1.Developmental history of the extent of lymph node dissection in pancreatic cancer surgery
Journal of Clinical Hepatology 2017;33(1):57-60
Pancreatic cancer is one of the digestive malignant tumors with the worst prognosis and has an overall 5 -year survival rate as low as 5%.Even though radical resection is performed,the 5 -year survival rate is only about 20%.Recurrence and metastasis are the most important influencing factors for the postoperative survival of patients with pancreatic cancer.Lymph node metastasis is an important feature of pancreatic cancer,and the extent of lymph node dissection has always been a hot topic in radical surgery for pancreatic cancer.This arti-cle summarizes the history and current status of the extent of lymph node dissection in pancreatic cancer and points out that standardized lymph node dissection is a key factor for improving patients′prognosis after pancreatic cancer surgery.
2.Effect of resveratrol on the proliferation and invasion of human pancreatic cancer PANC-1 cells
Jing CUI ; Gang ZHAO ; Shanmiao GOU ; Yanping YU ; Chunyou WANG
Chinese Journal of Digestive Surgery 2010;09(5):357-360
Objective To investigate the effect of resveratrol on the proliferation and invasion of human pancreatic cancer PANC-1 cells. Methods Five groups including blank control group, 0. 1% dimethylsulfoxide (DMSO) group and resveratrol groups (50, 100, 200 μmol/L) were established. The proliferation of PANC-1 cells was detected by MTT assay. The apoptosis and cell cycle change were analyzed by flow cytometry. The invasive ability of PANC-1 cells was observed with a Transwell cell culture chamber. The expressions of Bax, Bcl-2,matrix metalloproteinases 2 (MMP-2) and 9 (MMP-9) of the PANC-1 cells were assayed by real-time quantitative PCR and Western blot. All data were analyzed using the analysis of variance. Results ( 1 ) The inhibition rate of resveratrol on the proliferation of PANC-1 cells was 0 in the blank control group, 3.25% ±0.42% in the 0. 1% DMSO group, 13.23% ± 1.68% in the 50 μmol/L of resveratrol group, 42.25% ± 3.20% in the 100 μmol/L of resveratrol group, and 56.94% ±5.31% in the 200 μmol/L of resveratrol group. There was a significant difference in the inhibition rate among the five groups (F=460. 10, P<0.05). (2) The apoptosis rate was 0.05% ±0.03% in the blank control group, 3.39% ± 1.77% in the 0. 1% DMSO group, 6.92% ± 1.85% in the 50 μmol/L of resveratrol group, 19.05% ± 2.01% in the 100 μmol/L of resveratrol group, and 27. 17% ±6.43% in the 200 μmol/L of resveratrol group. There was a significant difference in the apoptosis rate among the five groups (F = 38.84, P < 0.05). (3) There was no significant effect of 0. 1% DMSO on the cell cycle of PANC-1 cells. The number of PANC-1 cells in the G0/G1 and S phase was increased. (4) The average number of invading PANC-1 cells was 61 ± 13 in the blank control group, 54 ± 13 in the 0. 1% DMSO group, 48 ± 15 in the 50 μmol/L of resveratrol group, 23 ±6 in the 100 μ mol/L of resveratrol group and 18 ±7 in the 200 μmol/L of resveratrol group. There was a significant difference in the number of invading PANC-1 cells among the five groups (F = 69.08, P < 0.05 ). (5) There were up-regulated mRNA and protein expressions of Bax and down-regulated mRNA and protein expressions of Bcl-2, and the expressions of MMP-2 and MMP-9 of the PANC-1 cells were inhibited in the resveratrol groups. The changes of the protein expressions of Bax, Bcl-2, MMP-2, MMP-9 were consistent with the changes of the mRNA expressions of the four indexes. Conclusion Resveratrol can significantly inhibit the proliferation and invasion, as well as induce apoptosis of PANC-1 cells in vitro.
