Changes in the gastric enteric nervous system and muscle: A case report on two patients with diabetic gastroparesis

<p>Abstract</p> <p>Background</p> <p>The pathophysiological basis of diabetic gastroparesis is poorly understood, in large part due to the almost complete lack of data on neuropathological and molecular changes in the stomachs of patients. Experimental models indicate various lesions affecting the vagus, muscle, enteric neurons, interstitial cells of Cajal (ICC) or other cellular components. The aim of this study was to use modern analytical methods to determine morphological and molecular changes in the gastric wall in patients with diabetic gastroparesis.</p> <p>Methods</p> <p>Full thickness gastric biopsies were obtained laparoscopically from two gastroparetic patients undergoing surgical intervention and from disease-free areas of control subjects undergoing other forms of gastric surgery. Samples were processed for histological and immunohistochemical examination.</p> <p>Results</p> <p>Although both patients had severe refractory symptoms with malnutrition, requiring the placement of a gastric stimulator, one of them had no significant abnormalities as compared with controls. This patient had an abrupt onset of symptoms with a relatively short duration of diabetes that was well controlled. By contrast, the other patient had long standing brittle and poorly controlled diabetes with numerous episodes of diabetic ketoacidosis and frequent hypoglycemic episodes. Histological examination in this patient revealed increased fibrosis in the muscle layers as well as significantly fewer nerve fibers and myenteric neurons as assessed by PGP9.5 staining. Further, significant reduction was seen in staining for neuronal nitric oxide synthase, heme oxygenase-2, tyrosine hydroxylase as well as for c-KIT.</p> <p>Conclusion</p> <p>We conclude that poor metabolic control is associated with significant pathological changes in the gastric wall that affect all major components including muscle, neurons and ICC. Severe symptoms can occur in the absence of these changes, however and may reflect vagal, central or hormonal influences. Gastroparesis is therefore likely to be a heterogeneous disorder. Careful molecular and pathological analysis may allow more precise phenotypic differentiation and shed insight into the underlying mechanisms as well as identify novel therapeutic targets.</p

An update on autonomic neuropathy affecting the gastrointestinal tract

The original publication is available at www.springerlink.comGastrointestinal symptoms and disordered gut motility occur frequently in the diabetic population and are generally regarded as manifestations of gastrointestinal "autonomic dysfunction," although the relationships between both symptoms and dysmotility with abnormal cardiovascular autonomic function are weak. It is now recognized that the blood glucose concentration is both a determinant of and determined by gastrointestinal function. An improved definition of the underlying pathophysiology should facilitate the development of therapies that are targeted more effectively.Liza K. Phillips, Christopher K. Rayner, Karen L. Jones, and Michael Horowit

New management approaches for gastroparesis

Copyright © 2005 Nature Publishing GroupManagement of patients with gastroparesis is challenging. Although the syndrome has multiple causes and knowledge of the pathophysiology and natural history is far from complete, a number of common management principles can be applied. The relatively poor correlation between uppergastrointestinal symptoms and disordered gastric emptying represents a major difficulty in the therapeutic approach, and evidence to support the efficacy of current management strategies is often suboptimal, especially in relation to long-term therapy. In this review, the common causes and pathophysiology of gastroparesis are summarized, the diagnostic approach considered, and the evidence to support medical and surgical therapies reviewed. These therapies include currently available prokinetic drugs, novel medical therapies, and the promising technique of gastric electrical stimulation.Christopher K Rayner and Michael Horowit