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1
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Cai Y, Wang W, Jiao Q, Hu T, Ren Y, Su X, Li Z, Feng M, Liu X, Wang Y. Nanotechnology for the Diagnosis and Treatment of Liver Cancer. Int J Nanomedicine 2024; 19:13805-13821. [PMID: 39735328 PMCID: PMC11681781 DOI: 10.2147/ijn.s490661] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Accepted: 12/04/2024] [Indexed: 12/31/2024] Open
Abstract
Liver cancer has become a major global health challenge due to its high incidence, high rate of late diagnosis and limited treatment options. Although there are many clinical treatments available for liver cancer, the cure rate is still very low, and now researchers have begun to explore new aspects of liver cancer treatment, and nanotechnology has shown great potential for improving diagnostic accuracy and therapeutic efficacy and is therefore a promising treatment option. In diagnosis, nanomaterials such as gold nanoparticles, magnetic nanoparticles, and silver nanoparticles can realize highly sensitive and specific detection of liver cancer biomarkers, supporting diagnosis and real-time monitoring of the disease process. In terms of treatment, nanocarriers can realize precise targeted delivery of drugs, improve the bioavailability of liver cancer therapeutic drugs and reduce systemic toxic side effects. In addition, advanced technologies such as nanoparticle-based photothermal therapy and photodynamic therapy provide innovative solutions to overcome drug resistance and local tumor ablation. Therefore, in this paper, we will introduce nanotechnology for hepatocellular carcinoma in terms of tumor marker detection, targeted drug delivery, and synergistic PDT/CDT therapy.
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Affiliation(s)
- Yuxuan Cai
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China
| | - Weiwei Wang
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China
| | - Qinlian Jiao
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China
| | - Tangbin Hu
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China
| | - Yidan Ren
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China
| | - Xin Su
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250033, People’s Republic of China
| | - Zigan Li
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250033, People’s Republic of China
| | - Maoxiao Feng
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China
| | - Xiaoyan Liu
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China
| | - Yunshan Wang
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China
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Zhang K, Liu M, Cong L, He X, Xu Y, Wang Q, Li C. A Comparative Study of Antitumor Immunity Induced by Radiofrequency Microwave and Cryoablation in Hepatocellular Carcinoma. Appl Biochem Biotechnol 2024; 196:4088-4104. [PMID: 37889403 DOI: 10.1007/s12010-023-04760-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/19/2023] [Indexed: 10/28/2023]
Abstract
PURPOSE This study aimed to compare the immune responses induced by microwave ablation (MWA), radiofrequency ablation (RFA), and cryoablation (CRYO) in hepatocellular carcinoma (HCC) and identify differences in immune responses and the timing of immune changes. MATERIALS AND METHODS A bilateral subcutaneous model was established in C57 mice, and the successfully modeled mice were divided into the microwave (n = 15), radiofrequency (n = 15), CRYO (n = 15), control (n = 9), and blank groups (n = 3). Mice in the control group were dissected before ablation, whereas mice in the three ablation groups underwent ultrasound-guided ablation of one axillary tumor. Three mice were sacrificed and dissected at 1-4 weeks after ablation. After tissue processing, flow cytometry was used to detect the levels of CD8 + T and regulatory T (Treg) cells in the tissue, and western blotting was used to assess the level of programmed cell death ligand 1 (PD-L1) protein in the tumor tissue. RESULTS The pattern of immune changes after the three types of ablation was consistent, with immune changes occurring at 3-4 weeks. CRYO induced the most significant increase in the percentage of CD8 + T cells. There were no significant differences in the levels of Treg cells and the level of PD-L1 protein among the three types of ablation (p > 0.05), but the decline in Treg cells and PD-L1 protein level caused by CRYO was the most pronounced. CONCLUSION In the HCC mouse model, the immune changes following the three types of ablation were consistent, with immune changes occurring at 3-4 weeks. Among them, CRYO elicited the strongest adaptive immune response, and RFA outperformed MWA.
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Affiliation(s)
- Kai Zhang
- Department of Ultrasound, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Ming Liu
- Department of Interventional MRI Shandong Provincial Hospital, Shandong First Medical University, Jinan, Shandong, China
| | - Lin Cong
- Department of Interventional Ultrasound Shandong Provincial Hospital Affiliated to Shandong, First Medical University, Jinan, Shandong, China
| | - Xiangmeng He
- Department of Interventional MRI Shandong Provincial Hospital, Shandong First Medical University, Jinan, Shandong, China
| | - Yujun Xu
- Department of Interventional MRI Shandong Provincial Hospital, Shandong First Medical University, Jinan, Shandong, China
| | - Qingwen Wang
- Department of Medical Image Shandong Provincial Hospital, Shandong First Medical University, Jinan, Shandong, China
| | - Chengli Li
- Department of Interventional MRI Shandong Provincial Hospital, Shandong First Medical University, Jinan, Shandong, China.
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Jiang D, Ma X, Zhang X, Cheng B, Wang R, Liu Y, Zhang X. New techniques: a roadmap for the development of HCC immunotherapy. Front Immunol 2023; 14:1121162. [PMID: 37426674 PMCID: PMC10323423 DOI: 10.3389/fimmu.2023.1121162] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Accepted: 06/09/2023] [Indexed: 07/11/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. The absence of effective early diagnostic methods and the limitations of conventional therapies have led to a growing interest in immunotherapy as a novel treatment approach for HCC. The liver serves as an immune organ and a recipient of antigens from the digestive tract, creating a distinctive immune microenvironment. Key immune cells, including Kupffer cells and cytotoxic T lymphocytes, play a crucial role in HCC development, thus offering ample research opportunities for HCC immunotherapy. The emergence of advanced technologies such as clustered regularly interspaced short palindromic repeats (CRISPR) and single-cell ribonucleic acid sequencing has introduced new biomarkers and therapeutic targets, facilitating early diagnosis and treatment of HCC. These advancements have not only propelled the progress of HCC immunotherapy based on existing studies but have also generated new ideas for clinical research on HCC therapy. Furthermore, this review analysed and summarised the combination of current therapies for HCC and the improvement of CRISPR technology for chimeric antigen receptor T cell therapy, instilling renewed hope for HCC treatment. This review comprehensively explores the advancements in immunotherapy for HCC, focusing on the use of new techniques.
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Li G, Liu Y, Zhang Y, Xu Y, Zhang J, Wei X, Zhang Z, Zhang C, Feng J, Li Q, Wang G. A Novel Ferroptosis-Related Long Non-Coding RNA Prognostic Signature Correlates With Genomic Heterogeneity, Immunosuppressive Phenotype, and Drug Sensitivity in Hepatocellular Carcinoma. Front Immunol 2022; 13:929089. [PMID: 35874689 PMCID: PMC9304774 DOI: 10.3389/fimmu.2022.929089] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 06/13/2022] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) with high heterogeneity is a common malignancy worldwide, but effective treatments are limited. Ferroptosis plays a critical role in tumors as a novel iron-dependent and reactive oxygen species-reliant type of cell death. Several studies have shown that long non-coding RNAs (lncRNAs) can drive HCC initiation and progression. However, the prognostic value of ferroptosis-related lncRNAs in patients with HCC has not been explored comprehensively. Gene set variation analysis (GSVA) based on gene set and RNA-seq profiles obtained from public databases indicated that ferroptosis is suppressed in HCC patients. Ferroptosis-related differentially expressed lncRNAs were screened by Pearson’s test. Univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox regression were performed to establish a novel five ferroptosis-related lncRNA signature in the training cohort with 60% patients, which was further verified in the testing cohort with 40% patients. Dimensionality reduction analysis, Kaplan–Meier curve, receiver operating characteristic (ROC) curve, independent prognostic analysis, and stratification analysis confirmed that our signature had a high clinical application value in predicting the overall survival of HCC patients. Compared to the clinicopathological factors and the other four published HCC prognostic signatures, the current risk model had a better predictive value. The comparison results of functional enrichment, tumor immune microenvironment, genomic heterogeneity, and drug sensitivity between the high- and low-risk groups showed that the risk score is associated with extensive genomic alterations, immunosuppressive tumor microenvironment, and clinical treatment response. Finally, cell experiments showed that silencing LNCSRLR expression inhibited the growth, proliferation, migration, and invasion of the HCC cell line. Thus, the model can function as an efficient indicator for predicting clinical prognosis and treatment of anticancer drugs in HCC patients.
