|
1
|
Lin Z, Wang W, Yan Y, Ma Z, Xiao Z, Mao K. A deep learning-based clinical-radiomics model predicting the treatment response of immune checkpoint inhibitors (ICIs)-based conversion therapy in potentially convertible hepatocelluar carcinoma patients: a tumor marker prognostic study. Int J Surg 2025; 111:3342-3355. [PMID: 40085751 DOI: 10.1097/js9.0000000000002322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Accepted: 03/02/2025] [Indexed: 03/16/2025]
Abstract
BACKGROUND The majority of patients with hepatocellular carcinoma (HCC) miss the opportunity of radical resection, making immune check-point inhibitors (ICIs)-based conversion therapy a primary option. However, challenges persist in predicting response and identifying the optimal patient subset. The objective is to develop a CT-based clinical-radiomics model to predict durable clinical benefit (DCB) of ICIs-based treatment in potentially convertible HCC patients. METHODS The radiomics features were extracted by pyradiomics in training set, and machine learning models was generated based on the selected radiomics features. Deep learning models were created using two different protocols. Integrated models were constructed by incorporating radiomics scores, deep learning scores, and clinical variables selected through multivariate analysis. Furthermore, we analyzed the relationship between integrated model scores and clinical outcomes related to conversion therapy in the entire cohort. Finally, radiogenomic analysis was conducted on bulk RNA and DNA sequencing data. RESULTS The top-performing integrated model demonstrated excellent predictive accuracy with an area under the curve (AUC) of 0.96 (95% CI: 0.94-0.99) in the training set and 0.88 (95% CI: 0.77-0.99) in the test set, effectively stratifying survival risk across the entire cohort and revealing significant disparity in overall survival (OS), as evidenced by Kaplan-Meier survival curves ( P < 0.0001). Moreover, integrated model scores exhibited associations with sequential resection among patients who achieved DCB and pathological complete response (pCR) among those who underwent sequential resection procedures. Notably, higher radiomics model was correlated with MHC I expression, angiogenesis-related processes, CD8 T cell-related gene sets, as well as a higher frequency of TP53 mutations along with increased levels of mutation burden and neoantigen. CONCLUSION The deep learning-based clinical-radiomics model exhibited satisfactory predictive capability in forecasting the DCB derived from ICIs-based conversion therapy in potentially convertible HCC, and was associated with a diverse range of immune-related mechanisms.
Collapse
Affiliation(s)
- Zijian Lin
- Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, China
| | - Weidong Wang
- Department of Interventional Radiography, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, China
| | - Yongcong Yan
- Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Zifeng Ma
- Shanghai Public Health Clinical Center, Shanghai, China
| | - Zhiyu Xiao
- Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Kai Mao
- Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| |
Collapse
|
|
2
|
Cassese G, C Giglio M, Vitale A, Lauterio A, Serenari M, Cipriani F, Ardito F, Perri P, Nicolini D, Di Gioia G, Fontana AP, Lai Q, Conci S, Fumagalli L, Iaria M, Garancini M, Molfino S, Zanello M, La Barba G, Conticchio M, Germani P, Famularo S, Romano M, Zimmitti G, De Angelis M, Troci A, Belli A, Izzo F, Crespi M, Boccia L, Abu Hilal M, Zanus G, Torzilli G, Tarchi P, Memeo R, Ercolani G, Jovine E, Baiocchi G, Romano F, Della Valle R, Chiarelli M, Ruzzenente A, Rossi M, Ferrero A, Maestri M, Vivarelli M, Grazi GL, Giuliante F, Aldrighetti L, Cescon M, De Carlis L, Cillo U, I Troisi R. Minimally invasive versus open liver resection for nonmetastatic hepatocellular carcinoma staged BCLC - B and - C: an Italian multicentric analysis. HPB (Oxford) 2025; 27:649-659. [PMID: 39956728 DOI: 10.1016/j.hpb.2025.01.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Revised: 01/12/2025] [Accepted: 01/16/2025] [Indexed: 02/18/2025]
Abstract
BACKGROUND Recent papers report significant survival gain after liver resection in BCLC-B and -C HCC patients. The results of minimally invasive liver surgery (MILS) in such patients have not been widely investigated so far. METHODS Data regarding patients undergoing MILS or open liver resection (OLR) for HCC staged BCLC -B and -C were extracted from the HERCOLES database. An inverse probability of treatment weighting (IPTW) method was adopted to balance the confounders. The primary outcome was a composite endpoint including post-hepatectomy liver failure, severe postoperative complications and in-hospital mortality. RESULTS 627 patients were included (459 undergoing OLR and 168 receiving MILS). After IPTW, no difference was found in the composite endpoint between MILS and OLR (OR 0.86 [95%CI 0.46-1-60]; p = 0.62). MILS reduced the risk of receiving intra-operative transfusions (OR 0.28 [95%CI 0.13-0.58]; p < 0.001) and of developing postoperative ascites (OR 0.56 [95%CI 0,32-0,98]; p = 0.039), with reduced length of stay (OR 0.82 [95%CI 0.66-1.01]; p = 0.045). The survival analysis showed no differences between MILS and OLR for both OS (p = 0.13) and DFS (p = 0.491). CONCLUSION MILS was shown to be safe and feasible for selected non-metastatic HCC patients staged BCLC B and C, reducing the risk of perioperative transfusions and postoperative ascites, and shortening the length of stay.
Collapse
Affiliation(s)
- Gianluca Cassese
- Department of Clinical Medicine and Surgery, Division of Minimally Invasive and Robotic HPB Surgery, Transplantation Service, Federico II University Hospital, Naples, Italy
| | - Mariano C Giglio
- Department of Clinical Medicine and Surgery, Division of Minimally Invasive and Robotic HPB Surgery, Transplantation Service, Federico II University Hospital, Naples, Italy
| | - Alessandro Vitale
- Department of Surgical Oncological and Gastroenterological Sciences, Padua University, Padua, Italy
| | - Andrea Lauterio
- General Surgery and Abdominal Transplantation Unit, Niguarda-Cà Granda Hospital, Milan, Italy; Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
| | - Matteo Serenari
- Hepato-biliary and Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Federica Cipriani
- Division of Hepatobiliary Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Francesco Ardito
- Department of Medical and Surgical Sciences, IRCCS Fondazione Policlinico Universitario A. Gemelli, Rome, Italy
| | - Pasquale Perri
- Hepatobiliary and Pancreatic Surgery, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Daniele Nicolini
- HPB Surgery and Transplantation Unit, Department of Clinical and Experimental Medicine, Polytechnic University of Marche, Ancona, Italy
| | - Giulio Di Gioia
- Unit of General Surgery 1, University of Pavia and Foundation IRCCS Policlinico San Matteo, Pavia, Italy
| | | | - Quirino Lai
- Division of General Surgery and Organ Transplantation, AUO Policlinico Umberto I of Rome, Sapienza University of Rome, Rome, Italy
| | - Simone Conci
- Division of General and Hepatobiliary Surgery, Department of Surgical Sciences, Dentistry, Gynecology, and Pediatrics, University of Verona, Verona, Italy
| | - Luca Fumagalli
- Department of Emergency and Robotic Surgery, ASST Lecco, Lecco, Italy
| | - Maurizio Iaria
- Department of Medicine and Surgery, HPB Unit, University of Parma - Parma University Hospital, Parma, Italy
| | - Mattia Garancini
- Department of General Surgery, Unit of Hepatobiliary Surgery, IRCCS San Gerardo dei Tintori, Milano-Bicocca University, Monza, Italy
| | - Sarah Molfino
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Matteo Zanello
- Alma Mater Studiorum, University of Bologna, AOU Sant'Orsola Malpighi, IRCCS at Maggiore Hospital, Bologna, Italy
| | - Giuliano La Barba
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, Forlì, Italy
| | - Maria Conticchio
- Department of Hepato-Pancreatc-Biliary Surgery, "F. Miulli" General Regional Hospital, Acquaviva delle Fonti, Bari, Italy
| | - Paola Germani
- Surgical Clinics, University Hospital of Trieste, Trieste, Italy
| | - Simone Famularo
- Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Maurizio Romano
- Department of Surgical, Oncological and Gastroenterological Science (DISCOG), University of Padua, Hepatobiliary and Pancreatic Surgery Unit, Treviso Hospital, Italy
| | - Giuseppe Zimmitti
- Department of General Surgery, Poliambulanza Foundation Hospital, Brescia, Italy
| | | | - Albert Troci
- Department of Surgery, L. Sacco Hospital, Milan, Italy
| | - Andrea Belli
- Istituto Nazionale Tumori, IRCCS "G. Pascale", Napoli, 80131, Italy
| | - Francesco Izzo
- Istituto Nazionale Tumori, IRCCS "G. Pascale", Napoli, 80131, Italy
| | | | - Luigi Boccia
- Department of General Surgery, Ospedale Carlo Poma, Mantua, Italy
| | - Mohamed Abu Hilal
- Department of General Surgery, Poliambulanza Foundation Hospital, Brescia, Italy
| | - Giacomo Zanus
- Department of Surgical, Oncological and Gastroenterological Science (DISCOG), University of Padua, Hepatobiliary and Pancreatic Surgery Unit, Treviso Hospital, Italy
| | - Guido Torzilli
- Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Paola Tarchi
- Department of Medicine and Surgery, LUM University, Casamassima, Bari, Italy
| | - Riccardo Memeo
- Department of Hepato-Pancreatc-Biliary Surgery, "F. Miulli" General Regional Hospital, Acquaviva delle Fonti, Bari, Italy; Department of Medicine and Surgery, LUM University, Casamassima, Bari, Italy
| | - Giorgio Ercolani
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, Forlì, Italy
| | - Elio Jovine
- Alma Mater Studiorum, University of Bologna, AOU Sant'Orsola Malpighi, IRCCS at Maggiore Hospital, Bologna, Italy
| | - Gianluca Baiocchi
- Department of General Surgery, Unit of Hepatobiliary Surgery, IRCCS San Gerardo dei Tintori, Milano-Bicocca University, Monza, Italy
| | - Fabrizio Romano
- Department of Medicine and Surgery, HPB Unit, University of Parma - Parma University Hospital, Parma, Italy
| | | | - Marco Chiarelli
- Division of General and Hepatobiliary Surgery, Department of Surgical Sciences, Dentistry, Gynecology, and Pediatrics, University of Verona, Verona, Italy
| | - Andrea Ruzzenente
- Division of General and Hepatobiliary Surgery, Department of Surgical Sciences, Dentistry, Gynecology, and Pediatrics, University of Verona, Verona, Italy
| | - Massimo Rossi
- Division of General Surgery and Organ Transplantation, AUO Policlinico Umberto I of Rome, Sapienza University of Rome, Rome, Italy
| | - Alessandro Ferrero
- Department of General and Oncological Surgery, Mauriziano Hospital "Umberto I," Turin, Italy
| | - Marcello Maestri
- Unit of General Surgery 1, University of Pavia and Foundation IRCCS Policlinico San Matteo, Pavia, Italy
| | - Marco Vivarelli
- HPB Surgery and Transplantation Unit, Department of Clinical and Experimental Medicine, Polytechnic University of Marche, Ancona, Italy
| | - Gian Luca Grazi
- Hepatobiliary and Pancreatic Surgery, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Felice Giuliante
- Department of Medical and Surgical Sciences, IRCCS Fondazione Policlinico Universitario A. Gemelli, Rome, Italy
| | - Luca Aldrighetti
- Division of Hepatobiliary Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Matteo Cescon
- Hepato-biliary and Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Luciano De Carlis
- General Surgery and Abdominal Transplantation Unit, Niguarda-Cà Granda Hospital, Milan, Italy; Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
| | - Umberto Cillo
- Department of Surgical Oncological and Gastroenterological Sciences, Padua University, Padua, Italy
| | - Roberto I Troisi
- Department of Clinical Medicine and Surgery, Division of Minimally Invasive and Robotic HPB Surgery, Transplantation Service, Federico II University Hospital, Naples, Italy.
| |
Collapse
|
|
3
|
Tong W, Zhong J, Yang Q, Lin H, Chen B, Lu T, Chen J, Luo N. Single-cell and bulk transcriptomic datasets enable the development of prognostic models based on dynamic changes in the tumor immune microenvironment in patients with hepatocellular carcinoma and portal vein tumor thrombus. Front Immunol 2024; 15:1414121. [PMID: 39530087 PMCID: PMC11550977 DOI: 10.3389/fimmu.2024.1414121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Accepted: 10/08/2024] [Indexed: 11/16/2024] Open
Abstract
Background Hepatocellular carcinoma (HCC) patients exhibiting portal vein tumor thrombosis (PVTT) face a high risk of rapid malignant progression and poor outcomes, with this issue being compounded by a lack of effective treatment options. The integration of bulk RNA-sequencing (RNA-seq) and single-cell RNA-seq (scRNA-seq) datasets focused on samples from HCC patients with PVTT has the potential to yield unprecedented insight into the dynamic changes in the tumor microenvironment (TME) and associated immunological characteristics in these patients, providing an invaluable tool for the reliable prediction of disease progression and treatment responses. Methods scRNA-seq data from both primary tumor (PT) and PVTT cells were downloaded from the Gene Expression Omnibus (GEO) database, while the International Cancer Genome Consortium (ICGC) and Cancer Genome Atlas (TCGA) databases were used to access bulk RNA-seq datasets. scRNA-seq, clustering, GSVA enrichment, mutational profiling, and predictive immunotherapeutic treatment analyses were conducted using these data with the goal of systematically assessing the heterogeneity of PT and PVTT cells and establishing a model capable of predicting immunotherapeutic and prognostic outcomes in patients with HCC. Results These analyses revealed that PVTT cells exhibited patterns of tumor proliferation, stromal activation, and low levels of immune cell infiltration, presenting with immune desert and immune rejection-like phenotypes. PT cells, in contrast, were found to exhibit a pattern of immunoinflammatory activity. Core PVTT-associated genes were clustered into three patterns consistent with the tumor immune rejection and immune desert phenotypes. An established clustering model was capable of predicting tumor inflammatory stage, subtype, TME stromal activity, and patient outcomes. PVTT signature genes were further used to establish a risk model, with the risk scores derived from this model providing a tool to evaluate patient clinicopathological features including clinical stage, tumor differentiation, histological subtype, microsatellite instability status, and tumor mutational burden. These risk scores were also able to serve as an independent predictor of patient survival outcomes, responses to adjuvant chemotherapy, and responses to immunotherapy. In vitro experiments were used to partially validate the biological prediction results. Conclusion These results offer new insight into the biological and immunological landscape of PVTT in HCC patients, By utilizing individual patient risk scores, providing an opportunity to guide more effective immunotherapeutic interventional efforts.
