Background and Aims:Intrahepatic cholangiocarcinoma(ICC)is a highly malignant liver tumor,with an increasing incidence worldwide,particularly in Asia.Although radical surgical resection is currently the only potentially curative treatment,the high recurrence rate and low postoperative overall survival(OS)rate of ICC remain major clinical challenges.Adjuvant therapy(AT)and neoadjuvant therapy(NAT)are important strategies to reduce postoperative recurrence and prolong OS.Several studies have shown certain efficacy of these treatments.However,the specific efficacy and safety of combined NAT and AT in ICC treatment require further validation.This study was conducted to evaluate the value of combining NAT and AT in improving the therapeutic outcomes of ICC patients through a multicenter retrospective analysis,so as to provide scientific evidence for optimizing treatment strategies.Methods:The clinicopathologic data of 576 patients with ICC who underwent radical resection and were pathologically confirmed from 13 hospitals in China between December 2011 and December 2017 were retrospectively collected.Patients were grouped based on their treatment modality:NAT+AT group,AT group,and non-NAT/AT group.The three patient groups were matched pairwise in a 1∶1 ratio using propensity score matching(PSM)to balance baseline data.The Kaplan-Meier method was used to analyze OS and disease-free survival(DFS),and subgroup analyses were conducted according to the 8th edition of the AJCC TNM staging system.Results:A total of 395 ICC patients were included in the final analysis,with 42 patients(10.6%)in the NAT+AT group,62 patients(15.7%)in the AT group,and 291 patients(73.7%)in the non-NAT/AT group.Before PSM,significant differences were observed between groups in terms of CA19-9,liver function Child-Pugh classification,intraoperative blood loss,surgical margin,differentiation grade,vascular invasion,ECOG score,and lymph node dissection ratio(all P<0.05).After PSM,there were no significant differences in baseline characteristics between the groups(all P>0.05).After matching,the median OS and DFS in the NAT+AT group were significantly better than in the AT and non-NAT/AT groups(both P<0.05),while there were no significant differences in OS and DFS between the AT and non-NAT/AT groups(both P>0.05).Subgroup analysis showed that in TNM stage I patients,DFS in the NAT+AT group was significantly better than in the non-NAT/AT group(P<0.05),but OS was not significantly different(P>0.05).In TNM stage Ⅱ and Ⅲ patients,both OS and DFS in the NAT+AT and AT groups were significantly better than in the non-NAT/AT group(both P<0.05),and DFS in the NAT+AT group was significantly better than in the AT group in TNM stage Ⅲ patients(P<0.05).Conclusion:NAT combined with AT provides better survival benefits for patients with locally advanced ICC,but its benefit for early-stage ICC patients is limited.However,the retrospective design and sample size limitations of this study may affect the stability of the results,and future large-sample,multicenter,prospective studies are needed for further validation.

