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1
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Fu Y, Zhang Y, Hu D, Zhou Z, Xu L, Chen M. Where Is the Future of Adjuvant Therapy for Hepatocellular Carcinoma? J Clin Oncol 2025:JCO2402615. [PMID: 39999399 DOI: 10.1200/jco-24-02615] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Revised: 01/16/2025] [Accepted: 02/03/2025] [Indexed: 02/27/2025] Open
Affiliation(s)
- Yizhen Fu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, P. R. China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P. R. China
| | - Yaojun Zhang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, P. R. China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P. R. China
| | - Dandan Hu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, P. R. China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P. R. China
| | - Zhongguo Zhou
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, P. R. China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P. R. China
| | - Li Xu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, P. R. China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P. R. China
| | - Minshan Chen
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, P. R. China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P. R. China
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Huang Y, Qian H. Advancing Hepatocellular Carcinoma Management Through Peritumoral Radiomics: Enhancing Diagnosis, Treatment, and Prognosis. J Hepatocell Carcinoma 2024; 11:2159-2168. [PMID: 39525830 PMCID: PMC11546143 DOI: 10.2147/jhc.s493227] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Accepted: 10/25/2024] [Indexed: 11/16/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is associated with high mortality rates due to late detection and aggressive progression. Peritumoral radiomics, an emerging technique that quantitatively analyzes the tissue surrounding the tumor, has shown significant potential in enhancing the management of HCC. This paper examines the role of peritumoral radiomics in improving diagnostic accuracy, guiding personalized treatment strategies, and refining prognostic assessments. By offering unique insights into the tumor microenvironment, peritumoral radiomics enables more precise patient stratification and informs clinical decision-making. However, the integration of peritumoral radiomics into routine clinical practice faces several challenges. Addressing these challenges through continued research and innovation is crucial for the successful implementation of peritumoral radiomics in HCC management, ultimately leading to improved patient outcomes.
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Affiliation(s)
- Yanhua Huang
- Department of Ultrasound, Shaoxing People’s Hospital, Shaoxing, People’s Republic of China
| | - Hongwei Qian
- Department of Hepatobiliary and Pancreatic Surgery, Shaoxing People’s Hospital, Shaoxing, People’s Republic of China
- Shaoxing Key Laboratory of Minimally Invasive Abdominal Surgery and Precise Treatment of Tumor, Shaoxing, People’s Republic of China
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3
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Lou X, Ma S, Ma M, Wu Y, Xuan C, Sun Y, Liang Y, Wang Z, Gao H. The prognostic role of an optimal machine learning model based on clinical available indicators in HCC patients. Front Med (Lausanne) 2024; 11:1431578. [PMID: 39086944 PMCID: PMC11288914 DOI: 10.3389/fmed.2024.1431578] [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: 05/12/2024] [Accepted: 06/26/2024] [Indexed: 08/02/2024] Open
Abstract
Although methods in diagnosis and therapy of hepatocellular carcinoma (HCC) have made significant progress in the past decades, the overall survival (OS) of liver cancer is still disappointing. Machine learning models have several advantages over traditional cox models in prognostic prediction. This study aimed at designing an optimal panel and constructing an optimal machine learning model in predicting prognosis for HCC. A total of 941 HCC patients with completed survival data and preoperative clinical chemistry and immunology indicators from two medical centers were included. The OCC panel was designed by univariate and multivariate cox regression analysis. Subsequently, cox model and machine-learning models were established and assessed for predicting OS and PFS in discovery cohort and internal validation cohort. The best OCC model was validated in the external validation cohort and analyzed in different subgroups. In discovery, internal and external validation cohort, C-indexes of our optimal OCC model were 0.871 (95% CI, 0.863-0.878), 0.692 (95% CI, 0.667-0.717) and 0.648 (95% CI, 0.630-0.667), respectively; the 2-year AUCs of OCC model were 0.939 (95% CI, 0.920-0.959), 0.738 (95% CI, 0.667-0.809) and 0.725 (95% CI, 0.643-0.808), respectively. For subgroup analysis of HCC patients with HBV, aged less than 65, cirrhosis or resection as first therapy, C-indexes of our optimal OCC model were 0.772 (95% CI, 0.752-0.792), 0.769 (95% CI, 0.750-0.789), 0.855 (95% CI, 0.846-0.864) and 0.760 (95% CI, 0.741-0.778), respectively. In general, the optimal OCC model based on RSF algorithm shows prognostic guidance value in HCC patients undergoing individualized treatment.
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Affiliation(s)
- Xiaoying Lou
- Department of Clinical Laboratory, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Beijing, China
| | - Shaohui Ma
- Department of Clinical Laboratory, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Beijing, China
| | - Mingyuan Ma
- Department of Statistics, Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, CA, United States
| | - Yue Wu
- Department of Clinical Laboratory, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Beijing, China
| | - Chengmei Xuan
- Department of Clinical Laboratory, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Beijing, China
| | - Yan Sun
- Department of Clinical Laboratory, Shanxi Province Cancer Hospital/Shanxi Hospital Chinese Academy of Medical Sciences, Taiyuan, Shanxi, China
| | - Yue Liang
- Department of Clinical Laboratory, Shanxi Province Cancer Hospital/Shanxi Hospital Chinese Academy of Medical Sciences, Taiyuan, Shanxi, China
| | - Zongdan Wang
- Department of Clinical Laboratory, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Beijing, China
| | - Hongjun Gao
- Department of Clinical Laboratory, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Beijing, China
- Department of Clinical Laboratory, Shanxi Province Cancer Hospital/Shanxi Hospital Chinese Academy of Medical Sciences, Taiyuan, Shanxi, China
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Liu Y, Zhang Z, Zhang H, Wang X, Wang K, Yang R, Han P, Luan K, Zhou Y. Clinical prediction of microvascular invasion in hepatocellular carcinoma using an MRI-based graph convolutional network model integrated with nomogram. Br J Radiol 2024; 97:938-946. [PMID: 38552308 DOI: 10.1093/bjr/tqae056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 02/07/2024] [Accepted: 03/06/2024] [Indexed: 05/09/2024] Open
Abstract
OBJECTIVES Based on enhanced MRI, a prediction model of microvascular invasion (MVI) for hepatocellular carcinoma (HCC) was developed using graph convolutional network (GCN) combined nomogram. METHODS We retrospectively collected 182 HCC patients confirmed histopathologically, all of them performed enhanced MRI before surgery. The patients were randomly divided into training and validation groups. Radiomics features were extracted from the arterial phase (AP), portal venous phase (PVP), and delayed phase (DP), respectively. After removing redundant features, the graph structure by constructing the distance matrix with the feature matrix was built. Screening the superior phases and acquired GCN Score (GS). Finally, combining clinical, radiological and GS established the predicting nomogram. RESULTS 27.5% (50/182) patients were with MVI positive. In radiological analysis, intratumoural artery (P = 0.007) was an independent predictor of MVI. GCN model with grey-level cooccurrence matrix-grey-level run length matrix features exhibited area under the curves of the training group was 0.532, 0.690, and 0.885 and the validation group was 0.583, 0.580, and 0.854 for AP, PVP, and DP, respectively. DP was selected to develop final model and got GS. Combining GS with diameter, corona enhancement, mosaic architecture, and intratumoural artery constructed a nomogram which showed a C-index of 0.884 (95% CI: 0.829-0.927). CONCLUSIONS The GCN model based on DP has a high predictive ability. A nomogram combining GS, clinical and radiological characteristics can be a simple and effective guiding tool for selecting HCC treatment options. ADVANCES IN KNOWLEDGE GCN based on MRI could predict MVI on HCC.
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Affiliation(s)
- Yang Liu
- Department of Radiology, Harbin Medical University Cancer Hospital, Harbin 150010, Heilongjiang, China
| | - Ziqian Zhang
- Department of Radiology, Harbin Medical University Cancer Hospital, Harbin 150010, Heilongjiang, China
| | - Hongxia Zhang
- Department of Radiology, Harbin Medical University Cancer Hospital, Harbin 150010, Heilongjiang, China
| | - Xinxin Wang
- Department of Radiology, Harbin Medical University Cancer Hospital, Harbin 150010, Heilongjiang, China
| | - Kun Wang
- College of Intelligent Systems Science and Engineering, Harbin Engineering University, Harbin 150001, China
| | - Rui Yang
- Department of Medical Oncology, Harbin Medical University Cancer Hospital, No.150 Haping Road, Nangang District, Harbin 150081, Heilongjiang Province, China
| | - Peng Han
- Department of Surgical Oncology, Harbin Medical University Cancer Hospital, No.150 Haping Road, Nangang District, Harbin 150081, Heilongjiang Province, China
| | - Kuan Luan
- College of Intelligent Systems Science and Engineering, Harbin Engineering University, Harbin 150001, China
| | - Yang Zhou
- Department of Radiology, Harbin Medical University Cancer Hospital, Harbin 150010, Heilongjiang, China
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Hao X, Xu L, Lan X, Li B, Cai H. Impact of hepatic inflammation and fibrosis on the recurrence and long-term survival of hepatitis B virus-related hepatocellular carcinoma patients after hepatectomy. BMC Cancer 2024; 24:475. [PMID: 38622578 PMCID: PMC11017619 DOI: 10.1186/s12885-024-12187-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Accepted: 03/26/2024] [Indexed: 04/17/2024] Open
Abstract
BACKGROUND Underlying liver disease is correlated with hepatocellular carcinoma (HCC) development in patients with hepatitis B virus (HBV) infection. However, the impact of hepatic inflammation and fibrosis on the patients' prognoses remains unclear. METHODS The clinicopathological data of 638 HBV-infected patients with early-stage HCC between 2017 and 2019 were prospectively collected. Hepatic inflammation and fibrosis were evaluated by experienced pathologists using the Scheuer score system. Survival analysis was analyzed using the Kaplan-Meier analysis. RESULTS Application of the Scheuer scoring system revealed that 50 (7.9%), 274 (42.9%), and 314 (49.2%) patients had minor, intermediate, and severe hepatic inflammation, respectively, and 125 (15.6%), 150 (23.5%), and 363 (56.9%) patients had minor fibrosis, advanced fibrosis, and cirrhosis, respectively. Patients with severe hepatitis tended to have a higher rate of HBeAg positivity, higher HBV-DNA load, elevated alanine aminotransferase (ALT) levels, and a lower proportion of capsule invasion (all Pp < 0.05). There were no significant differences in the recurrence-free and overall survival among the three groups (P = 0.52 and P = 0.66, respectively). Patients with advanced fibrosis or cirrhosis had a higher proportion of HBeAg positivity and thrombocytopenia, higher FIB-4, and larger tumor size compared to those with minor fibrosis (all P < 0.05). Patients with minor, advanced fibrosis, and cirrhosis had similar prognoses after hepatectomy (P = 0.48 and P = 0.70). The multivariate analysis results indicated that neither hepatic inflammation nor fibrosis was an independent predictor associated with prognosis. CONCLUSIONS For HBV-related HCC patients receiving antiviral therapy, hepatic inflammation and fibrosis had little impact on the post-hepatectomy prognosis.
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Affiliation(s)
- Xiangyong Hao
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, 610041, Chengdu, China
- Department of General Surgery, Gansu Provincial Hospital, 730000, Lanzhou, China
| | - Liangliang Xu
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, 610041, Chengdu, China
| | - Xiang Lan
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, 610041, Chengdu, China
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Chongqing Medical University, 400016, Chongqing, China
| | - Bo Li
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, 610041, Chengdu, China
| | - Hui Cai
- Department of General Surgery, Gansu Provincial Hospital, 730000, Lanzhou, China.
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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.
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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
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Pei YX, Su CG, Liao Z, Li WW, Wang ZX, Liu JL. Comparative effectiveness of several adjuvant therapies after hepatectomy for hepatocellular carcinoma patients with microvascular invasion. World J Gastrointest Surg 2024; 16:554-570. [PMID: 38463369 PMCID: PMC10921205 DOI: 10.4240/wjgs.v16.i2.554] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 12/24/2023] [Accepted: 01/18/2024] [Indexed: 02/25/2024] Open
Abstract
BACKGROUND For resectable hepatocellular carcinoma (HCC), radical hepatectomy is commonly used as a curative treatment. However, postoperative recurrence significantly diminishes the overall survival (OS) of HCC patients, especially with microvascular invasion (MVI) as an independent high-risk factor for recurrence. While some studies suggest that postoperative adjuvant therapy may decrease the risk of recurrence following liver resection in HCC patients, the specific role of adjuvant therapies in those with MVI remains unclear. AIM To conduct a network meta-analysis (NMA) to evaluate the efficacy of various adjuvant therapies and determine the optimal adjuvant regimen. METHODS A systematic literature search was conducted on PubMed, EMBASE, and Web of Science until April 6, 2023. Studies comparing different adjuvant therapies or comparing adjuvant therapy with hepatectomy alone were included. Hazard ratios (HRs) with 95% confidence intervals were used to combine data on recurrence free survival and OS in both pairwise meta-analyses and NMA. RESULTS Fourteen eligible trials (2268 patients) reporting five different therapies were included. In terms of reducing the risk of recurrence, radiotherapy (RT) [HR = 0.34 (0.23, 0.5); surface under the cumulative ranking curve (SUCRA) = 97.7%] was found to be the most effective adjuvant therapy, followed by hepatic artery infusion chemotherapy [HR = 0.52 (0.35, 0.76); SUCRA = 65.1%]. Regarding OS improvement, RT [HR: 0.35 (0.2, 0.61); SUCRA = 93.1%] demonstrated the highest effectiveness, followed by sorafenib [HR = 0.48 (0.32, 0.69); SUCRA = 70.9%]. CONCLUSION Adjuvant therapy following hepatectomy may reduce the risk of recurrence and provide a survival benefit for HCC patients with MVI. RT appears to be the most effective adjuvant regimen.
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Affiliation(s)
- Yin-Xuan Pei
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Chengde Medical University, Chengde 067000, Hebei Province, China
| | - Chen-Guang Su
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Chengde Medical University, Chengde 067000, Hebei Province, China
| | - Zheng Liao
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Chengde Medical University, Chengde 067000, Hebei Province, China
| | - Wei-Wei Li
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Chengde Medical University, Chengde 067000, Hebei Province, China
| | - Zi-Xiang Wang
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Chengde Medical University, Chengde 067000, Hebei Province, China
| | - Jin-Long Liu
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Chengde Medical University, Chengde 067000, Hebei Province, China
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Barteselli C, Mazza S, Ravetta V, Viera FT, Veronese L, Frigerio C, Gori G, Bergamaschi G, Sgarlata C, Facciorusso A, Maestri M, Di Sabatino A, Anderloni A. Ultrasound Patterns of Hepatocellular Carcinoma and Their Prognostic Impact: A Retrospective Study. Cancers (Basel) 2023; 15:5396. [PMID: 38001656 PMCID: PMC10670191 DOI: 10.3390/cancers15225396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Revised: 11/07/2023] [Accepted: 11/10/2023] [Indexed: 11/26/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death. Abdominal ultrasound (US) is by far the most widely used first-level exam for the diagnosis of HCC. We aimed to assess whether different ultrasound patterns were related to tumor prognosis. METHODS We retrospectively reviewed all patients with a new diagnosis of HCC (single nodule) and undergoing radiofrequency thermal ablation (RFTA) at our clinic between January 2009 and December 2021. Patients were classified according to four HCC ultrasound patterns: 1A, single capsulated nodule; 1B, well capsulated intra-node nodule; 1C, cluster consisting of capsulated nodules; and 2, non-capsulated nodule. RESULTS 149 patients were analysed; median follow-up time was 43 months. US patterns 1A (32.9%) and 1B (61.1%) were the most commonly seen. Median overall survival (OS) and recurrence-free survival (RFS) from RFTA were 54 months (95% CI, 42-66) and 22 months (95% CI, 12-32), respectively. Pattern 1A showed the best OS. Compared to pattern 1A, 1B was independently associated with worse OS (51 months (95% CI, 34-68) vs. 46 months (95% CI, 18-62)) and RFS (34 months (95% CI, 27-41) vs. 18 months (95% CI, 12-24)). Patterns 1C and 2 were associated with worse RFS compared to 1A, while no difference was seen for OS. Among baseline clinical variables, pattern 1B exhibited higher histological grade (p = 0.048) and tumor dimension (p = 0.034) compared to pattern 1A. CONCLUSIONS Our findings demonstrate that different US patterns correlate with different survival outcomes and tumor behavior in patients with HCC. Prospective studies are needed to confirm these results.
