Lipotoxic fingerprints in clinically relevant postoperative pancreatic fistula

This study investigates lipotoxic stress responses induced by postoperative pancreatic fistula (CR-POPF) effluents in non-malignant stromal cell types relevant for anastomotic healing. Postoperative drain effluents from patients undergoing pancreatoduodenectomy were characterized by gas chromatography–mass spectrometry to identify lipolysis-derived lipid species. Based on functional cytotoxicity screening, two CR-POPF effluents with reproducible biological effects were selected for transcriptomic profiling. Primary human peritoneal mesothelial cell preparations and human foreskin fibroblasts were exposed in vitro to patient-derived effluents, a defined lipolysis-derived lipid (monopalmitin), or medium control. RNA sequencing was performed to characterize stimulus-specific transcriptional stress responses. The dataset enables comparative analysis of metabolic, inflammatory, and stress-associated gene expression programs induced by distinct lipolytic stimuli in stromal and mesothelial cells.