Clinical-histological associations in gastroparesis: results from the Gastroparesis Clinical Research Consortium

Abstract

Background: Cellular changes associated with diabetic (DG) and idiopathic gastroparesis (IG) have recently been described from patients enrolled in the Gastroparesis Clinical Research Consortium. The association of these cellular changes with gastroparesis symptoms and gastric emptying is unknown. The aim of this study was to relate cellular changes to symptoms and gastric emptying in patients with gastroparesis.

Methods: Earlier, using full thickness gastric body biopsies from 20 DG, 20 IG, and 20 matched controls, we found decreased interstitial cells of Cajal (ICC) and enteric nerves and an increase in immune cells in both DG and IG. Here, demographic, symptoms [gastroparesis cardinal symptom index score (GCSI)], and gastric emptying were related to cellular alterations using Pearson's correlation coefficients.

Key results: Interstitial cells of Cajal counts inversely correlated with 4 h gastric retention in DG but not in IG (r = -0.6, P = 0.008, DG, r = 0.2, P = 0.4, IG). There was also a significant correlation between loss of ICC and enteric nerves in DG but not in IG (r = 0.5, P = 0.03 for DG, r = 0.3, P = 0.16, IG). Idiopathic gastroparesis with a myenteric immune infiltrate scored higher on the average GCSI (3.6 ± 0.7 vs 2.7 ± 0.9, P = 0.05) and nausea score (3.8 ± 0.9 vs 2.6 ± 1.0, P = 0.02) as compared to those without an infiltrate.

Conclusions & inferences: In DG, loss of ICC is associated with delayed gastric emptying. Interstitial cells of Cajal or enteric nerve loss did not correlate with symptom severity. Overall clinical severity and nausea in IG is associated with a myenteric immune infiltrate. Thus, full thickness gastric biopsies can help define specific cellular abnormalities in gastroparesis, some of which are associated with physiological and clinical characteristics of gastroparesis.

Figure 1

Correlations between % gastric retention at 4 hours and average GCSI with ICC, CD45 positive myenteric plexus cells and PGP9.5 positive nerve fibers in diabetic gastroparesis A: ICC and % gastric retention at 4 hours (r=−0.59, p=0.008*, slope=−7.3, 95% CI=−12.4 to −2.2), B: CD45 positive cells and % gastric retention at 4 hours (r=0.05, p=0.83), C: PGP9.5 nerve fibers and % gastric retention at 4 hours (r=−0.19, p=0.43), D: ICC and GCSI-average (r=0.10, p=0.69), E: CD45 positive cells and GCSI-average (r=0.13, p=0.63), F: PGP9.5 nerve fibers and GCSI-average (r=0.19, p=0.46).

Figure 2

Correlations between ICC, CD45 positive myenteric plexus cells and PGP9.5 positive nerve fibers in Diabetic Gastroparesis- A: ICC-PGP9.5 positive nerve fibers (r=0.47, p=0.03*, slope=0.11, 95% CI=0.008–0.2), B: ICC-CD45 positive myenteric cells (r=0.1, p=0.65), C: PGP9.5 positive nerve fibers-CD45 positive myenteric cells (r=0.11, p=0.63). Correlations between ICC, CD45 positive myenteric plexus cells and PGP9.5 positive nerve fibers in Idiopathic Gastroparesis- D: ICC-PGP9.5 positive nerve fibers (r=0.32, p=0.16), E: ICC-CD45 positive myenteric cells (r=−0.09, p=0.71), F: PGP9.5 positive nerve fibers-CD45 positive myenteric cells (r=0.06, p=0.78).

Figure 3

Correlations between % gastric retention at 4 hours and average GCSI with ICC, CD45 positive myenteric plexus cells and PGP9.5 positive nerve fibers in idiopathic gastroparesis A: ICC and % gastric retention at 4 hours (r=0.21, p=0.38), B: CD45 positive cells and % gastric retention at 4 hours (r=−0.10, p=0.68), C: PGP9.5 nerve fibers and % gastric retention at 4 hours (r=0.22, p=0.37), D: ICC and GCSI-average (r=−0.34, p=0.15), E: CD45 positive cells and GCSI-average (r=0.36, p=0.13), F: PGP9.5 nerve fibers and GCSI-average (r=0.20, p=0.40). * Some graphs have less than 20 data points because of missing data on either the counts, GE or GCSI on these patients.