1.Comparison of the efficacy of anatomical resection versus hepatic parenchymal preservation preference in patients with solitary small hepatocellular carcinoma and cirrhosis: a multicenter retrospective study
Liming HUANG ; Yun YANG ; Yuntong LI ; Xianming WANG ; Siming ZHENG ; Qiang LU ; Zisen LAI ; Yongping LAI ; Zongren DING ; Jiahui LYU ; Jiacheng ZHANG ; Xinfeng QIU ; Weiping ZHOU ; Kongying LIN ; Yongyi ZENG
Chinese Journal of Hepatology 2025;33(4):348-358
Objective:To investigate the efficacy of anatomical resection (AR) in the early stages of treating solitary hepatocellular carcinoma (HCC) combined with liver cirrhosis with a diameter of ≤5 cm in comparison to different surgical methods of preferential hepatic parenchymal preservation (non-anatomical liver resection, NAR).Methods:The clinical data of 1 390 cases with solitary HCC combined with liver cirrhosis at an early stage who underwent liver resection at Mengchao Hepatobiliary Hospital of Fujian Medical University and six other medical centers from September 2013 to May 2019 were retrospectively analyzed. Patients were divided into the AR group (486 cases) and the NAR group (904 cases) and the wide surgical margin (WSM) group (745 cases) and the narrow surgical margin (NSM) group (645 cases) according to whether they received AR and the width of the surgical margin (1 cm). The basic information of the patients, preoperative evaluation index data, and postoperative follow-up (follow-up every 3 months) were collected. The Kaplan-Meier method was used to plot the survival curve.The log-rank test was used to compare the difference in survival between the two groups. The Cox proportional hazards regression model was used to analyze the factors affecting the prognosis. Propensity score matching (PSM) was applied to reduce intergroup bias.Results:The overall survival (OS) rates for all patients at 1, 3, and 5 years were 95.5%, 79.9%, and 63.5%, respectively. The recurrence-free survival (RFS) rates were 81.5%, 59.0%, and 43.7%, respectively. There was a statistically significant difference in RFS rate between the AR group and the NAR group prior to PSM, but no statistically significant difference in OS rate (RFS rate: 47.0% vs. 41.9%, P<0.05; OS rate: 64.4% vs. 62.9%, P>0.05). The postoperative RFS rate and OS rate were significantly superior in the WSM group than those of the NSM group (RFS rate: 47.8% vs. 37.2%, P<0.001; OS rate: 69.0% vs. 57.3%, P<0.001). There was no statistically significant difference in OS rate and RFS rate between the AR group and the NAR group following PSM (RFS: 46.3% vs. 45.1%, P>0.05; OS rate: 64.0% vs. 64.3%, P>0.05).The 5-year OS and RFS rates in the WSM group were 66.8% and 60.2%, respectively. The 5-year OS and RFS rates for the NSM group were 48.7% and 41.4%, respectively, with a statistically significant difference ( P<0.05). Cox multivariate analysis indicated that serum albumin, tumor diameter, microvascular invasion, and surgical margin were independent prognostic factors affecting OS and RFS. The Child-Pugh grade and satellite lesions were independent prognostic factors affecting OS. Conclusion:Anatomical liver resection is not an independent risk factor for prognosis, but the state of the resection margin determines the prognosis of patients with solitary HCC combined with cirrhosis. Therefore, hepatic resection margins should be prioritized in such patients.
