Objective:To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma.Methods:This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect.Results:Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.092, P=0.039),and had a positive predictive effect on the surgical method ( β=0.244, P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions:The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.

Objective:To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma.Methods:This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect.Results:Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.092, P=0.039),and had a positive predictive effect on the surgical method ( β=0.244, P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions:The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.

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.

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.

【Objective】 To investigate the expression of pyruvate kinase M2 (PKM2) in intrahepatic cholangiocarcinoma (ICC) and the effect of PKM2 on the proliferation and epithelial-to-mesenchymal transition (EMT) of ICC cells. 【Methods】 PKM2 expression was evaluated in ICC tissues and cell lines by Real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR), and immunohistochemistry assays. In vitro, we knocked down PKM2 expression in ICC cell lines and investigated the biological function and the underlying mechanism of PKM2 in ICC. 【Results】 RT-PCR results showed that PKM2 was highly expressed in ICC (P<0.05). Moreover, PKM2 knockdown inhibited cell proliferation and the invasive capacities of ICC cells, and inhibited Wnt/ β-Catenin signaling, which subsequently regulated EMT signaling pathway in vitro. 【Conclusion】 PKM2 expression in cholangiocarcinoma is significantly higher than that in adjacent tissues. PKM2 can regulate EMT and invasion and metastasis of ICC via the Wnt/β-Catenin signal.

Objective:To examine a survival prognostic model applicable for patients with intrahepatic cholangiocarcinoma (ICC) based on Bayesian network.Methods:The clinical and pathological data of ICC patients who underwent curative intent resection in ten Chinese hepatobiliary surgery centers from January 2010 to December 2018 were collected.A total of 516 patients were included in the study. There were 266 males and 250 females.The median age( M( Q R)) was 58(14) years.One hundred and sixteen cases (22.5%) with intrahepatic bile duct stones,and 143 cases (27.7%) with chronic viral hepatitis.The Kaplan-Meier method was used for survival analysis.The univariate and multivariate analysis were implemented respectively using the Log-rank test and Cox proportional hazard model.One-year survival prediction models based on tree augmented naive Bayesian (TAN) and na?ve Bayesian algorithm were established by Bayesialab software according to different variables,a nomogram model was also developed based on the independent predictors.The receiver operating characteristic curve and the area under curve (AUC) were used to evaluate the prediction effect of the models. Results:The overall median survival time was 25.0 months,and the 1-,3-and 5-year cumulative survival rates was 76.6%,37.9%,and 21.0%,respectively.Univariate analysis showed that gender,preoperative jaundice,pathological differentiation,vascular invasion,microvascular invasion,liver capsule invasion,T staging,N staging,margin,intrahepatic bile duct stones,carcinoembryonic antigen,and CA19-9 affected the prognosis(χ 2=5.858-54.974, all P<0.05).The Cox multivariate model showed that gender,pathological differentiation,liver capsule invasion, T stage,N stage,intrahepatic bile duct stones,and CA19-9 were the independent predictive factors(all P<0.05). The AUC of the TAN model based on all 19 clinicopathological factors was 74.5%,and the AUC of the TAN model based on the 12 prognostic factors derived from univariate analysis was 74.0%,the AUC of the na?ve Bayesian model based on 7 independent prognostic risk factors was 79.5%,the AUC and C-index of the nomogram survival prediction model based on 7 independent prognostic risk factors were 78.8% and 0.73,respectively. Conclusion:The Bayesian network model may provide a relatively accurate prognostic prediction for ICC patients after curative intent resection and performed superior to the nomogram model.

Objective:To examine a survival prognostic model applicable for patients with intrahepatic cholangiocarcinoma (ICC) based on Bayesian network.Methods:The clinical and pathological data of ICC patients who underwent curative intent resection in ten Chinese hepatobiliary surgery centers from January 2010 to December 2018 were collected.A total of 516 patients were included in the study. There were 266 males and 250 females.The median age( M( Q R)) was 58(14) years.One hundred and sixteen cases (22.5%) with intrahepatic bile duct stones,and 143 cases (27.7%) with chronic viral hepatitis.The Kaplan-Meier method was used for survival analysis.The univariate and multivariate analysis were implemented respectively using the Log-rank test and Cox proportional hazard model.One-year survival prediction models based on tree augmented naive Bayesian (TAN) and na?ve Bayesian algorithm were established by Bayesialab software according to different variables,a nomogram model was also developed based on the independent predictors.The receiver operating characteristic curve and the area under curve (AUC) were used to evaluate the prediction effect of the models. Results:The overall median survival time was 25.0 months,and the 1-,3-and 5-year cumulative survival rates was 76.6%,37.9%,and 21.0%,respectively.Univariate analysis showed that gender,preoperative jaundice,pathological differentiation,vascular invasion,microvascular invasion,liver capsule invasion,T staging,N staging,margin,intrahepatic bile duct stones,carcinoembryonic antigen,and CA19-9 affected the prognosis(χ 2=5.858-54.974, all P<0.05).The Cox multivariate model showed that gender,pathological differentiation,liver capsule invasion, T stage,N stage,intrahepatic bile duct stones,and CA19-9 were the independent predictive factors(all P<0.05). The AUC of the TAN model based on all 19 clinicopathological factors was 74.5%,and the AUC of the TAN model based on the 12 prognostic factors derived from univariate analysis was 74.0%,the AUC of the na?ve Bayesian model based on 7 independent prognostic risk factors was 79.5%,the AUC and C-index of the nomogram survival prediction model based on 7 independent prognostic risk factors were 78.8% and 0.73,respectively. Conclusion:The Bayesian network model may provide a relatively accurate prognostic prediction for ICC patients after curative intent resection and performed superior to the nomogram model.