Collapse
Affiliation(s)
- Wangxia Tong
- Department of Hepatology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Jieyue Zhong
- Department of Hepatology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Qiuyan Yang
- Department of Hepatology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Han Lin
- Department of Hepatology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Bolun Chen
- Department of Hepatology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Tao Lu
- Department of Hepatobiliary Surgery, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Jibing Chen
- Center for Translational Medicine of Integrated Traditional Chinese and Western Medicine, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Ning Luo
- Department of Neurology, RuiKang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| |
Collapse
|
|
4
|
Gonvers S, Martins-Filho SN, Hirayama A, Calderaro J, Phillips R, Uldry E, Demartines N, Melloul E, Park YN, Paradis V, Thung SN, Alves V, Sempoux C, Labgaa I. Macroscopic Characterization of Hepatocellular Carcinoma: An Underexploited Source of Prognostic Factors. J Hepatocell Carcinoma 2024; 11:707-719. [PMID: 38605975 PMCID: PMC11007400 DOI: 10.2147/jhc.s447848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Accepted: 02/29/2024] [Indexed: 04/13/2024] Open
Abstract
The macroscopic appearance of a tumor such as hepatocellular carcinoma (HCC) may be defined as its phenotype which is de facto dictated by its genotype. Therefore, macroscopic characteristics of HCC are unlikely random but rather reflect genomic traits of cancer, presumably acting as a valuable source of information that can be retrieved and exploited to infer prognosis. This review aims to provide a comprehensive overview of the available data on the prognostic value of macroscopic characterization in HCC. A total of 57 studies meeting eligible criteria were identified, including patients undergoing liver resection (LR; 47 studies, 83%) or liver transplant (LT; 9 studies, 16%). The following macroscopic variables were investigated: tumor size (n = 42 studies), number of nodules (n = 28), vascular invasion (n = 24), bile duct invasion (n = 6), growth pattern (n = 15), resection margin (n = 11), tumor location (n = 6), capsule (n = 2) and satellite (n = 1). Although the selected studies provided insightful data with notable prognostic performances, a lack of standardization and substantial gaps were noted in the report and the analysis of gross findings. This topic remains incompletely covered. While the available studies underscored the value of macroscopic variables in HCC prognostication, important lacks were also observed. Macroscopic characterization of HCC is likely an underexploited source of prognostic factors that must be actively explored by future multidisciplinary research.
Collapse
Affiliation(s)
- Stéphanie Gonvers
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), Lausanne, Switzerland
- Faculty of Biology & Medicine (FBM), University of Lausanne (UNIL), Lausanne, Switzerland
| | | | - André Hirayama
- Department of Pathology, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Julien Calderaro
- Department of Pathology, APHP, Henri Mondor University Hospital, Creteil, Val-de-Marne, France
| | - Rebecca Phillips
- Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada
| | - Emilie Uldry
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), Lausanne, Switzerland
- Faculty of Biology & Medicine (FBM), University of Lausanne (UNIL), Lausanne, Switzerland
| | - Nicolas Demartines
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), Lausanne, Switzerland
- Faculty of Biology & Medicine (FBM), University of Lausanne (UNIL), Lausanne, Switzerland
| | - Emmanuel Melloul
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), Lausanne, Switzerland
- Faculty of Biology & Medicine (FBM), University of Lausanne (UNIL), Lausanne, Switzerland
| | - Young Nyun Park
- Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Valérie Paradis
- Department of Pathology, APHP, Beaujon University Hospital, Clichy, France
| | - Swan N Thung
- Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Venancio Alves
- Department of Pathology, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Christine Sempoux
- Faculty of Biology & Medicine (FBM), University of Lausanne (UNIL), Lausanne, Switzerland
- Department of Pathology, Lausanne University Hospital (CHUV), Lausanne, Switzerland
| | - Ismail Labgaa
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), Lausanne, Switzerland
- Faculty of Biology & Medicine (FBM), University of Lausanne (UNIL), Lausanne, Switzerland
| |
Collapse
|
|
5
|
Lu H, Zheng C, Liang B, Xia X, Fan H. Efficacy and safety analysis of TACE + PEI + lenvatinib compared with TACE + lenvatinib for the treatment of hepatocellular carcinoma with PVTT: a retrospective study. Front Oncol 2024; 14:1280837. [PMID: 38298738 PMCID: PMC10827889 DOI: 10.3389/fonc.2024.1280837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Accepted: 01/03/2024] [Indexed: 02/02/2024] Open
Abstract
Objective The aim of this study was to investigate the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with percutaneous ethanol injection (PEI) and lenvatinib in HCC patients with PVTT (Vp2-3), thus providing a safe and effective treatment strategy for advanced HCC patients. Materials and methods Clinical data of 227 patients with unresectable HCC and PVTT treated at the Union Hospital from January 2018 to December 2021 were retrospectively analyzed. The patients were divided into two groups according to their treatment methods: TACE+PEI+lenvatinib group (N=103) and TACE+lenvatinib group (N=124). Results The proportion of patients with disappearance, shrinkage, or no change of PVTT after treatment was significantly higher in the TACE+PEI+lenvatinib group compared to the TACE+lenvatinib group, with statistical significance (P<0.001). The TACE+PEI+lenvatinib group had higher objective response rate (ORR) (50.5% vs. 25.8%, P<0.001) and disease control rate (DCR) (87.4% vs. 74.2%, P=0.013) than the TACE+lenvatinib group. The median progression-free survival (mPFS) of the TACE+PEI+lenvatinib group was longer than that of the TACE+lenvatinib group (8.1 months vs. 6.5 months, P<0.001). Consistently, the median overall survival (mOS) of the TACE+PEI+lenvatinib group was longer than that of the TACE+lenvatinib group (17.1 months vs. 13.9 months, P<0.001). Conclusion Among HCC patients with PVTT (Vp2-3), TACE+PEI+lenvatinib is more effective comparing to TACE+lenvatinib in prolonging PFS and OS. The control of PVTT in the TACE+PEI+lenvatinib group was significantly more satisfactory than that in the TACE+lenvatinib group. TACE+PEI+lenvatinib is a safe and effective treatment strategy for HCC patients with PVTT (Vp2-3).
Collapse
Affiliation(s)
- Haohao Lu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Bin Liang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Xiangwen Xia
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Hongjie Fan
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| |
Collapse
|
|
6
|
Ichida A, Kokudo T, Shimada S, Hatano E, Kubo S, Kato Y, Ishikawa Y, Mori A, Baba H, Matsuyama Y, Endo I, Yamaue H, Yamamoto M, Kokudo N, Hasegawa K. Liver Resection for Hepatocellular Carcinoma With Tumor Thrombus in the Inferior Vena Cava or Right Atrium: A Large-scale Multicenter Survey Conducted in Japan. Ann Surg 2023; 278:e549-e555. [PMID: 36591790 DOI: 10.1097/sla.0000000000005789] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
OBJECTIVE To clarify the short and long-term postoperative outcomes and surgical indications for patients accompanied by hepatocellular carcinoma with tumor thrombus (TT) in the inferior vena cava (IVC) or right atrium (RA). BACKGROUND These patients are known to have an extremely poor prognosis; however, the postoperative outcomes have not been fully verified because of the rarity of this disease. METHODS We contacted 211 specialized centers in Japan and collected data on liver resection for hepatocellular carcinoma with TT in the IVC or RA from centers with experience performing surgery for such patients. The patient characteristics, operative procedures, and surgical outcomes were then analyzed. RESULTS A total of 119 patients from 23 institutions were enrolled; 49 patients had TT in the IVC below the diaphragm (type I), 42 had TT in the IVC above the diaphragm (type II), and 28 had TT entering the RA (type III). The severity and frequency of postoperative complications did not differ among the 3 groups. There was one surgery-related death in the type III group. The median survival times were 2.47 years in the type I group, 1.77 years in the type II group, and 1.02 years in the type III group. Multivariate analysis identified an indocyanine green retention rate at 15 minutes >15% and ≥3 tumors as prognostic factors affecting survival, whereas the use of cardiopulmonary bypass and ≥3 tumors were risk factors for recurrence. CONCLUSIONS As the postoperative prognosis of patients with type I or type II disease and of patients with no risk factors is relatively good, surgery should be considered for these patient populations.
Collapse
Affiliation(s)
- Akihiko Ichida
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Takashi Kokudo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Shingo Shimada
- Department of Gastroenterological Surgery I, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Etsuro Hatano
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Shoji Kubo
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Yutaro Kato
- Department of Surgery, Fujita Health University, Toyoake, Japan
| | - Yoshiya Ishikawa
- Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Akira Mori
- Department of Surgery, Japanese Red Cross Osaka Hospital, Osaka, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Yutaka Matsuyama
- Department of Biostatistics, School of Public Health, The University of Tokyo, Tokyo, Japan
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University, Yokohama, Japan
| | - Hiroki Yamaue
- Second Department of Surgery, Wakayama Medical University, Wakayama, Japan
| | - Masakazu Yamamoto
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Norihiro Kokudo
- Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| |
Collapse
|
|
7
|
Li Z, Zhao M, Qi X, Tang Y, Cheng S. Mechanisms of portal vein tumour thrombus formation and development in patients with hepatocellular carcinoma. J Cell Mol Med 2023; 27:2103-2111. [PMID: 37349905 PMCID: PMC10399540 DOI: 10.1111/jcmm.17808] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 05/17/2023] [Accepted: 06/01/2023] [Indexed: 06/24/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common and aggressive human malignancies worldwide. Portal vein tumour thrombus (PVTT) is considered one of most fearful complications of HCC and is strongly associated with a poor prognosis. Clarification of the mechanisms underlying the formation and development of PVTT is crucial for developing novel therapeutic strategies for HCC patients. Several studies have been made to uncover that tumour microenvironment, stem cells, abnormal gene expression and non-coding RNAs deregulation are associated with PVTT in patients with HCC in the last decade. However, the exact molecular mechanisms of PVTT in patients with HCC are still largely unknown. In the present review, we briefly summarized the molecular mechanisms underlying the formation and development of PVTT in HCC.
Collapse
Affiliation(s)
- Zhenli Li
- Department of Hepatobiliary SurgeryGeneral Hospital of Northern Theater CommandShenyangChina
- Department of General SurgeryThe 963rd Hospital of the Joint Service Support Force of the PLAJiamusiChina
| | - Mingda Zhao
- Department of Hepatobiliary SurgeryGeneral Hospital of Northern Theater CommandShenyangChina
- Dalian Medical UniversityDalianChina
| | - Xingshun Qi
- Department of GastroenterologyGeneral Hospital of Northern Theater CommandShenyangChina
| | - Yufu Tang
- Department of Hepatobiliary SurgeryGeneral Hospital of Northern Theater CommandShenyangChina
| | - Shuqun Cheng
- Sixth Department of Liver Surgery, Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghaiChina
| |
Collapse
|
|
8
|
Kim SH, Moon DB, Park YH, Lee SG, Kim KH, Hwang S, Ahn CS, Ha TY, Song GW, Jung DH, Park GC, Kim M, Na BG, Yang G, Kim SM, Oh RK. Favorable Prognostic Factors for Survival Outcomes of Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis After Hepatectomy. Ann Surg Oncol 2023:10.1245/s10434-023-13316-7. [PMID: 37043034 DOI: 10.1245/s10434-023-13316-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Accepted: 02/17/2023] [Indexed: 04/13/2023]
Abstract
BACKGROUND This study aimed to investigate prognostic factors of recurrence and survival associated with hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). PATIENTS AND METHODS This retrospective study included 161 patients with HCC with PVTT who underwent hepatectomy between January 2003 and January 2014 at the Asan Medical Center. Regression analyses were conducted to identify favorable predictive factors for overall survival (OS) and recurrence-free survival (RFS). RESULTS The median follow-up was 15.9 months, while 1-, 3-, and 5-year OS was 65.0%, 38.4%, and 36.0%, respectively, and 1-year RFS was 25.5%. There were no significant differences in OS and RFS between the patients with portal vein invasion (Vp) 1-2 and Vp3-4 PVTT. Patients with intrahepatic recurrence had significantly better overall survival than patients with extrahepatic recurrence. Transcatheter arterial chemoembolization and radiofrequency ablation were the most effective treatments for intrahepatic metastasis, and surgery was the most effective treatment for extrahepatic metastasis. On multivariate analysis, absence of esophageal varices, maximal tumor size < 5 cm, tumor location in single lobe, and anatomical resection were favorable prognostic factors for OS and R0 resection, and absence of microvascular invasion was a favorable prognostic factor for RFS. CONCLUSION The long-term outcome of patients with HCC with PVTT can be improved under consideration of favorable prognostic factors including absence of esophageal varices, maximal tumor size < 5 cm, tumor location in single lobe, and anatomical resection, R0 resection, and absence of microvascular invasion. In addition, recurrent HCC required aggressive management to prolong overall survival.
