Generation of a pseudo-timeline describing progressive human exocrine and endocrine pancreatic pathology in cystic fibrosis through novel semi-quantitative scoring and AI-driven quantitative image analysis
Authors' conclusion
The natural history of pancreatic CF progresses rapidly from duct blockage and dilatation associated with periductal fibrosis to global fat replacement in keeping with early onset of PEI in the majority of affected individuals. Beta cell proportional area is reduced at birth before clinical evidence of pancreatic endocrine dysfunction without significant further loss of islet/beta cell mass with age. Increasing islet disorganisation and intra-islet collagen deposition in older donors temporo-spatially implicates fibrosis in and around the islet as being aetiologically important in the development of CF-related diabetes.
Study context
- Population
- Human pancreatic tissue from cystic fibrosis (CF) and control donors
- Participants
- 29 vs 58
- Exposure
- CF vs control donors without pancreatic disease
- CFn = 29
- Controln = 58reference
- Outcome
- Exocrine and endocrine pancreatic changes with progressive CF
Methodological detailspathologist-led iterative approach, light-microscopy semi-quantitative scoring, AI-driven quantitative image analysis
- Pathologist-led iterative approach
- Light-microscopy semi-quantitative scoring
- AI-driven quantitative image analysis
Main finding
As reported in the abstract
- Rapid loss of acinar tissue with virtually complete absence and replacement by adipocytes by age 7 years
- Ductal blockage by thickened secretions associated with increasing ductal dilatation and periductal fibrosis, followed by ductal loss with involution of fibrosis in parallel with increasing adipocyte proportional area
- Remaining ducts relatively small, surrounded by residual fibrosis
- Islets increasingly clustered, initially surrounded by pancreatic stellate cells and fibrosis, then disorganised by interposing fibrotic tissue and surrounded by residual collagen stranding in a 'lipotic' pancreas
- Overall islet mass not reduced
- Proportional beta cell area reduced from birth without further loss over progressive disease
Observational data: associations, not effects.
Original publication
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