Cellular Changes in Diabetic and Idiopathic Gastroparesis

Abstract

Background-Cellular changes associated with diabetic and idiopathic gastroparesis are not well described.Aim-Describe histologic abnormalities in gastroparesis and compare findings in idiopathic versus diabetic gastroparesis.Methods-Full thickness gastric body biopsies were obtained from 40 gastroparetics (20 diabetic) and matched controls. Sections were stained for H&E and trichrome, and immunolabeled with antibodies against PGP 9.5, nNOS, VIP, substance P and tyrosine hydroxylase to quantify nerves, S100β for glia, Kit for interstitial cells of Cajal (ICC), CD45 and CD68, for immune cells and smoothelin for smooth muscle cells. Tissue was also examined by transmission electron microscopy (TEM).Results-Histological abnormalities were found in 83% of patients. Most common defects were loss of ICC with remaining ICC showing injury, an abnormal immune infiltrate containing macrophages, and decreased nerve fibers. On light microscopy, no significant differences were found between diabetic and idiopathic gastroparesis with the exception of nNOS expression which was decreased in more idiopathic gastroparetics (40%) compared to diabetic (20%) patients by visual grading. On electron microscopy, a markedly increased connective tissue stroma was present in both disorders.Conclusion-This study suggests that on full thickness biopsies, cellular abnormalities are found in the majority of patients with gastroparesis. Most common findings were loss of Kit expression suggesting loss of ICC and an increase in CD45 and CD68 immunoreactivity. These findings suggest that examination of tissue can lead to valuable insights into the pathophysiology of these disorders and offers hope that new therapeutic targets can be found.

Understanding the Differences Between Gastroparesis and Gastroparesis-Like Syndrome: Filling a GaPing Hole?

“…Considering the low amount of fibrosis reported by other studies such as by Grover et al [10], the authors' findings suggesting a correlation of antral fibrosis and pyloric fibrosis are difficult to interpret given the data of patients with GP where a minority have fibrosis present yet most have symptoms of gastroparesis. Faussone-Pelligrini et al [16] reported ultrastructural differences between idiopathic and diabetic GP with more severe changes present in idiopathic GP.…”

“…In a previous study comparing idiopathic-and diabetic-GP patients with healthy controls, surgical biopsy documented loss of ICC in 83% of gastroparesis patients though only 3/40 total GP patients had fibrosis on antral biopsies [10]. Considering the low amount of fibrosis reported by other studies such as by Grover et al [10], the authors' findings suggesting a correlation of antral fibrosis and pyloric fibrosis are difficult to interpret given the data of patients with GP where a minority have fibrosis present yet most have symptoms of gastroparesis.…”

“…Significant heterogeneity exists among studies examining the number of ICC in the gastric antrum. Few studies have investigated ICC networks in the pylorus, with only one other human study to date (conducted by the current study's author) [9][10][11].…”

Estrogens and Gastroparesis: A Clinical Relevance

“…Several cell types, including the extrinsic innervation to the stomach, enteric nerves, glia, smooth muscle cells, interstitial cell of Cajal (ICC), and immune cells are known to be responsible for normal gastric motility functions. It has been shown that, in diabetic as well as idiopathic patients, the lack of functional coordination between these cell types may have been lost; therefore, the motility of the stomach is impaired and thus leads to abnormal gastric emptying [1].…”

“…The most common forms include idiopathic, diabetic, and post-surgical complications [1][2][3]. The majority of idiopathic patients are either obese or overweight [3].…”