3.Insulin mediates hypoxia-inducible factor-1α in human pancreatic cancer ASPC-1 cells
Wei ZHOU ; Tao LIU ; Shanmiao GOU ; Li WANG ; Liang LI ; Chunyou WANG
Chinese Journal of General Surgery 2011;26(3):233-236
ObjectiveTo investigate the effect of insulin on the expression of hypoxia-inducible factor-1α in human pancreatic cancer cell line ASPC-1.MethodsWe divided ASPC-1 cells into five groups: normoxia; normoxia stimulated with insulin; hypoxia; hypoxia pretreated with different concentration of insulin; hypoxia of different time points pretreated with same concentration of insulin. Real-time PCR was used to test the expression of HIF-1α mRNA. Immunohistochemistry was used to examine the expression of HIF-1α in ASPC-1 of insulin treated cancer cells. Western blot was used to determine the expression of HIF-1 α protein in those cells. Transwell was used to test whether insulin could enhance the invasion ability of ASPC-1 pancreatic cancer cells.ResultsInsulin promotes HIF-1α protein expression. ASPC-1 cells expressed low levels of HIF-1α protein under normoxic condition.After stimulated with insulin, the expression of HIF-1 α protein significantly increased (P < 0. 05 ). After treated with hypoxia, the expression of HIF-1α protein also increased(P < 0. 05 ). Low concentrations of insulin didn't increase the expression of HIF-1α under hypoxic environment ( P > 0. 05 ), while high concentration of insulin could increase its expression(P < 0. 05). When ASPC-1 cells pretreated with insulin suffered from hypoxia, the expression of HIF-1α first increased then decreased moderately( P <0. 05). Insulin could enhance the invasion ability of pancreatic cancer cells( P < 0. 05 ).ConclusionsInsulin mediates the expression of HIF-1α protein in human pancreatic cancer ASPC-1 cells with the characteristics of dose and time dependency. Insulin could enhance the invasion ability of ASPC-1 cells.
4.Duodenum-preserving total pancreatic head resection for chronic pancreatitis: a report of 35eases
Feng ZHOU ; Chunyou WANG ; Heshui WU ; Jiongxin XIONG ; Tao LIU ; Shanmiao GOU
Chinese Journal of General Surgery 2009;24(3):179-181
Objective To evaluate a duodenum-preserving total pancreatic head resection procedure for the treatment of chronic panereatitis in patients with a pain-inducing enlarged pancreatic head. Methods From January 1999 to December 2006, 35 cases underwent duodenum-preserving total pancreatic head resection procedure without segment resection of the duodenum, as a modified Beger's procedure. Pain scale in the EORTC QLQ-C30 questionnaire was used to estimate the effect of the surgical procedure on pain relief, and oral glucose tolerance test (OGTF) was used to estimate the maintenance of endocrine function. Results For the anastomosis of the distal pancreas and the jejunum, end-to-end invagination anastomosis was performed in 21 cases, end-to-side duct to mucosa anastomosis was performed in 10 cases, and side-to-side duct drainage procedure was performed in 4 cases. Additional T-tube drainage of the common bile duct was adopted in 4 cases for a possible injury of the common bile duct, and anastomosis of the common bile duct and the duodenum was performed in 1 case for common bile duct obstruction. The mean operation time was 286±55 min, and the mean red blood cell (RBC) transfusion was 1.4±1.3 units. The mean hospital stay was 13±4 days. The mortality of the surgical procedure was 0. The overall morbidity was 17%. Pancreatic fistula developed in 1 case, bile leakage in 3 cases, wound disruption in 1 case, intraabdominal bleeding in 1 case, and there was no duodenal fistula. After the surgery, the mean EORTC QLQ-C30 pain scale decreased from 59±27 to 13±21. On follow-up the endocrine function remained stable, and no new case of diabetes was found. Conclusion The duodenum-preserving total pancreatic head resection procedure without segment resection of the duodenum has good postoperative outcomes, and benefits extirpation of inflammatory pancreatic lesions of the head and uncinate process. It is a safe and effective surgical procedure for chronic pancreatitis with an enlarged and painful pancreatic head.
5.Effects of insulin on proliferation and invasion of human pancreatic cancer PANC1 cells
Tao LIU ; Tongling WANG ; Shanmiao GOU ; Tao YIN ; Li WANG ; Wei ZHOU ; Yongfeng LI ; Chunyou WANG
Chinese Journal of Pancreatology 2012;12(1):19-21
ObjectiveTo investigate the effects of insulin on the proliferation and invasion of human pancreatic cancer cells PANC1,and on its HIF-1α,VEGF expression.MethodsPANC1 was pretreated with insulin of different concentrations (0.1,1,10,100 nmol/L).The proliferation of PANC1 was tested by MTTmethod,and transwell assay was used to test the invasion ability of PANC1.HIF-1α,VEGF and PCNA protein expression was assessed by Western blots,and HIF-1α,VEGF mRNA was detected by real-time PCR.Results Insulin could increase the proliferation of PANC1 in a dose-dependent manner (p <0.05 ),and increase the expression of HIF-1α,VEGF protein.After 100 nmol/L insulin treatment for4 d,the PCNA protein expression in the insulin group was significantly higher than that in the control group (1.196 ±0.014 vs 1.157 ±0.013,P < 0.05).The cancer cells passed through the chamber in insulin group were much more than that in the control group ( 141.0 ± 2.1 vs 89.0 ± 1.4,P <0.05 ).The expression of HIF-1α protein was significantly increased (1.139 ±0.020 vs 0.598 ±0.013,P <0.05),while there was no significant change of HIF-1αmRNA expression.Both the expression of VEGF protein and mRNA were significantly increased (1.011 ± 0.023 vs 0.627 ± 0.013 0.970 ± 0.016 vs 0.350 ± 0.01 3,P < 0.05 ).Conclusions High insulin microenvironment could enhance the proliferation and invasion of PANC1 cells by up-regulating the expression of HIF-1α and VEGF.