2.Prognostic analysis of postoperative adjuvant therapy for hepatocellular carcinoma after con-version therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy: a multicenter study
Kongying LIN ; Jia LIN ; Zisen LAI ; Yongping LAI ; Kui WANG ; Jinhong CHEN ; Zhibo ZHANG ; Jingdong LI ; Sheng TAI ; Shifeng WANG ; Siming ZHENG ; Jianxi ZHANG ; Lu ZHENG ; Kai WANG ; Jiacheng ZHANG ; Jiahui LYU ; Liming HUANG ; Yongyi ZENG
Chinese Journal of Digestive Surgery 2025;24(1):103-112
Objective:To investigate the prognosis of postoperative adjuvant therapy for hepatocellular carcinoma after conversion therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 103 patients with initially unresectable hepatocellular carcinoma (HCC) who were admitted to 11 medical centers in China, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from November 2019 to May 2023 were collected. There were 83 males and 20 females, aged (54±12)years. All 103 patients underwent conversion therapy of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) successfully followed by sequential hepatectomy, of which 72 patients undergoing postoperative adjuvant therapy were divided into the adjuvant therapy group, and 31 patients undergoing postoperative follow-up monitoring were divided into the follow-up monitoring group. Observation indicators: (1) follow-up and postoperative condi-tions; (2) analysis of factors influencing recurrence-free survival time of patients; (3) stratified ana-lysis. Comparison of count data between group was conducted using the chi-square test or Fisher exact probability. The R software was used to draw survival curves, and the Log-rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the Cox proportional hazard model. Results:(1) Follow-up and postoperative conditions. All 103 patients were followed up for 21.0(range, 1.9?47.2)months, with the median recurrence-free survival time of 28.7 months and the 1-, 2-, 3-year recurrence-free survival rates of 68.6%, 55.6%, 41.2%. The median overall survival time of 103 patients was unreached, and the 1-, 2-, 3-year overall survival rates were 90.9%, 82.1%, 69.6%, respectively. The median recurrence-free survival time was 33.1 months in patients of the adjuvant therapy group, with the 1-, 2-year recurrence-free survival rates as 77.2%, 61.5%. The median recurrence-free survival time was 11.1 months in patients of the follow-up monitoring group, with the 1-, 2-year recurrence-free survival rates as 46.6%, 40.8%. There was a significant difference in recurrence-free survival between the two groups of patients ( χ2=5.492, P<0.05). (2) Analysis of factors influencing recurrence-free survival time of patients. Results of multivariate analy-sis showed that pathologic complete response and postoperative adjuvant therapy were independent factors influencing recurrence-free survival time of HCC patients undergoing conversion therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy ( hazard ratio=0.297, 0.492, 95% confidence interval as 0.137?0.647, 0.268?0.903, P<0.05). (3) Stratified analysis. Of the 71 patients with non-pathologic complete response, the median recurrence-free survival time of 48 patients in the adjuvant therapy group was 24.0 months, with the 1-, 2-year recurrence-free survival rates as 67.4%, 48.8%. The median recurrence-free survival time of 23 patients with non-pathological complete response in the follow-up monitoring group was 7.4 months, with the 1-, 2-year recurrence-free survival rates as 35.0%, 26.3%. There was a significant difference in recurrence-free survival between the 48 patients with non-pathologic complete response in the adjuvant therapy group and the 23 patients with non-pathologic complete response in the follow-up monitoring group ( χ2=5.241, P<0.05). Conclusion:For HCC patients with conversion therapy of TKIs and ICIs followed by sequential hepatectomy, postoperative adjuvant therapy, compared to postoperative follow-up monitoring, can prolong the recurrence-free survival time of patients, of whom cases with non-pathologic complete response can benefit from adjuvant therapy.
