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Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.
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Hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) is rare and enhanced CT or MRI can be used for its diagnosis. Surgical procedure is the main treatment for HCC with BDTT. The authors introduce the experiences of recurrent patient with HCC and BDTT who was treated with targeted therapy plus immunotherapy, in order to provide reference for its clinical diagnosis and treatment.
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Objective@#To explore the clinical efficacy of S-1 single agent adjuvant chemotherapy for the patients undergoing radical resection of extrahepatic biliary carcinoma.@*Methods@#The clinical data of 108 patients with extrahepatic biliary carcinoma receiving radical resection who were admitted from January 2014 to June 2017 were retrospectively analyzed. There were 62 males(57.4%)and 46 females(42.6%),with a median age of 59 years (range:26 to 79 years),10 cases(9.3%) in stage Ⅱ,85 cases(78.7%) in stage Ⅲ, and 13 cases (12.0%) in stage Ⅳ, 40 cases(37.0%) of hilar cholangiocarcinoma, 8 cases(7.4%) of middle cholangiocarcinoma, 25 cases (23.2%) of distal cholangiocarcinoma, 35 cases(32.4%) of gallbladder carcinoma.After radical resection of extrahepatic biliary carcinoma, 49 patients receiving S-1 single agent chemotherapy and 59 patients receiving non-special treatment were divided into the chemotherapy group and the operation group,respectively. All the dates of the patients were followed up and collected with the overall survival time,tumor-free survival time,1,2 and 3-year survival rate after operation,and the rate of major toxic reaction during chemotherapy of the chemotherapy group. Survival curve was drawn by the Kaplan-Meier method, and survival analysis was done using the Log-rank test.@*Results@#There were no significant differences in the general date of two groups(sex, age, tumor size, tumor site, TNM stages, degree of differentiation). The median overall survival time and the median tumor-free survival time in the chemotherapy group were 27 months and 21 months,respectively,and in the operation group were 21 months and 17 months,respectively. There were differences between the two groups in the overall survival rates(χ2=3.967,P<0.05) and the 2 and 3-year survival rate(63.3%,36.6%;41.6%,20.4%;χ2=4.510,P<0.05;χ2=6.143,P<0.05),but the 1-year overall survival rate (83.4%,79.7%)was not statistically significant(χ2=0.286,P>0.05). There were no significant differences in the tumor-free survival time,1,2 and 3-year tumor-free survival rate(77.6%,41.4%,33.1%;62.7%,30.9%,21.2%)between the two groups(χ2=0.876,P>0.05;χ2=0.252,P>0.05;χ2=1.571,P>0.05;χ2=3.323,P>0.05,respectively). The main toxic reaction during chemotherapy were dyspepsia(28.6%, 14/49), anemia(26.5%, 13/49), and leukopenia(22.5%, 11/49), all of which were mild.@*Conclusion@#S-1 single agent chemotherapy after radical reseetion of extrahepatic biliary carcinoma could effectly improve the survival of patients and all of the main toxic reaction during chemotherapy were mild.
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Objective To investigate the application value of choledochoscopy and imaging examination in the diagnosis and treatment of residual bile duct stones.Methods The retrospective descriptive study was conducted.The clinical data of 618 patients who underwent choledochoscopy and imaging examination after operation of hepatolithiasis in the First Affiliated Hospital of Zhengzhou University between April 2014 and September 2018 were collected,including 300 males and 318 females,aged from 19 to 89 years,with an average age of (58 ± 12)years.Observation indicators:(1) situations of residual bile duct stones diagnosed by choledochoscopy and imaging examination;(2) stone extraction situations of patients with hepatolithiasis.Measurement data with normal distribution were represented as Mean±SD,and measurement data with skewed distribution were described as M (range).Count data were represented as absolute number or percentage,and analyzed using the chi-square test or Fisher exact propability.Results (1) Situations of residual bile duct stones diagnosed by choledochoscopy and imaging examination:all the 618 patients underwent choledochoscopy,and 505 of them underwent the imaging examination before choledochoscopy.① Of patients undergoing single imaging examination,72 received ultrasonography,with false-negative rate of 29.17％ (21/72);37 received CT examination,with false-negative rate of 10.81％(4/37);33 received T-tube cholangiography,with false-negative rate of 39.39％ (13/33).② Of patients undergoing combined two imaging examinations,61 received ultrasonography + CT,with false-negative rate of 8.20％ (5/61);129 received ultrasonography + T-tube cholangiography,with false-negative rate of 12.40％ (16/129);52 received CT + T-tube cholangiography,with false-negative rate of 5.77％(3/52).③ There were 121 receiving ultrasound+CT+T-tube cholangiography,with false-negative rate of 7.44％ (9/121).There were statistically significant differences in the false-negative rates of combined two or three examinations of ultrasound + CT+ T-tube cholangiography and single imaging examination (x2=40.83,P＜0.05).The further analysis showed a statistically significant difference among the single imaging examination (x2=7.70,P＜0.05).There was no statistically significant difference among the combined two of imaging examinations (x2=2.10,P＞0.05).There were statistically significant differences in the combined three examinations of ultrasound +CT+T-tube cholangiography and ultrasound and T-tube cholangiography examination respectively (x2=16.23,21.62,P＜0.05).There was no statistically significant difference in the combined three of imaging examinations and CT examination and combination of CT+T-tube cholangiography respectively (P＞ 0.05).There was no statistically significant difference in the combined three of imaging examinations and combination of ultrasound+CT examinations and combination of ultrasound+T-tube cholangiography (x2=0.33,1.71,P＞0.05).Seventy-one patients without residual bile duct stone by preoperative imaging examination were detected residual bile duct stones by intraoperative choledochoscopy,and residual bile duct stones of 36,31 and 4 patients are respectively distributed around the distal common bile duct,small intrahepatic bile duct,left and right hepatic ducts,common hepatic duct and remaining common bile duct.(2) Stone extraction situations of patients with hepatolithiasis:of 618 patients,cases with 1,2,3,4,5,6,7,8,9 and 10 times of residual bile duct stones clearance were respectively 392,116,48,39,9,6,3,2,2 and 1.Residual bile duct stones clearance frequency of patients was an average of 1.73 times.There were 63.43％(392/618) and 96.28％(595/618) of patients had stone clearance with once and ≤ 4 times of stone extraction,respectively.Conclusion The negative results of preoperative imaging examinations cannot be as standards of bile duct stone clearance before choledochoscopy,and the best choice is to detect whether there are residual bile duct stones and remove the stones combined with choledochoscopy.
