP3 in NLRP3-/-mice and specific knockdown of NLRP3 in the hippocampus restored autophagic flux,suppressed tau hyperphosphorylation,and ameliorated cognitive deficits induced by chronic SD,while GSK-3βactivity was not regulated by the NLRP3 inflammasome in chronic SD.Notably,deletion of NLRP3 reversed NLRP3 inflammasome activation,autophagy deficits,and tau hyperphosphorylation induced by GSK-3βactivation in primary hippocampal neurons,suggesting that GSK-3β,as a regulator of NLRP3-mediated autophagy dysfunction,plays a significant role in promoting tau hyperphosphorylation.Thus,gut microbiota dysbiosis was identified as a contributor to chronic SD-induced tau pathology via NLRP3-mediated autophagy dysfunction,ultimately leading to cognitive deficits.Overall,these findings highlight GSK-3βas a regulator of NLRP3-mediated autophagy dysfunction,playing a critical role in promoting tau hyperphosphorylation.

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.

Digital pathology-based artificial intelligence models for differential diagnosis and prognosis of sporadic odontogenic keratocysts

Odontogenic keratocyst(OKC)is a common jaw cyst with a high recurrence rate.OKC combined with basal cell carcinoma as well as skeletal and other developmental abnormalities is thought to be associated with Gorlin syndrome.Moreover,OKC needs to be differentiated from orthokeratinized odontogenic cyst and other jaw cysts.Because of the different prognosis,differential diagnosis of several cysts can contribute to clinical management.We collected 519 cases,comprising a total of 2157 hematoxylin and eosinstained images,to develop digital pathology-based artificial intelligence(AI)models for the diagnosis and prognosis of OKC.The Inception_v3 neural network was utilized to train and test models developed from patch-level images.Finally,whole slide imagelevel AI models were developed by integrating deep learning-generated pathology features with several machine learning algorithms.The AI models showed great performance in the diagnosis(AUC=0.935,95%CI:0.898–0.973)and prognosis(AUC=0.840,95%CI:0.751–0.930)of OKC.The advantages of multiple slides model for integrating of histopathological information are demonstrated through a comparison with the single slide model.Furthermore,the study investigates the correlation between AI features generated by deep learning and pathological findings,highlighting the interpretative potential of AI models in the pathology.Here,we have developed the robust diagnostic and prognostic models for OKC.The AI model that is based on digital pathology shows promise potential for applications in odontogenic diseases of the jaw.

Efficacy of fexuprazan compared with rebamipide in Korean patients with gastritis:A matching-adjusted indirect comparison

BACKGROUND Gastritis is one of the most frequently diagnosed diseases requiring medical treatment in South Korea.Fexuprazan,a novel potassium-competitive acid blocker,has been approved for treating gastritis and erosive esophagitis.Meanwhile,rebamipide is the most commonly used mucoprotective agent for acute and chronic gastritis in real-world settings in South Korea.However,there have been no studies comparing the efficacy of these two drugs yet.AIM To compare the efficacy of fexuprazan with that of rebamipide for acute and chronic gastritis.METHODS This was a matching-adjusted indirect comparison.Individual patient data from a phase III study of fexuprazan(10 mg BID)were compared with cumulative data from two matching studies of rebamipide(100 mg TID).Erosion improvement and healing rates were compared between two weeks of fexurapan,two weeks of rebamipide,and four weeks of rebamipide.The two main outcome variables were presented as percentages,and the risk differences(RD)and 95%confidence intervals(CI)were calculated for the relative treatment effects.RESULTS In the primary analysis,the erosion improvement and healing rates after a twoweek treatment with fexuprazan were 64.5%and 53.2%,respectively,while a twoweek treatment with rebamipide resulted in erosion improvement and healing rates of 43.6%(RD:21.0%;95%CI:9.6-32.3;P<0.01)and 35.6%(RD:17.6%;95%CI:6.1-29.2;P=0.003),respectively.In the additional analysis,the erosion improvement and healing rates for the two-week fexuprazan treatment(64.2%and 51.2%,respectively)were similar to those obtained during a four-week treatment with rebamipide(60.6%;RD:3.6%;95%CI:-9.8,17.0;P=0.600 and 53.5%;RD:-2.3%;95%CI:-16.1,11.5;P=0.744,respectively).CONCLUSION The two-week fexuprazan treatment was superior to the two-week rebamipide treatment and similar to the fourweek rebamipide treatment for patients with gastritis.