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Affiliation(s)
- Chiara Barteselli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Stefano Mazza
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Valentina Ravetta
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Francesca Torello Viera
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Letizia Veronese
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Chiara Frigerio
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Giulia Gori
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, 27100 Pavia, Italy
| | - Gaetano Bergamaschi
- First Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Carmelo Sgarlata
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Antonio Facciorusso
- Gastroenterology Unit, Department of Medical and Surgical Sciences, University of Foggia, Viale Luigi Pinto 1, 71122 Foggia, Italy
| | - Marcello Maestri
- General Surgery I, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy;
| | - Antonio Di Sabatino
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, 27100 Pavia, Italy
- First Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Andrea Anderloni
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
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9
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Ouyang J, Wang Z, Yuan K, Yang Y, Zhou Y, Li Q, Yang N, Zhao H, Zhao H, Zhou J. Adjuvant Lenvatinib Plus PD-1 Antibody for Hepatocellular Carcinoma with High Recurrence Risks After Hepatectomy: A Retrospective Landmark Analysis. J Hepatocell Carcinoma 2023; 10:1465-1477. [PMID: 37701564 PMCID: PMC10493137 DOI: 10.2147/jhc.s424616] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Accepted: 08/29/2023] [Indexed: 09/14/2023] Open
Abstract
Purpose To evaluate the efficacy and safety of lenvatinib plus programmed death-1 (PD-1) antibody as postoperative adjuvant therapy in patients with hepatocellular carcinoma (HCC) at high risks of recurrence. Patients and Methods A series of 137 patients with HCC at high risks of recurrence who underwent hepatectomy at our hospital between October 2019 and January 2022 were retrospectively analyzed. Recurrence-free survival (RFS), overall survival (OS), and treatment-related adverse events (TRAEs) were assessed. Landmark analysis was used to compare short- and long-term RFS. Univariable and multivariable analyses were used to identify prognostic factors, and subgroup analyses were performed according to high risks of recurrence. Results A total of 85 patients underwent hepatectomy alone and 52 patients received postoperative adjuvant therapy. Compared with the hepatectomy group (HG), RFS was significantly improved in the adjuvant therapy group (ATG) (P < 0.001), but OS was not (P = 0.098). Landmark analysis revealed that RFS within 6 months of the HG was significantly different from that of the ATG (P < 0.001) but not after 6 months (P = 0.486). Multivariable analysis showed that without adjuvant therapy, high Child-Pugh classification, high alpha-fetoprotein levels, microvascular invasion, and satellite lesions were independent risk factors for recurrence within 6 months after hepatectomy. Subgroup analysis revealed that patients with MVI significantly benefited from adjuvant therapy in RFS. But for OS, adjuvant therapy was only significantly effective in patients with single tumor. The most common treatment-related adverse events during adjuvant therapy were hypertension (36.5%), rash or itching (28.8%), diarrhea (23.1%), and fatigue (21.2%). Conclusion Postoperative adjuvant lenvatinib plus PD-1 antibody significantly improved RFS in patients with HCC at high risks of recurrence with acceptable safeties.
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Affiliation(s)
- Jingzhong Ouyang
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, People’s Republic of China
| | - Zhengzheng Wang
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, People’s Republic of China
| | - Kun Yuan
- School of Public Health, Capital Medical University, Beijing, People’s Republic of China
| | - Yi Yang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
- Key Laboratory of Gene Editing Screening and Research and Development (R&D) of Digestive System Tumor Drugs, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
| | - Yanzhao Zhou
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, People’s Republic of China
| | - Qingjun Li
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, People’s Republic of China
| | - Nanmu Yang
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, People’s Republic of China
| | - Haitao Zhao
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
| | - Hong Zhao
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
- Key Laboratory of Gene Editing Screening and Research and Development (R&D) of Digestive System Tumor Drugs, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
| | - Jinxue Zhou
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, People’s Republic of China
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10
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Suh SW, Lee SE, Choi YS. Influence of Intraoperative Blood Loss on Tumor Recurrence after Surgical Resection in Hepatocellular Carcinoma. J Pers Med 2023; 13:1115. [PMID: 37511728 PMCID: PMC10381288 DOI: 10.3390/jpm13071115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Revised: 07/03/2023] [Accepted: 07/08/2023] [Indexed: 07/30/2023] Open
Abstract
The high incidence of hepatocellular carcinoma (HCC) recurrence after surgical resection worsens the long-term prognosis. Besides tumor-related factors, operative factors such as perioperative blood transfusion have been reported to be related to HCC recurrence. However, excessive intraoperative blood loss (IBL) always necessitates blood transfusion, where IBL and blood transfusion may influence oncologic outcomes. We enrolled 142 patients with newly diagnosed single HCC who underwent hepatic resection between March 2010 and July 2021. Patients were stratified into two groups by IBL volume: Group A (IBL ≥ 700 mL, n = 47) and Group B (IBL < 700 mL, n = 95). The clinic-pathologic findings, operative outcomes, and cumulative probability of tumor recurrence and overall survival were compared between the two groups. In the study, increased IBL (1351 ± 698 vs. 354 ± 166, p < 0.001) and blood transfusion (63.8% vs. 6.3%, p < 0.001) were common in Group A, with a greater HCC recurrence (p = 0.001) and poor overall survival (p = 0.017) compared to those in Group B. Preoperative albumin (hazard ratio [HR], 0.471; 95% confidence interval [CI], 0.244-0.907, p = 0.024), microvascular invasion (HR, 2.616; 95% CI, 1.298-5.273; p = 0.007), and IBL ≥ 700 mL (HR, 2.325; 95% CI, 1.202-4.497; p = 0.012) were significant risk factors for tumor recurrence after surgical resection for HCC. In conclusion, efforts to minimize IBL during hepatic resection are important for improving long-term prognosis in HCC patients.
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Affiliation(s)
- Suk-Won Suh
- Department of Surgery, College of Medicine, Chung-Ang University, Seoul 156-755, Republic of Korea
| | - Seung Eun Lee
- Department of Surgery, College of Medicine, Chung-Ang University, Seoul 156-755, Republic of Korea
| | - Yoo Shin Choi
- Department of Surgery, College of Medicine, Chung-Ang University, Seoul 156-755, Republic of Korea
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11
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Qiu ZC, Li C, Zhang Y, Xie F, Yu Y, Leng SS, Chen TH, Wen TF. Tumor burden score-AFP-albumin-bilirubin grade score predicts the survival of patients with hepatocellular carcinoma after liver resection. Langenbecks Arch Surg 2023; 408:250. [PMID: 37382724 DOI: 10.1007/s00423-023-02993-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2022] [Accepted: 06/17/2023] [Indexed: 06/30/2023]
Abstract
PURPOSE There is little information regarding the overall survival (OS) predictive ability of the combination of tumor burden score (TBS), α-fetoprotein (AFP), and albumin-bilirubin (ALBI) grade for patients with hepatocellular carcinoma (HCC). Here, we aimed to develop a model including TBS, AFP, and ALBI grade to predict HCC patient OS following liver resection. METHODS Patients (N = 1556) from six centers were randomly divided 1:1 into training and validation sets. The X-Tile software was used to determine the optimal cutoff values. The time-dependent area under the receiver operating characteristic curve (AUROC) was calculated to assess the prognostic ability of the different models. RESULTS In the training set, tumor differentiation, TBS, AFP, ALBI grade, and Barcelona Clinic Liver Cancer (BCLC) stage were independently related to OS. According to the coefficient values of TBS, AFP, and ALBI grade, we developed the TBS-AFP-ALBI (TAA) score using a simplified point system (0, 2 for low/high TBS, 0, 1 for low/high AFP and 0,1 for ALBI grade 1/2). Patients were further divided into low TAA (TAA ≤ 1), medium TAA (TAA = 2-3), and high TAA (TAA= 4) groups. TAA scores (low: referent; medium, HR = 1.994, 95% CI = 1.492-2.666; high, HR = 2.413, 95% CI = 1.630-3.573) were independently associated with patient survival in the validation set. The TAA scores showed higher AUROCs than BCLC stage for the prediction of 1-, 3-, and 5-year OS in both the training and validation sets. CONCLUSION TAA is a simple score that has better OS prediction performance than the BCLC stage in predicting OS for HCC patients after liver resection.
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Affiliation(s)
- Zhan-Cheng Qiu
- Department of liver Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Chuan Li
- Department of liver Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China.
| | - Yu Zhang
- Department of HPB Surgery, Sichuan Province People's Hospital, Chengdu, 610072, China
| | - Fei Xie
- Department of HPB Surgery, the First People's Hospital of Neijiang, Neijiang, 641099, China
| | - Yu Yu
- Department of HPB Surgery, the Second People's Hospital of Yibin, Yibin, 644002, China
| | - Shu-Sheng Leng
- Department of HPB Surgery, the Affiliated Hospital of Chengdu University, Chengdu, 610081, China
| | - Ting-Hao Chen
- Department of HPB Surgery, the First People's Hospital of Ziyang, Ziyang, 641399, China
| | - Tian-Fu Wen
- Department of liver Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China
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12
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Kao WY, Tan ECH, Lee HL, Huang YH, Huo TI, Chang CC, Chiou JF, Hou MC, Wu JC, Su CW. Entecavir versus tenofovir on prognosis of hepatitis B virus-related hepatocellular carcinoma after curative hepatectomy. Aliment Pharmacol Ther 2023; 57:1299-1312. [PMID: 36914943 DOI: 10.1111/apt.17438] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 01/27/2023] [Accepted: 02/15/2023] [Indexed: 03/16/2023]
Abstract
BACKGROUND There is still controversy about whether tenofovir disoproxil fumarate (TDF) and entecavir (ETV) have different effects on the outcomes of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). AIMS The aim of this study was to compare the prognoses between ETV and TDF treatment among patients with HBV-related HCC after hepatectomy. METHODS An analysis was done on data from the Taiwan Cancer Registry, which was linked to Taiwan National Health Insurance Research Database, for the years 2011-2016. We identified 7107 patients with HBV-related HCC after curative hepatectomy, and 25.3% of them used ETV or TDF after surgery. After propensity score overlap weighting, 1797 patients treated with ETV (n = 1365) or TDF (n = 432) were included for analyses. Cox proportional hazards models were used to compare the efficacy of ETV and TDF for recurrence and overall survival (OS). RESULTS After hepatectomy, the recurrence rate per 100 person-years was 14.87 for the ETV group and 9.25 for the TDF group. The risk of recurrence was similar in the TDF group and the ETV group (HR [95% CI]: 0.91 [0.69-1.19; p = 0.479]), as was the risk of all-cause mortality (HR [95% CI]: 0.67 [0.42-1.07]; p = 0.091). When considering early recurrence (<2 years) and late recurrence (≧2 years), the TDF and ETV groups showed no significant differences. Subgroup analyses and sensitivity analyses demonstrated consistent results. CONCLUSION Both TDF and ETV showed similar health benefits in terms of recurrence and OS in patients with HBV-related HCC patients after hepatectomy.
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Affiliation(s)
- Wei-Yu Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.,TMU Research Center for Digestive Medicine, Taipei Medical University, Taipei, Taiwan
| | - Elise Chia-Hui Tan
- Department of Health Service Administration, College of Public Health, China Medical University, Taichung, Taiwan
| | - Hsin-Lun Lee
- Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.,Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan.,Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Internal Medicine, School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Teh-Ia Huo
- Division of Basic Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.,Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chun-Chao Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,TMU Research Center for Digestive Medicine, Taipei Medical University, Taipei, Taiwan
| | - Jeng-Fong Chiou
- Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.,Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan.,Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Internal Medicine, School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Jaw-Ching Wu
- Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chien-Wei Su
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Internal Medicine, School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Division of Holistic and Multidisciplinary Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
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13
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Li J, Yang F, Li J, Huang ZY, Cheng Q, Zhang EL. Postoperative adjuvant therapy for hepatocellular carcinoma with microvascular invasion. World J Gastrointest Surg 2023; 15:19-31. [PMID: 36741072 PMCID: PMC9896490 DOI: 10.4240/wjgs.v15.i1.19] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 10/29/2022] [Accepted: 12/21/2022] [Indexed: 01/17/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most lethal tumors in the world. Liver resection (LR) and liver transplantation (LT) are widely considered as radical treatments for early HCC. However, the recurrence rates after curative treatment are still high and overall survival is unsatisfactory. Microvascular invasion (MVI) is considered to be one of the important prognostic factors affecting postoperative recurrence and long-term survival. Unfortunately, whether HCC patients with MVI should receive postoperative adjuvant therapy remains unknown. In this review, we summarize the therapeutic effects of transcatheter arterial chemoembolization, hepatic arterial infusion chemotherapy, tyrosine protein kinase inhibitor-based targeted therapy, and immune checkpoint inhibitors in patients with MVI after LR or LT, aiming to provide a reference for the best adjuvant treatment strategy for HCC patients with MVI after LT or LR.
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Affiliation(s)
- Jiang Li
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, College of Medicine, Shihezi University, Shihezi 832000, Xinjiang Uygur Autonomous Regions, China
| | - Fan Yang
- Department of General Surgery, Affiliated Hospital of Hubei Minzu University, Enshi 445000, Hubei Province, China
| | - Jian Li
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Zhi-Yong Huang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Qi Cheng
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Er-Lei Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
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14
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Yue Q, Zhou Z, Zhang X, Xu X, Liu Y, Wang K, Liu Q, Wang J, Zhao Y, Yin Y. Contrast-enhanced CT findings-based model to predict MVI in patients with hepatocellular carcinoma. BMC Gastroenterol 2022; 22:544. [PMID: 36577952 PMCID: PMC9798548 DOI: 10.1186/s12876-022-02586-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Accepted: 11/16/2022] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Microvascular invasion (MVI) is important in early recurrence and leads to poor overall survival (OS) in hepatocellular carcinoma (HCC). A number of studies have reported independent risk factors for MVI. In this retrospective study, we designed to develop a preoperative model for predicting the presence of MVI in HCC patients to help surgeons in their surgical decision-making and improve patient management. PATIENTS AND METHODS We developed a predictive model based on a nomogram in a training cohort of 225 HCC patients. We analyzed patients' clinical information, laboratory examinations, and imaging features from contrast-enhanced CT. Mann-Whitney U test and multiple logistic regression analysis were used to confirm independent risk factors and develop the predictive model. Internal and external validation was performed on 75 and 77 HCC patients, respectively. Moreover, the diagnostic performance of our model was evaluated using receiver operating characteristic (ROC) curves. RESULTS In the training cohort, maximum tumor diameter (> 50 mm), tumor margin, direct bilirubin (> 2.7 µmol/L), and AFP (> 360.7 ng/mL) were confirmed as independent risk factors for MVI. In the internal and external validation cohort, the developed nomogram model demonstrated good diagnostic ability for MVI with an area under the curve (AUC) of 0.723 and 0.829, respectively. CONCLUSION Based on routine clinical examinations, which may be helpful for clinical decision-making, we have developed a nomogram model that can successfully assess the risk of MVI in HCC patients preoperatively. When predicting HCC patients with a high risk of MVI, the surgeons may perform an anatomical or wide-margin hepatectomy on the patient.