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Objective@#To explore the prognosis of patients with T1b stage gallbladder carcinoma underwent different surgical procedure.@*Methods@#The clinicopathological data of 97 patients with T1b stage gallbladder carcinoma came from 8 clinical centers from January 2010 to December 2016 and 794 patients who were admitted to the SEER database of USA from January 1973 to December 2014 were analyzed.There were 891 patients including 254 males and 637 females (1.0∶2.5) with age of (69.5±12.0)years. There were 380 patients who were less than 70 years old, 511 patients who were more than 70 years old. And there were 213 patients with the diameter of tumor less than 20 mm, 270 patients with the diameter of tumor more than 20 mm, 408 patients were unclear. There were 196 patients with well differentiation, 407 patients with moderately differentiation, 173 patients with poorly differentiation, 8 patients with undifferentiated, 107 patients were unclear. In the 891 patients with T1b stage gallbladder carcinoma, there were 562 cases accepted the simple cholecystectomy, 231 cases with simple cholecystectomy plus lymphadenectomy, and 98 cases with radical cholecystectomy. The time of follow-up were until June 2017. χ2 test was used to analyze the enumeration data, rank-sum test was used to analyze the measurement data, the analyses of prognostic factors were used Cox proportional hazards model, the survival analysis was performed using Kaplan-Meier method.@*Results@#The results of Cox proportional hazards model indicated, age, differentiation, surgical procedure were the risk factors of prognostic(1.929(1.594-2.336), P<0.01; 1.842(1.404-2.416), P<0.01; 1.216(0.962-1.538), P<0.01). The results of Kaplan Meier test indicated, the overall survival of T1b stage gallbladder carcinoma were (85.5±3.8)months, the overall survival of patients with simple cholecystectomy were (71.3±4.4)months, the overall survival of patients with cholecystectomy plus lymphadenectomy were(87.6±5.8)months, and the overall survival of patients with radical cholecystectomy were(101.7±9.3)months. The overall survival of patients with cholecystectomy plus lymphadenectomy and radical cholecystectomy were more than simple cholecystectomy(P<0.05). There were 329 patients with Lymph nodes examined in and after operations(231 patients with cholecystectomy plus lymphadenectomy, 98 patients with radical cholecystectomy). There were 265 patients with negative lymph node metastasis, the overall survival were(98.3±4.2)months. There were 64 patients with positive lymph node metastasis, the overall survival were(75.5±3.1)months. The overall survival of 38 patients with cholecystectomy plus lymphadenectomy were(62.7±2.6) months, and 26 patients with radical cholecystectomy were (82.2±3.7)months. The overall survival of patients with radical cholecystectomy were more than cholecystectomy plus lymphadenectomy(P<0.05).@*Conclusions@#The T1b stage gallbladder carcinoma patients with cholecystectomy plus lymphadenectomy or radical cholecystectomy has improved the prognosis comparing with simple cholecystectomy, significantly. When lymph node metastasis occurs, radical cholecystectomy has improved the prognosis comparing with cholecystectomy plus lymphadenectomy.
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Objective@#To investigate the clinical value of Bayesian network in predicting survival of patients with advanced gallbladder cancer(GBC)who underwent curative intent surgery.@*Methods@#The clinical data of patients with advanced GBC who underwent curative intent surgery in 9 institutions from January 2010 to December 2015 were analyzed retrospectively.A median survival time model based on a tree augmented naïve Bayes algorithm was established by Bayesia Lab software.The survival time, number of metastatic lymph nodes(NMLN), T stage, pathological grade, margin, jaundice, liver invasion, age, sex and tumor morphology were included in this model.Confusion matrix, the receiver operating characteristic curve and area under the curve were used to evaluate the accuracy of the model.A priori statistical analysis of these 10 variables and a posterior analysis(survival time as the target variable, the remaining factors as the attribute variables)was performed.The importance rankings of each variable was calculated with the polymorphic Birnbaum importance calculation based on the posterior analysis results.The survival probability forecast table was constructed based on the top 4 prognosis factors. The survival curve was drawn by the Kaplan-Meier method, and differences in survival curves were compared using the Log-rank test.@*Results@#A total of 316 patients were enrolled, including 109 males and 207 females.The ratio of male to female was 1.0∶1.9, the age was (62.0±10.8)years.There was 298 cases(94.3%) R0 resection and 18 cases(5.7%) R1 resection.T staging: 287 cases(90.8%) T3 and 29 cases(9.2%) T4.The median survival time(MST) was 23.77 months, and the 1, 3, 5-year survival rates were 67.4%, 40.8%, 32.0%, respectively.For the Bayesian model, the number of correctly predicted cases was 121(≤23.77 months) and 115(>23.77 months) respectively, leading to a 74.86% accuracy of this model.The prior probability of survival time was 0.503 2(≤23.77 months) and 0.496 8(>23.77 months), the importance ranking showed that NMLN(0.366 6), margin(0.350 1), T stage(0.319 2) and pathological grade(0.258 9) were the top 4 prognosis factors influencing the postoperative MST.These four factors were taken as observation variables to get the probability of patients in different survival periods.Basing on these results, a survival prediction score system including NMLN, margin, T stage and pathological grade was designed, the median survival time(month) of 4-9 points were 66.8, 42.4, 26.0, 9.0, 7.5 and 2.3, respectively, there was a statistically significant difference in the different points(P<0.01).@*Conclusions@#The survival prediction model of GBC based on Bayesian network has high accuracy.NMLN, margin, T staging and pathological grade are the top 4 risk factors affecting the survival of patients with advanced GBC who underwent curative resection.The survival prediction score system based on these four factors could be used to predict the survival and to guide the decision making of patients with advanced GBC.
