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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.

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.)

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.

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.

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.

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: 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.

Ménétrier disease and gastrointestinal stromal tumors (GISTs) are hyperproliferative disorders of the stomach caused by dysregulated receptor tyrosine kinases (RTKs). In Ménétrier disease, overexpression of TGF-alpha, a ligand for the RTK EGFR, results in selective expansion of surface mucous cells in the body and fundus of the stomach. In GISTs, somatic mutations of the genes encoding the RTK KIT (or PDGFRA in a minority of cases) result in constitutive kinase activity and neoplastic transformation of gut pacemaker cells (interstitial cells of Cajal). On the basis of the involvement of these RTKs in the pathogenesis of these disorders, Ménétrier disease patients have been effectively treated with a blocking monoclonal antibody specific for EGFR and GIST patients with KIT and PDGFRA tyrosine kinase inhibitors.

Vascular endothelial growth factor (VEGF) promotes protein leakage from blood vessels and endothelial cell growth. The expression of transforming growth factor (TGF)-alpha and its receptor is increased in the gastric mucosa of patients with Ménétrier's disease. Since TGF-alpha stimulates the expression of VEGF mRNA in cultured keratinocytes, we hypothesized that VEGF may play an important role in the protein leakage of Ménétrier's disease. Immunohistochemistry was performed using specific antibodies against VEGF and CD31 in gastric tissue specimens from 7 patients with Ménétrier's disease and 10 controls. The effect of recombinant TGF-alpha on VEGF production by cultured lamina propria mononuclear cells (LPMCs) was assessed. VEGF expression was detected for LPMCs and occasional epithelial cells of the gastric mucosa of Ménétrier's patients. VEGF-positive LPMCs were increased in tissues from patients with Ménétrier's disease (P<0.001). Of the LPMCs, T-lymphocytes and macrophages were the major sources of VEGF. CD31-positive blood vessels were increased in Ménétrier's tissue. (P<0.05). Recombinant TGF-alpha induced the production of VEGF in cultured LPMCs (P<0.05). In conclusion, the increased expression of VEGF, as a result of overproduction of TGF-alpha, may play a key role in the pathophysiology of Ménétrier's disease.

Chronic inflammation of the gastric epithelium is believed to induce mucosal changes that can eventually develop into gastric cancer. In gastrin-deficient (G-/-) mice exhibiting chronic inflammation in the hypochlorhydric stomach, we documented a prominent fundic mucous cell lineage sharing morphological similarity with preneoplastic changes reported in Helicobacter-infected mice. To study the identity and origin of this cell lineage, we screened for different gastric mucosal cell markers. The clusters of large, foamy cells stained for trefoil factor 2 (TFF2/SP), MUC6 and the lectin Griffonia Simplicifolia II (GSII), but not for the intestine-specific transcription factor Cdx2, suggested that they arise from gastric mucous neck cells. Ki67-labeled GSII-positive neck cells in Helicobacter felis-infected, but not G-/- stomachs, suggested that mucous neck cell proliferation accounted for expansion of this compartment in the H. felis model of gastritis, but not the G-/- model. Using RNase protection assays and quantitative PCR, we found that interferon gamma (IFNgamma) was the most abundant proinflammatory cytokine in the G-/- stomach. We also found that this Th1 cytokine can increase the abundance of mucous neck cells, since its infusion into mice recapitulated the appearance of these cells as observed in both G-/- and H. felis-infected mice. Using the human gastric cell line NCI-N87, we showed that IFNgamma induces the secretion of mucus and expression of MUC6, TFF2 and pepsinogen II, but not of pepsinogen I and intrinsic factor. In conclusion, our results demonstrate that inflammation, specifically the proinflammatory cytokine IFNgamma, induced expansion of the fundic mucous neck cell compartment, which likely represents both increased mucus production and cell number.

