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Shin YS, Yun JK, Jung J, Park JH, Song SY, Choi EK, Choi S, Kim HR, Kim YH, Kim DK, Lee GD, Yoon SM. Comparison of Metastasectomy and Stereotactic Body Radiation Therapy for Pulmonary Oligometastasis From Hepatocellular Carcinoma: A Propensity Score-Weighted Analysis. Int J Radiat Oncol Biol Phys 2025; 121:432-441. [PMID: 39299553 DOI: 10.1016/j.ijrobp.2024.09.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 06/20/2024] [Accepted: 09/08/2024] [Indexed: 09/22/2024]
Abstract
PURPOSE Although there is a growing role for local therapy in patients with hepatocellular carcinoma (HCC) and pulmonary oligometastasis, it remains unclear whether metastatectomy or stereotactic body radiation therapy (SBRT) is the more effective treatment for these patients. We aimed to compare the oncologic outcomes of metastasectomy and SBRT for HCC with pulmonary oligometastasis. METHODS AND MATERIALS We retrospectively analyzed 209 patients with HCC with 322 metastatic lung lesions who underwent either metastasectomy (150 patients with 241 lesions) or SBRT (59 patients with 81 lesions) between January 2008 and December 2018. Propensity score-based inverse probability of treatment weighting was used to minimize potential bias between the 2 groups. RESULTS The median follow-up duration was 39.8 months (range, 2.3-166.9 months). The 2-year rate of freedom from local progression was 98.2% in the metastasectomy group and 97.0% in the SBRT group (P = .197). The 2-year rates of overt systemic progression-free survival (PFS) (51.0% vs 46.1%; P = .274), PFS (26.3% vs 9.1%; P = .074), and overall survival (OS, 74.0% vs 57.6%; P = .006) were higher in the metastasectomy group. After the probability of treatment weighting adjustment, the 2-year rates of overt systemic PFS (50.8% vs 52.7%; P = .396), PFS (23.0% vs 24.7%; P = .478), and OS (72.6% vs 83.0%, P = .428) were not significantly different between the 2 groups. In multivariate analysis, viable intrahepatic lesions and the number of prior liver-directed therapies were found to be significant prognostic factors for OS and PFS. The time interval between HCC diagnosis and the development of pulmonary metastases was also significantly associated with OS. CONCLUSIONS Both metastasectomy and SBRT demonstrated excellent local control and comparable oncologic outcomes in patients with pulmonary oligometastasis from HCC. The treatment modality for these patients could be determined based on the individual patient's condition and intrahepatic disease status.
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Affiliation(s)
| | - Jae Kwang Yun
- Thoracic and Cardiovascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | | | | | | | | | - Sehoon Choi
- Thoracic and Cardiovascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Hyeong Ryul Kim
- Thoracic and Cardiovascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Yong-Hee Kim
- Thoracic and Cardiovascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Dong Kwan Kim
- Thoracic and Cardiovascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Geun Dong Lee
- Thoracic and Cardiovascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
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Zhou Q, Li R, Wu S, Zhang Y, Wang W, Zhu K, Wang M, Huang Z, Duan F. Metastasis-directed ablation of hepatocellular carcinoma with pulmonary oligometastases: a long-term multicenter study. LA RADIOLOGIA MEDICA 2025; 130:25-36. [PMID: 39531158 DOI: 10.1007/s11547-024-01907-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Accepted: 10/23/2024] [Indexed: 11/16/2024]
Abstract
PURPOSE Ablation is a promising approach for eliminating intrathoracic metastases. We compared the effectiveness of a combination of metastasis-directed ablation and systemic therapy with that of systemic therapy alone for patients with hepatocellular carcinoma (HCC) having pulmonary oligometastases. MATERIALS AND METHODS We analyzed 679 patients with HCC and pulmonary oligometastases from seven tertiary hospitals. A total of 372 patients received systemic therapy (System group), whereas 307 patients received the combination therapy of pulmonary oligometastases ablation and systemic therapy (Ablation + System group). RESULTS The median progression-free survival (PFS) was 9.7 ± 0.6 and 11.5 ± 0.6 months in the System and Ablation + System groups, respectively. The Ablation + System group exhibited significantly better PFS (hazard ratio [HR], 0.71; 95% confidence interval [CI] 0.60-0.85; P < 0.001) and overall survival (OS) (HR, 0.65; 95% CI 0.52-0.81; P < 0.001) than the System group. The subgroup analysis revealed that OS (HR, 0.91; 95% CI 0.65-1.28; P = 0.590) and PFS (HR, 0.81; 95% CI 0.62-1.05; P = 0.100) did not differ between tyrosine kinase inhibitor (TKI) and TKI plus programmed cell death protein-1 (PD-1) inhibitor therapies in the Ablation + system group. In addition, PFS (HR, 0.53; 95% CI 0.38-0.74; P < 0.001) and OS (HR, 0.66; 95% CI 52-0.84; P < 0.001) showed obviously different for intrahepatic tumors with partial response (PR) status. CONCLUSION The application of a combination of ablation of pulmonary oligometastases and systemic therapy resulted in longer PFS and OS than systemic therapy alone.
