1.Current status and prospects of postoperative adjuvant therapy for hepatocellular carcinoma
Yongyi ZENG ; Jun FU ; Kongying LIN ; Luobin GUO
Chinese Journal of Digestive Surgery 2024;23(2):221-227
The high recurrence and metastasis rate of hepatocellular carcinoma (HCC) in patients after hepatectomy significantly impact the prognosis. Exploring effective strategies and indications of postoperative adjuvant therapy for HCC is of great clinical significance in reducing postoperative recurrence rate and improving long-term survival. Traditional local treatment modalities, including transcatheter arterial chemoembolization, hepatic artery infusion chemotherapy, and radiotherapy, continue to play a crucial role in postoperative adjuvant therapy. Recently, the emergence of novel systemic therapy agents, including molecular targeted drugs and immune checkpoint inhibitors, has transformed the landscape of postoperative adjuvant therapy, making the selection of adjuvant therapy more intricate and diverse. The author combines the latest progress in adjuvant therapy to explore the strategies and challenges of postoperative adjuvant therapy for HCC.
2.The evaluation of alpha-fetoprotein response on efficacy and prognosis in targeted therapy combined with immunotherapy for intermediate-to-advanced hepatocellular carcinoma: a multicenter clinical study
Kongying LIN ; Qingjing CHEN ; Luobin GUO ; Yun YANG ; Yufeng CHEN ; Jianxi ZHANG ; Fuqun WEI ; Hui ZHANG ; Zhiqing CHENG ; Yuntong LI ; Congren WANG ; Yabin JIANG ; Kecan LIN ; Weiping ZHOU ; Yongyi ZENG
Chinese Journal of Digestive Surgery 2024;23(2):248-256
Objective:To investigate the evaluation efficacy and predictive prognostic value of alpha-fetoprotein (AFP) response in tyrosine kinase inhibitors (TKIs) in combination with PD-1 inhibitors (α-PD-1) for intermediate-to-advanced hepatocellular carcinoma (HCC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 205 patients with intermediate-to-advanced HCC who were admitted to 9 medical centers, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from March 2020 to July 2022 were collected. There were 178 males and 27 females, aged (52±12)years. Based on AFP response at 6-8 weeks after treatment, patients were divided into the AFP response group (AFP level decreased by ≥50% compared to baseline) and the AFP no response group (AFP level decreased by <50% compared to baseline). Observation indicators: (1) AFP response evaluation of anti-tumor efficacy; (2) comparison of patient prognosis; (3) analysis of factors affecting patient prognosis. Measurement data with normal distrubution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range) and M( Q1, Q3). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to draw survival curve and calculate survival rate, and the Log-Rank test was used for survival analysis. The COX proportional risk model was used for univariate analysis and the COX stepwise regression model was used for multivariate analysis. Results:(1) AFP response evaluation of anti-tumor efficacy. Before treatment, all 205 patients were positive of AFP, with a baseline AFP level of 1 560(219,3 400)μg/L. All 205 patients were treated with TKIs in combination with α-PD-1, and the AFP level was 776(66,2 000)μg/L after 6 to 8 weeks of treatment. Of the 205 patients, 88 cases were classified as AFP response and 117 cases were classified as AFP no response. According to the response evaluation criteria in solid tumors version 1.1, the objective response rate (ORR) and disease control rate (DCR) were 42.05%(37/88) and 94.32%(83/88) in patients of the AFP response group and 16.24% (19/117) and 64.10% (75/117) in patients of the AFP no response group, showing significant differences between them ( χ2=16.846, 25.950, P<0.05). According to the modified response evaluation criteria in solid tumors, the ORR and DCR were 69.32% (61/88) and 94.32% (83/88) in patients of the AFP response group and 33.33% (39/117) and 64.10% (75/117) in patients of the AFP no response group, showing significant differences between them ( χ2=26.030, 25.950, P<0.05). (2) Comparison of patient prognosis. All 205 patients were followed up for 12.4(range, 2.4-34.0)months after treatment. The median progression free survival time and total survival time were 5.5 months and 17.8 months, respectively. The 1-year, 2-year progression free survival rates were 20.8% and 7.2%, and the 1-year, 2-year overall survival rates were 68.7% and 31.5%, respectively. The median progression free survival time, 1-year and 2-year progression free survival rates were 9.7 months, 39.6% and 14.2% in patients of the AFP response group and 3.7 months, 7.8% and 2.0% in patients of the AFP no response group, showing a significant difference in progression free survival between them ( χ2=43.154, P<0.05). The median overall survival time, 1-year and 2-year overall survival rates were not reached, 85.2% and 56.3% in patients of the AFP response group and 14.6 months, 56.3% and 14.5% in patients of the AFP no response group, showing a significant difference in overall survival between them ( χ2=33.899, P<0.05). (3) Analysis of factors affecting patient prognosis. Results of multivariate analysis showed that invasion of large blood vessels, extrahepatic metastasis, combined hepatic artery intervention therapy, and AFP response were independent factors influencing progression free survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1 ( hazard ratio=1.474, 1.584, 0.631, 0.367, 95% confidence interval as 1.069-2.033, 1.159-2.167, 0.446-0.893, 0.261-0.516, P<0.05), and Eastern Cooperative Oncology Group score, invasion of large blood vessels, extrahepatic metastasis, and AFP response were independent factors influencing overall survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1 ( hazard ratio= 1.347, 1.914, 1.673, 0.312, 95% confidence interval as 1.041-1.742, 1.293-2.833, 1.141-2.454, 0.197-0.492, P<0.05). Conclusions:AFP response at 6-8 weeks after treatment can effectively evaluate anti-tumor efficacy of TKIs in combination with α-PD-1 for intermediate-to-advanced HCC. AFP response is the independent factor influencing progression free survival and overall survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1.