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Affiliation(s)
- Qi Yue
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
- Department of Hepatobiliary Surgery, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, China
| | - Zheyu Zhou
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
- Department of General Surgery, Nanjing Drum Tower Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Graduate School of Peking Union Medical College, Nanjing, China
| | - Xudong Zhang
- Department of Hepato-Biliary-Pancreatic Surgery, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, China
| | - Xiaoliang Xu
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Yang Liu
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Kun Wang
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Qiaoyu Liu
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Jincheng Wang
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Yu Zhao
- Department of Medical Imaging, School of Medical Imaging, Nanjing Medical University, Jiangning, Nanjing, China
| | - Yin Yin
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
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15
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Wu JY, Wu JY, Li YN, Qiu FN, Zhou SQ, Yin ZY, Chen YF, Li B, Zhou JY, Yan ML. Lenvatinib combined with anti-PD-1 antibodies plus transcatheter arterial chemoembolization for neoadjuvant treatment of resectable hepatocellular carcinoma with high risk of recurrence: A multicenter retrospective study. Front Oncol 2022; 12:985380. [PMID: 36212494 PMCID: PMC9534527 DOI: 10.3389/fonc.2022.985380] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Accepted: 09/06/2022] [Indexed: 01/27/2023] Open
Abstract
Background Early recurrence is common after surgical resection (SR) for hepatocellular carcinoma (HCC) with high risk of recurrence and is associated with poor prognosis. The combinations of lenvatinib (LEN), anti-PD-1 antibodies (PD-1) and transcatheter arterial chemoembolization (TACE) (triple therapy) has shown better trend in tumor response and survival outcomes on unresectable HCC. It is unknown whether triple therapy for neoadjuvant treatment of resectable HCC with high risk of recurrence is effective. This article aimed to compare the outcomes of surgery alone and neoadjuvant combination treatment with triple therapy before SR in patients with HCC with high risk of recurrence. Methods A retrospective study was conducted on patients diagnosed with HCC with high risk of recurrence who received treatment with or without triple therapy. The records of 24 patients in the triple therapy group and 76 patients in the surgery-alone group were analyzed. Propensity score matching (PSM) was performed to minimize the influence of potential confounders. Results One hundred patients were enrolled. In the triple therapy group, 8 (33.3%) and 12 (50.0%) patients had complete and partial responses, respectively, as assessed by an investigator. Before PSM, the overall survival (OS) rates for the triple therapy group at 6, 12, 18, and 24 months were 100.0%, 100.0%, 100.0%, and 85.7%, respectively, compared with corresponding 92.1%, 73.7%, 53.9%, and 48.7% for the surgery-alone group (P<0.001). The disease-free survival (DFS) rates were 82.2%, 66.95%, 48.8%, and 48.8% for the triple therapy and 41.92%, 28.34%, 27.05%, and 22.99% for the surgery-alone group (P=0.003). After PSM, DFS and OS were significantly longer in the triple therapy group than in the surgery-alone group (DFS, p=0.019; OS, p=0.003). Conclusions Neoadjuvant combination treatment before SR had a high rate of tumor response and provided significantly better postoperative survival outcomes than surgery alone in patients with HCC with high risk of recurrence.
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Affiliation(s)
- Jun-Yi Wu
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Jia-Yi Wu
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Yi-Nan Li
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Fu-Nan Qiu
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Song-Qiang Zhou
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Zhen-Yu Yin
- Department of Hepatobiliary Surgery, Xiamen Traditional Chinese Medical Hospital, Xiamen, China
| | - Yu-Feng Chen
- Department of Hepatobiliary Surgery, The Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China
| | - Bin Li
- Department of Hepato-Biliary-Pancreatic and Vascular Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Jian-Yin Zhou
- Department of Hepatobiliary Surgery, Zhongshan Hospital of Xiamen University, Xiamen, China
| | - Mao-Lin Yan
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
- *Correspondence: Mao-Lin Yan,
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16
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Contrast-enhanced magnetic resonance imaging perfusion can predict microvascular invasion in patients with hepatocellular carcinoma (between 1 and 5 cm). ABDOMINAL RADIOLOGY (NEW YORK) 2022; 47:3264-3275. [PMID: 35113174 DOI: 10.1007/s00261-022-03423-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Revised: 01/12/2022] [Accepted: 01/12/2022] [Indexed: 01/18/2023]
Abstract
PURPOSE To evaluate the role of perfusion parameters with MR imaging of the liver in diagnosing MVI in hepatocellular carcinoma (HCC) (between 1 and 5 cm). MATERIALS AND METHODS This retrospective study was approved by the institutional review board. In 80 patients with 43 MVI( +) and 42 MVI( -) HCC, whole-liver perfusion MR imaging with Cartesian k-space undersampling and compressed sensing reconstruction was performed after injection of 0.1 mmol/kg gadopentetate dimeglumine. Parameters derived from a dual-input single-compartment model of arterial flow (Fa), portal venous flow (Fp), total blood flow (Ft = Fa + Fp), arterial fraction (ART), distribution volume (DV), and mean transit time (MTT) were measured. The significant parameters between the two groups were included to correlate with the presence of MVI at simple and multiple regression analysis. RESULTS In MVI-positive HCC, Fp was significantly higher than in MVI-negative HCC, whereas the reverse was seen for ART (p < 0.001). Tumor size (β = 1.2, p = 0.004; odds ratio, 3.20; 95% CI 1.45, 7.06), Fp (β = 1.1, p = 0.004; odds ratio, 3.09; 95% CI 1.42, 6.72), and ART (β = - 3.1, p = 0.001; odds ratio, 12.13; 95% CI 2.85, 51.49) were independent risk factors for MVI. The AUC value of the combination of all three metrics was 0.931 (95% CI 0.855, 0.975), with sensitivity of 97.6% and specificity of 76.2%. CONCLUSION The combination of Fp, ART, and tumor size demonstrated a higher diagnostic accuracy compared with each parameter used individually when evaluating MVI in HCC (between 1 and 5 cm).
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17
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Huang T, Qi H, Shen L, Wu Y, Song Z, Cao F, Liu Y, Xie L, Chen S, Tang T, Li H, Zhang Y, Feng L, Zhang H, Chen J, Fan W. Benefits of step-by-step debulking microwave ablation for huge unresectable hepatocellular carcinoma patients after transcatheter arterial chemoembolization refractoriness. Int J Hyperthermia 2022; 39:935-945. [PMID: 35853727 DOI: 10.1080/02656736.2022.2093413] [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: 10/17/2022] Open
Abstract
OBJECTIVES To compare the safety and efficacy of step-by-step debulking Microwave Ablation (MWA) with Transarterial Chemoembolization (TACE) monotherapy for huge (≥10 cm in diameter) unresectable hepatocellular carcinoma (HCC) after TACE refractoriness. METHODS This is a multi-center retrospective study carried out on 599 patients with huge unresectable HCC who received TACE as first-line therapy at five hospitals from January 2009 to December 2018. A total of 103 patients with TACE refractoriness were divided into two cohorts: monthly step-by-step debulking MWA (n = 52) or continued TACE (n = 51). Overall survival (OS) and progression-free survival (PFS) after refractory TACE were evaluated. Residual liver and tumor volume were recorded for the MWA group. RESULTS Median follow-up period was 24.3 months and median OS and PFS were significantly longer in the MWA group than in the TACE group (OS 21.0 vs. 11.7 months, PFS 6.1 vs. 3.0 months, both p < 0.001). The one-, two-, and three-year OS rates in the MWA and TACE groups were 73.1%, 46.6%, and 37.2% versus 43.1%, 15.5%, and 2.9%, respectively. Furthermore, the 0.5-, 1-, and 2-year PFS rates in the MWA and TACE groups were 51.9%, 36.5%, and 25.0% versus 27.5%, 11.8%, and 0, respectively. Multivariate analyses confirmed that switching to debulking MWA treatment was an independent favorable prognostic factor for PFS and OS. In the MWA group, the average additions of residual liver volume/total liver volume were 7.7% ± 6.7%, 7.2% ± 10.2%, and 10.1% ± 8.8% after the first, second, and third MWA procedure. CONCLUSION Step-by-step debulking MWA can significantly improve long-term OS and PFS in patients with huge unresectable HCCs compared with repeated TACE after TACE refractoriness. Key PointThe debulking MWA therapy provides significantly longer OS and PFS than continued TACE for patients with huge unresectable HCCs after TACE-refractory, especially with complete tumor ablation.The most common complications were fever (48.1%) and pain (46.2%) in the MWA group. Two major complications (abdominal infection) were recorded in the MWA group, which recovered after symptomatic treatment.During the course of repeated MWAs, liver hyperplasia appeared mainly after the second MWA procedure and the average maximum increased RLV/TLV rate was 16.3%±12.7%.
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Affiliation(s)
- Tao Huang
- Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, China
| | - Han Qi
- Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, China
| | - Lujun Shen
- Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, China
| | - Ying Wu
- Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, China
| | - Ze Song
- Department of Oncology, the Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Fei Cao
- Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, China
| | - Yin Liu
- Department of Oncology, Jinshazhou Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Lin Xie
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Shuanggang Chen
- Department of Oncology, Yue Bei people's Hospital, Shaoguan, China
| | - Tian Tang
- Department of Interventional Therapy, Hunan Cancer Hospital, Changsha, China
| | - Hailiang Li
- Department of Interventional Therapy, Henan Cancer Hospital, Zhengzhou, China
| | - Yanfang Zhang
- Department of Interventional Therapy, Shenzhen people's Hospital, Shenzhen, China
| | - Long Feng
- Department of Oncology, the Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Hao Zhang
- Center for Interventional Medicine, the Affiliated Hospital of Qingdao University, Qingdao, China
| | - Jin Chen
- Department of Radiology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Weijun Fan
- Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, China
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18
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Salehi O, Vega EA, Kutlu OC, Lunsford K, Freeman R, Ladin K, Alarcon SV, Kazakova V, Conrad C. Poorly differentiated hepatocellular carcinoma: resection is equivalent to transplantation in patients with low liver fibrosis. HPB (Oxford) 2022; 24:1100-1109. [PMID: 34969618 DOI: 10.1016/j.hpb.2021.12.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 11/28/2021] [Accepted: 12/08/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Organ allocation criteria for liver transplantation focus on tumor size and multifocality while tumor differentiation and existing liver damage are omitted. This study analyzes the impact of hepatocellular carcinoma (HCC) grade and liver fibrosis comparing resection (SX) to transplantation (LT). METHODS The National Cancer Database was queried between 2004 and 2016 for solitary HCC meeting Milan criteria undergoing SX vs LT. Two groups were created: low fibrosis (LF) vs high fibrosis (HF) and stratified by grade. Cox multivariable regression models, Kaplan-Meier survival analyses and log-rank tests were performed. RESULTS 1515 patients were identified; 780 had LT and 735 had SX. Median overall survival (mOS) was 39.7 months; LT mOS was 47.9 months vs SX mOS of 34.9 months (P < .001). Multivariate analysis revealed SX, no chemotherapy, longer hospital stays, and age to be associated with worse survival. However, while transplantation conferred survival benefit for well-moderately differentiated tumors, SX vs LT did not impact survival for poorly differentiated HCC in LF patients, independent of tumor size. DISCUSSION HCC differentiation and liver fibrosis, but not size, synergistically determine efficacy of SX vs LT. Therefore, current HCC transplantation criteria should incorporate tumor grade or liver fibrosis for optimal organ allocation.
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Affiliation(s)
- Omid Salehi
- Department of Surgery, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA, USA
| | - Eduardo A Vega
- Department of Surgery, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA, USA
| | - Onur C Kutlu
- Department of Surgery, University of Miami Health System, Miller School of Medicine, Miami, FL, USA
| | - Keri Lunsford
- Department of Surgery, Division of Transplant and Hepatobiliary Surgery, Rutgers New Jersey Medical School, Newark, NJ, USA
| | - Richard Freeman
- Department of Surgery, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA, USA
| | - Keren Ladin
- Department of Occupational Therapy and Community Health, Tufts University, Boston, MA, USA
| | - Sylvia V Alarcon
- Department of Medical Oncology, Dana-Farber Cancer Institute at St. Elizabeth's Medical Center, Harvard Medical School, Boston, MA, USA
| | - Vera Kazakova
- Department of Medical Oncology, Dana-Farber Cancer Institute at St. Elizabeth's Medical Center, Harvard Medical School, Boston, MA, USA
| | - Claudius Conrad
- Department of Surgery, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA, USA.
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19
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Chen Q, Xiao H, Gu Y, Weng Z, Wei L, Li B, Liao B, Li J, Lin J, Hei M, Peng S, Wang W, Kuang M, Chen S. Deep learning for evaluation of microvascular invasion in hepatocellular carcinoma from tumor areas of histology images. Hepatol Int 2022; 16:590-602. [PMID: 35349075 PMCID: PMC9174315 DOI: 10.1007/s12072-022-10323-w] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Accepted: 02/16/2022] [Indexed: 11/23/2022]
Abstract
BACKGROUND Microvascular invasion (MVI) is essential for the management of hepatocellular carcinoma (HCC). However, MVI is hard to evaluate in patients without sufficient peri-tumoral tissue samples, which account for over a half of HCC patients. METHODS We established an MVI deep-learning (MVI-DL) model with a weakly supervised multiple-instance learning framework, to evaluate MVI status using only tumor tissues from the histological whole slide images (WSIs). A total of 350 HCC patients (2917 WSIs) from the First Affiliated Hospital of Sun Yat-sen University (FAHSYSU cohort) were divided into a training and test set. One hundred and twenty patients (504 WSIs) from Dongguan People's Hospital and Shunde Hospital of Southern Medical University (DG-SD cohort) formed an external test set. Unsupervised clustering and class activation mapping were applied to visualize the key histological features. RESULTS In the FAHSYSU and DG-SD test set, the MVI-DL model achieved an AUC of 0.904 (95% CI 0.888-0.920) and 0.871 (95% CI 0.837-0.905), respectively. Visualization results showed that macrotrabecular architecture with rich blood sinus, rich tumor stroma and high intratumor heterogeneity were identified as the key features associated with MVI ( +), whereas severe immune infiltration and highly differentiated tumor cells were associated with MVI (-). In the simulation of patients with only one WSI or biopsies only, the AUC of the MVI-DL model reached 0.875 (95% CI 0.855-0.895) and 0.879 (95% CI 0.853-0.906), respectively. CONCLUSION The effective, interpretable MVI-DL model has potential as an important tool with practical clinical applicability in evaluating MVI status from the tumor areas on the histological slides.
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Affiliation(s)
- Qiaofeng Chen
- Department of Gastroenterology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Han Xiao
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, the First Affiliated Hospital of Sun Yat-Sen University, No. 58, Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China
| | - Yunquan Gu
- Clinical Trials Unit, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Zongpeng Weng
- Clinical Trials Unit, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Lihong Wei
- Department of Pathology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Bin Li
- Clinical Trials Unit, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Bing Liao
- Department of Pathology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Jiali Li
- Department of Liver and Pancreatobiliary Surgery, Dongguan People's Hospital, Dongguan, Guangdong, China
| | - Jie Lin
- Department of Liver and Pancreatobiliary Surgery, Shunde Hospital of Southern Medical University, Shunde, Guangdong, China
| | - Mengying Hei
- Department of Pathology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Sui Peng
- Department of Gastroenterology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Clinical Trials Unit, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Wei Wang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, the First Affiliated Hospital of Sun Yat-Sen University, No. 58, Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China.
| | - Ming Kuang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, the First Affiliated Hospital of Sun Yat-Sen University, No. 58, Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China.
- Department of Liver Surgery, Cancer Center, Institute of Precision Medicine, the First Affiliated Hospital of Sun Yat-Sen University, No. 58, Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China.
| | - Shuling Chen
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, the First Affiliated Hospital of Sun Yat-Sen University, No. 58, Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China.
