ABSTRACT

No abstract

Objectives Clinical Practice Guidelines for Pancreatic Cancer were first published in 2006 by the Japan Pancreas Society, and they were revised in 2009, 2013, and 2016. In July 2019, the Clinical Practice Guidelines for Pancreatic Cancer 2019 were newly revised in Japanese. Methods For this version, we developed the new guidelines according to the Minds Manual for Guideline Development 2017, which includes the concepts of GRADE (Grading Recommendations Assessment, Development, and Evaluation), to enable a better understanding of the current guidelines. Results The guidelines show algorithms for the diagnosis, treatment, and chemotherapy of pancreatic cancer and address 7 subjects: diagnosis, surgical therapy, adjuvant therapy, radiation therapy, chemotherapy, stent therapy, and supportive and palliative medicine. They include 56 clinical questions and 84 statements. There are statements corresponding to clinical questions, evidence levels, recommendation strengths, and agreement rates. Conclusions These guidelines represent the most standard clinical and practical management guidelines at this time in Japan. This is the English synopsis of the Clinical Practice Guidelines for Pancreatic Cancer 2019 in Japanese and is an attempt to disseminate the Japanese guidelines worldwide for introducing the Japanese approach for clinical management of pancreatic cancer.

These results suggest that TLR/MyD88/NF-kappaB signaling pathway plays a significant role in connecting inflammation and cancer invasion and progression.

The hedgehog (Hh) signaling pathway, which functions as an organizer in embryonic development, is implicated in the development of various tumors. In pancreatic cancer, pathway activation is reported to result from aberrant expression of the ligand, sonic Hh (Shh). However, the details of the mechanisms regulating Shh expression are not yet known. We hypothesized that nuclear factor-KB (NF-KB), a hallmark transcription factor in inflammatory responses, contributes to the overexpression of Shh in pancreatic cancer. In the present study, we found a close positive correlation between NF-KB p65 and Shh expression in surgically resected pancreas specimens, including specimens of chronic pancreatitis and pancreatic adenocarcinoma. We showed that blockade of NF-KB suppressed constitutive expression of Shh mRNA in pancreatic cancer cells. Further activation of NF-KB by inflammatory stimuli, including interleukin-1B, tumor necrosis factor-A, and lipopolysaccharide, induced overexpression of Shh, resulting in activation of the Hh pathway. Overexpression of Shh induced by these stimuli was also suppressed by blockade of NF-KB. NF-KB-induced Shh expression actually activated the Hh pathway in a ligand-dependent manner and enhanced cell proliferation in pancreatic cancer cells. In addition, inhibition of the Hh pathway as well as NF-KB suppressed the enhanced cell proliferation. Our data suggest that NF-KB activation is one of the mechanisms underlying Shh overexpression in pancreatic cancer and that proliferation of pancreatic cancer cells is accelerated by NF-KB activation in part through Shh overexpression.