3.Prognostic analysis of postoperative adjuvant therapy for hepatocellular carcinoma after con-version therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy: a multicenter study
Kongying LIN ; Jia LIN ; Zisen LAI ; Yongping LAI ; Kui WANG ; Jinhong CHEN ; Zhibo ZHANG ; Jingdong LI ; Sheng TAI ; Shifeng WANG ; Siming ZHENG ; Jianxi ZHANG ; Lu ZHENG ; Kai WANG ; Jiacheng ZHANG ; Jiahui LYU ; Liming HUANG ; Yongyi ZENG
Chinese Journal of Digestive Surgery 2025;24(1):103-112
Objective:To investigate the prognosis of postoperative adjuvant therapy for hepatocellular carcinoma after conversion therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 103 patients with initially unresectable hepatocellular carcinoma (HCC) who were admitted to 11 medical centers in China, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from November 2019 to May 2023 were collected. There were 83 males and 20 females, aged (54±12)years. All 103 patients underwent conversion therapy of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) successfully followed by sequential hepatectomy, of which 72 patients undergoing postoperative adjuvant therapy were divided into the adjuvant therapy group, and 31 patients undergoing postoperative follow-up monitoring were divided into the follow-up monitoring group. Observation indicators: (1) follow-up and postoperative condi-tions; (2) analysis of factors influencing recurrence-free survival time of patients; (3) stratified ana-lysis. Comparison of count data between group was conducted using the chi-square test or Fisher exact probability. The R software was used to draw survival curves, and the Log-rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the Cox proportional hazard model. Results:(1) Follow-up and postoperative conditions. All 103 patients were followed up for 21.0(range, 1.9?47.2)months, with the median recurrence-free survival time of 28.7 months and the 1-, 2-, 3-year recurrence-free survival rates of 68.6%, 55.6%, 41.2%. The median overall survival time of 103 patients was unreached, and the 1-, 2-, 3-year overall survival rates were 90.9%, 82.1%, 69.6%, respectively. The median recurrence-free survival time was 33.1 months in patients of the adjuvant therapy group, with the 1-, 2-year recurrence-free survival rates as 77.2%, 61.5%. The median recurrence-free survival time was 11.1 months in patients of the follow-up monitoring group, with the 1-, 2-year recurrence-free survival rates as 46.6%, 40.8%. There was a significant difference in recurrence-free survival between the two groups of patients ( χ2=5.492, P<0.05). (2) Analysis of factors influencing recurrence-free survival time of patients. Results of multivariate analy-sis showed that pathologic complete response and postoperative adjuvant therapy were independent factors influencing recurrence-free survival time of HCC patients undergoing conversion therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy ( hazard ratio=0.297, 0.492, 95% confidence interval as 0.137?0.647, 0.268?0.903, P<0.05). (3) Stratified analysis. Of the 71 patients with non-pathologic complete response, the median recurrence-free survival time of 48 patients in the adjuvant therapy group was 24.0 months, with the 1-, 2-year recurrence-free survival rates as 67.4%, 48.8%. The median recurrence-free survival time of 23 patients with non-pathological complete response in the follow-up monitoring group was 7.4 months, with the 1-, 2-year recurrence-free survival rates as 35.0%, 26.3%. There was a significant difference in recurrence-free survival between the 48 patients with non-pathologic complete response in the adjuvant therapy group and the 23 patients with non-pathologic complete response in the follow-up monitoring group ( χ2=5.241, P<0.05). Conclusion:For HCC patients with conversion therapy of TKIs and ICIs followed by sequential hepatectomy, postoperative adjuvant therapy, compared to postoperative follow-up monitoring, can prolong the recurrence-free survival time of patients, of whom cases with non-pathologic complete response can benefit from adjuvant therapy.
