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.

Incidence and prevalence of gastric neuroendocrine tumors in patients with chronic atrophic autoimmune gastritis

BACKGROUND The incidence of type I gastric neuroendocrine neoplasms(gNENs)has increased significantly over the past 50 years.Although autoimmune gastritis(AIG)increases the likelihood of developing gNENs,the exact incidence and prevalence of this association remain unclear.AIM To evaluate the incidence and prevalence of type I gNENs in a cohort of patients with a histological diagnosis of AIG.METHODS Patients with a histological diagnosis of AIG were enrolled between October 2020 and May 2022.Circulating levels of CgA and gastrin were assessed at enrollment.Included patients underwent regular endoscopic follow-up to detect gastric neoplastic lesions,enterochromaffin-like(ECL)cell hyperplasia,and the development of gNEN.RESULTS We included 176 patients[142 women(80.7%),median age 64 years,interquartile range(IQR)53–71 years]diagnosed with AIG between January 1990 and June 2022.At enrollment.One hundred and sixteen patients(65.9%)had ECL hyperplasia,of whom,29.5%had simple/linear,30.7%had micronodular,and 5.7%had macronodular type.The median follow-up time was 5(3–7.5)years.After 1032 person-years,33 patients developed a total of 50 type I gNENs,with an incidence rate of 0.057 person-years,corresponding to an annual cumulative incidence of 5.7%.Circulating CgA levels did not significantly differ between AIG patients who developed gNENs and those who did not.Conversely,gastrin levels were significantly higher in AIG patients who developed gNENs[median 992 pg/mL IQR=449–1500 vs 688 pg/mL IQR=423–1200,P=0.03].Calculated gastrin sensitivity and specificity were 90.9%and 1.4%,respectively,with an overall diagnostic accuracy of 30%and a calculated area under the gastrin receiver operating characteristic curve(AUROC or AUC)of 0.53.CONCLUSION Type I gNENs are a significant complication in AIG.Gastrin’s low diagnostic accuracy prevents it from serving as a marker for early diagnosis.Effective strategies for early detection and treatment are needed.

Research status and hotspots of autoimmune gastritis:A bibliometric analysis

BACKGROUND As an emerging potential risk factor for gastric cancer,autoimmune gastritis(AIG)has garnered increasing attention from researchers.AIM To analyze the research overview and popular topics in the field of AIG using bibliometrics.METHODS Relevant publications on AIG in the Web of Science Core Collection were collated,and data visualization and analysis of the number of publications,countries,institutions,journals,authors,keywords,and citations were performed using software such as VOSviewer,CiteSpace,and Scimago Graphic.RESULTS In total,316 relevant articles were included in the analysis.From 2015 to 2022,the number of publications increased annually.The countries,institutions,authors,and journals with the highest number of publications in this field were Italy,Monash University,Toh BH,and Internal Medicine.The main keywords used in this field of research were pathogenesis,Helicobacter pylori,autoantibody,parietal cell antibody,atrophic gastritis,classification,diagnosis,autoimmune disease,risk,cancer,gastric cancer,vitamin B12 deficiency,and pernicious anemia.The following directions may be popular for future research:(1)The role of Helicobacter pylori in the pathogenesis of AIG;(2)diagnostic criteria for AIG and reference values for serum antibodies;(3)comorbidity mechanisms between AIG and other autoimmune diseases;(4)specific risks of AIG complicating gastric and other cancers;and(5)the role of vitamin B12 supplementation in patients with early-stage AIG.CONCLUSION This bibliometric analysis reported on popular topics and emerging trends in AIG,with diagnosis and prognosis being research hotspots in this field.

Micronutrient deficiencies in patients with chronic atrophic autoimmune gastritis: A review

Chronic atrophic autoimmune gastritis (CAAG) is an organ-specific autoimmune disease characterized by an immune response, which is directed towards the parietal cells and intrinsic factor of the gastric body and fundus and leads to hypochlorhydria, hypergastrinemia and inadequate production of the intrinsic factor. As a result, the stomach’s secretion of essential substances, such as hydrochloric acid and intrinsic factor, is reduced, leading to digestive impairments. The most common is vitamin B12 deficiency, which results in a megaloblastic anemia and iron malabsorption, leading to iron deficiency anemia. However, in the last years the deficiency of several other vitamins and micronutrients, such as vitamin C, vitamin D, folic acid and calcium, has been increasingly described in patients with CAAG. In addition the occurrence of multiple vitamin deficiencies may lead to severe hematological, neurological and skeletal manifestations in CAAG patients and highlights the importance of an integrated evaluation of these patients. Nevertheless, the nutritional deficiencies in CAAG are largely understudied. We have investigated the frequency and associated features of nutritional deficiencies in CAAG in order to focus on any deficit that may be clinically significant, but relatively easy to correct. This descriptive review updates and summarizes the literature on different nutrient deficiencies in CAAG in order to optimize the treatment and the follow-up of patients affected with CAAG.

