1.Long-term efficacy of sequential surgery after immune combined with targeted therapy for initially unresectable hepatocellular carcinoma
Xuerui LI ; Junfeng LI ; Wenwen ZHANG ; Zhijun WANG ; Bingyang HU ; Haowen TANG ; Bing LIU ; Tao WAN ; Zhe LIU ; Zhanbo WANG ; Shichun LU
Chinese Journal of Hepatobiliary Surgery 2024;30(1):9-14
Objective:To assess the long-term outcome of sequential radical surgery after immune combined with targeted therapy for patients with initially unresectable hepatocellular carcinoma (HCC).Methods:Clinical data of 100 patients with initially unresectable HCC undergoing sequential radical surgery after immune combined with targeted therapy at the Faculty of Hepato-Pancreato-Biliary Surgery of Chinese PLA General Hospital from December 2018 to August 2023 were prospectively collected, including 87 males and 13 females, with a median age of 55 (24-73) years. The pre-treatment tumor staging was determined using the China liver cancer staging (CNLC). The efficacy of immune combined with targeted therapy was accessed using the modified response evaluation criteria in solid tumor (mRECIST). The cycles of immune combined with targeted therapy were analyzed. The tumor residual of resected tissue was analyzed through a standard pathological protocol. The prognosis was analyzed using the Kaplan-Meier method.Results:Upon initial diagnosis, there were 46 cases (46.0%) staged CNLC-Ⅲa and 40 (40.0%) staged CNLC-Ⅲb. There were also 14 cases (14.0%) staged CNLC-Ⅰb, Ⅱa, and Ⅱb who underwent immune combined with targeted therapy due to rupture of tumor or insufficient liver remnant. All patients received a median of 5 (3-28) cycles of immune combined with targeted therapy and underwent radical surgery after successful conversion. According to mRECIST, 14 (14.0%) were determined as complete remission, 63 (63.0%) as partial remission, 18 (18.0%) as stable disease, and 5 (5.0%) as disease progression. Of 24 (24.0%) were defined as pathologically complete remission by postoperative pathology. Furthermore, pathological tumor residue was less than 10% in 61 (61.0%) cases and less than 50% in 82 (82.0%) cases. The 1, 3, and 5 year-overall survival rates of patients were 98.0%, 83.1%, and 74.5%, respectively. The 1, 2 and 3 year-recurrence-free survival rates were 67.5%, 54.8%, and 49.6%, respectively.Conclusion:Sequential radical surgery after immune combined with targeted therapy benefits the long-term survival of patients with initially unresectable HCC.
2.Effect of thrombocytosis on prognosis of hepatocellular carcinoma after TACE
Tingsong YING ; Hao XU ; Zichen WU ; Zhixiang FAN ; Wang LIU
Chinese Journal of Hepatobiliary Surgery 2024;30(1):15-20
Objective:To analyze the prognosis of hepatocellular carcinoma (HCC) patients with thrombocytosis (platelet count ≥350×10 9) after transcatheter arterial chemoembolization (TACE), and the effect of thrombocytosis on the prognosis of patients with HCC after TACE. Methods:Clinical data of 867 patients with HCC admitted to the Department of Interventional Radiology, the Affiliated Hospital of Xuzhou Medical University from January 2013 to May 2018 were retrospectively analyzed. After propensity score matching, 99 patients were enrolled, including 70 males and 29 females, aged (60.1±12.1) years. Patients were divided into the groups with thrombocytosis ( n=33) and without thrombocytosis ( n=66). The gender, maximum tumor diameter, Barcelona clinical liver cancer (BCLC) stage, and total bilirubin were compared between the two groups. The association of thrombocytosis with the prognosis of HCC after TACE treatment were analyzed using univariate and multivariate Cox regression. Results:After propensity score matching, the male proportion, maximum tumor diameter, BCLC stage, and serum level of total bilirubin were comparable between the groups (all P>0.05). Before TACE treatment, the platelet count of patients with thrombocytosis was (394.4±54.5)×10 9/L, which was higher than that after TACE [(278.2±86.4)×10 9/L, t=7.63, P<0.001]. The progression-free survival rates after TACE in without thrombocytosis group were 83.3%, 24.2%, and 7.6% at 3, 6 and 9 months, respectively, better than those in thrombocytosis group (51.5%, 3.0%, and 3.0%, respectively; χ2=31.24, P<0.001). The overall survival rates after TACE in without thrombocytosis group were 81.8%, 30.3%, and 4.5% at 1, 2 and 3 years, respectively, better than those in thrombocytosis group (15.2%, 9.1%, and 3.0%, respectively; χ2=27.89, P<0.001). Multivariate Cox regression analysis showed that patients of HCC with thrombocytosis had an increased risk of tumor progression ( HR=5.785, 95% CI: 3.291-10.168, P<0.001) and increased risk of death ( HR=4.090, 95% CI: 2.482-6.740, P<0.001) after TACE. Conclusion:The prognosis of TACE for HCC might be worse in patients with thrombocytosis. Thrombocytosis is a risk factor for cumulative survival and progression-free survival of HCC patients after TACE.