3.The impact of lymph node dissection on textbook outcomes of intrahepatic cholangiocarci-noma and prognostic analysis
Tingfeng HUANG ; Hongzhi LIU ; Kongying LIN ; Shichuan TANG ; Jun FU ; Qizhu LIN ; Ruilin FAN ; Weiping ZHOU ; Jingdong LI ; Jiangtao LI ; Yongyi ZENG
Chinese Journal of Digestive Surgery 2024;23(7):944-951
Objective:To analyze the impact of lymph node dissection on textbook outcomes (TO) and the prognosis of intrahepatic cholangiocarcinoma (ICC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 376 ICC patients who underwent hepatectomy in 4 medical centers, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from December 2011 to December 2017 were collected. There were 242 males and 134 females, aged 57(range, 48-63)years. According to the criteria of TO, patients were classified as two cate-gories, including patients achieving TO and not achieving TO. Measurement data with normal distri-bution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were represented as absolute numbers, and comparison between groups was conducted using the chi-square test, Yates adjusted chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the non-parameter rank sum test. Univariate and multivariate analyses were conducted using the Logistic regression model. The Kaplan-Meier method was used to draw survival curve. Survival analysis was conducted using the Log-rank test. Results:(1) TO situations. Of the 376 ICC patients who underwent hepatectomy, 199 cases achieved TO, including 40 cases with lymph node dissection and 159 cases without lymph node dissection, 177 cases did not achieve TO, including 76 cases with lymph node dissection and 101 cases without lymph node dissection. (2) Influencing factors for TO after hepatectomy of ICC patients. Results of multivariate analysis showed that lymph node dissection, microvascular invasion, nerve invasion and the volume of intraoperative blood loss >800 mL were independent risk factors for achieving TO after hepatec-tomy of ICC patients ( odds ratio=2.22, 2.95, 3.58, 4.09,95% confidence interval as 1.34-3.69, 1.43-6.07, 1.40-9.17, 1.35-12.43, P<0.05). Of the 116 patients with lymph node dissection, 40 cases achieved TO, 103 cases achieved R 0 resection, 38 cases had postoperative complications, 67 cases had delayed hospital stay. The above indicators were 159, 255, 41, 65 of 260 patients without lymph node dissection. There were significant differences in the above indicators between patients with and without lymph node dissection ( χ2=22.90, 15.16, 13.95, 37.78, P<0.05). (3) Follow-up. All the 376 patients were followed up for 19(range, 1-74)months. Of 199 patients achieving TO, the 1-, 2-and 3-year survival rates of 40 patients with lymph node dissection were 54.0%, 36.6% and 26.1%, respectively, versus 67.7%, 42.7% and 34.4% of 159 patients without lymph node dissection, showing no significant difference between them ( χ2=1.89, P>0.05). Of 177 patients not achieving TO, the 1-, 2-and 3-year survival rates of 76 cases with lymph node dissection were 58.9%, 25.7% and 10.3%, respectively, versus 53.0%, 28.5% and 17.2% of 101 cases without lymph node dissection, showing no significant difference between them ( χ2=0.25, P>0.05). Conclusions:Lymph node dissec-tion, microvascular invasion, nerve invasion and the volume of intraoperative blood loss >800 mL are independent risk factors for achieving TO after hepatectomy of ICC patients. Lymph node dissec-tion may increase the postoperative complication rate, prolong the hospital stay and decrease the rate of achieving TO. However, it does not affect the prognosis of patients.
