Impact of Liver Disease and Parenchymal Changes on Patterns of Liver Recurrence in Patients with Resected PDAC: A New Insight into the Biological Behavior of This Lethal Disease

Abstract

Introduction: Signaling from primary pancreatic ductal adenocarcinoma (PDAC) that directs hepatic pre-metastatic niche formation is suggested to play an important role in liver metastasis. The impact of preexisting liver disease or parenchymal changes (LD) on rates of liver metastasis in PDAC remains unexplored. Method: An institutional registry was used to identify PDAC patients who underwent resection between 2010 and 2017. LD was identified from patient records and classified as type-1 (fatty liver disease or perfusion changes) or type-2 (cirrhosis, fibrosis, other textural changes). Factors associated with liver-specific recurrence-free survival (LS-RFS) were analyzed. Results: Of 1,193 patients, 257 (21.5%) had LD and were similar in terms of clinicopathological and treatment characteristics as compared to non-LD patients. Higher 2-year LS-RFS (65.8% vs. 76.9%) was observed in LD patients (p=0.022). The overall rate of hepatic recurrence in non-LD, type-1 LD, and type-2 LD patients was 30.6%, 26.8%, and 6.8% respectively (p<0.001)(Figure). On multivariable analysis presence of LD was independently associated with LS-RFS (p=0.006). No difference was observed in median extra-hepatic RFS between LD (24.3 months) and non-LD (23.0 months) patients (p=0.527). Conclusions: Presence and type of LD is associated with development of liver metastasis in PDAC. This suggests that LD could affect hepatic premetastatic niche formation in PDAC. Further studies are needed to elucidate this mechanism.