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Affiliation(s)
- Guanghao Li
- Department of Bone and Soft Tissue Tumors, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
- Department of Hepatobiliary Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
| | - Yongheng Liu
- Department of Bone and Soft Tissue Tumors, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
| | - Yanting Zhang
- Department of Bone and Soft Tissue Tumors, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
| | - Yao Xu
- Department of Bone and Soft Tissue Tumors, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
| | - Jin Zhang
- Department of Bone and Soft Tissue Tumors, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
| | - Xianfu Wei
- Department of Bone and Soft Tissue Tumors, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
| | - Zhongmin Zhang
- Department of Bone and Soft Tissue Tumors, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
| | - Chao Zhang
- Department of Bone and Soft Tissue Tumors, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
| | - Jinyan Feng
- Department of Bone and Soft Tissue Tumors, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
- *Correspondence: Guowen Wang, ; Qiang Li, ; Jinyan Feng,
| | - Qiang Li
- Department of Hepatobiliary Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
- *Correspondence: Guowen Wang, ; Qiang Li, ; Jinyan Feng,
| | - Guowen Wang
- Department of Bone and Soft Tissue Tumors, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
- *Correspondence: Guowen Wang, ; Qiang Li, ; Jinyan Feng,
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Altannavch N, Zhou X, Khan MA, Ahmed A, Naranmandakh S, Fu JJ, Chen HC. Anti-oxidant and Anticancerous Effect of Fomitopsis officinalis (Vill. ex Fr. Bond. et Sing) Mushroom on Hepatocellular Carcinoma Cells In Vitro through NF-kB Pathway. Anticancer Agents Med Chem 2022; 22:1561-1570. [PMID: 34102992 DOI: 10.2174/1871520621666210608101152] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 02/19/2021] [Accepted: 03/05/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Fomitopsis officinalis (Vill. ex Fr. Bond. et Sing) is a medicinal mushroom, commonly called 'Agarikon'; it has traditionally been used to treat cough and asthma in the Mongolian population. OBJECTIVE The objective of the study was to examine the significance of biological activity of F. officinalis and evaluation of the antioxidant activity and anticancer activity of six fractions of F. officinalis residues (Fo1-powder form dissolved in ethanol, Fo2-petroleum ether residue, Fo3-chloroformic, Fo4-ethylacetate, Fo5-buthanolic, and Fo6-waterethanolic) against hepatocellular carcinoma cells. METHODS We performed in vitro studies of cell proliferation and viability assay, annexin V-FITC/Propidium Iodide assay, and NF-kB signaling pathway by immunoblot analysis. RESULTS Our findings revealed that all six fractions/extracts have antioxidant activity, and somehow, they exert anticancerous effects against cancer cells. In cancerous cell lines (HepG2 and LO2), Fo3 chloroformic extract promoted the cancer cell apoptosis and cell viability, activated G2/M-phase cell cycle, and selectively induced NF-kB proteins, revealing as a novel antitumor extract. CONCLUSION This study reports that Fo3-chloroformic extract is rich in antitumor activity, which was previously not investigated in cancer. To develop the impact of F. officinalis among natural products to treat/prevent oxidative stress disorders or cancers, further examinations of F. officinalis are needed to develop new natural drugs to treat cancer. However, this study assessed only one extract, Fo3-chloroformic, which has a significant impact against cancer cell lines.
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Affiliation(s)
- Nyamsambuu Altannavch
- Department of Biochemistry and Molecular Biology, School of Life Sciences, Central South University, 172 Tongzipo Road, Changsha, Hunan 410013, China
| | - Xi Zhou
- Department of Biochemistry and Molecular Biology, School of Life Sciences, Central South University, 172 Tongzipo Road, Changsha, Hunan 410013, China
| | - Md Asaduzzaman Khan
- Department of Biochemistry and Molecular Biology, School of Life Sciences, Central South University, 172 Tongzipo Road, Changsha, Hunan 410013, China
- Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Ashfaque Ahmed
- Department of Biochemistry and Molecular Biology, School of Life Sciences, Central South University, 172 Tongzipo Road, Changsha, Hunan 410013, China
| | - Shinen Naranmandakh
- School of Arts and Sciences, National University of Mongolia, Ulaanbaatar 14201, Mongolia
| | - Jun-Jiang Fu
- Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Han-Chun Chen
- Department of Biochemistry and Molecular Biology, School of Life Sciences, Central South University, 172 Tongzipo Road, Changsha, Hunan 410013, China
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6
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Xu L, Jian X, Liu Z, Zhao J, Zhang S, Lin Y, Xie L. Construction and Validation of an Immune Cell Signature Score to Evaluate Prognosis and Therapeutic Efficacy in Hepatocellular Carcinoma. Front Genet 2021; 12:741226. [PMID: 34646307 PMCID: PMC8503558 DOI: 10.3389/fgene.2021.741226] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Accepted: 08/30/2021] [Indexed: 12/24/2022] Open
Abstract
Background: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy with high morbidity and mortality worldwide. Tumor immune microenvironment (TIME) plays a pivotal role in the outcome and treatment of HCC. However, the effect of immune cell signatures (ICSs) representing the characteristics of TIME on the prognosis and therapeutic benefit of HCC patients remains to be further studied. Materials and methods: In total, the gene expression profiles of 1,447 HCC patients from several databases, i.e., The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium, and Gene Expression Omnibus, were obtained and applied. Based on a comprehensive collection of marker genes, 182 ICSs were evaluated by single sample gene set enrichment analysis. Then, by performing univariate and multivariate Cox analysis and random forest modeling, four significant signatures were selected to fit an immune cell signature score (ICSscore). Results: In this study, an ICSscore-based prognostic model was constructed to stratify HCC patients into high-risk and low-risk groups in the TCGA-LIHC cohort, which was successfully validated in two independent cohorts. Moreover, the ICSscore values were found to positively correlate with the current American Joint Committee on Cancer staging system, indicating that ICSscore could act as a comparable biomarker for HCC risk stratification. In addition, when setting the four ICSs and ICSscores as features, the classifiers can significantly distinguish treatment-responding and non-responding samples in HCC. Also, in melanoma and breast cancer, the unified ICSscore could verify samples with therapeutic benefits. Conclusion: Overall, we simplified the tedious ICS to develop the ICSscore, which can be applied successfully for prognostic stratification and therapeutic evaluation in HCC. This study provides an insight into the therapeutic predictive efficacy of prognostic ICS, and a novel ICSscore was constructed to allow future expanded application.
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Affiliation(s)
- Linfeng Xu
- School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai, China.,Shanghai Center for Bioinformation Technology, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China
| | - Xingxing Jian
- Shanghai Center for Bioinformation Technology, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China.,Bioinformatics Center, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Zhenhao Liu
- Shanghai Center for Bioinformation Technology, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China.,Bioinformatics Center, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Jingjing Zhao
- Shanghai Center for Bioinformation Technology, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China.,College of Food Science and Technology, Shanghai Ocean University, Shanghai, China
| | - Siwen Zhang
- Shanghai Center for Bioinformation Technology, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China.,College of Food Science and Technology, Shanghai Ocean University, Shanghai, China
| | - Yong Lin
- School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai, China
| | - Lu Xie
- Shanghai Center for Bioinformation Technology, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China.,Bioinformatics Center, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.,College of Food Science and Technology, Shanghai Ocean University, Shanghai, China
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7
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Safarpour AR, Askari H, Ejtehadi F, Azarnezhad A, Raeis-Abdollahi E, Tajbakhsh A, Abazari MF, Tarkesh F, Shamsaeefar A, Niknam R, Sivandzadeh GR, Lankarani KB, Ejtehadi F. Cholangiocarcinoma and liver transplantation: What we know so far? World J Gastrointest Pathophysiol 2021; 12:84-105. [PMID: 34676129 PMCID: PMC8481789 DOI: 10.4291/wjgp.v12.i5.84] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 04/28/2021] [Accepted: 08/11/2021] [Indexed: 02/06/2023] Open
Abstract
Cholangiocarcinoma (CCA) is a type of cancer with increasing prevalence around the world that originates from cholangiocytes, the epithelial cells of the bile duct. The tumor begins insidiously and is distinguished by high grade neoplasm, poor outcome, and high risk for recurrence. Liver transplantation has become broadly accepted as a treatment option for CCA. Liver transplantation is expected to play a crucial role as palliative and curative therapy for unresectable hilar CCA and intrahepatic CCA. The purpose of this study was to determine which cases with CCA should be subjected to liver transplantation instead of resection, although reported post-transplant recurrence rate averages approximately 20%. This review also aims to highlight the molecular current frontiers of CCA and directions of liver transplantation for CCA.
