Abstract
Background: Evidence suggests that the biliary microbiome influences the progression of pancreatic ductal adenocarcinoma (PDAC) in patients undergoing adjuvant chemotherapy. Specifically, Gammaproteobacteria (GPB) has been shown to have the potential to develop mutations which can metabolise gemcitabine into an inactive form. This study hypothesised that GPB influences survival in patients with PDAC undergoing adjuvant gemcitabine-based chemotherapy following surgery. Methods: This was a retrospective study of patients undergoing pancreatoduodenectomy from 2010 to 2020. Associations between patient and tumour characteristics, survival data, and results of intraoperative bile cultures (GPB + or GPB-) were investigated. Analysis of patients matched by chemotherapy regimen and numbers of cycles of adjuvant therapy was also performed. Survival was analysed using Kaplan-Meier curves and Cox regression analysis. Results: Analysis of 313 patients revealed that adjuvant gemcitabine-based therapy improved overall survival (OS). Patients who receive gemcitabine-based chemotherapy with a GPB + biliary culture had a shorter OS compared to those who were GPB-, and a median survival of 17.9 vs 26.2 months, P = 0.002. After matching for key chemotherapy variables, survival was greater in the GPB-group 26.8 vs 19.8 months, P = 0.016. This association was not seen among patients who received no adjuvant therapy or non-gemcitabine based therapy. Conclusion: Patients receiving gemcitabine-based chemotherapy after surgery are likely to have reduction in OS if they have a biliary culture positive for GPB.