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Table of Content

    30 September 2023, Volume 10 Issue 3
    Special topic
    Summary of research status of vascular intervention for primary liver cancer
    Fan Weijun
    2023, 10(3):  27-30. 
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    In 1978, Professor Yamada summarized his many years of experience in interventional therapy and pioneered the concept of transcatheter arterial chemoembolization (TACE), which marked a new stage of transvascular inter-ventional therapy. Thanks to the innovation of interventional devices and advances in treatment concepts in recent years, new local treatment modalities such as drug-eluting bead TACE (DEB-TACE) and transarterial radioembolization have emerged on the basis of traditional interventional therapy. Since 2018, with the advent of the era of targeted and immunotherapy, the comprehensive treatment model of transvascular interventional therapy combined with targeted and immunotherapy has gained widespread esteem and application, and the corresponding research advances are accelerating to change the treatment norms of liver cancer.
    Progress of vascular intervention combined with targeted therapy and immunotherapy for hepatocellular carcinoma
    Miao Jixuan, Jin Yong
    2023, 10(3):  31-37. 
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    Vascular interventional therapy represented by transcatheter arterial chemoembolization(TACE)and hepatic artery infusion chemotherapy is the main clinical treatment of unresectable hepatocellular carcinoma(HCC). Among them, TACE was used throughout the treatment of stage Ib to IIIb HCC. Targeted drugs such as multi-target tyrosine kinase inhibitors and angiogenesis inhibitors have played an important role in the treatment and adjuvant therapy of advanced liver cancer, and their clinical application has been quite mature. In recent years, immunotherapy led by immune checkpoint inhibitors has gradually become the latest hot spot in clinical research and application. Patients with high rates of HCC, most often found for the first time has been in the middle-late stage. For the treatment of such patients with HCC, existing vascular intervention targeted therapy and immunotherapy, a single treatment curative effect is not very desirable, this makes the combination therapy in treating HCC has become a new trend.
    The global status and development trends of radioembolization for liver cancer with yttrium-90: a bibliometric analysis
    Tang Fan, Luo Yingen, Ou Aixin, Xu Haoran, Li Xiao
    2023, 10(3):  38-47. 
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    Objective:To investigate the global status and development trends of radioembolization for liver cancer with yttrium-90 through bibliometric analysis.
    Method:All available data of the articles concerning radioembolization for liver cancer with yttrium-90, based on Web of Science database from 1991 to 2021, were analyzed with bibliometric analysis for creating visual knowledge maps of the countries, institutions, authors, journals and keywords by VOS viewer.
    Result:According to the search strategy and screening criteria, a total of 989 articles related to radioembolization for liver cancer with yttrium-90 were included in this study, involving 4 406 researchers from 1 055 institutions in 47 countries. The overall number of annual and cumulative publications significantly showed an upward trend, reaching a peak in 2021. United States dominated in national cooperation and number of articles. The top three institutions of total publications were Northwestern University, University of Navarra and Washington University. The top three authors of total publications and citations were Salem R, Lewandowski RJ and Mulcahy MF. Journal of Vascular and Interventional Radiology and other journals have played a vital role in promoting the development of this field. The top 10 keywords with occurrence frequency were radioembolization, hepatocellular carcinoma, yttrium-90, Y-90 microspheres, survival, cancer, liver metastases, microspheres, selective internal radiation therapy and internal radiation therapy.
    Conclusion:Radioembolization for liver cancer with yttrium-90 is one of the important research hotspots of liver cancer. Chinese researchers should not only pay attention to the frontier research in this field, but also actively carry out multicenter clinical research projects.
    The expression and clinical significance of PD-1 in peripheral blood of hepatocellular carcinoma treated with m-TACE
    Ren Zhizhong, Yue Yuanxun, Wang Yaqin, Wang Yajing, Zhang Yuewei
    2023, 10(3):  48-51. 
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    Objective:To explore the changes and significance of CD4+programmed death receptor 1(PD-1) and CD8+PD-1 in peripheral blood after hepatocellular carcinoma(HCC) patient streated with microparticles transcatheter arterial chemoembolization(m-TACE).