Diagnosis of autoimmune gastritis by high resolution magnification endoscopy

Endoscopic visualisation of gastric atrophy is usually not feasible with conven.tional endoscopy. Magnifying endoscopy is helpful to analyze the subepithelial microvascular architecture as well as the mucosal surface microstructure without tissue biopsy. Using this technique we were able to describe the normal gastric microvasculature pattern and we also identified characteristic patterns in two cases of autoimmune atrophic gastritis.

Autoimmune gastritis presenting as iron deficiency anemia in childhood

AIM: To characterize clinical, laboratorial, and histological profile of pediatric autoimmune gastritis in the setting of unexplained iron deficiency anemia investigation.

Effect of endogenous hypergastrinemia on gallbladder volume and ejection fraction in patients with autoimmune gastritis

BACKGROUND: Gastrin has a cholecystokinetic action on gallbladder motility, and cholecystokinin and gastrin act directly on the smooth muscle of the gallbladder. The aim of this study was to investigate the effect of endogenous hypergastrinemia on gallbladder motility in patients with autoimmune gastritis. METHODS: Forty-one patients (29 females, 12 males; mean age, 46 years) with autoimmune gastritis and 29 healthy subjects (17 females, 12 males; mean age, 44.8 years) were enrolled in the study. Fasting and postprandial gallbladder volumes were measured ultrasonographically with the ellipsoid technique and the ejection fraction of the gallbladder was calculated from fasting and postprandial volumes. All subjects were investigated after 12 hours of fasting and 30 minutes after a standard test meal. RESULTS: The gallbladder ejection fraction (%) of the patients with autoimmune gastritis was lower than that of the control group (46.06±18.28% vs 55.03±14.67%, P=0.032). There was no difference between patients with autoimmune gastritis and the control group in terms of the mean fasting gallbladder volume (30.38±12.85 vs 29.27±9.91 cm 3 , P=0.189) and the mean postprandial gallbladder volume (15.67±8.32 vs 13.44±7.69 cm 3 , P=0.258). Logistic regression analysis of baseline parameters revealed that 'abdominal bloating' was a risk factor for the low gallbladder ejection fraction in autoimmune gastritis patients (P=0.045, F=4.40). In addition, logistic regression analysis of baseline parameters revealed that smoking (n=5, P=0.025, F=5.44) is a predictor of low gallbladder ejection fraction in patients with autoimmune gastritis.CONCLUSIONS: Patients with endogenous hypergastrinemia have a low gallbladder ejection fraction compared with healthy controls. This study shows that at least part of upper gastrointestinal symptoms observed in this patient population may be due to altered gallbladder motility.

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.

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.

Association of autoimmune type atrophic corpus gastritis with Helicobacter pylori infection

AIM:To study the association between Helicobacter pylori(H.pylori)infection and autoimmune type atrophic gastritis. METHODS:Twenty-three patients with different grades of atrophic gastritis were analysed using enzyme immunoassay-based serology,immunoblot-based serology,and histology to reveal a past or a present H.pylori infection.In addition,serum markers for gastric atrophy(pepsinogenⅠ,pepsinogenⅠ/Ⅱand gastrin)and autoimmunity[parietal cell antibodies(PCA), and intrinsic factor(IF),antibodies]were determined. RESULTS:Of the 14 patients with severe gastricatrophy,as demonstrated by histology and serum markers,and no evidence for an ongoing H.pylori infection,eight showed H.pylori antibodies by immunoblotting.All eight had elevated PCA and 4/8 also had IF antibodies.Of the six immunoblot-negative patients with severe corpus atrophy,PCA and IF antibodies were detected in four.Among the patients with low to moderate grade atrophic gastritis(all except one with an ongoing H.pylori infection),serum markers for gastric atrophy and autoimmunity were seldom detected.However,one H.pylori negative patient with mild atrophic gastritis had PCA and IF antibodies suggestive of a pre-atrophic autoimmune gastritis. CONCLUSION:Signs of H.pylori infection in autoimmune gastritis,and positive autoimmune serum markers in H.pylori gastritis suggest an etiological role for H.pylori in autoimmune gastritis.