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Affiliation(s)
- Qunfang Zhou
- Department of Interventional Radiology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, China
| | - Ruixia Li
- Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Er Road, Guangzhou, Guangdong Province, China
| | - Songsong Wu
- Department of Ultrasonography, Fujian Provincial Hospital, East Road 134, Fuzhou, Fujian Province, China
| | - Yanyang Zhang
- Department of Interventional Radiology, The Third Affiliated Hospital of Sun Yat-Sen University, Tianhe Road 600, Guangzhou, Guangdong Province, China
| | - Wei Wang
- Department of General Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning Province, China
| | - Kangshun Zhu
- Department of Minimally Invasive Interventional Radiology, The Second Affiliated Hospital of Guangzhou Medical University, 250 Changgang East Road, Guangzhou, Guangdong Province, China
| | - Murong Wang
- Department of Minimally Invasive Interventional Radiology, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, Guangdong Province, China
| | - Zhimei Huang
- Department of Minimally Invasive Interventional Radiology, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, Guangdong Province, China.
| | - Feng Duan
- Department of Interventional Radiology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, China.
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Emmamally M, Sobnach S, Khan R, Kotze U, Bernon M, Sonderup MW, Spearman CW, Jonas E. Prevalence, management and outcomes of pulmonary metastases in hepatocellular carcinoma: a systematic review and meta-analysis. HPB (Oxford) 2024; 26:1339-1348. [PMID: 39168776 DOI: 10.1016/j.hpb.2024.08.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Revised: 06/11/2024] [Accepted: 08/02/2024] [Indexed: 08/23/2024]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) presents a significant global health burden, with varying survival rates across regions. The presence of pulmonary metastases (PM) in HCC predicts a poorer prognosis, yet the global understanding of the progression and management is limited. METHODS This study aims to systematically review the burden of PM in HCC, document current treatment approaches, and evaluate treatment effectiveness through meta-analysis. A comprehensive literature search was conducted across multiple databases. Articles were screened, and data extraction was performed independently by two reviewers. Statistical analyses were conducted to synthesise data and assess treatment outcomes. RESULTS A total of 82 articles were included, comprising a population of 3241 participants with documented PM. Our analysis revealed a linear relationship between the HCC population size and the occurrence of PM (p < 0.005). Surgical intervention demonstrated the lowest hazard ratio (0.128) and significantly improved survival rates compared to other treatment modalities. However, data quality limitations underscore the need for further research to delineate patient subsets benefitting from surgical intervention for PM. CONCLUSION Our findings advocate for continued investigation into PM management strategies, notably the role of surgical resection alongside systemic therapies, to improve outcomes in HCC patients with PM.
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Affiliation(s)
- Muhammad Emmamally
- Surgical Gastroenterology Unit, Division of General Surgery, University of Cape Town Health Sciences Faculty and Groote Schuur Hospital, Cape Town, South Africa
| | - Sanju Sobnach
- Surgical Gastroenterology Unit, Division of General Surgery, University of Cape Town Health Sciences Faculty and Groote Schuur Hospital, Cape Town, South Africa
| | - Rufaida Khan
- Surgical Gastroenterology Unit, Division of General Surgery, University of Cape Town Health Sciences Faculty and Groote Schuur Hospital, Cape Town, South Africa
| | - Urda Kotze
- Surgical Gastroenterology Unit, Division of General Surgery, University of Cape Town Health Sciences Faculty and Groote Schuur Hospital, Cape Town, South Africa
| | - Marc Bernon
- Surgical Gastroenterology Unit, Division of General Surgery, University of Cape Town Health Sciences Faculty and Groote Schuur Hospital, Cape Town, South Africa
| | - Mark W Sonderup
- Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town Faculty and Groote Schuur Hospital, Cape Town, South Africa
| | - C Wendy Spearman
- Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town Faculty and Groote Schuur Hospital, Cape Town, South Africa
| | - Eduard Jonas
- Surgical Gastroenterology Unit, Division of General Surgery, University of Cape Town Health Sciences Faculty and Groote Schuur Hospital, Cape Town, South Africa.