Metabolic dynamics in chronic gastritis:Examining urinary profiles post Helicobacter pylori eradication

Chronic gastritis is the persistent and insidious inflammation of the gastric lining.Helicobacter pylori(H.pylori)has been identified as the most common cause of chronic gastritis and consequently elimination of H.pylori can lead to its cure.This editorial explores the use of urinary metabolic profiles before and after eradication to identify biomarkers that can aid in prognosis and treatment.Despite providing promising insights,there are limitations such as a small sample size(17 patients),a narrow treatment period of 2 wk,and treatment heterogeneity,which raise concerns.Nevertheless,these findings have opened a gateway to enhancing the treatment and prognosis of chronic gastritis through urinary metabolomics.

Going straight for the gut:gut-brain axis pathology and treatment of Parkinson's disease

This perspective focuses on the recent literature regarding the role of the gut-brain axis(GBA) in fecal microbiota transplantation(FMT) and stem cell therapy(SCT) in Parkinson's disease(PD).PD is the second most common neurodegenerative disease in the United States,yet therapies remain limited.Current research suggests that the GBA may play a role in the pathogenesis of PD.GBAbased FMT as well as SCT offer promising new avenues for PD treatment.Pro bing the interactions between FMT and SCT with the GBA may reveal novel therapeutics for PD.

Amyloid-beta pathology-induced nanoscale synaptic disruption:the case of the GABA_B-GIRK assembly

Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic plasticity.AD has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.

Hysterectomies for Gynaecological Pathology: 56 Cases at the Segou Regional Hospital in Mali

Introduction: Hysterectomy is a surgical procedure involving partial or total removal of the uterus. It is the most common gynaecological surgery in the world. Objective: To describe the epidemio-clinical and prognostic aspects of gynaecological hysterectomies. Patients and methods: This was an 18-month retrospective prospective descriptive study with a six-month follow-up period from 1 December 2020 to 31 May 2022 carried out in the gynaecology department of the Segou regional hospital. Results: Fifty-six (56) hysterectomies were performed out of 118 gynaecological surgical procedures (47.45%). The mean age was 47 ± 11.77 years. Large multiparous women were the most common (50%), with an average parity of 4.58. The main indications were uterine fibroids (30.4%), precancerous lesions of the cervix (17.85%) and uterine prolapse (17.85%). The abdominal route was the most commonly used surgical route (82.14%). Hysterectomy was total in 100% of cases and associated with bilateral adnexectomy in 48.2% of cases. The intra- and post-operative prognosis was satisfactory in 94.6% of cases. No deaths were recorded. The average length of stay was 3.28 days, irrespective of the surgical approach. Three cases of dyspareunia were noted among those who had resumed sexual activity.

Estimate the Prevalence of Helicobacter pylori Infection among Diabetes & Non-Diabetes Mellitus Patients and Its Correlation with Malignant Gastritis Patients Attending in Lower Shabelle Region (Somalia)

Background: Several conducted studies have reported a higher and more frequent Helicobacter pylori infection rate in type 2 diabetes mellitus (T2DM). The aim of this study was to estimation the prevalence of H. pylori and its association between H. pylori infection and T2DM. Materials and Methods: A sectional-cross study was conducted based on 200 patients studded with socioeconomic characteristics through a questionnaire & H. pylori was diagnosed by serum anti-H. pylori immunoglobulin G (IgG) and IgA. Furthermore, patients were investigated for fasting blood glucose (FBG) levels, glycosylated hemoglobin (HbA1c), serum cholesterol, and other biochemistry parameters. Results: The findings showed The prevalence of Hp positive infection was significantly higher in the total sample was 134 with (67%). While 66 out of 200 patients with (33%) was H. pylori negative infection. of H. pylori. Further, the mean values were statistically significant for diabetes with H. pylori infection for IgG > 300 titer and IgA > 250 titer, regarding, HbA1C (7.52 ± 0.41) (P Conclusions: The current study revealed that H. pylori prevalence infections were significantly higher in diabetic patients studied compared to non-diabetic patients. Furthermore, T2DM patients infected with H. pylori positive reported a higher prevalence rate of symptoms than H. pylori negative.

Gastric microbiota transplantation as a potential treatment for immune checkpoint inhibitor-associated gastritis

Immune-related adverse events(irAEs)are complications of the use of immune checkpoint inhibitors(ICIs).ICI-associated gastritis is one of the main irAEs.The gastric microbiota is often related to the occurrence and development of many gastric diseases.Gastric microbiota adjustment may be used to treat gastric disorders in the future.Faecal microbiota transplantation can alter the gut microbiota of patients and has been used for treating ICI-associated colitis.Therefore,we propose gastric microbiota transplantation as a supplementary treatment for patients with ICI-associated gastritis who do not respond well to conventional therapy.