    Method:From 2021 to 2022, 20 patients with intermediate and advanced HCC with indications for m-TACE treatment were selected from the Hepatobiliary and Pancreatic Center of Beijing Tsinghua Chang Gung Hospital (HCC group), and 12 patients with non-alcoholic cirrhosis and 12 healthy volunteers were selected as cirrhosis group and healthy group. Flow cytometry was used to detect the expression of CD4+PD-1 and CD8+PD-1 in peripheral blood of healthy, cirrhotic, and liver cancer patients before and 1-2 weeks after m-TACE.
    Result:The expression of CD4+/CD8+PD-1 in peripheral blood of the HCC group was significantly higher than that of the liver cirrhosis group and the healthy group. After 1-2 weeks of m-TACE, the expression of CD4+/CD8+PD-1 of HCC patients decreased compared to before treatment(P<0.05). Patients with good therapeutic effects after m-TACE have lower expression of CD4+/CD8+PD-1 in peripheral blood(P<0.05).
    Conclusion:m-TACE treatment for HCC can reduce the expression of CD4+/CD8+PD-1 in peripheral blood.
    An experimental study on the automatic segmentation of organs in computed tomography images based on transfer learning and data augmentation
    Zhang Yumeng, Kang Wendi, Xi Junqing, Chi Chen, Yang Zhengqiang
    2023, 10(3):  52-57. 
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    Objective:To explore the role of transfer learning in the recognition, extraction, and automatic segmentation of anatomical structures in graphic software during machine deep learning, and the impact of data augmentation algorithms on the ability of transfer learning.
    Method:The Efficient Net b1 neural network is used as the backbone network for deep learning on the platform of HyVision Ablation Planning V1.0 graphic software. 51 sets of VX2 rabbit liver cancer model computed tomography (CT) scan images are used for transfer learning training through data augmentation. The graphic software's existing functions of identifying, extracting, and automatically segmenting organs on human abdominal CT images are reproduced on animal models. The differences in Dice and normalized surface Dice (NSD) values under different learning models, as well as the differences between the image quality of 3D reconstruction and the doctor-marked animal model training set, are compared.
    Result:From the model with "data augmentation without transfer learning" to the model with "data augmentation with transfer learning", the Dice index for automatic organ segmentation of VX2 rabbit CT scan images increased from 0.525 to 0.676, an increase of 28.76%, and the NSD index increased from 0.448 to 0.616, an increase of 37.50%. From the model with "no data augmentation but with transfer learning" to the model with "data augmentation with transfer learning", the Dice index for automatic organ segmentation of VX2 rabbit CT scan images increased from 0.502 to 0.676, an increase of 34.66%, and the NSD index increased from 0.459 to 0.616, an increase of 34.20%. This indicates that in the process of machine deep learning if studying new anatomical objects, transfer learning and data augmentation have equally important roles.
    Conclusion:In the process of machine deep learning, the function of transfer learning can obtain better graphic recognition, extraction, and automatic segmentation results with the help of "data augmentation" algorithm.
    Original article
    Long-term outcomes of radiotherapy combined with immune checkpoint blockade inhibitor and lenvatinib therapy in hepatocellular carcinoma with portal vein tumor thrombus
    Zhao Ying, Li Kewei, Yang Yanmei, Li Wei, Li Guangxin, Li Gong
    2023, 10(3):  58-63. 
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    Objective:To explore the efficacy and safety of radiotherapy combined with immune checkpoint blockade inhibitor(PD-1 inhibitor) and lenvatinib in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT).
    Methods:Between March 2018 to October 2020, patients diagnosed with unresectable HCC with PVTT who were admitted to our hospital were screened. In whom we included patients who met Barcelona Clinic Liver Cancer (BCLC) stage C, with Vp3 or Vp4 type portal vein tumor thrombus, and had no prior systemic treatment. The primary endpoints were 3-year overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) of PVTT. Kaplan-Meier analysis was used for survival analysis and log-rank test was performed.
    Results:47 patients were enrolled in the study, 39 of whom had Vp4 type PVTT. The median follow-up duration was 33.9 (range: 3.1-57.1) months. The median OS tuime was 11.9 (95%CI:7.5-16.3) months, and the 3-year OS rate was 18%. The median PFS tiume was 5 months(95%CI:3.5-6.5 months) , and the 3-year PFS rate was 10%. Among patients with Vp4 type PVTT, the median OS time was 9.4 months (95%CI:8.3-10.5 months) , and the 3-year OS rate was 13%. The median PFS time was 4.9 months (95%CI:3.2-6.6 months), and the 3-year PFS rate was 9%. The objective response rate of PVTT was 75%. No grade 3 or higher adverse events occurred.