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Osuga T, Tanaka S, Kubo T, Hamaguchi K, Ito R, Sakurada A, Ishikawa K, Miyanishi K. Pulmonary Metastasectomy after Radiofrequency Ablation of Hepatocellular Carcinoma. Case Rep Oncol 2024; 17:407-416. [PMID: 38435446 PMCID: PMC10907002 DOI: 10.1159/000536498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Accepted: 01/23/2024] [Indexed: 03/05/2024] Open
Abstract
Introduction Single distant metastases after radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) are rare. There are no guidelines for treating patients without liver tumors after resecting lung metastases. Case Presentation Here, we report a patient with HCC recurring as a single lung metastasis 14 months after RFA. A 76-year-old woman with primary biliary cholangitis without hepatitis B virus or hepatitis C virus infection had been treated by RFA for a single 16-mm-sized HCC lesion in liver S8. Fourteen months thereafter, despite lack of intrahepatic recurrence, a single new 26-mm-sized mass was found in S10 of the right lung. The patient underwent right lower lobectomy. The histopathological diagnosis was HCC metastasis. Because no residual disease could be found, she was followed up without any additional treatment after surgery. She remains alive with no signs of recurrence 3 years later. Conclusion HCC patients who relapse with lung metastases but without intrahepatic recurrence after RFA are extremely rare, especially when RFA is used to treat HCC lesions <30 mm. However, it should be noted that, although rare, HCC may recur in the form of extrahepatic metastases after RFA. Furthermore, it is suggested that, as in the presently-described case, at least some patients without intrahepatic recurrence whose lung metastases are completely resected have a good prognosis even without additional treatment for HCC.
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Affiliation(s)
- Takahiro Osuga
- Department of Medical Oncology, Sapporo Medical University School of Medicine, Hokkaido, Japan
| | - Shingo Tanaka
- Department of Medical Oncology, Sapporo Medical University School of Medicine, Hokkaido, Japan
- Department of Infection Control and Laboratory Medicine, Sapporo Medical University School of Medicine, Hokkaido, Japan
| | - Tomohiro Kubo
- Department of Medical Oncology, Sapporo Medical University School of Medicine, Hokkaido, Japan
| | - Kota Hamaguchi
- Department of Medical Oncology, Sapporo Medical University School of Medicine, Hokkaido, Japan
| | - Ryo Ito
- Department of Medical Oncology, Sapporo Medical University School of Medicine, Hokkaido, Japan
| | - Akira Sakurada
- Gastroenterology, Otaru Ekisaikai Hospital, Hokkaido, Japan
| | | | - Koji Miyanishi
- Department of Medical Oncology, Sapporo Medical University School of Medicine, Hokkaido, Japan
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Xiang C, Xiao Y, Ma Z, Peng Y, Li X, Mao X, Li L. Liver resection for large and huge hepatocellular carcinoma: Predictors of failure, recurrence patterns, and prognoses. Asia Pac J Clin Oncol 2023; 19:e60-e70. [PMID: 35404506 DOI: 10.1111/ajco.13777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Revised: 03/03/2022] [Accepted: 03/08/2022] [Indexed: 01/27/2023]
Abstract
BACKGROUND Characteristic symptoms and signs are often absent in patients with hepatocellular carcinoma (HCC). As a result, many patients are not diagnosed until their tumors have grown to large (> 5cm) or huge sizes (> 10cm). Liver resection has traditionally been reserved for patients with small HCC, but more recently it is being used for patients with large and huge tumors. The aim of this study was to determine risk predictors of recurrence, patterns of recurrence, and survival rates for large and huge HCC patients who underwent curative liver resection. MATERIALS AND METHODS We retrospectively identified a subgroup of patients who underwent liver resection for HCC with diameters 5 cm or larger. Overall survival (OS) and recurrence-free survival (RFS) rates were calculated using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were performed to investigate potential risk factors for recurrence and death. RESULTS Among 897 patients, the median follow-up was 48 (range, 5-140) months. The 1-, 3-, and 5-year RFS rates were 51.6%, 36.1%, and 30.1%, respectively, and OS rates were 80.2%, 55.4%, and 47.7%, respectively. Significant independent predictors of recurrence were preoperative satellite nodule (HR = 2.25; 95% CI, 1.17-4.31; p = .02), preoperative AFP levels above 400 ng/ml (HR = 1.23; 95% CI, 1.04-1.45; p = .01), resection margins of 1 cm or less (HR = 1.21; 95% CI, 1.00-1.46; p = .047), cirrhosis (HR = 2.64; 95% CI, 2.13-3.28; p < .001), and microvascular invasion (HR = 1.71; 95% CI, 1.45-2.20; p < .001). All of these except narrow resection margin were also independent risk factors of OS. CONCLUSIONS Hepatic resection for patients with large and huge HCC without hepatic vascular invasion, extrahepatic metastases, or severe chronic liver disease results in acceptable long-term outcomes.