Collapse
Affiliation(s)
- Sang-Hoon Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Deok-Bog Moon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
| | - Yo-Han Park
- Division of Hepatobiliary Surgery, Department of Surgery, On Hospital, Busan, Korea
| | - Sung-Gyu Lee
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ki-Hun Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Shin Hwang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chul-Soo Ahn
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Tae-Yong Ha
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gi-Won Song
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dong-Hwan Jung
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gil-Chun Park
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Minjae Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Byeong-Gon Na
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Geunhyeok Yang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung Min Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Rak-Kyun Oh
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| |
Collapse
|
|
9
|
Wang J, Wu R, Sun JY, Lei F, Tan H, Lu X. An overview: Management of patients with advanced hepatocellular carcinoma. Biosci Trends 2022; 16:405-425. [PMID: 36476621 DOI: 10.5582/bst.2022.01109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Hepatocellular carcinoma (HCC) has constituted a significant health burden worldwide, and patients with advanced HCC, which is stage C as defined by the Barcelona Clinic Liver Cancer staging system, have a poor overall survival of 6-8 months. Studies have indicated the significant survival benefit of treatment based on sorafenib, lenvatinib, or atezolizumab-bevacizumab with reliable safety. In addition, the combination of two or more molecularly targeted therapies (first- plus second-line) has become a hot topic recently and is now being extensively investigated in patients with advanced HCC. In addition, a few biomarkers have been investigated and found to predict drug susceptibility and prognosis, which provides an opportunity to evaluate the clinical benefits of current therapies. In addition, many therapies other than tyrosine kinase inhibitors that might have additional survival benefits when combined with other therapeutic modalities, including immunotherapy, transarterial chemoembolization, radiofrequency ablation, hepatectomy, and chemotherapy, have also been examined. This review provides an overview on the current understanding of disease management and summarizes current challenges with and future perspectives on advanced HCC.
Collapse
Affiliation(s)
- Jincheng Wang
- The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, Jiangsu, China.,Graduate School of Biomedical Science and Engineering, Hokkaido University, Sapporo, Japan
| | - Rui Wu
- The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Jin-Yu Sun
- The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Feifei Lei
- Department of Infectious Diseases, Liver Disease Laboratory, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, China
| | - Huabing Tan
- Department of Infectious Diseases, Liver Disease Laboratory, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, China
| | - Xiaojie Lu
- Department of General Surgery, Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| |
Collapse
|
|
10
|
Jin Z, Wu G, Xu B, Wang J, Zhu H, Guo Y, Peng M, Peng T, Wen Z. Case Report: Combining liver partition and portal vein ligation after thrombectomy for tumor isolation (CLAPT) to treat advanced hepatocellular carcinoma with portal vein tumor thrombosis. Front Surg 2022; 9:928452. [PMID: 36176342 PMCID: PMC9513360 DOI: 10.3389/fsurg.2022.928452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Accepted: 08/25/2022] [Indexed: 01/27/2023] Open
Abstract
Background Primary liver cancer is the third leading cause of cancer-related deaths worldwide in 2020, and hepatocellular carcinoma (HCC) is the major pathological type. Patients with HCC complicated with portal vein tumor thrombosis (PVTT) have a poor prognosis, and controversies regarding treatment options exist among international scholars. Patients with VP4 or Cheng’s type III classification are generally considered ineligible for surgical treatment. Methods We retrospectively analyzed three cases of HCC with PVTT who underwent a novel modified surgical procedure. The procedure included portal vein thrombectomy and portal vein ligation with liver parenchymal separation for the resection of the tumor thrombus involving the main portal vein trunk and for the isolation of the giant tumor. The three cases were then treated with targeted drugs postoperatively. Results One case developed acute renal failure in the perioperative period, and the renal function gradually recovered after the treatment. The two remaining cases recovered uneventfully postoperatively. The prognosis of the three patients was encouraging. Only one patient died of lung metastasis after 13 months, and the remaining patients were still alive after 41 and 21 months, respectively. Conclusions We provide a new possible surgical option for patients with advanced HCC with PVTT. The surgical procedure was inspired by associating liver partition with portal vein ligation for staged hepatectomy and portal vein thrombectomy. The survival time was significantly prolonged after the patients underwent thrombectomy, tumor isolation, and postoperative nonsurgical treatment. Hence, the combination of liver partition and portal vein ligation after thrombectomy for tumor isolation has the potential for the treatment of advanced HCC with PVTT.
Collapse
|
|
11
|
Wei JW, Fu SR, Zhang J, Gu DS, Li XQ, Chen XD, Zhang ST, He XF, Yan JF, Lu LG, Tian J. CT-based radiomics to predict development of macrovascular invasion in hepatocellular carcinoma: A multicenter study. Hepatobiliary Pancreat Dis Int 2022; 21:325-333. [PMID: 34674948 DOI: 10.1016/j.hbpd.2021.09.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 09/24/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND Macrovascular invasion (MaVI) occurs in nearly half of hepatocellular carcinoma (HCC) patients at diagnosis or during follow-up, which causes severe disease deterioration, and limits the possibility of surgical approaches. This study aimed to investigate whether computed tomography (CT)-based radiomics analysis could help predict development of MaVI in HCC. METHODS A cohort of 226 patients diagnosed with HCC was enrolled from 5 hospitals with complete MaVI and prognosis follow-ups. CT-based radiomics signature was built via multi-strategy machine learning methods. Afterwards, MaVI-related clinical factors and radiomics signature were integrated to construct the final prediction model (CRIM, clinical-radiomics integrated model) via random forest modeling. Cox-regression analysis was used to select independent risk factors to predict the time of MaVI development. Kaplan-Meier analysis was conducted to stratify patients according to the time of MaVI development, progression-free survival (PFS), and overall survival (OS) based on the selected risk factors. RESULTS The radiomics signature showed significant improvement for MaVI prediction compared with conventional clinical/radiological predictors (P < 0.001). CRIM could predict MaVI with satisfactory areas under the curve (AUC) of 0.986 and 0.979 in the training (n = 154) and external validation (n = 72) datasets, respectively. CRIM presented with excellent generalization with AUC of 0.956, 1.000, and 1.000 in each external cohort that accepted disparate CT scanning protocol/manufactory. Peel9_fos_InterquartileRange [hazard ratio (HR) = 1.98; P < 0.001] was selected as the independent risk factor. The cox-regression model successfully stratified patients into the high-risk and low-risk groups regarding the time of MaVI development (P < 0.001), PFS (P < 0.001) and OS (P = 0.002). CONCLUSIONS The CT-based quantitative radiomics analysis could enable high accuracy prediction of subsequent MaVI development in HCC with prognostic implications.
Collapse
Affiliation(s)
- Jing-Wei Wei
- Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; Beijing Key Laboratory of Molecular Imaging, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Si-Rui Fu
- Zhuhai Interventional Medical Center, Zhuhai Precision Medical Center, Zhuhai People's Hospital, Zhuhai Hospital of Jinan University, Zhuhai 519000, China
| | - Jie Zhang
- Department of Radiology, Zhuhai Precision Medical Center, Zhuhai People's Hospital, Zhuhai Hospital of Jinan University, Zhuhai 519000, China
| | - Dong-Sheng Gu
- Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; Beijing Key Laboratory of Molecular Imaging, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Xiao-Qun Li
- Department of Interventional Treatment, Zhongshan City People's Hospital, Zhongshan 528400, China
| | - Xu-Dong Chen
- Department of Radiology, Shenzhen People's Hospital, Shenzhen 518000, China
| | - Shuai-Tong Zhang
- Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; Beijing Key Laboratory of Molecular Imaging, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Xiao-Fei He
- Interventional Diagnosis and Treatment Department, Nanfang Hospital, Southern Medical University, Guangzhou, 510000, China
| | - Jian-Feng Yan
- Department of Radiology, Yangjiang People's Hospital, Yangjiang 529500, China
| | - Li-Gong Lu
- Zhuhai Interventional Medical Center, Zhuhai Precision Medical Center, Zhuhai People's Hospital, Zhuhai Hospital of Jinan University, Zhuhai 519000, China.
| | - Jie Tian
- Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; Beijing Key Laboratory of Molecular Imaging, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China; Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Medicine and Engineering, Beihang University, Beijing 100191, China; Engineering Research Center of Molecular and Neuro Imaging of Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an 710126, China.
| |
Collapse
|
|
12
|
Benatatos N, Papadopoulou I, Assimakopoulos SF, Mulita F, Iliopoulos E, Germanos S, Vailas M, Kalogeropoulou C, Kitrou P, Maroulis I. Surgical management in hepatocellular carcinoma with portal vein tumour thrombosis: is this the end of the road or a chance to expand the criteria for resectability? PRZEGLAD GASTROENTEROLOGICZNY 2022; 17:257-265. [PMID: 36514454 PMCID: PMC9743323 DOI: 10.5114/pg.2022.118138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 05/19/2022] [Indexed: 12/16/2022]
Abstract
Portal vein thrombosis is a common complication associated with malignancies such as hepatocellular carcinoma, with a dismal and negative impact on prognosis. A thorough literature search in Pubmed and Google Scholar, under the terms 'hepatocellular carcinoma AND portal vein thrombosis', regarding the surgical management of portal vein thrombosis was conducted by the authors, and the associated results are presented in this narrative review. Precise classification of portal vein thrombosis and identification of subgroups of patients that will benefit from surgery is of paramount importance. Evolution of novel surgical techniques in liver resection and associated low morbidity and mortality rates in specialized hepatobiliary centres worldwide have been linked with promising results from the adoption of surgical management in these patients, when compared to systemic chemotherapy or arterial chemoembolization management that has traditionally been followed in such cases.
Collapse
Affiliation(s)
| | | | - Stelios F. Assimakopoulos
- Department of Internal Medicine and Infectious Diseases, University Hospital of Patras, Patras, Greece
| | - Francesk Mulita
- Department of Surgery, University Hospital of Patras, Patras, Greece
| | | | | | - Michail Vailas
- Department of Surgery, University Hospital of Patras, Patras, Greece
| | | | - Panagiotis Kitrou
- Department of Interventional Radiology, University Hospital of Patras, Patras, Greece
| | - Ioannis Maroulis
- Department of Surgery, University Hospital of Patras, Patras, Greece
| |
Collapse
|
|
13
|
Lian D, Wang W, Liu L, Wang J, Rao S, Zhou J. CT volumetry helps predict prognosis of large hepatocellular carcinoma after resection. Clin Radiol 2022; 77:e599-e605. [PMID: 35483982 DOI: 10.1016/j.crad.2022.03.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Accepted: 03/23/2022] [Indexed: 11/03/2022]
Abstract
AIM To determine whether the tumour volume measurement on preoperative contrast-enhanced computed tomography (CT) could be used to predict the overall survival patients with large hepatocellular carcinoma (>5 cm) after resection. MATERIALS AND METHODS This study included 171 patients with surgically confirmed hepatocellular carcinoma who underwent preoperative CT. The largest diameter, the product of the axial dimension, tumour volume, and tumour-to-liver volume ratio (TTLVR) on CT images were measured and calculated. The univariate and multivariate Cox proportional hazard ratio regression models were used to identify the impact of the tumour burden-related risk factors on overall survival. RESULTS In multivariate analysis, TTLVR (p=0.042) and major vascular invasion (p=0.006) were independently associated with overall survival of patients with hepatocellular carcinoma after the resection. The group in which the patients had a low TTLVR showed higher cumulative survival rates than patients with a TTLVR (p=0.004). Patients with a low TTLVR (≤26.23%) and absence of major vascular invasion had significantly higher cumulative survival rates compared to those patients with hepatocellular carcinoma with either or both the risk factors (p=0.001). CONCLUSION A higher TTLVR in combination with the presence of major vascular invasion was associated with poorer overall survival in patients with large hepatocellular carcinoma after resection.
Collapse
Affiliation(s)
- D Lian
- Department of Radiology, Xiamen Branch, Zhongshan Hospital, Fudan University, No. 668 Jinhu Road, Huli District, Xiamen 361015, China
| | - W Wang
- Department of Radiology, Cancer Center, Zhongshan Hospital, Fudan University and Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai 200032, China
| | - L Liu
- Department of Radiology, Cancer Center, Zhongshan Hospital, Fudan University and Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai 200032, China
| | - J Wang
- Department of Radiology, Cancer Center, Zhongshan Hospital, Fudan University and Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai 200032, China
| | - S Rao
- Department of Radiology, Cancer Center, Zhongshan Hospital, Fudan University and Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai 200032, China.
| | - J Zhou
- Department of Radiology, Xiamen Branch, Zhongshan Hospital, Fudan University, No. 668 Jinhu Road, Huli District, Xiamen 361015, China.
| |
Collapse
|
|
14
|
Tao ZW, Cheng BQ, Zhou T, Gao YJ. Management of hepatocellular carcinoma patients with portal vein tumor thrombosis: A narrative review. Hepatobiliary Pancreat Dis Int 2022; 21:134-144. [PMID: 34955380 DOI: 10.1016/j.hbpd.2021.12.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 11/05/2021] [Indexed: 02/09/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is one of the main reasons for malignancy-related death. Portal vein tumor thrombosis (PVTT) is the most common form of macrovascular invasion related to HCC occurring in 10%-60% of patients. HCC with PVTT is usually characterized by worsening liver function, vulnerability to blood metastasis, higher incidence of complications associated with portal hypertension, and intolerance to treatment when compared with that without PVTT. If only treated with supportive care, the median survival of HCC with PVTT is about 2.7 months. In the past, sorafenib was the only recommended therapy by guidelines with limited effectiveness. This narrative review aimed to describe the current management options for HCC with PVTT. DATA SOURCES We have reviewed literature from PubMed on the treatment of HCC with PVTT and compiled evidence-based facts on effective therapies available for different types of PVTT. RESULTS Sorafenib monotherapy is not much effective, but combining it with other methods can improve survival. Each type of PVTT can benefit from the combination of transarterial chemoembolization and sorafenib than sorafenib monotherapy. The tumor downstaging can be realized possibly after transarterial chemoembolization, but tumor invasion into the main trunk of the portal vein greatly impairs efficacy. Although surgery is a curative approach, it is often not recommended for Vp4 PVTT. Some new methods can broaden the indication, but further explorations are needed. Radiotherapy can decrease the possibility of Vp3 progression to Vp4, but building a forecast model of best radiation dose and response is necessary. Systemic chemotherapy, hepatic arterial infusion chemotherapy, radiofrequency ablation, portal stenting, and traditional Chinese medicine are also beneficial in Vp3-4 PVTT. The accurate diagnosis of PVTT can be made by radiomics, and prognostic classification models can be used to design personalized treatments. The application of new treatment methods such as the atezolizumab plus bevacizumab scheme may increase survival. CONCLUSIONS HCC with PVTT is still a thorny problem, and effective therapeutics need to be explored.
