A Rare Case of Hypertrophic Gastropathy with Adenocarcinoma Arising from a Gastric-type Adenoma.

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.

MIB2 variants altering NOTCH signalling result in left ventricle hypertrabeculation/non-compaction and are associated with Ménétrier-like gastropathy.

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.

A case of Ménétrier's disease seemingly caused by hilar cholangiocarcinoma.

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.

[MENETRIER DISEASE].

Menetrier disease (MD) is a very rare stomach pathology of unknown etiology characterized by manifest hypertrophy of gastric mucosa. The main causes of MD are believed to be Helicobacter pylori and cytomegalovirus infections. The most frequent symptom is epigastric pain. Also common are peripheral oedema due to hypoalbuminemia and increased permeability of gastric mucosa. The main diagnostic signs of MD include diffusive enhancement of mucosal folds, foveolar hyperplasia and glandular atrophy with a decrease in the number of main and parietal cells, hypoalbuminemia and peripheral oedema. MD being a very rare condition, the optimal methodfor its treatment is unknown.

Ménétrier's disease-like hypertrophic gastritis in two red-capped mangabeys (Cercocebus torquatus).

Chronic lymphoplasmacytic gastritis in two red-capped mangabeys (Cercocebus torquatus) at a zoological facility progressed to severe hypertrophic gastropathy similar to Ménétrier's disease that affects humans. Clinical signs included emesis, diarrhea, hunched posture consistent with abdominal pain, anemia, and hypoproteinemia. Large gastric masses were present and in one case created a gastric outflow obstruction. Both cases were positive for simian immunodeficiency virus and Helicobacter spp. were variably isolated, although the association with the hypertrophic gastropathy is unclear. Medical treatment had varying success and included sucralfate, H2 receptor antagonists, proton pump inhibitors, diet manipulations, and antibiotic therapies targeting Helicobacter spp. Surgical resection of a large portion of the stomach resulted in some palliative improvement in one case. Overall, this disease presented many challenges regarding identification, confirmation of diagnosis, and clinical management. Both aggressive medical and surgical treatments were unrewarding for long-term management of hypertrophic gastropathy in this pair of red-capped mangabeys and resulted in a poor prognosis in these cases.

A case of Ménétrier's disease without Helicobacter pylori infection.

Ménétrier's disease (MD) is a rare, acquired, premalignant disorder of the stomach characterized by enlarged gastric folds with foveolar hyperplasia, the phenotype of antralization of gastric glands, hypochlorhydria and hypoproteinemia. The etiology of MD is unknown, but both increased signaling by transforming growth factor-α and infection with Helicobacter pylori (H. pylori) have been implicated. Here, a case involving 70-year-old man who lost weight after developing anorexia and diarrhea is reported. He was diagnosed as MD without H. pylori infection, and in spite of intensive care, he died 40 days after admission. An autopsy confirmed MD. Immunohistochemistry revealed overexpression of transforming growth factor-α in the foveolar region of the gastric mucosa. The autopsy also distinguished this H. pylori-negative MD from hyperplastic polyp of the stomach, which is important in clarifying the entity of H. pylori-negative MD.

Pierre Ménétrier and his disease.

In 1888, Pierre Ménétrier first described the disease that bears his name. Many of the findings he reported then remain accepted features of the disease. Based on studies performed in our laboratory over the past 20 years, we have implicated increased transforming growth factor-α (TGFα) expression and heightened epidermal growth factor receptor (EGFR) activity in the pathogenesis of Ménétrier's disease. Herein, we provide a historical perspective of this rare disorder, review our experience with Ménétrier's disease, and discuss future challenges and opportunities posed by this disorder.

Ménétrier's disease of the stomach: a clinical challenge.

Ménétrier's disease is a rare hyperproliferative protein-losing gastropathy of the gastric foveolar epithelium. Most common symptoms include epigastric pain with fullness and vomiting, and generalized peripheral edema with hypoalbuminemia. Radiologically, the wall of the gastric body and fundus is diffusely thickened, often with antral sparing. Giant rugal edematous folds are seen on gastroscopy, and histology of biopsy material shows diffuse foveolar hyperplasia with cystic dilatation of the glandular portion of the gastric mucosa in the absence of significant inflammatory infiltrate. The recent discovery of transforming growth factor α overexpression opens the way of epidermal growth factor receptor blockade with cetuximab as first-line treatment modality in severe cases of Ménétrier's disease.

