Abstract:To investigate the antimigratory and antiinvasive effect of somatostatin receptor type 2 (SSTR2) gene transfection mediated by adenovirus in human pancreatic carcinoma cell and the mechanisms involved in this effect. Methods;The full length human SSTR2 cDNA was introduced into pancreatic cancer cell line BXPC3 by adenovirusmediated transfection, and stable expression of RNA and protein of SSTR2 were detected by RTPCR and Westenblot. The Matrigel coated Transwell was used to detect the migratory and invasive ability of SSTR2expressing cells, AdvGFP control cells and mock control cells. Furthermore, the expressions of matrix metalloproteinase2 (MMP2) and tissue inhibitor of metalloproteinase2(TIMP2) were detected by RTPCR method in these cells. Results;The stable expression of SSTR2 was detected in BXPC3 cells transfected by AdvGFPSSTR2. A dramatic decrease of BXPC3 expressing SSTR2 cell migratedthrough a Matrigelcoated filter was observed, as compared with AdvGFP control cells and mock control cells(P<0.01). Moreover, expressions of MMP2 mRNA were significantly increased in the SSTR2expressing cells and conversely the expressions of TIMP2 mRNA were significantly reduced in the SSTR2expressing cells compared with the AdvGFP control and mock control (P<0.01). Conclusions;The expression of reintroduced human SSTR2 gene in BXPC3 cell by AdvGFPSSTR2 exerts mankedly antimigratory and antiinvasive effect on pancreatic cancer cells, and the mechanisms involved in this effect may be by atteration of the MMP2/TMP2 ratio and thus suppress the degradation of extracellular matrix by cancer cells.

Abstract:To investigate the effect of integrinβ1 antisense oligodeoxynucleotide(ASODN) on humanpancreatic cancinoma transplanted subcutaneously in nude mice.Methods;The models of human pancreaticcancinoma transplanted subcutaneously were established in nude mice, then divided randomly into 3 groups and different treatment was given respectively(control group, random oligodeoxynucleotide group and ASODN group). After treatment, the weight of nude mice and tumor volume were observed, and the tumor growth inhibitory rate and the tumor response rate were calculated. The expressions of integrinβ1 mRNA and protein in tumor tissue were determined by RTPCR and Westernblot. Results;The tumor growth inhibitory rate in the random oligodexynucleotide group and the ASODN group was 4.75％ and 72.70％, respectively. The tumor decrease rate of the ASODN group was 10.91％. The expression level of integrinβ1 mRNA and protein was decreased in the ASODN group compared with other 2 control groups. Conclusions;Our findings suggest that integrinβ1 antisense oligodeoxynucleotides result in marked inhibition of human pancreatic cancinomagrowth in nude mice. It may be a novel treatment approach for human pancreatic carcinoma.

Abstract:Objective;To investigate the expression of 5LOX in pancreatic cancer tissue and the relationship between 5LOX expression and expression of VEGF.Methods;The expression of 5LOXmRNA, VEGFmRNAin 35 pancreatic cancer fresh tissue samples were detected by semiquantitive reverse transcriptasepolymerase chain reaction method.Results;Expression of 5LOXmRNA，VEGFmRNA in pancreaticcancer tissue were 74.3%, 60% respectively,and the expression was correlated to the with clinicalstages of the tumor; also expression of VEGFmRNA was correlated to the differentiation of the tumor. Expression of 5LOXmRNA and VEGFmRNA were synergetic in pancreatic cancer(P<0.05), and were closely correlated(P<0.01). III~IV stages of pancreatic cancer showed significantly stronger expressions of 5LOX compared to in I~II stages of pancreatic cancer（P<0.05）. Conclusions;Expression of 5LOX，VEGF in pancreatic cancer tissue was markedly elevated,and correlated to the clinical stages of the tumor; expression of 5LOX and VEGF were positively related in pancreatic cancer.

