Language

English

Publication Date

10-1-2025

Journal

Clinical and Translational Gastroenterology

DOI

10.14309/ctg.0000000000000897

PMID

40758192

PMCID

: PMC12543235

PubMedCentral® Posted Date

8-4-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Introduction: Chronic pancreatitis (CP) is a disease associated with chronic inflammation, fibrosis, and pain. There is a lack of tools available that facilitate early diagnosis, when intervention could prevent irreversible damage. Pilot data suggested prostaglandin E2 (PGE2) as a candidate biomarker for early CP. PGE2 activates signaling pathways that promote inflammation, pain, and fibrosis.

Methods: We assessed PGE2, metabolites, and downstream targets in pancreatic fluid collected endoscopically 0-10 (n = 110) and 10-20 (n = 111) minutes after intravenous secretin administration. PGE2 and metabolites were measured in plasma (n = 75) and urine (n = 71) from the same subjects. Subjects were enrolled in the PROCEED study and classified symptomatic controls, acute/recurrent acute pancreatitis (AP/RAP), or CP.

Results: A significant main effect was detected in 10-20 minutes pancreas fluid ( P = 0.027) and plasma ( P = 0.046); post hoc testing showed PGE2 was lower in the AP/RAP group compared with symptomatic controls. There was also trend toward lower PGE2 in urine ( P = 0.062). To elucidate the active downstream pathways, calcitonin gene-related peptide, substance P, and matrix metalloproteinases (MMPs) 1, 2, 3, 7, 9, and 13 were measured in pancreas fluid. A significant difference between the 3 groups was detected for both MMP7 and MMP9. MMP7 was elevated in individuals with CP vs AP/RAP ( P = 0.012) for samples collected early but both time points for MMP9 ( P = 0.027, P = 0.002).

Discussion: While PGE2 is detectable in pancreas fluid, these data suggest that it may not be sensitive enough to distinguish between AP/RAP and CP. However, MMPs may distinguish between stages of pancreatitis and require further testing as potential diagnostic biomarkers.

Keywords

Humans, Pancreatitis, Chronic, Dinoprostone, Biomarkers, Male, Female, Middle Aged, Adult, Secretin, Pancreatic Juice, Calcitonin Gene-Related Peptide, Substance P, Aged, Case-Control Studies, Early Diagnosis, pancreatitis, pancreatic fluid, prostaglandin, matrix metalloproteinases, biomarkers

Published Open-Access

yes

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