Pancreatic Steatosis as a Risk Phenotype for Pancreatic Ductal Adenocarcinoma: A Narrative Review.

Background and

Objectives

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related mortality, largely due to late-stage diagnosis and the absence of effective population-based screening. Intrapancreatic fat deposition (IPFD) has emerged as a potential risk phenotype. This narrative review critically appraises the clinical, metabolic, epidemiologic, and mechanistic evidence linking IPFD to PDAC and discusses its implications for risk stratification and prevention. Materials and

Methods

A structured literature search was conducted in PubMed/MEDLINE and Scopus for studies published between 2007 and 2025 using predefined terms related to pancreatic steatosis and pancreatic cancer. After duplicate removal and screening according to predefined inclusion and exclusion criteria, 42 articles were included. Evidence was synthesized focusing on epidemiologic associations, mechanistic pathways, and imaging-based quantification methods.

Results

A strong association between IPFD and PDAC was found. Although definitive causality remains unproven, some studies support temporal correlation between IPFD and PDAC, suggesting that IPFD precedes PDAC. A possible pathophysiological explanation to this correlation has been advanced in experimental models indicating IPFD as a pro-inflammatory factor cooperating with oncogenic KRAS to facilitate neoplastic progression. Finally, variability in IPFD definitions and heterogeneity in imaging assessment limit interpretability.

Conclusions

Current evidence links IPFD to PDAC risk, suggesting a strong suspicion that pancreatic steatosis may represent an independent risk factor for PDAC. Still robust causal inference remains unproven. Well-designed prospective studies, standardized imaging protocols, and mechanistic investigations are required to clarify causality and determine whether pancreatic steatosis can be incorporated into risk-based screening and preventive strategies.