Differential diagnosis of gastric low- and high grade dysplasia using C6orf15 protein.

OBJECTIVE: To investigate the expression of C6orf15 protein in gastric endoscopic biopsy specimens and its usage as an ancillary diagnostic biomarker in determining the grade of gastric dysplasia. METHODS: We selected 102 patients with gastric endoscopic biopsy specimens from Jinling Hospital. These were divided into four groups: 22 cases of gastric mucosal benign lesions, 28 with low-grade dysplasia (LGD, intestinal-type: 21 cases，foveolar-type: 7cases), 28 with high-grade dysplasia (HGD, intestinal-type: 20 cases，foveolar-type: 8 cases), and 24 cases of gastric adenocarcinoma. We examined the expressions of C6orf15, P53, and Ki67 in 102 gastric endoscopic biopsy specimens, including 47 cases with accompanying endoscopic submucosal dissection (ESD) specimens, using immunohistochemistry. RESULTS: In gastric HGD and gastric adenocarcinoma, the c6orf15 protein exhibits diffuse and strong cytoplasmic expression in tumor cells. Conversely, in gastric LGD and benign gastric mucosal lesions, the c6orf15 protein shows negative or faint yellow cytoplasmic staining. The expression rate of C6orf15 in high-grade gastric dysplasia (HGD, 93 %) and gastric adenocarcinoma (100 %) was significantly higher than in the gastric mucosal benign lesion group (0 %) and the low-grade dysplasia (LGD, 7 %) group (P < 0.001). CONCLUSION: The detection of C6orf15 protein expression could serve as a valuable adjunctive diagnostic tool for distinguishing between gastric HGD, LGD, and benign lesions. The combined assessment of C6orf15, P53, and Ki67 expressions may be beneficial in determining the grade of gastric dysplasia and evaluating the risk of progression in gastric mucosal lesions in clinical practice.

Microbiota-Gastric Cancer Interactions and the Potential Influence of Nutritional Therapies.

Gastric cancer (GC) is one of the most common causes of cancer deaths, and GC treatments represent a large area of research. Although initially regarded as a sterile organ and unsuitable for microbial communities, the discovery of Helicobacter pylori made us realize that some microbes can colonize the stomach. In recent years, growing interest in gastric bacteria has expanded to the gut microbiota and, more recently, to the oral microbiota. Indeed, the oral-gastric-gut microbiota axis may play a crucial role in maintaining homeostasis, while changes in microbiota composition in GC patients can influence clinical outcomes. On the one hand, the microbiota and its metabolites may significantly influence the progression of GC, while anti-GC treatments such as gastrectomy and chemotherapy may significantly impact the oral-gastric-gut microbiota axis of GC patients. In this context, the role of nutritional therapies, including diet, prebiotics, and probiotics, in treating GC should not be underestimated. Wit this review, we aim to highlight the main role of the gastric, oral, and gut microbiota in GC onset and progression, representing potential future biomarkers for early GC detection and a target for efficient nutritional therapies during the course of GC.

Heat shock protein 70 is involved in polaprezinc driven cell protection against Helicobacter pylori-induced injury.

Polaprezinc (PZ) plays a role in the protection of gastric mucosa and inhibiting Helicobacter pylori (H. pylori) growth in vitro. The objective of this study was to determine the protective effects of PZ on human gastric epithelial cells (GES-1) against H. pylori-induced damage, while also examining heat shock protein 70 (HSP70) as a potential underlying factor in this protection. Our findings revealed that PZ exerted bactericidal effects against H. pylori strains. We also observed that PZ mitigated the H. pylori-induced damage to GES-1 cells by increasing cell viability, reducing LDH release, and decreasing the secretion of pro-inflammatory factors such as MCP-1 and IL-6. Co-culturing PZ with GES-1 cells significantly up-regulated the GES-1 HSP70 expression in both a time and dose-dependent manner. Pre-incubating (for 12 h) or co-culturing (for 24 h) GES-1 cells with PZ reversed the down-regulation of HSP70 in GES-1 cells caused by H. pylori infection. However, when quercetin was used to inhibit the up-regulation of HSP70 in GES-1 cells, the protective effect of PZ on GES-1 cells was significantly reduced. Based on the results of this study, PZ exhibits a protective role on GES-1 cells against H. pylori injury, as well as a direct bactericidal effect on H. pylori. HSP70 is involved in the PZ-driven host cell protection against H. pylori injury. These findings provide insight into alternative strategies for H. pylori treatment.