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Affiliation(s)
- Cailing Xiang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
- Department II of General Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China
| | - Yating Xiao
- School of Molecular Medicine, Hangzhou Institute for Advanced Study, UCAS, Hangzhou, China
| | - Zhongzhi Ma
- Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China
| | - Yuchong Peng
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Xun Li
- School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Xianhai Mao
- Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China
| | - Lequn Li
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
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Yoon JH, Choi SK, Cho SB, Kim HJ, Ko YS, Jun CH. Early extrahepatic recurrence as a pivotal factor for survival after hepatocellular carcinoma resection: A 15-year observational study. World J Gastroenterol 2022; 28:5351-5363. [PMID: 36185633 PMCID: PMC9521522 DOI: 10.3748/wjg.v28.i36.5351] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 08/11/2022] [Accepted: 09/08/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Surgical resection is one of the most widely used modalities for the treatment of hepatocellular carcinoma (HCC). Early extrahepatic recurrence (EHR) of HCC after surgical resection is considered to be closely associated with poor prognosis. However, data regarding risk factors and survival outcomes of early EHR after surgical resection remain scarce. AIM To investigate the clinical features and risk factors of early EHR and elucidate its association with survival outcomes. METHODS From January 2004 to December 2019, we enrolled treatment-naïve patients who were ≥ 18 years and underwent surgical resection for HCC in two tertiary academic centers. After excluding patients with tumor types other than HCC and/or ineligible data, this retrospective study finally included 779 patients. Surgical resection of HCC was performed according to the physicians' decisions and the EHR was diagnosed based on contrast-enhanced computed tomography or magnetic resonance imaging, and pathologic confirmation was performed in selected patients. Multivariate Cox regression analysis was performed to identify the variables associated with EHR. RESULTS Early EHR within 2 years after surgery was diagnosed in 9.5% of patients during a median follow-up period of 4.4 years. The recurrence-free survival period was 5.2 mo, and the median time to EHR was 8.8 mo in patients with early EHR. In 52.7% of patients with early EHR, EHR occurred as the first recurrence of HCC after surgical resection. On multivariate analysis, serum albumin < 4.0 g/dL, serum alkaline phosphatase > 100 U/L, surgical margin involvement, venous and/or lymphatic involvement, satellite nodules, tumor necrosis detected by pathology, tumor size ≥ 7 cm, and macrovascular invasion were determined as risk factors associated with early EHR. After sub-categorizing the patients according to the number of risk factors, the rates of both EHR and survival showed a significant correlation with the risk of early EHR. Furthermore, multivariate analysis revealed that early EHR was associated with substantially worse survival outcomes (Hazard ratio, 6.77; 95% confidence interval, 4.81-9.52; P < 0.001). CONCLUSION Early EHR significantly deteriorates the survival of patients with HCC, and our identified risk factors may predict the clinical outcomes and aid in postoperative strategies for improving survival.
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Affiliation(s)
- Jae Hyun Yoon
- Department of Gastroenterology and Hepatology, Chonnam National University Hospital and College of Medicine, Gwangju 61469, South Korea
| | - Sung Kyu Choi
- Department of Gastroenterology and Hepatology, Chonnam National University Hospital and College of Medicine, Gwangju 61469, South Korea
| | - Sung Bum Cho
- Department of Gastroenterology and Hepatology, Hwasun Chonnam National University Hospital and College of Medicine, Hwasun 58128, South Korea
| | - Hee Joon Kim
- Department of Surgery, Chonnam National University Hospital and College of Medicine, Gwangju 61469, South Korea
| | - Yang Seok Ko
- Department of Surgery, Hwasun Chonnam National University Hospital and College of Medicine, Hwasun 58128, South Korea
| | - Chung Hwan Jun
- Department of Internal Medicine, Mokpo Hankook Hospital, Mokpo 58643, South Korea
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Commander SJ, Cerullo M, Arjunji N, Leraas HJ, Thornton S, Ravindra K, Tracy ET. Improved Survival and Higher Rates of Surgical Resection Associated with Hepatocellular Carcinoma in Children as Compared to Young Adults. Int J Cancer 2022; 151:2206-2214. [PMID: 35841394 DOI: 10.1002/ijc.34215] [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: 01/17/2022] [Revised: 07/07/2022] [Accepted: 07/11/2022] [Indexed: 11/06/2022]
Abstract
Hepatocellular adenocarcinoma (HCC) is the second most common primary hepatic malignancy in children with a 5-year overall survival of 30%. Few studies have examined the similarities and differences between pediatric and adult HCC. This paper aims to examine the relationship between tumor characteristics, treatments, and outcomes in pediatric and adult patients with HCC. The 2019 National Cancer Database was queried for patients with HCC. Patients were stratified by age: pediatric <21 years (n = 214) and young adults 21-40 (n = 1102). Descriptive statistics and chi square were performed. The mean age at diagnosis was 15.5 years (SD 5.6) in the pediatric and 33 years (5.3) in the adult group. Children had a comparable rate of metastasis (30% vs 28%, P = 0.47) and increased fibrolamellar histology (32% vs 9%). Surgical resection was more common in children compared with adults (74% vs 62%, P < 0.001), children also had more lymph nodes examined (39% vs 19%, P < 0.001), positive lymph nodes (35% vs 17%, P = 0.02), and surgical resection when metastasis were present at diagnosis (46% vs 18%, P < 0.001). The 1, 3, and 5-year overall survival was higher for pediatric patients than adults (81%, 65%, 55%, vs 70%, 54%, 48%,) Despite higher prevalence of fibrolamellar histology, greater number of positive lymph nodes, and comparable rates of metastasis at diagnosis, children with HCC have improved overall survival compared with adults. Age did not significantly contribute to survivorship, so it is likely that the more aggressive surgical approach contributed to the improved overall survival in pediatric patients. This article is protected by copyright. All rights reserved.