Abstract:Objective;To study the expression of Survivin and the relationship with proliferative activity in pancreatic carcinoma (PC). Methods;The expression of SurvivinmRNA was investigated by reverse transcriptasepolymerase chain reaction (RTPCR) in 62 cases of PC samples, 12 cases of chronic pancreatitis(CP) samples, and 10 cases of normal pancreatic tissue samples. Meanwhile,the expression of proliferative cell nuclear antigen(PCNA) was detected by immunohistochemical assay. Results;The expressionof Survivin gene was detected in a significantly greater proportion in PC (74.2%) than CP (0/12) and normal pancreatic tissue(0/10) (P＜0.05). There was no relationship between Survivin gene expression and histological differentiation, clinical stage, or lymph nodes metastasis of PC. Furthermore, Survivinpositive PC had higher PCNALI than that of survivin negative PC (P<0.01). Conclusions;The expression of Survivin gene is increased in PC and related to higher proliferation potential of PC, and that Suggested that survivin may play an important role in the pathogenesis and progression of PC. Survivin may be identified as a new potential diagnostic/therapeutic target of PC.

Abstract:Objective;To investigate the pathogentic factor of severe acute pancreatitis(SAP)associated lung injury and the protective function of octreotide combined with alinastatin on SAPassociated lung injury in rats. Methods;Eighty SD rats were randomly divided into 5 groups. Sham operative （S）group, SAP group, octreotide（O）group, ulinastatin （U）group and octreotide + ulinastatin （O+U）group, and each group was divided into 6h,12h subgroups. After AP models were induced, the serum concentration of amylase(AMY),tumor necrosis factorα(TNFα), malondiadehyde (MDA), and the concentration of myeloperoxidase(MPO) in lung tissue were determined; and the pancreas and lung pathology were graded, the changes of the abovementioned indexes after using octreotide and ulinastatin were compared.Results;（1）Compared to SAP group , AMY, TNFα,MDA, MPO, and pancreas pathology score were decreased significantly in each of the 3 therapy groups during the same period;and at 12h, in O+U subgroup,lung pathology score also decreased compared to SAP group(P<0.05 ).（2）Compared to O group, in O+U group, MPO significantly decreased(P<0.05);and compared to U group, MDA also had significant decline(P<0.05 ).(3)TNFα significantly decrease in SAP group at 12h compared to 6h.（4）There was a positive correlation between AMY, TNFα,MDA,and MPO with pancreas and lung tissue pathology scores (r=0.343~0.781，P<0.01). Conclusions;(1)TNFα,MDA，and MPO are important pathogenetic factors for SAPassociated lung injury. (2)Octreotide and ulinastatin can decrease the degree of SAPassociated lung injury,and a better effect could resulte from combination of octreotide with ulinastatin.

Abstract:Objective;To investigate the effects of regional arterial infusion of urokinase (LAI) on the pancreaticmicrocirculation in rats with severe acute pancreatitis(SAP). Methods;Rats were divided into 4 groups: sham operation(A) group, SAP(B) group, urokinase LAI(C) group and normal saline LAI(D) group. Pancreatic blood flow was measured by laser Doppler instrument, pancreatic microvascular permeability was determined by measurement of extravasation of Evans Blue, and pathological changes of pancreas were observed. Results;(1)Pancreatic blood flow(PBF):at 1h and 3h,PBF in A group was significantly higherthan that in B,C,D group(all P<0.05),but there was not significant difference between B and D group(P>0.05); however,PBF in C group was significantly higer than that in B and D group(P<0.05). (2)Extravasation of Evans Blue:in normal pancreat tissue was（149.11±17.93）ug/g， which was significantly lower than that in B,C,D group((all P>0.05),but there was not obvious difference betweenB,C,D group(all P>0.05).(3)Pathological score of C group at 1h and 3h was significantly higher than the A group(P<0.05), but was significantly lower than that of B and D group(P<0.05); howerer there was not significant difference between B and D group(P>0.05). Conclusions;UrokinaseLAI can improve the microcirculation of rats with SAP, but can not completely prevent the pathologicalchanges of SAP.