Collapse
Affiliation(s)
- Zi-Wen Tao
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Bao-Quan Cheng
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Tao Zhou
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Yan-Jing Gao
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
| |
Collapse
|
|
15
|
Famularo S, Donadon M, Cipriani F, Giuliante F, Ferri S, Celsa C, Ferrero A, Foschi FG, Baiocchi GL, Biasini E, Campani C, Valle RD, Pelizzaro F, Baroni GS, Raimondo G, Mega A, Chiarelli M, Maestri M, Gasbarrini A, Jovine E, Grazi GL, Rapaccini GL, Ruzzenente A, Morisco F, Sacco R, Memeo R, Crespi M, Antonucci A, Bernasconi DP, Romano F, Griseri G, Aldrighetti L, Torzilli G, Trevisani F. Hepatectomy Versus Sorafenib in Advanced Nonmetastatic Hepatocellular Carcinoma: A Real-life Multicentric Weighted Comparison. Ann Surg 2022; 275:743-752. [PMID: 35081572 DOI: 10.1097/sla.0000000000005373] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
OBJECTIVE The aim of the study was to compare SURG vs SOR regarding the OS and progression-free survival (PFS) in a real-world clinical scenario. BACKGROUND DATA The treatment for advanced nonmetastatic HCC belonging to the Barcelona Clinic Liver Cancer stage C (BCLC C) is still controversial. METHODS BCLC C patients without extrahepatic spread and tumoral invasion of the main portal trunk were considered. Surgical patients were obtained from the HE.RC.O.LE.S. Register, whereas sorafenib patients were obtained from the ITA.LI.CA register The inverse probability weighting (IPW) method was adopted to balance the confounders between the 2 groups. RESULTS Between 2008 and 2019, 478 patients were enrolled: 303 in SURG and 175 in SOR group. Eastern Cooperative Oncological Group Performance Status (ECOG-PS), presence of cirrhosis, steatosis, Child-Pugh grade, hepatitis B virus and hepatitis C virus, alcohol intake, collateral veins, bilobar disease, localization of the tumor thrombus, number of nodules, alpha-fetoprotein, age, and Charlson Comorbidity index were weighted by IPW to create two balanced pseudo-populations: SURG = 374 and SOR = 263. After IPW, 1-3-5 years OS was 83.6%, 68.1%, 55.9% for SURG, and 42.3%, 17.8%, 12.8% for SOR (P < 0.001). Similar trends were observed after subgrouping patients by ECOG-PS = 0 and ECOG-PS >0, and by the intrahepatic location of portal vein invasion. At Cox regression, sorafenib treatment (hazard ratio 4.436; 95% confidence interval 3.19-6.15; P < 0.001) and Charlson Index (hazard ratio 1.162; 95% confidence interval 1.06-1.27; P = 0.010) were the only independent predictors of mortality. PFS at 1-3-5 years were 65.9%, 40.3%, 24.3% for SURG and 21.6%, 3.5%, 2.9% for SOR (P = 0.007). CONCLUSIONS In BCLC C patients without extrahepatic spread but with intrahepatic portal invasion, liver resection, if feasible, was followed by better OS and PFS compared with sorafenib.
Collapse
Affiliation(s)
- Simone Famularo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
- School of Medicine and Surgery, University of Milan-Bicocca, Department of Surgery, San Gerardo Hospital, Monza, Italy
| | - Matteo Donadon
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Federica Cipriani
- Hepatobiliary Surgery Division, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Felice Giuliante
- Hepatobiliary Surgery Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Catholic University of the Sacred Heart, Rome, Italy
| | - Silvia Ferri
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Ciro Celsa
- Division of Gastroenterology and Hepatology, Department Promozione della Salute, Materno Infantile, Medicina Interna e Specialistica di Eccellenza (PROMISE), University of Palermo, Palermo, Italy
| | - Alessandro Ferrero
- Department of General and Oncological Surgery, Mauriziano Hospital "Umberto I," Turin, Italy
| | | | - Gian Luca Baiocchi
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Elisabetta Biasini
- Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | - Claudia Campani
- Internal Medicine and Hepatology Unit, Department of Experimental and Clinical Medicine, University of Firenze, Florence, Italy
| | | | - Filippo Pelizzaro
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, Padua University, Padua, Italy
| | | | - Giovanni Raimondo
- Division of Clinical and Molecular Hepatology, University of Messina, Messina, Italy
| | - Andrea Mega
- Division of Gastroenterology, Bolzano Regional Hospital, Bolzano, Italy
| | - Marco Chiarelli
- Department of Emergency and Robotic Surgery, ASST Lecco, Lecco, Italy
| | - Marcello Maestri
- Unit of General Surgery 1, University of Pavia and Foundation IRCCS Policlinico San Matteo, Pavia, Italy
| | - Antonio Gasbarrini
- Division of Internal Medicine and Gastroenterology, Policlinico Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Elio Jovine
- Alma Mater Studiorum, University of Bologna, AOU Sant'Orsola Malpighi, IRCCS at Maggiore Hospital, Bologna, Italy
| | - Gian Luca Grazi
- Division of Hepatobiliarypancreatic Unit, IRCCS - Regina Elena National Cancer Institute, Rome, Italy
| | - Gian Ludovico Rapaccini
- Division of Internal Medicine and Gastroenterology, Complesso Integrato Columbus, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Andrea Ruzzenente
- Division of General and Hepatobiliary Surgery, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy
| | - Filomena Morisco
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, University of Napoli "Federico II," Napoli, Italy
| | - Rodolfo Sacco
- Gastroenterology and Digestive Endoscopy Unit, Foggia University Hospital, Foggia, Italy
| | - Riccardo Memeo
- Department of Hepato-Pancreatic-Biliary Surgery, Miulli Hospital, Bari, Italy
| | | | | | - Davide P Bernasconi
- Center of Biostatistics for Clinical Epidemiology, School of Medicine and Surgery, University of Milan - Bicocca, Monza, Italy
| | - Fabrizio Romano
- School of Medicine and Surgery, University of Milan-Bicocca, Department of Surgery, San Gerardo Hospital, Monza, Italy
| | - Guido Griseri
- HPB Surgical Unit, San Paolo Hospital, Savona, Italy
| | - Luca Aldrighetti
- Hepatobiliary Surgery Division, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Guido Torzilli
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Franco Trevisani
- IRCCS Azienda Ospedaliero-universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, Semeiotics Unit, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| |
Collapse
|
|
16
|
Jia J, Sun J, Duan X, Li W. Clinical Values and Markers of Radiation-Induced Liver Disease for Hepatocellular Carcinoma With Portal Vein Tumor Thrombus Treated With Stereotactic Body Radiotherapy. Front Oncol 2022; 11:760090. [PMID: 34970485 PMCID: PMC8712705 DOI: 10.3389/fonc.2021.760090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Accepted: 11/08/2021] [Indexed: 11/24/2022] Open
Abstract
Background Information about radiation-induced liver disease (RILD) in hepatocellular carcinoma (HCC) patients preexisting hepatitis B cirrhosis with portal vein tumor thrombus (PVTT) extended to the main portal vein treated with stereotactic body radiotherapy (SBRT) is still inadequate and the predictive markers for RILD have not been cleared in these patients. The aim of the study is to identify factors that can be used to predict RILD and to evaluate the influence of RILD in these patients. Methods In our study, 59 patients were analyzed and evaluated from December 2015 to June 2019, according to the entry criteria. After treatment, 59 patients were followed up within the first month and then every 3 months. Hematology test, tumor markers, three-phasic CT scan of the lungs, and CT or MRI scan of the liver were performed at each follow up. Results Median overall survival time was 10.7 months (range, 5.8 to 14.9). RILD appeared in 17 of the 59 patients (28.8%) at the 3rd month after SBRT. In the univariate analysis, not only the CP score class (A or B) but also each different pretreatment CP score (p < 0.05) was a significant predictive factor of RILD. More RILD cases were detected with the increase of CP score. The recovery rate decreased as the baseline CP score increased (p < 0.05). It was found that the overall survival time was affected by only baseline CP score and RILD (p < 0.05). Conclusions The development of RILD has a dependency on the CP score in these patients. CP scores before treatment and RILD are significantly associated with overall survival. SBRT is an effective and safe method for patients with CP ≤ B7. For patients with CP-B8, liver function should be monitored more frequently. It is not safe enough for the SBRT treatment in CP-B9 patients.
Collapse
Affiliation(s)
- Jun Jia
- Radiation Oncology Department, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Jing Sun
- Radiation Oncology Department, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Xuezhang Duan
- Radiation Oncology Department, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Wengang Li
- Radiation Oncology Department, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| |
Collapse
|
|
17
|
Pan Y, Mei J, Chen J, Zhang D, Wang J, Wang X, Yi M, Zhou Z, Zhang Y, Chen M, Guo R, Xu L. Comparison Between Portal Vein Perfusion Chemotherapy and Neoadjuvant Hepatic Arterial Infusion Chemotherapy for Resectable Intermediate to Advanced Stage Hepatocellular Carcinoma. Ann Surg Oncol 2021; 29:2016-2029. [PMID: 34637058 DOI: 10.1245/s10434-021-10903-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Accepted: 09/19/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Patients with intermediate to advanced stage hepatocellular carcinoma (HCC; Barcelona Clinic Liver Cancer [BCLC] stage B/C) have few choices of curable treatments and thus suffer from dismal outcomes. Although surgical resection could prolong survival in certain selected patients with BCLC stage B/C HCC, the frequent postoperative recurrence and poor survival of these patients need to be improved by combining other therapies perioperatively. OBJECTIVE This study was conducted to investigate the survival associations of adjuvant portal vein perfusion chemotherapy (PVC) and neoadjuvant hepatic arterial infusion chemotherapy (HAIC) in patients with resectable BCLC stage B/C HCC. METHODS A retrospective study was conducted in consecutive patients who underwent R0 resection for intermediate to advanced stage HCC, combined with either PVC or HAIC perioperatively between January 2017 and December 2018. Patients treated with PVC or HAIC were analyzed according to intention-to-treat (ITT) and per protocol (PP) principles, respectively. The chemotherapy regimen of adjuvant PVC and neoadjuvant HAIC included 5-fluorouracil/leucovorin/oxaliplatin. Survival analysis and Cox regression for overall survival (OS) and event-free survival (EFS) were used to compare the outcomes. RESULTS Among all 64 patients enrolled in this study, 28 received perioperative PVC and 36 received HAIC for ITT analysis. Age (median 44.00 vs. 46.50 years; p = 0.364), sex (male: 25/28 vs. 35/36; p = 0.435), and tumor size (median 9.55 vs. 8.10 cm; p = 0.178) were comparable between the two groups. In the ITT analysis, the median OS was significantly longer in patients in the HAIC group compared with the PVC group (median OS not reached vs. 19.47 months; p = 0.004); in the PP analysis, patients who received neoadjuvant HAIC followed by hepatectomy presented with much better EFS than patients in the PVC group (modified EFS 16.90 vs. 3.17 months; p = 0.022); and in the multivariate analysis, neoadjuvant HAIC presented as a significant predictor for enhanced EFS (hazard ratio [HR] 0.296; p = 0.007) and OS (HR 0.095; p = 0.007) for BCLC stage B/C HCC patients who received hepatectomy. CONCLUSIONS Compared with adjuvant PVC, neoadjuvant HAIC treatment was associated with better survival and fewer recurrences in HCC patients who received R0 resection at the intermediate to advanced stage. These results need to be further validated prospectively.
Collapse
Affiliation(s)
- Yangxun Pan
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.,Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Stockholm, Sweden
| | - Jie Mei
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Jinbin Chen
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Deyao Zhang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Juncheng Wang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Xiaohui Wang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Minjiang Yi
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Zhongguo Zhou
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Yaojun Zhang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Minshan Chen
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Rongping Guo
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Li Xu
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China. .,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.
| |
Collapse
|
|
18
|
Shehta A, Farouk A, Elghawalby AN, Elshobary M, Aboelenin A, Fouad A, Ali MA. Outcomes of Hepatic Resection for Hepatocellular Carcinoma Associated with Portal Vein Invasion. J Surg Res 2021; 266:269-283. [PMID: 34038849 DOI: 10.1016/j.jss.2021.04.011] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 04/02/2021] [Accepted: 04/10/2021] [Indexed: 01/27/2023]
Abstract
BACKGROUND To evaluate our experience of liver resection for hepatocellular carcinoma (HCC) patients associated with macroscopic portal vein invasion (PVI). METHODS Consecutive HCC patients who underwent liver resection for HCC between November 2009 & June 2019 were included. To overcome selection bias between patients with and without macroscopic PVI, we performed 1:1 match using propensity score matching (PSM). RESULTS Macroscopic PVI was detected in 37 patients (12.8%). We divided our patients into two groups according to the presence of macroscopic PVI. After PSM, 36 patients of PVI group were matched with 36 patients from Non-PVI group. After PSM, both groups were well balanced regarding tumor site, number, liver resection extent and type. Longer operation time and more blood loss were noted in PVI group. Higher incidence of post-operative morbidities occurred in PVI group especially, post-hepatectomy liver dysfunction. The 1-, 2-, and 3-y overall survival rates for Non-PVI group were 85.3%, 64.6%, and 64.6% & 69.8%, 42%, and 0% for PVI group, respectively (P = 0.009). There were no significant differences regarding the recurrence rate, site, and its management. The 1-, 2-, and 3-y disease-free survival (DFS) rates for Non-PVI group were 81.7%, 72.3%, and 21.7% & 67.7%, 42.3%, and 0% for PVI group, respectively (P = 0.172). CONCLUSION Surgical management of advanced HCCs with macroscopic PVI is feasible, and associated with comparable DFS but poorer overall survival, compared to patients without PVI.