Background and Aims:Intrahepatic cholangiocarcinoma(ICC)is a highly malignant liver tumor,with an increasing incidence worldwide,particularly in Asia.Although radical surgical resection is currently the only potentially curative treatment,the high recurrence rate and low postoperative overall survival(OS)rate of ICC remain major clinical challenges.Adjuvant therapy(AT)and neoadjuvant therapy(NAT)are important strategies to reduce postoperative recurrence and prolong OS.Several studies have shown certain efficacy of these treatments.However,the specific efficacy and safety of combined NAT and AT in ICC treatment require further validation.This study was conducted to evaluate the value of combining NAT and AT in improving the therapeutic outcomes of ICC patients through a multicenter retrospective analysis,so as to provide scientific evidence for optimizing treatment strategies.Methods:The clinicopathologic data of 576 patients with ICC who underwent radical resection and were pathologically confirmed from 13 hospitals in China between December 2011 and December 2017 were retrospectively collected.Patients were grouped based on their treatment modality:NAT+AT group,AT group,and non-NAT/AT group.The three patient groups were matched pairwise in a 1∶1 ratio using propensity score matching(PSM)to balance baseline data.The Kaplan-Meier method was used to analyze OS and disease-free survival(DFS),and subgroup analyses were conducted according to the 8th edition of the AJCC TNM staging system.Results:A total of 395 ICC patients were included in the final analysis,with 42 patients(10.6%)in the NAT+AT group,62 patients(15.7%)in the AT group,and 291 patients(73.7%)in the non-NAT/AT group.Before PSM,significant differences were observed between groups in terms of CA19-9,liver function Child-Pugh classification,intraoperative blood loss,surgical margin,differentiation grade,vascular invasion,ECOG score,and lymph node dissection ratio(all P<0.05).After PSM,there were no significant differences in baseline characteristics between the groups(all P>0.05).After matching,the median OS and DFS in the NAT+AT group were significantly better than in the AT and non-NAT/AT groups(both P<0.05),while there were no significant differences in OS and DFS between the AT and non-NAT/AT groups(both P>0.05).Subgroup analysis showed that in TNM stage I patients,DFS in the NAT+AT group was significantly better than in the non-NAT/AT group(P<0.05),but OS was not significantly different(P>0.05).In TNM stage Ⅱ and Ⅲ patients,both OS and DFS in the NAT+AT and AT groups were significantly better than in the non-NAT/AT group(both P<0.05),and DFS in the NAT+AT group was significantly better than in the AT group in TNM stage Ⅲ patients(P<0.05).Conclusion:NAT combined with AT provides better survival benefits for patients with locally advanced ICC,but its benefit for early-stage ICC patients is limited.However,the retrospective design and sample size limitations of this study may affect the stability of the results,and future large-sample,multicenter,prospective studies are needed for further validation.

Objective To retrospectively analyze multicenter data from domestic sources, aiming to explore the link between intrahepatic cholangiocarcinoma (ICC) tumor size and prognosis, establishing a classification system based on tumor size. Methods Between December 2011 and September 2018, 280 ICC patients from 13 hospitals were included. The tumor size prognosis cutoff was identified by the minimum P-value method, and the classification's overall survival related effectiveness was assessed by Kaplan-Meier analysis. Results All 280 patients were divided into the group of tumor maximum diameter ≤4 cm and >4 cm. Tumor size was confirmed as an independent prognosis factor by multivariate COX regression analysis (HR=2.110, 95% CI: 1.358-3.280). Conclusions The tumor size dichotomy classification system based on the Chinese patient group can expediently predict ICC prognosis and offers an important basis for selecting post-operative individualized adjuvant therapy and follow up plans.

Objective To establish and validate a Nomogram model for predicting the overall survival(OS)of the patients with intrahepatic cholangiocarcinoma(ICC)based on domestic multicenter data,and screen the beneficiaries of adjuvant chemotherapy based on the prediction model.Methods From December 2011 to December 2017,the data of 278 patients with postoperative pathological diagnosis of ICC from 4 medical centers in our country were collected retrospectively COX regression model was used to screen the independent risk factors of OS and constructed a Nomogram model.This model was used to stratify the risk of OS for all patients and to screen the beneficiaries of adjuvant chemotherapy.Results A total of 278 patients were enrolled,and 23 cases(8.3%)received adjuvant chemotherapy.COX multivariate analysis showed that drinking history,ECOG score,method of hepatectomy,lymph node status,number of tumors,and tumor differentiation were independent risk factors for postoperative OS.The Nomogram model had a C-index of 0.690(95%CI:0.646-0.734)in the training cohort and 0.740(95%CI:0.863-0.617)in the validation cohort.According to risk stratification by Nomogram model,in the high-risk group there was a statistically significant difference in survival between adjuvant chemotherapy and non-adjuvant chemotherapy(P=0.033),whereas in the low-risk group,there was no significant difference in survival(P=0.59).Conclusions Nomogram model based on independent risk factors of OS demonstrated excellent predictive capability for survival and could be used to screen,and identify the patients with ICC who benefit from adjuvant chemotherapy.

