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Background/aims: : Accurately diagnosing diffuse gastric wall thickening is challenging. Hypertrophic gastritis (HG), while benign, mimics the morphology of Borrmann type 4 advanced gastric cancer (AGC B-4). We compared the features of endoscopy and endoscopic ultrasonography (EUS) between them., Methods: : We retrospectively reviewed patients who underwent EUS for gastric wall thickening between 2000 and 2021, selecting HG and pathologically confirmed advanced gastric cancer cases. Ulceration and antral wall thickening were determined via endoscopy, while EUS assessed the 5-layered gastric wall structure, measuring the proper muscle (PM) layer and total wall thickness., Results: : Male dominance was observed in AGC B-4, and the hemoglobin and albumin levels were significantly lower. The rate of antral wall thickening and presence of ulceration were significantly higher in AGC B-4 cases. Destruction of the PM layers was observed only in AGC B-4 cases, and the PM was significantly thicker in AGC B-4 cases. Forceps biopsy had an excellent success rate in ulcer-present AGC B-4 cases, but only a 42.6% success rate was observed for cases without ulcers, necessitating additional diagnostic modalities. A PM thickness of 2.39 mm distinguished between AGC B-4 and HG effectively. The multivariable analysis showed that a thickened PM layer and the presence of ulceration were significant risk factors for the diagnosis of AGC B-4., Conclusions: : Endoscopic findings of a thickened gastric wall, including antral involvement, and presence of ulcer were significant risk factors for the diagnosis of AGC B-4. EUS findings of destroyed wall layers and a thickened PM of >2.39 mm were the key points of differentiation between HG and AGC B-4.

A 9-year-old male's entire Boston Terrier was presented with persistent hyporexia and weight loss for 6 weeks prior to referral admission. A CT scan showed marked hypertrophy of the rugal folds protruding into the gastric lumen, which had a cerebriform appearance. Changes were consistent with the ultrasonographic findings, which showed marked hyperechogenicity of the gastric mucosa, mucosal cysts, and otherwise normal wall layering. Histopathology of the fundic gastric mucosa showed foveolar hyperplasia and cystic dilation which were findings consistent with Ménétrier-like disease. Based on the reviewed literature, this is the first case report describing CT findings of Ménétrier-like disease in a dog., (© 2024 The Author(s). Veterinary Radiology & Ultrasound published by Wiley Periodicals LLC on behalf of American College of Veterinary Radiology.)

Tuft cells are chemosensory cells associated with luminal homeostasis, immune response, and tumorigenesis in the gastrointestinal tract. We aimed to elucidate alterations in tuft cell populations during gastric atrophy and tumorigenesis in humans with correlative comparison to relevant mouse models. Tuft cell distribution was determined in human stomachs from organ donors and in gastric pathologies including Ménétrier's disease, Helicobacter pylori gastritis, intestinal metaplasia (IM), and gastric tumors. Tuft cell populations were examined in Lrig1-Kras G12D , Mist1-Kras G12D , and MT-TGFα mice. Tuft cells were evenly distributed throughout the entire normal human stomach, primarily concentrated in the isthmal region in the fundus. Ménétrier's disease stomach showed increased tuft cells. Similarly, Lrig1-Kras mice and mice overexpressing TGFα showed marked foveolar hyperplasia and expanded tuft cell populations. Human stomach with IM or dysplasia also showed increased tuft cell numbers. Similarly, Mist1-Kras mice had increased numbers of tuft cells during metaplasia and dysplasia development. In human gastric cancers, tuft cells were rarely observed, but showed positive associations with well-differentiated lesions. In mouse gastric cancer xenografts, tuft cells were restricted to dysplastic well-differentiated mucinous cysts and were lost in less differentiated cancers. Taken together, tuft cell populations increased in atrophic human gastric pathologies, metaplasia, and dysplasia, but were decreased in gastric cancers. Similar findings were observed in mouse models, suggesting that, while tuft cells are associated with precancerous pathologies, their loss is most associated with the progression to invasive cancer., (© 2023 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)

