The condition which is called hypertrophic gastropathy, hypertrophic gastritis, or hyperplastic gastropathy, is uncommon and is characterized by massive enlargement of rugal folds in the body and fundus of the stomach (Fig. 1) 949. It is most widely known by its eponymic title, Ménétrier's disease. Ménétrier (1859–1935) did not define a syndrome; rather he reported in 1888 the postmortem observations of two patients showing extraordinary gastric pathology in association with gastric cancer. The stomachs of both patients were filled with tenacious mucus and demonstrated similar microscopic pathology. One patient had ascites and peripheral oedema; the other had recently suffered a major cerebral infarction. Although Ménétrier acknowledged that others had observed patients exhibiting such giant enlargement of gastric folds before him, his name has been linked with this condition.

Although conceptions of the disorder differ widely in detail, there is agreement that the finding of enlarged gastric rugae in the body and fundus, largely sparing the antrum, and exclusive of those of granulomatous or neoplastic origin, is central to the diagnosis of Ménétrier's disease. Radiological criteria reflecting this gross pathology are similarly broadly accepted. Microscopically, the foveolar compartment is typically expanded with elongated and branched gastric pits, often with focal cystic dilatation. The deep compartment may be hyperplastic, normal, or atrophic, with cystic dilation of gastric glands. Ming has attempted to define three microscopic patterns of hypertrophic gastropathy: mucous cell predominant, glandular cell predominant, and a mixed mucous– glandular type. Some authors have suggested that only the mucous cell type should be considered representative of Ménétrier's disease, but Ming made no such claim; in fact he suggested that the patient reported by Ménétrier probably had the mixed cell type hyperplasia.

In the middle of this century several studies identified hypoproteinaemia and hypochlorhydria as frequently associated findings in patients exhibiting pathological findings similar to those reported by Ménétrier. Since then, some authors have applied one or both of these as diagnostic criteria, but this policy is far from universal.

Attempts to subdivide hypertrophic gastropathies on the basis of such criteria have resulted in a plethora of descriptive labels, but have been largely unsuccessful in clarifying the disorder because of overlap among groups of patients. There is poor correlation between acid secretion and serum protein levels. Furthermore, there is an imperfect relationship between these parameters and the mucosal histology as defined by Ming's criteria. Additional confusion stems from inconsistencies in evaluation of cases of suspected Ménétrier's disease, making it difficult to be certain that all are in fact bona fide. In a recent review of 125 cases diagnosed as Ménétrier's disease over a 26-year period, sufficient data to merit an unequivocal diagnosis were available for only six patients.

This quagmire is best avoided by focusing on the hallmarks of each case. As each of the diagnostic features appears to lie along a spectrum which may vary not only between patients, but possibly over time within the same individual, we have suggested the rubric trivalent gastropathy, emphasizing the importance of defining these parameters in each instance and without arbitrarily implying relationships among these aspects. In all cases of suspected Ménétrier's disease measurement of serum albumin and gastrin levels (to rule out the Zollinger-Ellison syndrome, which can also produce gastric mucosal hypertrophy), gastric acid secretion studies, and a full-thickness gastric biopsy are mandatory.

Therapy is directed to relieving pain (present in over 80 per cent of cases) blood loss (34 per cent), and symptoms of hypoproteinaemia (40 per cent). Anticholinergic therapy may diminish acid secretion and possibly tighten gastric cell junctions, reducing protein losses via this route. H&sub2;-receptor blockers may have similar effects. These are only temporary measures, however, and do not address the risk of gastric carcinoma. Furthermore, it is unclear whether they have any effect on the hypercoagulable state often associated with Ménétrier's syndrome.

Surgical resection offers a definitive solution. Distal subtotal gastrectomy with a Billroth I or Billroth II reconstruction is to be discouraged, as it would entail anastomosis of abnormal stomach to normal intestine with the attendant risks of anastomotic leakage and obstruction. Vagotomy and pyloroplasty avoids such an anastomosis and offers a reduction in acid output, but fails to address the risk of neoplasia. Total gastrectomy is the best therapeutic solution to Ménétrier's disease and is generally well tolerated. Employing only normal tissues in the reconstruction, all abnormalities are corrected, and the risk of gastric neoplasia is removed.

The risk of gastric cancer in the setting of Ménétrier's disease is difficult to quantify. Retrospective analyses have found neoplasia in 10 to 15 per cent of reported cases; prospective studies are difficult, given the rarity of the condition. The increased cell proliferation essential for carcinogenesis in most epithelial systems might be expected to create a fertile field for the development of carcinoma in hyperplastic gastric mucosa. In two of the six cases we have recently reported, gastric carcinoma developed years after the initial diagnosis of Ménétrier's disease and, in another, the full spectrum of preneoplastic to malignant epithelial changes was seen. The safety of medical management with routine endoscopy is uncertain, because the sensitivity of such surveillance with random biopsy in the setting of such a diffusely abnormal organ is unknown. The association of adenocarcinoma with Ménétrier's disease appears real and makes the argument for total gastrectomy stronger.

Sundt TM III, Compton CC, Malt RA. Ménétrier's disease: a trivalent gastropathy. Ann Surg 1988; 208: 694–701.