Helicobacter pylori-positive chronic atrophic gastritis and cellular senescence.

BACKGROUND: Chronic atrophic gastritis (CAG) is a pathological stage in the Correa's cascade, whereby Helicobacter pylori (H. pylori) infection is the primary cause. Cellular senescence is an inducing factor for cancer occurrence and cellular senescence is an obvious phenomenon in gastric mucosal tissues of H. pylori-positive CAG patients. METHODS: In this review, we collated the information on cellular senescence and H. pylori-positive CAG. RESULTS: At present, only a few studies have observed the effect of cellular senescence on precancerous lesions. In combination with the latest research, this review has collated the information on cellular senescence and H. pylori-positive CAG from four aspects- telomere shortening, DNA methylation, increased reacive oxygen species (ROS) production, and failure of autophagy. CONCLUSION: This is expected to be helpful for exploring the relevant mechanisms underlying inflammatory cancerous transformation and formulating appropriate treatment strategies.

Rat Experimental Autoimmune Gastritis Model.

BACKGROUND: Autoimmune gastritis (AIG) is an autoimmune disease of the stomach characterized by the destruction of the oxyntic mucosa, which stops producing acid and becomes both functionally and morphologically atrophic. The pathogenic mechanisms behind the disease are still poorly understood. There is no early diagnosis and specific AIG therapy. To elucidate the pathogenesis of AIG, to search for early diagnostic markers, as well as to test new therapeutic approaches, an adequate and easily reproducible experimental model for autoimmune gastritis (EAG) is needed. Existing EAG models have some limitations, including slow development of signs, absence of advanced gastritis, irrational use of animals to obtain antigen. The aim was to find out whether it is possible to cause autoimmune gastritis similar to human disease in Wistar rats through immunization with a homologous gastric mucosa extract. METHODS: Wistar rats were immunized with gastric mucosa extract. Histology studies and evaluation of serological parameters were performed 56 and 91 days later. RESULTS: Destruction of oxyntic glands by infiltrating T lymphocytes were detected in rats on 56 and 91 days after initial immunization with gastric mucosa extract. Hyperplasia of enterochromaffin-like (ECL) cells was detected on the 91st day. Antral mucosa remained unchanged. CONCLUSION: Wistar rats, immunized with gastric mucosa extract, developed EAG similar to human AIG. The advantages of received EAG model are the ease of obtaining, the rapid development of oxyntic mucosa damage, which may progress to ECL cell hyperplasia.

Esophageal Inlet Patch: Association with Barrett's Esophagus.

BACKGROUND: Esophageal inlet patch (IP) with heterotopic gastric mucosa is an incidental finding on esophagogastroduodenoscopy (EGD). Although IP is thought to be embryologic in nature, IP has been associated with Barrett's esophagus (BE). AIMS: The aim of this study was to compare prevalence, symptoms, demographic factors, and esophageal testing in patients with IP and BE. METHODS: We retrospectively analyzed endoscopic findings of EGDs, high-resolution esophageal manometry and esophageal pH impedance studies from January 2010 to January 2021 at a single academic medical center. Patients were grouped by presence or absence of IP and BE. RESULTS: Of 27,498 patients evaluated, 1.3% had endoscopic evidence of IP and 4.9% had BE. Of 362 patients with IP, 17.1% had BE; of 1356 patients with BE, 4.6% had IP. Both IP and BE patients presented primarily with heartburn and/or regurgitation. Patients with BE and/or IP were older and had higher BMI than those without (p < 0.001). Mean lower esophageal sphincter pressure was lower and mean acid exposure time (AET) was higher in patients with IP and/or BE than those without (p < 0.05). CONCLUSIONS: Our study reports an IP prevalence of 1.3%, with 17.1% patients having concomitant BE; and a BE prevalence of 4.9%, with 4.6% also having IP. Patients with IP alone presented with similar symptoms to patients with concomitant BE. Esophageal function testing showed that patients with either IP or BE had decreased LES pressures and increased esophageal AET. During endoscopy, patients found to have one of these findings should be carefully examined for the other.