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Affiliation(s)
- Ali Reza Safarpour
- Department of Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz 7134814336, Iran
| | - Hassan Askari
- Department of Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz 7134814336, Iran
| | - Farshid Ejtehadi
- The Princess Alexandra Hospital HNS Trust, Harlow, Essex CM20 1QX, United Kingdom
| | - Asaad Azarnezhad
- Liver and Digestive Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj 6617913446, Iran
| | - Ehsan Raeis-Abdollahi
- Department of Basic Medical Sciences, Qom Medical Branch, Islamic Azad University, Qom, Iran
| | - Amir Tajbakhsh
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz 7134814336, Iran
| | - Mohammad Foad Abazari
- Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran 1417653761, Iran
| | - Firoozeh Tarkesh
- Department of Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz 7134814336, Iran
| | - Alireza Shamsaeefar
- Shiraz Organ Transplant Center, Shiraz University of Medical Sciences, Shiraz 7193711351, Iran
| | - Ramin Niknam
- Department of Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz 7134814336, Iran
| | - Gholam Reza Sivandzadeh
- Department of Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz 7134814336, Iran
| | | | - Fardad Ejtehadi
- Department of Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz 7134814336, Iran
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Woodford R, Brungs D, Leighton C, Grimison P, Sjoquist KM, Becker T, Robinson S, Gebski V, Wilson K, Chantrill L, Aghmesheh M. Combination chemotherapy with NAB ® -paclitaxel and capecitabine for patients with advanced biliary tract cancer (NAP-CAPABIL Pilot Study). Asia Pac J Clin Oncol 2021; 18:e220-e226. [PMID: 34180586 DOI: 10.1111/ajco.13599] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Accepted: 03/04/2021] [Indexed: 01/17/2023]
Abstract
BACKGROUND Advanced biliary tract cancer (ABTC) is a highly aggressive malignancy, with a 5-year overall survival of < 10%. Although preliminary evidence suggests a role of targeted treatments or immunotherapy in a subset of patients, chemotherapy remains the standard second-line treatment in the majority. We conducted a pilot study of second-line chemotherapy with capecitabine and nab-paclitaxel after failure of gemcitabine and platinum. METHODS Eligible patients had histologically proven, unresectable biliary tract cancer, which had progressed on a gemcitabine/platinum doublet. In this single-arm, multicenter trial, all patients received capecitabine (825 mg/m2 bd PO D1-14 q21d) and nab-paclitaxel (125 mg/m2 IV D1,8 q21d) until progression or unacceptable toxicity. The primary objective was feasibility of delivering the proposed regimen, with secondary objectives of disease control measures and QOL outcomes. RESULTS Ten patients were enrolled between 2015 and 2016 from four cancer centers in NSW. Treatment was generally well tolerated with grade III toxicities in five patients (including infection, cholangitis, obstruction, and intestinal perforation) and no grade IV toxicity. Median treatment duration was 4.3 months, with a disease control rate of 80% (8/10), and median progression-free and overall survival of 5.7 and 12.1 months, respectively. Quality of life data and specimens for translational research have been collected. CONCLUSIONS Our pilot study demonstrates that combination of capecitabine and nab-paclitaxel is feasible as a second-line treatment in ABTC. Adequate safety and promising early efficacy signals make further assessment of the combination in a formal phase II or III trial reasonable. CLINICAL TRIAL INFORMATION ACTRN12615000504516.
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Affiliation(s)
| | - Daniel Brungs
- Illawarra Health and Medical Research Institute and School of Medicine, University of Wollongong, Wollongong, New South Wales, Australia.,Illawarra Cancer Care Centre, The Wollongong Hospital, Wollongong, New South Wales, Australia
| | - Carly Leighton
- Illawarra Cancer Care Centre, The Wollongong Hospital, Wollongong, New South Wales, Australia
| | - Peter Grimison
- Chris O'Brien Lifehouse, Sydney, New South Wales, Australia.,NHMRC Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, Australia
| | - Katrin M Sjoquist
- St George Hospital, Sydney, New South Wales, Australia.,NHMRC Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, Australia
| | - Therese Becker
- Centre for Circulating Tumour Cell Diagnostics and Research, Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia
| | - Samuel Robinson
- Illawarra Cancer Care Centre, The Wollongong Hospital, Wollongong, New South Wales, Australia
| | - Val Gebski
- NHMRC Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, Australia
| | - Kate Wilson
- NHMRC Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, Australia
| | - Lorraine Chantrill
- Illawarra Cancer Care Centre, The Wollongong Hospital, Wollongong, New South Wales, Australia
| | - Morteza Aghmesheh
- Illawarra Health and Medical Research Institute and School of Medicine, University of Wollongong, Wollongong, New South Wales, Australia.,Illawarra Cancer Care Centre, The Wollongong Hospital, Wollongong, New South Wales, Australia
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9
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Peng Y, Liu C, Li M, Li W, Zhang M, Jiang X, Chang Y, Liu L, Wang F, Zhao Q. Identification of a prognostic and therapeutic immune signature associated with hepatocellular carcinoma. Cancer Cell Int 2021; 21:98. [PMID: 33568167 PMCID: PMC7877064 DOI: 10.1186/s12935-021-01792-4] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 01/27/2021] [Indexed: 02/07/2023] Open
Abstract
Background Hepatocellular carcinoma (HCC) is one of the most prevalent and inflammation-associated cancers. The tumor microenvironment (TME) plays an essential role in HCC development and metastasis, leading to poor prognosis. The overall TME immune cells infiltration characterizations mediated by immune-related genes (IRGs) remain unclear. In this study, we aimed to investigate whether immune-related genes could be indicators for the prognosis of HCC patients and TME cell infiltration characterization as well as responses to immunotherapy. Methods We obtained differentially expressed immune-related genes (DE IRGs) between normal liver tissues and liver cancer tissues from The Cancer Genome Atlas (TCGA) database. To identify the prognostic genes and establish an immune risk signature, we performed univariable Cox regression survival analysis and the Least Absolute Shrinkage and Selector Operation (LASSO) regression based on the DE IRGs by robust rank aggregation method. Cox regression analysis was used to identify independent prognostic factors in HCC. We estimated the immune cell infiltration in TME via CIBERSORT and immunotherapy response through TIDE algorithm. Results We constructed an immune signature and validated its predictive capability. The immune signature included 7 differentially expressed IRGs: BIRC5, CACYBP, NR0B1, RAET1E, S100A8, SPINK5, and SPP1. The univariate and multivariate cox analysis showed that the 7-IRGs signature was a robust independent prognostic factor in the overall survival of HCC patients. The 7-IRG signature was associated with some clinical features, including gender, vascular invasion, histological grade, clinical stage, T stage. We also found that the 7-IRG signature could reflect the infiltration characterization of different immunocytes in the tumor microenvironment (TME) and had a good correlation with immune checkpoint molecules, revealing that the poor prognosis might be partly due to immunosuppressive TME. The Tumour Immune Dysfunction and Exclusion (TIDE) analysis data showed that the 7-IRG signature had great potential for indicating the immunotherapy response in HCC patients. The mutation analysis demonstrated a significant difference in the tumor mutation burden (TMB) between the high- and low-risk groups, partially explaining this signature's predictive value. Conclusion In a word, we constructed and validated a novel, immune-related prognostic signature for HCC patients. This signature could effectively indicate HCC patients' survival and immunotherapy response. And it might act as potential immunotherapeutic targets for HCC patients.
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Affiliation(s)
- Yanan Peng
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China.,Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan, China
| | - Chang Liu
- Department of Obstetrics, Renmin Hospital of Wuhan University, Wuhan, China
| | - Mengting Li
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China.,Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan, China
| | - Wenjie Li
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China.,Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan, China
| | - Mengna Zhang
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China.,Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan, China
| | - Xiang Jiang
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China.,Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan, China
| | - Ying Chang
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China.,Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan, China
| | - Lan Liu
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China.,Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan, China
| | - Fan Wang
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China. .,Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan, China.
| | - Qiu Zhao
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China. .,Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan, China.
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10
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Zhou N, Hu A, Shi Z, Wang X, Zhu Q, Zhou Q, Ma J, Zhao F, Kong W, He J. Inter-observer agreement of computed tomography and magnetic resonance imaging on gross tumor volume delineation of intrahepatic cholangiocarcinoma: an initial study. Quant Imaging Med Surg 2021; 11:579-585. [PMID: 33532258 PMCID: PMC7779918 DOI: 10.21037/qims-19-1093] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2019] [Accepted: 09/28/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver tumor, and local radiotherapy has a positive effect on patients with an unresectable tumor. Accurate delineation of gross tumor volume (GTV) is crucial to improve the efficacy of radiotherapy. The purpose of this article was to evaluate the consistency of CT, diffusion weighted imaging (DWI) and Gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced MRI on GTV delineation of ICC. METHODS Fourteen patients with ICC underwent CT (Plain and Portal, CT scans before and 70 s after the injection of Omnipaque, respectively), DWI, and Gd-EOB-DTPA-enhanced MRI (EOB 70 s and EOB 15 min, mDIXON scans at 70 s and 15 min after the injection of Gd-EOB-DTPA, respectively) examinations before radiotherapy. Volumes of GTV delineation on CT and MRI images were recorded. Dice similarity coefficient (DSC) was calculated to evaluate the spatial overlap. RESULTS Tumor volume on DWI and EOB 15 min were larger than that on EOB 70 s significantly (both P=0.004). DSC of DWI was significantly larger than that of other CT and MRI sequences (all P≤0.002). DSC of EOB 15 min tended to be larger than that of other CT sequences and EOB 70 s, however, without significances (all P>0.005). Significant correlation was found between DSC and tumor volume (R=0.35, P=0.003). CONCLUSIONS DWI had significantly higher agreement on GTV delineation of ICC. GTV delineations of ICC on Gd-EOB-DTPA-enhanced MRI showed excellent inter-observer agreement. Fusion of CT and MRI images should be considered to improve the accuracy of GTV delineation.