Background & Aims: Increase of intramucosal transforming growth factor alpha (TGFalpha) levels in the gastric fundus leads to oxyntic atrophy and massive foveolar hyperplasia in both metallothionein (MT)-TGFalpha mice and patients with Ménétrier's disease. We have evaluated the hypothesis that increased levels of TGFalpha in the fundus induces an antral pattern of cell differentiation in fundic glands by studying Pdx1, a transcription factor whose expression normally is confined to the gastric antrum., Methods: Induction of Pdx1 expression was evaluated in Pdx1(lacZ/+)/MT-TGFalpha bigenic mice treated with zinc. The distribution of Pdx1 in MT-TGFalpha mice and Ménétrier's disease patients was evaluated with anti-Pdx1 antibodies. Transcript levels were evaluated by quantitative polymerase chain reaction in mouse and human tissues and AGS cells., Results: In Pdx1(lacZ/+) mice, Pdx1 was expressed in antral mucosal cells including gastrin cells and TFF2-expressing deep glandular mucous cells. Zinc treatment for 2 to 8 weeks in Pdx1(lacZ/+)/MT-TGFalpha transgenic mice resulted in expression of Pdx1 throughout the fundus. No ectopic fundic Pdx1 expression was observed in either H. felis-infected or DMP777-treated mice. In MT-TGFalpha mice, 8 weeks of zinc treatment elicited nuclear Pdx1 staining throughout the fundic mucosa. TGFalpha treatment in AGS cells led to increases in Pdx1 and gastrin messenger RNA expression. Fundic sections from Ménétrier's disease patients showed nuclear Pdx1 staining throughout the fundic glands. Treatment of a Ménétrier's disease patient with an anti-epidermal growth factor receptor monoclonal antibody reduced fundic expression of both Pdx1 and gastrin., Conclusions: Overexpression of TGFalpha in MT-TGFalpha mice and Ménétrier's disease patients elicits ectopic expression in the fundus of Pdx1, consistent with the phenotype of antralization.

Menetrier's disease is a rare disease of the stomach generally described as hypertrophic gastropathy associated with hypoproteinemia. Gastric resection is still the most definitive treatment for the disease, but the appropriate extent of resection has not been determined. One of the major factors that would determine the extent of gastric resection in Menetrier's disease is its malignant potential. We present two recent cases of Menetrier's disease treated in our institution and review cases of the disease reported in Korea where the incidence of gastric cancer is one of the highest in the world.

In this paper a 21 year old patient was presented with Ménétrier's disease, associated with ulcerative colitis. The first symptoms of ulcerative colitis occurred at the age of eleven, since when the patient has been conservatively treated several times because of the exacerbations of the disease. During control examinations presence of polyploid changes in stomach was discovered by upper endoscopy. Gastrectomy was suggested because the patient had excessive anemic syndrome which required weekly substitutional therapy with deplasmatic eritrocytes, as well as hypoproteinemia, while multiple polyploid changes suspect for malignancy were gastroscopically identified. Patient accepted surgical treatment, and was transferred to the Clinic of Surgery. Total gastrectomy was performed, and patohistological finding confirmed Ménétrier's disease. After two weeks, the patient was released from the hospital in good general condition, with regular clinical and laboratory findings.

Menetrier's disease (MD) or polyadenomes en nappe is a form of hypertrophic gastropathy occurring primarily in middle-aged males. Patients generally present clinically with dyspepsia and, on occasion, with hypoproteinemic edema and anemia. The latter feature, when combined with the radiographic appearance of the stomach in MD, can lend to confusion with carcinoma and malignant lymphoma. To illustrate this diagnostic problem, a case is reported of a 41-year-old female who initially presented to her family physician with symptoms of easy fatigue and dyspnea on exertion and signs of pallor and ankle edema. Pertinent laboratory findings included a hemoglobin of 2.8 g/dL, hematocrit of 10.3 percent, mean corpuscular volume of 63.4 mu 3, a serum albumin of 2.7 g/dL, and heme positive stools. Endoscopic examination revealed a circumferential polypoid mass involving the cardia and fundus of the stomach with relative sparing of the antrum. A CT scan of the abdomen and pelvis showed a large mass in the stomach which the radiologists and gastroenterologists believed probably represented a lymphoma or gastric carcinoma. A total gastrectomy specimen exhibited features of MD. Routine bright-field microscopy and immunohistochemical reactivity for transforming growth factor-alpha confirmed the diagnosis of MD. Moreover, ulceration of the tips of some of the hypertrophied gastric folds provided an explantation for the iron deficiency anemia. Awareness that MD may present with anemia will help in the differential diagnosis with lymphoma and carcinoma.