TBBPA causes inflammation and cell death via the ROS/NF-κB pathway in the gastric mucosa.

Tetrabromobisphenol A (TBBPA) is a common brominated flame retardant that has a wide range of toxic effects on organisms. However, the mechanism of the toxic effects of TBBPA on the digestive system has rarely been studied. The purpose of this study was to investigate the mechanism of TBBPA toxicity on the gastric mucosa. In this study, TBBPA (mixed with corn oil) was administered by gavage at doses of 0 mg/kg (CG), 10 mg/kg and 20 mg/kg. The results showed that the levels of ROS, MDA and LPO were increased, and the activities of antioxidant enzymes were decreased. Large amounts of ROS activated the NF-κB pathway, leading to the development of an inflammatory response. The expression of BCL family and Caspase (Cas) family genes was increased, inducing apoptosis. The RIP3/MLKL pathway was activated, leading to cell necrosis. In summary, TBBPA can cause damage to the gastric mucosa through oxidative stress, leading to increased ROS activation of the NF-κB pathway. Treatment with the antioxidant NAC alleviated the damage to the gastric mucosa caused by TBBPA.

Heterotopic Gastric Mucosa in the Proximal Esophagus: Prospective Study and Systematic Review on Relationships with Endoscopic Findings and Clinical Data.

Cervical inlet patches (CIP) are common endoscopic findings with uncertain pathogenesis and clinical significance. We aimed to perform a systematic review and prospective study of clinical data and endoscopic findings related to CIP. It was a prospective single-center study conducted between 10/01/2017 and 9/01/2018. Forty patients with histopathologically confirmed CIP were compared with 222 individuals in the reference group. The systematic review was executed in accordance with the PRISMA guideline. Alcohol consumption tended to be higher among patients with CIP (3.0 ± 4.6 vs. 1.9 ± 5.0 standard drinks/week CIP patients and reference group, respectively; p < 0.001). Dysphagia was more frequent among patients with CIP (25% vs. 1.4%, CIP patients and reference group, respectively; p < 0.001), and sore throat and hoarseness were less frequent in patients with CIP (17.5% vs. 26.6% CIP patients and reference group, respectively; p < 0.01). In the multivariate regression analysis, the only risk factor of CIP occurrence was dysphagia (OR 21.9, 95%CI 4.9-98.6; p < 0.001). Sore throat and hoarseness were a reverse-risk factor of CIP diagnosis (OR 0.3, 95%CI 0.1-0.93; p = 0.04). Clinical data and coexisting endoscopic findings were not related to CIP. In the presented study, dysphagia was related to CIP occurrence, and sore throat and hoarseness tended to be less frequent among patients with CIP.

Description of the normal gastric mucosa in anatomy education: How many leukocytes are acceptable?

Textbooks covering normal human histology illustrate an allegedly normal gastric mucosa containing significant infiltrates of mononuclear cells in the lamina propria. This standard description seems to conflict with the pathologist's criterion for normality, which specifies only a few or a complete absence of inflammatory cells. Eventually, both anatomists and pathologists face the dilemma: how much infiltrate should their students and medical colleagues be told is acceptable for the gastric mucosa to be classified as normal? Summarizing the suggestions of experts in gastroenterology and our own experience, a simple approach could be to accept no more than five mononuclear and plasma cells per high power field as normal (400-fold magnification with a field area of 0.24 mm2 ). The divergence of views on this topic illustrates the need for anatomists and pathologists to find a consensus about the definition of "normal" tissues.

Analysis of Genetic Relatedness between Gastric and Oral Helicobacter pylori in Patients with Early Gastric Cancer Using Multilocus Sequence Typing.