4.Comparison of the efficacy of anatomical resection versus hepatic parenchymal preservation preference in patients with solitary small hepatocellular carcinoma and cirrhosis: a multicenter retrospective study
Liming HUANG ; Yun YANG ; Yuntong LI ; Xianming WANG ; Siming ZHENG ; Qiang LU ; Zisen LAI ; Yongping LAI ; Zongren DING ; Jiahui LYU ; Jiacheng ZHANG ; Xinfeng QIU ; Weiping ZHOU ; Kongying LIN ; Yongyi ZENG
Chinese Journal of Hepatology 2025;33(4):348-358
Objective:To investigate the efficacy of anatomical resection (AR) in the early stages of treating solitary hepatocellular carcinoma (HCC) combined with liver cirrhosis with a diameter of ≤5 cm in comparison to different surgical methods of preferential hepatic parenchymal preservation (non-anatomical liver resection, NAR).Methods:The clinical data of 1 390 cases with solitary HCC combined with liver cirrhosis at an early stage who underwent liver resection at Mengchao Hepatobiliary Hospital of Fujian Medical University and six other medical centers from September 2013 to May 2019 were retrospectively analyzed. Patients were divided into the AR group (486 cases) and the NAR group (904 cases) and the wide surgical margin (WSM) group (745 cases) and the narrow surgical margin (NSM) group (645 cases) according to whether they received AR and the width of the surgical margin (1 cm). The basic information of the patients, preoperative evaluation index data, and postoperative follow-up (follow-up every 3 months) were collected. The Kaplan-Meier method was used to plot the survival curve.The log-rank test was used to compare the difference in survival between the two groups. The Cox proportional hazards regression model was used to analyze the factors affecting the prognosis. Propensity score matching (PSM) was applied to reduce intergroup bias.Results:The overall survival (OS) rates for all patients at 1, 3, and 5 years were 95.5%, 79.9%, and 63.5%, respectively. The recurrence-free survival (RFS) rates were 81.5%, 59.0%, and 43.7%, respectively. There was a statistically significant difference in RFS rate between the AR group and the NAR group prior to PSM, but no statistically significant difference in OS rate (RFS rate: 47.0% vs. 41.9%, P<0.05; OS rate: 64.4% vs. 62.9%, P>0.05). The postoperative RFS rate and OS rate were significantly superior in the WSM group than those of the NSM group (RFS rate: 47.8% vs. 37.2%, P<0.001; OS rate: 69.0% vs. 57.3%, P<0.001). There was no statistically significant difference in OS rate and RFS rate between the AR group and the NAR group following PSM (RFS: 46.3% vs. 45.1%, P>0.05; OS rate: 64.0% vs. 64.3%, P>0.05).The 5-year OS and RFS rates in the WSM group were 66.8% and 60.2%, respectively. The 5-year OS and RFS rates for the NSM group were 48.7% and 41.4%, respectively, with a statistically significant difference ( P<0.05). Cox multivariate analysis indicated that serum albumin, tumor diameter, microvascular invasion, and surgical margin were independent prognostic factors affecting OS and RFS. The Child-Pugh grade and satellite lesions were independent prognostic factors affecting OS. Conclusion:Anatomical liver resection is not an independent risk factor for prognosis, but the state of the resection margin determines the prognosis of patients with solitary HCC combined with cirrhosis. Therefore, hepatic resection margins should be prioritized in such patients.
5.Effect of mesenchymal stem cells combined with immunosuppressants on immune rejection in a rat model of liver transplantation
Haitao LI ; Saihua YU ; Lihong CHEN ; Zisen LAI ; Haiyan LIU ; Hongzhi LIU ; Conglong SHEN
Journal of Clinical Hepatology 2024;40(6):1209-1214
Objective To investigate the effect of mesenchymal stem cells(MSCs)combined with immunosuppressants(IS)on immune rejection in a rat model of liver transplantation.Methods F344 rats were divided into Normal group(without any intervention),PS group(injected with an equal volume of normal saline),MSC group(injected with MSC),IS group(injected with IS),and MSC+IS group(injected with MSC and IS),with 8 rats in each group.For all rats except those in the Normal group,the Kamada's double-cuff method was used to establish a model of orthotopic liver transplantation,without reconstruction of the hepatic artery.HE staining and Masson staining were performed for rat liver tissue,and the degree of liver fibrosis was analyzed;immunohistochemical experiments were used to measure the infiltration of T cells and NK cells,and immunofluorescence assay was used to analyze macrophage M2 polarization.A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups.The Kaplan-Meier method was used to plot survival curves,and the log-rank test was used for survival analysis.Results Compared with the PS group,the MSC+IS group had a significantly prolonged survival time(P<0.01),and the MSC group,the IS group,and the MSC+IS group had a significant improvement in the histological structure of the liver and a significant reduction in the degree of liver fibrosis(all P<0.000 1),as well as a significant reduction in the infiltration of NK and T cells(all P<0.000 1)and a significant increase in the degree of macrophage M2 polarization(all P<0.000 1).The MSC+IS group had a significantly better effect than the MSC group and the IS group.Conclusion MSCs combined with IS can improve liver histopathology,reduce inflammatory cell infiltration,promote macrophage M2 polarization,and exert an immunosuppressive effect in rats after liver transplantation.