Collapse
Affiliation(s)
- Ahmed Shehta
- Gastrointestinal Surgery Center, Department of Surgery, College of Medicine, Mansoura University, Mansoura, Egypt.
| | - Ahmed Farouk
- Gastrointestinal Surgery Center, Department of Surgery, College of Medicine, Mansoura University, Mansoura, Egypt
| | - Ahmed Nabieh Elghawalby
- Gastrointestinal Surgery Center, Department of Surgery, College of Medicine, Mansoura University, Mansoura, Egypt
| | - Mohamed Elshobary
- Gastrointestinal Surgery Center, Department of Surgery, College of Medicine, Mansoura University, Mansoura, Egypt
| | - Ahmed Aboelenin
- Gastrointestinal Surgery Center, Department of Surgery, College of Medicine, Mansoura University, Mansoura, Egypt
| | - Amgad Fouad
- Gastrointestinal Surgery Center, Department of Surgery, College of Medicine, Mansoura University, Mansoura, Egypt
| | - Mahmoud Abdelwahab Ali
- Gastrointestinal Surgery Center, Department of Surgery, College of Medicine, Mansoura University, Mansoura, Egypt
| |
Collapse
|
|
19
|
Nevarez NM, Yopp AC. Challenging the Treatment Paradigm: Selecting Patients for Surgical Management of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus. J Hepatocell Carcinoma 2021; 8:851-860. [PMID: 34350140 PMCID: PMC8327188 DOI: 10.2147/jhc.s291530] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 07/14/2021] [Indexed: 01/06/2023] Open
Abstract
Portal vein tumor thrombus (PVTT) remains a common presentation in patients with hepatocellular carcinoma (HCC). Approximately 30-50% of patients newly diagnosed with HCC will present with a concomitant PVTT. Current guidelines recommend systemic therapy for treatment of HCC with PVTT. Real-world application of partial hepatectomy in HCC patients with PVTT has increased over the past two decades, as perioperative complications have declined. However, it is unclear if there is an association between the extent of PVTT and overall survival and rates of recurrence and whether the perioperative morbidity outweighs these potential benefits. Partial hepatectomy with en bloc resection of PVTT in second-order branches and distal can offer significant benefits in carefully selected patients; however, once the HCC-associated PVTT extends into first-order portal venous branches or more proximal into the superior mesenteric vein, the risks of surgical resection outweigh the benefits. The aim of this review is to determine which patients with HCC presenting with PVTT benefit from surgical resection. We will discuss the classification systems of PVTT and review both outcome and perioperative measures in patients undergoing partial hepatectomy with extirpation of HCC-related PVT.
Collapse
Affiliation(s)
- Nicole M Nevarez
- Department of Surgery, Division of Surgical Oncology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA
| | - Adam C Yopp
- Department of Surgery, Division of Surgical Oncology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA
| |
Collapse
|
|
20
|
Bae B, Song SK, Choi E, Chung CW, Park Y. Secondarily estimated cure fraction and five-year recurrence-free conditional survival probabilities among patients undergoing surgical resection for hepatocellular carcinoma presenting with minor gross vascular invasion. World J Surg Oncol 2021; 19:222. [PMID: 34311741 PMCID: PMC8314459 DOI: 10.1186/s12957-021-02331-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Accepted: 07/10/2021] [Indexed: 01/27/2023] Open
Abstract
BACKGROUND Surgical resection (SR) has been selectively applied in hepatocellular carcinoma (HCC) presenting with minor gross vascular invasion (mGVI) which is defined when tumor invasion is confined to second-order portal branches or segmental branches of hepatic vein. However, little data of long-term outcomes are available for supporting the role of SR as a potentially curable therapeutic option for HCC presenting with mGVI. This study is aimed to estimate a statistical cure fraction and the improvement of recurrence-free conditional survival (RFCS) over time among patients undergoing SR for HCC presenting with mGVI. METHODS The literature search was conducted focusing on previous studies that investigated the long-term survival rates of patients after SR for HCC presenting with mGVI. The reference cohort was extracted from a study including patients undergoing SR for HCC without vascular invasion. A non-mixture cure model was adopted to estimate the statistical cure fraction. The 5-year RFCS probabilities were also calculated. RESULTS Three retrospective studies were secondarily analyzed. The probability of being statistically cured after SR for HCC presenting with mGVI was 7.3% (95% confidence interval, 4.4%-11.2%) in the mGVI group, lower than that of the reference cohort (hazard ratio, 1.81; 95% confidence interval, 1.59-2.05). The estimated 5-year RFCS probabilities improved with each additional year of survival. Moreover, 1 year after SR, the 5-year RFCS probabilities of patients with HCC presenting with mGVI was essentially the same as that of the reference cohort. CONCLUSIONS This study shows that a cure can be expected in around seven percent of patients undergoing SR for HCC presenting with mGVI. Furthermore, recurrence-free survival expectancy improves dramatically over time among those patients who do not have recurrence. Overall, these findings suggest that SR should be considered as a potentially curable treatment for patients with HCC presenting with mGVI.
Collapse
Affiliation(s)
- Byungje Bae
- Department of Surgery, Catholic Kwandong University International St. Mary's Hospital, Catholic Kwandong University College of Medicine, 25 Simgokro 100gil, Seo-gu, 22711, Incheon, Korea
| | - Sung Kyu Song
- Department of Surgery, Catholic Kwandong University International St. Mary's Hospital, Catholic Kwandong University College of Medicine, 25 Simgokro 100gil, Seo-gu, 22711, Incheon, Korea.,Catholic Kwandong University College of Medicine, Incheon, Korea
| | - Eunyoung Choi
- Catholic Kwandong University College of Medicine, Incheon, Korea
| | - Chul-Woon Chung
- Department of Surgery, Catholic Kwandong University International St. Mary's Hospital, Catholic Kwandong University College of Medicine, 25 Simgokro 100gil, Seo-gu, 22711, Incheon, Korea.,Catholic Kwandong University College of Medicine, Incheon, Korea
| | - Yongkeun Park
- Department of Surgery, Catholic Kwandong University International St. Mary's Hospital, Catholic Kwandong University College of Medicine, 25 Simgokro 100gil, Seo-gu, 22711, Incheon, Korea. .,Catholic Kwandong University College of Medicine, Incheon, Korea.
| |
Collapse
|
|
21
|
Carr BI, Guerra V, Donghia R, Yilmaz S. Tumor multifocality and serum albumin levels can identify groups of patients with hepatocellular carcinoma and portal vein thrombosis having distinct survival outcomes. Ann Med Surg (Lond) 2021; 66:102458. [PMID: 34141428 PMCID: PMC8187816 DOI: 10.1016/j.amsu.2021.102458] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 05/26/2021] [Accepted: 05/26/2021] [Indexed: 02/07/2023] Open
Abstract
Background Macroscopic portal vein thrombosis (PVT) is a major poor prognosis factor in patients with hepatocellular carcinoma (HCC), but constitute a heterogeneous group. Aims To examine blood and tumor parameters of 1667 HCC patients who had PVT to identify factors that could differentiate different survival subsets. Methods a large HCC database was examined for presence of patients with PVT and analyzed retrospectively for PVT-associated factors and prognosis. Results A logistic regression model was calculated for presence of PVT. Highest odds ratios were found for tumor multifocality and serum albumin levels, as well as serum alpha-fetoprotein (AFP) and bilirubin levels. A Kaplan-Meier and Cox model on survival also showed the highest hazard ratios for tumor multifocality and serum albumin. A model was constructed on all 4 possible combinations of tumor focality and serum albumin in PVT patients. The longest survival group had <2 tumor nodules plus serum albumin >3.5 g/dL. Conversely, the shortest survival group had >2 tumor nodules plus serum albumin <3.5 g/dL. These 2 patient groups differed in maximum tumor diameter and levels of serum AFP, AST and bilirubin. Conclusions Combination low tumor focality and high serum albumin identifies prognostically better PVT patient subgroups that might benefit from aggressive therapies.
Portal vein thrombosis (PVT) is a major poor prognosis factor in HCC patients. We found that the highest odds ratios for PVT included number of tumor foci and serum albumin levels. A model was constructed with all 4 possible combinations of these 2 parameters. The longest survival group had <2 tumor nodules plus normal albumin. Conversely, the shortest survival group had >2 tumor nodules plus low albumin. These 2 PVT groups had a 3-fold difference in survival and had significantly different AFP and bilirubin levels. These findings provide simple patient selection criteria for treating in PVT patients.
Collapse
Affiliation(s)
- B I Carr
- Liver Transplantation Institute, İnönü University, Malatya, Turkey
| | - V Guerra
- National Institute of Gastroenterology, S. de Bellis Research Hospital, Turkey
| | - R Donghia
- National Institute of Gastroenterology, S. de Bellis Research Hospital, Turkey
| | - S Yilmaz
- Liver Transplantation Institute, İnönü University, Malatya, Turkey
| |
Collapse
|
|
22
|
Li X, Ye Z, Lin S, Pang H. Predictive factors for survival following stereotactic body radiotherapy for hepatocellular carcinoma with portal vein tumour thrombosis and construction of a nomogram. BMC Cancer 2021; 21:701. [PMID: 34126955 PMCID: PMC8204556 DOI: 10.1186/s12885-021-08469-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Accepted: 06/08/2021] [Indexed: 02/06/2023] Open
Abstract
Background We evaluated the treatment response and predictive factors for overall survival (OS) in patients with hepatocellular carcinoma (HCC) and portal vein tumour thrombosis (PVTT), who underwent stereotactic body radiotherapy (SBRT). Additionally, we developed and validated a personalised prediction model for patient survival. Methods Clinical information was retrospectively collected for 80 patients with HCC and PVTT, who were treated with SBRT at the Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) between December 2015 and June 2019. A multivariate Cox proportional hazard regression model was used to identify the independent predictive factors for survival. Clinical factors were subsequently presented in a nomogram. The area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA) were used to evaluate the accuracy of the model and the net clinical benefit. Results All patients completed the planned radiotherapy treatment, and the median follow-up duration was 10 months (range, 1–35.3 months). The median survival duration was 11.5 months, with 3-, 6-, and 12-month survival rates of 92.5, 74.5, and 47.5%, respectively. The multivariable Cox regression model indicated that the following were significant independent predictors of OS: clinical T stage (p = 0.001, hazard ratio [HR] = 3.085, 95% confidence interval [CI]: 1.514–6.286), cirrhosis (p = 0.014, HR = 2.988, 95% CI: 1.246–7.168), age (p = 0.005, HR = 1.043, 95% CI: 1.013–1.075), alpha-fetoprotein level (p = 0.022, HR = 1.000, 95% CI: 1.000–1.000), and haemoglobin level (p = 0.008, HR = 0.979, 95% CI: 0.963–0.994). A nomogram based on five independent risk factors and DCA demonstrated a favourable predictive accuracy of patient survival (AUC = 0.74, 95% CI: 0.63–0.85) and the clinical usefulness of the model. Conclusions SBRT is an effective treatment for patients with HCC with PVTT. Notably, clinical T stage, presence of cirrhosis, age, alpha-fetoprotein levels, and haemoglobin levels are independent prognostic factors for survival. The presented nomogram can be used to predict the survival of patients with HCC and PVTT, who underwent SBRT.
Collapse
Affiliation(s)
- Xiaojie Li
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Zhimin Ye
- Department of Radiation Oncology, Cancer Hospital of The University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, 310022, China
| | - Sheng Lin
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China.
| | - Haowen Pang
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China.
| |
Collapse
|
|
23
|
HCC with portal vein tumor thrombosis: how to manage? Hepatol Int 2020; 14:609-611. [PMID: 32949378 DOI: 10.1007/s12072-020-10090-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Accepted: 09/04/2020] [Indexed: 10/23/2022]
|
|
24
|
Hou Z, Zhu K, Yang X, Zhou H, Chen P, Yu G, Zhu X, Cui Y, Song T, Li Q, Li H, Zhang T. Resection of "down-staged" advanced hepatocellular carcinoma after treatment with the VEGFR2 inhibitor apatinib: five cases report. Transl Cancer Res 2020; 9:4999-5007. [PMID: 35117862 PMCID: PMC8799223 DOI: 10.21037/tcr-19-3019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Accepted: 07/03/2020] [Indexed: 11/06/2022]
Abstract
Sorafenib and lenvatinib are currently standard treatments for advanced hepatocellular carcinoma (HCC); however, the therapeutic effect is unsatisfying. Indeed, very few patients with HCC under sorafenib treatment were eligible for surgery in the past ten years. In addition, there is no report of a patient with the opportunity to undergo radical resection after treatment with lenvatinib. Here, we describe five patients with advanced and unresectable HCC that were able to receive curative resection within 1 year of treatment with the tyrosine kinase inhibitor apatinib that selectively inhibits vascular endothelial growth factor receptor 2 (VEGFR2). The five patients with advanced and unresectable HCC were treated with apatinib (250 mg po, qd), and all the five patients obtained an objective response to the treatment, allowing for subsequent resection, and the second patient even obtained a pathological complete response. The latest follow-up date was August 20, 2019, and all patients were alive at the latest follow-up. The disease-free survival of the first patient was 13 months. Lung metastasis was found 12 months later after surgery for patient 5. The other three patients have no recurrence. This is the first report of a single drug with promising therapeutic effects in patients with advanced HCC within one year at a single center. Therefore, apatinib may be promising for some patients with locally advanced HCC to undergo radical resection and improve outcomes.
