Effect of Chronic Neurostimulation on the Number of Interstitial Cells of Cajal in Gastric Smooth Muscle in Patients With Severe Gastroparesis

Introduction: There is increasing evidence for specific cellular changes in the gastric smooth muscle of patients with diabetic (DM) and idiopathic (ID) gastroparesis (GP). The most significant findings are loss of interstitial cells of Cajal (ICC) per high power fields (HPF), in addition there can be neuronal abnormalities and an immune cellular infiltrates. Gastric electrical stimulation (GES) therapy is provided for GP patients who are documented to be refractory to all available medical therapies. During the surgical implantation of GES, a biopsy sample of the antral smooth muscle from the gastric wall is obtained for further analyses. The aim of our preliminary report was to investigate if chronic GES therapy delivered to the gastric smooth muscle, could induce regeneration or changes in the status of the ICC. Methods: Full-thickness antral biopsies were obtained from GP patients who underwent at least 2 abdominal surgeries, for the placement, relocation, replacement, as well as removal of the GES device based on clinical status. Thus a second sample of the antral smooth muscle was able to be acquired months to years after the initial biopsy when the electrodes were first implanted. The tissues were stained with H&E, C-Kit for ICC and trichrome to identify fibrosis. Based on our previous control data, depletion of ICC was defined as less than 10 cells per high power field (HPF) in the antral smooth muscle. Results: Tissue data reported in 3 GP patients are summarized: 1) 62 year old female patient with DG: Number of antral ICC before GES therapy was 5/HPF; 15 months later it changed to 8/HPF. 2) 33 year old female patient with IG: Number of antral ICC before GES therapy was 7/HPF; 60 months later it was 16/HPF. 3) 32 year old female with DG: Number of antral ICC before GES therapy was 20/HPF; 19 months later it decreased to 15/HPF Overall, the mean number of ICC present in the gastric smooth muscle before initiation of GES was 11/HPF, and after 15-60 months of chronic GES therapy with neurostimulation the mean number was 13/HPF. Conclusion: Our preliminary data indicate that chronic GES therapy doesn't “regenerate” or increase the number of ICC in the antral smooth muscle of GP patients. Thus restoration of normal electrical rhythm or reversal of electrical slow waves dysrhythmia with improved gastric emptying would not be an expectation of chronic GES therapy.