6.Management of inoperable advanced pancreatic head carcinoma without gastric outlet obstruction: an analysis of 441 patients
Chong YANG ; Bo WANG ; Yongfeng LI ; Shanmiao GOU ; Chunyou WANG ; Heshui WU
Chinese Journal of General Surgery 2013;(5):347-350
Objective To explore the optimal management strategies for unresectable advanced pancreatic head carcinoma without preoperative gastric outlet obstruction(GOO).Methods Clinical data of 441 cases of advanced pancreatic head carcinoma without GOO undergoing surgery from Jan 2001 to Dec 2010 were analyzed retrospectively.Results Among the 441 cases of advanced pancreatic head carcinoma without GOO,101 patients received simple Roux-en-Y cholecystojejunostomy (group A),133 patients received simple Roux-en-Y choledochojejunostomy (group B),83 patients received Roux-en-Y cholecystojejunostomy combined gastrojejunostomy(group C) and the other 124 patients received Roux-en-Y choledochojejunostomy combined gastrojejunostomy (group D).The postoperative recurrent obstructive jaundice rates were 7.9% and 6.0% in group A and C,respectively; the postoperative de novo GOO rates were 8.9% and 8.3% in group A and B,respectively; there were no differences in median survivals among the four groups (F =1.933,P =0.123).Conclusions Choledochojejunostomy is effective for the reduction of recurrent obstructive jaundice for advanced pancreatic head carcinoma patients without GOO,combined prophylactic gastrojejunostomy during surgical biliary drainage could decrease the rate of postoperative GO0.Cholecystojejunostomy could be only applied for patients with poor health or when choledochojejunostomy is a taboo.
7.Insulin promotes proliferative vitality and invasive capability of pancreatic cancer cells via hypoxia-inducible factor 1alpha pathway.
Li, WANG ; Wei, ZHOU ; Shanmiao, GOU ; Tongling, WANG ; Tao, LIU ; Chunyou, WANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2010;30(3):349-53
This study examined whether insulin-stimulated hypoxia-inducible factor 1alpha (HIF-1alpha) expression plays a crucial role in promoting the proliferative vitality and invasive capability in human pancreatic cancer cells. PANC-1 cells were divided into three groups: Control group, insulin group and insulin+YC-1 (a pharmacological inhibitor of HIF-1alpha) group in terms of different treatments. Cells in the insulin group or insulin+YC-1 group were treated with insulin (0.1, 1, 10 and 100 nmol/L) alone or combined with 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1, 0.1, 1, 10 and 100 mumol/L). HIF-1alpha mRNA and protein expression in PANC-1 cells was determined by real-time RT-PCR and Western blotting respectively. Cell proliferation and invasion were measured by using growth curve and invasion assay, respectively. Western blot analysis demonstrated that insulin dose-dependently increased the HIF-1alpha protein expression, and YC-1 could dose-dependently block this effect. However, neither insulin nor YC-1 altered HIF-1alpha mRNA levels in PANC-1 cells. Moreover, insulin could enhance the proliferation and invasion of PANC-1 cells, while YC-1 could weaken this effect. It was concluded that the malignant proliferation and local invasion of pancreatic cancer cells may be related to high-insulin microenvironment. The tumor biological behavior change resulting from high-insulin microenvironment may be associated with the increased expression of HIF-1alpha protein.
8.Insulin Promotes Proliferative Vitality and Invasive Capability of Pancreatic Cancer Cells via Hypoxia-inducible Factor 1α Pathway
WANG LI ; ZHOU WEI ; GOU SHANMIAO ; WANG TONGLING ; LIU TAO ; WANG CHUNYOU
Journal of Huazhong University of Science and Technology (Medical Sciences) 2010;30(3):349-353
This study examined whether insulin-stimulated hypoxia-inducible factor 1α(HIF-1α)expression plays a crucial role in promoting the proliferative vitality and invasive capability in human pancreatic cancer cells.PANC-1 cells were divided into three groups: Control group,insulin group and insulin+YC-1(a pharmacological inhibitor of HIF-1α)group in terms of different treatments.Cells in the insulin group or insulin+YC-1 group were treated with insulin(0.1,1,10 and 100 nmol/L)alone or combined with 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole(YC-1,0.1,1,10 and 100μmol/L).HIF-1α mRNA and protein expression in PANC-1 cells was determined by real-time RT-PCR and Western blotting respectively.Cell proliferation and invasion were measured by using growth curve and invasion assay,respectively.Western blot analysis demonstrated that insulin dose-dependently increased the HIF-1α protein expression,and YC-1 could dose-dependently block this effect.However,neither insulin nor YC-1 altered HIF-1α mRNA levels in PANC-1 cells.Moreover,insulin could enhance the proliferation and invasion of PANC-1 cells,while YC-1 could weaken this effect.It was concluded that the malignant proliferation and local invasion of pancreatic cancer cells may be related to high-insulin microenvironment.The tumor biological behavior change resulting from high-insulin microenvironment may be associated with the increased expression of HIF-1αprotein.