Background: We have previously shown that eradication of Helicobacter pylori increases acid secretion in H. pylori-associated enlarged fold gastritis., Aim: To investigate whether locally produced interleukin-1 beta is possibly involved in the inhibition of acid secretion in H. pylori gastritis., Methods: IL-1 beta release from the gastric body mucosa was determined by short-term culture of biopsy specimens in 13 patients with enlarged fold gastritis (all H. pylori-positive), five H. pylori-positive and 10 H. pylori-negative patients without enlarged folds. The acid-inhibitory effect of locally produced IL-1 beta was examined by [14C]-aminopyrine uptake assay using isolated rabbit gastric glands., Results: IL-1 beta release was significantly greater in patients with enlarged fold gastritis, significantly correlated with both basal and tetragastrin-stimulated acid outputs in the H. pylori-positive patients (r = -0.591 and r = -0.641, respectively; P < 0.01), and significantly decreased with concomitant increases in acid secretions after eradication of H. pylori. [14C]-aminopyrine uptake was inhibited by IL-1 beta in a dose-dependent manner., Conclusions: Increased production of IL-1 beta caused by H. pylori infection is possibly involved in the inhibition of acid secretion in enlarged fold gastritis.

Background and Aims: It has been reported that eradication of Helicobacter pylori improves fold width in H pylori associated enlarged fold gastritis. The aim of this study was to clarify the mechanism of fold thickening in this condition., Patients and Methods: In eight patients with enlarged fold gastritis and 13 patients without enlarged folds, the presence of H pylori infection, inflammatory infiltrates, mucosal plasia, and epithelial cell proliferation in the body mucosa were investigated, and production of transforming growth factor alpha (TGF alpha), hepatocyte growth factor (HGF), and interleukin 1 beta (IL 1 beta) was determined by a competitive reverse transcription/polymerase chain reaction method and in vitro short-term culture of biopsy specimens., Results: In the patients with enlarged fold gastritis, inflammatory infiltrates including macrophages increased with H pylori colonisation in the body. Foveolar thickness and proliferating cell nuclear antigen (PCNA) labelling index were increased. Messenger RNA levels of HGF, but not TGF alpha, were increased, and release of HGF and IL 1 beta was increased. HGF release, which was positively correlated with IL 1 beta release and foveolar thickness, decreased in the presence of IL 1 receptor antagonist. After eradication of H pylori, inflammatory infiltrates, IL 1 beta and HGF release decreased with concomitant decreases in PCNA labelling index, foveolar thickness and fold width., Conclusions: Increased IL 1 beta and HGF production caused by H pylori infection may contribute to fold thickening of the stomach by stimulating epithelial cell proliferation and foveolar hyperplasia in patients with enlarged fold gastritis.

A patient with pigmentary retinopathy, nephrotic syndrome, Ménétrier's disease, and diabetes mellitus is presented. Other complications were congestive heart failure, hypothyroidism, hypertension, and hypertriglyceridemia. Hypogenitalism was also suspected. Pigmentary retinopathy is known to associate with many systemic diseases, which are classified into several syndromes. This case superficially resembles Alström's disease due to the common characteristics of pigmentary retinopathy, diabetes mellitus, renal disease, and hypogenitalism. But clinically and histologically, there are distinct differences. To our knowledge, this association has never been reported.

