脂肪肝與代謝異常對脂肪胰與胰臟癌的影響

Fatty Liver and Metabolic Alterations in Fatty Pancreas and Pancreatic Adenocarcinoma

胰臟腺癌（PDAC）是最致命的癌症之一，目前是美國第三大癌症死亡原因。由於絕大多數病人無法早期發現PDAC，以及在纖維化背景下，基質細胞活化，造成新基質導致氧水平和營養灌注降低，PDAC的防治受到阻礙。PDAC的一個先兆是胰臟內脂肪沉積過多，即脂肪胰，這會影響器官內的腫瘤宏觀和微環境。超過一半的PDAC病人在診斷時患有糖尿病（DM），而脂肪胰與隨後的DM發展有關。此外，脂肪胰臟和脂肪肝之間透過肥胖有密切的聯繫，且患有糖尿病的急性胰臟炎病人，胰臟內脂肪百分比高於非糖尿病人者。所有這些證據顯示，脂肪胰和PDAC之間的關聯，可能透過與糖尿病相關或非糖尿病相關的代謝改變而發生。基於臨床、體內和體外證據，本篇綜述重點介紹了脂肪胰的病因（包括脂肪浸潤和替代），以及與腫瘤發生有關的脂肪胰相關代謝改變，以提供預防、檢測和/或有效治療PDAC的關鍵目標。

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest types of cancer, and it is currently the third most common cause of cancer death in the U.S.A. Progress in the fight against PDAC has been hampered by an inability to detect it early in the overwhelming majority of patients, and also by the reduced oxygen levels and nutrient perfusion caused by new matrix formation through the activation of stromal cells in the context of desmoplasia. One harbinger of PDAC is excess intrapancreatic fat deposition, namely, fatty pancreas, which specifically affects the tumor macro- and microenvironment in the organ. Over half of PDAC patients have diabetes mellitus (DM) at the time of diagnosis, and fatty pancreas is associated with subsequent DM development. Moreover, there is a strong association between fatty pancreas and fatty liver through obesity, and a higher intrapancreatic fat percentage has been noted in acute pancreatitis patients with DM than in those without DM. All these findings suggest that the link between fatty pancreas and PDAC might occur through metabolic alterations, either DM-related or non-DM-related. Based on clinical, in vivo and in vitro evidence, the current review highlights the etiologies of fatty pancreas (including fatty infiltration and replacement) and the fatty pancreas-associated metabolic alterations involved in oncogenesis to provide crucial targets to prevent, detect, and/or effectively treat PDAC.