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Acute pancreatitis in mice with lipoprotein lipase deficiency

Yan ZHAO ; Li CHENG ; Xingpeng WANG ; Yuhui WANG ; Guoqing LIU

Chinese Journal of Pancreatology.2009;9(5):340-342. doi:10.3760/cma.j.issn.1674-1935.2009.05.017

Objective To establish an experimental animal model of hypertriglyceridemic(HTG)panereatitis by using special lipoprotein lipase(LPL)deficient HTG heterozygous mice.Methods LPL deficient HTG heterozygous mice and wild type mice were divided into experiment group and control group,then each group was subdivided into 12 h,24 h subgroup.Acute pancreatitis(AP)was induced by caerulein intra-abdominal injection for 7 times(50μg/kg)at the interval of 1 h;the mice in the control group received same amount of normal ssline.The serum level of TG,amylase was determined,and morphologic changes were scored.Results The serum level of TG in LPL deficient HTG heterozygous mice was(3.55±0.27)mmol/L,which was significantly higher than that of wild type mice[(0.94±0.18)mmol/L,P＜0.05].The serum level of TG and amylase in heterozygous mice at 12 h was(3.55±0.27)mmol/L and(3685±484)U/L,which was significantly higher than those in wild type mice[(0.92±0.11)mmol/L and(2501±410)U/L,P＜0.05].The pancreatic tissue edema,necrosis,bleeding and inflammatory cell infiltration score was 3.94 ±0.21,3.94±0.21,1.84±0.25 and 1.84±0.25 in heterozygous mice,which was significantly higher than that of wild type mice(3.06±0.01,2.52±0.51,0.46±0.22 and 0.58±0.38,P＜0.05).Conclusions The serum level of TG was moderately and stably elevated in heterozygous mice.The mice developed more severe panereatitis after caemlein induction.which was an ideal experimental model for study of mechanism of HTG pancreatitis.

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Expression of stem cell markers in pancreatic cancer cells resistant to chemoradiotherapy

Zhiyong DU ; Cuifeng WEI ; Rui TIAN ; Jianxin JIANG ; Min WANG ; Renyi QIN

Chinese Journal of Pancreatology.2009;9(5):321-323. doi:10.3760/cma.j.issn.1674-1935.2009.05.011

Objective To investigate the expression of Bcl-2,survivin and pancreatic cancer stem cells markers Oct-4 and ABCG2 in pancreatic cancer cells resistance to chemoradiotherapy.and explore its mechanism.Methods Concurrent ehemoradiotherapy was used to obtain pancreatic cancer cells resistant to chemoradiotherapy,the pancreatic cancer cells without chemoradiotherapy treatment were used as control.Western-blot was applied to detect the expression of Bcl-2,survivin,Oct-4,ABCG2.Results The expression of Bcl-2 was 0.7955±0.0326,0.5718±0.0212,0.6137±0.0382 and 0.8733±0.0461,respectively;the expression of survivin protein was 0.8207±0.0490,0.6973±0.0211,0.7967±0.0346 and 0.8013±0.0398,respectively;the expression of Oct-4 protein was 0.8728±0.0177,0.7861±0.0139,0.4794±0.0932 and 0.4216±0.1043,respectively;the expression of ABCG2 protein was 0.7810±0.1370,0.4957±0.1126,0.6102±0.1358 and 0.4670±0.1274,respectively.in resistant pancreatic cancer cells of SW1990,BxPC3,pc3,jf305 cell line.The corresponding values in the control group were 0.4723±0.018,0.2954±0.0103.0.3587±0.0201 and 0.2718±0.0136;0.4717±0.0274,0.3587±0.0113,0.3891±0.0147 and 0.3326±0.0124;0.6053±0.0142,0.4236±0.0086.0.2385±0.0671 and 0.1985±0.0582;0.3156±0.0582.0.2360±0.0423,0.2813±0.0512 and 0.1808±0.a0370.The expression of all the four proteins significantly increased after ehemoradiotherapy(P＜0.05).Conclusions Pancreatic cancer cells resistant to chemoradiotherapy may contain cancer stem cells.

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Suspension culture of human pancreatic cancer stem cells

Shineng ZHANG ; Shuli WEI ; Fengting HUANG ; Wa ZHONG ; Xiaohong ZHUANG ; Aixin LIANG

Chinese Journal of Pancreatology.2009;9(5):315-317. doi:10.3760/cma.j.issn.1674-1935.2009.05.009

