title: Cellular changes in diabetic and idiopathic gastroparesis.
abstract: OBJECTIVE
  Cellular changes associated with diabetic and idiopathic gastroparesis are not well described. The aim of this study was to describe histologic abnormalities in gastroparesis and compare findings in idiopathic versus diabetic gastroparesis.
  
  
  METHODS
  Full-thickness gastric body biopsy specimens were obtained from 40 patients with gastroparesis (20 diabetic) and matched controls. Sections were stained for H&E and trichrome and immunolabeled with antibodies against protein gene product (PGP) 9.5, neuronal nitric oxide synthase (nNOS), vasoactive intestinal peptide, 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.
  
  
  RESULTS
  Histologic abnormalities were found in 83% of patients. The 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 patients with idiopathic gastroparesis (40%) compared with diabetic patients (20%) by visual grading. On electron microscopy, a markedly increased connective tissue stroma was present in both disorders.
  
  
  CONCLUSIONS
  This study suggests that on full-thickness biopsy specimens, cellular abnormalities are found in the majority of patients with gastroparesis. The 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 offer hope that new therapeutic targets can be found.
authors.affiliation: Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Madhusudan
authors.initials: M
authors.lastname: Grover
authors.forename: Gianrico
authors.initials: G
authors.lastname: Farrugia
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Lurken
authors.forename: Cheryl E
authors.initials: CE
authors.lastname: Bernard
authors.forename: Maria Simonetta
authors.initials: MS
authors.lastname: Faussone-Pellegrini
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Smyrk
authors.forename: Henry P
authors.initials: HP
authors.lastname: Parkman
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Abell
authors.forename: William J
authors.initials: WJ
authors.lastname: Snape
authors.forename: William L
authors.initials: WL
authors.lastname: Hasler
authors.forename: Aynur
authors.initials: A
authors.lastname: Ünalp-Arida
authors.forename: Linda
authors.initials: L
authors.lastname: Nguyen
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Koch
authors.forename: Jorges
authors.initials: J
authors.lastname: Calles
authors.forename: Linda
authors.initials: L
authors.lastname: Lee
authors.forename: James
authors.initials: J
authors.lastname: Tonascia
authors.forename: Frank A
authors.initials: FA
authors.lastname: Hamilton
authors.forename: Pankaj J
authors.initials: PJ
authors.lastname: Pasricha
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D003920:Diabetes Mellitus / Q000473:pathology*; D005260:Female; D005746:Gastric Emptying / Q000502:physiology*; D018589:Gastroparesis / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D056885:Interstitial Cells of Cajal / Q000648:ultrastructure; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D013270:Stomach / Q000473:pathology* / Q000503:physiopathology; D055815:Young Adult