Abstract:Objective;To study the clinical significance of changes of plasma GMP140 and lipid levels in patients with acute pancreatitis. Methods;GMP140 was determined by ELISA and plasm a lipid levels were determined with an autobiochemical analyzer in 58 patients with acute pancreatitis and in 33 healthy individualsas control group. Results;The levels of plasma GMP140 , total cholesterol (TC), lowdensity lipoprotein (LDLC) in acute pancreatitis were higher than in the that control group(P<0.01)；and the levels of plasma GMP140 , TC, LDLC in severe acute pancreatitis(SAP) were significantly higher than that in mild acute pancreatitis(MAP) and control group( P<0.01)；There was a positive correlation betweenGMP140 and TC, LDLC（γ=0.7189 and 0.6121）. Conclusions;SAP patients had a high level of platelet activation. The levels of TC and LDLC were elevated in all of the patients with SAP or MAP. Platelet activation is closely correlated with higher cholesterol level.

Abstract:Objective;To investigate the effect of plateletactivating factor acetylhydrolase(PAFAH) on severeacute pancreatitis(SAP). Methods;Fortyfive male Wistar rats were randomly divided into three groups(n=15 in each group),including group A(sham operation group),group B(SAP group) and group C(PAFAH treated group).PAFAH(5mg/kg) was infused through the dorsal artery of penis after 1 hour and 24 hours of establishing the model in group C.Fortyeight hours after animal models were established,the levels of maleic dialdehyde(MDA),thromboxane B2(TXB2),prostaglandin I2(PGI2),TXB2/PGI2,plateletactivating factor(PAF),endotoxin,tumor necrosis factor(TNFα) in serum,and the activity of myeloperoxidase(MPO) in lung tissue were examined in each group.The pancreas was scored on the basis of pathological changes. Results;Compared with group B, the levels of MDA, TXB2,TXB2/PGI2, PAF,endotoxin,TNFα in serum, and MPO activity in lung tissue and the pathological scores of pancreas were significantlylower in group C(P<0.05). There was no obvious difference in the level of PGI2 between group B and group C （P>0.05）. Conclusions;PAF plays a critical role during the course of SAP.Administrationof PAFAH can hydrolyze PAF,improve pancreatic microcirculatory dysfunction,suppress systemicinflammatory reaction,relieve pancreatitisassociated intestinal tract injury and lung injury and markedlyameliorate the state of SAP.

Abstract:Objective;To investigate the changes of Tolllike receptor 2 and 4 gene expression in lungs with acute injury induced by acute hemorrhagic necrotizing pancreatitis(AHNP) in rats. Methods;Forty SD male rats were randomly divided into shamoperated group(n=10), and AHNP group(n=30). Of all the rats, the lungs were dissected for lung histological scores and bronchoalveolar lavages were harvested for lung injury index. TLR2,4mRNA expression in the lungs was measured by RTPCR at different time points. Results;TLR2,4mRNA could be detected in lungs with low values in shamoperated group; but they were markedly increased at 3 hours in AHNP group, peaking at 6~12 hours(P<0.05 or P<0.01). Conclusions;These data suggestal that expression of TLR2/4mRNA is increased in lung tissuse in AHNP rats, and upregulation of TLR2,4mRNA expression in lung tissuse may be involved in the development of acutelung injury induced by AHNP.

Abstract:Objective;To investigate the repressing effects of cytosine deaminase(CD) and herpes simplex virusthymidine kinase(HSVtk) double suicide genes coexpression system on human cholangiocarcinoma QBC939 cells and QBC939 cells transplantated tumor in nude mice. Methods;CD and HSVtk double suicide genes were transfered into QBC939 cells using liposomes. After G418 selection, the positive clones of QBC939/CD+tk cells were picked up and cultured. The expression of CD and HSVtk genes was confirmedby RTPCR. In vitro, the QBC939/CD+tk cells were treated with 5Fc and/or GCV, and the cytoxicity efficacy was evaluated by microculture tetrajolium test (MTT) method. The QBC939/CD+tk cells were inoculated subcutaneously into nude mice, and when the tumors were palpable, 5Fc and GCV were injectedintraperitoneally, and the volumes of transplantated tumors were measured before and after medication. Results;Double suicide genes were stably expressed in QBC939/CD+tk cells. The repressing capability of combination of 5Fc and GCV on QBC939/CD+tk cells was more effective than that of using either 5Fc or GCV alone. The increase of cellrepressing was assaciated with increase the concentration of the prodrug. The repressing effect of combination of the 2 prodrugs on early period of transplantation tumor was obvious, even complete abolition of tumor was noted, and moreover a marked local bystander effect was observed. Conclusions;In vitro and in vivo, the cellrepressing efficacy of double suicide gene system on cholongiocarcinoma cells and the tramsplanted tumor of nude mice was significant, and the bystander effect was obvious.

