Laparoscopic combined with multi-video debridement in treatment of complicated infectious pancreatic necrosis / 中华肝胆外科杂志

Objective:To study the clinical application of laparoscopic combined with multi-video debridement in treatment of complicated infectious pancreatic necrosis (CIPN).Methods:The clinical data of 34 patients with CIPN who were treated at the Department of General Surgery, Xuanwu Hospital, Capital Medical University from August 2017 to December 2019 were retrospectively studied. Based on the different video methods used, these patients were divided into 3 groups: the laparoscopic combined with intraoperative ultrasound group, the laparoscopic combined with choledochoscopy group and the laparoscopic group. The number of operations, operation time, blood loss, postoperative complication rates, mortality rates and total length of hospital stay were compared.Results:There were 13 patients in the laparoscopic combined with intraoperative ultrasound group, with age of (56.4±13.4) years. There were 7 patients in the laparoscopic combined with choledochoscopy group, with age of (48.0±8.4) years. There were 14 patients in the laparoscopic group with age of (51.4±15.6) years. The number of operations of the laparoscopic combined with intraoperative ultrasound group, the laparoscopic combined with choledochoscopy group and the laparoscopic group were (2.2±1.1), (1.6±0.8), (2.9±1.4), respectively. The number of operations of the laparoscopic combined with choledochoscopy group were significantly less than that of the laparoscopic group ( P<0.05), but there were no significant differences among the other groups ( P>0.05). The operation time of the laparoscopic combined with intraoperative ultrasound group, the laparoscopic combined with choledochoscopy group and the laparoscopic group were (70.5±22.9) min, (65.7±19.9) min, (51.5±15.4) min, respectively. The operation time of the laparoscopic combined with intraoperative ultrasound group was significantly longer than that of the laparoscopic group ( P<0.05), but there were no significant differences among the other groups ( P>0.05). There were no differences in blood loss, postoperative complication rate, mortality rates and total lengths of hospital stay among the three groups ( P>0.05). Conclusion:Laparoscopic combined with multi-video debridement after making full use of the advantages of each of the video methods, can be used to improve treatment outcomes of patients with CIPN.

A retrospective analysis of clinical characteristics and prognosis of infected pancreatic necrosis in elderly patients / 中华肝胆外科杂志

Objective:To evaluate the clinical characteristics and prognosis of elderly patients with infected pancreatic necrosis (IPN).Methods:Clinical data of IPN patients admitted in the Acute Pancreatitis Clinical Center of Xuanwu Hospital of Capital Medical University from January 1, 2014 to October 30, 2018 were retrospectively collected analyzed. These patients were separated into elderly group (older than 65 years old) and young group (less than 65 years old). These clinical data were analyzed between the two groups, including age, sex, comorbidities, laboratory and imaging examinations, treatment methods and outcomes, length of hospital stay, length of ICU stay and mortality.Results:A total of 163 patients were included. In the elderly group, there were 42 patients aged 67.00(65.50, 77.00), with 22 males and 20 females. In the young group, there were 121 patients aged 44.00(33.25, 52.00), with 90 males and 31 females. The ratio of male to female in the elderly group was 47.62% (20/42), which was significantly higher than that in the young group [25.62% (31/121), P<0.05]. The etiological cause of acute pancreatitis for 83.33% (35/42) elderly IPN patients were biliary diseases, while only 43.80% (53/121) of young IPN patients were caused by biliary diseases ( P<0.05). Elderly IPN patients had higher rates of coronary artery disease and hypertension co-morbidities compared to those of the young patients (all P<0.05). The level of aspartate aminotransferase and blood urea nitrogen in the elderly group were significantly higher than those of the young group [37.00 (27.50, 58.00) IU/L vs. 28.00 (18.50, 44.00) IU/L; 6.36 (4.23, 10.89) mmol/L vs. 4.68 (3.23, 7.15) mmol/L, P<0.05]. However, the level of triglyceride was significantly lower [1.05 (0.78, 1.35) mmol/L vs. 2.26 (1.32, 18.55) mmol/L, P<0.05]. There were no significant differences in local complications, but the rate of persistent organ failure was significantly higher in the elderly group than that of the young group [30.95% (13/42) vs. 12.40% (15/121), P<0.05]. The duration of total parenteral nutrition for elderly IPN patients were significantly longer than those of young patients [22.00 (13.25, 43.50) d vs. 17.00 (9.00, 26.00) d, P<0.05]. However, the rate of patients that received surgery intervention was more than twice which was significantly lower in the elderly group than that of the young group [26.19% (11/42) vs. 43.80% (52/121), P<0.05]. The mortality rate for elderly IPN patients was significantly higher than those of young patients [21.43% (9/42) vs. 7.44% (9/121), P<0.05]. Conclusions:Elderly IPN patients were associated with a higher proportion of female than the young IPN patients. Elderly IPN patients usually have a higher proportion of cardiovascular comorbidities, and are associated with higher persistent organ failure rates and mortality rates.

