[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.

[Digestive insufficiency of the stomach in children from the positions of clinical morphology and its role in the assessment of the indications for nutritional support ].

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.

High-frequency ultrasonographic imaging of the gastrointestinal wall.

The gastrointestinal (GI) tract, with its layered structure, can be imaged by ultrasound using a transabdominal approach or intraluminal high-frequency probes. New ultrasound technology can be used to characterize tissue hardness, study motility in real-time, direct diagnostic and therapeutic intervention, evaluate GI wall perfusion and tissue viability, and perform 3D imaging. Ultrasound is a safe imaging modality, and development of smaller devices has improved its application as a flexible clinical tool, which also can be used bedside. Recently, microbubbles have been injected into the blood stream loaded with contrast agents, or other diagnostic and therapeutic agents. Such bubbles can be destroyed by ultrasound waves, thus releasing their content at a given area of interest. In this article, we present a review of the GI wall anatomy and discuss currently available ultrasound technology for diagnosis and treatment of GI wall disorders.

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.

Cytomegalovirus-associated protein-losing gastropathy in childhood.

Menetrier's disease is an uncommon disease in childhood, characterized by gastric hypertrophy and hypoalbuminemia secondary to protein loss through the gastric mucosa. This paper describes a series report of protein-losing gastropathy associated with cytomegalovirus (CMV) infection in children and reviews the literature. We reviewed the medical records of eight children with diagnosis of Menetrier's disease or protein-losing gastropathy with evidence of acute CMV infection. During a five-year period there were eight children that were diagnosed with CMV-associated protein-losing gastropathy, all in one medium-sized pediatric ward in a general hospital. The mean age was 32 months and there was no gender predominance. The most common presenting symptoms were vomiting and edema. Average symptoms' duration prior to admission was 3.2 weeks and mean albumin at presentation was 1.8 g/dl (range, 1.5-2.5 g/dl; normal values, 3.5-5 g/dl). All eight children fully recovered. In conclusion, CMV infection should be suspected in every child who presents with protein-losing gastropathy. The availability of newer, rapid diagnostic techniques such as polymerase chain reaction (PCR) may facilitate diagnosis, as serology studies may be misleading. Usually, only supportive care is required, but treatment with ganciclovir may be considered for severe or prolonged cases.

Chronic treatment of Ménétrier's disease with Erbitux: clinical efficacy and insight into pathophysiology.

BACKGROUND & AIMS: Ménétrier's disease is a rare premalignant hypertrophic gastropathy characterized by large rugal folds, foveolar hyperplasia with glandular atrophy, hypochlorhydria, and hypoalbuminemia. Patients with severe disease often exhibit refractory nausea and vomiting and require gastrectomy. Evidence from both mice and human beings suggests a critical role for epidermal growth factor receptor (EGFR) signaling in the pathogenesis of this disease. We previously reported significant clinical and biochemical improvement of a single patient treated for 1 month with Erbitux, a monoclonal antibody that blocks ligand binding to EGFR. METHODS/RESULTS: We describe 2 patients who were given longer-term treatment with Erbitux as an alternative to gastrectomy. The first patient presented with nausea, hypoalbuminemia, and peripheral edema that required total parenteral nutrition (TPN) and infusions of albumin. On institution of Erbitux, there was rapid improvement in nausea and vomiting and stabilization of serum albumin with discontinuation of TPN and albumin infusions. Serum albumin remained stable during a 1-year course of Erbitux without supplemental protein. Application before and after Erbitux of the radiopaque dye ruthenium red to biopsies of the gastric oxyntic gland mucosa demonstrated prompt and persistent closure of tight junctions by electron microscopy. The second patient presented with chronic gastric bleeding that required bimonthly blood transfusions. During a 4-month course of Erbitux, his hematocrit stabilized, and transfusion requirements were eliminated. CONCLUSIONS: The present report demonstrates the efficacy of prolonged Erbitux therapy in patients with different presentations of severe Ménétrier's disease and also provides insight into the pathophysiology of the protein-losing gastropathy.

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.

Evidence for repatterning of the gastric fundic epithelium associated with Ménétrier's disease and TGFalpha overexpression.

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.

[Ménétriér's disease in children].

Ménétriér's disease in children is a rare disorder that is characterized by the presence of marked protein losing gastropathy associated with enlarged and thickened gastric folds. Abnormal regulation of gastric epithelial growth, probably triggered by an infectious agent, has been suggested as an etiology for this disorder. We describe a case of Ménétriér's disease in a young child and review the current literature encompassing the different aspects of the disease.