The oral cavity is the second most colonized site of Helicobacter pylori after the stomach. This study aimed to compare the genetic relatedness between gastric and oral H. pylori in Japanese patients with early gastric cancer through multilocus sequence typing (MLST) analysis using eight housekeeping genes. Gastric biopsy specimens and oral samples were collected from 21 patients with a fecal antigen test positive for H. pylori. The number of H. pylori allelic profiles ranged from zero to eight since the yield of DNA was small even when the nested PCR was performed. MLST analysis revealed that only one patient had a matching oral and gastric H. pylori genotype, suggesting that different genotypes of H. pylori inhabit the oral cavity and gastric mucosa. The phylogenetic analysis showed that oral H. pylori in six patients was similar to gastric H. pylori, implying that the two strains are related but not of the same origin, and those strains may be infected on separate occasions. It is necessary to establish a culture method for oral H. pylori to elucidate whether the oral cavity acts as the source of gastric infection, as our analysis was based on a limited number of allele sequences.

Laryngopharyngeal symptoms and oesophageal disorder: The role of heterotopic gastric mucosa in upper oesophagus.

BACKGROUND: Heterotopic gastric mucosa in the upper oesophagus (HGMUE) was considered as geneogenous manifestation. However, its clinical characteristics may be beyond our knowledge if we focus on its extra-oesophageal presentation. So the aim of this study was to investigate the relationship between HGMUE and laryngopharyngeal symptoms. METHOD: Eight hundred and eleven patients who had gastric endoscopy examination were enrolled in this study and the cervical oesophagus was examined for the patch during withdrawal of the endoscope. Questionnaire for gastroesophageal reflux disease (GERD-Q) and Reflux Symptom Index (RSI) were completed by all the patients. Pathology feature and therapeutic effect of HGMUE patients were evaluated. RESULT: About 34.53% of the patients undergoing the gastroduodenoscopy had laryngopharyngeal (LP) symptoms. The relevance rate of HGMUE in LP(+) group (10.69%) was higher than that in LP(-) group (2%). The LP symptoms were related to the histological type and expression of H+-K+-ATPase in the histological sample of HGMUE patients. The positive rate of H+-K+-ATPase was 100% in LP(+) group, and that in LP(-) group was 28.6%. PPI therapy was effective for improving the LP symptoms in HGMUE patients. The RSI score in LP(+) patients decreased from 8.12 ± 1.46 at baseline to 4 ± 0.74 at the end of 8 weeks after treatment of PPI. CONCLUSION: HGMUE was an important cause of LP symptoms in patients, especially in those who had no evidence of GERD. The mechanism of HGMUE-induced LP symptoms was due to its location and the function of acid secretion according to the endoscopic finding and histologic characteristics.

Long Tubular Duplication of the Small Intestine - Lessons Learnt from a Common Presentation of a Rare Disease.

Long tubular duplication of the small intestine is one of the most difficult surgical challenges. The presence of heterotopic gastric mucosa necessitates resection of the duplicated bowel, but shared vascularity with the normal adjoining bowel makes the task daunting. We present a case of long tubular small intestinal duplication with certain special surgical and perioperative challenges which were successfully managed.

[Features of the upper gastrointestinal tract mucous membrane state in patients with atherosclerosis of the mesenteric arteries].

AIM: To evaluate the clinical and endoscopic features of diseases of the upper gastrointestinal tract (GIT) in patients with atherosclerosis of the mesenteric arteries (MA). MATERIALS AND METHODS: The study included 48 patients with atherosclerosis of MA and 43 patients without atherosclerosis of MA, who were hospitalized in the department of vascular surgery of the Chelyabinsk Regional Clinical Hospital in the period from 2019 to 2021. All patients underwent multispiral computed tomoangiography of the visceral and lower limb arteries, esophagogastroduodenoscopy. RESULTS: Assessment of lesions of the upper gastrointestinal tract revealed a higher incidence of erosive and ulcerative gastroduodenopathies among patients with atherosclerosis of MA (60.4%), compared with patients without atherosclerosis MA (39.5%); p=0.047. Signs of severe atrophy according to the data of histological examination were statistically significantly more frequent among patients with atherosclerosis of MA (29.2 and 11.6%; p=0.031). According to the results of logistic regression, the following predictors of erosions and ulcers of the upper gastrointestinal tract were revealed: the severity of stenosis of the superior mesenteric artery (SMA) is more than 35%, the body mass index (BMI) is less than 25.9 and the total score on the HADS scale is more than 6.5 points for depression (p=0.008). CONCLUSION: Erosive-ulcerative gastroduodenopathies and atrophy of the gastric mucosa are significantly more common in the group of patients with MA atherosclerosis. The main risk factors for erosions and ulcers of the upper gastrointestinal tract in patients with MA atherosclerosis are: the severity of SMA stenosis is more than 35%, a decrease in BMI is less than 25.9 and an increase in the HADS score is more than 6.5 points.