Re-exploration of minimally invasive surgery for infected pancreatic necrosis / 中华外科杂志

The application of minimally invasive technique in infected pancreatic necrosis has been matured gradually but has controversy and challenges in the same time. This paper further discusses the advantages, timing, combination of multi-video-assisted debridement and post-operative management of minimally invasive surgery. The greatest advantage of minimally invasive surgery lies in "No intervention for normal abdominal space" which not only can reduce unnecessary injury and complication but also promote intestinal function recovery after operation. The principle of delayed operation is controversial. Early PCD and "one-step" minimally invasive laparoscopic debridement and drainage have both achieved good results. The combination of multi-video-assisted minimally invasive technique can make up for the shortage of single technique to shorten the operation time and improve the debridement efficiency of patients with complicated infected pancreatic necrosis and provide new ideas for video-assisted debridement. Fully debridement and drainage are the key points and standardization for post-operative management. It′s a difficult problem and an important research direction to apply minimally invasive technique for patients with infected pancreatic necrosis reasonably and scientifically.

Clinical study of different surgical approaches in laparoscopic debridement for patients with infected pancreatic necrosis / 中华外科杂志

Objective@#To examine the indications and effects of different surgical approaches in laparoscopic debridement for patients with infected pancreatic necrosis(IPN).@*Methods@#The clinical data of 213 IPN patients treated by laparoscopic debridement at Department of General Surgery, Xuanwu Hospital, Capital Medical University from June 2012 to February 2019 were retrospectively analyzed.The therapeutic effects were summarized and analyzed according to different surgical approaches. There were 123 cases in retroperitoneal approach group, including 73 males and 50 females, aging of (51.3±12.4) years; 59 cases in omental sac approach group, including 32 males and 27 females, aging of (48.3±14.2) years; 23 cases in combined approach group, including 13 males and 10 females, aging of (54.3±19.7) years; 8 cases in digestive tract approach group, including 5 males and 3 females, aging of (50.2±12.5) years.@*Results@#The time from onset to operation in retro-peritoneal, omental sac, combined and digestive tract approach groups were (44.3±22.8), (47.3±24.3), (52.6±21.2), (51.2±30.1) days, respectively; the operation time was (52.3±26.4), (64.3±29.2), (82.8±24.7), (78.2±38.1) minutes respectively; the median bleeding volume was 18, 33, 42 and 30 ml, respectively; and the first time to eat after operation was (2.5±1.6), (3.8±1.8), (3.7±2.0), (8.4±3.9) days, respectively.The incidence of complications (Clavien-Dindo grade Ⅲ and above) was 10.6%(13/123), 10.2%(6/59), 17.4%(4/23), 1/8 and the mortality was 4.9%(6/123), 3.4%(2/59), 4.3%(1/23) and 0, respectively.The overall mortality of all patients was 4.2%(9/213). The levels of inflammatory factors were significantly lower in all groups 7 days after operation than before, and no patients was converted to open surgery.@*Conclusion@#Individualized selection of the optimal laparoscopic debridement approach of pancreatic necrosis plays an important role in improving the efficacy and prognosis of IPN patients.

Compositional and drug-resistance profiling of pathogens in patients with infected pancreatic necrosis / 中华肝胆外科杂志

Objective To analyze the data on the pathogenic bacteria responsible for infected pan creatic necrosis (IPN) and drug resistance,and to study the impact on prognosis of patients.Methods The clinical data from 101 patients who were diagnosed to have IPN in the Xuanwu Hospital of the Capital Medical University,Beijing,from January 2011 to August 2017,were analyzed retrospectively.Logistic regression and statistical analysis were performed to evaluate the species composition and drug-resistance in the pathogens obtained from the pancreatic necrosis tissues or the drainage culture fluids from these IPN patients in the first,second or third surgery.Results Among the 101 patients,80 had bacteria-positive cultures,of which 97 were pathogenic bacteria:74.2％ were Gram-negative,22.7％ were Gram-positive,and 3.1％ were fungi.The commonest bacterial strains included Escherichia coli (n =20),Klebsiella pneumonia (n =17),Pseudomonas aeruginosa (n =13),Acinetobacter baumannii (n =11),and Enterococcus (hereafter called Ent.) faecium (n =11).Drug resistance analysis showed that the Gram-negative bacilli were susceptible to carbapenems.The resistance rates for all the antibiotic types in K.pneumoniae exceeded 50％.The use of enzyme inhibitors significantly improved bacterial sensitivity to the beta-lactams.The Gram-positive bacteria were sensitive to vancomycin and tigecycline.Drug-resistant fungi were not identified.The multidrug resistance rates for E.coli,K.pneumoniae,P.aeruginosa and A.baumannii Gram-negative bacilli were 35.0％ (7/20),76.5％ (13/17),53.9％ (7/13) and 63.6％ (7/11),respectively,while that for Gram-positive Ent.faecium was 75.0％ (9/12).Forty patients underwent three or more surgeries.Regression analysis showed that the proportion of patients with severe acute pancreatitis who underwent three or more surgeries was higher than that of the patients who underwent fewer surgeries.However,neither the number of overall infections,nor the number of infections with multiple drug-resistant pathogens,was associated with the number of operations.Conclusions Gram-negative bacilli was mainly involved in the primary infections of patients with IPN.E.coli was the most common microbe.Our clinical experience showed that enzyme penicillins or carbapenems were the preferred treatment options.

