The abnormal expression of leucine-rich-alpha-2-glycoprotein 1 (LRG-1) is reported to be associated with multiple malignancies, but its role in the progression of pancreatic ductal adenocarcinoma (PDAC) remains to be determined. The expression of LRG-1 was assessed in PDAC tissues by RT-PCR, Western blot and immunohistochemistry. LRG-1-silenced or overexpressed cell lines were constructed using shRNA or LRG-1-overexpressing plasmids. EdU incorporation assay, Transwell invasion and wound-healing assays were performed to evaluate the proliferation, invasion and migration of PDAC cells. In addition, protein expression of the mitogen-activated protein kinase (MAPK) pathway was detected using Western blot. Finally, Co-immunoprecipitation assay was conducted in search of the potential interaction between LRG-1 and epidermal growth factor receptor (EGFR). The expression of LRG-1 in PDAC tissue was significantly higher than that in adjacent normal tissue, and high LRG-1 expression predicted poor survival and a late tumor stage. In addition, LRG-1 markedly promoted the viability, proliferation, migration and invasion of PDAC cells in vitro and facilitated tumor growth in vivo. More importantly, we revealed that these bioactivities of LRG-1 might result from its selective interaction with EGFR, which might further activate the p38/MAPK signaling pathways. LRG-1 may prove to be a promising biomarker for predicting prognosis of PDAC patients. Inhibition of LRG-1 or its downstream pathway could be a potential therapeutic target for the treatment of PDAC.

An enhanced recovery after surgery (ERAS) programme aims to reduce the stress response to surgery and thereby accelerate recovery. The experience of implementing the ERAS programmes in pancreatoduodenectomy (PD) is relatively limited. The aim of this study was to evaluate the feasibility, safety and clinical outcomes of the ERAS programme after PD at a high-volume Chinese university referral centre. Between September 2014 and July 2016, a retrospective analysis of 166 consecutive patients who underwent PD at a tertiary referral care center was carried out. Ninety-eight patients who received conventional perioperative management (the conventional group) were compared with 68 patients who received ERAS programme (the ERAS group). The incidences of postoperative complications, length of stay, expenses, postoperative readmissions, and reoperation rates were compared. A total of 166 patients who underwent PD were analysed (68 patients in the ERAS group, and 98 patients in the conventional group). There were no significant differences in mortality, reoperation, and readmission rates. The ERAS group had a lower morbidity rate than the conventional group (50% vs. 90.8%; P = 0.00), as well as a shorter length of hospital stay (7.5 vs 12 days; P = 0.00). Delayed gastric emptying was significantly reduced in the ERAS group (0 vs. 11.2%; P = 0.011). Pancreatic fistula (grade B,C) was significantly reduced in the ERAS group (14.7 vs 30.6%; P = 0.018). The median total hospital cost was also significantly reduced in the ERAS group (¥79790.40 vs ¥102982.81; P = 0.000). The ERAS programme is feasible and safe in patients who underwent PD, and it can reduce postoperative complications and improve clinical outcomes.

To establish an orthotopic mouse model of pancreatic cancer that mimics the pathological features of exocrine pancreatic adenocarcinoma. Pan02 cells were suspended in low-temperature Matrigel and injected into the parenchyma of pancreatic tails of C57BL/6 mice, with cells suspended in phosphate buffered saline (PBS) serving as a control. Primary and implanted tumors were confirmed pathologically. The rate of tumor formation and intraperitoneal implantation in the two groups were compared at different time points after injection. Leakage and intra-abdominal dispersion of Matrigel and PBS, both dyed with methylene blue, were compared after injection into the parenchyma of the pancreas. We observed adherence and proliferation in Pan02 cells suspended in Matrigel in vitro. We also compared the pathological manifestation of this orthotopic pancreatic cancer model in the head and tails of the pancreas. The characteristics of the origin of epithelial cells and exocrine markers of established orthotopic pancreatic tumors were confirmed using immunohistochemistry. Diluted Matrigel could form a gel drip in the pancreatic parenchyma, effectively preventing leakage from the injection site and avoiding dispersion in the abdominal cavity. Pan02 cells were able to adhere to a dish, proliferate, and migrate in the gel drip. The tumor formation rate in the Matrigel group was 100% at both 2 and 3 wk after injection, whereas it was 25.0% and 37.5% in the PBS group at 2 and 3 wk, respectively (P < 0.05). The intraperitoneal tumor implantation rate was 75.0% in the PBS group after 3 wk of injection, while it was 12.5% in the Matrigel group (P < 0.05). Hepatoduodenal ligament and duodenal invasions with obstructive jaundice and upper digestive obstruction with mesenteric lymph node metastasis were observed in the pancreatic head group. In the pancreatic tail group, spleen and gastric invasion were dominant, leading to retroperitoneal lymph nodes metastasis. Positive immunohistochemical staining of cytokeratin and negative staining of vimentin and chromogranin A confirmed that the orthotopic pancreatic tumor injected with Pan02 cells suspended in Matrigel was of epithelial origin and expressed exocrine markers of cancer. This method of low-temperature Matrigel suspension and injection is effective for establishing an orthotopic mouse model of pancreatic cancer.