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Affiliation(s)
- Nan Zhou
- Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Anning Hu
- Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Zhihao Shi
- Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Xiaolu Wang
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China
| | - Qiongjie Zhu
- Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Qun Zhou
- Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Jun Ma
- Department of Mathematics, Nanjing University of Science and Technology, Nanjing, China
| | - Feng Zhao
- Department of Radiation Oncology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Weiwei Kong
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China
- Department of Oncology of Yizheng Hospital, Nanjing Drum Tower Hospital Group, Yizheng, China
| | - Jian He
- Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
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11
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Pitchumoni CS, Ravindran N. Biliary Neoplasms. GERIATRIC GASTROENTEROLOGY 2021:1437-1448. [DOI: 10.1007/978-3-030-30192-7_105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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12
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Abstract
Cholangiocarcinoma is the second most common primary malignancy of the liver. This review will focus on the mass-forming intrahepatic type of this disease and discuss the role of medical, surgical, and radiation oncology in managing this difficult disease. A global understanding to the management of intrahepatic cholangiocarcinoma (ICC) can help the interventional radiologist understand the role of locoregional therapies such as ablation, transarterial chemoembolization, and radioembolization in the management of ICC.
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Affiliation(s)
- Pouya Entezari
- Section of Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Chicago, Illinois
| | - Ahsun Riaz
- Section of Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Chicago, Illinois
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13
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Javor D, Moyses J, Loewe C, Schernthaner RE. Radiation dose reduction capabilities of a new C-arm system with optimized hard- and software. Eur J Radiol 2020; 134:109367. [PMID: 33221618 DOI: 10.1016/j.ejrad.2020.109367] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Revised: 10/17/2020] [Accepted: 10/20/2020] [Indexed: 11/30/2022]
Abstract
PURPOSE To assess the radiation dose reduction capabilities and the image quality of a new C-arm system in comparison to a standard C-arm system. METHOD Prospective, randomized, IRB approved two-arm trial design. 49 consecutive patients with primary or secondary liver cancer were treated with transarterial chemoembolization (TACE) on two different angiography units. 28 patients were treated on a conventional angiography unit B, 21 patients on unit A which provides improved hardware and optimized image processing algorithms. Dose area product (DAP) and fluoroscopy time were recorded. DSA image quality of all procedures was assessed on a four-rank-scale by two independent and blinded readers. RESULTS Both cohorts showed no significant differences with regard to patient characteristics, tumor burden and fluoroscopy time. The new system resulted in a statistically significant reduction of cumulative DAP of 72% compared to the old platform (median 76 vs. 269 Gy*cm2). Individually, Fluoro-DAP and DSA-DAP decreased by 48% and 77% (p = 0.012 and p < 0.01), respectively. No statistically significant differences in DSA image quality were found between the two imaging platforms. CONCLUSIONS The new C-arm system significantly reduced radiation exposure for TACE procedures without increased radiation time or negative impact on DSA image quality. The combination of optimized hardware and software yields the highest radiation dose reduction and is of utmost importance for patients and interventionalists.
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Affiliation(s)
- Domagoj Javor
- Division of Cardiovascular and Interventional Radiology, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
| | - Johanna Moyses
- Division of Cardiovascular and Interventional Radiology, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Christian Loewe
- Division of Cardiovascular and Interventional Radiology, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Ruediger E Schernthaner
- Division of Cardiovascular and Interventional Radiology, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
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14
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Zhang FP, Huang YP, Luo WX, Deng WY, Liu CQ, Xu LB, Liu C. Construction of a risk score prognosis model based on hepatocellular carcinoma microenvironment. World J Gastroenterol 2020; 26:134-153. [PMID: 31969776 PMCID: PMC6962430 DOI: 10.3748/wjg.v26.i2.134] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 11/23/2019] [Accepted: 12/06/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a common cancer with a poor prognosis. Previous studies revealed that the tumor microenvironment (TME) plays an important role in HCC progression, recurrence, and metastasis, leading to poor prognosis. However, the effects of genes involved in TME on the prognosis of HCC patients remain unclear. Here, we investigated the HCC microenvironment to identify prognostic genes for HCC.
AIM To identify a robust gene signature associated with the HCC microenvironment to improve prognosis prediction of HCC.
METHODS We computed the immune/stromal scores of HCC patients obtained from The Cancer Genome Atlas based on the ESTIMATE algorithm. Additionally, a risk score model was established based on Differentially Expressed Genes (DEGs) between high‐ and low‐immune/stromal score patients.
RESULTS The risk score model consisting of eight genes was constructed and validated in the HCC patients. The patients were divided into high- or low-risk groups. The genes (Disabled homolog 2, Musculin, C-X-C motif chemokine ligand 8, Galectin 3, B-cell-activating transcription factor, Killer cell lectin like receptor B1, Endoglin and adenomatosis polyposis coli tumor suppressor) involved in our risk score model were considered to be potential immunotherapy targets, and they may provide better performance in combination. Functional enrichment analysis showed that the immune response and T cell receptor signaling pathway represented the major function and pathway, respectively, related to the immune-related genes in the DEGs between high- and low-risk groups. The receiver operating characteristic (ROC) curve analysis confirmed the good potency of the risk score prognostic model. Moreover, we validated the risk score model using the International Cancer Genome Consortium and the Gene Expression Omnibus database. A nomogram was established to predict the overall survival of HCC patients.
CONCLUSION The risk score model and the nomogram will benefit HCC patients through personalized immunotherapy.
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MESH Headings
- Aged
- Antineoplastic Agents, Immunological/pharmacology
- Antineoplastic Agents, Immunological/therapeutic use
- Biomarkers, Tumor/antagonists & inhibitors
- Biomarkers, Tumor/genetics
- Carcinoma, Hepatocellular/drug therapy
- Carcinoma, Hepatocellular/genetics
- Carcinoma, Hepatocellular/immunology
- Carcinoma, Hepatocellular/mortality
- Databases, Genetic/statistics & numerical data
- Datasets as Topic
- Female
- Gene Expression Profiling/methods
- Gene Expression Regulation, Neoplastic/immunology
- Humans
- Kaplan-Meier Estimate
- Liver/immunology
- Liver/pathology
- Liver Neoplasms/drug therapy
- Liver Neoplasms/genetics
- Liver Neoplasms/immunology
- Liver Neoplasms/mortality
- Male
- Middle Aged
- Models, Genetic
- Neoplasm Staging
- Nomograms
- Precision Medicine/methods
- ROC Curve
- Risk Assessment/methods
- Treatment Outcome
- Tumor Microenvironment/genetics
- Tumor Microenvironment/immunology
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Affiliation(s)
- Fa-Peng Zhang
- Department of Biliary Pancreatic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong Province, China
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong Province, China
| | - Yi-Pei Huang
- Department of Biliary Pancreatic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong Province, China
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong Province, China
| | - Wei-Xin Luo
- Department of Biliary Pancreatic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong Province, China
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong Province, China
| | - Wan-Yu Deng
- Department of Biliary Pancreatic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong Province, China
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong Province, China
- College of Life Science, Shangrao Normal University, Shangrao 334001, Jiangxi Province, China
| | - Chao-Qun Liu
- Department of Biliary Pancreatic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong Province, China
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong Province, China
| | - Lei-Bo Xu
- Department of Biliary Pancreatic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong Province, China
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong Province, China
| | - Chao Liu
- Department of Biliary Pancreatic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong Province, China
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong Province, China
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15
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Liu J, Zhong M, Feng Y, Zeng S, Wang Y, Xu H, Zhou H. Prognostic Factors and Treatment Strategies for Intrahepatic Cholangiocarcinoma from 2004 to 2013: Population-Based SEER Analysis. Transl Oncol 2019; 12:1496-1503. [PMID: 31446308 PMCID: PMC6717067 DOI: 10.1016/j.tranon.2019.05.020] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Revised: 05/21/2019] [Accepted: 05/23/2019] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND: Seventy percent of intrahepatic cholangiocarcinoma (ICC) patients are inoperable. Treatment for unresectable patients is essential to improve poor survival. AIMS: We aimed to evaluate the prognostic factors for ICC patients, and investigate the potential treatment strategies for unresectable patients. METHODS: ICC patients were identified in SEER registry in 2004–2013. Univariate and multivariate Cox proportional hazard regression analysis were performed to evaluate the effect of treatment strategies. RESULTS: Of 2248 cases diagnosed in 2010–2013 and staged according to the American Joint Committee on Cancer (AJCC) 7th edition, 1706 (76.13%) did not receive cancer-directed surgery. This portion increased compared to those diagnosed between 2004 and 2009 and staged according to the AJCC 6th edition (72.87%). In addition, the percentage of stage 4 cases increased, while stage 3 cases decreased, because AJCC 7th staging system categorized both T4 and N1 patients into stage IV, which were previously categorized into stage III by AJCC 6th staging system. Patients with radiofrequency ablation (RFA) showed a poorer survival in 2004–2009 (P = .0213), but an almost the same survival as patients with tumor resection in 2010–2013 (P = .51), suggesting that RFA performed better in recent years. Lymphadenectomy showed protective effect for unresectable patients. Radiotherapy improved cancer-specific survival in non-surgery patients (P < .0001).The proportion of stage IV patients increased tremendously from 37.4% in 2004–2009 to 58.7% in 2010–2013. Among 1319 stage IV patients (2010–2013), surgery at distant metastatic sites improved cancer-specific survival. CONCLUSIONS: For unresectable tumors, RFA, radiotherapy, lymphadenectomy, and surgery of distant metastases showed significant benefits to improve cancer-specific survival.