Menetrier disease is a rare disease characterised by hyperplasia of the gastric epithelium and large gastric folds. We present a case of a 58-year-old woman who was referred with iron deficiency anaemia, with a family history of a sibling who had undergone gastrectomy for presumed gastric malignancy. Endoscopy showed prominent gastric mucosal folds and biopsies showed hyperplastic gastric mucosa, with prominent foveolar hyperplasia suggestive of Menetrier disease. Further information about her brother's diagnosis was sought, and it was found that his pathology after gastrectomy showed diffuse glandular hyperplasia also in keeping with Menetrier disease. Adult familial Menetrier disease has so far been a rarity in the literature-review elicits five previous cases of this presentation in siblings., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

A 60-year-old man was referred for the investigation of giant gastric folds, life-threatening anemia and hypoproteinemia. A combination of multiple endoscopic procedures derived a clinical diagnosis of protein-losing gastropathy with two gastric adenomas. After two months of alimentary therapy, the patient received total gastrectomy and fully recovered. The final pathological diagnosis was hypertrophic gastropathy of unknown origin with concomitant adenocarcinoma arising from a gastric type adenoma.

We performed whole exome sequencing in individuals from a family with autosomal dominant gastropathy resembling Ménétrier disease, a premalignant gastric disorder with epithelial hyperplasia and enhanced EGFR signalling. Ménétrier disease is believed to be an acquired disorder, but its aetiology is unknown. In affected members, we found a missense p.V742G variant in MIB2, a gene regulating NOTCH signalling that has not been previously linked to human diseases. The variant segregated with the disease in the pedigree, affected a highly conserved amino acid residue, and was predicted to be deleterious although it was found with a low frequency in control individuals. The purified protein carrying the p.V742G variant showed reduced ubiquitination activity in vitro and white blood cells from affected individuals exhibited significant reductions of HES1 and NOTCH3 expression reflecting alteration of NOTCH signalling. Because mutations of MIB1, the homolog of MIB2, have been found in patients with left ventricle non-compaction (LVNC), we investigated members of our family with Ménétrier-like disease for this cardiac abnormality. Asymptomatic left ventricular hypertrabeculation, the mildest end of the LVNC spectrum, was detected in two members carrying the MIB2 variant. Finally, we identified an additional MIB2 variant (p.V984L) affecting protein stability in an unrelated isolated case with LVNC. Expression of both MIB2 variants affected NOTCH signalling, proliferation and apoptosis in primary rat cardiomyocytes.In conclusion, we report the first example of left ventricular hypertrabeculation/LVNC with germline MIB2 variants resulting in altered NOTCH signalling that might be associated with a gastropathy clinically overlapping with Ménétrier disease., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

A 54-year-old man presented to our department with abdominal discomfort and anorexia and was diagnosed as having Ménétrier's disease (MD) with hilar cholangiocarcinoma. Based on his clinical examination, there was no evidence of Helicobacter pylori or cytomegalovirus (CMV) infection. Although we administered proton pump inhibitor and high-calorie enteral nutrition, hypoproteinemia did not improve, and the refractory protein-losing enteropathy persisted. However, interestingly, MD improved immediately after resection of the hilar cholangiocarcinoma. Generally, the etiology of MD is unknown, but H. pylori and CMV infections have been implicated. To our knowledge, there has been no previous report indicating that a malignant tumor could be involved in the etiology of MD. Thus, we report an extremely rare case of MD which is seemingly caused by malignancy.

Successful pluripotent stem cell differentiation methods have been developed for several endoderm-derived cells, including hepatocytes, β-cells and intestinal cells. However, stomach lineage commitment from pluripotent stem cells has remained a challenge, and only antrum specification has been demonstrated. We established a method for stomach differentiation from embryonic stem cells by inducing mesenchymal Barx1, an essential gene for in vivo stomach specification from gut endoderm. Barx1-inducing culture conditions generated stomach primordium-like spheroids, which differentiated into mature stomach tissue cells in both the corpus and antrum by three-dimensional culture. This embryonic stem cell-derived stomach tissue (e-ST) shared a similar gene expression profile with adult stomach, and secreted pepsinogen as well as gastric acid. Furthermore, TGFA overexpression in e-ST caused hypertrophic mucus and gastric anacidity, which mimicked Ménétrier disease in vitro. Thus, in vitro stomach tissue derived from pluripotent stem cells mimics in vivo development and can be used for stomach disease models.