3.Development and validation of a postoperative infection nomogram for hepatitis B-associated hepatocellular carcinoma patients after hepatectomy
Bing TAN ; Yanan MA ; Zhen YU ; Chaoyi REN ; Jiandong ZHANG
Chinese Journal of Hepatobiliary Surgery 2024;30(1):21-26
Objective:To develop and validate a postoperative infection nomogram of hepatitis B-associated hepatocellular carcinoma (HCC) after hepatectomy.Methods:Clinical data of 229 patients with HCC undergoing hepatectomy at the Department of Hepatobiliary Surgery of Tianjin Third Central Hospital from January 2014 to December 2022 were retrospectively analyzed, including 174 males and 55 females, aged (58.2±11.4) years. LASSO regression analysis screened the factors associated with hepatitis B-associated HCC infection after hepatectomy, which were further incorporated into multivariate logistic regression analysis. A nomographic prediction model was established based on the results of multivariate logistic regression analysis. Concordance index (C-index), calibration curve and receiver operating characteristic (ROC) curve were used to evaluate the model, and decision curve analysis (DCA) was used to analyze the clinical applicability of the model. Internal validation of the model was performed using bootstrap method.Results:A total of nine variables were screened as factors associated with the postoperative infections using LASSO regression, including gender, smoking history, body mass index (BMI), serum level of alpha fetoprotein, resection fashion (anatomical or non-anatomical), intraoperative blood loss, surgical method (laparoscopy or open), serum level of creatinine, and postoperative biliary fistula. Multivariate logistic regression analysis showed that BMI, resection fashion, intraoperative blood loss >500 ml, and postoperative biliary fistula were risk factors for postoperative infection (all P<0.05). Based on the above risk factors, a postoperative infection nomogram of hepatitis B-associated HCC after hepatectomy was established. The C-index was 0.839 (95% CI: 0.768-0.910), and the area under ROC curve was 0.853 (95% CI: 0.795-0.912), indicating that the model had a good predictive ability. The calibration curve was basically consistent with the ideal curve. The DCA showed that the model had a good clinical applicability. Internal validation C-index was 0.829 (95% CI: 0.766-0.892). Conclusion:The nomogram based on BMI, surgical resection fashion, intraoperative blood loss >500 ml, and postoperative biliary fistula has a high predictive accuracy and can be used to predict postoperative infections after hepatectomy for HCC.