Objective:To investigate the feasibility and effectiveness of percutaneous transhepatic cholangioscopy(PTCS) in the treatment of bilioenteric anastomotic stricture after choledochojejunostomy.Methods:From April 2016 to April 2020, the clinical data of 9 patients (7 males and 2 females, aged 40-76 years) who underwent percutaneous transhepatic cholangioscopy(PTCS) for stricture expansion and lithotomy at Department of Hepatobiliary and Pancreatic Surgery, Second Affiliated Hospital of Zhejiang University School of Medicine were retrospectively analyzed. The operation was divided into two stages. In the first stage, ultrasound-guided percutaneous intrahepatic bile duct puncture was performed, and the sheath tube was inserted and fixed. In the second stage, percutaneous choledochoscopy was used for anastomotic stricture after sinus formation.The clinical outcome was evaluated by related biochemical indexes.Results:The operation time was (53.3±31.0)minutes(range:15-120 minutes).The postoperative hospital stay was (4.4±2.3)days(range:2-9 days).After systematic treatment, the preoperative symptoms, such as abdominal pain, jaundice, fever and shivering, disappeared in 8 patients. The range of alkaline phosphatase was 122-1 334 U/L before operation and 85-702 U/L after operation. The range of gamma glutamyl transpeptidase was 44-1 219 U/L before operation and 46-529 U/L after operation.Conclusion:PTCS is a safe and effective option for minimally invasive treatment of bilioenteric anastomotic stricture.

Objective:To investigate the feasibility and effectiveness of percutaneous transhepatic cholangioscopy(PTCS) in the treatment of bilioenteric anastomotic stricture after choledochojejunostomy.Methods:From April 2016 to April 2020, the clinical data of 9 patients (7 males and 2 females, aged 40-76 years) who underwent percutaneous transhepatic cholangioscopy(PTCS) for stricture expansion and lithotomy at Department of Hepatobiliary and Pancreatic Surgery, Second Affiliated Hospital of Zhejiang University School of Medicine were retrospectively analyzed. The operation was divided into two stages. In the first stage, ultrasound-guided percutaneous intrahepatic bile duct puncture was performed, and the sheath tube was inserted and fixed. In the second stage, percutaneous choledochoscopy was used for anastomotic stricture after sinus formation.The clinical outcome was evaluated by related biochemical indexes.Results:The operation time was (53.3±31.0)minutes(range:15-120 minutes).The postoperative hospital stay was (4.4±2.3)days(range:2-9 days).After systematic treatment, the preoperative symptoms, such as abdominal pain, jaundice, fever and shivering, disappeared in 8 patients. The range of alkaline phosphatase was 122-1 334 U/L before operation and 85-702 U/L after operation. The range of gamma glutamyl transpeptidase was 44-1 219 U/L before operation and 46-529 U/L after operation.Conclusion:PTCS is a safe and effective option for minimally invasive treatment of bilioenteric anastomotic stricture.