Long-term gastric changes in achlorhydric H(+)/K(+)-ATPase beta subunit deficient mice.

OBJECTIVE: Hypergastrinemia is known to induce enterochromaffin-like (ECL) cell derived tumors in rodents and man. In this study, we have examined the effect of life-long gastric anacidity and secondary hypergastrinemia in H(+)/K(+)-ATPase beta subunit knockout (KO) mice. MATERIAL AND METHODS: Female H(+)/K(+)-ATPase beta subunit KO mice and controls were followed up to 20 months before being sacrificed. At termination, intragastric acidity was measured and internal organs were examined for macroscopic and histological changes. Plasma gastrin and serum albumin were measured. RESULTS: KO mice were anacidic and hypergastrinemic. The oxyntic mucosa was markedly, and with increase in age, hyperplastic with cystic dilatations resembling the changes seen in patients with Menetrier's disease. Serum albumin in KO mice did not differ from controls. KO mice had a marked ECL cell hyperplasia, but only one gastric carcinoma was found. CONCLUSION: H(+)/K(+)-ATPase beta subunit KO mice develop Menetrier-like changes in the stomach, and may be useful in studying the pathogenesis and treatment of Menetrier's disease. The reason why only one KO mice developed gastric neoplasia whereas the histamine-2 blocker loxtidine has previously been found to regularly induce ECL cell carcinoids in mice is not known.

Osteoartropatía hipertrófica primaria (paquidermoperiostosis). Aportación de 2 casos familiares y revisión de la literatura / Primary hypertrophic osteoarthropathy (pachydermoperiostosis). Report of two familial cases and literature review

No disponible

Ménétrier's disease and severe gastric ulcers associated with cytomegalovirus infection in an immunocompetent child: a case report.

In pediatric patients, Ménétrier's disease is an uncommon clinical entity that has been rarely described only as sporadic cases, and the etiology is unclear. These patients usually have a self-limiting clinical course. Cytomegalovirus is an important pathogen in the immunocompromised host. However, cytomegalovirus infection can be detected in non-immunocompromised children. We discuss the possible role of cytomegalovirus infection in both Menetrier's disease and severe gastric ulcers in an immunocompetent child.

The edematous toddler: a case of pediatric Ménétrier disease.

Ménétrier disease is a protein-losing gastroenteropathy, characterized clinically by nonspecific gastrointestinal symptoms and generalized edema, biochemically by hypoalbuminemia, and pathologically by enlarged gastric folds. Distinct from its adult counterpart, Ménétrier disease of childhood usually remits spontaneously and has a very good prognosis. We present a case report of Ménétrier disease in an edematous toddler and a brief review.

Ménétrier disease and gastrointestinal stromal tumors: hyperproliferative disorders of the stomach.

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.

Mitochondrial neurogastrointestinal encephalomyopathy.

Mitochondrial neurogastrointestinal encephalomyopathy is an autosomal recessive disease characterized by progressive ophthalmoplegia, peripheral neuropathy, mitochondrial abnormalities and gastrointestinal involvement. We describe a 19-year-old male having chronic intestinal pseudoobstruction associated with ophthalmoplegia and proximal muscle weakness. The clinical and radiologic features suggested the diagnosis of mitochondrial neurogastrointestinal encephalomyopathy. Mitochondrial genetic defects should be considered in the differential diagnosis of unexplained chronic gastrointestinal symptoms accompanied by neurological findings, especially in families where there is more than one individual with the same kind of symptoms.

[Acetic acid-induced gastro-duodenal ulcers in experimental animals--examples of serendipity and pseudoserendipity].

Our understanding of the function and etiology of various gastric diseases has exponentially expanded over the past 40 years. In particular, several animal models had been devised and used for screening of anti-ulcer drugs and elucidation of pathogenesis. This review describes how water-immersion stress ulcer model, Helicobacter pylori ulcer model, and acetic acid ulcer models were established in experimental animals. In recent years, genetically modified mice allowed rapid accumulation of very important findings. H(2)-receptor knockout mice revealed to exhibit Menetrier's disease-like gastric mucosal changes. Gastrin-transgenic mice infected with H. pylori revealed to develop gastric cancer. The hypothesis for the origin of parietal cells was provided.