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Affiliation(s)
| | - Marcelo Cerullo
- Department of General Surgery, Duke University Medical Center
| | - Neha Arjunji
- School of Medicine, Duke University Medical Center
| | - Harold J Leraas
- Division of Pediatric Surgery, Duke University Medical Center
| | | | - Kadiyala Ravindra
- Division of Abdominal Transplantation, Duke University Medical Center
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Long HY, Huang TY, Xie XY, Long JT, Liu BX. Treatment strategies for hepatocellular carcinoma with extrahepatic metastasis. World J Clin Cases 2021; 9:5754-5768. [PMID: 34368295 PMCID: PMC8316954 DOI: 10.12998/wjcc.v9.i21.5754] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Revised: 04/20/2021] [Accepted: 05/25/2021] [Indexed: 02/06/2023] Open
Abstract
Extrahepatic metastasis (EHM) of hepatocellular carcinoma (HCC) has increasingly been seen due to improved survival with effective management of intrahepatic lesions. The presence of EHM indicates an advanced stage of HCC, for which systemic therapy serves as the standard treatment modality. Since the approval of Sorafenib as the first systemic agent in 2007, it took almost a decade to show its efficacy in both first and further lines of setting until the landscape of systemic drugs was finally expanded. Moreover, with inspiring results from immunotherapy trials in HCC, it appears that the introduction of immunotherapy may lead to an evolution in the portfolio of HCC treatment. Although the locoregional approach in the management of EHM is not recommended for advanced-stage HCC, efforts have been made to demonstrate its efficacy in symptom relief and potential benefit for overall survival. This review provides a summary of recent updates of the systemic agents in the treatment of advanced HCC, with an emphasis on aggressive locoregional management of EHM by various treatment modalities.
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Affiliation(s)
- Hai-Yi Long
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
| | - Tong-Yi Huang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
| | - Xiao-Yan Xie
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
| | - Jian-Ting Long
- Department of Medical Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
| | - Bao-Xian Liu
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
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Simple parameters predicting extrahepatic recurrence after curative hepatectomy for hepatocellular carcinoma. Sci Rep 2021; 11:12984. [PMID: 34155324 PMCID: PMC8217564 DOI: 10.1038/s41598-021-92503-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Accepted: 06/10/2021] [Indexed: 02/06/2023] Open
Abstract
Extrahepatic recurrence (EHR) after curative hepatectomy for hepatocellular carcinoma (HCC) is associated with a poor prognosis. We investigated the features of EHR and identified its predictive factors. This retrospective study included 398 treatment-naive patients who underwent curative hepatectomy for HCC at two tertiary hospitals. Multivariate Cox-regression analysis was performed to identify the variables associated with EHR. EHR was diagnosed in 94 patients (23.6%) over a median follow-up period of 5.92 years, most commonly in the lungs (42.6%). The 5-/10-year cumulative rates of HCC recurrence and EHR were 63.0%/75.6% and 18.1%/35.0%, respectively. The median time to EHR was 2.06 years. Intrahepatic HCC recurrence was not observed in 38.3% of patients on EHR diagnosis. On multivariate analysis, pathologic modified Union for International Cancer Control stage (III, IVa), surgical margin involvement, tumor necrosis, sum of tumor size > 7 cm, and macrovascular invasion were predictive factors of EHR. Four risk levels and their respective EHR rates were defined as follows: very low risk, 1-/5-year, 3.1%/11.6%; low risk, 1-/5-year, 12.0%/27.7%; intermediate risk, 1-/5-year, 36.3%/60.9%; and high risk, 1-year, 100.0%. Our predictive model clarifies the clinical course of EHR and could improve the follow-up strategy to improve outcomes.
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Li J, Huang L, Liu C, Qiu M, Yan J, Yan Y, Wei S. Risk factors and clinical outcomes of extrahepatic recurrence in patients with post-hepatectomy recurrent hepatocellular carcinoma. ANZ J Surg 2021; 91:1174-1179. [PMID: 33724680 DOI: 10.1111/ans.16737] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2020] [Revised: 02/27/2021] [Accepted: 03/01/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND Extrahepatic recurrence remains a major obstacle to an improved prognosis in patients with hepatocellular carcinoma (HCC) undergoing hepatectomy. METHODS From January 2001 to December 2014, we screened 1330 consecutive patients who underwent curative hepatectomy for HCC. Patients who experienced recurrence were enrolled in this study and divided into an extrahepatic recurrence (EHR) group and a pure intrahepatic recurrence (IHR) group. Clinical data and follow-up results were retrospectively collected and analysed. RESULTS A total of 556 patients were enrolled (EHR, 52; IHR, 504). In the EHR group, the lung was the most common site of extrahepatic recurrence (53.8%), among which 67.3% had associated intrahepatic lesions. Background Hepatitis B (HR 0.282; 95% CI 0.106-0.752; P = 0.011), tumour size ≥10 cm at initial diagnosis (HR 2.679; 95% CI 1.283-5.596; P = 0.009) and blood transfusion during initial surgery (HR 2.218; 95% CI 1.132-4.346; P = 0.020) were predictive of EHR. A multidisciplinary team treated recurrent HCC. After a median follow-up period of 46 months (range, 24-192 months), the 1-, 3- and 5-year overall survival rates in the EHR group were 60.7%, 8.9% and 0%, respectively, after recurrence, and 78.8%, 30.2% and 8.9%, respectively, after initial surgery, which were much lower than those in the IHR group. CONCLUSION Tumour size ≥10 cm and blood transfusion during initial surgery were predictive of extrahepatic recurrence in patients with post-hepatectomy recurrent HCC. Treatment options were limited, and long-term survival was unsatisfactory.