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Objective@#To investigate the effects of Kindlin-2 on malignant phenotypes of human gallbladder cancer cells and discuss the mechanisms.@*Methods@#The expression level of Kindlin-2 in 30 cases of gallbladder cancer tissues and adjacent non-tumoral tissues collected from the First Affiliated Hospital of Zhengzhou University between September 2012 and May 2013 was assessed by real-time PCR and immunohistochemistry.Lentivirus-mediated Kindlin-2 overexpression was used in gallbladder cancer cell lines GBC-SD and SGC-996.Transwell assay and adhesion assay were investigated to explore the functional role of Kindlin-2 on gallbladder cancer cells.Western Blot was used to test the protein change of epithelial-mesenchymal transition(EMT) characteristics. The t-test was used to analyzed results.@*Results@#The RNA and protein levels of Kindlin-2 in gallbladder cancer tissues were higher than in the non-tumoral tissues (t=4.372, P=0.001; t=7.477, P=0.000). The expression level of Kindlin-2 in gallbladder cancer tissues was correlated with Nevin stage(χ2=5.932, P=0.035). Compared with control groups, the cell-matrix adhesion ability of GBC-SD and SGC-996 with Kindlin-2 overexpression was obviously promoted(1.66±0.03 vs. 1.07±0.22, t=2.710, P=0.041; 2.66±0.24 vs. 1.03±0.02, t=6.610, P=0.020). The number of GBC-SD and SGC-996 cells with Kindlin-2 overexpression passing through the Transwell chamber matrix increased significantly compared with the control groups(116.1±13.9 vs. 54.7±8.4, t=3.781, P=0.019; 136.3±7.5 vs. 64.3±6.4, t=7.302, P=0.002). The wound healing rate of GBC-SD with Kindlin-2 overexpression at 12-hour and 24-hour was higher than that of the group ((42.9±2.2)% vs. (29.7±1.7)%, t=4.690, P=0.009; (65.0±2.4)% vs.(40.4±2.0)%, t=7.945, P=0.001). The wound healing rate of SGC-996 with Kindlin-2 overexpression at 12-hour and 24-hour was also higher than that of the group ((32.9±1.3)% vs. (24.1±1.5)%, t=4.518, P=0.011; (51.3±1.1)% vs. (39.2±1.1)%, t=8.001, P=0.001). The characteristics of EMT were induced in gallbladder cancer cells with Kindlin-2 overexpression, including the up-regulation of N-cadherin, Vemintin and the down-regulation of E-cadherin.@*Conclusion@#The expression of Kindlin-2 is up-regulated in gallbladder cancer tissues and Kindlin-2 promoted the malignant phenotypes of gallbladder cancer cells partially by epithelial-mesenchymal transition.
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Objective To analyze the clinicopathological features and lymph node metastases characteristics of intrahepatic cholangiocarcinoma (ICC).Methods The retrospective case-control study was conducted.The clinicopathological data of 1 321 ICC patients who were admitted to 12 hospitals from April 2007 to November 2017 were collected,including 182 in the Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University,173 in the First Affiliated Hospital of Xi'an Jiaotong University,156 in the First Hospital Affiliated to Army Medical University (Third Military Medical University),139 in the Cancer Center of Sun Yatsen University,128 in the Zhongshan Hospital of Fudan University,113 in the Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine,109 in the First Affiliated Hospital of Dalian Medical University,84 in the Tianjin Medical University Cancer Institute and Hospital,65 in the First Affiliated Hospital of Zhengzhou University,62 in the Affiliated Hospital of North Sichuan Medical College,58 in the Affiliated Drum Tower Hospital of Nanjing University Medical School and 52 in the Second Affiliated Hospital of Zhejiang University School of Medicine.Treatment planning was respectively determined by comprehensive hospitals according to clinical features and results of related examinations.Surgical procedures were performed based on the results of intraoperative examinations and patients' conditions.Observation indicators:(1) laboratory examination and treatment situations;(2) relationship between clinicopathological features and primary tumor location and diameter;(3) diagnosis of lymph node dissection and metastases;(4) relationship between clinicopathological features and lymph node metastases.Measurement data with normal distribution were represented as x±s,and comparison between groups was done by the t test.Measurement data with skewed distribution were described as M (range).Comparison of count data were analyzed using the chi-square test.Results (1) Laboratory examination and treatment situations:of 1 321 patients,cases and percentages of positive hepatitis B virus (HBV),positive serum alpha-fetoprotein (AFP) (＞ 20 μg/L),positive serum carcinoembryonic antigen (CEA) (＞ 5 μg/L),positive serum alanine transaminase (ALT) (＞75 U/L),positive serum CA19-9 (＞37 U/mL) and positive serum total bilirubin (TBil) (＞20 μmol/L) were respectively 202,80,329,207,590,300 and 15.586％ (202/1 296),7.339％(80/1 090),26.299％ (329/1 251),16.587％ (207/1 248),49.789％(590/1 185),24.000％ (300/1 250).Of 1 321 patients,1 206 underwent surgery,including 904 with hepatectomy,193 with transcatheter arterial chemoembolization (TACE),72 with percutaneous transhepatic biliary drainage (PTBD),3 with endoscopic retrograde cholangiopancreatography (ERCP),3 with PTBD + ERCP and 31 with other treatments;115 had missing registration of surgical procedures.(2) Relationship between clinicopathological features and primary tumor location and diameter:① Relationship between clinicopathological features and primary tumor location:cases with CA19-9 level ≤ 37 U/mL,38-200 U/mL and ＞ 200 U/mL were respectively 227,91,146 with primary tumor located in left liver and 282,134,137 with primary tumor located in right liver.Cases combined with hepatitis and intrahepatic bile duct stone were respectively 67,73 with primary tumor in left liver and 111,47 with primary tumor in right liver,with statistically significant differences in above indictors (x2 =6.710,5.656,12.534,P＜0.05).The results of further analysis showed that incidence age of ICC was (63± 10)years old in patients with hepatitis and (59± 10) years old in patients without hepatitis,with statistically significant differences (t =4.840,P＜0.05).