    Conclusions:Radiotherapy combined with PD-1 inhibitor and lenvatinib in HCC patients with PVTT demonstrated favorable long-term efficacy and low toxicity. This triple combination therapy may become one of the competitive treatment options for HCC with BCLC stage C.
    Recognition of bone metastasis driving genes in hepatocellular carcinoma by machine learning and analysis of in external-beam radiotherapy
    Wang Yu, Tong Liexing, Kang Wanying, Ding Xin, Qian Hesheng
    2023, 10(3):  64-75. 
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    Objective:To identify the driving genes of hepatocellular carcinoma with bone metastasis (HCC-BM) by machine learning and to explore the effect of external-beam radiotherapy (EBRT) on the expression level of driving genes.
    Methods:GSE14520 and GSE84402 data sets in Gene Expression Omnibus database were combined as test sets, and GSE121248 andGSE54236 data sets were used as validation sets respectively. The least absolute shrinkage and selection operator and support vector machine-regression feature elimination were performed to screen the key differentially expressed genes,and the intersection with HCC-BM related genes in the GeneCards database obtained HCC-BM driving genes. CIBERSORT evaluated the correlation between HCC-BM driver gene and immune cell infiltration.The 22 HCC-BM patients admitted to our hospital from 2020 to 2021 were selected as the study group. In the same period, 22 healthy people with normal physical examinations in our hospital were selected as the control group. The changes in HCC-BM driver gene expression before and after EBRT were compared, and the relationship between HCC-BM driver gene expression and and relationship with ASPM expression levels and pain relief.
    Results:Four HCC-BM driving genes were identified,it is respectively assembly factor for spindle microtubules (ASPM), C-type lectin domain family 4 member M (CLEC4M), extracellular matrix protein 1 (ECM1), and ficolin 2 (FCN2). The expression of ASPM in normal liver tissue was lower than that in HCC tissue (P<0.05), and the expression of clec4m, ECM1, and FCN2 was higher than that in HCC tissue (P<0.05). The same results were obtained in both validation sets GSE121248 and GSE54236. The prognosis of HCC patients with high ASPM expression is poor, while patients with low CLEC4M, ECM1 and FCN2 expression are better. ASPM was positively correlated with macrophages m2; CLEC4M was positively correlated with macrophages M2, neutrophils, and M1 macrophages; FCN2 was negatively correlated with macrophages M0. The expression of serum ASPM in 22 patients with HCC-BM was higher than that in the healthy control group (P < 0.05), and the expression of FCN2 was lower than that in the healthy control group (P<0.05). After EBRT, the expression level of serum ASPM in HCC-BM patients decreased (P<0.05). The expression level of serum ASPM in patients with complete remission was lower than that in patients with partial remission.
    Conclusions:ASPM, CLEC4M, ECM1, and FCN2 may be involved in the pathogenesis of HCC-BM. Among them, ASPM may be related to the effect of EBRT. Further exploration of driver genes is helpful to develop therapeutic targets, improve the effect of EBRT and then improve the prognosis.
    Review
    The progress of radiotherapy in hepatocellular carcinoma with portal vein tumor thrombus
    Xin Lingxia, Xu Xin, Zhai Yirui, Deng Min, Chen Bo
    2023, 10(3):  76-82. 
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    With a poor prognosis, hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) progresses rapidly and is life-threatening. Currently, the treatment options for HCC with PVTT mainly include transcatheter arterial intervention, radiotherapy, targeted therapy, immunotherapy, surgery, etc., but there is still no standard treatment strategy. Intensity-modulated radiotherapy can significantly raise the prescribed dose with the minimum dose delivery to the remaining liver, ensuring the safety of radiotherapy for HCC. Previous clinical studies have confirmed the safety and efficacy of radiotherapy for HCC with PVTT. With the deepening of the multidisciplinary treatment concept, radiotherapy combined with other treatments for HCC with PVTT has been continuously explored. Focusing on radiotherapy for HCC with PVTT, this review mainly discusses the progress of multidisciplinary combined therapy including radiotherapy, surgery, interventional therapy, targeted therapy, and immunotherapy.
    Research progress of radiotherapy for extrahepatic cholangiocarcinoma
    Yang Yongjing, Liu Tingting, Liu Shixin
    2023, 10(3):  83-88. 