Enfermedad de ménétrier: presentación de un caso infantil con diez años de seguimiento y degeneración maligna / Gastric adenocarcinoma in a patient with ménétrier disease after ten years of follow-up

Introducción. La enfermedad de Ménétrier ocurre con menor frecuencia en los niños que en los adultos. En los niños se reconoce como una enfermedad benigna, autolimitada, de buen pronóstico; en adultos por el contrario, puede malignizarse y degenerar en linfoma gástrico o adenocarcinoma. Se caracteriza por hipertrofia de los pliegues gástricos, hipoproteinemia con hipoalbuminemia e hipersecreción gástrica, con hipoclorhidria o aclorhidria. Caso clínico. Se presenta el caso de una niña con enfermedad de Ménétrier diagnosticada a los 12 años de edad con evolución atípica y seguimiento durante 10 años. Se describen los hallazgos clínicos, bioquímicos, endoscópicos e histológicos durante su evolución, así como tratamientos recibidos y su respuesta. Se describe la evolución atípica, degeneración maligna de la enfermedad. Se hace una revisión de la literatura en cuanto a las causas de la enfermedad, su fisiopatología, evolución natural y las posibilidades terapéuticas existentes. Conclusión. En este caso se demuestra la degeneración maligna de la enfermedad de Ménétier, con evolución a adenocarcinoma gástrico intramucoso, después de diez años de evolución, en una niña de doce años de edad, este tipo de evolución se ha descrito solamente en adultos.

Spontaneous remission of hypertrophic lymphocytic gastritis associated with hypoproteinemia.

A 54-year-old woman came to our office because of pretibial edema. She had no gastrointestinal symptoms. Laboratory tests revealed severe hypoproteinemia. Upper gastrointestinal endoscopy demonstrated enlarged gastric folds and multiple aphthoid nodules on the body and the fornix of the stomach. The biopsy specimen revealed a large number of CD8 positive intraepithelial T-lymphocytes infiltrating the gastric mucosa. Both serum total protein and the gastric lesions improved eight months after her first visit without any therapy for peptic ulcer or eradication of Helicobacter pylori. The data suggest that spontaneous remission may occur in lymphocytic gastritis without any gastrointestinal symptoms.

Gastritis hipertrófica infantil asociada a infección por citomegalovirus / Hypertrophic gastritis inn infancy associated with cytomegalovirus

En este trabajo relatamos el caso de un niño de 3 años con anasarca por hipoproteinemia y sin proteinuria,en el quen los estudios radiológicos,endoscópicos e histológicos permitieron reconocer una gastritis hipertrófica con hiperplasia y dilataciones quísticas de las gándulas con células positivas para el antígeno del citomegalovirus.El proceso siguió un curso de resolución espontánea clínica e histológica,confirmada 40 días más tarde

Eosinophil infiltration and degranulation in Helicobacter pylori-associated chronic gastritis.

Eosinophil granules contain cationic proteins, including the major basic protein, which are toxic to mammalian tissue. While eosinophils have been observed to comprise part of the inflammatory reaction in acute Helicobacter pylori gastritis, the role of the eosinophil in the pathogenesis of chronic gastritis is unknown. We evaluated whether eosinophil infiltration and degranulation are associated with chronic gastritis and H. pylori infection. We studied eight patients with chronic H. pylori antral gastritis, three with chronic antral gastritis in the absence of H. pylori, 11 healthy age-matched volunteers without antral gastritis, and eight patients with H. pylori-negative chronic specific gastritis (three Crohn's antral gastritis and five Ménétrier's disease). Serial sections were stained with hematoxylin and eosin, with Giemsa, and by a specific indirect immunofluorescence technique for eosinophil granule major basic protein. Specimens were graded independently by three observers and scores of 0-3 were given for eosinophil infiltration and degranulation (0 = none to 3 = confluent infiltration and/or degranulation). In H. pylori antral gastritis, significantly greater eosinophil infiltration and degranulation were found compared to the normal group, Ménétrier's disease, and chronic H. pylori-negative gastritis. There was no significant difference between gastric Crohn's disease and H. pylori gastritis. The severity of chronic gastritis was significantly correlated with the eosinophil score. Eosinophil degranulation did not appear to be greater at or near sites of bacterial colonization in the H. pylori gastritis specimens. The results suggest that eosinophil infiltration and degranulation may be associated with H. pylori gastritis. We postulate that the release of toxic cationic proteins from eosinophils contributes to the inflammatory changes present in H. pylori gastritis.

Gastritis hipertrófica infantil asociada a infección por citomegalovirus / Hypertrophic gastritis inn infancy associated with cytomegalovirus

En este trabajo relatamos el caso de un niño de 3 años con anasarca por hipoproteinemia y sin proteinuria,en el quen los estudios radiológicos,endoscópicos e histológicos permitieron reconocer una gastritis hipertrófica con hiperplasia y dilataciones quísticas de las gándulas con células positivas para el antígeno del citomegalovirus.El proceso siguió un curso de resolución espontánea clínica e histológica,confirmada 40 días más tarde