② Relationship between clinicopathological features and primary tumor diameter:cases with primary tumor diameter ≤ 3 cm,with 3 cm ＜ primary tumor diameter ≤ 5 cm and with primary tumor diameter ＞ 5 cm were respectively 159,250,229 with CEA level ≤ 5 pg/L and 40,65,95 with CEA level ＞ 5 μg/L and 165,258,286 with ALT level ≤ 75 U/L and 34,57,36 with ALT level ＞ 75 U/L and 148,242,281 with TBil level ≤ 20 μmol/L and 51,73,43 with TBil level ＞ 20 μmol/L,and 37,70 and 131 patients had satellite loci of tumor,with statistically significant differences in above indictors (x2=8.669,6.637,15.129,34.746,P＜0.05).(3) Diagnosis of lymph node dissection and metastases:of 904 patients with hepatectomy,346 received lymph node dissection,total number,number in each patient and median number of lymph node dissected were respectively 1 894.0,5.5 and 4.0 (range,1.0-26.0);157 had lymph node metastases,with a rate of lymph node metastasis of 45.376％ (157/346),number and number in each patient of positive lymph node were respectively 393.0 and 2.5.Of 346 patients with lymph node dissection,114 had lymph node metastasis by preoperative imaging examination,postoperative pathological examinations confirmed 64 with lymph node metastasis and 50 without lymph node metastasis;232 didn't have lymph node metastasis by preoperative imaging examination,postoperative pathological examinations confirmed 93 with lymph node metastasis and 139 without lymph node metastasis.The sensitivity,specificity and diagnostic accuracy by imaging examination were respectively 40.8％,73.5％ and 58.7％.(4) Relationship between clinicopathological characteristics and lymph node metastases:lymph node metastasis rate was respectively 51.397％ (92/179) in patients with primary tumor located in left liver,39.103％ (61/156) in patients with primary tumor located in right liver,34.615％(18/52) in patients with primary tumor diameter ≤ 3 cm,42.500％(51/120) in patients with 3 cm ＜ primary tumor diameter ≤ 5 cm,52.980％(80/151) in patients with primary tumor diameter ＞ 5 cm,48.790％(121/248) in patients with CEA ≤ 5 μg/L,59.302％ (51/86) in patients with CEA ＞ 5 μg/L,40.234％ (103/256) in patients with TBil ≤ 20 μmol/L,35.106％ (33/94) in patients with TBil ＞ 20 μmol/L,with statistically significant differences in above indictors (x2 =5.078,6.262,9.456,5.156,P ＜ 0.05).Conclusions The related etiological factors may be different due to different primary location of ICC.Primary tumor in left liver is significantly associated with intrahepatic bile duct stone of left liver,and primary tumor in right liver is associated with combined hepatitis,while combined hepatitis could lead early occurrence of ICC.At present,there is a low rate of lymph node dissection in ICC patients and a high lymph node metastasis rate in patients receiving lymph node dissection.Lymph node metastasis is associated with primary tumor location and diameter,levels of CEA and TBil.Lymph node metastasis rate in left liver is higher than that in right liver,and is getting higher with increased primary tumor diameter.
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Objective To analyze the pathological results and current treatment situation of patients with unexpected gallbladder carcinoma from multi-centers in China,and explore the diagnosis and treatment of unexpected gallbladder carcinoma.Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 223 patients with unexpected gallbladder carcinoma who were admitted to the 8 clinical centers from January 2010 to December 2016 were collected,including 86 in the First Affiliated Hospital of Xi'an Jiaotong University,41 in the First Affiliated Hospital of Zhengzhou University,30 in the Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University,27 in the Xinhua Hospital of Shanghai Jiaotong University,13 in the First Affiliated Hospital of Dalian Medical University,11 in the Tianjin Medical University Cancer Institute & Hospital,9 in the First Affiliated Hospital of Army Medical University (Third Military Medical University) and 6 in the Affiliated Hospital of North Sichuan Medical College.Treatment of patients with unexpected gallbladder carcinoma who were diagnosed by intraoperative frozen section biopsy and postoperative pathological examination followed guideline for the diagnosis and treatment of gallbladder carcinoma (2015 edition).According to tumor staging and patients' decision,postoperative adjuvant treatment was selectively performed.Observation indicators:(1) diagnosis and treatment of unexpected gallbladder carcinoma;(2) followup and survival.Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival up to June 2017.Measurement data with normal distribution were represented as (x)±s.Measurement data with skewed distribution were described as M (range).The survival time was calculated using the Kaplan-Meier method.Results (1) Diagnosis and treatment of unexpected gallbladder carcinoma:of 223 patients with unexpected gallbladder carcinoma,80 were initially diagnosed using intraoperative frozen section biopsy [20 received T stage results (intraoperative T stage of 14 patients had not matched postoperative results),and 60 didn't receive T stage results],and 143 were initially diagnosed using postoperative pathological examination (13 were initially diagnosed with gallbladder benign disease by intraoperative frozen section biopsy and 130 didn't intraoperatively receive frozen section biopsy).Of 223 patients,209,10,3 and 1 were respectively confirmed as adenocarcinoma,adenoma canceration,neuroendocrine tumor