4.The expression of SCAMP3 in hepatocellular carcinoma and its prognostic analysis based on TCGA database
Hanyang CHE ; Yajun ZHONG ; Xinliang LYU
Chinese Journal of Hepatobiliary Surgery 2024;30(1):27-32
Objective:To study the expression and prognostic impact of secretory carrier membrane protein 3 (SCAMP3) in hepatocellular carcinoma (HCC) and its gene set enrichment analysis.Methods:SCAMP3 expression and its prognosis were analyzed using The Cancer Genome Atlas (TCGA) database. The cancer tissue and paracancerous tissue were collected from four patients with HCC undergoing surgery in Lishui Central Hospital to detect the expression of SCAMP3. Based on TCGA database, univariate and multivariate Cox regression was performed to analyze the relevance of SCAMP3 with prognosis of HCC. Gene set enrichment analysis was utilized to clarify the biological role of SCAMP3.Results:In TCGA database, SCAMP3 expression was higher in HCC tissues than that in normal liver tissues ( Z=-8.38, P<0.001). Patients were divided into the low-expression group ( n=185) and high-expression group ( n=185) based on the median SCAMP3 expression, and the overall survival rate was lower in patients with high SCAMP3 expression. In our four patients. The expression of SCAMP3 mRNA and protein in cancer tissues was higher than that in paracancerous tissues ( t=8.55, 6.24, both P<0.001). In multivariate Cox regression analysis, the higher SCAMP3 expression was associated with a higher risk of death ( HR=1.466, 95% CI: 1.143-1.881, P<0.001). Gene set enrichment analysis in patients with high SCAMP3 expression, the coagulation cascade and three signaling pathways involving the complements, retinol metabolism, and peroxisome proliferator-activated receptor were identified. Conclusion:SCAMP3 expression elevated in HCC, patients with a higher expression of SCAMP3 might have a worse prognosis. High SCAMP3 expression is a risk factor for the survival of patients with HCC. High SCAMP3 expression is associated with the coagulation cascade and the complements, retinoid metabolism, and peroxisome proliferator-activated receptor pathways.
5.The relationship of age-adjusted Charlson comorbidity index and prognosis of patients undergoing laparoscopic resection for hilar cholangiocarcinoma
Chiyu CAI ; Liancai WANG ; Lianyuan TAO ; Dongxiao LI ; Erwei XIAO ; Guangjin TIAN ; Guanbin LUO ; Zhuangzhuang YAN ; Yanbo WANG ; Deyu LI
Chinese Journal of Hepatobiliary Surgery 2024;30(1):33-37
Objective:To study the impact of the age-adjusted Charlson comorbidity index (ACCI) on the prognosis of patients with hilar cholangiocarcinoma following laparoscopic surgical resection.Methods:Clinical data of 136 patients with hilar cholangiocarcinoma undergoing laparoscopic surgery at Zhengzhou University People's Hospital between January 2013 and January 2018 were retrospectively analyzed, including 81 males and 55 females, aged (63.6±9.8) years. Patients were divided into two groups based on the median ACCI score of 4.0: the high ACCI group (ACCI>4.0, n=49) and low ACCI group (ACCI≤4.0, n=87). The prognosis was compared between the two group. Univariate and multivariate Cox regression analyses were performed to analyze the effect of ACCI on survival after laparoscopic surgery. Results:The 1- and 3-year cumulative survival rates in low ACCI group were 87.4% and 48.3%, respectively, compared to 53.1% and 4.1% in high ACCI group ( χ2=27.97, P<0.001). Univariate Cox regression analysis indicated that ACCI >4.0 was associated with prognosis ( HR=3.73, 95% CI: 2.44-5.68, P<0.001). Multivariate Cox regression analysis also indicated that ACCI >4.0 was associated with an increased risk of postoperative mortality in patients with hilar cholangiocarcinoma ( HR=2.69, 95% CI: 1.65-4.37, P<0.001). Conclusion:The ACCI is a significant risk factor for survival of patients with hilar cholangiocarcinoma following laparoscopic surgery, which could facilitate a precise preoperative assessment of patient status and choice of surgical approach.