Collapse
Affiliation(s)
- Zhenyu Hou
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, China
| | - Keyun Zhu
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, China
| | - Xuejiao Yang
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, China
| | - Hongyuan Zhou
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, China
| | - Ping Chen
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, China
| | - Ge Yu
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, China
| | - Xiaolin Zhu
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, China
| | - Yunlong Cui
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, China
| | - Tianqiang Song
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, China
| | - Qiang Li
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, China
| | - Huikai Li
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, China
| | - Ti Zhang
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, China
| |
Collapse
|
|
25
|
Liu Y, Li Y, Wang X, Huang Y, Zhang Q, Shi K, Ran C, Hou J, Wang X. Fufang Banmao Capsule, a Traditional Chinese Medicinal Formulation, Enhances the Survival of Patients with Hepatocellular Carcinoma and Vp3-4 Portal Vein Tumor Thrombosis Undergoing Supportive Treatment. J Altern Complement Med 2020; 26:956-965. [PMID: 32614605 DOI: 10.1089/acm.2019.0334] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Objectives: Fufang Banmao (FFBM) capsule, a type of Chinese medicinal formulation, has decades of history in treating hepatocellular carcinoma (HCC). This retrospective study aimed to observe the effect of FFBM capsules on the 6-month survival of patients with advanced HCC and Vp3-4 portal vein tumor thrombosis (PVTT) who received supportive therapy alone. Design: In total, 320 HCC/Vp3-4 PVTT patients underwent treatment with supportive therapy, of whom 95 took FFBM capsules and were treated with supportive therapy (FFBM group) and 225 received supportive therapy alone (control group). Comparisons of the 6-month overall survival (OS) rate of the two groups were performed. Propensity score matching (PSM) was used to match the characteristics between individuals in the two groups. A nomogram was built based on independent predictive factors for OS. Results: Cox multivariate analysis revealed that hepatic encephalopathy, aspartate transaminase (AST) and γ-glutamyl transpeptidase levels, Child-Pugh class, prothrombin time, α-fetoprotein level, largest tumor diameter, and use of FFBM capsules were independent predictive factors of OS. Variceal bleeding, alanine transaminase, AST, total bilirubin, and Barcelona Clinic for Liver Cancer stage were different at baseline in the FFBM and control groups. Analysis revealed no significant adverse effects or toxicities relevant to the medications. After PSM (1:1), 95 patient pairs were analyzed as FFBM versus control. The OS probability was remarkably higher for patients in the FFBM group than in those in the control group at 6 months (p < 0.0001). The median survival time was 4 months in the FFBM group and 2.2 months in the control group. Kaplan-Meier analysis showed significant statistical differences in the 6-month OS rates in the patients with total nomogram scores ≥84 (p < 0.0001). Conclusions: Given the satisfying survival outcomes, the results suggested that FFBM capsules should be administered to patients with HCC/Vp3-4 PVTT in the high-risk group (score ≥84). FFBM capsules have the potential for improving patient survival time in those with advanced HCC and Vp3-4 PVTT who receive supportive therapy alone, especially those in the high-risk group (score ≥84).
Collapse
Affiliation(s)
- Yao Liu
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yuxin Li
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xiaojing Wang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yunyi Huang
- Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Qun Zhang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ke Shi
- Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Chongping Ran
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Jie Hou
- Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Xianbo Wang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| |
Collapse
|
|
26
|
Tang K, Zhang B, Dong L, Wang L, Jin Y, Tang Z. Successful treatment of a huge hepatic carcinoma with right portal vein thrombosis: A case report. Medicine (Baltimore) 2020; 99:e19636. [PMID: 32332607 PMCID: PMC7220512 DOI: 10.1097/md.0000000000019636] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
INTRODUCTION Unlike the traditional associating liver partition and portal vein ligation for staged hepatectomy, it is still controversial whether patients with portal vein thrombosis can receive benefits from liver partition. PATIENT CONCERNS Right upper abdominal distension for 2 months. DIAGNOSIS Hepatocellular carcinoma with portal vein invasion INTERVENTION:: Radiofrequency-assisted liver partition with portal vein ligation (RALPP) OUTCOMES:: Disease-free survival: 3 months, overall survival: 7 months CONCLUSION:: Our results advocate this variation of RALPP for use in patients with huge HCC with portal vein invasion, without enough future liver remnant. Patients can receive benefits from the operation, including a shorter operation time, better recovery, and lower overall costs of the 2-stage procedure.
Collapse
Affiliation(s)
| | - Bo Zhang
- Department of Surgery, 2nd Affiliated Hospital
| | | | | | - Yecheng Jin
- Department of Pharmacy, Affiliated Sir RunRun Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, PR China
| | - Zhe Tang
- Department of Surgery, 2nd Affiliated Hospital
| |
Collapse
|
|
27
|
Cerrito L, Annicchiarico BE, Iezzi R, Gasbarrini A, Pompili M, Ponziani FR. Treatment of hepatocellular carcinoma in patients with portal vein tumor thrombosis: Beyond the known frontiers. World J Gastroenterol 2019; 25:4360-4382. [PMID: 31496618 PMCID: PMC6710186 DOI: 10.3748/wjg.v25.i31.4360] [Citation(s) in RCA: 85] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2019] [Revised: 06/24/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma is one of the most frequent malignant tumors worldwide: Portal vein tumor thrombosis (PVTT) occurs in about 35%-50% of patients and represents a strong negative prognostic factor, due to the increased risk of tumor spread into the bloodstream, leading to a high recurrence risk. For this reason, it is a contraindication to liver transplantation and in several prognostic scores sorafenib represents its standard of care, due to its antiangiogenetic action, although it can grant only a poor prolongation of life expectancy. Recent scientific evidences lead to consider PVTT as a complex anatomical and clinical condition, including a wide range of patients with different prognosis and new treatment possibilities according to the degree of portal system involvement, tumor biological aggressiveness, complications caused by portal hypertension, patient's clinical features and tolerance to antineoplastic treatments. The median survival has been reported to range between 2.7 and 4 mo in absence of therapy, but it can vary from 5 mo to 5 years, thus depicting an extremely variable scenario. For this reason, it is extremely important to focus on the most adequate strategy to be applied to each group of PVTT patients.
Collapse
MESH Headings
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Carcinoma, Hepatocellular/complications
- Carcinoma, Hepatocellular/mortality
- Carcinoma, Hepatocellular/therapy
- Chemoembolization, Therapeutic/methods
- Contrast Media/administration & dosage
- Disease-Free Survival
- Hepatectomy
- Humans
- Hypertension, Portal/etiology
- Hypertension, Portal/mortality
- Hypertension, Portal/therapy
- Liver Neoplasms/complications
- Liver Neoplasms/mortality
- Liver Neoplasms/therapy
- Liver Transplantation
- Neoadjuvant Therapy/methods
- Neoplasm Invasiveness/pathology
- Neoplasm Recurrence, Local/epidemiology
- Neoplasm Recurrence, Local/pathology
- Neoplasm Recurrence, Local/prevention & control
- Patient Selection
- Portal Vein/diagnostic imaging
- Portal Vein/pathology
- Prognosis
- Survival Analysis
- Thrombectomy
- Time Factors
- Ultrasonography/methods
- Venous Thrombosis/etiology
- Venous Thrombosis/mortality
- Venous Thrombosis/therapy
Collapse
Affiliation(s)
- Lucia Cerrito
- Division of Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Brigida Eleonora Annicchiarico
- Division of Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Roberto Iezzi
- Department of Bioimaging and Radiological Sciences, Institute of Radiology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Antonio Gasbarrini
- Division of Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Maurizio Pompili
- Division of Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Francesca Romana Ponziani
- Division of Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| |
Collapse
|
|
28
|
Jiang LH, Hao YL, Zhu JW. Expression and prognostic value of HER-2/neu, STAT3 and SOCS3 in hepatocellular carcinoma. Clin Res Hepatol Gastroenterol 2019; 43:282-291. [PMID: 30385249 DOI: 10.1016/j.clinre.2018.09.011] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2018] [Revised: 09/18/2018] [Accepted: 09/28/2018] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS Hepatocellular carcinoma (HCC) is a complex and heterogeneous tumor with several genomic alterations, while the viral-chemical etiology along with molecular mechanisms of HCC pathogenesis remains largely unknown. This study aimed to determine expression profile and prognostic value of HER-2/neu, STAT3 and SOCS3 in HCC. METHODS Immunohistochemistry and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to evaluate the expression of HER-2/neu, STAT3 and SOCS3 in HCC tissues and adjacent normal tissues collected from 176 HCC patients. RESULTS HER-2/neu and STAT3 levels were higher and SOCS3 expression was lower in HCC tissues than in adjacent normal tissues. HER-2/neu, STAT3 and SOCS3 levels were associated with histological grade, tumor diameter, TNM stage, vascular invasion, lymph node metastasis and distant metastasis in HCC. SOCS3 expression was negatively associated with HER-2/neu and STAT3 expression. HCC patients with higher HER-2/neu and STAT3 levels had shorter overall, disease-free and disease-specific survival, whereas the opposite was found in patients with higher SOCS3 expression. In Cox regression analysis, tumor size, TNM stage, and STAT3 expression were identified as independent prognostic factors of HCC. CONCLUSION Taken together, these observations suggest that HER-2/neu, STAT3 and, SOCS3 are related to the aggressive tumor behavior and STAT3 has potential value as a prognostic factor for HCC.
Collapse
Affiliation(s)
- Li-Hua Jiang
- Department of Clinical Laboratory, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, No. 20, Yuhuangding East Road, Yantai 264000, Shandong Province, PR China
| | - Ying-Li Hao
- Department of Clinical Laboratory, Yantaishan Hospital, Yantai 264001, Shandong Province, PR China
| | - Jing-Wei Zhu
- Department of Clinical Laboratory, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, No. 20, Yuhuangding East Road, Yantai 264000, Shandong Province, PR China.
| |
Collapse
|
|
29
|
Zhang Y, Wu YF, Yue ZD, Zhao HW, Wang L, Fan ZH, He FL, Wang T, Liu FQ. Iodine-125 implantation with transjugular intrahepatic portosystemic shunt for main portal vein tumor thrombus. World J Gastrointest Oncol 2019; 11:310-321. [PMID: 31040896 PMCID: PMC6475673 DOI: 10.4251/wjgo.v11.i4.310] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2019] [Revised: 02/11/2019] [Accepted: 03/12/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Main portal vein tumor thrombus (MPVTT), which has a high incidence, is the major complication of terminal liver cancer. The occurrence of MPVTT is always a negative prognostic factor for patients with hepatocellular carcinoma (HCC). Therefore, attention should be paid to the treatment of MPVTT and its complications.
AIM To evaluate the efficacy of transarterial chemoembolization/transarterial embolization (TACE/TAE)+125I seeds implantation with transjugular intrahepatic portosystemic shunt (TIPS) in treating MPVTT and its complications.
METHODS From January 2007 to March 2015, 85 consecutive patients with MPVTT were nonrandomly assigned to undergo treatment with TACE/TAE + TIPS and 125I implantation (TIPS-125I group) or TACE/TAE + TIPS only (TIPS only group) in Beijing Shijitan Hospital, and all clinical data were collected. During 24 mo follow-up, the incidence of overall survival, stent stenosis and symptom recurrence was analyzed to evaluate the efficacy of TIPS-125I.
RESULTS During 24 mo follow-up of all patients, we collected data at 6, 12 and 24 mo. The rates of survival were 80%, 45%, and 20%, respectively, in the TIPS-125I group, whereas those in the TIPS only group were 64.4%, 24.4%, and 4.4%, respectively (P < 0.05). The rates of symptom recurrence were 7.5%, 22.5%, and 35%, respectively, in the TIPS-125I group, whereas those in the TIPS only group were 31.1%, 62.2%, and 82.2% (P < 0.05). The rates of stent restenosis were 12.5%, 27.5%, and 42.5%, respectively, in the TIPS-125I group, and 42.2%, 68.9%, and 84.4%, respectively, in the TIPS only group (P < 0.05). TIPS-125I was found to be significantly favorable in treating MPVTT and its complications in patients with HCC.
CONCLUSION TACE/TAE+125I combined with TIPS is effective in treating MPVTT and its complications, improving quality of life of patients and reducing mortality.
Collapse
Affiliation(s)
- Yue Zhang
- Department of Interventional Therapy, Peking University Ninth School of Clinical Medicine, Beijing Shijitan Hospital and Capital Medical University, Beijing 100038, China
| | - Yi-Fan Wu
- Department of Interventional Therapy, Beijing Shijitan Hospital and Capital Medical University, Beijing 100038, China
| | - Zhen-Dong Yue
- Department of Interventional Therapy, Beijing Shijitan Hospital and Capital Medical University, Beijing 100038, China
| | - Hong-Wei Zhao
- Department of Interventional Therapy, Beijing Shijitan Hospital and Capital Medical University, Beijing 100038, China
| | - Lei Wang
- Department of Interventional Therapy, Beijing Shijitan Hospital and Capital Medical University, Beijing 100038, China
| | - Zhen-Hua Fan
- Department of Interventional Therapy, Beijing Shijitan Hospital and Capital Medical University, Beijing 100038, China
| | - Fu-Liang He
- Department of Interventional Therapy, Beijing Shijitan Hospital and Capital Medical University, Beijing 100038, China
| | - Tao Wang
- Department of Interventional Therapy, The affiliated Yantai Yuhuangding Hospital of Qingdao University, No.20 Yuhuangding East Road, Yantai 264000, Shandong Province, China
| | - Fu-Quan Liu
- Department of Interventional Therapy, Peking University Ninth School of Clinical Medicine, Beijing Shijitan Hospital and Capital Medical University, Beijing 100038, China
| |
Collapse
|
|
30
|
Mähringer-Kunz A, Steinle V, Düber C, Weinmann A, Koch S, Schmidtmann I, Schotten S, Hinrichs JB, Graafen D, Pinto Dos Santos D, Galle PR, Kloeckner R. Extent of portal vein tumour thrombosis in patients with hepatocellular carcinoma: The more, the worse? Liver Int 2019; 39:324-331. [PMID: 30318826 DOI: 10.1111/liv.13988] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Revised: 10/03/2018] [Accepted: 10/04/2018] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS Portal vein tumour thrombosis (PVTT) has a significant impact on the prognosis of patients with hepatocellular carcinoma (HCC). The degree of PVTT varies from sub-/segmental invasion to complete occlusion of the main trunk. Aim of this study was to evaluate whether the degree of PVTT correlates with prognosis. METHODS A total of 1317 patients with HCC treated at our tertiary referral centre between January 2005 and December 2016 were included. PVTT was diagnosed by contrast-enhanced computed tomography or magnetic resonance imaging. The extent of PVTT was documented according to the Liver Cancer Study Group of Japan classification: Vp0 = no PVTT, Vp1 = segmental portal vein invasion, Vp2 = right anterior/posterior portal vein, Vp3 = right/left portal vein and Vp4 = main trunk. Median overall survival (OS) was calculated for each group. RESULTS Portal vein tumour thrombosis was present in 484 (36.8%) patients. Median OS without PVTT was 35.7 months, significantly longer than in patients with PVTT (7.2 months, P < 0.001). The patients with PVTT were subclassified as follows: 103 Vp1, 87 Vp2, 143 Vp3 and 151 Vp4. The corresponding median OS yielded 14.6, 9.4, 5.8 and 4.8 months for Vp1-Vp4, respectively (P < 0.001). CONCLUSIONS Portal vein tumour thrombosis in patients with HCC is associated with a dismal prognosis. The results indicate an association between the extent of PVTT and OS. However, the extent of PVTT is not that decisive, as even minor PVTT leads to a very poor prognosis. Therefore, meticulous evaluation of cross-sectional imaging is crucial for the clinical management of patients with HCC.