Epidemiological studies have demonstrated a close association between infection with Helicobacter pylori (H.pylori) and the development of gastric carcinoma. Chronic H.pylori infection increases the frequency of mutation in gastric epithelial cells. However, the mechanism by which infection of H.pylori leads to mutation in gastric epithelial cells is unclear. We suspected that components in H.pylori may be related to the mutagenic response associated with DNA alkylation, and could be detected with the Ames test using a more sensitive strain for alkylating agents. Our investigation revealed that an extract of H.pylori was mutagenic in the Ames test with Salmonella typhimurium YG7108, which is deficient in the DNA repair of O(6)-methylguanine. The extract of H.pylori may contain methylating or alkylating agents, which might induce O (6)-alkylguanine in DNA. Mutagenicity of the alkylating agents N-methyl-N-nitrosourea (MNU) and N-methyl-N'-nitro-N-nitrosoguanidine in the Ames test with S.typhimurium TA1535 was enhanced significantly in the presence of the extract of H.pylori. The tested extracts of H.pylori resulted in a significant induction of micronuclei in human-derived lymphoblastoid cells. Heat instability and dialysis resistance of the extracts of H.pylori suggest that the mutagenic component in the extracts of H.pylori is a heat-unstable large molecule or a heat-labile small molecule strongly attached or adsorbed to a large molecule. Proteins in the extracts of H.pylori were subsequently fractionated using ammonium sulphate precipitation. However, all fractions expressed enhancing effects toward MNU mutagenicity. These results suggest the mutagenic component is a small molecule that is absorbed into proteins in the extract of H.pylori, which resist dialysis. Continuous and chronic exposure of gastric epithelial cells to the alkylative mutagenic component from H.pylori chronically infected in the stomach might be a causal factor in the gastric carcinogenesis associated with H.pylori., (© The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Ménétrier's Disease (MD) is a rare acquired hypertrophic gastropathy characterized by giant hypertrophic rugal folds, hypochlorhydria, and hypoproteinemia. The definitive etiology of MD is controversial, although infection with Helicobacter pylori (H. pylori) has been implicated in adults. It presents as a constellation of symptoms including epigastric pain, fatigue, vomiting, weight loss, anorexia, and edema. None of these signs and symptoms is specific for the disease. The gastrointestinal symptoms and the degree of hypoalbuminemia can be profound, the latter resulting from the leakage of protein from the gastric lining. The disease is more common in males. Herein, we report a case of a young woman presenting with the chief complaint of peripheral edema with minimal gastrointestinal symptoms, which was diagnosed as MD on endoscopic evaluation and histopathological examination of gastric biopsy. A high index of suspicion is needed to correctly diagnose this condition for its optimal management.

Introduction: Ménétrier disease is a rare disorder characterized by gastric foveolar hyperplasia associated with secondary protein loss. In children, this condition is presented as an edematous syndrome without renal or hepatic impairment and differs from the adult form by the constant presence of edema and spontaneous remission. It has been related to infections in most published cases, especially to Cytomegalovirus (CMV) and Helicobacter pylori (H. pylori)., Objective: To present a pediatric case of Ménétrier disease and endoscopic imaging obtained during the evolution of the patient., Case Report: A five year old preschooler who presented a generalized edema, abdominal pain and malaise. After ruling out renal and hepatic pathologies, an upper endoscopy revealed a severe compromise of the gastric mucosa. Urease test for H. pylori and IgG test for CMV resulted positive. Albumin and H2 receptor antagonists were administered. The evolution was favorable and the patient was discharged after 14 days; 8 month follow-up endoscopy showed no abnormalities., Conclusion: The medical profile and endoscopy are enough evidence to suggest the diagnosis of hypertrophic protein-losing gastropathy. Further studies need to be developed that include a considerable number of patients to assess their association with CMV or H. pylori infections, as these viruses are very common in our population.

Menetrier`s disease is a rare form of acquired gastropathy that presents mostly during adulthood, but is extremely rare in children. It is a clinicopathological diagnosis that typically presents with abdominal pain, vomiting, and edema secondary to hypoalbuminemia. Endoscopy usually shows giant gastric mucosal folds, and gastric biopsy shows foveolar hyperplasia and decreased oxyntic glands. Here, we describe a 5-year-old boy from Saudi Arabia with typical presentation of Menetrier`s disease and serological evidence of acute cytomegalovirus infection.