Validation of diagnostic strategies of autoimmune atrophic gastritis:A case report

BACKGROUND Autoimmune atrophic gastritis(AAG)is a type of chronic gastritis that mainly affects the gastric corpus.Due to the lack of standard diagnostic criteria and overlaps with the courses of Helicobacter pylori-related atrophic gastritis,reports on the diagnostic strategy of AAG at an early stage are limited.CASE SUMMARY A 71-year-old woman with severe anemia was diagnosed with AAG.Endoscopic views and pathological findings showed the coexistence of normal mucosa in the gastric antrum and atrophic mucosa in the gastric fundus.Serological tests showed that anti-parietal cell antibodies and anti-intrinsic factor antibodies were both positive.Immunohistochemical results,which showed negative H^(+)-K^(+)ATPase antibody staining and positive chromogranin A(CgA)staining,confirmed the mechanism of this disease.After vitamin B12 and folic acid supplementation,the patient recovered well.CONCLUSION Successful diagnosis of AAG includes serological tests,endoscopic characteristics,and immunohistochemistry for H^(+)-K^(+)ATPase and CgA antibodies.

Endoscopic resection for early gastric cancer:Towards a global understanding

Gastric cancer is widespread globally,and disease diagnosis is accompanied by high mortality and morbidity rates.However,prognoses and survivability have improved following implementation of surveillance and screening programs,which have led to earlier diagnoses.Indeed,early diagnosis itself supports increased surgical curability,which is the main treatment goal and guides therapeutic choice.The most recent Japanese guidelines for endoscopic submucosal dissection and endoscopic mucosal resection for early gastric cancer consider the degree of endoscopic curability in relation to the characteristics of the gastric lesions.In clinical practice,the management approach for both prevention and treatment should be similar to that of colon lesions;however,unlike the established practices for colorectal cancer,the diagnostic and therapeutic pathways are not shared nor widespread for gastric cancer.Ultimately,this negatively impacts the opportunity to perform an endoscopic resection with curative intent.

Helicobacter pylori-induced inflammation masks the underlying presence of low-grade dysplasia on gastric lesions

BACKGROUND Helicobacter pylori(H.pylori)infection has been associated with a long-term risk of precancerous gastric conditions(PGC)even after H.pylori eradication.AIM To investigate the efficacy of High-Resolution White-Light Endoscopy with Narrow-Band Imaging in detecting PGC,before/after H.pylori eradication.METHODS We studied 85 consecutive patients with H.pylori-related gastritis with/without PGC before and 6 mo after proven H.pylori eradication.Kimura-Takemoto modified and endoscopic grading of gastric intestinal metaplasia classifications,were applied to assess the endoscopic extension of atrophy and intestinal metaplasia.The histological result was considered to be the gold standard.The Sydney System,the Operative-Link on Gastritis-Assessment,and the Operative-Link on Gastric-Intestinal Metaplasia were used for defining histological gastritis,atrophy and intestinal metaplasia,whereas dysplasia was graded according to World Health Organization classification.Serum anti-parietal cell antibody and anti-intrinsic factor were measured when autoimmune atrophic gastritis was suspected.RESULTS After H.pylori eradication histological signs of mononuclear/polymorphonuclear cell infiltration and Mucosal Associated Lymphoid Tissue-hyperplasia,disappeared or decreased in 100%and 96.5%of patients respectively,whereas the Operative-Link on Gastritis-Assessment and Operative-Link on Gastric-Intestinal Metaplasia stages did not change.Low-Grade Dysplasia prevalence was similar on random biopsies before and after H.pylori eradication(17.6%vs 10.6%,P=0.19),but increased in patients with visible lesions(0%vs 22.4%,P<0.0001).At a multivariate analysis,the probability for detecting dysplasia after resolution of H.pylori-related active inflammation was higher in patients with regression or reduction of Mucosal Associated Lymphoid Tissue hyperplasia,greater alcohol consumption,and anti-parietal cell antibody and/or anti-intrinsic factor positivity[odds ratio(OR)=3.88,95%confidence interval(CI):1.31-11.49,P=0.01;OR=3.10,95%CI:1.05-9.12,P=0.04 and OR=5.47,95%CI:1.33-22.39,P<0.04,respectively].CONCLUSION High-Resolution White-Light Endoscopy with Narrow-Band Imaging allows an accurate diagnosis of Low-Grade Dysplasia on visible lesions after regression of H.pylori-induced chronic gastritis.Patients with an overlap between autoimmune/H.pylori-induced gastritis may require more extensive gastric mapping.