Objective:To examine the role of the number of lymph nodes examined(NLNE) on the prognosis of patients with curatively resected gallbladder carcinoma(GBC).Methods:The clinicopathological data and prognosis of 401 patients with GBC who underwent radical surgery from six institutions of China from January 2013 to December 2017 were analyzed retrospectively. There were 153 males(38.2%) and 248 females(61.8%), with age of (62.0±10.5) years (range: 30-88 years). Fifty-three patients(22.2%) were accompanied by jaundice. All patients underwent radical resection+regional lymphadenectomy.R0 or R1 resection was confirmed by postoperative pathological examination.The different cut-off values of NLNE were determined by the X-tile software, the optimal cut-off values were identified by analyzing the relationship between different cut-off values of NLNE with survival rate. Kaplan-Meier method was used for survival analysis. Univariate and multivariate analysis were implemented respectively using the Log-rank test and Cox proportional hazard model.Results:Among the 401 patients enrolled, 135 cases (33.6%) had lymphatic metastasis, of which 98 cases were in N1 stage(24.4%) and 37 cases were in N2 stage(9.2%).A total of 2 794 NLNE were retrieved, with a median count of 6 (5).The median positive lymph nodes count was 0 (1), and the median positive lymph nodes ratio was 0 (IQR, 0-0.2). Since the 12 and 15 were determined as the cut-off values by X-tile, all patients were divided into three groups of 1-11, 12-15 and ≥16.The 3-year survival rate of the three groups was 45.2%, 74.5%, 12.0% respectively, with statistically significant difference between three groups (χ 2=10.94, P<0.01). The results of multivariate analysis showed that NLNE was an independent prognostic factor for overall survival ( P<0.05). Further analysis was performed specifically for subgroup of T stages. For T1b patients, the prognosis of the NLNE with 1-7 group was significantly better than that of the ≥8 group(χ 2=4.610, P<0.05). For T2 patients, the prognosis of the TLNE ≥7 group was significantly better than that of 1 -6 group (χ 2=4.287, P<0.05). For T3 and T4 patients, the prognosis of the TLNE with 12 - 15 group was significantly better than that of 1 -11 group (χ 2=5.007, P<0.01) and ≥16 group (χ 2=10.158, P<0.01). Conclusions:The NLNE is an independent factor affecting the prognosis of patients with GBC.For patients with stage T1b,8 lymph nodes should be retrieved; for patients with stage T2,extensive dissection of more than 6 lymph nodes can significantly improve the prognosis.For advanced patients (stages T3 and T4), extensive dissection with 12-15 lymph nodes is recommended. However, it fails to get more survival benefits by dissecting more than 16 lymph nodes.

Objective:To examine the role of the number of lymph nodes examined(NLNE) on the prognosis of patients with curatively resected gallbladder carcinoma(GBC).Methods:The clinicopathological data and prognosis of 401 patients with GBC who underwent radical surgery from six institutions of China from January 2013 to December 2017 were analyzed retrospectively. There were 153 males(38.2%) and 248 females(61.8%), with age of (62.0±10.5) years (range: 30-88 years). Fifty-three patients(22.2%) were accompanied by jaundice. All patients underwent radical resection+regional lymphadenectomy.R0 or R1 resection was confirmed by postoperative pathological examination.The different cut-off values of NLNE were determined by the X-tile software, the optimal cut-off values were identified by analyzing the relationship between different cut-off values of NLNE with survival rate. Kaplan-Meier method was used for survival analysis. Univariate and multivariate analysis were implemented respectively using the Log-rank test and Cox proportional hazard model.Results:Among the 401 patients enrolled, 135 cases (33.6%) had lymphatic metastasis, of which 98 cases were in N1 stage(24.4%) and 37 cases were in N2 stage(9.2%).A total of 2 794 NLNE were retrieved, with a median count of 6 (5).The median positive lymph nodes count was 0 (1), and the median positive lymph nodes ratio was 0 (IQR, 0-0.2). Since the 12 and 15 were determined as the cut-off values by X-tile, all patients were divided into three groups of 1-11, 12-15 and ≥16.The 3-year survival rate of the three groups was 45.2%, 74.5%, 12.0% respectively, with statistically significant difference between three groups (χ 2=10.94, P<0.01). The results of multivariate analysis showed that NLNE was an independent prognostic factor for overall survival ( P<0.05). Further analysis was performed specifically for subgroup of T stages. For T1b patients, the prognosis of the NLNE with 1-7 group was significantly better than that of the ≥8 group(χ 2=4.610, P<0.05). For T2 patients, the prognosis of the TLNE ≥7 group was significantly better than that of 1 -6 group (χ 2=4.287, P<0.05). For T3 and T4 patients, the prognosis of the TLNE with 12 - 15 group was significantly better than that of 1 -11 group (χ 2=5.007, P<0.01) and ≥16 group (χ 2=10.158, P<0.01). Conclusions:The NLNE is an independent factor affecting the prognosis of patients with GBC.For patients with stage T1b,8 lymph nodes should be retrieved; for patients with stage T2,extensive dissection of more than 6 lymph nodes can significantly improve the prognosis.For advanced patients (stages T3 and T4), extensive dissection with 12-15 lymph nodes is recommended. However, it fails to get more survival benefits by dissecting more than 16 lymph nodes.

