Ménétrier's disease in a patient with refractory ulcerative colitis: a clinical challenge and review of the literature.

Ménétrier's disease (MD) is a rare disease of the stomach, characterised by hypertrophic gastric folds leading to protein loss. The association with ulcerative colitis (UC) is rare but has been reported in the literature. We report a case of a 29-year-old male affected by UC with an additional diagnosis of MD 3 years after UC diagnosis. UC was refractory to several treatment lines (thiopurines, infliximab, vedolizumab and ustekinumab), and the patient underwent colectomy. Octreotide was administered for MD normalising blood biochemistry, but it was not effective in inducing endoscopic remission of the stomach. Treatment options in patients with MD and UC are discussed.

Menetrier's disease. A diagnostic and therapeutic challenge.

We present a rare case of hypertrophic gastropathy associated with protein loss. A 35-year-old man was hospitalized for bowel habit changes, abdominal pain, generalized edema and symptomatic anemia. Pertinent laboratory findings included iron deficiency anemia (Hb 6.7g/dl, ferritin 5 ng/ml) and marked hypoalbuminemia (albumin 2.5 g/dl). Endoscopic biopsy samples of giant gastric folds observed along the greater gastric curvature revealed foveolar hyperplasia and significant parietal cell loss. Endoscopic ultrasonography showed gastric parietal thickening with preserved architecture and normal gastric wall layers. Menetrier disease was diagnosed and the patient treated with cetuximab, a monoclonal antibody that inhibits ligand binding of transforming growth factor alpha (TGFa), preventing gastric mucosa cell proliferation. After twelve months of treatment, the patient referred symptoms improvement, and gastric biopsy levels of the proliferation marker protein Ki-67 had decreased.

Presentamos un caso infrecuente de gastropatía hipertrófica asociada a pérdida de proteínas. Un hombre de 35 años fue hospitalizado por cambios en los hábitos intestinales, dolor abdominal, edema generalizado y anemia sintomática. Los hallazgos de laboratorio pertinentes incluyeron anemia ferropénica (Hb 6.7 g/dl, ferritina 5 ng/ml) e hipoalbuminemia marcada (albúmina 2.5 g/dl). Las muestras de biopsia endoscópica de pliegues gástricos gigantes observados a lo largo de la curvatura mayor gástrica revelaron hiperplasia foveolar y pérdida significativa de células parietales. La ecografía endoscópica mostró engrosamiento parietal gástrico con arquitectura conservada y capas de pared gástrica normales. Se diagnosticó enfermedad de Menetrier y se trató al paciente con cetuximab, un anticuerpo monoclonal que inhibe la unión del ligando del factor de crecimiento transformante alfa (TGFa), evitando la proliferación de células de la mucosa gástrica. Después de doce meses de tratamiento, el paciente refirió mejoría de los síntomas y los niveles de la proteína marcadora de proliferación Ki-67 en biopsia gástrica habían disminuido.

Menetrier's disease. A diagnostic and therapeutic challenge / Enfermedad de Menetrier. Un desafío diagnóstico y terapéutico

Abstract We present a rare case of hypertrophic gastropathy associated with protein loss. A 35-year-old man was hospitalized for bowel habit changes, abdominal pain, generalized edema and symptomatic anemia. Pertinent laboratory findings included iron deficiency anemia (Hb 6.7g/dl, ferritin 5 ng/ml) and marked hypoalbuminemia (albumin 2.5 g/dl). Endoscopic biopsy samples of giant gastric folds observed along the greater gastric curvature revealed foveolar hyperplasia and significant parietal cell loss. Endoscopic ultrasonography showed gastric parietal thickening with preserved architecture and normal gastric wall layers. Menetrier disease was diagnosed and the patient treated with cetuximab, a monoclonal antibody that inhibits ligand binding of trans forming growth factor alpha (TGFa), preventing gastric mucosa cell proliferation. After twelve months of treatment, the patient referred symptoms improvement, and gastric biopsy levels of the proliferation marker protein Ki-67 had decreased.

Resumen Presentamos un caso infrecuente de gastropatía hipertrófica asociada a pérdida de proteínas. Un hombre de 35 años fue hos pitalizado por cambios en los hábitos intestinales, dolor abdominal, edema generalizado y anemia sintomática. Los hallazgos de laboratorio pertinentes incluyeron anemia ferropénica (Hb 6.7 g/dl, ferritina 5 ng/ml) e hipoal buminemia marcada (albúmina 2.5 g/dl). Las muestras de biopsia endoscópica de pliegues gástricos gigantes observados a lo largo de la curvatura mayor gástrica revelaron hiperplasia foveolar y pérdida significativa de células parietales. La ecografía endoscópica mostró engrosamiento parietal gástrico con arquitectura conservada y capas de pared gástrica normales. Se diagnosticó enfermedad de Menetrier y se trató al paciente con cetuximab, un anticuerpo monoclonal que inhibe la unión del ligando del factor de crecimiento transformante alfa (TGFa), evitando la proliferación de células de la mucosa gástrica. Después de doce meses de tratamiento, el paciente refirió mejoría de los síntomas y los niveles de la proteína marcadora de proliferación Ki-67 en biopsia gástrica habían disminuido.