The bombesin-like peptides gastrin releasing peptide (GRP) and neuromedin B are found in the submucosal and myenteric plexuses of the human gastrointestinal tract. These peptides are potent mitogens to Swiss 3T3 fibroblasts and are important autocrine growth factors in human small cell lung cancer cells. We have recently described the presence of receptors for the bombesin-like peptide, GRP, on the human gastric cancer cell line St42. In this study, we examined fresh resected gastric cancer and uninvolved mucosa from 23 patients for the presence of binding sites to the bombesin-like peptides. Thirteen of 23 gastric cancers expressed high affinity binding sites for bombesin (mean Kd = 3.42 nM; mean Bmax = 40.5 pmol/mg protein), of which 12 were subsequently characterized and found to be of the GRP-preferring subtype. One of 23 mucosal samples specifically bound bombesin and was the only sample from a patient with Ménétrier's disease, a disorder of mucosal growth known to be premalignant. The early gastric cancer from this patient also possessed high affinity binding sites for GRP. This is the first description of binding sites to bombesin-like peptides on human gastric cancer and Ménétrier's mucosa. The role of bombesin/GRP antagonists in the treatment of gastric cancer warrants investigation.

Background: Menetrier's disease is characterized by giant gastric folds and foveolar hyperplasia. The extent of mucosal inflammation and glandular atrophy, however, is controversial. The aim of this study was to test the hypothesis that patients previously diagnosed with Menetrier's disease actually represent at least two diseases: (1) Hypertrophic lymphocytic gastritis (HLG) and (2) Massive foveolar hyperplasia and minimal inflammation (MFH)., Methods: All cases of possible Menetrier's disease were identified, and their clinical, laboratory, and pathological data were reviewed. In twenty-three patients with giant fundal folds, full-thickness tissue specimens (n = 19) or large suction biopsy (n = 4) tissue specimens were obtained., Results: Two distinct, nonoverlapping histological patterns were found; 13 patients had HLG and 10 patients had MFH. Clinical features and frequency of Helicobacter pylori were similar in these two groups. Patients with HLG had severe inflammation with numerous intraepithelial lymphocytes and mild foveolar hyperplasia. Alternatively, patients with MFH had greater foveolar hyperplasia, significantly thicker mucosa, and greater mucosal edema., Conclusions: Patients with MFH represent a form of hypertrophic gastropathy and should be designated as having Menetrier's disease, whereas patients with HLG should be considered part of the spectrum of lymphocytic gastritis.

Ménétrier's disease is an uncommon disorder of unknown etiology characterized by enlarged gastric folds with foveolar hyperplasia and cystic dilatation of gastric glands. Biochemical features that are seen frequently include hypoproteinemia, hypochlorhydria, and increased gastric mucus. Because transforming growth factor alpha (TGF alpha) is an epithelial cell mitogen that inhibits gastric acid secretion and increases gastric mucin content, we hypothesized that its altered expression might be involved in the pathogenesis of this disease. Therefore, we characterized TGF alpha immunoreactivity in the gastric mucosa of 4 patients with Ménétrier's disease. In contrast to the normal pattern of TGF alpha immunostaining in which TGF alpha appears most concentrated in parietal cells, there was intense staining in the majority of mucous cells in the gastric mucosa of patients with Ménétrier's disease. In one patient from whom sufficient fresh tissue was obtained to isolate RNA, expression of TGF alpha and the epidermal growth factor receptor was higher in the gastric mucosa relative to a normal control. In addition, metallothionein-TGF alpha transgenic mice, which overexpress TGF alpha in gastric mucosa, show a number of features characteristic of Ménétrier's disease. These include foveolar hyperplasia and glandular cystic dilatation, increased gastric neutral mucin staining, and reduced basal and histamine-stimulated rates of acid production. Taken together, observations derived from the human material and correlation with data from a transgenic mouse model support an important role for TGF alpha in the pathogenesis of Ménétrier's disease.

