The relationship between multiple clinicopathological features and nerve invasion in pancreatic cancer

BACKGROUND:Nerve invasion is a specific type of tumor expansion and characteristic manifestation of pancreatic cancer(PC),with an incidence rate ranging from 50% to 100%.It is an important prognostic factor for pancreatic cancer,and its early detection is helpful in the management of the disease.This study was undertaken to analyze retrospectively the relationship between neural invasion and multiple clinicopathological features and to provide evidences for clinicians in the management of neural invasion in patients with PC.METHODS:Formalin-fixed paraffin-embeded specimens of PC taken from 215 patients were examined for the presence of neural invasion under a light microscope.Analyzed was the relationship between neural invasion and multiple clinicopathological feature including preoperative fasting blood glucose level,amylase level,serum CA19-9 level,abdominal pain,lumbar and back pain,and the expressions of p53 and Ki67 in tumor tissues.RESULTS:Preoperative fasting blood glucose level,serum CA19-9 level and p53 positive cells in cancer tissue were increased with the rise of pathological grade(P【0.05).These indices were significantly higher in patients with neural invasion than in those without(P【0.05).Further analysis revealed a positive correlation between p53 and Ki67 overexpression and lymphatic metastasis(P【0.05).Referred pain was positively correlated with neural invasion(P【0.05).Patients with PC perineural invasion were more likely to have a higher pathological grade(P【0.05).CONCLUSIONS:Our data indicated that the preoperative fasting blood glucose level,serum CA19-9 level,and referred pain are novel predictive markers for neural invasion in patients with PC.p53 and Ki67 play important roles in neural invasion of PC.Management of hyperglycemia may serve as an auxiliary treatment to curb neural invasion in PC.

Experimental study on operative methods of pancreaticojejunostomy with reference to anastomotic patency and postoperative pancreatic exocrine function

AIM:To assess the patency of pancreaticoenterostomy and pancreatic exocrine function after three surgical methods. METHODS: A pig model of pancreatic ductal dilation was made by ligating the main pancreatic duct. After 4 wk ligation, a total of 36 piglets were divided randomly into four groups. The piglets in the control group underwent laparotomy only; the others were treated by three anastomoses: (1) end-to-end pancreaticojejunostomy invagination (EEPJ); (2) end-to-side duct-to- mucosa sutured anastomosis (ESPJ); or (3) binding pancreaticojejunostomy (BPJ). Anastomotic patency was assessed after 8 wk by body weight gain, intrapancreatic ductal pressure, pancreatic exocrine function secretin test, pancreatography, and macroscopic and histologic features of the anastomotic site. RESULTS: The EEPJ group had significantly slower weight gain than the ESPJ and BPJ groups on postoperative weeks 6 and 8 (P < 0.05). The animals in both the ESPJ and BPJ groups had a similar body weight gain.Intrapancreatic ductal pressure was similar in ESPJ and BPJ. However, pressure in EEPJ was significantly higher than that in ESPJ and BPJ (P < 0.05). All three functional parameters, the secretory volume, the flow rate of pancreatic juice, and bicarbonate concentration, were significantly higher in ESPJ and BPJ as compared to EEPJ (P < 0.05). However, the three parameters were similar in ESPJ and BPJ. Pancreatography performed after EEPJ revealed dilation and meandering of the main pancreatic duct, and the anastomotic site exhibited a variable degree of occlusion, and even blockage. Pancreatography of ESPJ and BPJ, however, showed normal ductal patency. Histopathology showed that the intestinal mucosa had fused with that of the pancreatic duct, with a gradual and continuous change from one to the other. For EEPJ, the portion of the pancreatic stump protruding into the jejunal lumen was largely replaced by cicatricial fibrous tissue. CONCLUSION: A mucosa-to-mucosa pancreatico- jejunostomy is the best choice for anastomotic patency when compared with EEPJ. BPJ can effectively maintain anastomotic patency and preserve pancreatic exocrine function as well as ESPJ.

Hypoxia inducible factor-1α mediates protective effects of ischemic preconditioning on ECV-304 endothelial cells

AIM: To investigate whether hypoxia inducible factor-1α (HIF-1α) is linked to the protective effects of ischemic preconditioning (IP) on sinusoidal endothelial cells against ischemia/reperfusion injury. METHODS: Sinusoidal endothelial cell lines ECV-304 were cultured and divided into four groups: control group, cells were cultured in complete DMEM medium; cold anoxia/warm reoxygenation (A/R) group, cells were preserved in a 4℃ UW solution in a mixture of 95% N2 and 5% CO2 for 24 h; anoxia-preconditioning (APC) group, cells were treated with 4 cycles of short anoxia and reoxygenation before prolonged anoxia- preconditioning treatment; and anoxia-preconditioning and hypoxia inducible factor-1α (HIF-1α) inhibitor (I-HIF-1) group, cells were pretreated with 5 μm of HIF-1α inhibitor NS398 in DMEM medium before subjected to the same treatment as group APC. After the anoxia treatment, each group was reoxygenated in a mixture of 95% air and 5% CO2 incubator for 6 h. Cytoprotections were evaluated by cell viabilities from Trypan blue, lactate dehydrogenase (LDH) release rates, and intracellular cell adhesion molecule-1 (ICAM-1) expressions. Expressions of HIF-1α mRNA and HIF-1α protein from each group were determined by the RT-PCR method and Western blotting, respectively. RESULTS: Ischemia preconditioning increased cell viability, and reduced LDH release and ICAM-1 expressions. Ischemia preconditioning also upregulated the HIF-1α mRNA level and HIF-1α protein expression. However, all of these changes were reversed by HIF-1α inhibitor NS398.CONCLUSION: Ischemia preconditioning effectively inhibited cold hypoxia/warm reoxygenation injury to endothelial cells, and the authors showed for the first time HIF-1α is causally linked to the protective effects of ischemic preconditioning on endothelial cells.

Effect of siRNA-mediated knockdown of eIF3c gene on survival of colon cancer cells

Eukaryotic initiation factor subunit c(eIF3c) has been identified as an oncogene that is over-expressed in tumor cells and,therefore,is a potential therapeutic target for gene-based cancer treatment.This study was focused on investigating the effect of small interfering RNA(siRNA)-mediated eIF3c gene knockdown on colon cancer cell survival.The eIF3c gene was observed to be highly expressed in colon cancer cell models.The expression levels of the gene in eIF3c siRNA infected and control siRNA infected cells were compared via real-time polymerase chain reaction(PCR) and western blotting analysis.Cell proliferation levels were analyzed employing 3-(4,5-dimethylthiazol 2-yl)-2,5-diphenyltetrazolium bromide(MTT) and colony formation assays.Furthermore,the effects of eIF3c gene knockdown on the cell cycle and apoptosis were analyzed using flow cytometry.The results showed that suppression of eIF3c expression significantly(P<0.001) reduced cell proliferation and colony formation of RKO colon cancer cells.The cell cycle was arrested by decreasing the number of cells entering S phase.Further,apoptosis was induced as a result of eIF3c knockdown.Collectively,eIF3c deletion effectively reduced the survival of colon cancer cells and could be used as a therapeutic tool for colon cancer therapy.