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Affiliation(s)
- Jieqiong Liu
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, 410008, China.
| | - Meizuo Zhong
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, 410008, China.
| | - Yuhua Feng
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, 410008, China.
| | - Shan Zeng
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, 410008, China.
| | - Yikai Wang
- Department of Biostatistics and Bioinformatics, Emory University Rollins School of Public Health, Atlanta, 30322, US.
| | - Hongbo Xu
- Department of Surgery The third Xiangya Hospital, Central South University, Changsha, 4100013, China.
| | - Hui Zhou
- Affiliated Cancer Hospital of Xiangya Medical School, Central South University / Hunan Cancer Hospital, Changsha, 410013, China.
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Repeated Treatment with 90Y-Microspheres in Intrahepatic Cholangiocarcinoma Relapsed After the First Radioembolization. Cancer Biother Radiopharm 2019; 34:231-237. [DOI: 10.1089/cbr.2018.2718] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
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Xu F, Jin T, Zhu Y, Dai C. Immune checkpoint therapy in liver cancer. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2018; 37:110. [PMID: 29843754 PMCID: PMC5975687 DOI: 10.1186/s13046-018-0777-4] [Citation(s) in RCA: 279] [Impact Index Per Article: 39.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Accepted: 04/28/2018] [Indexed: 02/06/2023]
Abstract
Immune checkpoints include stimulatory and inhibitory checkpoint molecules. In recent years, inhibitory checkpoints, including cytotoxic T lymphocyte–associated antigen 4 (CTLA-4), programmed cell death protein-1 (PD-1), and programmed cell death ligand 1 (PD-L1), have been identified to suppress anti-tumor immune responses in solid tumors. Novel drugs targeting immune checkpoints have succeeded in cancer treatment. Specific PD-1 blockades were approved for treatment of melanoma in 2014 and for treatment of non-small-cell lung cancer in 2015 in the United States, European Union, and Japan. Preclinical and clinical studies show immune checkpoint therapy provides survival benefit for greater numbers of patients with liver cancer, including hepatocellular carcinoma and cholangiocarcinoma, two main primary liver cancers. The combination of anti-PD-1/PD-L1 with anti-CTLA-4 antibodies is being evaluated in phase 1, 2 or 3 trials, and the results suggest that an anti-PD-1 antibody combined with locoregional therapy or other molecular targeted agents is an effective treatment strategy for HCC. In addition, studies on activating co-stimulatory receptors to enhance anti-tumor immune responses have increased our understanding regarding this immunotherapy in liver cancer. Epigenetic modulations of checkpoints for improving the tumor microenvironment also expand our knowledge of potential therapeutic targets in improving the tumor microenvironment and restoring immune recognition and immunogenicity. In this review, we summarize current knowledge and recent developments in immune checkpoint-based therapies for the treatment of hepatocellular carcinoma and cholangiocarcinoma and attempt to clarify the mechanisms underlying its effects.
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Affiliation(s)
- Feng Xu
- Department of Hepatobiliary and Splenic Surgery, Shengjing Hospital affiliated to China Medical University, Shenyang, 110004, Liaoning, China.,Department of Surgery, University of Colorado Anschutz Medical Campus, RC1-North Building, P18-8116, Aurora, CO, 80045, USA
| | - Tianqiang Jin
- Department of Hepatobiliary and Splenic Surgery, Shengjing Hospital affiliated to China Medical University, Shenyang, 110004, Liaoning, China
| | - Yuwen Zhu
- Department of Surgery, University of Colorado Anschutz Medical Campus, RC1-North Building, P18-8116, Aurora, CO, 80045, USA.
| | - Chaoliu Dai
- Department of Hepatobiliary and Splenic Surgery, Shengjing Hospital affiliated to China Medical University, Shenyang, 110004, Liaoning, China.
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Effects of liver cirrhosis and patient condition on clinical outcomes in intrahepatic cholangiocarcinoma: a retrospective analysis of 156 cases in a single center. Eur J Gastroenterol Hepatol 2018; 30:552-556. [PMID: 29280922 DOI: 10.1097/meg.0000000000001036] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE The incidence of intrahepatic cholangiocarcinoma (iCCA) has been increasing over the past few decades. Liver cirrhosis is an independent risk factor for the development of iCCA. This study aimed to examine the prognostic impact of liver cirrhosis and patient condition on the treatment of iCCA. PATIENTS AND METHODS We retrospectively analyzed the cases of 156 patients diagnosed with iCCA between 1990 and 2014 in our center. Patients were divided into subgroups depending on the presence and severity of liver cirrhosis and the type of treatment. Clinical data, patient characteristics, and overall survival were compared between these groups. RESULTS Forty-seven (30%) of 156 patients had liver cirrhosis, predominantly with Child-Pugh scores A (n=27) and B (n=12). The median survival differed between patients receiving tumor resection (34 months), chemotherapy (10 months), and best supportive care (2 months). An Eastern Cooperative Oncology Group Performance Status score more than 1 was a predictor of poor survival in all patients (P<0.001), independent of the presence of cirrhosis. Resection could be performed less frequently in cirrhotic patients (6 vs. 31 patients; P=0.04). If resection was performed, the presence of cirrhosis A/B did not influence survival. Cirrhosis A/B did not influence the outcome in patients receiving chemotherapy either. In cirrhotic patients receiving chemotherapy, cancer antigen 19-9 levels above 129 U/ml were associated with a significantly shorter survival (22.5 vs. 3 months, P=0.0003). CONCLUSION The presence of liver cirrhosis in iCCA has been underestimated. There was no difference in survival between noncirrhotic patients and patients with compensated cirrhosis. Patients' general condition seems to be of more prognostic value in the treatment of iCCA than the presence of cirrhosis. Therefore, the presence of cirrhosis A/B should not prevent patients with a good Eastern Cooperative Oncology Group Performance Status score from receiving tumor resection or chemotherapy.
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19
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Abstract
Cholangiocarcinomas (CC) are rare tumors which usually present late and are often difficult to diagnose and treat. CCs are categorized as intrahepatic, hilar, or extrahepatic. Epidemiologic studies suggest that the incidence of intrahepatic CCs may be increasing worldwide. In this chapter, we review the risk factors, clinical presentation, and management of cholangiocarcinoma.
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20
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Fiorentini G, Mambrini A, Sarti D, Cantore M, Mulazzani L, Mattioli GM, Guadagni S. Hepatic intra-arterial and systemic chemotherapy followed by maintenance therapy for the treatment of cholangiocarcinoma. Hepat Oncol 2017; 4:45-53. [PMID: 30191053 DOI: 10.2217/hep-2017-0001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Accepted: 08/03/2017] [Indexed: 01/03/2023] Open
Abstract
Aim The aim is to report clinical outcomes of hepatic intra-arterial (IACHT) and systemic chemotherapy (SCHT), followed by gemcitabine-based maintenance therapy (maintenance), for the treatment of relapsed or unresectable cholangiocarcinoma. Patients & methods In this retrospective observational study, 145 cholangiocarcinoma patients were treated with Epirubicin-Cisplatin as IACHT associated with Capecitabine or 5-fluorouracil as SCHT. Maintenance was performed with gemcitabine-based schedule. Toxicity was assessed with NCI-CTCAE and tumor response with RECIST 1.1. Results Tumor response was complete in 1%, partial in 20%, stable disease in 48% and progression in 31% of patients (3 months after therapy). The most frequent adverse events were: anemia (24%), nausea and vomiting (33%), alopecia (60%). Conclusion Cholangiocarcinoma patients may benefit from IAHCT-SCHT. Maintenance may prolong clinical benefits. ClinicalTrials.gov registry Identifier: NCT01920503.
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Affiliation(s)
- Giammaria Fiorentini
- Oncology Unit, Azienda Ospedaliera "Ospedali Riuniti Marche Nord", 61122 Pesaro, Italy.,Oncology Unit, Azienda Ospedaliera "Ospedali Riuniti Marche Nord", 61122 Pesaro, Italy
| | - Andrea Mambrini
- Oncology Unit, Carrara General Hospital, Carrara, Italy.,Oncology Unit, Carrara General Hospital, Carrara, Italy
| | - Donatella Sarti
- Oncology Unit, Azienda Ospedaliera "Ospedali Riuniti Marche Nord", 61122 Pesaro, Italy.,Oncology Unit, Azienda Ospedaliera "Ospedali Riuniti Marche Nord", 61122 Pesaro, Italy
| | - Maurizio Cantore
- Oncology Unit, Azienda Ospedaliera Carlo Poma, Mantova, Italy.,Oncology Unit, Azienda Ospedaliera Carlo Poma, Mantova, Italy
| | - Luca Mulazzani
- Diagnostics for Images Unit & Interventional Radiology, Azienda Ospedaliera "Ospedali Riuniti Marche Nord", 61122 Pesaro, Italy.,Diagnostics for Images Unit & Interventional Radiology, Azienda Ospedaliera "Ospedali Riuniti Marche Nord", 61122 Pesaro, Italy
| | - Gian Maria Mattioli
- Diagnostics for Images Unit & Interventional Radiology, Azienda Ospedaliera "Ospedali Riuniti Marche Nord", 61122 Pesaro, Italy.,Diagnostics for Images Unit & Interventional Radiology, Azienda Ospedaliera "Ospedali Riuniti Marche Nord", 61122 Pesaro, Italy
| | - Stefano Guadagni
- Department of Applied Clinical Sciences and Biotechnology, Section of General Surgery, University of L'Aquila, via Vetoio 67100 L'Aquila, Italy.,Department of Applied Clinical Sciences and Biotechnology, Section of General Surgery, University of L'Aquila, via Vetoio 67100 L'Aquila, Italy
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Abstract
Cholangiocarcinoma is a malignant neoplasm originating from biliary epithelial cells. The incidence and mortality of this cancer are rising in the world. Currently, cholangiocarcinoma is accepted as a stem cell disease with many risk factors. Diagnosis is relatively simple but therapy is extremely difficult. Surgery is the mainstay of treatment for early stage patients. Endobiliary approaches, chemotherapy and radiotherapy are other therapeutic approaches.
