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Background: This study aimed to elucidate the clinical value of combined pancreaticoduodenectomy (PD) for advanced gallbladder cancer according to the mode of cancer spread in the pancreaticoduodenal region., Methods: Patients who underwent combined PD for advanced gallbladder cancer were retrospectively reviewed. The mode of cancer spread in the pancreaticoduodenal region was defined as involvement of peripancreatic organs/structures alone, peripancreatic nodal metastasis alone, or both. Surgical outcomes were compared among these modes of spread., Results: Fifty-seven patients were included. Rates of severe morbidity and mortality were 52.6% and 3.5%, respectively. The mode of cancer spread was involvement of peripancreatic organs/structures alone in 16 patients, peripancreatic nodal metastasis alone in 17, and both in 24; R0 resection rates differed significantly among the groups (87.5% vs. 94.1% vs. 37.5%; p < 0.001). Overall survival (OS) was significantly worse in patients with both modes of spread (5-year OS, 8.3%) than in those with involvement of peripancreatic organs/structures alone (5-year OS, 37.9%; p < 0.001) and those with peripancreatic nodal metastasis alone (5-year OS, 29.4%; p = 0.011). OS was similar between pM0 patients with both modes of spread and pM1 patients (5-year OS, 16.7% vs. 8.7%; p = 0.605). Multivariate analysis identified mode of cancer spread as an independent prognostic factor (p = 0.006)., Conclusions: Combined PD could be oncologically justified for advanced gallbladder cancer with involvement of peripancreatic organs/structures alone or peripancreatic nodal metastasis alone in the pancreaticoduodenal region. This procedure would not be indicated in patients with both modes of spread., Competing Interests: Declaration of competing interest No specific funding was received for this study and the authors have no conflicts of interest to disclose., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)