Activation of dopamine D2 receptor promotes pepsinogen secretion by suppressing somatostatin release from the mouse gastric mucosa.

In vivo administration of dopamine (DA) receptor (DR)-related drugs modulate gastric pepsinogen secretion. However, DRs on gastric pepsinogen-secreting chief cells and DA D2 receptor (D2R) on somatostatin-secreting D cells were subsequently acquired. In this study, we aimed to further investigate the local effect of DA on gastric pepsinogen secretion through DRs expressed on chief cells or potential D2Rs expressed on D cells. To elucidate the modulation of DRs in gastric pepsinogen secretion, immunofluorescence staining, ex vivo incubation of gastric mucosa isolated from normal and D2R-/- mice were conducted, accompanied by measurements of pepsinogen or somatostatin levels using biochemical assays or enzyme-linked immunosorbent assays. D1R, D2R, and D5R-immunoreactivity (IR) were observed on chief cells in mouse gastric mucosa. D2R-IR was widely distributed on D cells from the corpus to the antrum. Ex vivo incubation results showed that DA and the D1-like receptor agonist SKF38393 increased pepsinogen secretion, which was blocked by the D1-like receptor antagonist SCH23390. However, D2-like receptor agonist quinpirole also significantly increased pepsinogen secretion, and D2-like receptor antagonist sulpiride blocked the promotion of DA. Besides, D2-like receptors exerted an inhibitory effect on somatostatin secretion, in contrast to their effect on pepsinogen secretion. Furthermore, D2R-/- mice showed much lower basal pepsinogen secretion but significantly increased somatostatin release and an increased number of D cells in gastric mucosa. Only SKF38393, not quinpirole, increased pepsinogen secretion in D2R-/- mice. DA promotes gastric pepsinogen secretion directly through D1-like receptors on chief cells and indirectly through D2R-mediated suppression of somatostatin release.

MNPmApp: An image analysis tool to quantify mononuclear phagocyte distribution in mucosal tissues.

Mononuclear phagocytes (MNPs) such as dendritic cells and macrophages perform key sentinel functions in mucosal tissues and are responsible for inducing and maintaining adaptive immune responses to mucosal pathogens. Positioning of MNPs at the epithelial interface facilitates their access to luminally-derived antigens and regulates MNP function through soluble mediators or surface receptor interactions. Therefore, accurately quantifying the distribution of MNPs within mucosal tissues as well as their spatial relationship with other cells is important to infer functional cellular interactions in health and disease. In this study, we developed and validated a MATLAB-based tissue cytometry platform, termed "MNP mapping application" (MNPmApp), that performs high throughput analyses of MNP density and distribution in the gastrointestinal mucosa based on digital multicolor fluorescence microscopy images and that integrates a Monte Carlo modeling feature to assess randomness of MNP distribution. MNPmApp identified MNPs in tissue sections of the human gastric mucosa with 98 ± 2% specificity and 76 ± 15% sensitivity for HLA-DR+ MNPs and 98 ± 1% specificity and 85 ± 12% sensitivity for CD11c+ MNPs. Monte Carlo modeling revealed that mean MNP-MNP distances for both HLA-DR+ and CD11c+ MNPs were significantly lower than anticipated based on random cell placement, whereas MNP-epithelial distances were similar to randomly placed cells. Surprisingly, H. pylori infection had no significant impact on the number of HLA-DR and CD11c MNPs or their distribution within the gastric lamina propria. However, our study demonstrated that MNPmApp is a reliable and user-friendly tool for unbiased quantitation of MNPs and their distribution at mucosal sites.

Helicobacter species binding to the human gastric mucosa.