6.Clinical study on the expression of EGFR in pancreatic adenosquamous carcinoma
Yongchun FU ; Xin ZHAO ; Shaocheng LYU ; Zhizhao HU ; Qiang HE
Chinese Journal of Hepatobiliary Surgery 2024;30(1):38-43
Objective:Exploration of epidermal growth factor receptor (EGFR) expression and its clinical significance in pancreatic adenosquamous carcinoma (PASC).Methods:A total of 60 pancreatic cancer tissue samples and 8 normal pancreatic tissue samples were obtained from patients who were surgically treated at Beijing Chao-Yang Hospital, Capital Medical University from January 2016 to December 2021. A retrospective analysis of the clinical and pathological data of these 60 patients was conducted, including 23 males and 37 females with an age of (62.7±10.2) years. Among them, 20 cases were pathologically diagnosed as PASC, and 40 contemporaneous cases of pancreatic ductal adenocarcinoma (PDAC) were selected through propensity score matching. Immunohistochemistry (IHC) staining was used to measure the integrated optical density (IOD) of EGFR expression, and quantitative polymerase chain reaction (qPCR) was employed to detect the expression differences of EGFR mRNA. Based on the median IOD value of EGFR, the 20 PASC samples were divided into two groups, high and low expression groups. Kaplan-Meier survival analysis was performed to compare the impact of EGFR expression on the prognosis of PASC patients.Results:The IOD value of EGFR in PASC group (29.2 [25.7, 35.1]) was significantly higher than that in the PDAC group [9.5 (5.5, 13.0)] and they both exceeded the value in normal tissues [2.4 (1.7, 3.1)], with statistical significances ( all P<0.001 ). The level of EGFR mRNA expression in the PASC group was higher than that in the PDAC group [3.0 (1.8, 3.5) vs 1.2 (0.8, 1.2)], showing statistically significant difference ( P=0.0079). Patients with high EGFR expression had shorter overall survival compared with patients with low expression ( P=0.002). The incidence of vascular invasion in the PASC group [40.0% (8/20)] was higher than that in the PDAC group [17.5% (7/40)], with a significant difference ( P=0.002). The median survival time for the PASC group was 16.00 (9.25, 25.25) months, which was shorter than that of the PDAC group 21.50 (11.25, 40.75) months, showing a statistically significant difference ( P=0.033). The overall survival rate of the PASC group was lower than PDAC group ( P=0.028). Conclusion:EGFR expression is significantly elevated in PASC tissues and PASC patients have poor prognosis.
7.A preliminary clinical study of polyester spacer-enhanced pancreatico-intestinal anastomosis in pancreaticoduodenectomy
Xin LI ; Jiayi WANG ; Shaohua LI ; Ruili ZHU ; Zhenfei JIA ; Chengyun MA ; Xianbing WANG
Chinese Journal of Hepatobiliary Surgery 2024;30(1):44-49
Objective:To investigate the safety and utility of using polyester spacers in conventional pancreatico-enteric anastomosis in pancreaticoduodenectomy to achieve prevention of postoperative pancreatic fistula.Methods:The clinical data of 82 patients with pancreaticoduodenectomy completed by the same physician in Anyang People's Hospital from August 2018 to August 2023 were retrospectively analyzed, including 52 males and 30 females, aged (62.21±9.75) years. They were divided into two groups, test group ( n=40) and control group ( n=42) according to whether polyester spacers were used in pancreatico-intestinal anastomosis, the perioperative data of the two groups were compared, and Logistic analysis was used to analyze the risk factors affecting postoperative pancreatic fistula. Results:There was no statistically significant difference between the two groups in terms of biliary fistula, intestinal fistula, abdominal infection, abdominal bleeding, and postoperative mortality rate (all P>0.05). The incidence of postoperative pancreatic fistula in the test group was 20.0% (8/40) which was lower than that in the control group 45.2% (19/42), and the difference was statistically significant ( P=0.015). Soft pancreas texture ( OR=16.595, 95% CI: 1.891~145.657) was an independent risk factor for postoperative pancreatic fistula, while improved pancreatic enterostomy with polyester spacers ( OR=0.332, 95% CI: 0.114~0.969) could reduce the risk of postoperative pancreatic fistula. Conclusion:Use of polyester spacers to reinforce the pancreatico-enteric anastomosis during pancreaticoduodenectomy reduces the incidence of postoperative pancreatic fistulae with good safety and practicality.