4.Study on the distribution of pathogenic microorganisms and influencing factors in patients with abdominal infection after pancreaticoduodenectomy
Xiaoling YU ; Yao HUANG ; Yupeng TANG ; Ruixuan ZHANG ; Yongyi ZENG
Chinese Journal of Hepatobiliary Surgery 2024;30(8):597-601
Objective:To analyze the distribution of pathogenic microorganisms of abdominal infection in patients after pancreaticoduodenectomy and the influencing factors of postoperative abdominal infection.Methods:The clinical data of 108 patients with pancreatic diseases, including ampullary tumors, pancreatic tumors, duodenal tumors, and malignant tumors of the common bile duct, who underwent pancreaticoduodenectomy in Mengchao Hepatobiliary Hospital of Fujian Medical University from May 2019 to December 2022 were retrospectively analyzed. Among them, 65 were males, 43 were females, aged (59.28±17.88) years old. Patients who underwent pancreaticoduodenectomy were categorized into two distinct cohorts based on the occurrence of abdominal infection within a 30-day postoperative period: the infected group ( n=37) and the non-infected group ( n=71).General data, laboratory test indicators, pathogen types and drug susceptibility test results of patients were collected. Logistic regression was used to analyze the influencing factors of postoperative pancreaticoduodenal abdominal infection. Results:The postoperative abdominal infection rate was 34.26% (37/108), and a total of 105 pathogenic bacteria were detected, including 43 gram-negative bacteria (40.95%), 36 gram-positive bacteria (34.29%) and 26 fungi (24.76%). The top five pathogens were Enterococcus faecium, Candida albicans, Stenotrophomonas maltophilia, Pseudomonas aeruginosa and Staphylococcus haemolyticus. The drug sensitivity results showed that no tigecycline and vancomycin-resistant Enterococcus faecium strains. The sensitivity rate of Candida albicans to amphotericin B was 100%, and the resistance rate to fluconazole was only 4.8%. The resistance rates of Stenotrophomonas maltophilia to cefoperazone-sulbactam and levofloxacin are 11.1% and 33.3%, respectively. The resistance rates of Pseudomonas aeruginosa to imipenem and meropenem are 71.4% and 28.6%, respectively. Multivariate logistic regression analysis showed that postoperative intra-abdominal bleeding ( OR=10.997, 95% CI: 1.995-13.840, P=0.004) and pancreatic fistula ( OR=16.832, 95% CI: 1.938-146.174, P=0.010) were risk factors for the occurrence of abdominal infection after pancreatoduodenectomy. Conclusion:Non-fermented gram-negative bacteria, enterococcus and Candida albicans were the main pathogenic microorganisms in abdominal infection after pancreatoduodenectomy, and postoperative abdominal hemorrhage and pancreatic fistula were independent risk factors.
5.Recent advances in subtyping of biliary tract carcinoma
Zhiwen LIN ; Hongzhi LIU ; Yongyi ZENG
Journal of Surgery Concepts & Practice 2024;29(2):114-120
Biliary tract carcinoma exhibits high heterogeneity at the genomic,epigenetic,and molecular expression levels.The patients even with the same pathological morphology and clinical stage of biliary tract malignant tumors have substantial differences in the treatment response and prognosis.Traditional pathological histology and clinical classifications are no longer sufficient to meet the demands of the precision medicine era.Molecular subtyping has the potential to provide more personalized cancer treatment strategies.It not only helps to reveal the mechanisms of tumor development and accurately predict disease prognosis,but also plays a crucial role in guiding the development of novel targeted drugs and implementing targeted therapies for specific tumors.With the ongoing development of precision medicine,the role of molecular subtyping in cancer diagnosis,treatment option,and prognosis assessment is increasingly prominent.This paper systematically reviewed the recent progress in the molecular subtyping of biliary tract malignant tumors based on domestic and international clinical and basic research.
6.Screening and identification of the beneficiaries of adjuvant chemotherapy based on the prognostic model of intra-hepatic cholangiocarcinoma
Qizhu LIN ; Hongzhi LIU ; Tingfeng HUANG ; Ruilin FAN ; Weiping ZHOU ; Shuguo ZHENG ; Jianying LOU ; Yongyi ZENG
Journal of Surgery Concepts & Practice 2024;29(2):170-178
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.