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Affiliation(s)
- Jing Li
- Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.,Department of Hepatic Surgery, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - Liang Huang
- Department of Hepatic Surgery, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - Caifeng Liu
- Department of Hepatic Surgery, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - Maixuan Qiu
- Department of Hepatic Surgery, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - Jianjun Yan
- Department of Hepatic Surgery, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - Yiqun Yan
- Department of Hepatic Surgery, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - Shaohua Wei
- Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China
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Chen Y, Zeng J, Guo P, Zeng J, Liu J. Prognostic Significance of Platelet-to-Lymphocyte Ratio (PLR) in Extrahepatic Metastasis of Hepatocellular Carcinoma After Curative Resection. Cancer Manag Res 2021; 13:1395-1405. [PMID: 33603483 PMCID: PMC7886383 DOI: 10.2147/cmar.s290738] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Accepted: 01/13/2021] [Indexed: 12/16/2022] Open
Abstract
Background The prognosis for patients diagnosed of hepatocellular carcinoma (HCC) who have extrahepatic metastasis after liver resection is unsatisfactory. This study aimed to find out the relationship between the inflammation-related indexes and metastasis. Methods One thousand three hundred and sixty-six patients diagnosed of HCC who underwent curative resection were included in this study and divided into metastasis group (n=180) and non-metastasis group (n=1186). A receiver operating characteristic (ROC) curve was constructed to estimate the optimal cut-off value for inflammation-related indexes. Independent risk factors were identified by Cox regression analysis. The metastasis rate was analyzed by the Kaplan-Meier method, then the subgroup analyses were taken. Results The cut-off values of NLR, PLR, LMR, NγLR, PNLR, and PNI were 2.65, 107.67, 5.47, 134.52, 335.03, and 51.23, respectively. Multivariate Cox analysis revealed that elevated serum AFP level (P=0.004), tumor size more than 5cm (P<0.001), multiple tumors (P=0.040), and higher PLR (P=0.042) were independent risk factors associated with extrahepatic metastasis. The Kaplan-Meier method showed that the high PLR group has a higher extrahepatic metastasis rate than the low PLR group. Meanwhile, the results of subgroup analyses were consistent with the conclusion. Conclusion The PLR is an independent risk factor of extrahepatic metastasis after radical hepatectomy for HCC patients. The high PLR indicates a higher rate of extrahepatic metastasis.
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Affiliation(s)
- Yifan Chen
- Department of Hepatic Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People's Republic of China.,The First Affiliated Hospital of Fujian Medical University, Fuzhou, People's Republic of China
| | - Jianxing Zeng
- The First Affiliated Hospital of Fujian Medical University, Fuzhou, People's Republic of China
| | - Pengfei Guo
- Southeast Big Data Institute of Hepatobiliary Health, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People's Republic of China
| | - Jinhua Zeng
- Department of Hepatic Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People's Republic of China.,The First Affiliated Hospital of Fujian Medical University, Fuzhou, People's Republic of China.,The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, People's Republic of China
| | - Jingfeng Liu
- Department of Hepatic Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People's Republic of China.,The First Affiliated Hospital of Fujian Medical University, Fuzhou, People's Republic of China.,The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, People's Republic of China
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12
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Yang G, Zhou L, Xu Q, Meng F, Wan Y, Meng X, Wang L, Zhang L. LncRNA KCNQ1OT1 inhibits the radiosensitivity and promotes the tumorigenesis of hepatocellular carcinoma via the miR-146a-5p/ACER3 axis. Cell Cycle 2020; 19:2519-2529. [PMID: 32936716 PMCID: PMC7553536 DOI: 10.1080/15384101.2020.1809259] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death, and radiotherapy is currently one of the main treatments. Long non-coding RNAs (lncRNAs) are associated with the radiosensitivity and tumorigenesis of HCC. However, the role and molecular mechanism of potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1 (KCNQ1OT1) in HCC are still unclear. The relative expression of KCNQ1OT1, microRNA-146a-5p (miR-146a-5p) and alkaline ceramidase 3 (ACER3) was quantified by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Clonogenic assay was used to assess the radiosensitivity of cells. Cell apoptosis and metastasis were evaluated by flow cytometry and transwell assays, respectively. The protein levels of apoptosis markers, metastasis markers and ACER3 were detected by western blot (WB) analysis. The relationship between miR-146a-5p and KCNQ1OT1 or ACER3 was determined by dual-luciferase reporter assay. Additionally, animal experiments were carried out to explore the effect of KCNQ1OT1 silencing on HCC tumor growth in vivo. KCNQ1OT1 was highly expressed in HCC, and its knockdown hindered the proliferation and metastasis, while increased the radiosensitivity and apoptosis of HCC cells. MiR-146a-5p could interact with KCNQ1OT1, and its inhibition reversed the effects of silenced-KCNQ1OT1 on the radiosensitivity and tumorigenesis of HCC cells. Besides, ACER3 was a target of miR-146a-5p, and its overexpression inversed the effects of miR-146a-5p mimic on the radiosensitivity and tumorigenesis of HCC cells. The expression of ACER3 was regulated by KCNQ1OT1 and miR-146a-5p. Furthermore, KCNQ1OT1 also could reduce the growth of HCC by regulating the miR-146a-5p/ACER3 axis in vivo. Our study suggested that KCNQ1OT1 improved ACER3 expression to regulate the radiosensitivity and tumorigenesis of HCC through sponging miR-146a-5p, indicating that KCNQ1OT1 might be a new therapeutic target for HCC.