and squamous cell carcinoma;6,16,32,73,75,12 and 9 were respectively detected in Tis,T1a,T1b,T2,T3 and T4 stages and undefined stage;140 underwent reoperations,including 106 with radical resection of gallbladder carcinoma and 34 with extended radical resection of gallbladder carcinoma;operation of 126 patients reached the standard and operation of 97 patients didn't reach the standard.Of 27 patients with postoperative complications,12 with postoperative hemorrhage received successful hemostasis by reoperations (7 with cystic artery hemorrhage and 5 with blood oozing from gallbladder bed);8 with suppurative cholangitis received endoscopic retrograde cholangiopancreatography and choledochotomy with drainage,including 2 deaths and 6 with improvement;2 with common bile duct injury were improved by reoperation of choledochojejunostomy + T tube drainage;2 were complicated with bile leakage induced to peritonitis and underwent bile duct repair with drainage,including 1 death and 1 with improvement;2 with hepatic failure died of treatment failure;1 with colonic injury was improved by reoperation of anastomosis.Of 223 patients,207 didn't receive postoperative adjuvant treatment and 16 received postoperative adjuvant treatment,including 8 with chemotherapy,4 with radiotherapy,2 with immunologic therapy and 2 with Chinese medicine treatment.(2) Follow-up and survival:of 223 patients,193 were followed up for 6-90 months,with a median time of 33 months.Of 193 patients with follow-up:① The operation of 2 patients in stage Tis reached the standard,including 1 with cholecystectomy and 1 with radical resection of gallbladder carcinoma,and the postoperative survival time of them were respectively 28 months and 52 months.② The operation of 14 patients in stage T1a reached the standard,including 8 with cholecystectomy and 6 with radical resection of gallbladder carcinoma,and the postoperative survival time of them were respectively (74±5)months and (79±6)months.③ Of 26 patients in stage T1b,13 and 13 received respectively cholecystectomy and radical resection of gallbladder carcinoma (reaching the standard),and postoperative survival time of them were respectively (66±4)months and (76±8)months.④ Of 68 patients in stage T2,25,37,4 and 2 patients received respectively cholecystectomy,radical resection of gallbladder carcinoma (reaching the standard),extended radical resection of gallbladder carcinoma (reaching the standard) and palliative resection,and postoperative survival time of them were respectively (42±7) months,(66±6) months,(42±3) months and (26±3) months.⑤ Of 71 patients in stage T3,20,48 and 3 patients received respectively cholecystectomy,radical resection of gallbladder carcinoma (reaching the standard) and extended radical resection of gallbladder carcinoma (reaching the standard),and postoperative survival time of them were respectively (39±8) months,(48± 11) months and (10±6) months.⑥ Of 12 patients in stage T4,3,1,5 and 3 patients received respectively cholecystectomy,radical resection of gallbladder carcinoma (reaching the standard),extended radical resection of gallbladder carcinoma (reaching the standard) and palliative resection,and postoperative survival time of them were respectively (10±4) months,12 months,(9± 5) months and (11±3) months.Conclusions The intraoperative frozen section biopsy and pathological results are the key points for diagnosis and treatment of unexpected gallbladder carcinoma.Patients in stage Tis and T1a should undergo cholecystectomy,while patients in stage T1b and above should undergo radical resection of gallbladder carcinoma or extended radical resection of gallbladder carcinoma.
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Objective To explore the expression of calreticulin (CRT) in gallbladder cancer tissue and its effect on the biological behavior in gallbladder cancer GBC-SD cells.Methods Immunohistochemistry and RT-qPCR were applied to detect the expression of CRT.Small interfering RNA was transfected into gallbladder cancer GBC-SD cells and Western blotting were used to detect the expression of CRT.The proliferation was determined by using cell counting kit-8 (CCK-8) and clone assays.Flow cytometry were applied to detect the apoptosis and cell cycle.Migration was detected by wound healing and transwell assays,respectively.The expression of p-Akt and MMP-9 were detected by using Western blotting.Results Expression of CRT in gallbladder cancer tissues is higher than adjacent cancer tissues and chronic cholecystitis tissues(t =5.571,P ＜ 0.05).The relative growth rate in the siCRT-1,siCRT-2 experimental group for 24 hours,48 hourrs were 71.5％ ±6.3％,79.5％ ±2.7％;62.6％ ± 8.8％,55.6％ ±2.6％,respectively.The apoptosis rate in the blank group,the negative control group,siCRT-1 and siCRT-2 group were 3.0％ ± 1.8％,4.7％ ± 1.3％,13.6％ ± 1.0％,20.0％ ± 4.0％,respectively.Wound healing assays showed that the wound closure ratio in the blank group,negative control group,siCRT-1 and siCRT-2 group were(0.67 ±0.02),(0.58 ±0.02),(0.22 ±0.01),(0.37 ±0.04),respectively.Transwell experiments showed that the numbers of migration of GBC-SD cells in the blank group,negative control group,siCRT-1 and siCRT-2 group were (302 ± 11),(297 ± 15),(178 ± 10),(165 ± 12),respectively,compared with the blank group and the negative control group,the relative growth rate for 24 hours and 48 hours was significantly lower,the apoptosis rate was higher,the numbers of migration was lower (F =29.310,118.618,69.651,144.515,190.145,P ＜ 0.05).Compared with the blank group and the negative control group,the expression of p-Akt and MMP-9 decreased after down-regulating the expression of CRT.Conclusions The expression of CRT in gallbladder cancer tissue was higher.CRT downregulation mediated changes of biological behaviors in gallbladder cancer may be associated with p-Akt/MMP-9 signal pathway.