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20
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Herrero A, Boivineau L, Cassese G, Assenat E, Riviere B, Faure S, Bedoya JU, Panaro F, Guiu B, Navarro F, Pageaux GP. Progression of AFP SCORE is a Preoperative Predictive Factor of Microvascular Invasion in Selected Patients Meeting Liver Transplantation Criteria for Hepatocellular Carcinoma. Transpl Int 2022; 35:10412. [PMID: 35401038 PMCID: PMC8983829 DOI: 10.3389/ti.2022.10412] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Accepted: 02/24/2022] [Indexed: 12/24/2022]
Abstract
Microvascular invasion (MVI) is one of the main prognostic factors of hepatocellular carcinoma (HCC) after liver transplantation (LT), but its occurrence is unpredictable before surgery. The alpha fetoprotein (AFP) model (composite score including size, number, AFP), currently used in France, defines the selection criteria for LT. This study’s aim was to evaluate the preoperative predictive value of AFP SCORE progression on MVI and overall survival during the waiting period for LT. Data regarding LT recipients for HCC from 2007 to 2015 were retrospectively collected from a single institutional database. Among 159 collected cases, 34 patients progressed according to AFP SCORE from diagnosis until LT. MVI was shown to be an independent histopathological prognostic factor according to Cox regression and competing risk analysis in our cohort. AFP SCORE progression was the only preoperative predictive factor of MVI (OR = 10.79 [2.35–49.4]; p 0.002). The 5-year overall survival in the progression and no progression groups was 63.9% vs. 86.3%, respectively (p = 0.001). Cumulative incidence of HCC recurrence was significantly different between the progression and no progression groups (Sub-HR = 4.89 [CI 2–11.98]). In selected patients, the progression of AFP SCORE during the waiting period can be a useful preoperative tool to predict MVI.
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Affiliation(s)
- Astrid Herrero
- Department of Digestive Surgery and Liver Transplantation, Montpellier University Hospital, University of Montpellier, Montpellier, France
| | - Lucile Boivineau
- Liver Transplantation Unit, Department of Hepatology, Montpellier University Hospital, University of Montpellier, Montpellier, France
| | - Gianluca Cassese
- Department of Digestive Surgery and Liver Transplantation, Montpellier University Hospital, University of Montpellier, Montpellier, France.,Department of Clinical Medicine and Surgery, Minimally invasive and robotic HPB Surgery Unit, Federico II University, Naples, Italy
| | - Eric Assenat
- Department of Digestive Oncology, Montpellier University Hospital, University of Montpellier, Montpellier, France
| | - Benjamin Riviere
- Department of Pathology, Montpellier University Hospital, University of Montpellier, Montpellier, France
| | - Stéphanie Faure
- Liver Transplantation Unit, Department of Hepatology, Montpellier University Hospital, University of Montpellier, Montpellier, France
| | - José Ursic Bedoya
- Liver Transplantation Unit, Department of Hepatology, Montpellier University Hospital, University of Montpellier, Montpellier, France
| | - Fabrizio Panaro
- Department of Digestive Surgery and Liver Transplantation, Montpellier University Hospital, University of Montpellier, Montpellier, France
| | - Boris Guiu
- Department of Digestive Imaging, Montpellier University Hospital, University of Montpellier, Montpellier, France
| | - Francis Navarro
- Department of Digestive Surgery and Liver Transplantation, Montpellier University Hospital, University of Montpellier, Montpellier, France
| | - Georges-Philippe Pageaux
- Liver Transplantation Unit, Department of Hepatology, Montpellier University Hospital, University of Montpellier, Montpellier, France
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21
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Yan Q, Lin HM, Zhu K, Cao Y, Xu XL, Zhou ZY, Xu LB, Liu C, Zhang R. Immune Checkpoint FGL1 Expression of Circulating Tumor Cells Is Associated With Poor Survival in Curatively Resected Hepatocellular Carcinoma. Front Oncol 2022; 12:810269. [PMID: 35273912 PMCID: PMC8901582 DOI: 10.3389/fonc.2022.810269] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2021] [Accepted: 01/19/2022] [Indexed: 12/12/2022] Open
Abstract
LAG-3 is one of the common tumor immune checkpoints. LAG-3 can inhibit the activation and proliferation of T cells, and can also suppress immunity by regulating other immune-related cell functions. FGL1 was recently discovered to be the main ligand of immune checkpoint LAG-3 and play a critical role in the inhibition of T cells. However, the FGL1 expression in circulating tumor cells (CTCs) and its clinical significance in hepatocellular carcinoma (HCC) remain unclear. Therefore, this bioinformatics analysis was performed to assess the expression of FGL1 in various tumors and its association with immune infiltration. After that, CTCs from 109 HCC patients were detected and the immunofluorescence staining was performed (CD45, EpCAM, CK8/18/19, Vimentin, Twist, DAPI and FGL1). Then, we investigated FGL1 expression and EMT of CTCs and analyzed its relationship with patient survival and clinical relevance. Bioinformatic results showed that FGL1 expression was abnormal in various tumor and it was correlated with the infiltration level of several immune cells. FGL1 expression was detected in CTCs of 40 patients (36.7%). The proportion of advanced TNM stage (P<0.001) and distant metastasis(P=0.020) in FGL1 positive patients was higher than that of FGL1 negative patients. In addition, patients with FGL1 positive circulating tumor cells had worse postoperative survival than FGL1 negative patients (p=0.0297). The mixed phenotypic CTC presented a higher level of FGL1 expression than any other types, the number of which also predicted worse prognosis(p=0.0443). We also found that the expression of FGL1 on CTCs was associated with the level of FGL1 in tumor tissues. Of 12 patients receiving PD-1/PD-L1 blockade in a total of 109 cases, 8 out of 10 patients with FGL1 positive CTC showed immunotherapy resistance. It is the first study that suggested FGL1 expression in CTCs as an indicator of the poor prognosis in HCC patients. CTC detection may serve as a promising replacement for determination of tumor tissue FGL1 expression and provide evidence for the application of immunotherapy.
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Affiliation(s)
- Qing Yan
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Department of Hepatic Surgery, The First People’s Hospital of Foshan, Foshan, China
| | - Hao-Ming Lin
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Ke Zhu
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yi Cao
- Department of Emergency, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiao-Lin Xu
- Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zi-Yu Zhou
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Lei-bo Xu
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Chao Liu
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Rui Zhang
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
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22
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Wang J, Ding ZW, Chen K, Liu YZ, Li N, Hu MG. A predictive and prognostic model for hepatocellular carcinoma with microvascular invasion based TCGA database genomics. BMC Cancer 2021; 21:1337. [PMID: 34911488 PMCID: PMC8675478 DOI: 10.1186/s12885-021-09047-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Accepted: 11/15/2021] [Indexed: 02/08/2023] Open
Abstract
Background Microvascular invasion (MVI) adversely affects postoperative long-term survival outcomes in patients with hepatocellular carcinoma (HCC). There is no study addressing genetic changes in HCC patients with MVI. We first screened differentially expressed genes (DEGs) in patients with and without MVI based on TCGA data, established a prediction model and explored the prognostic value of DEGs for HCC patients with MVI. Methods In this paper, gene expression and clinical data of liver cancer patients were downloaded from the TCGA database. The DEG analysis was conducted using DESeq2. Using the least absolute shrinkage and selection operator, MVI-status-related genes were identified. A Kaplan-Meier survival analysis was performed using these genes. Finally, we validated two genes, HOXD9 and HOXD10, using two sets of HCC tissue microarrays from 260 patients. Results Twenty-three MVI-status-related key genes were identified. Based on the key genes, we built a classification model using random forest and time-dependent receiver operating characteristic (ROC), which reached 0.814. Then, we performed a survival analysis and found ten genes had a significant difference in survival time. Simultaneously, using two sets of 260 patients’ HCC tissue microarrays, we validated two key genes, HOXD9 and HOXD10. Our study indicated that HOXD9 and HOXD10 were overexpressed in HCC patients with MVI compared with patients without MVI, and patients with MVI with HOXD9 and 10 overexpression had a poorer prognosis than patients with MVI with low expression of HOXD9 and 10. Conclusion We established an accurate TCGA database-based genomics prediction model for preoperative MVI risk and studied the prognostic value of DEGs for HCC patients with MVI. These DEGs that are related to MVI warrant further study regarding the occurrence and development of MVI. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-021-09047-1.
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Affiliation(s)
- Jin Wang
- Faculty of Hepato-Biliary-Pancreatic Surgery, Chinese People's Liberation Army (PLA) General Hospital, 28 Fuxing Road, Beijing, 100853, China
| | - Zhi-Wen Ding
- Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200433, China
| | - Kuang Chen
- Faculty of Hepato-Biliary-Pancreatic Surgery, Chinese People's Liberation Army (PLA) General Hospital, 28 Fuxing Road, Beijing, 100853, China
| | - Yan-Zhe Liu
- Faculty of Hepato-Biliary-Pancreatic Surgery, Chinese People's Liberation Army (PLA) General Hospital, 28 Fuxing Road, Beijing, 100853, China
| | - Nan Li
- Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200433, China.
| | - Ming-Gen Hu
- Faculty of Hepato-Biliary-Pancreatic Surgery, Chinese People's Liberation Army (PLA) General Hospital, 28 Fuxing Road, Beijing, 100853, China.
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23
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Bae B, Kang K, Song SK, Chung CW, Park Y. Is partial hepatectomy a curable treatment option for hepatocellular carcinoma accompanied by cirrhosis? A meta-analysis and cure model analysis. Ann Hepatobiliary Pancreat Surg 2021; 26:47-57. [PMID: 34903677 PMCID: PMC8901985 DOI: 10.14701/ahbps.21-080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 08/14/2021] [Accepted: 08/17/2021] [Indexed: 11/17/2022] Open
Abstract
Backgrounds/Aims It is challenging to assess the efficacy of partial hepatectomy (PH) as a treatment option for patients with hepatocellular carcinoma (HCC) accompanied by cirrhosis. This study aimed to determine the cure fraction of PH for HCC accompanied by cirrhosis compared to that for HCC without cirrhosis. Methods A systematic review was performed on outcomes of previous studies that compared recurrence-free survival (RFS) after PH in patients with HCC with or without cirrhosis. A meta-analysis was conducted to obtain the cumulative hazard ratio for two patient groups: cirrhosis and non-cirrhosis. Cure fractions after PH in both groups were determined using a cure model analysis. Results A total of 18 studies were eligible for meta-analysis and 13 studies were selected for the cure model analysis. The cumulative hazard ratio for RFS of the cirrhosis group compared to that of the non-cirrhosis group was 1.66 (95% confidence interval [CI], 1.43–1.93). Survival data of 3,512 patients in both groups were reconstructed from survival curves of original articles for cure model analysis. The probability of being statistically cured after PH for HCC was 14.1% (95% CI, 10.6%–18.1%) in the cirrhosis group lower than that (32.5%) in the non-cirrhosis group (95% CI, 28.6%–36.4%). Conclusions The prognosis after PH for HCC accompanied by cirrhosis is inferior to that for HCC without cirrhosis. However, a cure can be expected for one-seventh of patients with HCC accompanied by cirrhosis after PH.
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Affiliation(s)
- Byungje Bae
- Department of Surgery, Catholic Kwandong University International St. Mary's Hospital, Incheon, Korea
| | - Keera Kang
- Department of Surgery, Catholic Kwandong University International St. Mary's Hospital, Incheon, Korea
| | - Sung Kyu Song
- Department of Surgery, Catholic Kwandong University International St. Mary's Hospital, Incheon, Korea
| | - Chul-Woon Chung
- Department of Surgery, Catholic Kwandong University International St. Mary's Hospital, Incheon, Korea
| | - Yongkeun Park
- Department of Surgery, Catholic Kwandong University International St. Mary's Hospital, Incheon, Korea
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24
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Ding J, Wen Z. Survival improvement and prognosis for hepatocellular carcinoma: analysis of the SEER database. BMC Cancer 2021; 21:1157. [PMID: 34715816 PMCID: PMC8555190 DOI: 10.1186/s12885-021-08904-3] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Accepted: 10/18/2021] [Indexed: 02/07/2023] Open
Abstract
Background Hepatocellular carcinoma (HCC) incidences have been increasing in the United States. This study aimed to examine temporal trend of HCC survival and determine prognostic factors influencing HCC survival within the U.S. population. Methods The Surveillance Epidemiology, and End Results (SEER) database was used to identify patients diagnosed with primary HCC from 1988 to 2015. Overall survival (OS) and disease-specific survival (DSS) were calculated by the Kaplan-Meier method. Univariate and multivariate Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for prognostic factors and comparing survival between patients diagnosed at different periods (per 5-year interval). Results A total of 80,347 patients were included. The proportions of both young patients (< 45 years) and old patients (≥75 years) decreased over time (P < 0.001) and the male-to-female ratio increased over time (P < 0.001). Significant decreasing temporal trends were observed for HCC severity at diagnosis, including SEER stage, tumor size, tumor extent, and lymph node involvement (P < 0.001 for all). OS and DSS of patients with HCC improved over time (P < 0.001). After adjusting for patient and tumor characteristics and treatment difference, period of diagnosis retained an independent factor for improved DSS and its prognostic significance was evident for localized and regional HCC (P < 0.001), but not for distant HCC. On multivariate analyses, young age, female gender, Hispanic ethnicity, and married status were predictors favoring DSS, whereas a worse DSS was observed for patients with tumor > 5 cm, with vascular invasion, and with lymph node involvement. Patients treated with liver-directed therapy (HR = 0.54, 95% CI: 0.35–0.56), hepatic resection (HR = 0.35, 95% CI: 0.33–0.37), and transplantation (HR = 0.14, 95% CI: 0.13–0.15) had significantly longer DSS compared with those who received no surgery. In stratified analyses, the beneficial effects of surgical approach, regardless therapy type, were significant across all stages. Conclusions Our results indicate a significant improvement in survival for HCC patients from 1988 to 2015, which may be attributable to advances in early diagnosis and therapeutic approaches.
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Affiliation(s)
- Jingli Ding
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, No. 169, Donghu Road, Hubei, Wuhan, 430071, China.,Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Jiangxi, Nanchang, 330006, China
| | - Zhili Wen
- Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Jiangxi, Nanchang, 330006, China.
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25
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Upregulation of a novel LncRNA AC104958.2 stabilized by PCBP2 promotes proliferation and microvascular invasion in hepatocellular carcinoma. Exp Cell Res 2021; 407:112791. [PMID: 34418457 DOI: 10.1016/j.yexcr.2021.112791] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Revised: 08/16/2021] [Accepted: 08/17/2021] [Indexed: 12/20/2022]
Abstract
Long non-coding RNAs (lncRNAs) were reported to be involved in tumorigenesis and progression of hepatocellular carcinoma (HCC). Microvascular invasion (MVI) is an independent predictor for early recurrence and overall survival in postoperative patients with HCC. However, the mechanisms how lncRNAs affect HCC and MVI remain elusive. By RNA sequencing (RNA-seq) in a series of 65 HCC samples and 30 paired adjacent non-tumor liver tissue, we identified a novel lncRNA AC104958.2 that was significantly upregulated in HCC tissues and associated with MVI. Overexpression of AC104958.2 obviously elevated cell viability, metastasis, invasion and epithelial-mesenchymal transition (EMT), while knockout of AC104958.2 mediated by CRISPR/Cas9 technique showed the opposite effects. In addition, the interaction between AC104958.2 and Poly (rC) binding protein 2 (PCBP2) was identified by RNA pull down and mass spectrometry (MS), which was further validated by RNA immunoprecipitation (RIP). PCBP2 was also upregulated in HCC and associated with MVI. High expression of both AC104958.2 and PCBP2 was correlated with tumor size, TNM stage and MVI in HCC. Overexpression of PCBP2 greatly increased the cell viability, metastasis, invasion and EMT. Moreover, actinomycin D assay showed that overexpression of PCBP2 enhanced the RNA stability of AC104958.2. In conclusion, our study showed that a novel lncRNA AC104958.2 exerted oncogenic roles in HCC and might be a promising biomarker and therapeutic target.