8.Comparison of clinicopathological features and prognostic analysis between patients with gallbladder adenosquamous carcinoma and gallbladder adenocarcinoma
Xueming ZHANG ; Leiming ZHANG ; Gong CHENG
Chinese Journal of Hepatobiliary Surgery 2024;30(1):50-55
Objective:To compare the clinicopathological features between patients with gallbladder adenosquamous carcinoma and gallbladder adenocarcinoma, and analyze the prognostic factors for overall survival.Methods:The clinical data of 135 patients with gallbladder cancer, confirmed by postoperative pathology, treated in Department of Hepatobiliary and Pancreatic Surgery of Ningbo Medical Center Lihuili Hospital within 5 years (from January 2018 to December 2022) were retrospectively analyzed. A total of 122 patients were enrolled in this study, including 55 males and 67 females, aged (68.0±9.8) years. Patients were divided into the adenosquamous carcinoma group ( n=14) and adenocarcinoma group ( n=108). The clinicopathological features (tumor size, differentiation of tumor, tumor TNM stage) and survivals of patients were compared. The survival rates were analyzed using the Kaplan-Meier method and log-rank test. Multivariate Cox regression analysis was performed to identify prognostic factors for overall survival. Results:Compared with the adenocarcinoma group, patients with adenosquamous carcinoma had a larger tumor size, higher incidence of liver invasion, higher proportion of poor differentiation of tumor, higher proportion of TNM stage Ⅲ-Ⅳ (all P<0.05). There was also a statistically significant difference in the extent of liver resection between the two groups ( χ2=9.22, P=0.016). The 1- and 2-year cumulative survival rates after surgery in adenosquamous carcinoma group were 28.6% and 9.5%, respectively, lower than those in adenocarcinoma group (78.7% and 60.5%, respectively; χ2=27.88, P<0.001). For patients with gallbladder adenosquamous carcinoma, the cumulative survival rate of patients who received postoperative adjuvant chemotherapy ( n=11) was significantly better than that of patients without postoperative adjuvant chemotherapy ( n=3) ( χ2=5.82, P=0.016). For patients with gallbladder adenocarcinoma, multivariate Cox regression analysis identified that the N stage (N 1/N 0HR=4.521, 95% CI: 1.399-14.612, P=0.012; N 2/N 0HR=8.644, 95% CI: 2.407-31.039, P=0.001) and M stage (M 1/M 0HR=4.699, 95% CI: 1.540-14.340, P=0.007) were associated with a poor survival. Conclusions:Compared to gallbladder adenocarcinoma, adenosquamous carcinoma had more aggressive features and a worse prognosis. For patients with gallbladder adenosquamous carcinoma, postoperative adjuvant chemotherapy was associated with an improved overall survival. For patients with gallbladder adenocarcinoma, N stage and M stage were independent risk factors for overall survival.