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Affiliation(s)
- Vedat Goral
- Department of Gastroenterology, School of Medicine, Istanbul Medipol University, Istanbul, Turkey.
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22
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The role of interventional radiology in the treatment of intrahepatic cholangiocarcinoma. Med Oncol 2017. [DOI: 10.1007/s12032-016-0866-1
expr 866809535 + 987807487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/16/2023]
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23
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Kwak TW, Park SB, Kim HJ, Jeong YIL, Kang DH. Anticancer activities of epigallocatechin-3-gallate against cholangiocarcinoma cells. Onco Targets Ther 2016; 10:137-144. [PMID: 28053547 PMCID: PMC5189709 DOI: 10.2147/ott.s112364] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
PURPOSE Epigallocatechin-3-gallate (EGCG) is an antioxidant agent derived from green tea. Because it has chemopreventive and anti-invasive effect against various cancer cells, EGCG can be used to inhibit proliferation and invasion of cholangiocarcinoma (CCA) cells. METHODS The anticancer effects of EGCG were studied using human CCA cells (HuCC-T1). Apoptosis was analyzed by Western blotting. Invasion and migration of cancer cells were assessed with Matrigel® and wound healing assays. An animal tumor xenograft model of HuCC-T1 was used to study the in vivo antitumor activities of EGCG. RESULTS EGCG effectively inhibited the growth of HuCC-T1 cells with no adverse effects on the viability of 293T cells. EGCG induced apoptotic cell death at 5 µg/mL concentration. It inhibited the expression of mutant p53 and induced apoptotic molecular signals such as Bax/Bcl-2, Caspase, and cytochrome C. Furthermore, EGCG dose-dependently inhibited the activity of matrix metalloproteinase (MMP)-2/9, invasion, and migration. In the animal tumor xenograft model of HuCC-T1 cells, EGCG was subcutaneously administered beside the tumor for local treatment. EGCG efficiently inhibited growth of the tumor and suppressed carcinogenic molecular signals such as Notch1, MMP-2/9, and proliferating cell nuclear antigen. CONCLUSION EGCG induced apoptosis of cancer cells without adverse effects on normal cells. EGCG inhibited growth, invasion, and migration of HuCC-T1 cells. We suggest EGCG as a promising candidate for local treatment of CCA.
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Affiliation(s)
- Tae Won Kwak
- Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital
| | - Su Bum Park
- Department of Internal Medicine, Pusan National University School of Medicine, Yangsan, Gyeongnam
| | | | - Young-IL Jeong
- Biomedical Research Institute, Pusan National University Hospital, Pusan, Republic of Korea
| | - Dae Hwan Kang
- Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital
- Department of Internal Medicine, Pusan National University School of Medicine, Yangsan, Gyeongnam
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24
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The role of interventional radiology in the treatment of intrahepatic cholangiocarcinoma. Med Oncol 2016; 34:11. [PMID: 28008570 DOI: 10.1007/s12032-016-0866-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2016] [Accepted: 12/07/2016] [Indexed: 12/21/2022]
Abstract
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy after hepatocellular carcinoma. Complete surgical resection remains the only potentially curative option for patients with ICC. However, until now, early diagnosis with potential surgical intervention has been the exception rather than the rule with only 30% of patients qualifying for attempted surgical cure. Many patients are unresectable because of disease stage, anatomic conditions, medical comorbidities, and small future remnant liver. Interventional radiology procedures are available for these types of patients with intra-arterial therapies and/or ablative treatments both for curative and for palliative treatment. The goals of interventional therapy are to control local tumor growth, to relieve symptoms, and to improve and preserve quality of life. The choice of treatment depends largely on tumor extent and patient performance. No randomized studies exist to compare treatments. The present review describes the current evidence of the interventional treatments in the management of the ICC. Moreover, interventional procedures available to increase the future liver reserve before surgery were analyzed.
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25
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Pinter M, Trauner M, Peck-Radosavljevic M, Sieghart W. Cancer and liver cirrhosis: implications on prognosis and management. ESMO Open 2016; 1:e000042. [PMID: 27843598 PMCID: PMC5070280 DOI: 10.1136/esmoopen-2016-000042] [Citation(s) in RCA: 196] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2016] [Accepted: 02/06/2016] [Indexed: 12/11/2022] Open
Abstract
Liver cirrhosis, the end-stage of every chronic liver disease, is not only the major risk factor for the development of hepatocellular carcinoma but also a limiting factor for anticancer therapy of liver and non-hepatic malignancies. Liver cirrhosis may limit surgical and interventional approaches to cancer treatment, influence pharmacokinetics of anticancer drugs, increase side effects of chemotherapy, render patients susceptible for hepatotoxicity, and ultimately result in a competitive risk for morbidity and mortality. In this review, we provide a concise overview about the impact of liver cirrhosis on the management and prognosis of patients with primary liver cancer or non-hepatic malignancies.
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Affiliation(s)
- Matthias Pinter
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Harvard Medical School & Massachusetts General Hospital, Boston, USA
| | - Michael Trauner
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III , Medical University of Vienna , Vienna , Austria
| | - Markus Peck-Radosavljevic
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Department of Gastroenterology & Hepatology, Endocrinology and Nephrology, Klinikum Klagenfurt am Wörthersee, Klagenfurt, Austria
| | - Wolfgang Sieghart
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Austrian Society of Gastroenterology & Hepatology, Working Group GI-Oncology
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26
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Brandi G, Venturi M, Pantaleo MA, Ercolani G. Cholangiocarcinoma: Current opinion on clinical practice diagnostic and therapeutic algorithms: A review of the literature and a long-standing experience of a referral center. Dig Liver Dis 2016; 48:231-41. [PMID: 26769568 DOI: 10.1016/j.dld.2015.11.017] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2015] [Revised: 11/05/2015] [Accepted: 11/20/2015] [Indexed: 02/06/2023]
Abstract
In the oncology landscape, cholangiocarcinoma is a challenging disease in terms of both diagnosis and treatment. Besides anamnesis and clinical examination, a definitive diagnosis of cholangiocarcinoma should be supported by imaging techniques (US, CT, MRI) and invasive investigations (ERC or EUS with brushing and FNA or US or CT-guided biopsy) followed by pathological confirmation. Surgery is the main curative option, so resectability of the tumour should be promptly assessed. Moreover, jaundice must be evaluated at the outset because biliary tract decompression with drainage and stent placement may be required. If the patient is resectable, pre-operative assessment of postoperative liver function is mandatory. After a curative resection, an adjuvant therapy may be administered. Otherwise, in cases with macroscopic residual disease after surgery or locally recurrent or unresectable cholangiocarcinoma at the diagnosis, first-line chemotherapy is the preferred strategy, possibly associated with radiotherapy and/or locoregional treatments. As the diagnostic and therapeutic pathway for cholangiocarcinoma can be declined in different modalities, patients should be promptly referred to a multidisciplinary team in a tertiary centre, familiar with this rare but lethal disease. Hence, the aim of the present paper is to focus on diagnostic and therapeutic algorithms based on the common guidelines and also on the clinical practice of multispecialist expert groups.
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Affiliation(s)
- Giovanni Brandi
- Haematological and Oncological Institute, Department of Experimental, Diagnostic and Specialty Medicine, St. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
| | - Michela Venturi
- Haematological and Oncological Institute, Department of Experimental, Diagnostic and Specialty Medicine, St. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
| | - Maria Abbondanza Pantaleo
- Haematological and Oncological Institute, Department of Experimental, Diagnostic and Specialty Medicine, St. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
| | - Giorgio Ercolani
- Department of Medical and Surgical Sciences, St. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
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27
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Schernthaner RE, Duran R, Chapiro J, Wang Z, Geschwind JFH, Lin M. A new angiographic imaging platform reduces radiation exposure for patients with liver cancer treated with transarterial chemoembolization. Eur Radiol 2015; 25:3255-3262. [PMID: 25956933 PMCID: PMC4595540 DOI: 10.1007/s00330-015-3717-0] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2014] [Revised: 03/15/2015] [Accepted: 03/16/2015] [Indexed: 01/01/2023]
Abstract
OBJECTIVES To quantify the reduction of radiation liver cancer patients are exposed to during transarterial chemoembolization (TACE), while maintaining diagnostic image quality, using a new C-arm imaging platform. METHODS In this prospective, HIPAA-compliant, IRB-approved, two-arm trial, 78 consecutive patients with primary or secondary liver cancer were treated with TACE on a C-arm imaging platform before and after an upgrade incorporating optimized acquisition parameters and advanced real-time image processing algorithms. Dose area product (DAP) and radiation time of each digital fluoroscopy (DF), digital subtraction angiography (DSA) and cone beam CT (CBCT) were recorded. DSA image quality was assessed by two blinded and independent readers on a four-rank scale. RESULTS Both cohorts showed no significant differences with regard to patient characteristics and tumour burden. The new system resulted in a statistically significant reduction of cumulative DAP of 66% compared to the old platform (median 132.9 vs. 395.8 Gy cm(2)). Individually, DAP of DF, DSA and CBCT decreased by 52%, 79% and 15% (p < 0.01, p < 0.01, p = 0.51), respectively. No statistically significant differences in DSA image quality were found between the two imaging platforms. CONCLUSIONS The new imaging platform significantly reduced radiation exposure for TACE procedures without increased radiation time or negative impact on DSA image quality. KEY POINTS • The new C-arm system allowed reduction of radiation exposure by two thirds • The procedure's course was not affected by the new platform • No decrease in DSA image quality was observed after the radiation reduction.