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26
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He YZ, He K, Huang RQ, Wang ZL, Ye SW, Liu LW, Luo QJ, Hu ZM. Preoperative evaluation and prediction of clinical scores for hepatocellular carcinoma microvascular invasion: a single-center retrospective analysis. Ann Hepatol 2021; 19:654-661. [PMID: 32768591 DOI: 10.1016/j.aohep.2020.07.002] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 07/07/2020] [Accepted: 07/08/2020] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Microvascular invasion (MVI) of is generally considered to be an important prognostic factor for hepatocellular carcinoma (HCC) after operation, An accurate prediction of MVI before operation is helpful for clinical decision-making before operation. MATERIAL AND METHODS A retrospective analysis of 227 cases of hepatocellular carcinoma patients after hepatectomy has been confirmed the pathological result whether there was MVI, and has been determined the independent risk factors of MVI. Based on these independent risk factors, we constructed a clinical scoring risk model for predicting MVI. RESULTS Among the 227 patients with HCC, 74 (34.6%) were MVI positive. Using receiver operating characteristic (ROC) curve and logistic regression model, we found that alpha-fetoprotein(AFP)≥158 ng/mL(odds ratio[OR] = 4.152,95% confidence interval [95%CI]:1.602∼10.760,p = 0.003), Des-γ-carboxy prothrombin (DCP)≥178mAU/mL(OR = 9.730,95%CI:3.392∼27.910,p < 0.001), circulating tumor cells (CTCs)≥3/3.2 ml(OR = 7.747,95%CI:3.019∼19.881,P < 0.001), maximum tumor diameter≥59 mm(OR = 3.467,95%CI:1.368∼8.669,p = 0.008) and tumor margin unsmoothness(OR = 0.235,95%CI:0.096∼0.573,p = 0.001) were independent risk factors for MVI, they predicted that the area under the curve of MVI was 0.752, 0.777, 0.857, 0.743 and 0.333, respectively. Based on these five independent risk factors, we constructed a clinical scoring risk model for predicting MVI. The model predicts that the area under the curve of MVI is 0.922, and its prevalence rate from 0 to 5 are 3.1%(1/32), 5.3%(4/76), 12.2%(5/41), 66.7%(20/30), 87.9%(29/33), 100%(15/15), respectively (P < 0.001). CONCLUSION Based on AFP, DCP, CTC, maximum tumor diameter and tumor margin unsmoothness, we constructed a model to predict the risk of MVI clinical score, so as to make a more accurate individualized treatment plan before operation, which has important clinical significance and application prospect to improve the curative effect of HCC.
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Affiliation(s)
- Yong Zhu He
- Department of Hepatobiliary Surgery, Zhongshan Hospital Affiliated to Sun Yat-sen University, Zhongshan City, Guangdong Province, China; Guangdong Medical University,Zhanjiang City, Guangdong Province, China
| | - Kun He
- Department of Hepatobiliary Surgery, Zhongshan Hospital Affiliated to Sun Yat-sen University, Zhongshan City, Guangdong Province, China
| | - Rui Qin Huang
- Department of Hepatobiliary Surgery, Zhongshan Hospital Affiliated to Sun Yat-sen University, Zhongshan City, Guangdong Province, China
| | - Ze Liang Wang
- Department of Hepatobiliary Surgery, Zhongshan Hospital Affiliated to Sun Yat-sen University, Zhongshan City, Guangdong Province, China; Guangdong Medical University,Zhanjiang City, Guangdong Province, China
| | - Shao Wei Ye
- Department of Hepatobiliary Surgery, Zhongshan Hospital Affiliated to Sun Yat-sen University, Zhongshan City, Guangdong Province, China; Guangdong Medical University,Zhanjiang City, Guangdong Province, China
| | - Li Wen Liu
- Department of Hepatobiliary Surgery, Zhongshan Hospital Affiliated to Sun Yat-sen University, Zhongshan City, Guangdong Province, China
| | - Qi Jie Luo
- Department of Hepatobiliary Surgery, Zhongshan Hospital Affiliated to Sun Yat-sen University, Zhongshan City, Guangdong Province, China
| | - Ze Min Hu
- Department of Hepatobiliary Surgery, Zhongshan Hospital Affiliated to Sun Yat-sen University, Zhongshan City, Guangdong Province, China.
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Shinkawa H, Tanaka S, Kabata D, Takemura S, Amano R, Kimura K, Kinoshita M, Kubo S. The Prognostic Impact of Tumor Differentiation on Recurrence and Survival after Resection of Hepatocellular Carcinoma Is Dependent on Tumor Size. Liver Cancer 2021; 10:461-472. [PMID: 34721508 PMCID: PMC8527909 DOI: 10.1159/000517992] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Accepted: 06/18/2021] [Indexed: 02/04/2023] Open
Abstract
INTRODUCTION The present study aimed to evaluate the effect of poor differentiation and tumor size on survival outcome after hepatic resection of hepatocellular carcinoma (HCC). METHODS A total of 1,107 patients who underwent initial and curative hepatic resection for HCC without macroscopic vascular invasion participated in the study. Using the multivariable Cox proportional hazards regression model, we evaluated changes in hazard ratios (HRs) for the association between tumor differentiation and survival based on tumor size. RESULTS In patients with poorly (Por) differentiated HCCs, the adjusted HRs of reduced overall survival (OS), recurrence-free survival (RFS), early RFS, and early extrahepatic RFS were 1.31 (95% confidence interval [CI]; 1.07-1.59), 1.07 (95% CI 0.89-1.28), 1.31 (95% CI 1.06-1.62), and 1.81 (95% CI 1.03-3.17), respectively. Moreover, based on an analysis of the effect modification of tumor differentiation according to tumor size, Por HCC was found to be associated with a reduced OS (p = 0.033). The HRs of Por HCCs sharply increased in patients with tumors measuring up to 5 cm. The adjusted HRs of reduced OS in patients with Por HCCs measuring <2, ≥2 and <5, and ≥5 cm were 1.22 (95% CI 0.69-2.14), 1.33 (95% CI 1.02-1.73), and 1.58 (95% CI 1.04-2.42), respectively. The corresponding adjusted HRs of reduced early RFS were 0.85 (95% CI 0.46-1.57), 1.34 (95% CI 1.01-1.8), and 1.57 (95% CI 1.03-2.39), respectively. The adjusted HRs of reduced early extrahepatic RFS were 1.89 (95% CI 0.83-4.3) in patients with tumors measuring ≥2 and <5 cm and 2.33 (95% CI 0.98-5.54) in those with tumors measuring ≥5 cm. CONCLUSIONS Por HCC measuring ≥2 cm was associated with early recurrence. Hence, it had negative effects on OS. After surgery, patients with Por HCC measuring ≥5 cm should be cautiously monitored for early extrahepatic recurrence. These findings will help physicians devise treatment strategies for patients with HCC.
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Affiliation(s)
- Hiroji Shinkawa
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan,*Hiroji Shinkawa,
| | - Shogo Tanaka
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Daijiro Kabata
- Department of Medical Statistics, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Shigekazu Takemura
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Ryosuke Amano
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Kenjiro Kimura
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Masahiko Kinoshita
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Shoji Kubo
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
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Liu SR, Yan Q, Lin HM, Shi GZ, Cao Y, Zeng H, Liu C, Zhang R. Anti-programmed cell death ligand 1-based immunotherapy in recurrent hepatocellular carcinoma with inferior vena cava tumor thrombus and metastasis: Three case reports. World J Clin Cases 2021; 9:5988-5998. [PMID: 34368318 PMCID: PMC8316958 DOI: 10.12998/wjcc.v9.i21.5988] [Citation(s) in RCA: 2] [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: 01/14/2021] [Revised: 02/15/2021] [Accepted: 05/20/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Recurrent hepatocellular carcinoma (HCC) with inferior vena cava tumor thrombus is a great challenge for oncologists and has a poor prognosis. To date, the safety and efficacy of programmed cell death ligand 1 (PD-L1) inhibitors are still unknown.
CASE SUMMARY A 59-year-old male was identified as having a tumor thrombus in the inferior vena cava 3 years after surgery. The patient underwent a second surgery and adjuvant chemotherapy. However, the level of alpha-fetoprotein was elevated after 2 mo, and lung metastases and mediastinal lymph node metastases were identified. The expression of PD-L1 in HCC and inferior vena cava tumor thrombus tissues was analyzed by immunohistochemistry. Then, the patient received atezolizumab immunotherapy. The level of alpha-fetoprotein dropped to normal, the mediastinal lymph node metastases decreased in size and the lung metastases disappeared after 3 mo of immunotherapy. The patient had no signs of recurrence at 21 mo of follow-up. A 60-year-old male underwent left hepatic tumor resection, inferior vena cava incision and thrombus removal, followed by regular chemotherapy. The patient developed lung and splenic metastases after surgery. Pembrolizumab was used for six courses, and the splenic metastasis shrank, after which splenectomy was performed. The patient continued to receive pembrolizumab for thirteen courses, and the lung metastases showed no progression. A 34-year-old male was diagnosed with liver cancer with inferior vena cava tumor thrombus. The patient underwent right hepatectomy and received tislelizumab for three courses. He is still receiving immunotherapy and in good condition.
CONCLUSION Anti-PD-L1 therapy in HCC patients with inferior vena cava tumor thrombus and metastasis is associated with relatively good patient outcomes.
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Affiliation(s)
- Shao-Ru Liu
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510288, Guangdong Province, China
| | - Qing Yan
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510288, Guangdong Province, China
| | - Hao-Ming Lin
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510288, Guangdong Province, China
| | - Guang-Zi Shi
- Department of Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China
| | - Yi Cao
- Department of Emergency, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China
| | - Hong Zeng
- Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China
| | - Chao Liu
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510288, Guangdong Province, China
| | - Rui Zhang
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510288, Guangdong Province, China
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Singal AG, Hoshida Y, Pinato DJ, Marrero J, Nault JC, Paradis V, Tayob N, Sherman M, Lim YS, Feng Z, Lok AS, Rinaudo JA, Srivastava S, Llovet JM, Villanueva A. International Liver Cancer Association (ILCA) White Paper on Biomarker Development for Hepatocellular Carcinoma. Gastroenterology 2021; 160:2572-2584. [PMID: 33705745 PMCID: PMC8169638 DOI: 10.1053/j.gastro.2021.01.233] [Citation(s) in RCA: 119] [Impact Index Per Article: 29.8] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 01/14/2021] [Accepted: 01/15/2021] [Indexed: 02/07/2023]
Affiliation(s)
- Amit G Singal
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, Texas.
| | - Yujin Hoshida
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, Texas
| | - David J Pinato
- Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, London, UK
| | - Jorge Marrero
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, Texas
| | - Jean-Charles Nault
- Service d'hépatologie, Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bondy, France; Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Paris, France; Centre de Recherche des Cordeliers, Inserm, Sorbonne Université, Université Paris, INSERM UMR 118 Functional Genomics of Solid Tumors Laboratory, F-75006, Paris, France
| | - Valerie Paradis
- Pathology Department, Beaujon hospital, Clichy, University Paris, France
| | - Nabihah Tayob
- Department of Data Science, Dana Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, Massachusetts
| | | | - Young Suk Lim
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Ziding Feng
- Biostatistics Program, Public Health Science Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Anna S Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan
| | - Jo Ann Rinaudo
- Cancer Biomarker Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Rockville, Maryland
| | - Sudhir Srivastava
- Cancer Biomarker Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Rockville, Maryland
| | - Josep M Llovet
- Division of Liver Diseases and Hematology/Medical Oncology, Liver Cancer Program, Tisch Cancer Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; Translational Research in Hepatic Oncology, Liver Unit, IDIBAPS, Hospital Clinic, University of Barcelona, Catalonia, Spain; Institució Catalana d'Estudis Avançats (ICREA), Barcelona, Catalonia, Spain
| | - Augusto Villanueva
- Division of Liver Diseases and Hematology/Medical Oncology, Liver Cancer Program, Tisch Cancer Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
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Hu H, Qi S, Zeng S, Zhang P, He L, Wen S, Zeng N, Yang J, Zhang W, Zhu W, Xiang N, Fang C. Importance of Microvascular Invasion Risk and Tumor Size on Recurrence and Survival of Hepatocellular Carcinoma After Anatomical Resection and Non-anatomical Resection. Front Oncol 2021; 11:621622. [PMID: 33816254 PMCID: PMC8010691 DOI: 10.3389/fonc.2021.621622] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Accepted: 02/15/2021] [Indexed: 12/12/2022] Open
Abstract
Purpose: To establish a valid prediction model to prognose the occurrence of microvascular invasion (MVI), and to compare the efficacy of anatomic resection (AR) or non-anatomic resection (NAR) for hepatocellular carcinoma (HCC). Methods: Two hundred twenty-eight patients with HCC who underwent surgical treatment were enrolled. Their hematological indicators, MRI imaging features, and outcome data were acquired. Result: In the multivariable analysis, alpha-fetoprotein >15 ng/mL, neutrophil to lymphocyte ratio >3.8, corona enhancement, and peritumoral hypointensity on hepatobiliary phase were associated with MVI. According on these factors, the AUROC of the predictive model in the primary and validation cohorts was 0.884 (95% CI: 0.829, 0.938) and 0.899 (95% CI: 0.821, 0.967), respectively. Patients with high risk of MVI or those with low risk of MVI but tumor size >5 cm in the AR group were associated with a lower rate of recurrence and death than patients in the NAR group; however, when patients are in the state of low-risk MVI with tumor size >5 cm, there is no difference in the rate of recurrence and death between AR and NAR. Conclusion: Our predictive model for HCC with MVI is convenient and accurate. Patients with high-risk of MVI or low-risk of MVI but tumor size >5 cm executing AR is of great necessity.
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Affiliation(s)
- Haoyu Hu
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Shuo Qi
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Silue Zeng
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Peng Zhang
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Linyun He
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Sai Wen
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Ning Zeng
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.,Guangdong Provincial Clinical and Engineering Center of Digital Medicine, Guangzhou, China
| | - Jian Yang
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.,Guangdong Provincial Clinical and Engineering Center of Digital Medicine, Guangzhou, China
| | - Weiqi Zhang
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Wen Zhu
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.,Guangdong Provincial Clinical and Engineering Center of Digital Medicine, Guangzhou, China
| | - Nan Xiang
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.,Guangdong Provincial Clinical and Engineering Center of Digital Medicine, Guangzhou, China
| | - Chihua Fang
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.,Guangdong Provincial Clinical and Engineering Center of Digital Medicine, Guangzhou, China
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31
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Mai RY, Zeng J, Meng WD, Lu HZ, Liang R, Lin Y, Wu GB, Li LQ, Ma L, Ye JZ, Bai T. Artificial neural network model to predict post-hepatectomy early recurrence of hepatocellular carcinoma without macroscopic vascular invasion. BMC Cancer 2021; 21:283. [PMID: 33726693 PMCID: PMC7962237 DOI: 10.1186/s12885-021-07969-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Accepted: 02/24/2021] [Indexed: 01/27/2023] Open
Abstract
BACKGROUND The accurate prediction of post-hepatectomy early recurrence (PHER) of hepatocellular carcinoma (HCC) is vital in determining postoperative adjuvant treatment and monitoring. This study aimed to develop and validate an artificial neural network (ANN) model to predict PHER in HCC patients without macroscopic vascular invasion. METHODS Nine hundred and three patients who underwent curative liver resection for HCC participated in this study. They were randomly divided into derivation (n = 679) and validation (n = 224) cohorts. The ANN model was developed in the derivation cohort and subsequently verified in the validation cohort. RESULTS PHER morbidity in the derivation and validation cohorts was 34.8 and 39.2%, respectively. A multivariable analysis revealed that hepatitis B virus deoxyribonucleic acid load, γ-glutamyl transpeptidase level, α-fetoprotein level, tumor size, tumor differentiation, microvascular invasion, satellite nodules, and blood loss were significantly associated with PHER. These factors were incorporated into an ANN model, which displayed greater discriminatory abilities than a Cox's proportional hazards model, preexisting recurrence models, and commonly used staging systems for predicting PHER. The recurrence-free survival curves were significantly different between patients that had been stratified into two risk groups. CONCLUSION When compared to other models and staging systems, the ANN model has a significant advantage in predicting PHER for HCC patients without macroscopic vascular invasion.