The structure of gastric mucosa (GM) of the stomach fundus (SF) was studied in children with various gastrointestinal diseases. In children, the main structural parameters of the SF (GM thickness, depth of glands and thickness of the mucosal epithelium area) varied widely (3.5-5.3 times). The following ranges were allocated: hypotrophy ("atrophy"), eutrophy (area of mean values) and hypertrophy of SF GM thickness, depth of the glands and thickness of the mucosal epithelium area. Hypotrophy ("atrophy") of the SF glands was found in approximately one third of the children of different age which could lead to decrease in the digestive function of the stomach and cause specific clinical symptoms of dyspepsia. Atrophic changes of SF GM were observed in children of all age groups. Most often (49%), fundic glands hypotrophy was observed in children of early age. With age, the incidence of atrophic changes of SF GM decreased. Atrophic changes in the GM can be detected during microanatomical or histopathological (using morphometry) examination of the SF.

Ménétrier disease is a rare hypertrophic gastropathy that is characterized by hyperplasia of the mucous cells with concurrent loss of chief and parietal cells within the gastric glands. There are few reports of this disease in dogs, and little is known about the clinical presentation and progression of canine Ménétrier disease. Three Cairn terrier littermates developed hypertrophic gastropathy with histological features of Ménétrier disease. One dog remained clinically asymptomatic for 2 years after diagnosis. The development of this disease in 3 siblings suggests a possible inherited predisposition. All 3 dogs also developed gastric neoplasia, which has been reported in human Ménétrier disease but has not been associated previously with hypertrophic gastropathy in domestic species.

Molecular imaging biomarkers of proliferation hold great promise for quantifying response to personalized medicine. One such approach utilizes the positron emission tomography (PET) tracer 3'-deoxy-3'[18F]-fluorothymidine ([18F]FLT), an investigational agent whose uptake reflects thymidine salvage-dependent DNA synthesis. The goal of this study was to evaluate [18F]FLT-PET in the setting of Ménétrier's disease (MD), a rare, premalignant hyperproliferative disorder of the stomach treatable with cetuximab therapy. Over 15 months, a patient with confirmed MD underwent cetuximab therapy and was followed with sequential [18F]FLT-PET. For comparison to MD, an [18F]FLT-PET study was conducted in another patient to quantify uptake in a normal stomach. Prior to cetuximab therapy, stomach tissue in MD was easily visualized with [18F]FLT-PET, with pre-treatment uptake levels exceeding normal stomach uptake by approximately fourfold. Diminished [18F]FLT-PET in MD was observed following the initial and subsequent doses of cetuximab and correlated with clinical resolution of the disease. To our knowledge, this study reports the first clinical use of [18F]FLT-PET to assess proliferation in a premalignant disorder. We illustrate that the extent of MD involvement throughout the stomach could be easily visualized using [18F]FLT-PET, and that response to cetuximab could be followed quantitatively and non-invasively in sequential [18F]FLT-PET studies. Thus, [18F]FLT-PET appears to have potential to monitor response to treatment in this and potentially other hyperproliferative disorders.

Background: Ménétrier disease is a rare disorder of the stomach, characterized by giant hypertrophic folds that usually involve the gastric body and fundus, associated to hypoalbuminemia due to serum protein loss across the gastric mucosa. We report a 55-years-old male presenting with abdominal pain, vomiting, weight loss and hypoalbuminemia. Diffuse hypertrophic gastric folds, elevated ulcerated sessile lesions and focal duodenal involvement were seen at endoscopy. Biopsies showed foveolar hyperplasia and glandular atrophy with cystic dilatation. A total gastrectomy was performed with a good outcome.

Hyperactivation of the epidermal growth factor receptor (EGFR) in gastric cells due to excess of its ligand transforming growth factor-α (TGFA) is associated with hyperplastic lesions in Ménétrier's disease patients and in transgenic mice. Other EGFR ligands, however, have never been associated with stomach diseases. Here, we report that overexpression of the EGFR ligand betacellulin (BTC) results in a severe, age-dependent hyperplasia of foveolar epithelium. The stomach weight of affected mice reached up to 3g representing more than 10% of total body weight. The preexisting corpus mucosa was severely depleted, and both parietal and chief cells were replaced by proliferating foveolar epithelium. The lesions were more severe in male as compared to female transgenic mice, and partially regressed in the former after castration-mediated androgen removal. The gastric hyperplasia fully disappeared when BTC-tg mice were crossed into the Egfr(Wa5) background expressing a dominant-negative EGFR, indicating that the phenotype is EGFR-dependent. This is, to our knowledge, the first report of hyperplastic gastric lesions due to the overexpression of an EGFR ligand other than TGFA. BTC-tg mice are therefore a new, promising model for studying EGFR-dependent gastric polyps., (© 2012 Elsevier B.V. All rights reserved.)

