Pancreatic ductal adenocarcinoma (PDAC) is currently an increasing contributor to cancer-related mortality. Despite advances in cancer treatment, PDAC survival rates have remained roughly unchanged over the years. Specifically, late diagnosis and insensitivity to currently available therapeutic regimens have been identified as the main causes for its poor survival. Pancreatic exocrine insufficiency (PEI) is a typical complication associated with PDAC diagnosis and pancreatic surgery. Pancreatic exocrine insufficiency, a major contributor to maldigestion in PDAC, is often not treated because it remains undetected because of lack of overt signs and symptoms. In this review, we will focus on the major consequences of PEI, including the inadequacy of lipase excretion, which results in deficiency of fat-soluble vitamins. Because PDAC is known for its immune-high jacking mechanisms, we describe key features in which deficiencies of fat-soluble vitamins may contribute to the aggressive biological behavior and immune evasion in PDAC. Because PEI has been shown to worsen survival rates in patients with PDAC, detecting PEI and the related fat-soluble vitamin deficits at the time of PDAC diagnosis is critical. Moreover, timely supplementation of pancreatic enzymes and fat-soluble vitamins may improve outcomes for PDAC patients.
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