7.Current status of surgery for portal hypertension in China: a national multi-center survey analysis
Lei ZHENG ; Haiyang LI ; Jizhou WANG ; Xiao LIANG ; Jian DOU ; Jitao WANG ; Qiang FAN ; Xiong DING ; Wenlong ZHAI ; Yun JIN ; Bo LI ; Songqing HE ; Tao LI ; Jun LIU ; Kui WANG ; Zhiwei LI ; Yongyi ZENG ; Yingmei SHAO ; Yang BU ; Dong SHANG ; Yong MA ; Cheng LOU ; Xinmin YIN ; Jiefeng HE ; Haihong ZHU ; Jincai WU ; Zhidan XU ; Dunzhu BASANG ; Jianguo LU ; Liting ZHANG ; Jianguo ZHAO ; Ling LYU ; Guoyue LYU ; Nim CHOI ; To Tan CHEUNG ; Meng LUO ; Wanguang ZHANG ; Xiaolong QI ; Xiaoping CHEN
Chinese Journal of Organ Transplantation 2023;44(3):152-159
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.
8.Advances and challenges of conversion therapy and neoadjuvant therapy in hepatocellular carcinoma
Yongyi ZENG ; Kongying LIN ; Qingjing CHEN
Chinese Journal of Digestive Surgery 2023;22(2):195-201
Hepatocellular carcinoma (HCC) is characterized by a low resection rate and a high postoperative recurrence rate. Conversion therapy and neoadjuvant therapy are effective stra-tegies to improve the long-term prognosis of patients with HCC. With the clinical application of new technologies and methods and the continuous emergence of new anti-tumor drugs, the conversion therapy and neoadjuvant therapy of HCC have ushered in an unprecedented development. At the same time, they are also facing many new challenges. Based on our own clinical experience and the latest progress in conversion therapy and neoadjuvant therapy of HCC, the authors classify and summarize the selection of treatment strategies and the challenges faced in HCC conversion therapy and neoadjuvant therapy.
9.A brief discussion of Glisson pedic-first approach in laparoscopic anatomical hepatectomy
Chinese Journal of Hepatobiliary Surgery 2023;29(7):481-485
With the continuous in-depth understanding of liver anatomy and the progress of surgical techniques, laparoscopic hepatectomy has been developed rapidly, especially the laparoscopic anatomic hepatectomy has become the most commonly surgical method. The dissection and treatment of liver Glisson pedicle is the core techniques of laparoscopic anatomic hepatectomy. The Glisson hepatic pedicle approach has been widely used in open and laparoscopic anatomical hepatectomy, especially in laparoscopic hepatectomy. The possible advantages over the traditional approach are still under debate, and there is no standard surgical approach for pedicle dissection to date. This article introduces Glisson pedicle approach and the advantages and clinical application of laparoscopic anatomical hepatectomy with Glisson pedicle approach.
10.Perioperative and long-term outcomes of laparoscopic versus open hepatectomy for hepatocellular carcinoma at specific sites of liver
Conglong SHEN ; Tingfeng HUANG ; Hongzhi LIU ; Liming HUANG ; Yongyi ZENG ; Kecan LIN
Chinese Journal of Hepatobiliary Surgery 2023;29(7):499-504
Objective:To compare the clinical efficacy of laparoscopic and open surgery in the treatment of hepatocellular carcinoma (HCC) at specific sites of liver.Methods:Data of patients with HCC undergoing hepatectomy in Mengchao Hepatobiliary Hospital of Fujian Medical University from September 2014 to May 2019 were retrospective analyzed. A total of 205 patients were enrolled, including 174 males and 31 females, aged (56.7±11.3) years. According to the surgical methods, patients were divided into laparoscopic group ( n=105) and open group ( n=100). The Child-Pugh score, maximum tumor diameter, tumor location, intraoperative blood loss, postoperative complication rate, liver function(glutamate transaminase, alanine transaminase, etc.) and length of hospital stay were compared between the two groups. Postoperative survival and recurrence were followed up. Survival curves and rates were analyzed by Kaplan-Meier and log-rank test. Results:There were no significant differences in Child-Pugh score, maximum tumor diameter, tumor location between the two groups. Compared to the open group, the laparoscopic group had a decreased blood loss [100 (50, 200) ml vs 150 (100, 200) ml], a lower incidence of postoperative complications[7.6%(8/105) vs 17.0%(17/100)], and a shorter hospital stay [(8.6±1.9) days vs (13.0±3.4) days](all P<0.05). The postoperative glutamate transaminase and alanine transaminase levels were lower in the laparoscopic group than those in the open group. The 1, 3, 5-year overall survival and recurrence-free survival were not significantly different between the two groups (χ 2=0.56, 0.21, P=0.456, 0.648). Conclusion:Laparoscopic surgery in the treatment of HCC at specific sites of liver is a safe, feasible and effective procedure.

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