Cellular changes in diabetic and idiopathic gastroparesis

Madhusudan Grover, Gianrico Farrugia, Matthew S. Lurken, Cheryl E. Bernard, Maria Simonetta Faussonepellegrini, Thomas Christopher Smyrk, Henry P. Parkman, Thomas L. Abell, William J. Snape, William L. Hasler, Aynur Unalparida, Linda Nguyen, Kenneth L. Koch, Jorges Calles, Linda Lee, James Tonascia, Frank A. Hamilton, Pankaj J. Pasricha

Research output: Contribution to journalArticle

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Abstract

Background & Aims: 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.

Original languageEnglish (US)
JournalGastroenterology
Volume140
Issue number5
DOIs
StatePublished - May 2011

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Gastroparesis
Interstitial Cells of Cajal
Nitric Oxide Synthase Type I
Biopsy
Vasoactive Intestinal Peptide
Tyrosine 3-Monooxygenase
Substance P
Transmission Electron Microscopy
Nerve Fibers
Neuroglia
Connective Tissue
Smooth Muscle Myocytes
Microscopy
Stomach
Electron Microscopy
Macrophages
Light
Antibodies
Wounds and Injuries

Keywords

  • Enteric Nerves
  • Gastric Emptying
  • Interstitial Cells of Cajal
  • Smooth Muscle

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Grover, M., Farrugia, G., Lurken, M. S., Bernard, C. E., Faussonepellegrini, M. S., Smyrk, T. C., ... Pasricha, P. J. (2011). Cellular changes in diabetic and idiopathic gastroparesis. Gastroenterology, 140(5). https://doi.org/10.1053/j.gastro.2011.01.046

Cellular changes in diabetic and idiopathic gastroparesis. / Grover, Madhusudan; Farrugia, Gianrico; Lurken, Matthew S.; Bernard, Cheryl E.; Faussonepellegrini, Maria Simonetta; Smyrk, Thomas Christopher; Parkman, Henry P.; Abell, Thomas L.; Snape, William J.; Hasler, William L.; Unalparida, Aynur; Nguyen, Linda; Koch, Kenneth L.; Calles, Jorges; Lee, Linda; Tonascia, James; Hamilton, Frank A.; Pasricha, Pankaj J.

In: Gastroenterology, Vol. 140, No. 5, 05.2011.

Research output: Contribution to journalArticle

Grover, M, Farrugia, G, Lurken, MS, Bernard, CE, Faussonepellegrini, MS, Smyrk, TC, Parkman, HP, Abell, TL, Snape, WJ, Hasler, WL, Unalparida, A, Nguyen, L, Koch, KL, Calles, J, Lee, L, Tonascia, J, Hamilton, FA & Pasricha, PJ 2011, 'Cellular changes in diabetic and idiopathic gastroparesis', Gastroenterology, vol. 140, no. 5. https://doi.org/10.1053/j.gastro.2011.01.046
Grover, Madhusudan ; Farrugia, Gianrico ; Lurken, Matthew S. ; Bernard, Cheryl E. ; Faussonepellegrini, Maria Simonetta ; Smyrk, Thomas Christopher ; Parkman, Henry P. ; Abell, Thomas L. ; Snape, William J. ; Hasler, William L. ; Unalparida, Aynur ; Nguyen, Linda ; Koch, Kenneth L. ; Calles, Jorges ; Lee, Linda ; Tonascia, James ; Hamilton, Frank A. ; Pasricha, Pankaj J. / Cellular changes in diabetic and idiopathic gastroparesis. In: Gastroenterology. 2011 ; Vol. 140, No. 5.
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abstract = "Background & Aims: 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.",
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AU - Grover, Madhusudan

AU - Farrugia, Gianrico

AU - Lurken, Matthew S.

AU - Bernard, Cheryl E.

AU - Faussonepellegrini, Maria Simonetta

AU - Smyrk, Thomas Christopher

AU - Parkman, Henry P.

AU - Abell, Thomas L.

AU - Snape, William J.

AU - Hasler, William L.

AU - Unalparida, Aynur

AU - Nguyen, Linda

AU - Koch, Kenneth L.

AU - Calles, Jorges

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AU - Tonascia, James

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N2 - Background & Aims: 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.

AB - Background & Aims: 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.

KW - Enteric Nerves

KW - Gastric Emptying

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KW - Smooth Muscle

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