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Objective To study the expression and the clinical significance of hypoxia-induced factor-1α (HIF-1α) in gallbladder cancer tissues,and the role and mechanism of HIF-1α in metformin-suppressed metastasis in gallbladder carcinoma GBC-SD cells.Methods 24 specimens of gallbladder cancer tissues and 5 specimens of chronic cholecystitis were collected from the First Affiliated Hospital of Zhengzhou University between June 2016 and February 2017.Immunohistochemistry and qPCR were used to detect the expression of HIF-1α in gallbladder cancer tissues,in adjacent non-cancer tissues and in chronic cholecystitis,and the clinical significance was analyzed.The model of metastasis was induced by hypoxia;the wound healing assay and the Transwell assay were used to detect the ability of cell metastasis;the expressions of HIF-1α and VEGF in gallbladder carcinoma GBC-SD cells were detected by western blotting assay and immunofiuorescence.Results The expression of HIF-1α in gallbladder cancer tissues was higher than the adjacent non-cancer tissues and in chronic cholecystitis.The expression of HIF-1α was correlated with lymph node metastasis and TNM staging in gallbladder cancer tissues (P ＜ 0.05).The wound healing rate after 48 h in the negative control group and in the treatment with hypoxia group (1％ O2) in GBC-SD cells were (46.5 ± 4.8) ％ and (67.3 ± 4.0) ％,respectively.The Transwell data showed that the numbers of metastasis after 24 h in the negative control group and in the treatment with hypoxia group GBC-SD cells were (147.4 ± 11.7) and (234.4 ± 17.7),respectively.When compared with the negative control group,treatment with hypoxia significantly increased the ability of metastasis and up-regulated the expression of HIF-1α and VEGF in GBC-SD cells (P ＜ 0.05).The wound healing rate after 48 h in the negative control group,the metformin group,the hypoxia group and the metformin and hypoxia group in GBC-SD cells were (40.6 ± 7.1) ％,(16.4 ± 9.4) ％,(69.5 ± 4.0) ％ and (22.4 ± 7.4) ％,respectively.The Transwell data showed that the numbers of metastasis after 24 h in the negative control group,the metformin group,the hypoxia group and the metformin and hypoxia group in GBC-SD cells were (148.4 ± 6.9),(90.0 ± 8.4),(185.8 ± 10.2) and (113.4± 8.6),respectively.When comparcd with the hypoxia group,treatment with metformin and hypoxia significantly decreased the ability of metastasis and down-regulated the expression of HIF-1α and VEGF in GBC-SD cells (P ＜ 0.05).The wound healing rate after 48 h in the negative control group,the 2MeoE2 group,the hypoxia group,the 2MeoE2 and hypoxia group in GBC-SD cells were (43.4 ±4.4)％,(25.9 ±9.0)％,(63.3 ±2.2)％,(46.2 ±4.5)％,respectively.The Transwell data showed that the numbers of metastasis after 24 h in the negative control group,the 2MeoE2 group,the hypoxia group,the 2MeoE2 and hypoxia group in GBC-SD cells were (144.2 ± 12.6),(80.2 ±7.7),(203.8 ±7.0),(124.0 ± 5.2),respectively.When compared with the hypoxia group,treatment with HIF-1α inhibitor 2MeoE2 and hypoxia significantly decreased the ability of metastasis and down-regulated the expression of HIF-1α and VEGF in GBC-SD cells (P ＜ 0.05).Conclusions The expression of HIF-1 α was correlated with lymph node metastasis and TNM staging in gallbladder cancer tissues.Treatment with hypoxia significantly increased the expression of HIF-1α and VEGF and promoted metastasis of GBC-SD cells,while treatment with metformin decreased the ability of metastasis induced by hypoxia via inhibiting the HIF-1o/VEGF pathway in GBC-SD cells.
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The 53rd annual meeting of the American Society of Clinical Oncology (ASCO) was held in Chicago,United States between June 2 and 6,2017.The latest advances in biliary tract cancer research from this meeting were summarized and analyzed in this paper.The adjuvant therapy in biliary tract cancer made a breakthrough in this meeting,the findings could provide the basis for a new standard of changing the current management model in the disease.The precision medicine and targeted therapy will be the development direction in the future.Doctors should attach great importance to the adjuvant and comprehensive therapy in biliary tract cancer and initiate high level multi-center clinical trials to improve the overall the diagnostic and treatment levels of biliary tract cancer.
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Objective To investigate the epidemiological characteristics,clinical features,diagnosis,treatment and prognosis of benign tumor of the bile ducts.Methods The retrospective cross-sectional multicenter study was conducted.The clinical data of 136 patients with benign tumor of the bile ducts who were admitted to the eight hospitals between January 2007 and December 2016 were collected,including 70 in the Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University,19 in the First Affiliated Hospital of Zhengzhou University,15 in the First Affiliated Hospital of Xi'an Jiaotong University,11 in the First Affiliated Hospital of Dalian Medical University,7 in the Affiliated Hospital of North Sichuan Medical College,6 in the Southwest Hospital of the Third Military Medical University,4 in the Cancer Center of Sun Yat-Sen University and 4 in the Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine.All the patients received laboratory and imaging examinations,and then underwent corresponding surgery when treatment planning was respectively determined by comprehensive hospitals according to clinical features and results of examinations.Surgical procedures were performed based on the results of intraoperative frozen section in rapid pathological diagnosis.Observation indicators:(1) epidemiological characteristics;(2) clinical features;(3) results of laboratory and imaging examinations;(4) treatment situations;(5) follow-up situations.Follow-up using outpatient examination and telephone interview was performed to detect the survival of patients up to March 2017.Measurement data with normal distribution were represented as-x±s.Results (1) Epidemiological characteristics:Of 136 patients,the male to female ratio was 1.78 ∶ 1.The incidence of whole bile duct tumors was from high to low,including 52 patients with duodenal papilla adenoma,32 with extrahepatic bile duct adenoma,24 with intrahepatic biliary cystadenoma,11 with intrahepatic papillary adenoma,9 with intrahepatic bile duct epithelial tumor,7 with epithelial tumor of duodenal papilla and 1 with neuroendocrine tumor of duodenal papilla.Among 136 patients,adenomas (including cystadenoma) was detected in 108 patients,papillomas in 11 patients,intraepithelial neoplasias in 16 patients,neuroendocrine tumor in 1 patient;intrahepatic bile duct benign tumors in 44 patients and extrahepatic bile duct (including duodenal papilla) benign tumors in 92 patients.