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Affiliation(s)
- Ganghua Yang
- Department of Geriatric Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Lijing Zhou
- Department of Geriatric Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Qinhong Xu
- Department of Geriatric Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Fandi Meng
- Department of Geriatric Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Yong Wan
- Department of Geriatric Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Xiankui Meng
- Department of Geriatric Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Lin Wang
- Department of Geriatric Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China,CONTACT Lin Wang ; Lei Zhang
| | - Lei Zhang
- Department of Geriatric Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
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13
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Invenizzi F, Iavarone M, Donato MF, Mazzucco A, Torre M, Conforti S, Rimessi A, Zavaglia C, Schiavon M, Comacchio G, Rea F, Boetto R, Cillo U, Dondossola D, De Carlis L, Lampertico P, Nosotti M, Mendogni P. Pulmonary Resection for Metastasis of Hepatocellular Carcinoma Recurring After Liver Transplant: An Italian Multicenter Experience. Front Oncol 2020; 10:381. [PMID: 32351877 PMCID: PMC7175841 DOI: 10.3389/fonc.2020.00381] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Accepted: 03/04/2020] [Indexed: 12/11/2022] Open
Abstract
Background and aim: Liver transplantation (LT) is a validated treatment for hepatocellular carcinoma (HCC). HCC recurrence occurred between 8 and 20% of patients and lung is the most frequent site. Pulmonary metastases resection (PMR) prolongs survival, however in LT-setting the impact on survival is unclear. To give new lights on this issue, we report the experience of three Italian LT Centers. Methods: All consecutive HCC transplanted patients in three Italian LT Centers, who developed pulmonary metastasis from HCC (PM-HCC), as first metastasis, from 2008 to 2018, were included whenever treated with PMR. Results: Twenty-five patients were enrolled (median age 58 yrs, 84% male, 3% cirrhotics). HCC recurred after 34 months (9–306) since LT and PMR was performed after 2.4 months (0–43.1). A total of 28 PMR (19 single resections; 9 multiple resections; 16 right; 2 left) have been performed on 24 patients while in one case percutaneous microwave ablation (MWA) was preferred. Four patients have been re-operated due to pulmonary HCC-recurrence after surgery. The majority of surgical resection type was wedge resection (26, 89%). Surgical access was: video-assisted thoracic surgery (VATS) in 17 cases (59%); thoracotomy in 11 (38%); MWA in 1 (3%). The 48% of nodule was in right lower lobe. Perioperative in-hospital mortality and 30 days mortality were nil; median surgical time 90 min (50–365); median post-operative overall stay 5 days (2–11). Post-operative ICU treatment was necessary in 1 case (3%) for 3 days; blood transfusions in 2 cases (7%). Overall, 5 complications (2 bleeding; 1 AKI; 1 major cardiac; 1 wound dehiscence) occurred, with an overall complications rate of 23%. Eight (32%) patients died during a follow-up after HCC recurrence of 32 months (7–213): 7 for HCC progression, 1 for severe liver failure due to chronic rejection. The 1 and 5 year cumulative probability of OS from recurrence were 100 and 43% (95%CI 12–74), respectively, with a median OS of 51 months (95%CI 24–78). Conclusion: Selected patients with isolated pulmonary HCC-recurrence after LT and with preserved hepatic function showed that a pulmonary metastasectomy could be efficacious in managing a PM-HCC and could give an opportunity for long-term survival.