6.Application value of indocyanine green injection via percutaneous transhepatic portal vein puncture under ultrasound guidance during laparoscopic anatomical liver resection
Zisen LAI ; Jiahui LYU ; Guangwen LIU ; Qian LIN ; Jiacheng ZHANG ; Liming HUANG ; Yongyi ZENG
Chinese Journal of Digestive Surgery 2024;23(12):1544-1549
Objective:To investigate the application value of indocyanine green (ICG) injection via percutaneous transhepatic portal vein under ultrasound guidance during laparoscopic anatomical liver resection.Methods:The retrospective and descriptive study was conducted. The clinicopatho-logical data of 17 male patients with hepatocellular carcinoma who underwent laparoscopic anatomical liver resection in Mengchao Hepatobiliary Hospital of Fujian Medical University from October 2022 to May 2024 were collected. The patients were aged 59(range, 27-74)years. Patients underwent ICG fluorescence-guided laparoscopic anatomical liver resection after ICG injection via percutaneous transhepatic portal vein under ultrasound guidance. Obsevation indicators: (1)surgical situations; (2) postoperative situations; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M(range). Count data were represented as absolute numbers. Results:(1) Surgical situations. All 17 patients were successfully punctured and injected with ICG via percutaneous transhepatic portal vein under ultrasound guidance, with a puncture time of 6(range,3-12)minutes. The fluorescence staining successfully displayed at the target liver segment without infiltration, and the distance from the fluorescence staining border to the tumor edge was greater than 1.0 cm, which was consistent with preoperative three-dimensional reconstruction imaging. Among the 17 patients, 11 cases had punctures in one branch of the portal vein, 4 cases had punctures in two branches, and 2 had punctures in three branches. The operation time was (229±51)minutes, volume of intraoperative blood loss was 200(range, 100-300)mL. No blood transfusion or conversion to open surgery was required during the operation. (2) Postoperative situations. Two of 17 patients had a small pleural effusion of grade Ⅰ-Ⅱ of Clavien-Dindo classification, and were recovered without treatment. The duration of postoperative hospital stay was 5(range, 5-6)days. Postoperative pathological examina-tion showed hepatocellular carcinoma with negative surgical margin. The tumor diameter was 4.5(range, 1.8-12.5)cm. (3) Follow-up. All the 17 patients were followed up for 14(range, 2-30)months, without tumor recurrence.Conclusion:Injection of ICG via percutaneous transhepatic portal vein under ultrasound guidance during laparoscopic anatomical liver resection is safe and feasible.
7.Application value of indocyanine green injection via percutaneous transhepatic portal vein puncture under ultrasound guidance during laparoscopic anatomical liver resection
Zisen LAI ; Jiahui LYU ; Guangwen LIU ; Qian LIN ; Jiacheng ZHANG ; Liming HUANG ; Yongyi ZENG
Chinese Journal of Digestive Surgery 2024;23(12):1544-1549
Objective:To investigate the application value of indocyanine green (ICG) injection via percutaneous transhepatic portal vein under ultrasound guidance during laparoscopic anatomical liver resection.Methods:The retrospective and descriptive study was conducted. The clinicopatho-logical data of 17 male patients with hepatocellular carcinoma who underwent laparoscopic anatomical liver resection in Mengchao Hepatobiliary Hospital of Fujian Medical University from October 2022 to May 2024 were collected. The patients were aged 59(range, 27-74)years. Patients underwent ICG fluorescence-guided laparoscopic anatomical liver resection after ICG injection via percutaneous transhepatic portal vein under ultrasound guidance. Obsevation indicators: (1)surgical situations; (2) postoperative situations; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M(range). Count data were represented as absolute numbers. Results:(1) Surgical