Helicobacter pylori infects half of the world population, being associated with several gastric disorders, such as chronic gastritis and gastric carcinoma. The Helicobacter genus also includes other gastric helicobacters, such as H. heilmannii¸ H. ailurogastricus, H. suis, H. felis, H. bizzozeronii, and H. salomonis. These gastric helicobacters colonize both the human and animal stomach. The prevalence of gastric non-Helicobacter pylori Helicobacter (NHPH) species in humans has been described as low, and the in vitro binding to the human gastric mucosa was never assessed. Herein, human gastric tissue sections were used for the evaluation of the tissue glycophenotype and for the binding of gastric NHPH strains belonging to different species. Histopathological evaluation showed that 37.5% of the patients enrolled in our cohort presented chronic gastritis, while the presence of neutrophil or eosinophilic activity (chronic active gastritis) was observed in 62.5% of the patients. The secretor phenotype was observed in 68.8% of the individuals, based on the expression of Lewis B antigen and binding of the UleX lectin. The in vitro binding assay showed that all the NHPH strains evaluated were able to bind, albeit in low frequency, to the human gastric mucosa. The H. heilmannii, H. bizzozeronii, and H. salomonis strains displayed the highest binding ability both to the gastric superficial epithelium and to the deep glands. Interestingly, we observed binding of NHPH to the gastric mucosa of individuals with severe chronic inflammation and intestinal metaplasia, suggesting that NHPH binding may not be restricted to the healthy gastric mucosa or slight chronic gastritis. Furthermore, the in vitro binding of NHPH strains was observed both in secretor and non-secretor individuals in a similar frequency. In conclusion, this study is the first report of the in vitro binding ability of gastric NHPH species to the human gastric mucosa. The results suggest that other glycans, besides the Lewis antigens, could be involved in the bacterial adhesion mechanism; however, the molecular intervenients remain unknown.

Clinicopathological characteristics of pancreatic acinar cell metaplasia associated with Helicobacter pylori infection.

BACKGROUND: Pancreatic acinar cell metaplasia (PACM) has been rarely reported in the gastric mucosa. In the present study, we aimed to elucidate the clinical and pathological characteristics of PACM associated with Helicobacter pylori (H. pylori). METHOD: 5930 patients who underwent five- or two-point gastric biopsy according to the updated Sydney system (USS) by upper gastrointestinal endoscopy were enrolled. The patients were categorized into current H. pylori infection (CHI), post-H. pylori eradication (PHE), and non-H. pylori infection (NHI) groups according to the H. pylori infection status, and the frequency and location of PACM were compared. Additionally, a case-control study was performed to compare the USS scores between patients with CHI and PACM and those with CHI but not PACM. RESULT: The frequencies of PACM were 0.49% (10/2039), 0.75% (25/3332), and 0% (0/559) in the CHI, PHE, and NHI groups, respectively. PACM was found in the greater curvature of the antrum in 33 of the 35 patients with PACM. Among the patients with CHI, the inflammation scores in the greater curvature of the antrum and the greater curvature of the corpus were lower in patients with PACM than in those without PACM. CONCLUSION: Although rarely reported in the gastric mucosa, PACM was closely related to H. pylori infection, especially in the antrum, and was associated with relatively mild inflammation.

Convergent dysbiosis of gastric mucosa and fluid microbiome during stomach carcinogenesis.

BACKGROUND: A complex microbiota in the gastric mucosa (GM) has been unveiled recently and its dysbiosis is identified to be associated with gastric cancer (GC). However, the microbial composition in gastric fluid (GF) and its correlation with GM during gastric carcinogenesis are unclear. METHODS: We obtained GM and GF samples from 180 patients, including 61 superficial gastritis (SG), 55 intestinal metaplasia (IM) and 64 GC and performed 16S rRNA gene sequencing analysis. The concentration of gastric acid and metabolite nitrite has been measured. RESULTS: Overall, the composition of microbiome in GM was distinct from GF with less diversity, and both were influenced by H. pylori infection. The structure of microbiota changed differentially in GM and GF across histological stages of GC, accompanied with decreased gastric acid and increased carcinogenic nitrite. The classifiers of GC based on microbial markers were identified in both GM and GF, including Lactobacillus, Veillonella, Gemella, and were further validated in an independent cohort with good performance. Interestingly, paired comparison between GM and GF showed that their compositional distinction remarkably dwindled from SG to GC, with some GF-enriched bacteria significantly increased in GM. Moreover, stronger interaction network between microbes of GM and GF was observed in GC compared to SG. CONCLUSION: Our results, for the first time, revealed a comprehensive profile of both GM and GF microbiomes during the development of GC. The convergent microbial characteristics between GM and GF in GC suggest that the colonization of carcinogenic microbes in GM might derive from GF.