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Affiliation(s)
- Rong-Yun Mai
- Department of Hepatobilliary & Pancreatic Surgery, Guangxi Medical University Cancer Hospital, 71 He Di Road, Nanning, China
- Department of Experimental Research, Guangxi Medical University Cancer Hospital, Nanning, 530021, China
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, 530021, China
| | - Jie Zeng
- Department of Experimental Research, Guangxi Medical University Cancer Hospital, Nanning, 530021, China
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, 530021, China
| | - Wei-da Meng
- Department of Hepatobilliary & Pancreatic Surgery, Guangxi Medical University Cancer Hospital, 71 He Di Road, Nanning, China
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, 530021, China
| | - Hua-Ze Lu
- Department of Hepatobilliary & Pancreatic Surgery, Guangxi Medical University Cancer Hospital, 71 He Di Road, Nanning, China
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, 530021, China
| | - Rong Liang
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, 530021, China
- Department of First Chemotherapy, Guangxi Medical University Cancer Hospital, Nanning, 530021, China
| | - Yan Lin
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, 530021, China
- Department of First Chemotherapy, Guangxi Medical University Cancer Hospital, Nanning, 530021, China
| | - Guo-Bin Wu
- Department of Hepatobilliary & Pancreatic Surgery, Guangxi Medical University Cancer Hospital, 71 He Di Road, Nanning, China
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, 530021, China
| | - Le-Qun Li
- Department of Hepatobilliary & Pancreatic Surgery, Guangxi Medical University Cancer Hospital, 71 He Di Road, Nanning, China
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, 530021, China
| | - Liang Ma
- Department of Hepatobilliary & Pancreatic Surgery, Guangxi Medical University Cancer Hospital, 71 He Di Road, Nanning, China
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, 530021, China
| | - Jia-Zhou Ye
- Department of Hepatobilliary & Pancreatic Surgery, Guangxi Medical University Cancer Hospital, 71 He Di Road, Nanning, China.
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, 530021, China.
| | - Tao Bai
- Department of Hepatobilliary & Pancreatic Surgery, Guangxi Medical University Cancer Hospital, 71 He Di Road, Nanning, China.
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, 530021, China.
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Chen HL, Chen YH, Du L, Song YP, Zhu B. Elevated serum alpha-fetoprotein levels are associated with poor prognosis of hepatocellular carcinoma after surgical resection: A systematic review and meta-analysis. Arab J Gastroenterol 2021; 22:12-22. [PMID: 33551350 DOI: 10.1016/j.ajg.2020.09.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Revised: 06/22/2020] [Accepted: 09/08/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND STUDY AIMS The relationship between the alpha-fetoprotein (AFP) level and the prognosis of hepatocellular carcinoma (HCC) after surgical resection remains unknown. This study aims to assess this relationship. PATIENTS AND METHODS PubMed and Web of Science were systematically utilised. Meta-analysis was conducted for the outcomes of the recurrence-free survival (RFS) and the overall survival (OS) by comparing the high AFP group with the low AFP group. RESULTS The studies included 61 manuscripts with 35,461 patients. The summary hazard ratio (HR) for RFS was 1.501 (95% CI 1.355-1.662; Z = 7.81, P < 0.00001) when comparing the high AFP group with the low AFP group. Sensitivity analysis only included adjusted HRs, with the summary HR being 1.563 (95% CI 1.381-1.768; Z = 7.10, P < 0.00001). The summary HR for OS was 1.565 (95% CI 1.439-1.701; Z = 10.52, P < 0.00001) when comparing two AFP groups. Sensitivity analysis showed that the summary HR was 1.611 (95% CI 1.456-1.782; Z = 9.24, P < 0.00001). CONCLUSION Our meta-analysis indicated that elevated serum AFP levels are associated with poor prognosis of HCC after surgical resection.
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Affiliation(s)
- Hong-Lin Chen
- Nantong University, School of Public Health, Nantong City, Jiangsu Province, China
| | - Yu-Hua Chen
- Nantong Health College of Jiangsu Province, Nantong City, Jiangsu Province, China
| | - Lin Du
- Nantong University, School of Public Health, Nantong City, Jiangsu Province, China
| | - Yi-Ping Song
- Nantong University, School of Public Health, Nantong City, Jiangsu Province, China
| | - Bin Zhu
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Nantong University, China.
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Xia W, Li H, Li Y, Li M, Fan J, Sun W, Li N, Li R, Shao K, Peng X. In Vivo Coinstantaneous Identification of Hepatocellular Carcinoma Circulating Tumor Cells by Dual-Targeting Magnetic-Fluorescent Nanobeads. NANO LETTERS 2021; 21:634-641. [PMID: 33264027 DOI: 10.1021/acs.nanolett.0c04180] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Circulating tumor cells (CTCs) have been considered as a potential biomarker for evaluation of cancer metastasis and prognosis, especially in hepatocellular carcinoma (HCC). However, the isolation and detection of rare CTCs in HCC patients face enormous challenges due to omittance and nonspecific binding. We previously designed a small molecular NIR fluoresent agent, named MLP, which had high affinity with a tumor cell-overexpressed enzyme, aminopeptidase N (APN). Based on that, in this work we introduced a novel strategy via coassembling the antiepithelial cell adhesion molecule (EpCAM) antibody and MLPinto theFe3O4 magnetic nanobeads (MB-MLP-EpCAM) to isolate and identify HCC-CTCs coinstantaneously. MB-MLP-EpCAM significantly improved the CTC-capture efficiency (>85%) without sacrificing cell viability (>90%). Most importantly, the advantages of precise dual-targetability, high resolution of fluorescence imaging, and prominent selectivity make our nanoplatform have great potential to achieve in vivo real-time identification and monitoring of CTCs clinically.
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Affiliation(s)
- Wenxi Xia
- State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Dalian 116024, P.R. China
| | - Haidong Li
- State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Dalian 116024, P.R. China
| | - Yueqing Li
- School of Pharmaceutical Science and Technology, Dalian University of Technology, 2 Linggong Road, Dalian 116024, P.R. China
| | - Miao Li
- State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Dalian 116024, P.R. China
| | - Jiangli Fan
- State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Dalian 116024, P.R. China
| | - Wen Sun
- State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Dalian 116024, P.R. China
| | - Na Li
- Department of Medical Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, P.R. China
| | - Ruojie Li
- Interventional Therapy Department, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, P.R. China
| | - Kun Shao
- State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Dalian 116024, P.R. China
| | - Xiaojun Peng
- State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Dalian 116024, P.R. China
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Red blood cell transfusions and the survival in patients with cancer undergoing curative surgery: a systematic review and meta-analysis. Surg Today 2021; 51:1535-1557. [PMID: 33389174 DOI: 10.1007/s00595-020-02192-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Accepted: 10/26/2020] [Indexed: 02/08/2023]
Abstract
Allogenic red blood cell transfusions exert a potential detrimental effect on the survival when delivered to cancer patients undergoing surgery with curative intent. We performed a systematic review and meta-analysis to assess the association between perioperative allogenic red blood cell transfusions and risk of death as well as relapse after surgery for localized solid tumors. PubMed, the Cochrane Library, and EMBASE were searched from inception to March 2019 for studies reporting the outcome of patients receiving transfusions during radical surgery for non-metastatic cancer. Risk of death and relapse were pooled to provide an adjusted hazard ratio with a 95% confidence interval [hazard ratio (HR) (95% confidence interval {CI})]. Mortality and relapse associated with perioperative transfusion due to cancer surgery were evaluated among participants (n = 123 studies). Overall, RBC transfusions were associated with an increased risk of death [HR = 1.50 (95% CI 1.42-1.57), p < 0.01] and relapse [HR = 1.36 (95% CI 1.26-1.46), p < 0.01]. The survival was reduced even in cancer at early stages [HR = 1.45 (1.36-1.55), p < 0.01]. In cancer patients undergoing surgery, red blood cell transfusions reduced the survival and increased the risk of relapse. Transfusions based on patients' blood management policy should be performed by applying a more restrictive policy, and the planned preoperative administration of iron, if necessary, should be pursued.
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Gelli M, Sebagh M, Porcher R, Romanelli E, Vibert E, Sa Cunha A, Castaing D, Rosmorduc O, Samuel D, Adam R, Cherqui D. Liver Resection for Early Hepatocellular Carcinoma: Preoperative Predictors of Non Transplantable Recurrence and Implications for Treatment Allocation. Ann Surg 2020; 272:820-826. [PMID: 32833755 DOI: 10.1097/sla.0000000000004259] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND AND AIMS LR and LT are the standard curative options for early HCC. LT provides best long-term survival but is limited by organ shortage. LR, readily available, is hampered by high recurrence rates. Salvage liver transplantation is an efficient treatment of recurrences within criteria. The aim of the study was to identify preoperative predictors of non transplantable recurrence (NTR) to improve patient selection for upfront LR or LT at initial diagnosis. STUDY DESIGN Consecutive LR for transplantable HCC between 2000 and 2015 were studied. A prediction model for NTR based on preoperative variables was developed using sub-distribution hazard ratio after multiple imputation and internal validation by bootstrapping. Model performance was evaluated by the concordance index after correction for optimism. RESULTS A total of 148 patients were included. Five-year overall survival and recurrence free survival were 73.6% and 29.3%, respectively (median follow-up 45.8 months). Recurrence rate was 54.8%. NTR rate was 38.2%. Preoperative model for NTR identified >1 nodule [sub-distribution hazard ratio 2.35 95% confidence interval (CI) 1.35-4.09], AFP >100 ng/mL (2.14 95% CI 1.17-3.93), and F4 fibrosis (1.93 95% CI 1.03-3.62). The apparent concordance index of the model was 0.664 after correction for optimism. In the presence of 0, 1, and ≥2 factors, NTR rates were 2.6%, 22.7%, and 40.9%, respectively. The number of prognostic factors was significantly associated with the pattern of recurrence (P = 0.001) and 5-year recurrence free survival (P < 0.001). CONCLUSIONS Cirrhosis, >1 nodule, and AFP >100 ng/mL were identified as preoperative predictors of NTR. In the presence of 2 factors or more upfront transplantation should be probably preferred to resection in regard of organ availability. Other patients are good candidates for LR and salvage liver transplantation should be encouraged in eligible patients with recurrence.
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Affiliation(s)
- Maximiliano Gelli
- Hepatobiliary Center Paul Brousse Hospital, APHP-Université Paris Saclay, Villejuif, France
| | - Mylène Sebagh
- Department of Pathology, APHP - Université Paris Saclay, Hôpital Paul Brousse, Villejuif, France
| | - Raphaël Porcher
- Centre de Recherche Épidémiologie et Statistique (CRESS-UMR1153) Université Paris Descartes-Hôpital Hôtel-Dieu, Paris, France
| | - Elena Romanelli
- Hepatobiliary Center Paul Brousse Hospital, APHP-Université Paris Saclay, Villejuif, France
| | - Eric Vibert
- Hepatobiliary Center Paul Brousse Hospital, APHP-Université Paris Saclay, Villejuif, France
| | - Antonio Sa Cunha
- Hepatobiliary Center Paul Brousse Hospital, APHP-Université Paris Saclay, Villejuif, France
| | - Denis Castaing
- Hepatobiliary Center Paul Brousse Hospital, APHP-Université Paris Saclay, Villejuif, France
| | - Olivier Rosmorduc
- Hepatobiliary Center Paul Brousse Hospital, APHP-Université Paris Saclay, Villejuif, France
| | - Didier Samuel
- Hepatobiliary Center Paul Brousse Hospital, APHP-Université Paris Saclay, Villejuif, France
| | - René Adam
- Hepatobiliary Center Paul Brousse Hospital, APHP-Université Paris Saclay, Villejuif, France
| | - Daniel Cherqui
- Hepatobiliary Center Paul Brousse Hospital, APHP-Université Paris Saclay, Villejuif, France
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A nomogram based on liver stiffness predicts postoperative complications in patients with hepatocellular carcinoma. J Hepatol 2020; 73:855-862. [PMID: 32829930 DOI: 10.1016/j.jhep.2020.04.032] [Citation(s) in RCA: 71] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Revised: 04/16/2020] [Accepted: 04/17/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS Liver stiffness measurement (LSM), assessed by transient elastography (Fibroscan), has been demonstrated to predict post-hepatectomy liver failure in patients who undergo hepatic resection for hepatocellular carcinoma (HCC). However, other complications are also likely to be related to the underlying grade of liver fibrosis. Herein, we aimed to identify predictors of postoperative complications and to build and develop a novel nomogram able to identify patients at risk of developing severe complications. METHODS Data from patients who underwent hepatectomy for HCC between 2006 and 2016 at 2 referral centres were retrospectively reviewed. All surgical complications were recorded and scored using the comprehensive complication index (CCI), ranging from 0 (uneventful course) to 100 (death). A CCI ≥26.2 was used as a threshold to define severe complications. RESULTS During the study period, 471 patients underwent hepatic resection for HCC. Among them, 50 patients (10.6%) had a CCI ≥26.2. Age, model for end-stage liver disease (MELD) score and LSM values, together with serum albumin, were independent predictors of high CCI. The nomogram built on these variables was internally validated and showed good performance (optimism-corrected c-statistic = 0.751). A regression equation to predict the CCI was also established by multiple linear regression analysis: [LSM (kPa) × 0.254] + [age (years) × 0.118] + [MELD score (pt.) × 1.050] - [albumin (g/dl) × 2.395] - 3.639. CONCLUSION A novel nomogram, combining LSM values, age and liver function tests provided an excellent preoperative prediction of high CCI in patients with resectable HCC. This predictive model could be used as a reference for clinicians and surgeons to help them in clinical decision-making. LAY SUMMARY Liver stiffness measurement is increasingly being used to assess the degree of liver fibrosis in patients with cirrhosis and/or chronic hepatitis. Using Fibroscan, we developed a novel nomogram to predict severe complications following liver resection for hepatocellular carcinoma, according to the new comprehensive complication index. This tool could be used as a reference for clinicians and surgeons to help them in clinical decision-making.
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Impact of perioperative allogeneic blood transfusion on the long-term prognosis of patients with different stage tumors after radical resection for hepatocellular carcinoma. Eur J Surg Oncol 2020; 47:620-627. [PMID: 32988700 DOI: 10.1016/j.ejso.2020.09.021] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Revised: 08/20/2020] [Accepted: 09/18/2020] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND We previously reported that perioperative allogeneic blood transfusion (PABT) did not affect long-term survival after radical resection for hepatocellular carcinoma (HCC). This study aimed to investigate the effects of PABT on the prognosis of HCC patients with different stage tumors. METHODS Patients with primary HCC who underwent curative liver resection between 2003 and 2012 were retrospectively enrolled and divided into the early-stage (stage I) and non-early-stage (stages II, III and IV) groups. The impacts of PABT on the long-term prognosis of patients in different groups after resection were investigated using propensity score matching (PSM) and multivariable Cox regression analyses. RESULTS We enrolled 426 HCC patients, including 53 matched pairs of patients with early-stage tumors and 51 matched pairs of patients with non-early-stage tumors. Survival analyses of the patients with early-stage tumors showed that the recurrence-free survival (RFS) and overall survival (OS) rates of the transfusion group were significantly worse than those of the nontransfusion group both before and after PSM. Multivariable Cox analyses identified that PABT was an independent predictor of RFS and OS of the patients with early-stage tumors. However, survival analyses of the propensity-matched patients with non-early-stage tumors showed no significant differences in RFS and OS rates between the transfusion and nontransfusion groups (p = 0.296; p = 0.472). CONCLUSIONS This study demonstrates that PABT has negative impacts on the long-term prognosis of patients with early-stage tumors after radical resection of HCC but has no impact on the long-term prognosis of patients with non-early-stage tumors.