Abstract:Objective;To improve the technique of pancreatoduodenectomy in order to facilitate the managementof complications and direct observation on follow up.Methods;Pancreatoduodenectomy and Child′s method of digestive tract reconstruction was performed in 42 paltents. A blind loop of jejunum 5 to 6 cm in length was constructed beyond the pancreatojejular anastomosis and it was fixed to the subcutaneous tissueof the adjacent abdominal wall.Results;Thirtytwo cases recovered uneventfully,and 10 cases had complications induding pancreatic and biliary leakage and hemorrhage. These complications were successfully treated under direct vision by choledochoscope passed into the blind jejunal loop. This method of observation was used for longtime follow up in 22 cases,and revealed ercurrent tumor(n=5),bile duct stricture(n=4) and bile duct ascariasis(n=1).Conclusions; This operative method did not cause new complicationsand it can be combined with the traditional operation. Postoperatively, direct observation and management of leakage of pancreatojejular anastomosis and biliointestinal anastomosis and hemorrhage can be accomplished, and the anastomoses and pancreatic stump can be directly observed at followup.

Abstract:Objective;To analyse the causes of postoperative complications of pancreatoduodenectomy (PD) and study measures for prevention and treatment of the complications.Methods;A retrospective study was carried out on the data of 139 cases of pancreatoduodenectomy performed during recent 3 years in our hospital. They included 91 cases of radical resection operation and 43 cases of pancreatoduodenectomy combinedwith vascular resection.Results;There were 38 cases (27.4%) occurred complications after PD,including 10 cases (7.2%) of upper gastrointestinal hemorrhage,4 cases (2.9%) of hemorrhage in the abdominal cavity,and 6(4.3%) cases of pancreatic leakage,4cases (2.9%) of bile duct leakage,3(2.2%) cases of intraabdominal infection,5 cases (3.6%) of pulmonary infection,and 6 cases (4.3%) of functional delayed gastric emptying. Four cases died during the perioperative period.The overall mortality rate were 2.9%.Conclusions;The main complications after PD were hemorrhage,pancreatic leakage,bile duct leakage and intraabdominal cavity infection.Meticulons operative technique, the selection of appropriate anastomoses technique, careful observation and timely aggressive management in the postoperative period are the key points to reduce postoperative morbidity and motality rate after PD.

Abstract:Objective;To investigate the proper selection of methods of hepatic vascular control during resectionof liver carcinoma. Methods;Ninetyfoury cases of liver carcinoma underwent hepatectomy using 4 different types of hapatic vascular control in our hospital. The operative time, amount of intraoperative blood loss, transfusion, and postoperative drainage, changes of postoperative liver function and complications were analyzed and compared between the 4 groups. Results;Of the 94 cases, 38 (40.4%) underwent routine Pringle′s maneuver, 34 (36.2%) had selective hemihepatic vascular exclusion, 18(19,1%) without hepaticinflow occlasion and 4 (4.3%) had total vascular exclusion during hepatectomies. All tumors were entirely removed and operations were performed smoothly. Postoperative complications occurred 24 casetimes and 2 patients (2.1%) died. Conclusions;The selection of method of hepatic vascular control during hepatectomyfor massive liver carcinoma should be comprehensively determined, based on the size and location of tumor, preoperative liver function, diffculty of hepatectomy and findings at intraoperative exploration. Proper method manner of hepatic vascular control is crucial for successful operation and uneventful recovery of the patient.