9.Effect of Target-directed Regulation of Uncoupling Protein-2 Gene Expression on Ischemia-reperfusion Injury of Hepatocytes
WAN CHIDAN ; WANG HONGBO ; Cheng RUI ; GOU SHANMIAO ; LIU TAO
Journal of Huazhong University of Science and Technology (Medical Sciences) 2008;28(5):558-563
Summary: The effect of target-directed regulation of the uncoupling protein-2 (UCP-2) gene expression on the ischemia-reperfusion injury of hepatocytes under different conditions was investigated. The expression plasmid and RNAi plasmid targeting UCP-2 gene were constructed and transfected into normal hepatocytes and fatty liver cells, respectively. The expression of UCP-2 mRNA was detected by real time PCR. The cells were divided into normal cell group (NCG), group of normal cells transfected with empty vector (EVNCG), group of normal cells transfected with expression plasmid (EPNCG), fatty liver cell group (FCG) and group of fatty liver cells transfected with RNAi plasmid (RPFCG). The ischemia-reperfusion model in vitro was established. One, 6, 12 and 24h after reperfusion, Annexin V/PI flow cytometry was used to measure cell necrosis rate, apoptosis rate and survival rate. Simultaneously, the intracellular ATP, ROS and MDA levels were determined. The resuits showed that 1, 6, 12 and 24h after ischemia-reperfusion, the intracellular ROS, MDA and ATPlevels and cell survival rate in EPNCG were significantly lower, and cell necrosis rate significantly higher than in NCG and EVNCG, but there was no significant difference in apoptosis rate among NCG, EVNCG and EPNCG (P005). Six, 12 and 24h after reperfusion there was no significant difference in ROS, MDA levels and apoptosis rate between FCG and RPFCG (P0.05), but the ATP level and survival rate of cells in RPFCG were higher than in FCG (P<0.05). It was concluded that down-regulation of the UCP-2 gene expression in steatotic hepatocytes could alleviate the ischemia-reperfusion injury of liver cells.
10. Treatment of pancreatic diseases and prevention of infection during outbreak of 2019 coronavirus disease
Shanmiao GOU ; Tao YIN ; Jiongxin XIONG ; Tao PENG ; Yao LI ; Heshui WU
Chinese Journal of Surgery 2020;58(0):E006-E006
Objective:
To explorethe proper protective measures for pancreaticdiseases treatment during theoutbreak of 2019 coronavirus disease(COVID-19).
Method:
Clinical data of four cases of patients that suffered COVID-19from February 2nd, 2020 to February 9th, 2020 in pancreatic surgery were reviewed.After the first patientscuffednosocomial infection of COVID-19, the general protective measures in our department wereupdated.Only one patient was admitted to each room alone, with no more than one caregiver.The body temperature of care givers was measuredtwice a day.Primary protections were applied to all staff.The floor was sterilized using disinfectant with an effective chlorine concentration of 1000 mg/L.The protective measures for interventional procedures were as follow.Primary protection was applied to the operators ofcentral venipuncture catheter, percutaneous abdominal/pleural drainage, percutaneous retroperitoneal drainage, percutaneous transhepatic cholangial drainage and other surgical procedures with local anesthesiaand epidural anesthesia.Secondary protection was applied to the operators of endoscopic retrograde cholangiopancreatography and surgical procedures with general anesthesia.
Results:
During Feb 2nd, 2020 to Feb 9th, 2020, four patients in our department were diagnosed with COVID-19, of which one was died of COVID-19, two were cured, and one is still in hospital for COVID-19.After the update ofprotective measures in our department, no more nosocomial infection of COVID-19occurred.Two central venipuncture catheter, three percutaneous abdominal/pleural drainage, one percutaneous retroperitoneal drainage, one percuteneous transhepatic cholecyst drainage and one open surgery with general anesthesia were performed with no infection of operators.
Conclusions
The caregivers of patients are potential infection source of COVID-19.Enhanced protective measures including the management measures of caregivers can decrease the risk of nosocomial infection of COVID-19.