(2) Clinical features:of 44 patients with intrahepatic bile duct benign tumors,29 had abdominal pain,fever and abdominal masses,4 had jaundice,11 had no obvious clinical symptoms and were diagnosed by physical examination.Among 92 patients with extrahepatic bile duct benign tumors,76 developed obstructive jaundice,68 were accompanied by abdominal pain or colicky pain,8 were combined with pancreatitis and 2 deveIoped hemobilia,some patients were combined with multiple clinical symptoms.(3) Results of laboratory and imaging examinations:82 patients received CA19-9 test,results of 22 patients were abnormal,with a level of (148-± 126)U/mL.Ninety-seven patients received carcinoembryonic antigen (CEA) test,with a level of test of (2.7±2.0) μg/L,and a level of CEA in 1 patient was slight abnormal,with a level of 11.2 pμg/L.One hundred and thirty-six patients underwent preoperative ultrasound examinations,showing unqualified hepatic and bile duct space occupying lesions and bile duct dilatation.Ninetyfive patients underwent preoperative computed tomography (CT),80 underwent preoperative magnetic resonance imaging (MRI) or magnetic resonanced cholangio-pancreatography (MRCP),and 13 underwent preoperative endoscopic ultrasonography (EUS).Twenty-nine patients were considered for intrahepatic bile duct benign tumors;76 were diagnosed with obstructive jaundice,with uncertain benign or malignant tumors;other patients had bile duct space occupying,considering bile duct tumor (including cancer).Twelve patients with bile duct obstruction underwent ERCP,showing obstruction site and morphology.(4) Treatment situations:among 136 patients,65 underwent pancreaticoduodenectomy,17 underwent right hemihepatectomy + cholecystectomy,16 underwent cholecystectomy + hepatic left lateral lobectomy,11 underwent left hemihepatectomy + cholecystectomy,11 underwent duodenal papillary local excision+papilla reconstruction,11 underwent Roux-en-Y choledochojejunostomy anastomosis,4 underwent cholecystectomy + extrahepatic bile duct local excision + end-to-end bile duct anastomosis and 1 underwent endoscopic mucosal resection of duodenal papillary adenomna.Of 136 patients with postoperative complications,25 were complicated with pancreatic leakage,11 with bile leakage,2 with postoperative hemorrhage and 1 with hepatic failure.Two patients with pancreatic leakage died of massive hemorrhage caused by abdominal infection,1 died of hepatic failure and other patients were discharged from hospital after symptomatic treatment.(5) Follow-up situations:47 of 136 patients were followed up for 3-123 months,with a follow-up rate of 34.6％.During follow-up,2 patients undergoing duodenal papillary local excision + papilla reconstruction had canceration,and other patients had good survival.Conclusions There is a low clinical incidence of benign tumor of the bile ducts,which is more common in male than in female,and in adenomas (including cystadenoma) and papillomas.The preoperative imaging examinations or ERCP biopsy pathological examination can increase an accuracy of preoperative diagnosis.Benign tumors with high canceration rates need positive surgical treatment.
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As a nuclear transcription repressor,the functions of TGIF are complicated,not only represses target genes expression directly,but also takes part in the regulation of multiple important cellular signaling pathways,which are associated with the differentiation of cells and tissues,inflammation,metabolism and tumors.In past few years,more and more studies on the role of TGIF in tumors suggest TGIF may be a new therapy target in the diagnosis and treatment of tumours.This article mainly reviews the research progress of TGIF in some signaling pathways like TGF-β,MAPK,PI3K/AKT,and tumours like hepatocellular carcinoma,lung carcinoma and urinary tract urothelial carcinoma.
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Objective:To investigate the mechanism of endoplasmic reticulum (ER) stress-induced chemoresistance to cisplatin in gastric cancer cells. Methods:ER stress models were established in both BGC823 and SGC7901 gastric cancer cells. The expression of GRP78, an ER stress marker, was examined by Western blot analysis. Moreover, whether ER stress can decrease the sensitivity of gastric cancer cells to cisplatin and activate P38 was explored by flow cytometry and Western blot analysis, respectively. Whether ER stress-induced chemoresistance to cisplatin can be abrogated by blocking P38 activity in gastric cancer was also elucidated using flow cytometry. Results:GRP78 protein expression markedly increased after treating BGC823 and SGC7901 gastric cancer cells with tunica-mycin (TM) or thapsigargin (TG) for 8, 16, and 24 h (P0.05). Both P38 inhibitors, either SB203580 or PD169316, can inhibit the activation of P38. The inhibition of P38 activity can overcome ER stress-induced chemoresistance to cisplatin in gastric cancer cells (P<0.05). Con-clusion:ER stress can trigger the chemoresistance to cisplatin by activating P38 in gastric cancer cells.
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Pancreatic tuberculosis (PTB) is a rare,chronic,specific and infectious disease which is generally secondary to tuberculosis at the common sites of pancreas,and it has a high misdiagnosis rate due to the hidden onset and nonspecific symptoms of PTB.A patient with PTB was admitted to the First Affiliated Hospital of Zhengzhou University in June 2014.Before operation,the space-occupying lesions of the head of pancreas were detected by preoperative imaging examination,and the patient was regarded as with pancreatic cancer.Intraoperative exploration showed cystic duct involvement,and the granulomatous inflammation was detected by rapid pathological examination using frozen section technique,after that the patient received granuloma resection+cholecystectomy according to suspected PTB.The diagnosis of PTB was confirmed by postoperative pathological examination,and the patient received liver-protective and anti-tuberculosis treatments after discharge.