Objective To establish the method of suspension culture for stem cells from human pancreatic cancer cell line PANC1.Methods PANC1 cells were cultured in serum-free medium under floating-culture system.Tumor cell spheres were observed by optical microscope.Expression of CD133 and cell cycle were detected by flow cytometry.Cancer stem cells were induced to differentiate with 10%FBS,and expression of CK18,was evaluated with immunofluorescence microscope.Spheres cells were injected into the subcutaneous space of NOD/SCID rat and tumor formation was monitored weekly.Results PANC1 cells could form the stem cells spheres,and the rate of sphere formation was stable between 4%0 and 5%0 after 20 passages in vitro.The expression of CD133(5.91±0.7%)and proportion of G0/G1 phase cell(80.99±2.60%)was significantly increased in spheres cells compared with parental PANC1 cells(1.44±0.52%and 69.01±5.03%),and the difference was statistically significant(P＜0.05).When these spheres cells were cultured in media with serum,these cells gradually returned to the status of parental cells and expressed CK18,2×103 sphere cells injection could initiate tumor fornmtion in NOD/SCID rat.Conclusions Tumor spheres stem cellscould be generated under serum-free floating-culture system.The sphere cells possessed the capacities of self renew,difierentiation,and tumorigenic potential.

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Clinical application of duct-to-mucosa anastomosis technique for pancreaticoduodenectomy

Shun ZHANG ; Bin ZHANG ; Weidong GUO ; Fabo QIU ; Liqun WU

Chinese Journal of Pancreatology.2009;9(5):300-302. doi:10.3760/cma.j.issn.1674-1935.2009.05.004

Objective To investigate the effect and safety of duct-to-mucosa anastomosis technique for pancreaticoduodenectomy(PD).Methods The clinical data,including pancreatic fistula and other complications,of 189 patients underwent PD with end-to-side pancreaticojejunostomy at our institution from Jan 2001 to Jan 2009 were analyzed retrospectively.The definition of pancreatic fistula was threefold increase over the serum amylase level 7 days after operation,and draining volume was more than 50 ml per day.Results Totally 177 Whipple procedures were performed,while 12 pylorus-preserving pancreateduodenectomy procedures were performed.Five patients developed pancreatic fistula with a incidence of 2.65%(5/189).In which 3 were mild Cases,who fully recovered after conservative management,and the other 2 cages were cured by surgical intervention.Other complications included 9 cases of wound infection(4.76%,9/189),11 cases of empty dysfunction(5.82%,11/189),5 Cases of delayed hemorrhage(2.65%,5/189),and 4 cases of intra-abdominal infection(2.12%,4/189),and 2 patients died due to severe intra-abdominal infection and acute pulmonary infarction.Conclusions Duet-to-mucesa anastomosis technique resembles physiological state with low incidence of pancreatic fistula and delayed anastomosis hemorrhage.It may be used for different kinds of anastomosis for pancreatic stump.

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Prevalence and clinical features of pain in patients with pancreatic cancer

Lin JIA ; Jianjun ZHENG ; Yuanyuan SHANG ; Shineng ZHANG ; Kaihong HUANG ; Derong XIE

Chinese Journal of Pancreatology.2009;9(5):294-296. doi:10.3760/cma.j.issn.1674-1935.2009.05.002

Objective To investigate the prevalence and the clinical features of pancreatic cancer pain in a Chinese patient population.Methods The study was carried out in 415 cages of pancreatic cancer which were admitted to the First Municipal people's Hospital of Guangzhou Medical college and the Second Affiliated Hospital of Sun Yat-sen University from 1999 to 2007.The prevalence,clinical features of pancreatic cancer pain and its correlations with the cancer site and the clinical staging were analyzed.Results Of the 415 patients.the prevalence of pain wag 65.1%and 60.5%of all the patients presented pain as the initial symptom;the incidence of pain in pancreatic body/tail cancer patients was 80.7%.while it was 71.4%in total pancreatic cancer patients.and the incidence was 58.2%in pancreatic head cancer patients;the incidence between pancreatic body/tail cancer and pancreatic head cancer patients was statistically different (P＜0.05).The incidence of pain in patients with stage Ⅰ,Ⅱ,Ⅲ,and Ⅳ was 28.6%,58.1%,66.2%and 78.6%.and the difference was statistically significant(P＜0.01).The incidence of moderate to severe degree of pain in patients with stage Ⅰ,Ⅱ,Ⅲ,and Ⅳ was 18.8%,44.4%,53.1%and 68.2%,and the differenee was statistically significant(P＜0.01).Conclusions Pain was very common in patients with advanced pancreatic cancer.The incidence and severity of pain increased with the progression of pancreatic cancer.