Higher proportions of a healthy gastric mucosa in healthy Japanese adults with later birth year: analysis of 41 957 participants.

BACKGROUND: In Japan, most gastric cancers are associated with gastric mucosal atrophy caused by chronic infection with Helicobacter pylori (H. pylori). Recognizing the condition of the gastric mucosa and determining the infection status of H. pylori are important for predicting the individual risk of gastric cancer. This study aimed to determine the proportion of Japanese adults with a healthy gastric mucosa (without H. pylori infection) among 12 birth-year groups encompassing 1935-1990 by morphological images. METHODS: The gastric mucosa was classified as healthy or having gastritis based on routine double-contrast upper gastrointestinal barium X-ray radiography. The participants included 41 957 healthy Japanese adults. Serum or urine H. pylori antibody levels were also assessed. RESULTS: In total, 25 424 participants had healthy mucosa without a history of H. pylori eradication. The proportions of participants with a healthy mucosa by birth year were 19.8% (57/288), 27.1% (306/1128), 32.4% (569/1756), 37.6% (1808/4811), 49.2% (3207/6522), 60.1% (3966/6550), 71.2% (5224/7342), 77.2% (5114/6624), 80.6% (3342/4149), 85.0% (1404/1652), 85.3% (302/354) and 94.7% (125/132) in 1935, 1940, 1945, 1950, 1955, 1960, 1965, 1970, 1975, 1980, 1985 and after 1990, respectively (P for trend <0.01). All the participants with a healthy mucosa showed negative results in the H. pylori antibody tests. CONCLUSIONS: The proportion of participants with normal gastric mucosa linearly increased with the birth years. The prevalence of morphologically healthy gastric mucosa could have consistently increased with decreasing prevalence of H. pylori infection.

Life-threatening gastrointestinal bleeding caused by jejunal heterotopic gastric mucosa in an adult dog: a rare case report.

BACKGROUND: Heterotopic gastric mucosa has been scarcely reported in the veterinary literature. Its presence can be asymptomatic or associated with various clinical signs ranging from apathy, vomiting, to abdominal pain. This report illustrates the presence of heterotopic gastric mucosa in the jejunum of an adult dog. It is the first to describe severe anemia, requiring acute blood transfusion, following intestinal hemorrhage caused by heterotopic gastric mucosa. CASE PRESENTATION: A twelve-year-old, intact male Maltese dog was presented with a history of apathy, vomiting and anemia. The dog was on a strict diet for recurrent diarrhea, food intolerance and skin allergy. Clinical examination revealed severe anemic mucous membranes and painful abdominal palpation. Blood examination confirmed severe regenerative anemia. Ultrasonography showed an intestinal neoplasm, gall bladder sludge and non-homogeneous liver parenchyma. Three-view thoracic radiographs failed to show any metastatic lesions or enlarged lymph nodes. After initial stabilization and blood transfusion, a midline exploratory laparotomy was performed. Three different masses were found in the jejunum. Resection and anastomosis of approximately 40 cm of jejunum was performed, followed by liver and lymph node biopsy and placement of an esophagostomy tube. Two days after surgery the dog started to clinically improve and was discharged from the hospital on the sixth day after surgery. Histopathology revealed the intestinal masses to be heterotopic gastric mucosa associated with intramural cystic distensions, multifocal ulceration and bleeding into the intestinal lumen. Two years after surgery, the dog did not have a recurrence of anemia or gastrointestinal signs. CONCLUSIONS: This case demonstrates that heterotopic gastric mucosa can be considered one of the differential diagnoses in case of severe anemia due to gastrointestinal hemorrhage and suspected intestinal tumors. Although in most described cases in literature the finding seems to be incidental on necropsy, our report shows that heterotopic gastric mucosa can be the etiology of life-threatening signs. In addition, because no recurrent diarrhea episodes occurred after surgical resection of the ectopic tissue, it is likely that the heterotopic gastric mucosa was the cause of the food intolerance signs in this dog.