Objective:To examine the value of number of metastatic lymph nodes(NMLN), lymph node ratio(LNR) and log odds of metastatic lymph nodes(LODDS) in assessing the prognosis of patients with intrahepatic cholangiocarcinoma(ICC).Methods:The clinical and pathological data of 440 ICC patients who underwent curative-intent resection in 10 of Chinese hepatobiliary surgery centers from January 2010 to December 2018 were collected, and the deadline of follow-up was April 30th, 2019. Among them, 205 were males and 235 were females, with age of (57.0±9.9) years (range:23-83 years).Eighty-five cases (19.3%) had intrahepatic bile duct stones, and 98 cases (22.3%) had chronic viral hepatitis.The Kaplan-Meier method was used for survival analysis. The univariate and multivariate analysis were implemented respectively using the Log-rank test and Cox proportional hazard model.Results:A total of 440 patients underwent curative-intent resection and lymphadenectomy.R0 resection were achieved in 424 cases (96.4%) and R1 resection were in 16 cases (3.6%). The results of postoperative pathological examination showed that high, moderate and poor differentiation was 4.2%(18/426), 60.6%(258/426) and 35.2%(150/426), respectively.Adenocarcinoma was seen in 90.2%(397/440) and non-adenocarcinoma was seen in 9.8%(43/440), respectively. T stage: 2 cases (0.5%) with Tis, 83 cases(18.9%) with T1a, 97 cases(22.0%) with T1b, 95 cases(21.6%) with T2, 122 cases (27.7%) with T3 and 41 cases(9.3%) with T4.The overall median survival time was 24.0 months, and the 1-,3-, and 5-year survival rate was 74.3%, 37.7% and 18.3%, respectively. Lymphatic metastasis occurred in 175 patients(39.8%), the median total number of TNLE( M( Q R)) was 6(5), the median number of NMLN was 0(1), the median number of LNR was 0 (0.33) and the median number of LODDS was -0.70(-0.92). Rerults of univariate analysis showed that combined stones, pathological differentiation, vascular invasion, LODDS, margin and T staging affected the prognosis (all P<0.05). Rerults of multivariate analysis showed that pathological differentiation, LODDS, margin, and T staging were independent risk factors affecting the prognosis of ICC patients (all P<0.05). Conclusion:LODDS could be used as an optimal prognostic lymph node staging index for ICC, and it is also an independent risk factor for survival after curative intent resection.

Objective:To examine the value of number of metastatic lymph nodes(NMLN), lymph node ratio(LNR) and log odds of metastatic lymph nodes(LODDS) in assessing the prognosis of patients with intrahepatic cholangiocarcinoma(ICC).Methods:The clinical and pathological data of 440 ICC patients who underwent curative-intent resection in 10 of Chinese hepatobiliary surgery centers from January 2010 to December 2018 were collected, and the deadline of follow-up was April 30th, 2019. Among them, 205 were males and 235 were females, with age of (57.0±9.9) years (range:23-83 years).Eighty-five cases (19.3%) had intrahepatic bile duct stones, and 98 cases (22.3%) had chronic viral hepatitis.The Kaplan-Meier method was used for survival analysis. The univariate and multivariate analysis were implemented respectively using the Log-rank test and Cox proportional hazard model.Results:A total of 440 patients underwent curative-intent resection and lymphadenectomy.R0 resection were achieved in 424 cases (96.4%) and R1 resection were in 16 cases (3.6%). The results of postoperative pathological examination showed that high, moderate and poor differentiation was 4.2%(18/426), 60.6%(258/426) and 35.2%(150/426), respectively.Adenocarcinoma was seen in 90.2%(397/440) and non-adenocarcinoma was seen in 9.8%(43/440), respectively. T stage: 2 cases (0.5%) with Tis, 83 cases(18.9%) with T1a, 97 cases(22.0%) with T1b, 95 cases(21.6%) with T2, 122 cases (27.7%) with T3 and 41 cases(9.3%) with T4.The overall median survival time was 24.0 months, and the 1-,3-, and 5-year survival rate was 74.3%, 37.7% and 18.3%, respectively. Lymphatic metastasis occurred in 175 patients(39.8%), the median total number of TNLE( M( Q R)) was 6(5), the median number of NMLN was 0(1), the median number of LNR was 0 (0.33) and the median number of LODDS was -0.70(-0.92). Rerults of univariate analysis showed that combined stones, pathological differentiation, vascular invasion, LODDS, margin and T staging affected the prognosis (all P<0.05). Rerults of multivariate analysis showed that pathological differentiation, LODDS, margin, and T staging were independent risk factors affecting the prognosis of ICC patients (all P<0.05). Conclusion:LODDS could be used as an optimal prognostic lymph node staging index for ICC, and it is also an independent risk factor for survival after curative intent resection.

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.