Ménétrier-like disease in a Pointer with concurrent granulomatous gastritis, helicobacteriosis and leishmaniosis: a case report.

BACKGROUND: Ménétrier-like disease is a rare hypertrophic canine gastropathy, reported in only seven dogs. Clinical signs are vomiting, anorexia and weight loss. Macroscopically, giant cerebriform gastric mucosal folds are typically seen in the corpus and fundus of the stomach. Histopathologically, fundic mucous cell hyperplasia and loss of parietal and chief cells are typical. CASE PRESENTATION: A nine-year-old spayed female Pointer had a history of intermittent vomiting, marked weight loss and hypoalbuminaemia. A gastroduodenoscopy was performed three times within three months with macroscopic changes remaining the same. The gastric mucosa of the corpus, fundus and proximal antrum was markedly irregular, with cerebriform mucosal folds. In the first gastric biopsies, histopathology revealed a moderate granulomatous gastritis, with a severe manifestation of Helicobacter-like organisms. Treatment for Helicobacter spp. decreased the vomiting slightly. The dog was diagnosed with concurrent leishmaniosis; the conventional anti-Leishmania treatment decreased the vomiting moderately, the hypoalbuminaemia resolved and the dog gained weight back to a normal body condition. Granulomatous gastritis was not present in the gastric biopsies after these treatments. The dog increased vomiting when palliative treatment (maropitant citrate, ondansetron and esomeprazole) was discontinued, and thus, full-thickness biopsies of the stomach were taken and Ménétrier-like disease was diagnosed. The affected area was too large to be surgically removed; thus, palliative treatment was reinstated. The dog remained clinically well 39 months after the first clinical presentation. CONCLUSIONS: This is the first report of Ménétrier-like disease in a dog with a simultaneous manifestation of granulomatous gastritis, helicobacteriosis and leishmaniosis. The clinical signs decreased after treatment of helicobacteriosis and leishmaniosis, but vomiting remained probably as a sign of Ménétrier-like disease. Treatment options for dogs are surgical removal of the abnormal area or palliative treatment. In humans, promising results for a cure have been shown with cetuximab treatment, a human monoclonal antibody, but no canine antibody is commercially available yet. The dog here was doing well 39 months after first presentation, which is the longest reported survival time for Ménétrier-like disease with only palliative treatment in dogs. Full-thickness biopsies are preferred in macroscopic hypertrophic lesions of the stomach for better assessment of Ménétrier-like disease.

Ménétrier's disease : a case of successful treatment using long-acting octreotide.

The authors describe a 31 years old male, admitted for hematemesis, epigastric pain and lower limb edema. Laboratorial data showed haemoglobin 18.4g/dl, total proteins 2.8g/dl, albumin 1.6g/dl and hipogammaglobulinaemia. 24h urinary proteins were normal. HIV and CMV serology were negative. Upper GI endoscopy revealed markedly enlarged gastric folds covered by abundant exudative fluid. Endoscopic ultrasound showed ascites, pleural effusion and gastric wall thickening with mucosa expansion and intact submucosa. In gastric biopsies foveolar hyperplastic and regenerative mucosa were observed being suggestive of Ménétrier´s disease. Helicobacter pylori was not detected. Albumin replacement and diuretics corrected anasarca and long-acting octreotide was instituted. Nine months later, the patient was asymptomatic, serum proteins were normal (albumin 4.6g/dl and total proteins 6.5g/dl), signs of endoscopic improvement were observed with marked reduction in gastric folds and mucosal inflammation and no ultrastructural changes were detected in gastric specimens sent for electron microscopy. Ménétrier´s Disease (MD) is a rare form of hypertrophic gastropathy characterized by massive enlargement of gastric folds causing marked protein exudation. The increase in tight junction diameter is the most consistent ultraestrutural change. Octreotide is a somatostatin analogue that acts by modulating TGFαEGFR pathway, which has been associated with the pathogenic mechanisms. As well as other cases reported in literature, this case report highlights the potential of long-acting octreotide for MD treatment avoiding more expensive therapies like cetuximab and gastrectomy.

A case of Ménétriere´s disease treated with the monoclonal antibody cetuximab.

Ménétriere´s disease is a rare disorder of the body and fundus of the stomach, characterized by a massive proliferation of the foveolar cells and subsequent excess mucous secretion. This results in hypoproteinemia due to loss of serum proteins across the gastric mucosa. The cause of Ménétriere´s disease is unknown, and due to the irreversible and premalignant character of the disorder, the patients affected have been subdued to gastrectomy as the only curable treatment. Epidermial growth factor (EGF) has been implicated in the pathogenesis, a finding that makes the disorder receptive to monoclonal antibody treatment against the EGF receptor. In this case report, we present a 41-year-old woman referred to our emergency department due to dizziness, nausea, and vomiting. A thorough medical investigation, combining clinical history, laboratory investigations, an upper endoscopy with full-thickness snare biopsies, and a CT scan confirmed Ménétriere´s disease, and she was successfully treated with the monoclonal antibody cetuximab.