Objective: To investigate the clinical value of lymph node dissection (LND) in the radical resection of intrahepatic cholangiocarcinoma (ICC). Methods: The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 448 patients with ICC who were admitted to 12 medical centers from December 2011 to December 2017 were collected, including 279 in the Eastern Hepatobiliary Surgery Hospital of Navy Medical University, 32 in the Mengchao Hepatobiliary Hospital of Fujian Medical University, 21 in the First Hospital Affiliated to Army Medical University, 20 in the Cancer Hospital Chinese Academy of Medical Science and Peking Union Medical College, 19 in the West China Hospital of Sichuan University, 18 in the Second Hospital Affiliated to Zhejiang University School of Medicine, 18 in the Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 16 in the Beijing Friendship Hospital Affiliated to Capital Medical University, 10 in the Xuanwu Hospital Affiliated to Capital Medical University, 7 in the Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, 5 in the Beijing Tiantan Hospital Affiliated to Capital Medical University, and 3 in the Affiliated Hospital of North Sichuan Medical College. There were 281 males and 167 females, aged from 22 to 80 years, with a median age of 57 years. Of the 448 patients, 143 with routinely intraoperative LND were divided into LND group and 305 without routinely intraoperative LND were divided into control group, respectively. Observation indicators: (1) the propensity score matching conditions and comparison of general data between the two groups after matching; (2) intraoperative and postoperative situations; (3) follow-up; (4) survival analysis. Patients were followed up by outpatient examination, telephone interview and email to detect survival of patients and tumor recurrence up to October 31, 2018 or death. Follow-up was conducted once every 3 months within postoperative 1-2 years, once every 6 months within postoperative 2-5 years, and once a year after 5 years. The propensity score matching was realized using the nearest neighbor method with 1∶1 ratio. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M (range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Kaplan-Meier method was used to calculate survival rates and draw survival curve, and Log-rank test was used to perform survival analysis. Univariate analysis and multivaraiate analysis were conducted using the Log-rank test and COX regression model, respectively. Results: (1) The propensity score matching conditions and comparison of general data between the two groups after matching: 286 of 448 patients had successful matching, including 143 in each group. The number of males and females, cases with hepatitis, cases with grade A and B of Child-Pugh classification, cases with distance from margin to tumor <1 cm and ≥1 cm, cases with highly, moderately, and poorly differentiated tumor, cases with anatomical hepatectomy and nonanatomical hepatectomy before propensity score matching were 77, 66, 33, 96, 47, 70, 73, 105, 38, 79, 64 in the LND group, and 204, 101, 121, 165, 140, 207, 98, 251, 54, 124, 181 in the control group, respectively, showing significant differences in the above indices between the two groups (χ²=7.079, 11.885, 7.098, 14.763, 5.184, 8.362, P<0.05). After propensity score matching, the above indices were 77, 66, 33, 96, 47, 70, 73, 105, 38, 79, 64 in the LND group, and 79, 64, 29, 88, 55, 71, 72, 112, 31, 74, 69 in the control group, respectively, showing no significant difference in the above indices between the two groups (χ²=0.056, 0.329, 2.158, 0.014, 0.936, 1.400, P>0.05). (2) Intraoperative and postoperative situations: the operation time, volume of intraoperative blood loss, cases with intraoperative blood transfusion, cases with postoperative complications, and duration of postoperative hospital stay were 265 minutes (range, 160-371 minutes), 300 mL (range, 200-500 mL), 37, 46, 12 days (range, 9-17 days) for the LND group, and 59 minutes (range, 46-250 minutes), 200 mL (range, 100-400 mL), 24, 25, 9 days (range, 7-11 days) for the control group, respectively. There was no significant difference in the volume of intraoperative blood loss or cases with