Transforming growth factor alpha (TGF alpha) is thought to participate in the normal and pathologic processes of numerous tissues, including the gastric mucosa. To explore its role in vivo, transgenic mice were generated overexpressing TGF alpha in the stomach. TGF alpha induced dramatic structural and functional lesions of the glandular stomach that were similar to Ménétrier's disease in humans. Transgenic mice developed severe adenomatous hyperplasia that resulted in a striking nodular thickening or hypertrophy of the gastric mucosa. Secretions obtained from affected stomachs contained no detectable gastric acid, suggesting that parietal cell function had been greatly impaired. These findings demonstrate that overproduction of TGF alpha can stimulate cellular proliferation, suppress acid secretion, and perturb organogenesis of the stomach of transgenic mice. Moreover, TGF alpha may contribute to the pathogenesis of related human hypertrophic gastropathies, such as Ménétrier's disease.

A case of Ménétrier's disease in a 3 year old child presenting with subtotal pyloric stenosis and fatal outcome due to postoperative complications is reported. It is emphasized that although radiographic and gastroscopic studies are helpful, a full-thickness mucosal biopsy is essential for the diagnosis of Ménétrièr's disease.

A 38-year-old man developed prominent hypoproteinemia after acute elevation of serum transaminase levels. Giant hypertrophy of the gastric mucosa, a short serum albumin half-life, and the absence of massive hepatocyte necrosis established the diagnosis of protein-losing gastropathy. The hypoproteinemia, gastric fold hypertrophy and hepatitis remitted spontaneously within 4 months. A high antibody titer against cytomegalovirus suggested an association between the viral infection and the patient's disease.

Lymphocytic gastritis is a form of gastric inflammation characterised by a pronounced increase in lymphocytes in gastric surface and foveolar epithelium. Lymphocytic gastritis is often associated with endoscopic evidence of 'varioliform gastritis'. Lymphocytic gastritis has recently been reported to be associated with other forms of hypertrophic gastropathies. We present a case of hypertrophic gastropathy with gastric adenocarcinoma, with both Menetrier's disease and lymphocyte gastritis. Immunohistochemical studies showed that the intraepithelial lymphocytes were predominantly alpha/beta T cells as in the normal stomach and not gamma/delta T cells as in coeliac sprue. This case together with the six recently published cases suggests that Menetrier's disease and lymphocytic gastritis may be part of the same disease spectrum.

We report a rare case of gastric collision tumor (carcinoid and adenocarcinoma) with gastritis cystica profunda that developed in a 49-year-old Japanese man. Early gastric cancer (moderately differentiated tubular adenocarcinoma) was present at the edge of an ulcer in the posterior wall of the upper gastric body. In addition, a carcinoid tumor was found adjacent to adenocarcinoma. This tumor displayed ribbonlike or trabecular patterns, and numerous constituent cells were positive for the argyrophil reaction with Grimelius' stain and serotonin. Electron microscopic features of this tumor confirmed typical carcinoid. There was no merged appearance between both tumors, suggesting collision-type tumor.

A case of an unusual hypertrophic gastropathy confined to the gastric antrum which presented with chronic anaemia is described. The clinical and pathological features are contrasted with Menetrier's disease and hypersecretory hypertrophic gastropathy, and a possible relation to solitary hyperplastic (regenerative) polyps is discussed.

Two cases of Ménétrier's disease are reported to illustrate the clinical presentation and diagnosis of this unusual condition. The literature has been reviewed of all the reported cases to establish the relative importance of the individual symptomatology, the value of the diagnostic methods, and to highlight the diagnostic pitfalls. Recognition of the barium meal appearances and snare biopsy at gastroscopy may avoid the necessity of diagnostic laparotomy.