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    Extrahepatic cholangiocarcinoma has a high risk of local recurrence after surgical resection, so adjuvant therapy is needed to improve relapse-free survival and overall survival, among which radiotherapy is an important treatment. This article reviews the role of adjuvant radiotherapy, neoadjuvant radiotherapy, radical radiotherapy and palliative radiotherapy in the treatment of extrabiliary cholangiocarcinoma. Some studys showed that postoperative adjuvant chemoradiotherapy could improve the disease-free survival and overall survival of patients with extrahepatic cholangiocarcinoma. The results of liver transplantation alone have been disappointing for unresectable hilar cholangiocarcinoma, and neoadjuvant chemoradiotherapy combined with liver transplantation has been explored with encouraging results in unresectable hilar cholangiocarcinoma. For unresectable extrahepatic cholangiocarcinoma, radical chemoradiotherapy prolongs survival. Stenting combined with palliative radiotherapy can improve stent patency and improve the quality of life of patients. Radiotherapy combined with effective multimodal therapy holds promise for improving the survival rate of extrahepatic cholangiocarcinoma.
    Nursing field
    Effect of narrative nursing model based on evidence-based medicine on early ambulation and compliance of patient
    Pan Wenbing, Lu Yao, Li Yan, Shi Zhuolin, Liu Yudi
    2023, 10(3):  89-92. 
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    Objective:To explore the effect of narrative nursing model based on evidence-based medicine on early ambulation and compliance of patients with primary liver cancer after transcatheter arterial chemoembolization (TACE).
    Methods:From December 2019 to February 2022, 70 patients with primary liver cancer undergoing TACE in our hospital were randomly divided into the control group (n=35) and the observation group (n=35) with conventional perioperative nursing and narrative nursing model based on evidence-based medicine. The early ambulation and early recovery, compliance before and after receiving nursing, quality of life score changes and postoperative complications were compared between the two groups.
    Results:The observation group had shorter first time out of bed activity and longer activity duration than the control group (P<0.05). The observation group had shorter anal exhaust, general food recovery, and hospitalization time in sequence compared to the control group (P<0.05). After nursing, the compliance and QLICP-LI scores of the observation group were higher than those of the control group (P<0.05). Compared with the control group, the observation group had a lower incidence of postoperative complications (P<0.05).
    Conclusion:The narrative nursing model based on evidence-based medicine for patients with primary liver cancer after TACE can shorten the time of early ambulation, promote postoperative recovery, reduce the occurrence of postoperative complications, improve patient compliance, and improve the quality of life.
    Medical education
    Visualization research of multivariate statistics and social network analysis for change in the medical education in surgery and liver surgery
    Li Bingmin, Gong Shuyue, Ran Zikun, Meng Xuan, Tang Haowen
    2023, 10(3):  97-103. 
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    Objective:To study the subject domain knowledge of surgery and liver surgery education using multiple statistical and social network analysis, then to build visualized knowledge-mapping and predict the future development trend.
    Methods:Pubmed database was systematically searched using key words “(education, student, general surgery, liver surgery, and hepatobiliary surgery)” from 2010 to 2022. A total of 5157 articles were returned. The co-occurrence matrix was built by the Bicomb. Transformation, dimensionality reduction and clustering of the co-occurrence matrix were analyzed by SPSS 22.0, and visualized network was drawn by Ucinet 6.0.
    Results:The visualized domain knowledge-mapping of surgery and liver surgery education was successfully built. By comparing the time periods before and after COVID-19, the current study explored the impact of epidemic situation on surgery and liver surgery education. Computer aided technology and virtual reality technology have become the technical driving force of liver surgery education. At the same time, as a subject that emphasizes clinical practice and operation, the monitoring of teaching quality and the evaluation and certification of training effect have become the key contents of liver surgery education. Moreover, the epidemic situation has brought changes to the education mode of liver surgery.The combination of endoscopic and endoscopic surgery, 3D reconstruction and visualization technology, digital surgery technology and surgical navigation system can further promote the teaching of surgery in the epidemic situation.
    Conclusions:A variety of advanced teaching technologies have been applied in surgery education in the epidemic situation. The visualized domain knowledge-mapping has promoted the rapid development of the surgical teaching quality evaluation system, and new teaching technologies are also in urgent need of application in general surgery education.