intraoperative blood transfusion between the two groups (Z=1.700, χ²=3.520, P>0.05). There were significant differences in the operation time, cases with postoperative complications, and duration of postoperative hospital stay (Z=6.520, χ²=8.260, Z=4.270, P<0.05). (3) Follow-up: 143 patients in the LND group was followed up for 18-26 months. The 1-, 3-, 5-year survival rates were 66.9%, 32.8%, 25.0%, and the median survival time was 22.0 months (range, 18.0-26.0 months). In the control group, 143 patients were followed up for 11-32 months. The 1-, 3-, 5-year survival rates were 71.7%, 38.0%, 31.0%, and the median survival time was 22.0 months (range, 11.0-32.0 months). There was no significant difference in the overall survival between the two groups (χ²=0.466, P>0.05). (4) Survival analysis: results of univariate analysis showed that distance from margin to tumor, tumor diameter, the number of tumors, microvascular tumor thrombus, and lymph node metastasis by pathological examination were related factors for prognosis of patients undergoing radical resection of ICC (χ²=10.662, 9.477, 16.944, 6.520, 11.633, P<0.05). Results of multivariate analysis showed that distance from margin to tumor<1 cm, tumor diameter>5 cm, multiple tumors, microvascular tumor thrombus, positive lymph node metastasis by pathological examination were independent risk factors for prognosis of patients undergoing radical resection of ICC (hazard ratio=0.600, 1.571, 1.601, 1.750, 1.723, 95% confidence interval: 0.430-0.837, 1.106-2.232, 1.115-2.299, 1.083-2.829, 1.207-2.460, P<0.05). Conclusion Lymph node metastasis is an independent risk factor affecting the prognosis of ICC patients, and it is necessary to perform LND in radical resection for patients with ICC and lymph node metastasis.

Objectives: To propose a novel clinical classification system of gallbladder cancer, and to investigate the differences of clinicopathological characteristics and prognosis based on patients who underwent radical resection with different types of gallbladder cancer. Methods: The clinical data of 1 059 patients with gallbladder cancer underwent radical resection in 12 institutions in China from January 2013 to December 2017 were retrospectively collected and analyzed.There were 389 males and 670 females, aged (62.0±10.5)years(range:22-88 years).According to the location of tumor and the mode of invasion,the tumors were divided into peritoneal type, hepatic type, hepatic hilum type and mixed type, the surgical procedures were divided into regional radical resection and extended radical resection.The correlation between different types and T stage, N stage, vascular invasion, neural invasion, median survival time and surgical procedures were analyzed.Rates were compared by χ² test, survival analysis was carried by Kaplan-Meier and Log-rank test. Results: Regional radical resection was performed in 940 cases,including 81 cases in T1 stage,859 cases in T2-T4 stage,119 cases underwent extended radical resection;R0 resection was achieved in 990 cases(93.5%).The overall median survival time was 28 months.There were 81 patients in Tis-T1 stage and 978 patients in T2-T4 stage.The classification of gallbladder cancer in patients with T2-T4 stage: 345 cases(35.3%)of peritoneal type, 331 cases(33.8%) of hepatic type, 122 cases(12.5%) of hepatic hilum type and 180 cases(18.4%) of mixed type.T stage(χ²=288.60,P<0.01),N stage(χ²=68.10, P<0.01), vascular invasion(χ²=128.70, P<0.01)and neural invasion(χ²=54.30, P<0.01)were significantly correlated with the classification.The median survival time of peritoneal type,hepatic type,hepatic hilum type and mixed type was 48 months,21 months,16 months and 11 months,respectively(χ²=80.60,P<0.01).There was no significant difference in median survival time between regional radical resection and extended radical resection in the peritoneal type,hepatic type,hepatic hilum type and mixed type(all P>0.05). Conclusion With application of new clinical classification, different types of gallbladder cancer are proved to be correlated with TNM stage, malignant biological behavior and prognosis, which will facilitate us in preoperative evaluation,surgical planning and prognosis evaluation.