Menetrier's disease is a rare entity characterized by large, tortuous gastric mucosal folds. The mucosal folds in Menetrier's disease are often most prominent in the body and fundus. Histologically, massive foveolar hyperplasia (hyperplasia of surface and glandular mucous cells) is noted, which replaces most of the chief and parietal cells. Profuse mucus is usually observed during the endoscopy but there have been few cases that show interesting endoscopic findings such as mucus bridge or water pearl. Herein, we report a case of Menetrier's disease showing mucus bridge by excessive mucus observed during the endoscopy.

Objective: Ménétrier's disease (MD) is a rare hypertrophic gastropathy characterised by giant rugal folds, hypochlorhydria, protein loss and a classic constellation of symptoms (nausea, vomiting, abdominal pain and peripheral oedema). It is considered a clinical diagnosis that may at times be difficult to establish. Firm diagnostic criteria for MD are proposed by delineating the clinicopathological features that best differentiate MD from its mimics., Method: 48 patients referred to Vanderbilt University Medical Center for consideration of enrolment in a clinical trial of treatment of patients with MD with cetuximab were evaluated for a definitive diagnosis by assessing the clinical presentation, pertinent laboratory values and histopathological features., Results: MD was confirmed in 25 of the 48 patients (52%). The remaining 23 patients were considered to be mimics of MD, the most common diagnoses being gastric polyps or polyposis syndromes (13/23, 57%). Gastric slides were available from 40 of the 48 patients for detailed histological analysis (22/25 MD and 18/23 non-MD). Foveolar hyperplasia, glandular tortuosity and dilation, and a marked reduction in parietal cell number were present in all 22 cases of MD. Lamina propria smooth muscle hyperplasia and oedema characterised most cases (18/22 and 19/22, respectively). More than half had prominent eosinophils (11/22) and/or plasma cells (12/22) in the lamina propria. The clinical presentation of patients with MD was characterised by significantly younger age of onset, male predominance and increased vomiting compared with non-MD patients, and a lower prevalence of anaemia compared with MD patients with polyps. There was a trend towards increased frequency of peripheral oedema in patients with MD compared with non-MD patients., Conclusions: MD is most accurately diagnosed by clinicohistopathological analysis including oesophagogastroduodenoscopy with gastric pH, appropriate laboratory tests (complete blood count, serum albumin, serum gastrin, Helicobacter pylori and cytomegalovirus serology) and full-thickness mucosal biopsy of the involved gastric mucosa.

Ménétrier disease is a rare disorder of unknown etiology. An overexpression of TGF-alpha has been proposed to play a role in the pathophysiology. HIV-1 tat gene product has been shown to stimulate TGF-alpha production leading to a positive feedback autocrine loop. The case of a 41-year-old male with AIDS who presented with weight loss, abdominal pain, ascites, edema, nausea, vomiting, and diarrhea is discussed. A computed tomography (CT) scan of the abdomen showed avid enhancement of the stomach mucosa. Magnetic resonance angiography revealed gastric and small bowel distention with diffuse wall thickening. Biopsies of the stomach showed marked foveolar hyperplasia with active inflammation and gland changes consistent with Ménétrier disease.

Ménétrier's Disease is a giant fold gastropathy whose precise etiology has remained enigmatic. However, mucosal changes characteristic of Ménétrier's Disease have been linked to diverse pathologies, both infectious and malignant. Here, we describe a novel association: Ménétrier's mucosa developing on top of underlying Kaposi's Sarcoma. Two male patients, ages 24 and 31, with HIV/AIDS underwent gastric biopsies that demonstrated Kaposi's Sarcoma. When the former patient expired, a more complete postmortem histologic examination of his stomach was undertaken. For each patient, endoscopic findings at the time of biopsy revealed thickened gastric mucosa overlying the Kaposi's changes. Microscopically, this thickened mucosa comprised hyperplastic foveolar cells that extended to the muscularis mucosa, characteristic of Ménétrier's mucosa. In both cases, special stains confirmed this impression. Dissection of the 24 year-old patient's stomach at autopsy demonstrated that the Ménétrier's mucosa was limited to areas where there was underlying Kaposi's Sarcoma, and that this mucosa was not present when the underlying stroma was normal. Our findings indicate, therefore, an association between Ménétrier's mucosal changes and Kaposi's Sarcoma; such an association has not, to our knowledge, been described previously in the literature.