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Affiliation(s)
- Ruediger E Schernthaner
- Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, The Johns Hopkins Hospital, Sheikh Zayed Tower, Suite 7203, 1800 Orleans St, Baltimore, MD, 21287, USA
| | - Rafael Duran
- Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, The Johns Hopkins Hospital, Sheikh Zayed Tower, Suite 7203, 1800 Orleans St, Baltimore, MD, 21287, USA
| | - Julius Chapiro
- Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, The Johns Hopkins Hospital, Sheikh Zayed Tower, Suite 7203, 1800 Orleans St, Baltimore, MD, 21287, USA
| | - Zhijun Wang
- Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, The Johns Hopkins Hospital, Sheikh Zayed Tower, Suite 7203, 1800 Orleans St, Baltimore, MD, 21287, USA
| | - Jean-François H Geschwind
- Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, The Johns Hopkins Hospital, Sheikh Zayed Tower, Suite 7203, 1800 Orleans St, Baltimore, MD, 21287, USA.
| | - MingDe Lin
- Ultrasound Imaging and and Interventions (UII), Philips Research North America, Briarcliff Manor, NY, USA
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Gulamhusein AF, Sanchez W. Liver transplantation in the management of perihilar cholangiocarcinoma. Hepat Oncol 2015; 2:409-421. [PMID: 30191020 DOI: 10.2217/hep.15.30] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Cholangiocarcinoma (CCA) is the second most common primary hepatic neoplasm and accounts for 10-20% of hepatobiliary cancer-related deaths. The prognosis of patients with CCA is poor with 5-year survival rates of 10%, partially due to the limited effective treatment options that exist for this disease. In this review, we discuss the evolving role of liver transplantation in the management of patients with perihilar CCA (pCCA). We specifically discuss the Mayo Clinic protocol of neoadjuvant chemoradiation followed by liver transplantation in selected patients with pCCA and describe pretransplant, peritransplant, and post-transplant considerations and challenges with this approach. Finally, we review local, national and international outcomes and discuss future directions in optimizing this treatment strategy for patients who otherwise have few therapeutic options and limited survival.
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Affiliation(s)
- Aliya F Gulamhusein
- Division of Gastroenterology & Hepatology, Mayo Clinic College of Medicine, Rochester, MN, USA
| | - William Sanchez
- Division of Gastroenterology & Hepatology, Mayo Clinic College of Medicine, Rochester, MN, USA
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29
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Hwang S, Lee YJ, Song GW, Park KM, Kim KH, Ahn CS, Moon DB, Lee SG. Prognostic Impact of Tumor Growth Type on 7th AJCC Staging System for Intrahepatic Cholangiocarcinoma: a Single-Center Experience of 659 Cases. J Gastrointest Surg 2015; 19:1291-304. [PMID: 25820487 DOI: 10.1007/s11605-015-2803-6] [Citation(s) in RCA: 54] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2015] [Accepted: 03/15/2015] [Indexed: 01/31/2023]
Abstract
OBJECTIVE Because noticeable changes were made to the 7th American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging for intrahepatic cholangiocarcinoma (IHCC), we validated the prognostic impact of tumor staging after macroscopic curative resection of IHCC. METHODS A cohort of 659 IHCC patients who underwent R0 (n = 539) or R1 (n = 120) resection were selected with exclusion of R2 resection (n = 111). Study patients were followed up for ≥24 months or until death with no patient lost during survival analysis. RESULTS Anatomical resection was performed in 599 (90.9%) and concurrent bile duct resection was conducted in 97 (14.7%). Median survival periods following R0, R1, and R2 resections were 28, 12, and 3 months, respectively (p = 0.000). In the R0 resection group, the 1-, 3-, 5-, and 10-year tumor recurrence rates were 36.4%, 57.9%, 64.7%, and 65.0%, respectively, and the 1-, 3-, 5-, and 10-year patient survival rates were 73.1%, 44.2%, 33.0%, and 23.1%, respectively. Independent risk factors for tumor recurrence and patient survival were tumor growth type, tumor size > 5 cm, perineural invasion, and lymph node metastasis. According to the 7th AJCC staging system, the prognostic contrast was marginal in stage T2-4 tumors without lymph node metastasis (p > 0.8). With our redefined staging system with tumor growth types and risk factors including tumor number and perineural/lymphovascular invasion, clear prognostic contrast was achieved among T1-3 stages (p = 0.000). CONCLUSION Growth type of IHCC seems to be essential for determining tumor stage. Although the stratification of the 7th AJCC IHCC staging system seems reasonably established, refinements and further validation could improve prognostic predictability.
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Affiliation(s)
- Shin Hwang
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea,
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Schernthaner RE, Chapiro J, Sahu S, Withagen P, Duran R, Sohn JH, Radaelli A, van der Bom IM, Geschwind JFH, Lin M. Feasibility of a Modified Cone-Beam CT Rotation Trajectory to Improve Liver Periphery Visualization during Transarterial Chemoembolization. Radiology 2015; 277:833-41. [PMID: 26000642 DOI: 10.1148/radiol.2015142821] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
PURPOSE To compare liver coverage and tumor detectability by using preprocedural magnetic resonance (MR) images as a reference, as well as radiation exposure of cone-beam computed tomography (CT) with different rotational trajectories. MATERIALS AND METHODS Fifteen patients (nine men and six women; mean age ± standard deviation, 65 years ± 5) with primary or secondary liver cancer were retrospectively included in this institutional review board-approved study. A modified cone-beam CT protocol was used in which the C-arm rotates from +55° to -185° (open arc cone-beam CT) instead of -120° to +120° (closed arc cone-beam CT). Each patient underwent two sessions of transarterial chemoembolization between February 2013 and March 2014 with closed arc and open arc cone-beam CT (during the first and second transarterial chemoembolization sessions, respectively, as part of the institutional transarterial chemoembolization protocol). For each cone-beam CT examination, liver volume and tumor detectability were assessed by using MR images as the reference. Radiation exposure was compared by means of a phantom study. For statistical analysis, paired t tests and a Wilcoxon signed rank test were performed. RESULTS Mean liver volume imaged was 1695 cm(3) ± 542 and 1857 cm(3) ± 571 at closed arc and open arc cone-beam CT, respectively. The coverage of open arc cone-beam CT was significantly higher compared with closed arc cone-beam CT (97% vs 86% of the MR imaging liver volume, P = .002). In eight patients (53%), tumors were partially or completely outside the closed arc cone-beam CT field of view. All tumors were within the open arc cone-beam CT field of view. The open arc cone-beam CT radiation exposure by means of weighted CT index was slightly lower compared with that of closed arc cone-beam CT (-5.1%). CONCLUSION Open arc cone-beam CT allowed for a significantly improved intraprocedural depiction of peripheral hepatic tumors while achieving a slight radiation exposure reduction.