Collapse
Affiliation(s)
- Aline Mähringer-Kunz
- Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Verena Steinle
- Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Christoph Düber
- Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Arndt Weinmann
- Department of Internal Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.,Clinical Registry Unit (CRU), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Sandra Koch
- Clinical Registry Unit (CRU), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Irene Schmidtmann
- Institute of Medical Biostatistics, Epidemiology and Informatics, Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Sebastian Schotten
- Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Jan B Hinrichs
- Department of Interventional and Diagnostic Radiology, Hannover Medical School, Hannover, Germany
| | - Dirk Graafen
- Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | | | - Peter R Galle
- Department of Internal Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Roman Kloeckner
- Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| |
Collapse
|
|
31
|
Peng SY, Wang XA, Huang CY, Li JT, Hong DF, Wang YF, Xu B. Better surgical treatment method for hepatocellular carcinoma with portal vein tumor thrombus. World J Gastroenterol 2018; 24:4527-4535. [PMID: 30386102 PMCID: PMC6209573 DOI: 10.3748/wjg.v24.i40.4527] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2018] [Revised: 09/11/2018] [Accepted: 10/05/2018] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) is a disease that is not uncommon, but the treatments vary drastically between Eastern and Western countries. In Europe and America, the first line of treatment is systemic therapy such as sorafenib and the surgical treatment is not a recommend option. While an increasing number of studies from China and Japan have suggested that surgical treatment results in better outcomes when compared to transcatheter arterial chemoembolization (TACE), sorafenib, or other nonsurgical treatments, and two classification systems, Japanese Vp classification and Chinese Cheng's classification, were very useful to guide the surgical treatment. We have also found that surgical treatment may be more effective, as we have performed surgical treatment for HCC-PVTT patients over a period of approximately 15 years and achieved good results with the longest surviving time being 13 years and onward. In this study, we review the efficacy and principles of current surgical treatments and introduce our new, more effective surgical technique named "thrombectomy first", which means the tumor thrombus in the main portal vein, the bifurcation or the contralateral portal vein should be removed prior to liver resection. Thus, compression and crushing of PVTT during the operation could be avoided and new intrahepatic metastases caused by tumor thrombus to the remnant liver minimized. The new technique is even beneficial to the prognosis of Cheng's classification Types III and IV PVTT. The vital tips and tricks for the surgical approach are described.
Collapse
Affiliation(s)
- Shu-You Peng
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
| | - Xu-An Wang
- Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
| | - Cong-Yun Huang
- Department of General Surgery, Yuebei People’s Hospital Affiliated to Shantou University School of Medicine, Shaoguan 512025, Guangdong Province, China
| | - Jiang-Tao Li
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
| | - De-Fei Hong
- Department of Hepatobiliary and Pancreatic Surgery, Sir Run Run Shaw Hospital Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310016, Zhejiang Province, China
| | - Yi-Fang Wang
- Department of Hepatobiliary and Pancreatic Surgery, Sir Run Run Shaw Hospital Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310016, Zhejiang Province, China
| | - Bin Xu
- Department of Hepatobiliary and Pancreatic Surgery, Sir Run Run Shaw Hospital Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310016, Zhejiang Province, China
| |
Collapse
|
|
32
|
Macroscopic Portal Vein Thrombosis in HCC Patients. Can J Gastroenterol Hepatol 2018; 2018:3120185. [PMID: 30009156 PMCID: PMC6020651 DOI: 10.1155/2018/3120185] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2017] [Accepted: 03/22/2018] [Indexed: 12/13/2022] Open
Abstract
Macroscopic portal vein invasion (PVT) by hepatocellular carcinoma (HCC) in the liver is one of the most important negative prognostic factors for HCC patients. The characteristics of a large cohort of such patients were examined. We found that the percent of patients with PVT significantly increased with increasing maximum tumor diameter (MTD), from 13.7% with tumors of MTD <5cm to 56.4% with tumors of MTD >10cm. There were similar numbers of HCC patients with very large tumors with and without PVT. Thus, MTD alone was insufficient to explain the presence of PVT, as were high AFP levels, since less than 50% of high AFP patients had PVT. However, the percent of patients with PVT was also found to significantly increase with increasing blood alpha-fetoprotein (AFP) levels and tumor multifocality. A logistic regression model that included these 3 factors together showed an odds ratio of 17.9 for the combination of MTD>5.0cm plus tumor multifocality plus elevated AFP, compared to low levels of these 3 parameters. The presence or absence of macroscopic PVT may therefore represent different HCC aggressiveness phenotypes, as judged by a significant increase in tumor multifocality and AFP levels in the PVT positive patients. Factors in addition to MTD and AFP must also contribute to PVT development.
Collapse
|
|
33
|
Ashida R, Okamura Y, Ohshima K, Kakuda Y, Uesaka K, Sugiura T, Ito T, Yamamoto Y, Sugino T, Urakami K, Kusuhara M, Yamaguchi K. The down-regulation of the CYP2C19 gene is associated with aggressive tumor potential and the poorer recurrence-free survival of hepatocellular carcinoma. Oncotarget 2018; 9:22058-22068. [PMID: 29774122 PMCID: PMC5955155 DOI: 10.18632/oncotarget.25178] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2018] [Accepted: 04/05/2018] [Indexed: 02/07/2023] Open
Abstract
Project HOPE (High-tech Omics-based Patient Evaluation) began in 2014 using integrated gene expression profiling (GEP) of cancer tissues as well as diathesis of each patient who underwent an operation at our institution. The aim of this study was to clarify the association between the expression of cytochrome P450s (CYP) genes and recurrence of hepatocellular carcinoma (HCC). The present study included 92 patients. Genes with aberrant expression were selected based on a ≥10-fold difference in the expression between tumor and non-tumor tissues. The GEP analysis showed that the down-regulated genes in tumor tissue were CYP3A4 in 56 patients (61%), CYP2C8 in 44 patients (48%), CYP2C19 in 30 patients (33%), CYP2D6 in 11 patients (12%), CYP3A5 in 7 patients (8%) and CYP1B1 in 2 patients (2%). There was no patients with down-regulation of the CYP17A1 gene. A multivariate analysis revealed that the presence of microscopic portal invasion (hazard ratio [HR] 2.57, 95% confidence interval [CI] 1.30–5.05 P = 0.006), the presence of intrahepatic-metastasis (HR 3.09 95% CI 1.52–6.29 P = 0.002) and down-regulation of the CYP2C19 gene (HR 3.69 95% CI 1.83–7.46 P < 0.001) were independent predictors for the recurrence-free survival (RFS). The down-regulation of the CYP2C19 gene were correlated with the RFS in HCC.
Collapse
Affiliation(s)
- Ryo Ashida
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Yukiyasu Okamura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Keiichi Ohshima
- Medical Genetics Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan
| | - Yuko Kakuda
- Division of Pathology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Katsuhiko Uesaka
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Teiichi Sugiura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Takaaki Ito
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Yusuke Yamamoto
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Takashi Sugino
- Division of Pathology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Kenichi Urakami
- Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan
| | - Masatoshi Kusuhara
- Regional Resources Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan
| | - Ken Yamaguchi
- Shizuoka Cancer Center Hospital and Research Institute, Shizuoka, Japan
| |
Collapse
|
|
34
|
Yasui D, Murata S, Ueda T, Sugihara F, Onozawa S, Kawamoto C, Kumita S. Novel treatment strategy for advanced hepatocellular carcinoma: combination of conventional transcatheter arterial chemoembolization and modified method with portal vein occlusion for cases with arterioportal shunt: a preliminary study. Acta Radiol 2018. [PMID: 28651444 DOI: 10.1177/0284185117717762] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Background A novel strategy to combine conventional transcatheter arterial chemoembolization (TACE) and TACE during portal vein occlusion (TACE-PVO) in the presence of high-flow arterioportal shunt (APS) has been developed to treat hepatocellular carcinoma (HCC) with portal invasion. Purpose To evaluate the efficacy of this strategy. Material and Methods Twenty-five cases of HCC with portal invasion, treated between April 2006 and December 2015, were evaluated. Balloon occlusion of the portal venous outlet was performed in eight cases of high-flow APS when performing TACE. Conventional TACE was performed in the other 17 cases. The primary endpoint was overall survival. Adverse events and deterioration of liver function were also evaluated. Results The median survival time (MST) was 12 months. One-, two-, and three-year survival rates were 48.0%, 39.3%, and 26.2%, respectively. Subgroup analysis and multivariate analysis revealed the CLIP score as prognostic factor. MST was 2.5 months in the subgroup with CLIP score ≥4 and 26.0 months in the subgroup with CLIP score ≤3 (hazard ratio = 7.7, 95% confidence interval = 2.3-25.8). Transient elevations of the levels of transaminase and bilirubin were observed; however, deterioration of liver function was infrequent; upgrading of Child-Pugh class in 9.1% of cases. Conclusion A novel strategy, combining conventional TACE and TACE-PVO, is effective for HCC with portal invasion. The CLIP score may be useful for considering treatment indication.
Collapse
|
|
35
|
Kamiyama T, Kakisaka T, Orimo T, Wakayama K. Hepatectomy for hepatocellular carcinoma with portal vein tumor thrombus. World J Hepatol 2017; 9:1296-1304. [PMID: 29359012 PMCID: PMC5756718 DOI: 10.4254/wjh.v9.i36.1296] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2017] [Revised: 11/10/2017] [Accepted: 12/07/2017] [Indexed: 02/06/2023] Open
Abstract
Despite surgical removal of tumors with portal vein tumor thrombus (PVTT) in hepatocellular carcinoma (HCC) patients, early recurrence tends to occur, and overall survival (OS) periods remain extremely short. The role that hepatectomy may play in long-term survival for HCC with PVTT has not been established. The operative mortality of hepatectomy for HCC with PVTT has also not been reviewed. Hence, we reviewed recent literature to assess these parameters. The OS of patients who received hepatectomy in conjunction with multidisciplinary treatment tended to be superior to that of patients who did not. Multidisciplinary treatments included the following: preoperative radiotherapy on PVTT; preoperative transarterial chemoembolization (TACE); subcutaneous administration of interferon-alpha (IFN-α) and intra-arterial infusion of 5-fluorouracil (5-FU) with infusion chemotherapy in the affected hepatic artery; cisplatin, doxorubicin and 5-FU locally administered in the portal vein; and subcutaneous injection of IFN-α, adjuvant chemotherapy (5-FU + Adriamycin) administration via the portal vein with postoperative TACE, percutaneous isolated hepatic perfusion and hepatic artery infusion and/or portal vein chemotherapy. The highest reported rate of operative mortality was 9.3%. In conclusion, hepatectomy for patients affected by HCC with PVTT is safe, has low mortality and might prolong survival in conjunction with multidisciplinary treatment.
Collapse
Affiliation(s)
- Toshiya Kamiyama
- Department of Gastroenterological Surgery I, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan
| | - Tatsuhiko Kakisaka
- Department of Gastroenterological Surgery I, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan
| | - Tatsuya Orimo
- Department of Gastroenterological Surgery I, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan
| | - Kenji Wakayama
- Department of Gastroenterological Surgery I, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan
| |
Collapse
|
|
36
|
Glantzounis GK, Paliouras A, Stylianidi MC, Milionis H, Tzimas P, Roukos D, Pentheroudakis G, Felekouras E. The role of liver resection in the management of intermediate and advanced stage hepatocellular carcinoma. A systematic review. Eur J Surg Oncol 2017; 44:195-208. [PMID: 29258719 DOI: 10.1016/j.ejso.2017.11.022] [Citation(s) in RCA: 61] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2017] [Revised: 11/15/2017] [Accepted: 11/23/2017] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The ideal management for patients with intermediate and advanced stage hepatocellular carcinoma (HCC) is controversial. The main purpose of this systematic review is to examine the role of liver resection in patients with intermediate stage HCC (multinodular HCCs) and in advanced stage HCC [mainly patients with portal vein tumor thrombosis (PVTT)]. METHODS A systematic search of the literature was performed in Pud Med and the Cochrane Library from 01.01.2000 to 30.06.2016. RESULTS Twenty-three articles with 2412 patients with multinodular HCCs were selected. Also, 29 studies with 3659 patients with HCCs with macrovascular invasion were selected. In patients with multinodular HCCs the median post-operative morbidity was 25% and the 90-day mortality was 2.7%. The median survival was 37 months and the 5-year survival 35%. The 5-year survival was much better for patients with a number of HCCs ≤3 vs. HCCs >3 (49% vs. 23%). In patients with macrovascular invasion, who underwent hepatic resection, the median post-operative morbidity was 33% and the in-hospital mortality 2.7%. The median survival was 15 months. The 3 and 5year survival was 33% and 20% respectively. Moreover a significant difference in survival was noted according to PVTT stage: 5- year survival for distal PVTT, PVTT of the main intrahepatic PV branch and PVTT extending to the main PV was 45%, 19% and 14.5% respectively. CONCLUSIONS Liver resection in patients with multinodular HCCs and HCCs with PVTT offers satisfactory long-term survival and should be considered in selected patients.
