Background and purpose: Pancreatic intraepithelial neoplasia (PanIN) is thought to be a precursor lesion of infiltrating pancreatic ductal adenocarcinoma. The mutation of the phenotypic impact of K-ras G12D alone, silencing of p53 and p16 could promote this process. The role of Smad4 in this progression was poorly understood. In the present study, we investigated the role of Smad4 in the development of pancreatic tumor, based on PanIN cell line from mice with K-ras G12D mutation in order to investigate the effect of Smad4 silencing on PanIN cells in the development and malignant transformation in nude mice. Methods: Smad4 knock-down PanIN cells (PanIN-S) were established by stable transfeetion with lentiviral-mediated Smad4 RNA interference (RNAi). In xenograft model experiments, BALB/c nude mice were randomly divided into 2 groups (5 mice per group) implanted with PanIN or PanlN-S cells subcutaneously. Two weeks after tumor cells inoculation, tumor volume and weight were estimated. PCNA staining was used to evaluate cell proliferation and CD31 polyclonal antibody was used to assess micro-vessel density (MVD) in tumors. Results: Effect of siRNA of Smad4 gene in PanlN cells was confirmed by RT-PCR and Western blot. Compared with PanlN groups, there was a dramatic increase in tumor volume and weight in PanIN-S groups (P<0.05). Furthermore, immunohistochemical analysis of the harvested tumors suggested that Smad4 silencing was associated with 'increased tumor cell proliferation (PCNA reactivity) and angiogenesis (micro-vessel density, MVD). The percentage of PCNA-positive cells in the PanlN-S groups were significantly increased than PanIN groups (P<0.05). CD31 staining revealed a significant increase in the PanlN-S groups compared to the PanlN groups (P<0.05). Conclusion: Silencing of Smad4 in PanlN cells with endogenous expression of K-ras G12D, enhanced progression to invasive adenocarcinomas. Cell proliferation and vascularization may be its important mechanisms.

Pancreatic cancer is a highly malignant tumor in the digestive system.The role of neoadjuvant therapy in pancreatic cancer has been highlighted with the understanding of pancreatic cancer biological behavior and popularization of comprehensive treatment.Therefore,Study group of Pancreatic Surgery in China Society of Surgery of Chinese Medical Association and Pancreatic Disease Committee of China Research Hospital Association has formulated the guidelines for neoadjuvant therapy of pancreatic cancer in China(2020 edition).This guidelines elaborated key issues of the neoadjuvant therapy of pancreatic cancer,and provided reference for clinical practice.This article aims to interpret the guidelines about the preparation before neoadjuvant therapy, indication, regimen selection, therapeutic effect evaluation and surgery strategy, with further discussion about controversial issues of neoadjuvant therapy in pancreatic cancer.

Pancreatic cancer is a highly malignant tumor in the digestive system.The role of neoadjuvant therapy in pancreatic cancer has been highlighted with the understanding of pancreatic cancer biological behavior and popularization of comprehensive treatment.Therefore,Study group of Pancreatic Surgery in China Society of Surgery of Chinese Medical Association and Pancreatic Disease Committee of China Research Hospital Association has formulated the guidelines for neoadjuvant therapy of pancreatic cancer in China(2020 edition).This guidelines elaborated key issues of the neoadjuvant therapy of pancreatic cancer,and provided reference for clinical practice.This article aims to interpret the guidelines about the preparation before neoadjuvant therapy, indication, regimen selection, therapeutic effect evaluation and surgery strategy, with further discussion about controversial issues of neoadjuvant therapy in pancreatic cancer.

Pancreatic fistula is a common complication of pancreatic surgery and also a leading cause of postoperative death. The 2016 International Study Group on Pancreatic Surgery definition and grading criterion of postoperative pancreatic fistula (POPF) is instructive to clinical practice and scientific research. Although the criterion is widely applied, further optimization is required. It has established a variety of risk prediction models, which forwards the early diagnosis of POPF. However, the inconsistency of the criteria and the potential mutual influence of multiple factors hindered the model extrapolation. Moreover, it remains controversial in specific strategies of perioperative nutritional support, surgical methods, postoperative drainage, and somatostatin application in the prevention and treatment of POPF. Thus, more prospective studies are needed to explore safer, more effective and economical POPF prediction and intervention methods.

Pancreatic fistula is a common complication of pancreatic surgery and also a leading cause of postoperative death. The 2016 International Study Group on Pancreatic Surgery definition and grading criterion of postoperative pancreatic fistula (POPF) is instructive to clinical practice and scientific research. Although the criterion is widely applied, further optimization is required. It has established a variety of risk prediction models, which forwards the early diagnosis of POPF. However, the inconsistency of the criteria and the potential mutual influence of multiple factors hindered the model extrapolation. Moreover, it remains controversial in specific strategies of perioperative nutritional support, surgical methods, postoperative drainage, and somatostatin application in the prevention and treatment of POPF. Thus, more prospective studies are needed to explore safer, more effective and economical POPF prediction and intervention methods.