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Relation between pleural effusion and severity of acute pancreatitis

Xiuying LU ; Jun HU ; Zhen DING ; Xiaohua HOU

Chinese Journal of Pancreatology.2009;9(5):309-311. doi:10.3760/cma.j.issn.1674-1935.2009.05.007

Objective To investigate the incidence of pleural effusion in acute panereatitis(AP)and the relation between pleural effusion and severity of AP.Methods The medical records of 766 patients with AP were analyzed retrospectively.The incidence of pleural effusion was documented and its relationship with age of onset,sex,Ranson score,CTSI,serum albumin and hospital day was analyzed.Results In the 766 AP patients,there were 129(16.8%)patients had pleural effusion.In 171 SAP patients,there were 91 (15.3%)patients had pleural effusion.In the 595 MAP patients,there were 129(16.8%)patients had pleural effusion.The difference in the incidence of pleural effusion between MAP and SAP patients was statistically significant(P＜0.05).The serum amylase,albumin,Ranson score,CTSI,and hospital day in patients with pleural effusion were(795±1013)U/L,(36±7)g/L,1.12±1.15,4.02±1.16 and(23.4±23.4)d,respectively;while the corresponding values in patients without pleural effusion were(592±856)U/L,(38±6)g/L,0.85±0.98,3.15±16.60 and(17.3±16.6)d,respectively.The difference in Ranson score,serum amylase,CTSI between the two groups was statistically significantly(P＜0.05 or＜0.01＝,the serum level of albumin in patients with pleural effusion was significantly lower than that in patients without pleural effusion(P＜0.01),the hospital day in patients with pleural effusion was significantly longer than that in patients without pleural effusion(P＜0.01).Pleural effusion of both sides was present in 92 patients,while pleural effusion of right side was present in 11 patients,pleural effusion of left side was present in 26 patients;the site of pleural effusion was not associated with the severity of AP,however,patients with pleural effusion of left side tended to have longer hospital day(P＜0.05).Conclusions Patients with pleural effusion during AP were more likely to be complicated with severe conditions,and the presence of pleural effusion may be a good marker for severity evaluation.

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Methylation status of MUC2 gene in pancreatic carcinoma cell lines and peripheral blood of pancreatic carcinoma patients

Lumin BO ; Zhaoshen LI ; Jun GAO ; Yanfang GONG ; Hongyu WU ; Jing JIN

Chinese Journal of Pancreatology.2009;9(5):331-333. doi:10.3760/cma.j.issn.1674-1935.2009.05.014

Objective To analyze the methylation status of MUC2 gene in pancreatic carcinoma cell lines and peripheral blood of pancreatic carcinoma patients,and to explore the role of MUC2 methylation in the early diagnosis of pancreatic carcinoma.Methods Human pancreatic cancer cell lines of SW1990,ASPC,PANC1,BxPC3,PaTu8988 and CFPAC1,and 40 peripheral blood samples of pancreatic carcinoma patients,15 cases of chronic pancreatitis,25 cases of normal controls were collected,and the methylation status of MUC2 gene was detected by methylation sensitive restriction endonuclease PCR.Results MUC2 methylation was not detected in PANC1,BxPC3,PaTu8988,but was detected in ASPC,CFPAC1,SW1990.Among the peripheral blood samples,the rate of methylation in pancreatic cancer was 40.O%(n=16),in chronic pancreatitis was 0%,in normal controls was 4.0%(n=1),and the difference among the three groups was statistically significant(P＜0.01).The methylation of MUC2 gene CpG islands for the diagnosis of pancreatic carcinoma had a sensitivity of 40%,specificity of 97.5%,accuracy of 68.8%,positive predictive value of 94.1%and negative predictive value of 61.9%.Conclusions The detection of MUC2 hypermethylation in peripheral blood samples may be an potential marker for early diagnosis of pancreatic carcinoma.

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Effect of recombinant intestinal trefoil factor on intestinal mucosa of acute necrotizing pancreatitis in rats

Linlin SHI ; Lina MENG ; Xiande YE ; Chengman ZHAO ; Haibiao BAO

Chinese Journal of Pancreatology.2009;9(5):324-327. doi:10.3760/cma.j.issn.1674-1935.2009.05.012

Objective To investigate the effect of recombinant intestinal trefoil factor(rITF)on the intestinal mucosa of acute necrotizing pancreatitis(ANP)rats and explore the mechanism.Methods 60 male SD rats were randomly divided into control group(n=20),ANP group(n=20),rITF group(n=20).ANP was induced by retrograde injection of 5%sodium taurocholate(100μl/100 g)into biliopancreatic duct.Rats in rITF group were injected with rITF(0.5 mg/100 g)before and after ANP induction.The rats in ANP group and control group received same amount of normal sailne.Each group were sacrificed 12 h or 24 h later.respectively.Blood sample was taken to determine the serum level of amylase.Terminal ileum was resected to observe the pathologic changes;immunohistochemistry method was applied to detect the activity of NF-κB;the expression of TNF-α mRNA,ICAM-1 mRNA in intestinal mucosa was measured by RT-PCR.Results Intestinal injury score of ANP group was higher than that ofcontrol group(P＜0.05),intestinal injury score of ANP 12 h group was higher than that of rITF 12 h group(P＜0.05),but there was no significant difference between ANP 24 h group and rITF 24 h group.The number of positive NF-κB cells was 26±4,55±8,49±4,respectively;the relatively expression of TNF-α mRNA in terminal ileum was 0.050±0.005,1.040±0.031 and 0.792±0.0256,respectively;the relatively expression of ICAM-1 mBNA was 0.045±0.010,0.795±0.037 and 0.400±0.031,respectively,in control group,ANP group and rITF 12 h group.The corresponding values in the ANP group were significantly increased compared with those values in the control group (P＜0.05 or P＜0.01).Conclusions rITF may protect the intestinal mucosa.the mechanism may include inhibit NF-κB activation,down-regulate TiNF-α mBNA,ICAM-1 mRNA expression.