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Fahrner R, Dennler SGC, Inderbitzin D. Risk of malignancy in Caroli disease and syndrome: A systematic review. World J Gastroenterol 2020; 26:4718-4728. [PMID: 32884228 PMCID: PMC7445861 DOI: 10.3748/wjg.v26.i31.4718] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Revised: 05/15/2020] [Accepted: 08/01/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Congenital intrahepatic bile duct dilatation without fibrosis is called Caroli disease (CD), and is called Caroli syndrome (CS) when it has fibrotic and cirrhotic liver morphology. The development of intrahepatic carcinoma is described in both conditions, but the reported incidence varies extensively. Potential risk factors for the malignant transformation were not described. Furthermore, conservative or surgical treatment is performed depending on the extent of cystic malformation, hepatic dysfunction and structural hepatic changes, but little is known about which treatment should be offered to patients with CD or CS and cancer.
AIM To further investigate the malignant transformation in these conditions.
METHODS A systematic review of the current literature until January 2019 was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. A search using Medline (PubMed) was performed using a combination of Medical Subject Headings terms “caroli disease”, “caroli syndrome”, “tumor”, “malignant”, and “cholangiocarcinoma”. Only human studies published in English were used for this systematic review. The following parameters were extracted from each article: year of publication, type of study, number of patients, incidence of malignant tumor, duration of symptoms, age, sex, diagnostics, identification of tumor, surgical therapy, survival and tumor recurrence.
RESULTS Twelve retrospective studies reporting the courses of 561 patients (53% females) were included in this systematic review. With a mean age of 41.6 years old (range 23 to 56 years old), patients were younger than other populations undergoing liver surgery. Depending on the size of the study population the incidence of cholangiocarcinoma varied from 2.7% to 37.5% with an overall incidence of 6.6%. There were only few detailed reports about preoperative diagnostic work-up, but a multimodal work-up including ultrasound of the liver, computed tomography, magnetic resonance imaging and endoscopic retrograde cholangiopancreatography was used in most studies. Disease duration was variable with up to several years. Most patients had episodes of cholangitis, sepsis, fever or abdominal pain. Tumor detection was an incidental finding of the surgical specimen in most cases because it is currently often impossible to detect tumor manifestation during preoperative diagnostics. Liver resection or liver transplantation was performed depending on the extent of the biliary pathology and additional alterations of the liver structure or function. No postoperative adjuvant chemotherapy was reported, but chemotherapy was administered in selected cases of tumor recurrence. Overall survival rates after one year were low at 36% and a high recurrence rate of up to 75% during the observation period.
CONCLUSION Only few retrospective studies reported a low tumor incidence. Despite the high rate of mortality and tumor recurrence, definite surgical treatment should be offered as soon as possible.
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Affiliation(s)
- René Fahrner
- Department of Surgery, Bürgerspital Solothurn, Solothurn 4500, Switzerland
| | - Sandra GC Dennler
- Department of Surgery, University Hospital Dresden, Dresden 01307, Germany
| | - Daniel Inderbitzin
- Department of Surgery, Bürgerspital Solothurn, Solothurn 4500, Switzerland
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Li L, Li B, Zhang M. Postoperative adjuvant transarterial chemoembolization improves the prognosis of hepatocellular carcinoma patients with microvascular invasion: a systematic review and meta-analysis. Acta Radiol 2020; 61:723-731. [PMID: 31594382 DOI: 10.1177/0284185119878357] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Microvascular invasion has been widely accepted as a major risk factor of hepatocellular carcinoma prognoses after surgery. It is still controversial whether postoperative adjuvant transarterial chemoembolization could improve the survival of hepatocellular carcinoma patients with microvascular invasion. PURPOSE To evaluate the effect of postoperative adjuvant transarterial chemoembolization for postoperative hepatocellular carcinoma patients with microvascular invasion. MATERIAL AND METHODS PubMed, Web of Science, and Embase databases were searched for eligible studies, and the one-, three-, and five-year recurrence rates and overall survival rates were extracted for meta-analysis. RESULTS A total of eight studies were included in this study. The results showed that the one-, three-, and five-year recurrence rate of the postoperative adjuvant transarterial chemoembolization group were better than those of the hepatectomy alone group, with a pooled risk ratio (RR) of 0.66 (95% confidence interval [CI] 0.58-0.75, P < 0.00001), 0.82 (95% CI 0.76-0.88, P < 0.00001), and 0.89 (95% CI 0.82-0.97, P = 0.007), respectively. The overall survival rates with one-, three-, and five-year pooled RR were 0.34 (95% CI 0.25-0.47, P < 0.00001), 0.69 (95% CI 0.60-0.79, P < 0.00001), and 0.78 (95% CI 0.69-0.89, P = 0.0001), respectively. No serious side effects have been reported, indicating that postoperative intervention is safe. CONCLUSION For hepatocellular carcinoma patients with microvascular invasion confirmed by postoperative pathology, postoperative adjuvant transarterial chemoembolization is a safe treatment, which could reduce the tumor recurrence rate and improve the patient's overall survival.
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Affiliation(s)
- Lian Li
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Bo Li
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Ming Zhang
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
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Shinkawa H, Tanaka S, Takemura S, Ishihara T, Yamamoto K, Kubo S. Tumor Size Drives the Prognosis After Hepatic Resection of Solitary Hepatocellular Carcinoma Without Vascular Invasion. J Gastrointest Surg 2020; 24:1040-1048. [PMID: 31197685 DOI: 10.1007/s11605-019-04273-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2019] [Accepted: 05/17/2019] [Indexed: 02/07/2023]
Abstract
PURPOSE We assessed the association of tumor size with patient survival following diagnosis of solitary hepatocellular carcinoma without vascular invasion. METHODS The overall population comprised 638 patients who initially underwent hepatic resection with curative intent for a solitary hepatocellular carcinoma without macroscopic vascular invasion (487 had no microscopic vascular invasion). We set 5 cm as the tumor cutoff size for a solitary tumor based on the Milan criteria, and we used a multivariate Cox proportional hazards model and propensity score matching to evaluate the impact of tumor size on survival. RESULTS Tumor size was significantly associated with a proportional increase in cancer-specific survival in the overall population (P = 0.001) and the subgroup with no microscopic vascular invasion (P = 0.029); however, multivariate analysis revealed no significant risk associated with recurrence-free survival (P = 0.055 and 0.59, respectively). After propensity score matching, the cancer-specific survival of patients with tumors > 5 cm was significantly worse than for those with tumors ≤ 5 cm in the overall population (P = 0.0077); the corresponding 2-year cumulative recurrence rates were 45.8% and 23.5%, respectively (P = 0.0027). Finally, the proportions of extrahepatic to total recurrences were 8% for those with tumors ≤ 5 cm and 29.1% for those with tumors > 5 cm in the unmatched overall population (P < 0.001). CONCLUSION Tumor size was associated with recurrence within 2 years of surgery and with poor cancer-specific survival in patients with solitary hepatocellular carcinoma, even in the absence of microscopic vascular invasion.
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Affiliation(s)
- Hiroji Shinkawa
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.
| | - Shogo Tanaka
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan
| | - Shigekazu Takemura
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan
| | - Takuma Ishihara
- Division of Data Management, Gifu University Hospital Innovative and Clinical Research Promotion Center, 1-1 Yanagido, Gifu City, 501-1194, Japan
| | - Kouji Yamamoto
- Department of Medical Statistics, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan
| | - Shoji Kubo
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan
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Shimada S, Kamiyama T, Orimo T, Nagatsu A, Asahi Y, Sakamoto Y, Kamachi H, Taketomi A. Long-term prognostic factors of patients with hepatocellular carcinoma who survive over 10 years after hepatectomy. J Surg Oncol 2020; 121:1209-1217. [PMID: 32198765 DOI: 10.1002/jso.25910] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Accepted: 03/07/2020] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND OBJECTIVES The aim was to evaluate long-term prognostic factors in hepatocellular carcinoma (HCC) patients who survived over 10 years after hepatectomy and compare prognostic factors between patients with recurrence who died and survived 10 years after initial hepatectomy. METHODS We analyzed the HCC patients without recurrence over 10 years after hepatectomy (n = 35), those with recurrence who survived over 10 years (n = 48), and those who died within 10 years (n = 132). RESULTS The rate of recurrence was 16.3%, 10-year overall survival rate was 38.6%, and the 10-year recurrence-free survival (RFS) rate was 16.7%. Nonviral, solitary tumor, well differentiation, and without severe fibrosis were independent favorable factors for long-term RFS. High cholinesterase levels, small tumors and without portal vein invasion were independent favorable factors for long-term survival among patients with recurrence. Long-term survivors with recurrence showed significantly low early recurrence, extrahepatic recurrence, multiple intrahepatic recurrences. CONCLUSION Important factors for long-term prognoses in HCC patients were a solitary tumor, small tumors, and no advanced fibrosis. A treatment for nonviral hepatitis is needed to achieve long-term RFS. Even patients who relapse might survive long term if they have a late or solitary intrahepatic recurrence, nonsevere cirrhosis, and curative treatment at recurrence.
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Affiliation(s)
- Shingo Shimada
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Toshiya Kamiyama
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Tatsuya Orimo
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Akihisa Nagatsu
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Yoh Asahi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Yuzuru Sakamoto
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Hirofumi Kamachi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Akinobu Taketomi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
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Yue YY, Zhou WL. Hepatic Resection Is Associated With Improved Long-Term Survival Compared to Radio-Frequency Ablation in Patients With Multifocal Hepatocellular Carcinoma. Front Oncol 2020; 10:110. [PMID: 32117759 PMCID: PMC7026243 DOI: 10.3389/fonc.2020.00110] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Accepted: 01/21/2020] [Indexed: 01/27/2023] Open
Abstract
Background: The prognosis of patients with hepatocellular carcinoma (HCC) is of major public health interest. However, studies comparing hepatic resection (HR) and radio-frequency ablation (RFA) applied to multifocal HCC are limited. This study aimed to compare the efficacies of HR and RFA in patients with multifocal HCC. Methods: We retrospectively analyzed a cohort from the Surveillance, Epidemiology, and End Results database between 2004 and 2015. Disease-specific survival and overall survival rates were assessed before and after propensity score matching (PSM). Results: In total, 2,201 patients with multifocal HCC treated with HR (n = 1,095) or RFA (n = 1,106) were included; 1,096 patients were identified after nearest-neighbor PSM at a ratio of 1:1 (HR: n = 548; RFA: n = 548). In the multivariate Cox regression model, HR was associated with significantly improved disease-specific survival [before PSM: hazard ratio 0.67, 95% confidence interval (CI) 0.57–0.79, p < 0.001; after PSM: hazard ratio 0.69, 95% CI 0.58–0.82, p < 0.001] and overall survival (before PSM: hazard ratio 0.67, 95% CI 0.58–0.78, p < 0.001; after PSM: hazard ratio 0.69, 95% CI 0.59–0.80, p < 0.001) compared to RFA in patients with multifocal HCC. In the survival curve analysis, the disease-specific survival of the HR group was similar to that of the RFA group before PSM (p = 0.936, log-rank test) but was significantly longer after PSM (p < 0.001) in all patients. Multivariate analyses revealed that differentiation grade, alpha-fetoprotein, tumor size, and tumor extension were independent predictors of poor prognosis in patients with multifocal HCC. Conclusions: The long-term survival rate of HR is better than that of RFA in patients with multifocal HCC. HR may serve as a first-line treatment for patients with multifocal HCC. The presence of large tumors and vascular invasion are not contraindications for HR.
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Affiliation(s)
- Yang-Yang Yue
- Department of Health Management, Sheng-Jing Hospital of China Medical University, Shenyang, China
| | - Wei-Li Zhou
- Department of General Surgery, Sheng-Jing Hospital of China Medical University, Shenyang, China
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Wei CY, Chen PC, Chau GY, Lee RC, Chen PH, Huo TI, Huang YH, Su YH, Hou MC, Wu JC, Su CW. Comparison of prognosis between surgical resection and transarterial chemoembolization for patients with solitary huge hepatocellular carcinoma. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:238. [PMID: 32309385 PMCID: PMC7154415 DOI: 10.21037/atm.2019.12.157] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Background For patients with solitary huge (>10 cm in size) hepatocellular carcinoma (HCC) and without major vascular invasion, the treatment efficacy between surgical resection (SR) and transarterial chemoembolization (TACE) is not well studied. We aimed to compare the prognoses between SR and TACE for patients with solitary huge HCC. Methods We enrolled 143 patients with treatment-naïve, solitary HCC (>10 cm) who had received either SR or TACE treatment between 2007–2016. Factors of overall survival (OS) were analyzed by multivariate analysis. Propensity scores matching (PSM) method was adopted to adjust baseline demographic differences for further analysis. Results Ninety patients underwent SR and 53 patients received TACE. After a median follow-up of 17.0 (interquartile range 7.7–45.6) months, 83 patients had died. The cumulative 5-year OS rate was 44.7% and 11.7% for the SR group and the TACE group, respectively (P<0.001). A multivariate analysis showed that TACE [hazard ratio (HR): 3.515, 95% confidence interval (CI): 2.202–5.610, P<0.001], and albumin-bilirubin (ALBI) grade >1 (HR: 2.181, 95% CI: 1.343–3.543, P=0.002) were the independent risk factors associated with poorer OS. After PSM, 37 pairs of matched patients were selected from each treatment arm. After matching, patients who underwent SR still evinced a significantly higher OS than did those who underwent TACE (P=0.010). Conclusions SR provided a better OS than did TACE for patients with solitary huge (≥10 cm) HCC. As such, SR is recommended as the therapeutic priority for these patients.
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Affiliation(s)
- Cheng-Yi Wei
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei
| | - Po-Chun Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei.,Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei
| | - Gar-Yang Chau
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei.,Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei
| | - Rheun-Chuan Lee
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei.,Department of Radiology, Taipei Veterans General Hospital, Taipei
| | - Ping-Hsien Chen
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei.,Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei.,Institute of Biophotonics, National Yang-Ming University, Taipei
| | - Teh-Ia Huo
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei.,Institute of Pharmacology, National Yang-Ming University, Taipei.,Department of Medical Research, Taipei Veterans General Hospital, Taipei
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei.,Institute of Clinical Medicine, National Yang-Ming University, Taipei
| | - Yu-Hui Su
- Department of Accounting, School of Business, Soochow University, Taipei
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei.,Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei
| | - Jaw-Ching Wu
- Department of Medical Research, Taipei Veterans General Hospital, Taipei.,Institute of Clinical Medicine, National Yang-Ming University, Taipei
| | - Chien-Wei Su
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei.,Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei
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Poor Prognoses of Young Hepatocellular Carcinoma Patients with Microvascular Invasion: A Propensity Score Matching Cohort Study. Gastroenterol Res Pract 2020; 2020:4691425. [PMID: 32148477 PMCID: PMC7042502 DOI: 10.1155/2020/4691425] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2019] [Revised: 11/11/2019] [Accepted: 12/14/2019] [Indexed: 02/05/2023] Open
Abstract
The relationship between age and the prognosis of patients with hepatocellular carcinoma (HCC) has been widely investigated. However, few studies have focused on the influence of patient age on the prognosis of HCC with microvascular invasion (MVI). Patients with histologically confirmed HCC with MVI who underwent hepatectomy between 2008 and 2016 were retrospectively enrolled in this study and allocated to younger (young group) and older age groups (old group) according to age< or ≥60 years. A propensity score matching analysis was performed, and prognostic factors evaluated by Kaplan–Meier curves and Cox proportional hazards regression. Intraoperative and postoperative characteristics were compared between the two groups. A total of 374 patients were enrolled in this study. There were 84 patients in each group after a 1 : 1 propensity score matching analysis. The rates of both disease-free survival (DFS) and overall survival (OS) differed significantly between the age groups. By univariate and multivariate analyses, age < 60 years was significantly associated with DFS (hazard ratio, 1.590; 95% CI, 1.135–2.228) and OS (hazard ratio, 1.837; 95% CI, 1.259–2.680). There were no significant differences in intraoperative or postoperative characteristics between the two age groups. In patients with histologically confirmed HCC with MVI, the prognosis is poorer for those aged younger than 60 years than for those aged 60 years or older. Hepatectomy can be safely performed in selected older patients.