Collapse
Affiliation(s)
- G K Glantzounis
- Department of Surgery, University Hospital of Ioannina and School of Medicine, University of Ioannina, 45 500, Ioannina, Greece.
| | - A Paliouras
- Department of Surgery, University Hospital of Ioannina and School of Medicine, University of Ioannina, 45 500, Ioannina, Greece
| | - M-C Stylianidi
- Department of Surgery, University Hospital of Ioannina and School of Medicine, University of Ioannina, 45 500, Ioannina, Greece
| | - H Milionis
- Department of Internal Medicine, University Hospital of Ioannina and School of Medicine, University of Ioannina, Ioannina, Greece
| | - P Tzimas
- Department of Anesthesia and Postoperative Intensive Care, University Hospital of Ioannina and School of Medicine, University of Ioannina, Ioannina, Greece
| | - D Roukos
- Department of Surgery, University Hospital of Ioannina and School of Medicine, University of Ioannina, 45 500, Ioannina, Greece
| | - G Pentheroudakis
- Department of Medical Oncology, University Hospital of Ioannina and School of Medicine, University of Ioannina, Ioannina, Greece
| | - E Felekouras
- 1st Department of Surgery, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| |
Collapse
|
|
37
|
Yin J, Bo WT, Sun J, Xiang X, Lang JY, Zhong JH, Li LQ. New Evidence and Perspectives on the Management of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus. J Clin Transl Hepatol 2017; 5:169-176. [PMID: 28660155 PMCID: PMC5472938 DOI: 10.14218/jcth.2016.00071] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2016] [Revised: 03/02/2017] [Accepted: 03/04/2017] [Indexed: 02/06/2023] Open
Abstract
Portal vein tumor thrombosis (PVTT) is an intractable condition but common phenomenon in hepatocellular carcinoma (HCC). HCC patients with PVTT may have worse liver function, a higher chance of comorbidity related to portal hypertension, lower tolerance to treatment and poorer prognoses. In Western guidelines, patients are offered palliative treatment with sorafenib or other systemic agents because HCC with PVTT is grouped together with metastatic HCC during the planning of its management. In recent years, various treatment options have become available for patients with HCC and PVTT. Therapy has also shifted toward evidence-based treatment. However, policies for the management of HCC with PVTT have not been established. This comprehensive literature review aims to present current and available management options for patients with HCC and PVTT. Evidence is mainly based on studies published after 2010.
Collapse
Affiliation(s)
- Jun Yin
- Department of Radiation Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Wen-Tao Bo
- Department of Hepatobiliary Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Jian Sun
- Department of Medical Affairs, ZiBo Hospital of Integrated Traditional Chinese and Western Medicine, Zibo, China
| | - Xiao Xiang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Jin-Yi Lang
- Department of Radiation Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Jian-Hong Zhong
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Le-Qun Li
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| |
Collapse
|
|
38
|
Jiang JF, Lao YC, Yuan BH, Yin J, Liu X, Chen L, Zhong JH. Treatment of hepatocellular carcinoma with portal vein tumor thrombus: advances and challenges. Oncotarget 2017; 8:33911-33921. [PMID: 28430610 PMCID: PMC5464922 DOI: 10.18632/oncotarget.15411] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2016] [Accepted: 02/02/2017] [Indexed: 02/06/2023] Open
Abstract
Portal vein tumor thrombus is a frequent, challenging complication in hepatocellular carcinoma. Hepatocellular carcinoma patients with portal vein tumor thrombus may show worse liver function, less treatment tolerance and worse prognosis than patients without portal vein tumor thrombus, and they may be at higher risk of comorbidity related to portal hypertension. Western and some Asian guidelines stratify hepatocellular carcinoma with portal vein tumor thrombus together with metastatic hepatocellular carcinoma and therefore recommend only palliative treatment with sorafenib or other systemic agents. In recent years, more treatment options have become available for hepatocellular carcinoma patients with portal vein tumor thrombus, and an evidence-based approach to optimizing disease management and treatment has become more widespread. Nevertheless, consensus policies for managing hepatocellular carcinoma with portal vein tumor thrombus have not been established. This comprehensive literature review, drawing primarily on studies published after 2010, examines currently available management options for patients with hepatocellular carcinoma and portal vein tumor thrombus.
Collapse
Affiliation(s)
- Jin-Fang Jiang
- Department of Chemotherapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Yong-Cong Lao
- Department of Chemotherapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Bao-Hong Yuan
- Department of General Surgery, Yan’An Hospital Affiliated to Kunming Medical University, Kunming, China
| | - Jun Yin
- Department of Radiation Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Xin Liu
- Department of Chemotherapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Long Chen
- Department of Radiology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Jian-Hong Zhong
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| |
Collapse
|
|
39
|
Feng LH, Dong H, Lau WY, Yu H, Zhu YY, Zhao Y, Lin YX, Chen J, Wu MC, Cong WM. Novel microvascular invasion-based prognostic nomograms to predict survival outcomes in patients after R0 resection for hepatocellular carcinoma. J Cancer Res Clin Oncol 2017; 143:293-303. [PMID: 27743138 DOI: 10.1007/s00432-016-2286-1] [Citation(s) in RCA: 98] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2016] [Accepted: 10/07/2016] [Indexed: 02/06/2023]
Abstract
PURPOSE To propose a novel histopathological classification system for microvascular invasion (MVI) and to establish nomograms to predict postoperative survival and early tumor recurrence in patients with hepatocellular carcinoma (HCC) after R0 liver resection. METHODS The clinicopathological and follow-up data of 686 consecutive patients with HCC who underwent R0 liver resection in our hospital between December 2009 and April 2010 were retrospectively reviewed. A classification system was established based on histological characteristics of MVI. Nomograms were then formulated using a multivariate Cox proportional hazards model to analyze. The results were validated using bootstrap resampling and a new 225-patient validation cohort operated in May and June 2010 at the same institution. RESULTS A 4-stratification classification system of MVI was established, which satisfactorily determined the risk of survival and early tumor recurrence. Then, an eight-factor nomogram for survival prediction and a seven-factor nomogram for prediction of early tumor recurrence were established. The concordance indices were 0.78 for the survival-prediction nomogram and 0.72 for the recurrence-prediction nomogram. These indices were both significantly higher than the following three commonly used staging systems: tumor-node-metastasis staging system (seventh edition, 0.67/0.65), Japan Integrated Staging System (0.58/0.58) and Chinese University Prognostic Index (0.52/0.51). The calibration curves showed good agreement between predictions by the nomograms and actual survival outcomes. These results were confirmed in the validation cohort. CONCLUSIONS The novel classification system of MVI and the nomograms enabled more accurate predictions of risk of tumor recurrence and overall survival in patients with HCC after R0 liver resection.
Collapse
Affiliation(s)
- Long-Hai Feng
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, 225 Changhai Road, Shanghai, China
- Department of Pathology, Changhai Hospital, The Second Military Medical University, 168 Changhai Road, Shanghai, China
| | - Hui Dong
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, 225 Changhai Road, Shanghai, China
| | - Wan-Yee Lau
- Department of Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, 225 Changhai Road, Shanghai, China
- Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, China
| | - Hua Yu
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, 225 Changhai Road, Shanghai, China
| | - Yu-Yao Zhu
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, 225 Changhai Road, Shanghai, China
| | - Yun Zhao
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, 225 Changhai Road, Shanghai, China
| | - Yu-Xi Lin
- Department of Laboratory Medicines, 234 Military Hospital of China, The Fourth Section, Chaoyang Street, Chaoyang, Liaoning Province, China
| | - Jia Chen
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, 225 Changhai Road, Shanghai, China
| | - Meng-Chao Wu
- Department of Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, 225 Changhai Road, Shanghai, China
| | - Wen-Ming Cong
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, 225 Changhai Road, Shanghai, China.
| |
Collapse
|
|
40
|
Ma KW, Cheung TT. Surgical resection of localized hepatocellular carcinoma: patient selection and special consideration. J Hepatocell Carcinoma 2016; 4:1-9. [PMID: 28097107 PMCID: PMC5207474 DOI: 10.2147/jhc.s96085] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Localized hepatocellular carcinoma (HCC) refers to a solitary or few tumors located within either the left or right hemiliver without evidence of bilobar or extrahepatic spread. This term encompasses a heterogeneous morphology with no regard to stage of prognosis of the disease. Surgical resection remains the mainstay of curative treatment for the localized HCC. Various biochemical and radiological tests constitute an indispensible part of preoperative assessment. Emergence of laparoscopic hepatectomy has brought liver resection into a new era. Improved understanding of the pathophysiology of HCC allows more aggressive surgical resection without compromising outcomes. New insights into the management of special situations, such as ruptured HCC, pyogenic transformation of HCC, and HCC with portal vein tumor thrombus, rekindle the hopes of curative resection in these terminal events. Amalgamating salvage liver transplantation into the surgical management of resectable HCC has revolutionized the treatment paradigm of this deadly disease.
Collapse
Affiliation(s)
- Ka Wing Ma
- Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Tan To Cheung
- Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Pok Fu Lam, Hong Kong
| |
Collapse
|
|
41
|
Kokudo T, Hasegawa K, Matsuyama Y, Takayama T, Izumi N, Kadoya M, Kudo M, Ku Y, Sakamoto M, Nakashima O, Kaneko S, Kokudo N. Survival benefit of liver resection for hepatocellular carcinoma associated with portal vein invasion. J Hepatol 2016; 65:938-943. [PMID: 27266618 DOI: 10.1016/j.jhep.2016.05.044] [Citation(s) in RCA: 361] [Impact Index Per Article: 40.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2016] [Revised: 05/20/2016] [Accepted: 05/30/2016] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS The presence of portal vein tumor thrombosis (PVTT) in patients with hepatocellular carcinoma (HCC) is regarded as indicating an advanced stage, and liver resection (LR) is not recommended. The aim of this study was to evaluate the survival benefit of LR for HCC patients with PVTT through the analysis of the data from a Japanese nationwide survey. METHODS We analyzed data for 6474 HCC patients with PVTT registered between 2000 and 2007. Of these patients, 2093 patients who underwent LR and 4381 patients who received other treatments were compared. The propensity scores were calculated and we successfully matched 1058 patients (66.1% of the LR group). RESULTS In the Child-Pugh A patients, the median survival time (MST) in the LR group was 1.77years longer than that in the non-LR group (2.87years vs. 1.10years; p<0.001) and 0.88years longer than that in the non-LR group (2.45years vs. 1.57years; p<0.001) in a propensity score-matched cohort. A subgroup analysis revealed that LR provides a survival benefit regardless of age, etiology of HCC, tumor marker elevation, and tumor number. The survival benefit was not statistically significant only in patients with PVTT invading the main trunk or contralateral branch. In the LR group, the postoperative 90-day mortality rate was 3.7% (68 patients). CONCLUSIONS As long as the PVTT is limited to the first-order branch, LR is associated with a longer survival outcome than non-surgical treatment. LAY SUMMARY The presence of portal vein tumor thrombosis in patients with hepatocellular carcinoma is regarded as indicating an advanced stage, and liver resection is not recommended. We performed a multicenter, nationwide study to assess the survival benefit of liver resection in hepatocellular carcinoma patients with portal vein tumor thrombosis using propensity score-based matching. As long as the portal vein tumor thrombosis is limited to the first-order branch, liver resection is associated with a longer survival outcome than non-surgical treatment.
Collapse
Affiliation(s)
- Takashi Kokudo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Japan; Division of Gastroenterological Surgery, Saitama Cancer Center, Japan
| | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Japan
| | - Yutaka Matsuyama
- Department of Biostatistics, School of Public Health, The University of Tokyo, Japan
| | - Tadatoshi Takayama
- Department of Digestive Surgery, Nihon University School of Medicine, Japan
| | - Namiki Izumi
- Department of Gastroenterology, Musashino Red Cross Hospital, Japan
| | - Masumi Kadoya
- Department of Radiology, Shinshu University School of Medicine, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Japan
| | - Yonson Ku
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Japan
| | - Michiie Sakamoto
- Department of Pathology, Keio University School of Medicine, Japan
| | - Osamu Nakashima
- Department of Clinical Laboratory Medicine, Kurume University Hospital, Japan
| | - Shuichi Kaneko
- Department of Gastroenterology, Kanazawa University Hospital, Japan
| | - Norihiro Kokudo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Japan.
| | | |
Collapse
|
|
42
|
Low Alpha-Fetoprotein Levels Are Associated with Improved Survival in Hepatocellular Carcinoma Patients with Portal Vein Thrombosis. Dig Dis Sci 2016; 61:937-47. [PMID: 26576554 DOI: 10.1007/s10620-015-3922-3] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2015] [Accepted: 10/05/2015] [Indexed: 12/15/2022]
Abstract
BACKGROUND Macroscopic portal vein thrombosis (PVT) is a common and dire prognostic feature of patients with hepatocellular carcinoma (HCC) and often precludes many treatments as a result. Little is known about its causes or mechanisms or clinical associations. AIMS To examine patients with PVT in order to possibly identify prognostically different subsets. METHODS A large cohort of non-curable patients with advanced and biopsy-proven HCC in which survival was documented, were retrospectively examined. RESULTS We analyzed a large HCC cohort containing 366 (63.3%) PVT-positive patients and found that PVT is associated with patients having larger tumors and higher levels of alpha-fetoprotein (AFP) and des-gamma carboxyprothrombin (DCP). We identified in patients with normal bilirubin levels (≤ 2.0 mg/dl) two PVT-positive patients, having higher and lower AFP levels, respectively. They differed in the significantly better prognosis of the low AFP patients, which may be useful for patient management decisions. CONCLUSIONS Patients with PVT are heterogeneous with respect to AFP levels. AFP-negative patients have a significantly better survival than those who have elevated AFP.
Collapse
|