Ménétrier's disease presenting as recurrent unprovoked venous thrombosis: a case report.

BACKGROUND: Acquired thrombophilia is a potential sequela of malignancy, chronic inflammation, and conditions characterized by severe protein deficiency (for example, nephrotic syndrome, protein-losing enteropathy). As such, venous thrombosis is often a feature, and occasionally a presenting sign, of systemic disease. Ménétrier's disease is a rare hyperplastic gastropathy that may lead to gastrointestinal protein loss and hypoalbuminemia. To date, reports of venous thrombosis associated with Ménétrier's disease are exceedingly scarce. CASE PRESENTATION: We report the case of a 40-year-old white man who presented with unprovoked deep venous thrombosis, pulmonary embolism, and renal vein thrombosis. Upon receiving therapeutic anticoagulation, he developed severe gastrointestinal bleeding, and endoscopic evaluation led to a diagnosis of Ménétrier's disease. A laboratory workup revealed deficiency of protein C, protein S, and antithrombin III, as well as markedly elevated levels of factor VIII. He was determined to have an acquired thrombophilia as a direct result of Ménétrier's disease. CONCLUSIONS: This case describes an acquired thrombophilic state in a patient with Ménétrier's disease and profound hypoalbuminemia. Although this association is rarely described, we discuss the probable mechanisms leading to our patient's thrombosis. Specifically, we posit that his gastrointestinal protein loss led to a deficiency of several anticoagulant proteins and a compensatory elevation in factor VIII, as occurs in nephrotic syndrome and inflammatory bowel disease. Of note, this patient's recurrent venous thrombosis was the initial clinical sign of his gastrointestinal pathology.

Ménétrier's disease: Long-term remission with lanreotide.

Ménétrier's disease is a rare hypertrophic gastropathy, causing protein leak. An overexpression of transforming growth factor alpha is involved. In inhibiting the epidermal growth factor receptor, cetuximab and somatostatin analogues are the two most promising treatments, allowing to avoid radical gastrectomy. We report the case of a patient with a sustained clinical remission after treatment with lanreotide, but without complete endoscopic healing. We discuss the available therapeutic options and present a literature review of somatostatin analogues for the treatment of Ménétrier's disease.

Disease recurrence following cetuximab completion and declining a gastrectomy: what next to manage Ménétriers disease?

Ménétriers disease is a rare mucosal hyperproliferative disorder of the stomach, however, the evidence for long-term care remains limited, especially if a gastrectomy is declined. We present a case of 25-year-old Caucasian woman with a history of end-stage renal failure (ESRF) who experienced worsening symptoms of abdominal pain, haematemesis and abdominal swelling, with her serum albumin dropping to 20 g/L and haemoglobin to 4.9 g/dL. Endoscopy showed markedly hyperplastic gastric folds consistent with Ménétriers disease, confirmed histologically by gland dilation and gastric pit expansion. Intravenous cetuximab was prescribed for 12 months, with clinical, biochemical and endoscopic improvement. However, 5 weeks post cetuximab completion, there was relapse to 50% gastric coverage with Ménétriers. A discussion around gastrectomy was rejected by the patient. This is the first report of relapsing Ménétriers disease in a female patient with ESRF; we suggest that long-term cetuximab should be considered if a gastrectomy is declined.

[Hypertrophic protein-losing gastropathy: Ménétrier disease. A clinical case]. / Gastropatía hipertrófica perdedora de proteínas: enfermedad de Ménétrier. Caso clínico.

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.

[18F]FLT-PET to predict pharmacodynamic and clinical response to cetuximab therapy in Ménétrier's disease.

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.

Evolving molecular targets in the treatment of nonmalignant gastrointestinal diseases.

Novel treatments for gastrointestinal (GI) diseases are based on molecular targets. Novel pharmacologic and biological agents with greater selectivity and specificity are being developed for a variety of epithelial diseases, including eosinophilic esophagitis (EoE), gastroesophageal reflux disease (GERD), celiac disease, short bowel syndrome (SBS), and inflammatory bowel diseases (IBDs; Crohn's disease and ulcerative colitis). Motility and secretory agents are being developed for gastroparesis, irritable bowel syndrome (IBS), functional constipation, and diarrhea. Here we focus on data from clinical trials involving validated pharmacodynamic or patient response outcomes.

A pediatric non-protein losing Menetrier's disease successfully treated with octreotide long acting release.

Pediatric Menetrier's disease (MD) is an uncommon, acute, self-limited hypertrophic gastropathy characterized by enlarged gastric folds associated with epithelial hyperplasia and usually accompanied by protein losing gastropathy. Gastric cytomegalovirus infection is found in one third of MD children and its treatment is often associated with remission. Diagnosis often requires full-thickness biopsy due to inability to detect typical histological findings with conventional endoscopic biopsy. We report an uncommon case of non self-limited pediatric MD needing endoscopic mucosal resection for diagnosis which was then successfully treated with octreotide long-acting release (LAR). To the best of our knowledge, this is the first pediatric MD case successfully treated with octreotide LAR. Our experience suggests octreotide LAR as treatment for refractory MD before gastrectomy.