The role of chronic pancreatic inflammation in tumor progression has been demonstrated to be major.[2,19] It has been known that IL-6 or IL-8, proinflammatory cytokines, are involved with tumor progression in PDAC patients.[3–6] This study defined the tumor progression pattern according to the hepatic metastatic burden of PDAC at the last follow-up. We attempted to investigate whether serum IL-6 and IL-8 could predict tumor progression pattern and overall survival. The serum level of IL-6 of the progressed group was significantly greater than the limited group, and higher IL-6 was the only independent risk factor for progression to extensive hepatic metastasis. Therefore, it would be suggested that more aggressive treatment from the beginning might be considered in PDAC patients with high IL-6.
IL-6 is a proinflammatory cytokine that is synthesized by many cell types, including macrophages, fibroblasts, endothelial cells, and myeloid cells, and it promotes synthesis of CRP from hepatocyte.[20,21] This study revealed that IL-6 is correlated with inflammatory markers such as CRP and NLR, and that it was an independent risk factor for progression to extensive hepatic metastasis.
Previous autopsy studies showed that most PDAC patients die with a broad range of metastatic burden, from limited to extensive.[11,23] Furthermore, 10 to 20% of PDAC patients die of locally advanced disease, without metastatic disease.[11,24] This study revealed that mortality due to disease progression account for almost all causes of death in the progressed group patients. However, in limited group patients, localized infection and tumor bleeding in relation to the primary tumor, in addition to disease progression, accounted for 25% of overall death. Findings of this study were consistent with a previous autopsy study.
The present study has limitations. First, it is retrospective design. Second, the tumor progression pattern was assessed by the abdomen computed tomography not autopsy, and by using measurable lesion of the hepatic metastatic burden except for nonmeasurable lesion such as peritoneal seeding, lymphatic pulmonary metastasis, and bone destructive metastasis. To the best of our knowledge, we investigate of the relationship between proinflammatory cytokines and tumor progression pattern for the first time. In conclusion, higher serum IL-6 was an independent risk factor for progression to extensive hepatic metastasis of PDAC, even though it did not correlate with survival. Therefore, more aggressive chemotherapy from the beginning should be considered in PDAC patients with high IL-6.
The authors thank the Medical Research Collaborating Center at Seoul National University Bundang Hospital for statistical analyses. The authors are indebted to J. Patrick Barron, Professor Emeritus, Tokyo Medical University and Adjunct Professor, Seoul National University Bundang Hospital for his pro bono editing of this manuscript.
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