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Dong KS, Liang BY, Zhang ZY, Zhang EL, Yang G, Xia SL, Chen XP, Huang ZY. Histologic severity of liver cirrhosis: A key factor affecting surgical outcomes of hepatocellular carcinoma in patients with portal hypertension. Asian J Surg 2019; 42:981-989. [PMID: 30782497 DOI: 10.1016/j.asjsur.2019.01.009] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2018] [Revised: 01/06/2019] [Accepted: 01/22/2019] [Indexed: 02/08/2023] Open
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Wang H, Feng LH, Qian YW, Cao ZY, Wu MC, Cong WM. Does microvascular invasion in Barcelona Clinic Liver Cancer stage A multinodular hepatocellular carcinoma indicate early-stage behavior? ANNALS OF TRANSLATIONAL MEDICINE 2019; 7:428. [PMID: 31700864 DOI: 10.21037/atm.2019.08.114] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Background To identify the impact of tumor number on Barcelona Clinic Liver Cancer (BCLC) early-stage hepatocellular carcinoma (HCC) and the impact of microvascular invasion (MVI) on multinodular HCC (MHCC). Methods We retrospectively analyzed 1,548 patients who had early-stage HCC [solitary HCC (SHCC, n=1,481) and MHCC (n=67)], according to the BCLC classification, after curative resection. Recurrence-free survival (RFS) and overall survival (OS) were compared. Propensity score matching (PSM) was used to balance potential confounding factors. Results Both before and after PSM, significant differences were noted between the MHCC group and the SHCC group in RFS but not in OS. For the PSM cohort, the 5-year RFS rates were 7.5% and 41.2% for the MVI-positive MHCC group and the SHCC group, respectively (P<0.001). The 5-year OS rates were 48.9% and 75.2% for the MVI-positive MHCC group and the SHCC group, respectively (P=0.017). The RFS and OS were not significantly different between the MVI-negative MHCC group and the SHCC group. MVI (P=0.029) and multiple nodules (P=0.029) were associated with early recurrence. Conclusions The presence of MVI in BCLC early-stage MHCC was highly suggestive of a poor prognosis and should not be classified as early-stage biological behavior.
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Affiliation(s)
- Han Wang
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200438, China.,Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer (The Second Military Medical University) Ministry of Education, Shanghai 200438, China.,Shanghai Key Laboratory of Hepatobiliary Tumor Biology (Eastern Hepatobiliary Surgery Hospital), Shanghai 200438, China
| | - Long-Hai Feng
- Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, The Key Laboratory for Carcinogenesis and Cancer Invasion, The Ministry of Education of China, Shanghai 200032, China
| | - You-Wen Qian
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200438, China.,Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer (The Second Military Medical University) Ministry of Education, Shanghai 200438, China.,Shanghai Key Laboratory of Hepatobiliary Tumor Biology (Eastern Hepatobiliary Surgery Hospital), Shanghai 200438, China
| | - Zhen-Ying Cao
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200438, China.,Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer (The Second Military Medical University) Ministry of Education, Shanghai 200438, China.,Shanghai Key Laboratory of Hepatobiliary Tumor Biology (Eastern Hepatobiliary Surgery Hospital), Shanghai 200438, China
| | - Meng-Chao Wu
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200438, China
| | - Wen-Ming Cong
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200438, China.,Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer (The Second Military Medical University) Ministry of Education, Shanghai 200438, China.,Shanghai Key Laboratory of Hepatobiliary Tumor Biology (Eastern Hepatobiliary Surgery Hospital), Shanghai 200438, China
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Simplified nomograms based on platelet-associated models for survival prediction in Asian hepatocellular carcinoma patients after surgery. Surg Oncol 2019; 30:131-138. [PMID: 31500777 DOI: 10.1016/j.suronc.2019.07.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Revised: 07/04/2019] [Accepted: 07/22/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Accumulating evidence showed platelets were closely related to hepatocellular carcinoma (HCC) prognosis. We here aimed to develop two simple-to-use nomograms based on the PLT-associated modified models to refine prognostic prediction of Asian HCC. METHODS The nomograms were established using 684 eligible Asian patients who received curative resection for HCC, among which 456 and 228 were randomly assigned to the derivation and validation cohorts, respectively. Univariate and multivariate Cox analyses in the derivation set were used to identify the independent prognostic factors of the hepatectomy patients as the nomogram variables. We evaluated the discrimination and calibration of the nomograms by concordance indexes (C-index), calibration plots and Kaplan-Meier curves. The discrimination ability of the PLT-based nomograms was compared with the conventional staging systems using time-dependent receiver operating characteristic (ROC) curves. RESULTS The nomogram for overall survival (OS) estimation was comprised of MPV/PC [mean platelet volume/platelet count], SII [systemic immune-inflammation index], NPS [neutrophil-platelet score], PAPAS [platelet count/age/ALP/AFP/AST index] and S index. And the nomogram for recurrence-free survival (RFS) prediction was of NPS, PAPAS and S index. The C-indexes of the OS nomogram in the derivation and validation sets were 0.704 and 0.707, and those of the RFS nomogram were 0.668 and 0.703. The calibration plots fitted well. The survival curves showed great discriminatory powers. The area under the curve (AUC) of our nomograms were significantly larger than that of the three conventional models (P < 0.05). CONCLUSIONS The two PLT-based nomograms were accurate in predicting the OS and RFS of Asian HCC patients after hepatectomy.
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Abstract
To discuss the prognostic correlation between hepatitis B virus DNA (HBV DNA) level and HBV-related hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI).Data from HCC patients undergoing hepatectomy with pathological evidence of MVI were retrospectively collected and 1:1 propensity scoring matching (PSM) analysis was performed. According to the HBV DNA levels before and after surgery, the disease-free survival (DFS) and overall survival (OS) were evaluated using the Kaplan-Meier method, and the Cox proportional hazards regression was used to analyze the risk factors associated with the postoperative prognosis. After 1:1 PSM, 139 pairs of patients were enrolled in the high preoperative HBV DNA level group (H group) and low preoperative HBV DNA level group (L group), and after operation, patients with high preoperative HBV DNA levels were divided into the persistently high HBV DNA level group (P group) and the decreased HBV DNA level group (D group).According to the multivariate analysis, the HBV DNA level of 2000 IU/ml or greater before operation was significantly associated with the DFS (hazard ratio, 1.322; 95%CI, 1.016-1.721) and OS (hazard ratio, 1.390; 95%CI, 1.023-1.888). A persistent HBV DNA level of 2,000 IU/ml or greater after operation was also the independent risk factor of DFS (hazard ratio, 1.421; 95%CI, 1.018-1.984) and OS (hazard ratio, 1.545; 95%CI, 1.076-2.219).For the HBV-related HCC patients with MVI, preoperative high HBV DNA copies are prognostication of poorer prognosis, and effective antivirus treatment would significantly improve the patients' prognosis.
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Affiliation(s)
- Lian Li
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu
| | - Bo Li
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu
| | - Ming Zhang
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu
- Department of General Surgery, Mianzhu Hospital of West China hospital, Sichuan University, Mianzhu, Sichuan Province, China
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N'Kontchou G, Nault JC, Sutter O, Bourcier V, Coderc E, Grando V, Nahon P, Ganne-Carrié N, Diallo A, Sellier N, Seror O. Multibipolar Radiofrequency Ablation for the Treatment of Mass-Forming and Infiltrative Hepatocellular Carcinomas > 5 cm: Long-Term Results. Liver Cancer 2019; 8:172-185. [PMID: 31192154 PMCID: PMC6547257 DOI: 10.1159/000489319] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2017] [Accepted: 04/16/2018] [Indexed: 02/04/2023] Open
Abstract
AIMS AND BACKGROUND Only few patients with cirrhosis and hepatocellular carcinoma (HCC) larger than 5 cm are amenable to resection or straight liver transplantation, and in such circumstances, multibipolar radiofrequency ablation (mbp-RFA) could be a reliable alternative. This study was aimed to assess the long-term outcome in patients treated with mbp-RFA for unresectable HCC > 5 cm. METHODS Eighty-three consecutive patients with cirrhosis (median age 70 years [37-93 years], 67 males, BCLC A/B/C: 54/21/8, 74 naive) with up to three HCCs, the largest > 5 cm in diameter (median: 6.2 cm, 5.1-9 cm, 22 infiltrative forms, 12 with segmental portal invasion of which 10 were infiltrative forms) were treated with mbp-RFA. Overall (OS) and recurrence-free (RFS) survival and their associated predictive factors were assessed. RESULTS Complete ablation was observed in 78/83 (94%) patients. Thirty-one side effects occurred, including 6 (7%) severe complications. After a median follow-up of 26.1 months (1-112 months), in naive patients the 3- and 5-year OS was 51% (38-62) and 24% (13-36), 63 and 30% for mass-forming and 25 and 6% for infiltrative form, respectively. Infiltrative form (HR: 2.5 [1.33-4.69], p = 0.004) was the only independent OS predictor. In naive patients with mass-forming and infiltrative form, the 3- and 5-year RFS were 47 and 17 and 18 and 18%, respectively. Alpha-fetoprotein (HR: 2.86 [1.32-6.21], p = 0.008), multinodular form (HR: 2.74 [1.4-5.38], p = 0.003) and infiltrative form (HR: 3.43 [1.67-7.01], p = 0.0007) were independent RFS predictors. CONCLUSIONS mbp-RFA offers good OS in inoperable patients with cirrhosis and large HCC, with acceptable safety profile. For infiltrative forms, although mbp-RFA leads to complete responses in more than 80% cases, few only remain tumor progression-free in long-term.
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Affiliation(s)
- Gisele N'Kontchou
- Service d'Hépatologie de l'Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance Publique Hôpitaux de Paris, Bondy, France
| | - Jean-Charles Nault
- Service d'Hépatologie de l'Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance Publique Hôpitaux de Paris, Bondy, France,Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France,Unité Mixte de Recherche 1162, Génomique Fonctionnelle des Tumeurs Solides, Institut National de la Santé et de la Recherche Médicale, Paris, France
| | - Olivier Sutter
- Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France,Service de Radiologie de l'Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance Publique Hôpitaux de Paris, Bondy, France
| | - Valerie Bourcier
- Service d'Hépatologie de l'Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance Publique Hôpitaux de Paris, Bondy, France
| | - Emmanuelle Coderc
- Service de Radiologie de l'Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance Publique Hôpitaux de Paris, Bondy, France
| | - Veronique Grando
- Service d'Hépatologie de l'Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance Publique Hôpitaux de Paris, Bondy, France
| | - Pierre Nahon
- Service d'Hépatologie de l'Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance Publique Hôpitaux de Paris, Bondy, France,Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France,Unité Mixte de Recherche 1162, Génomique Fonctionnelle des Tumeurs Solides, Institut National de la Santé et de la Recherche Médicale, Paris, France
| | - Nathalie Ganne-Carrié
- Service d'Hépatologie de l'Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance Publique Hôpitaux de Paris, Bondy, France,Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France,Unité Mixte de Recherche 1162, Génomique Fonctionnelle des Tumeurs Solides, Institut National de la Santé et de la Recherche Médicale, Paris, France
| | - Abou Diallo
- Département d'Information Médical de l'Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance Publique Hôpitaux de Paris, Bobigny, France
| | - Nicolas Sellier
- Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France,Service de Radiologie de l'Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance Publique Hôpitaux de Paris, Bondy, France
| | - Olivier Seror
- Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France,Unité Mixte de Recherche 1162, Génomique Fonctionnelle des Tumeurs Solides, Institut National de la Santé et de la Recherche Médicale, Paris, France,Service de Radiologie de l'Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance Publique Hôpitaux de Paris, Bondy, France,*Olivier Seror, Service de Radiologie, Hôpital Jean Verdier, Avenue du 14 juillet, FR–93140 Bondy (France), E-Mail
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Zhang XP, Chen ZH, Zhou TF, Li LQ, Chen MS, Wen TF, Shi J, Guo WX, Wu MC, Lau WY, Cheng SQ. A nomogram to predict early postoperative recurrence of hepatocellular carcinoma with portal vein tumour thrombus after R0 liver resection: A large-scale, multicenter study. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2019; 45:1644-1651. [PMID: 30982657 DOI: 10.1016/j.ejso.2019.03.043] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Revised: 02/20/2019] [Accepted: 03/28/2019] [Indexed: 02/05/2023]
Abstract
BACKGROUND Portal vein tumour thrombus (PVTT) is a significant poor prognostic factor for hepatocellular carcinoma (HCC). Patients with PVTT limited to a first-order branch or above of the main portal vein (MPV) could benefit from R0 liver resection (LR). A nomogram is needed to predict early postoperative recurrence (ER) in HCC patients with PVTT and to guide selection of these patients for adjuvant therapy to reduce postoperative recurrence risks. METHODS HCC patients with PVTT limited to a first-order branch or above of the MPV after R0 LR as an initial therapy were included. A nomogram using data from a retrospective training cohort was developed with the Cox regression model. The model was tested in a prospective internal validation cohort and three external validation cohorts. RESULTS Of 979 patients, 657 developed postoperative ER (67.1%). ER occurred in 165 of 264 patients (62.5%) in the training cohort, 146 of 218 patients (70.0%) in the internal validation cohort, and 204 of 284 patients (71.8%), 77 of 113 patients (68.1%), and 65 of 100 patients (65%) in the three external validation cohorts, respectively. The nomogram included the following variables: hepatitis B surface antigen (HBsAg), PVTT, HBV DNA, satellite nodules, α-fetoprotein, and tumour diameter. The ROC were 0.836, 0.763, 0.802, 0.837, and 0.846 in predicting ER in the five respective cohorts. CONCLUSION A nomogram was developed and validated to predict postoperative ER in patients with HCC with PVTT after R0 LR. This nomogram could select appropriate patients with high ER risks for postoperative adjuvant therapy.
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Affiliation(s)
- Xiu-Ping Zhang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University Shanghai, China
| | - Zhen-Hua Chen
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University Shanghai, China
| | - Teng-Fei Zhou
- The No.313 Hospital of PLA, Huludao, Liaoning, China
| | - Le-Qun Li
- Department of Hepatobiliary Surgery, Affiliated Tumour Hospital of Guangxi Medical University, Nanning, China
| | - Min-Shan Chen
- Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Tian-Fu Wen
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, 610041, China
| | - Jie Shi
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University Shanghai, China
| | - Wei-Xing Guo
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University Shanghai, China
| | - Meng-Chao Wu
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University Shanghai, China
| | - Wan Yee Lau
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University Shanghai, China; Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
| | - Shu-Qun Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University Shanghai, China.
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