The Influence of Vitamin C on Stromal and Epithelial Cells of the Pancreas in Malignant and Benign/Inflammatory Pancreatic Diseases: Protocol for a Scoping Review

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Background: With a 5-year survival rate of less than 10% in most regions worldwide, pancreatic ductal adenocarcinoma (PDAC) has been considered as one of the deadliest tumor diseases. In addition, the incidence of acute and chronic pancreatitis is also increasing worldwide. Both diseases-tumorous and inflammatory-involve pronounced stromal changes, including stellate cell activation, fibrosis, immune cell recruitment, and a proinflammatory microenvironment that is able to drive malignant progression. Vitamin C is increasingly coming into focus as a treatment option, as it has the potential to act both as an antioxidant and anti-inflammatory agent on pancreatitis tissue and as a cytotoxic and modulatory agent on tumor-relevant signaling pathways in PDAC. While the influence of vitamin C on tumor cells has been extensively studied and classified, there is a lack of consideration in the context of stromal and epithelial cells in PDAC and benign/inflammatory pancreatic diseases. Objective: This review aims to map the currently scattered literature and, thus, detect possible gaps in research. The research question posed for this purpose is as follows: what data are available on the influence of vitamin C on pancreatic stromal cells and pancreatic cells in benign/inflammatory and malignant diseases of the pancreas? Methods: The scoping review will be conducted using the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines and the recommendations of the Joanna Briggs Institute. The main systematic search will use PubMed, MEDLINE, and Web of Science, with gray literature identified via the Bielefeld Academic Search Engine. Two independent reviewers will then conduct title and abstract screening, followed by full-text screening. The main inclusion criteria are (1) pancreatic cells in malignant and inflammatory pancreatic diseases, (2) vitamin C intervention, and (3) effects studied at the cellular level. Relevant data will be extracted using a standardized Microsoft Excel spreadsheet. This information will include the title, author, year, study design, model, cell lines, vitamin C isoform, concentration, treatment duration, control, outcomes for pancreatic and stromal cells, methods, and key findings. This list may be expanded during screening. Data analysis will be descriptive, complemented by thematic grouping and visual representations. In accordance with the PRISMA-ScR recommendations, a formal risk-of-bias assessment will not be performed. Results: As of April 13, 2026, a total of 475 database hits have been evaluated during the title and abstract screening process. The entire review process will extend from January 2026 to December 2026. Final results are expected in January 2027. Conclusions: This review aims to provide a comprehensive overview of the current state of knowledge in this field of research to structure it and, thus, highlight possible gaps in knowledge. This could serve as a basis for preclinical studies addressing specific gaps identified in this review to further elucidate the potential therapeutic role of vitamin C.

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