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Affiliation(s)
- Rüdiger E Schernthaner
- From the Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, The Johns Hopkins Hospital, 1800 Orleans St, Sheikh Zayed Tower, Suite 7203, Baltimore, MD 21287 (R.E.S., J.C., S.S., R.D., J.H.S., J.F.H.G.); Philips Healthcare, Best, the Netherlands (P.W., A.R., I.M.v.d.B.); and Department of Ultrasound and Interventions, Philips Research North America, Briarcliff Manor, NY (M.L.)
| | - Julius Chapiro
- From the Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, The Johns Hopkins Hospital, 1800 Orleans St, Sheikh Zayed Tower, Suite 7203, Baltimore, MD 21287 (R.E.S., J.C., S.S., R.D., J.H.S., J.F.H.G.); Philips Healthcare, Best, the Netherlands (P.W., A.R., I.M.v.d.B.); and Department of Ultrasound and Interventions, Philips Research North America, Briarcliff Manor, NY (M.L.)
| | - Sonia Sahu
- From the Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, The Johns Hopkins Hospital, 1800 Orleans St, Sheikh Zayed Tower, Suite 7203, Baltimore, MD 21287 (R.E.S., J.C., S.S., R.D., J.H.S., J.F.H.G.); Philips Healthcare, Best, the Netherlands (P.W., A.R., I.M.v.d.B.); and Department of Ultrasound and Interventions, Philips Research North America, Briarcliff Manor, NY (M.L.)
| | - Paul Withagen
- From the Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, The Johns Hopkins Hospital, 1800 Orleans St, Sheikh Zayed Tower, Suite 7203, Baltimore, MD 21287 (R.E.S., J.C., S.S., R.D., J.H.S., J.F.H.G.); Philips Healthcare, Best, the Netherlands (P.W., A.R., I.M.v.d.B.); and Department of Ultrasound and Interventions, Philips Research North America, Briarcliff Manor, NY (M.L.)
| | - Rafael Duran
- From the Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, The Johns Hopkins Hospital, 1800 Orleans St, Sheikh Zayed Tower, Suite 7203, Baltimore, MD 21287 (R.E.S., J.C., S.S., R.D., J.H.S., J.F.H.G.); Philips Healthcare, Best, the Netherlands (P.W., A.R., I.M.v.d.B.); and Department of Ultrasound and Interventions, Philips Research North America, Briarcliff Manor, NY (M.L.)
| | - Jae Ho Sohn
- From the Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, The Johns Hopkins Hospital, 1800 Orleans St, Sheikh Zayed Tower, Suite 7203, Baltimore, MD 21287 (R.E.S., J.C., S.S., R.D., J.H.S., J.F.H.G.); Philips Healthcare, Best, the Netherlands (P.W., A.R., I.M.v.d.B.); and Department of Ultrasound and Interventions, Philips Research North America, Briarcliff Manor, NY (M.L.)
| | - Alessandro Radaelli
- From the Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, The Johns Hopkins Hospital, 1800 Orleans St, Sheikh Zayed Tower, Suite 7203, Baltimore, MD 21287 (R.E.S., J.C., S.S., R.D., J.H.S., J.F.H.G.); Philips Healthcare, Best, the Netherlands (P.W., A.R., I.M.v.d.B.); and Department of Ultrasound and Interventions, Philips Research North America, Briarcliff Manor, NY (M.L.)
| | - Imramsjah Martin van der Bom
- From the Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, The Johns Hopkins Hospital, 1800 Orleans St, Sheikh Zayed Tower, Suite 7203, Baltimore, MD 21287 (R.E.S., J.C., S.S., R.D., J.H.S., J.F.H.G.); Philips Healthcare, Best, the Netherlands (P.W., A.R., I.M.v.d.B.); and Department of Ultrasound and Interventions, Philips Research North America, Briarcliff Manor, NY (M.L.)
| | - Jean-François H Geschwind
- From the Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, The Johns Hopkins Hospital, 1800 Orleans St, Sheikh Zayed Tower, Suite 7203, Baltimore, MD 21287 (R.E.S., J.C., S.S., R.D., J.H.S., J.F.H.G.); Philips Healthcare, Best, the Netherlands (P.W., A.R., I.M.v.d.B.); and Department of Ultrasound and Interventions, Philips Research North America, Briarcliff Manor, NY (M.L.)
| | - MingDe Lin
- From the Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, The Johns Hopkins Hospital, 1800 Orleans St, Sheikh Zayed Tower, Suite 7203, Baltimore, MD 21287 (R.E.S., J.C., S.S., R.D., J.H.S., J.F.H.G.); Philips Healthcare, Best, the Netherlands (P.W., A.R., I.M.v.d.B.); and Department of Ultrasound and Interventions, Philips Research North America, Briarcliff Manor, NY (M.L.)
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Ohkawa A, Mizumoto M, Ishikawa H, Abei M, Fukuda K, Hashimoto T, Sakae T, Tsuboi K, Okumura T, Sakurai H. Proton beam therapy for unresectable intrahepatic cholangiocarcinoma. J Gastroenterol Hepatol 2015; 30:957-63. [PMID: 25376272 DOI: 10.1111/jgh.12843] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/27/2014] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIM Treatment for unresectable intrahepatic cholangiocarcinoma (ICC) has not been established. The aim of the study was to evaluate the outcome of proton beam therapy (PBT) for patients with unresectable ICC. METHODS Up to 2010, 20 patients (11 males, 9 females, median age 63 years old) with unresectable ICC (two, seven, seven, and four in stages II, IIIA, IIIC, and IV, respectively) were treated with PBT. The largest dimensions of the tumors ranged from 15 to 140 mm (median: 50 mm). The intrahepatic region and lymph nodes received median total proton doses of 72.6 GyE in 22 fractions and 56.1 GyE in 17 fractions, respectively. Four patients received concurrent chemotherapy (tegafur, gimeracil, and oteracil; TS-1) during PBT. Twelve patients were treated curatively, and eight were treated palliatively because tumors were present outside the irradiation field. RESULTS In the curative group, nine tumors within the irradiated field were controlled in follow-up of 8.6-62.6 months (median: 20.8 months). Median survival rates in the curative and palliative groups were 27.5 and 9.6 months, respectively, and overall 1- and 3-year survival rates were 82% and 38%, and 50% and 0%, respectively. Eight patients survived for > 2 years, and there was no distant metastasis in five of these patients after 2 years. No severe side-effects occurred. CONCLUSIONS The results suggest that long-term survival can be achieved using PBT for patients with unresectable ICC without distant metastasis. Further studies are required to determine the optimal treatment schedule and best combination of PBT and chemotherapy.
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Affiliation(s)
- Ayako Ohkawa
- Department of Radiation Oncology, University of Tsukuba, Tsukuba, Ibaraki, Japan
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Imaging bile duct tumors: pathologic concepts, classification, and early tumor detection. ACTA ACUST UNITED AC 2014; 38:1334-50. [PMID: 23925840 DOI: 10.1007/s00261-013-0027-3] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Cholangiocarcinoma is the most common primary malignancy of the bile ducts which has several predisposing factors such as hepatolithiasis and primary sclerosing cholangitis, and can develop from precancerous conditions such as biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct. As surgical resection of early stage cholangiocarcinoma or precancerous lesions may provide better prognosis, early detection of those lesions is very important. Imaging studies play important roles in the diagnosis of bile duct tumors followed by appropriate management. Indeed, not only diagnosis of cholangiocarcinoma but also appropriate categorization of bile duct tumors based on their morphologic features and location on cross-sectional imaging studies, including computed tomography and magnetic resonance imaging, is important to predict their biologic behaviors, and choose relevant treatment strategies. We herein review the classification system of the bile duct tumors with their radiologic and pathologic findings as well as role of imaging in the early detection of bile duct tumors.
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Amini A, Gamblin TC. Palliation: treating patients with inoperable biliary tract and primary liver tumors. Surg Oncol Clin N Am 2013; 23:383-97. [PMID: 24560116 DOI: 10.1016/j.soc.2013.10.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
This article summarizes the current literature in treatment of unresectable biliary tract and primary liver tumors. Locoregional therapies including radiofrequency ablation, percutaneous ethanol injection, cryoablation, microwave ablation, transarterial chemoembolization, hepatic artery infusion, radioembolization ((90)Y), and bland embolization are discussed and clinical trials compared. Palliative strategies including surgical, percutaneous, and endoscopic techniques to decompress the biliary system and improve symptoms are also summarized. Systemic chemotherapy and sorafenib used in conjunction with locoregional therapies or as sole therapeutic options are discussed.
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Affiliation(s)
- Albert Amini
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI 53226-3596, USA
| | - T Clark Gamblin
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI 53226-3596, USA.
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Ilyas SI, Gores GJ. Pathogenesis, diagnosis, and management of cholangiocarcinoma. Gastroenterology 2013; 145:1215-29. [PMID: 24140396 PMCID: PMC3862291 DOI: 10.1053/j.gastro.2013.10.013] [Citation(s) in RCA: 954] [Impact Index Per Article: 79.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2013] [Revised: 10/08/2013] [Accepted: 10/10/2013] [Indexed: 12/13/2022]
Abstract
Cholangiocarcinomas (CCAs) are hepatobiliary cancers with features of cholangiocyte differentiation; they can be classified anatomically as intrahepatic CCA (iCCA), perihilar CCA (pCCA), or distal CCA. These subtypes differ not only in their anatomic location, but in epidemiology, origin, etiology, pathogenesis, and treatment. The incidence and mortality of iCCA has been increasing over the past 3 decades, and only a low percentage of patients survive until 5 years after diagnosis. Geographic variations in the incidence of CCA are related to variations in risk factors. Changes in oncogene and inflammatory signaling pathways, as well as genetic and epigenetic alterations and chromosome aberrations, have been shown to contribute to the development of CCA. Furthermore, CCAs are surrounded by a dense stroma that contains many cancer-associated fibroblasts, which promotes their progression. We have gained a better understanding of the imaging characteristics of iCCAs and have developed advanced cytologic techniques to detect pCCAs. Patients with iCCAs usually are treated surgically, whereas liver transplantation after neoadjuvant chemoradiation is an option for a subset of patients with pCCAs. We review recent developments in our understanding of the epidemiology and pathogenesis of CCA, along with advances in classification, diagnosis, and treatment.
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Affiliation(s)
- Sumera I Ilyas
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
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