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Objective To explore the effect of calreticulin (CRT) on cell proliferation and invasion of human hepatocellular carcinoma cell line SMMC-7721 and HepG2.Methods SMMC-7721 and HepG2 cells were transfected with small interfering RNA (siRNA).The transfection rate was detected by immunoflurescence and western blot.The cell proliferation,invasion and apoptosis of SMMC-7721 and HepG2 cells were determined by using cell counting kit-8 (CCK-8) assays,transwell assays and flow cytometry,respectively.The p-Akt and Akt levels were detected by western blot.Results The growth inhibition rate in the siRNA experimental group of SMMC-7721 and HepG2 cells for 24,36 and 48 h were (41.0 ±2.2) ％,(46.5 ±1.6)％,(59.7 ±2.2)％ and (36.8 ±2.7)％,(47.3 ± 1.8)％,(61.5 ±3.2)％,respectively.The apoptosis rate after down-regulating the expression of CRT in SMMC-7721 and HepG2 cells for 36h were (45.2 ± 9.1) ％ and (48.9 ± 8.0) ％,respectively.Compared with the blank group and the negative control group,the growth inhibition rate in the siRNA experimental group was lower (P ＜0.05),but the apoptosis rate was significantly higher (P ＜ 0.05).Transwell experiments confirmed that the numbers of invaded SMMC-7721 and HepG2 cells in the blank group and the negative control group and siRNA experimental group were (96.8±7.3),(95.6±5.4),(34.0±4.2) and (124.0 ±9.9),(121.6 ±7.0),(70.4±9.5),respectively,indicating that cell invasion in the siRNA experimental group was significantly suppressed (P ＜ 0.05).The expression of p-Akt was decreased (P ＜ 0.05) after down-regulating the expression of CRT for 36h.Conclusion CRT gene silencing by siRNA can inhibit the SMMC-7721 and HepG2 cell proliferation and invasion,but increase the cell apoptosis by regulating PI3K/Akt signal pathway.
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Objective:To evaluate the efficacy of allicin combined with cyclophosphamide on neuroblastoma (NB)-bearing mice and explore the immunological mechanism in it.Methods:A total of30 NB-bearing mice were equally randomized into model group, cyclophosphamide group and combined therapy group,10 nudemice were set as normal saline(NS) group.Cyclophosphamide group and combined therapy group were weekly injected with60 mg/kg cyclophosphamide for four weeks; besides, combined therapy group was given with allicin(10 mg/kg/d) by gastric perfusion for4 weeks; model group and NS group were given with the same volume of NS.Serum VEGF content was detected byELISA pre-treating(0 d) and on the3rd d,14th d and28th d; on 29th d, all mice were sacrificed and the tumor, liver, spleen and thymic tissues were weighted. Tumors were made into paraffin section for detecting tumor cell apoptosis and proliferation by TUNEL and BrdU method, respectively.Survival curves were drawn byKaplan-Meier method. Results:After treatment, both treatment groups relieved on viscera indexes,VEGF level,T cell subsets distribution and tumor growth and each index of combined therapy group was better than cyclophosphamide group(P<0.05 or0.01); only combined therapy group could significantly increase the lifetime of NB-bearing mice(χ2=5.667,P=0.017).Conclusions:Allicin can improve T cell subsets distribution and inhibitVEGF expression through its immunomodulatory activity, thereby improve the efficiency onNB in coordination with cyclophosphamide.
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Objective To study the efficacy and the safe dosage of high intensity focused ultrasound (HIFU) ablation in pancreatic cancer.Methods From November 2010 to May 2013,21 patients with advanced pancreatic cancer were treated by HIFU at the First Affiliated Hospital of Zhengzhou University.These patients who were randomly divided into two groups (10 and 11 patients respectively),were given a low-power (100～249 W) treatment and a high power (250 ～350 W) treatment.These two groups of 21 patients received a total of 25 times of HIFU treatment (3 patients received twice of low-power treatment,while 1 patient received twice of high-power treatment).The two groups were compared by analyzing the treatment parameters (average power,total treatment time,treatment total energy,treatment volume,etc.) and volume of tumour response as shown on postoperative imaging (CT or MRI) examinations.Also,the complications,degree of pain relief and survival were compared.The energy efficiency factor (EEF) and the ablation ratio were calculated.A preliminary study was conducted on the relationship of the ultrasound dose and the ablation effect of HIFU treatment for pancreatic cancer.Results (1) The EEF of the high-power group (≥250 W) and the low-power group (＜ 250 W) were (10.39 ± 5.71) J/mm3 and (21.62 ± 9.81) J/mm3,the former group was significantly lower than the latter group (P ＜0.05) ; the ablation ratio of the high-power group was higher than the low-power group,(91.52 ± 4.18)％ versus (51.59 ± 7.66)％ respectively,the difference was statistically significant (P ＜ 0.001).(2) The efficiency factor and the ablation volume for the HIFU treatment showed a linear trend,and both were negatively correlated (Pearson correlation coefficient r =-0.485,P ＜ 0.05).(3) There was no serious complication after the HIFU treatment.In the low-power group,six of ten patients were alleviated of his pain (60％) ; the CA19-9 decreased in four of ten patients after HIFU treatment (40％).In the high-power group,nine of eleven patients were significantly relieved of pain after treatment (82％),the CA19-9 decreased in five of nine patients after HIFU treatment (56％).(4) On Kaplan-Meier survival analysis,HIFU treatment of patients with pancreatic cancer,the median survival was 8 months and 9 months in the low-power group and high power group,respectively (Log-rank test x2 =0.05,P =0.944).Conclusion During HIFU treatment of patients with pancreatic cancer,if the ultrasound power was between 250 W and 350 W,there was a higher proportion of tumor ablation,but with no serious complications.Thus,this dose was safe.
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Objective To study the efficacy and safety of high intensity focused ultrasound (HIFU) treatment for advanced pancreatic cancer.Methods In this study,25 patients with advanced pancreatic cancer received high-intensity focused ultrasound (HIFU) treatment.Liver and kidney function,CA19-9 levels,tumor size changes,pain relief,survival rate before and after treatment were evaluated.Results The blood routine test,liver and kidney function,blood amylase did not alter significantly after HIFU treatment in all patients.The CA19-9 level of 12 patients decreased.The appetite of 15 patients improved,5 patients with body weight gain after HIFU treatment.Pain was relieved after HIFU treatment in 18 cases,pain relief rate was 72％ (18/25).In 15 cases tumor ablation volume ＞ 90％ after HIFU treatment,5 patients with tumor ablation volume ＞ 50％,tumor ablation effective rate was 80％ (20/25).There were no major complications such as acute pancreatitis,gastrointestinal injury after HIFU treatment.After HIFU treatment,the median survival period was 8 months,1 year survival rate was 30％.Conclusions High-intensity focused ultrasound is a safe and effective method of palliative treatment for advanced inoperable pancreatic cancer.