Video assisted retroperitoneal debridement for infected necrotizing pancreatitis / 中华普通外科杂志

Objective To evaluate the clinical efficacy of video-assisted retroperitoneal debridement (VARD) in the treatment of infected pancreatic necrosis (IPN).Methods 48 infected necrotizing pancreatitis patients underwent video-assisted retroperitoncal debridement from Jan 2013 to Aug 2017.Results There were 30 males and 18 females.After operation,4 patients suffered from postoperative bleeding and underwent angiography.One patient had gastrointestinal fistula,4 patients had newly devoloped organ dysfunction altogether,7 patients had postoperative complications.The incidence of complications was 14.58％ (7/48).3 cases died,the mortality was 6.25％ (3/48).Conclusion The video-assisted retroperitoneal debridement for pancreatic necrotic tissue is effective,safe and minimally invasive for the treatment of infected necrosis of the pancreas.

Silencing pancreatic adenocarcinoma up-regulated factor increases the sensitivity of pancreatic cancer cell line to gemcitabine / 中华肝胆外科杂志

Objective To observe the influence on the sensitivity of pancreatic cancer cell line BxPC-3 to gemcitabine of silencing PAUF gene.Methods BxPC-3 cells,which overexpress PAUF,was stably transfected with PAUF-shCtrl and PAUF-shRNA to establish BxPC-3_shCtrl and BxPC-3_shPAUF cells as control and experiment group.Then the mRNA and protein expression level of PAUF in these two cell lines were detected by RT-PCR and western blot,respectively.The growth inhibition rates of these two cell lines treated with different concentrations of gemcitabine (0,3.1,6.25,12.5,25,50,100,200 nmol/L) were detected by MTT.Apoptosis rates in the cells treated with different concentrations of gemcitabine (0,75,100 nmol/L) were then observed by flow cytometry.Results The relative PAUF mRNA expression level in BxPC-3_shCtrl and BxPC-3 cells were 1.00 ± 0.06 and 0.83 ± 0.07,which were significantly high er than that in BxPC-3_shPAUF cells (0.25 ± 0.02;both P ＜ 0.05).The relative PAUF protein expression level in BxPC-3_shCtrl and BxPC-3 cells were 0.89 ± 0.07 and 0.95 ± 0.04,which were significantly high er than that in BxPC-3_shPAUF cells (0.31 ± 0.03;both P ＜ 0.05).The IC50 value of gemcitabine to BxPC-3_shCtrl cell was (22.88 ± 2.43) nmol/L,which was significantly higher than that of BxPC-3_shPAUF cells [(1.06 ± 0.02) nmol/L;P ＜ 0.05];apoptosis rate of BxPC-3_shPAUF cells treated by gemcitabine increased faster than that of BxPC-3_shCtrl cells.Conclusion PAUF silencing could greatly enhance the sensitivity of BxPC-3 cells to gemcitabine.

Mechamism of PAUF in pancreatic cancer pathogenesis and progression / 中华肝胆外科杂志

Pancreatic adenocarcinoma up-regulated factor(PAUF),a newly discovered gene,is highly expressed in pancreatic cancer.PAUF promotes the metastasis and progression of pancreatic cancer through many ways,such as the activation of signal pathway (CXCR4,β-catenin,TPL2/MEK/ERK,FAK/Scr),increasing the adhesiveness of pancreatic cancer cells,promoting angiogenesis and vascular permeability.Simultaneously,CXCR4,β-catenin,TPL2/MEK/ERK and FAK/Scr are closely related with gemcitabine-resistance.Based on this theory,we infer that PAUF plays a role in gemcitabine-resistance of pancreatic cancer cells.So far,no related research has been done domestic and overseas.The research may find a clue for the mechanism of chemotherapy-resistance and provide a new target spot for the therapy of pancreatic cancer.