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Affiliation(s)
- Federica Invenizzi
- Division of Gastroenterology and Hepatology, CRC "A. M. and A. Migliavacca" Center for Liver Disease, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Massimo Iavarone
- Division of Gastroenterology and Hepatology, CRC "A. M. and A. Migliavacca" Center for Liver Disease, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Maria Francesca Donato
- Division of Gastroenterology and Hepatology, CRC "A. M. and A. Migliavacca" Center for Liver Disease, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Alessandra Mazzucco
- Thoracic Surgery and Lung Transplant Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Massimo Torre
- Thoracic Surgery Unit, Ospedale Niguarda, Milan, Italy
| | | | | | - Claudio Zavaglia
- Hepatology and Gastroenterology Department, Niguarda Ca' Granda Hospital, Milan, Italy
| | - Marco Schiavon
- Department of Cardiac, Thoracic, Vascular Sciences and Public Health, Padua University Hospital, Padua, Italy
| | - Giovanni Comacchio
- Department of Cardiac, Thoracic, Vascular Sciences and Public Health, Padua University Hospital, Padua, Italy
| | - Federico Rea
- Department of Cardiac, Thoracic, Vascular Sciences and Public Health, Padua University Hospital, Padua, Italy
| | - Riccardo Boetto
- Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplantation, Padua University Hospital, Padua, Italy
| | - Umberto Cillo
- Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplantation, Padua University Hospital, Padua, Italy
| | - Daniele Dondossola
- HBP Surgery and Liver Transplantation Unit, Fondazione IRCCS Ca' Granda Maggiore Hospital, University of Milan, Milan, Italy
| | - Luciano De Carlis
- Department of General Surgery and Transplantation, Niguarda Ca' Granda Hospital, Milan, Italy
| | - Pietro Lampertico
- Division of Gastroenterology and Hepatology, CRC "A. M. and A. Migliavacca" Center for Liver Disease, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.,University of Milan, Milan, Italy
| | - Mario Nosotti
- Thoracic Surgery and Lung Transplant Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.,Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Paolo Mendogni
- Thoracic Surgery and Lung Transplant Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
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Yang H, Liu HS, Hou W, Gao JX, Duan Y, Wei D, Gong XQ, Wang HJ, Wu XL, Chang J. An NIR-responsive mesoporous silica nanosystem for synergetic photothermal-immunoenhancement therapy of hepatocellular carcinoma. J Mater Chem B 2019; 8:251-259. [PMID: 31799596 DOI: 10.1039/c9tb01891c] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
To create a more precise, efficient imaging and therapeutic strategy is a big challenge for the current treatment of hepatocellular carcinoma (HCC). Photothermal therapy (PTT) has attracted enormous attention due to its non-invasive property and precise spatial and temporal control. Here, we developed a strategy to realize superior imaging performance and treatment, utilizing an indocyanine green (ICG) and sorafenib (S) co-loaded mesoporous silica nanosystem for synergetic PTT/immuno-enhanced therapy. We proved that (ICG+S)@mSiO2 could be easily endocytosed by H22 cells, carried out outstanding real-time fluorescence imaging, and enhanced cytotoxicity abilities by near-infrared radiation (NIR) in vitro. Moreover, (ICG+S)@mSiO2 also had excellent fluorescence imaging ability, displayed a remarkable photothermal tumor killing effect and immune enhancement capability under 808 nm irradiation in an H22 tumor-bearing mice model, without apparent adverse effects in other organs. This study provides a new strategy for the development of a PTT/immuno-enhanced synergistic theranostic nanosystem of HCC.
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Affiliation(s)
- Han Yang
- School of Life Sciences, Tianjin University, 92 Weijin Road, Nankai District, Tianjin 300072, P. R. China.
| | - Hong-Sheng Liu
- NHC Key Laboratory of Critical Care Medicine (Tianjin First Central Hospital), Yashi Road, Xiqing District, Tianjin 300072, P. R. China
| | - Wen Hou
- NHC Key Laboratory of Critical Care Medicine (Tianjin First Central Hospital), Yashi Road, Xiqing District, Tianjin 300072, P. R. China
| | - Jun-Xiao Gao
- School of Life Sciences, Tianjin University, 92 Weijin Road, Nankai District, Tianjin 300072, P. R. China.
| | - Yue Duan
- School of Life Sciences, Tianjin University, 92 Weijin Road, Nankai District, Tianjin 300072, P. R. China.
| | - Daohe Wei
- School of Life Sciences, Tianjin University, 92 Weijin Road, Nankai District, Tianjin 300072, P. R. China.
| | - Xiao-Qun Gong
- School of Life Sciences, Tianjin University, 92 Weijin Road, Nankai District, Tianjin 300072, P. R. China.
| | - Han-Jie Wang
- School of Life Sciences, Tianjin University, 92 Weijin Road, Nankai District, Tianjin 300072, P. R. China.
| | - Xiao-Li Wu
- School of Life Sciences, Tianjin University, 92 Weijin Road, Nankai District, Tianjin 300072, P. R. China.
| | - Jin Chang
- School of Life Sciences, Tianjin University, 92 Weijin Road, Nankai District, Tianjin 300072, P. R. China.
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