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Cost-utility analysis of surgical treatment for SAP

Dan LUO ; Ruoqing LEI ; Zhiwei XU ; Tianquan HAN ; Yaoqing TANG ; Shengdao ZHANG

Chinese Journal of Pancreatology.2009;9(5):303-305. doi:10.3760/cma.j.issn.1674-1935.2009.05.005

Objective To assess the cost-utility and medical economics of surgjcal treatment for SAP.Methods A retrospective study of SAP patients admitted from January to December 2003 to Ruijin Hospital was carried out.The cost of treatment was obtained from financial department and patients questionnaire;health-related quality of life was assessed by using the SF-36 brief questionnaire and the results were compared with normal population and were converted into rQALY,then utility scores were obtained so as to conduct CUA (cost-utility analysis)and related factors were analyzed.Results 98 patients with SAP were discharged,85 were discharged healthy;of them,59 patients had complete records were followed up,2 died during follow up,with a mortality of 3.4%,one patients could not finish the questionnaire and 6 did not respond,finally 50 finished the questionnaire;the total cost in hospital was 9899095 yuan,per capita 101011 yuan;the corrected post-discharge cost was 681737 yuan;the total cost was 10580832 yuan.The cost of medication was the highest,which accounted for 56%of all the cost.The means and deviations for each of eight scales(PF,RP,RE,BP,VT,MH,SF,GH)scores of SF-36 in SAP patients were 83.00±14.64,61.5.0±42.32,68.67±36.52,79.98±14.90,68.80±18.94,72.40±14.75,75.00±17.53,64.70±18.28.compared with normal population,gained 1929.05 QALYs;the cost-utility analysis was 5485 yuan per QALY.The patient's age,length of stay,chronic co-morbidity was associated with the cost of treatment.Conclusions SAP treatment in surgery department was justified in medical economics.Medication contributed to the most part of total costs.The related factors of cost included age,length of stay and chronic co-morbidity.

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Treatment of non-biliary severe acute pancreatitis by endoscopic sphincterotomy

Xiaofeng ZHANG ; Xiao ZHANG ; Jianfeng YANG ; Zhen FAN ; Wen LV ; Yinghui GUO ; Xiuying LIN

Chinese Journal of Pancreatology.2009;9(5):297-299. doi:10.3760/cma.j.issn.1674-1935.2009.05.003

Objective To investigate the role of endoscopic sphincterotomy(EST)and endoscopic nasobiliary drainage(ENBD)in the treatment of non-biliary severe acute pancreatitis(SAP).Methods 73 patients were randomly divided into the endoscopic treatment group(35 cases)and control group(38 cases).The patients in control group received non-surgical treatment.EST plus ENBD were performed in patients in the endoscopic treatment group 72h within hospitalization.Serum levels of amylase before EST and 1d,3 d,7 d after EST were measured;the ease of pain and recovery of bowel function were documented;the mortality rate,complication rate,surgery rote and hospital stay were also observed.Results The successful cannulation rate in the EST group was 94.3%(33/35),and there was no procedure related complication.Serum levels of amylase before EST and 1d,3 d,7 d after EST were(1376±131)U/L,(675±49)U/L,(238±49)U/L,(75±13)U/L,the serum levels of amylase before EST and 1d after EST in the EST group were not significantly different from those in the control group,but the corresponding values at 3 d,7 d were significantly lower than those in the control group(P＜0.01).The apparent effective rate and total effective rate of pain relief was 37.1%and 48.6%.which was significantly higher than those in the control group (26.3%and 28.9%,P＜0.05).There was no mortality in both groups.The complication rate in the EST group within 30 d was 14.3%,which was signiilcanfly higher than that in the control group(44.7%,P＜0.01).The gurgery rate in EST group was 2.86%,which was significantly lower than that in the control group (21.1%,P＜0.05).The hospital stay in EST group was(27.6±4.0)d,which was significantly shorter than that in the control group[(41.7±5.9)d,P＜0.05].Conclusions EST and ENBD treatment for non-biliary SAP was superior to non-surgical treatment within 72 h of symptom onset with excellent safety and feasibility profile.

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