Non-improvement of atrophic gastritis in cases of gastric cancer after successful Helicobacter pylori eradication therapy

BACKGROUND Helicobacter pylori(H.pylori)infection is closely related to the development of gastric cancer(GC).However,GC can develop even after H.pylori eradication.Therefore,it would be extremely useful if GC could be predicted after eradication.The Kyoto classification score for gastritis(GA)is closely related to cancer risk.However,how the score for GC changes after eradication before onset is not well understood.AIM To investigate the characteristics of the progression of Kyoto classification scores for GC after H.pylori eradication.METHODS Eradication of H.pylori was confirmed in all patients using either the urea breath test or the stool antigen test.The Kyoto classification score of GC patients was evaluated by endoscopy at the time of event onset and three years earlier.In ad-dition,the modified atrophy score was evaluated and compared between the GC group and the control GA group.RESULTS In total,30 cases of early GC and 30 cases of chronic GA were evaluated.The pathology of the cancer cases was differentiated adenocarcinoma,except for one case of undifferentiated adenocarcinoma.The total score of the Kyoto classifi-cation was significantly higher in the GC group both at the time of cancer onset and three years earlier(4.97 vs 3.73,P=0.0034;4.2 vs 3.1,P=0.0035,respectively).The modified atrophy score was significantly higher in the GC group both at the time of cancer onset and three years earlier and was significantly improved only in the GA group(5.3 vs 5.3,P=0.5;3.73 vs 3.1,P=0.0475,respectively).CONCLUSION The course of the modified atrophy score is useful for predicting the onset of GC after eradication.Patients with severe atrophy after H.pylori eradication require careful monitoring.

Managing immune checkpoint inhibitor-associated gastritis: Insights and strategies

Immune checkpoint inhibitors(ICIs)are widely used due to their effectiveness in treating various tumors.Immune-related adverse events(irAEs)are defined as adverse effects resulting from ICI treatment.Gastrointestinal irAEs are a common type of irAEs characterized by intestinal side effects,such as diarrhea and colitis,which may lead to the discontinuation of ICIs.

Autoimmune gastritis studies and gastric cancer: True renaissance or bibliometric illusion

A bibliometric analysis of studies dedicated to autoimmune gastritis(AIG)recently published demonstrated a noteworthy surge in publications over the last three years.This can be explained by numerous publications from different regions of the world reporting the results of several studies that stimulated reassessment of our view of AIG as a precancerous condition.Follow-up studies and retrospective analyses showed that the risk of gastric cancer(GC)in AIG patients is much lower than expected if the patients ever being infected with Helicobacter pylori(H.pylori)were excluded.The low prevalence of precancerous lesions,such as the incomplete type of intestinal metaplasia,may explain the low risk of GC in AIG patients because the spasmolytic polypeptide-expressing metaplasia commonly observed in AIG does not involve clonal reprogramming of the gastric gland and can be considered as an adaptive change rather than a true precancerous lesion.However,changes in gastric secretion due to the progression of gastric atrophy during the course of AIG cause changes in the gastric microbiome,stimulating the growth of bacterial species such as streptococci,which may promote the development of precancerous lesions and GC.Thus,Streptococcus anginosus exhibited a robust proinflammatory response and induced the gastritis-atrophy-metaplasia-dysplasia sequence in mice,reproducing the wellestablished process for carcinogenesis associated with H.pylori.Prospective studies in H.pylori-naïve patients evaluating gastric microbiome changes during the long-term course of AIG might provide an explanation for the enigmatic increase in GC incidence in the last decades in younger cohorts,which has been reported in economically developed countries.

Using MsfNet to Predict the ISUP Grade of Renal Clear Cell Carcinoma in Digital Pathology Images

Clear cell renal cell carcinoma(ccRCC)represents the most frequent form of renal cell carcinoma(RCC),and accurate International Society of Urological Pathology(ISUP)grading is crucial for prognosis and treatment selection.This study presents a new deep network called Multi-scale Fusion Network(MsfNet),which aims to enhance the automatic ISUP grade of ccRCC with digital histopathology pathology images.The MsfNet overcomes the limitations of traditional ResNet50 by multi-scale information fusion and dynamic allocation of channel quantity.The model was trained and tested using 90 Hematoxylin and Eosin(H&E)stained whole slide images(WSIs),which were all cropped into 320×320-pixel patches at 40×magnification.MsfNet achieved a micro-averaged area under the curve(AUC)of 0.9807,a macro-averaged AUC of 0.9778 on the test dataset.The Gradient-weighted Class Activation Mapping(Grad-CAM)visually demonstrated MsfNet’s ability to distinguish and highlight abnormal areas more effectively than ResNet50.The t-Distributed Stochastic Neighbor Embedding(t-SNE)plot indicates our model can efficiently extract critical features from images,reducing the impact of noise and redundant information.The results suggest that MsfNet offers an accurate ISUP grade of ccRCC in digital images,emphasizing the potential of AI-assisted histopathological systems in clinical practice.

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.