situations. All 17 patients were successfully punctured and injected with ICG via percutaneous transhepatic portal vein under ultrasound guidance, with a puncture time of 6(range,3-12)minutes. The fluorescence staining successfully displayed at the target liver segment without infiltration, and the distance from the fluorescence staining border to the tumor edge was greater than 1.0 cm, which was consistent with preoperative three-dimensional reconstruction imaging. Among the 17 patients, 11 cases had punctures in one branch of the portal vein, 4 cases had punctures in two branches, and 2 had punctures in three branches. The operation time was (229±51)minutes, volume of intraoperative blood loss was 200(range, 100-300)mL. No blood transfusion or conversion to open surgery was required during the operation. (2) Postoperative situations. Two of 17 patients had a small pleural effusion of grade Ⅰ-Ⅱ of Clavien-Dindo classification, and were recovered without treatment. The duration of postoperative hospital stay was 5(range, 5-6)days. Postoperative pathological examina-tion showed hepatocellular carcinoma with negative surgical margin. The tumor diameter was 4.5(range, 1.8-12.5)cm. (3) Follow-up. All the 17 patients were followed up for 14(range, 2-30)months, without tumor recurrence.Conclusion:Injection of ICG via percutaneous transhepatic portal vein under ultrasound guidance during laparoscopic anatomical liver resection is safe and feasible.
8.Clinical efficacy of rigid choledochoscopic percutaneous transhepatic biliary fistulation lithotripsy for hepatolithiasis: a meta-analysis
Xin HUANG ; Cairu HUANG ; Kecan LIN ; Shunfeng LUO ; Qizhen HUANG ; Zisen LAI ; Yongyi ZENG
Chinese Journal of Hepatobiliary Surgery 2023;29(10):760-767
Objective:To analyze and predict the clinical efficacy of rigid choledochoscopic percutaneous transhepatic biliary fistulation (PTBF) lithotripsy for the treatment of hepatolithiasis.Methods:Databases including PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang were searched for literatures from January 1, 1990 to March 1, 2022 on rigid choledochoscopic PTBF lithotripsy for hepatolithiasis studies. The primary outcomes including the final clearance rate, recurrence rate and overall postoperative complication rate, were analyzed by the random effects model in meta analysis and Bayesian network. The Markov Chain Monte Carlo was used for evaluation and prediction.Results:Fifteen articles were ultimately included, involving 1 296 patients, of which 1 008 patients were clearly shown to have complex intrahepatic bile duct stones in the literature [divided into two groups, the percutaneous transhepatic one-step biliary fistulation (PTOBF) stone removal group ( n=568) and the percutaneous transhepatic two-step biliary fistulation (PTTBF) stone removal group ( n=440)]. The results of Bayesian single-arm meta-analysis showed that the final clearance rate, recurrence rate and overall postoperative complication rate of PTOBF for hepatolithiasis were 84.19% (95% HPD: 79.08%-88.93%), 15.79% (95% HPD: 11.01%-21.07%) and 10.85% (95% HPD: 7.93%-14.21%). For complex hepatolithiasis, the final clearance rate, recurrence rate and overall postoperative complication rate of PTOBF were 82.58% (95% HPD: 75.46%-88.83%), 17.99% (95% HPD: 11.51%-25.45%), 10.34% (95% HPD: 6.42%-15.40%). For PTTBF, they were respectively 73.56% (95% HPD: 65.67%-80.30%), 29.48% (95% HPD: 23.13%-36.01%), 11.42% (95% HPD: 6.18%-17.67%). In comparison to PTTBF, the patients treated with PTOBF has a higher clearance rate ( OR=1.74, 95% CI: 1.17-2.60) and a lower recurrence rate ( OR=0.56, 95% CI: 0.37-0.84)but the overall complication rate did not improve ( OR=1.03, 95% CI: 0.66-1.62). Conclusions:Rigid choledochoscopic PTBF lithotripsy for hepatolithiasis is safe, effective and feasible. For complex hepatolithiasis, PTOBF has a higher clearance rate and a lower recurrence rate.

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