9.Expression of BCL7A in hepatocellular carcinoma and its effects on prognosis, invasion and migration of hepatocellular carcinoma
Jiawei JIANG ; Wei HUANG ; Jing CHEN ; Tao MA ; Han XUAN ; Yang YAN ; Ruochun WANG ; Jinxia LIU
Chinese Journal of Hepatobiliary Surgery 2024;30(1):56-61
Objective:To analyze the expression and prognosis of B-cell lymphoma 7 protein family member A (BCL7A) in hepatocellular carcinoma, as well as the effect and mechanism of BCL7A expression on the invasion and migration of hepatocellular carcinoma cells.Methods:The cancer tissues and adjacent tissues of 40 patients with hepatocellular carcinoma who underwent radical hepatobiliary resection in the Department of Hepatobiliary Surgery, Affiliated Hospital of Nantong University from November 2017 to March 2018 were prospectively collected for protein extraction, including 29 males and 11 females, aged (58.5±10.4) years. The information of 374 cases of hepatocellular carcinoma and 50 cases of adjacent tissues were downloaded from The Cancer Genome Atlas (TCGA) database, and the hepatocellular carcinoma cell lines Hep3B and SMMC-7721 were transfected with overexpressing BCL7A plasmid and empty vector plasmid (negative control), respectively. Western blotting and immunohistochemistry were used to detect the expression of BCL7A, and Western blotting was also used to detect the expression of proteins related to epithelial-mesenchymal transition (N-cadherin, E-cadherin, snail). Transwell and cell scratch assays were used to detect cell invasion and migration.Results:Compared with adjacent tissues, the mRNA expression of BCL7A in 50 patients with hepatocellular carcinoma in TCGA was significantly increased ( t=13.38, P<0.001). According to the median mRNA expression level of BCL7A, 374 patients were divided into BCL7A high expression group ( n=187) and low expression group ( n=187), and the cumulative survival rate of BCL7A high expression patients was lower than that of low expression group, and the difference was statistically significant ( χ2=6.95, P=0.009). Western blot was used to detect the relative expression of BCL7A protein in cancer tissues, and found it was higher compared to adjacent tissues. Compared with the negative control group, the number of cells invaded by the BCL7A overexpression group of hepatoma cells Hep3B and SMMC-7721 was more than the negative control group respectively, (153.7±1.3) vs (63.7±4.7) and (307.7±25.14) vs (72.3±12.5), and the differences were statistically significant ( t=7.97, 8.38, both P=0.001) .The results of the cell scratch assay were consistent with the results of the Transwell invasion assay. The expressions of N-cadherin and snail in the BCL7A overexpression group were higher than those in the negative control group, and the E-cadherin was lower, and the difference was statistically significant (all P<0.05). Conclusions:The expression of BCL7A in cancer tissues of patients with hepatocellular carcinoma is elevated and is associated with poor prognosis. BCL7A may promote hepatocellular carcinoma cell metastasis and invasion by promoting epithelial-mesenchymal transition.
10.A meta-analysis of the efficacy and safety of robotic surgery versus open surgery in the treatment of hilar cholangiocarcinoma
Manqin HU ; Dingwei XU ; Yan ZHANG ; Ao LI ; Xincheng LI ; Jie HUANG
Chinese Journal of Hepatobiliary Surgery 2024;30(1):62-66
Objective:To compare the efficacy and safety of robotic surgery and open surgery in the treatment of hilar cholangiocarcinoma.Methods:PubMed, Embase, Cochrane Library, Web of Science, CNKI and Wanfang database were searched to compare the treatment of hilar cholangiocarcinoma by robotic surgery and traditional open surgery. Literatures were searched from the establishment of the database to July 2023. Compare operation time, intraoperative blood transfusion rate, R 0 resection rate, lymph node metastasis rate, postoperative complication rate and hospital stays between the two groups. The combined odds ratio ( OR) and mean difference ( MD) and 95% confidence interval (95% CI) were calculated using RevMan 5.4 software. Results:A total of 4 studies were included, including 267 patients with hilar cholangiocarcinoma. There were 177 males and 90 females, aged (58.8±5.7) years. A total of 267 patients were divided into open surgery group ( n=165) and robotic surgery group ( n=102) according to the surgical formula. The extract results show: operative time ( MD=-103.96, 95% CI: -216.90-8.98, P=0.070) and intraoperative blood transfusion rate ( OR=1.32, 95% CI: 0.43-4.07, P=0.630), R 0 resection rate ( OR=1.41, 95% CI: 0.71-2.81, P=0.330), lymph node metastasis rate ( OR=1.62, 95% CI: 0.46-5.63, P=0.450), postoperative complications ( OR=0.60, 95% CI: 0.28-1.31, P=0.200), and postoperative hospital stay ( MD=2.17, 95% CI: -11.56-15.90, P=0.760). Conclusion:In the treatment of hilar cholangiocarcinoma, robotic surgery is as safe and feasible as open surgery. However, due to the limited number and quality of included studies, the above conclusions need to be verified by more high-quality studies.

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