Effects of MMI-166 on apoptosis and apoptosis-related protein expression in human pancreatic cancer SW1990 cells / 中华胰腺病杂志

Objective To investigate the effects of MMI-166 on apoptosis and apoptosis-related protein expression of human pancreatic cancer SW1990 cells and its transplanted tumor,and explore possible mechanism.Methods The human pancreatic cancer xenograft model was constructed by using human pancreatic cancer SW1990 cells.Tumor-bearing nude mice were randomly divided into control and MMI-166 groups,and they were treated with normal saline or MMI-166 (200 mg · kg-1 · d-1) for 28 days.Apoptosis index (AI),p53,c-Myc,Bax,Bcl-2,Survivin,Caspase-1,Fas proteins were detected by deoxynucl-eotidyl transferase-mediated nick end labeling (TUNEL method) and Western blot.MMI-166 of different concentrations (0,50,100 μg/ml) were used to treat human pancreatic cancer SW1990 cell for 24 h.The c-Myc,Survivin proteins expressions were measured by Western blotting.Results Apoptosis index in MMI-166 group was 81.1 ±7.9,which was significantly higher than that in control group (21.3 ±2.2,P =0.000) ; the expressions of c-Myc,Survivin were 7715 ± 2229,4594 ± 1240,which were significantly higher than those in control group (16870 ± 2446,15208 ± 1903,P =0.000) ; the expressions of p53,Bax,Bcl-2,Caspase-1,Fas were not significantly different from those in control group.After 50,100 μg/ml MMI-166 treatment,the expression of c-Myc was significantly down-regulated (0.098 ± 0.003,0.073 ± 0.008 vs.0.169 ± 0.007,F =189.361,P ＜ 0.05) ; and the expression of Survivin was not significantly changed.Conclusions MMI-166 may induce cell apoptosis of SW1990 by down-regulating the expression of c-Myc.

Effects of a new matrix metalloproteinase inhibitor, MMI-166, in nude mouse xenografts of human pancreatic cancer / 中华肝胆外科杂志

Objective To investigate of the MMI-166 on the expression of MMP-2,MMP-9 and the cell apoptosis of nude mouse xenografts of SW1990 human pancreatic cancer cells.Methods Establishment of control and experimental groups,randomly,the human pancreatic cancer xenograft model of SW1990 was constructed.The control group was treated with normal saline,and experimental group was treated with MML-166 (200 mg · kg-1 · d-1).The tumor volume and tumor inhibition rate was measured by vernier caliper through length and short diameter.The expression of MMP-2 and MMP-9 protein was observed using immunohistochemistry in the tumor tissues.Apoptosis index was detected by deoxynucleotidyl transferase-mediated nick end labeling (TUNEL method).Results The tumor volume of MMI-166 group (1252.30± 464.84) mm3 was less than the control group (2241.82±208.06) mm3,significantly.The inhibition rate was 34.47％ between the experimental groups (treat with MMI-166) (1.42±0.15) g and control group (2.17±0.20) g.The expression of MMP-2 (2.80 ± 1.10) ％ and MMP-9 (2.60 ± 1.52) ％ protein was significantly downregulated in MMI-166 group,compared with the control group.Apoptotic index in the experimental group (75.60±9.71) ％ was higher than the control group (17.40 ± 10.14) ％,significantly.Conclusion The mechanism of MMI-166 inhibiting pancreatic tumor growth and inducing apoptosis may be related to the suppression of MMP-2 and MMP-9 protein expression.

Effects of MMI-166 on proliferation and apoptosis in human pancreatic cancer SW1990 cell / 中华胰腺病杂志

ObjectiveTo investigate the effects of MMI-166 on the proliferation and apoptosis of human pancreatic cancer SW1990 cells.MethodsMMI-166 of different concentrations (25,50,100 μg/ml) were used to treat human pancreatic cancer SW1990 cell for 24,48 h.Effect of MMI-166 on cell proliferation wasdetected by 3- (4,5-dimethyl-2-thiazole) -2-5-biphenly-tetrazole bromide ( MTT ) method and effect on cell apoptosis was tested by Annexin V-PI method and flow cytometry (FCM).ResultsTwenty-four hours after MMI-166 treatment of different concentrations (25,50,100 μg/ml),the inhibitory rates of the cells were (34.23±3.87)％,(44.81 ±2.01)％,(53.91 ±1.74)％,and the corresponding values were (39.95 ± 1.83) ％,( 52.26 ± 3.46 ) ％,( 63.20 ± 2.48 ) ％ at 48 h,which suggested a time-and concentrationdependent manner.The cell's apoptosis rates were (11.19 ±0.47)％,(23.01 ±0.53)％,(28.10 ± 0.52) ％ at 24 h,and the corresponding values were ( 11.19 ± 0.47 ) ％,( 23.01 ± 0.53 ) ％,( 28.10 ± 0.52)％ at 48 h,which were significantly higher than those in control group [ (0.09 ±0.12)％,P ＜0.05].ConclusionsMMI-166 can inhibit proliferation and induce apoptosis of human pancreatic SW1990 cell in a time- and concentration-dependent manner.