We present a case of protein-losing gastropathy with hypertrophic gastric folds. A 38-year-old man was hospitalized for severe epigastric pain suggestive of hypoproteinemia. Endoscopic and radiologic examination revealed enlarged gastric folds on the greater curvature of the stomach. Endoscopic sonography revealed marked thickening of the second layer on the greater curvature of the stomach. Endoscopic mucosal resection was performed, and the diagnosis was hypertrophic gastritis. After prednisolone treatment, hypoproteinemia and the enlarged gastric folds of the stomach resolved., ((c) 2007 Wiley Periodicals, Inc.)

Objective: Analyze retrospectively the clinical, histopathological and surgical characteristics of patients with Mindtrier's disease (MD) at our Institution., Background Data: Ménétrier's disease (MD) includes hipertophy of gastric mucosa, hipo or hiperchloridria and severe hipoalbuminemia. In the literature, it has been underestimated its relationship with the development of gastric carcinoma., Methods: We analyzed retrospectively the clinical trials of patients with MD treated surgically at our Institution during the last three decades (From 1970 through 2002)., Results: Three patients with clinical diagnosis of MD underwent total gastrectomy during the study period. All of them were corroborated histopathologically and in one patient carcinoma in situ was demonstrated in the surgical specimen., Conclusions: There is a very limited experience with surgical treatment of MD and it is limited to patients who have severe hipoalbuminemia or associated malignant disease. However accordig to our experience and literature review, surgical treatment should be considered early in the course of the disease for the relationship between MD and gastric adenocarcinoma.

Diagnosis of edema secondary to hypoprotidemia but without nutritional, renal, hepatic or cardiac cause, must consider exudative digestive disease, of which the lymphocytic gastritis, as the authors report here a new observation diagnosed in a 73 year-old woman. Gastroscopy reveals varioliform gastritis and biopsy demonstrates diffuse infiltration of the gastric epithelium by lymphocytes, making of it a real histopathologic entity among the gastropathies. Etiology and pathogeny remain still unknown but proton pump gastric inhibitors are an effective treatment.

Background: A unique pathological feature of murine autoimmune gastritis (AIG) is its pronounced mucosal hypertrophy, which is different from human type A chronic atrophic gastritis with pernicious anemia. The aim of this study was to clarify the mechanism of gastric hypertrophy in murine AIG, especially in relation to inflammatory cells infiltrating the gastric mucosa., Methods: Neonatally thymectomized (NTx) BALB/c and (BALB/c x DBA/2) F1 mice with gastritis were examined histologically and serologically. The T-helper (Th1/Th2) immune balance in the spleen was evaluated by intracellular cytokine staining for interferon-gamma and a flow-cytometric beads array for several cytokines. Additionally, NTx AIG BALB/c mice were orally administered an H(2)-blocker to decrease eosinophils., Results: NTx AIG BALB/c mice exhibited gastritis without stomach hypertrophy at 2 months of age, and developed gastritis with mucous gland hypertrophy accompanied by eosinophil infiltration at 6 months of age. In contrast, NTx AIG (BALB/c x DBA/2) F1 mice displayed gastritis with neither stomach hypertrophy nor eosinophil infiltration even at the age of 6 months. Upregulation of interleukin-4 and granulocyte-macrophage colony-stimulating factor in the spleen was observed in BALB/c mice but not in (BALB/c x DBA/2) F1 mice. Additionally, some NTx AIG BALB/c mice did not show gastric hypertrophy or eosinophil infiltration owing to the administration of an H(2)-blocker., Conclusions: There are two different pathological phenotypes of murine AIG, chronic gastritis and hypertrophic gastritis, in NTx AIG BALB/c mice. Furthermore, eosinophil infiltration and the Th2 immune response might play a key role in the phenotypic shift from chronic gastritis to hypertrophic gastritis in these mice.