|
1
|
Susman S, Santoso B, Makary MS. Locoregional Therapies for Hepatocellular Carcinoma in Patients with Nonalcoholic Fatty Liver Disease. Biomedicines 2024; 12:2226. [PMID: 39457538 PMCID: PMC11504147 DOI: 10.3390/biomedicines12102226] [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: 09/01/2024] [Revised: 09/17/2024] [Accepted: 09/23/2024] [Indexed: 10/28/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide with an average five-year survival rate in the US of 19.6%. With the advent of HBV and HCV treatment and prevention, along with the rising rates of obesity, nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome are set to overtake infectious causes as the most common cause of HCC. While surgical resection and transplantation can be curative when amenable, the disease is most commonly unresectable on presentation, and other treatment approaches are the mainstay of therapy. In these patients, locoregional therapies have evolved as a vital tool in both palliation for advanced disease and as a bridge to surgical resection and transplantation. In this review, we will be exploring the primary locoregional therapies for HCC in patients with NAFLD, including transarterial chemoembolization (TACE), bland transarterial embolization (TAE), transarterial radioembolization (TARE), and percutaneous ablation.
Collapse
Affiliation(s)
- Stephen Susman
- Department of Radiology, Yale University Medical Center, New Haven, CT 06510, USA
| | - Breanna Santoso
- Heritage College of Osteopathic Medicine, Ohio University, Dublin, OH 43016, USA
| | - Mina S. Makary
- Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH 43202, USA
| |
Collapse
|
|
2
|
Gu XY, Huo JL, Yu ZY, Jiang JC, Xu YX, Zhao LJ. Immunotherapy in hepatocellular carcinoma: an overview of immune checkpoint inhibitors, drug resistance, and adverse effects. ONCOLOGIE 2024; 26:9-25. [DOI: 10.1515/oncologie-2023-0412] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Abstract
Hepatocellular carcinoma (HCC) is a concerning liver cancer with rising incidence and mortality rates worldwide. The effectiveness of traditional therapies in managing advanced HCC is limited, necessitating the development of new therapeutic strategies. Immune checkpoint inhibitors (ICIs) have emerged as a promising strategy for HCC management. By preventing tumor cells from evading immune surveillance through immunological checkpoints, ICIs can restore the immune system’s ability to target and eliminate tumors. While ICIs show promise in enhancing the immune response against malignancies, challenges such as drug resistance and adverse reactions hinder their efficacy. To address these challenges, developing individualized ICI treatment strategies is critical. Combining targeted therapy and immunotherapy holds the potential for comprehensive therapeutic effects. Additionally, biomarker-based individualized ICI treatment strategies offer promise in predicting treatment response and guiding personalized patient care. Future research should explore emerging ICI treatment methods to optimize HCC immunotherapy. This review provides an overview of ICIs as a new treatment for HCC, demonstrating some success in promoting the tumor immune response. However, drug resistance and adverse reactions remain important considerations that must be addressed. As tailored treatment plans evolve, the prospect of immunotherapy for HCC is expected to grow, offering new opportunities for improved patient outcomes.
Collapse
Affiliation(s)
- Xuan-Yu Gu
- Department of General Surgery , Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University , Zunyi , China
| | - Jin-Long Huo
- Department of General Surgery , Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University , Zunyi , China
| | - Zhi-Yong Yu
- Department of General Surgery , Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University , Zunyi , China
| | - Ji-Chang Jiang
- Department of General Surgery , Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University , Zunyi , China
| | - Ya-Xuan Xu
- Department of General Surgery , Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University , Zunyi , China
| | - Li-Jin Zhao
- Department of General Surgery , Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University , Zunyi , China
| |
Collapse
|
|
3
|
Shuyun W, Lin F, Pan C, Zhang Q, Tao H, Fan M, Xu L, Kong KV, Chen Y, Lin D, Feng S. Laser tweezer Raman spectroscopy combined with deep neural networks for identification of liver cancer cells. Talanta 2023; 264:124753. [PMID: 37290333 DOI: 10.1016/j.talanta.2023.124753] [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: 02/28/2023] [Revised: 05/25/2023] [Accepted: 05/28/2023] [Indexed: 06/10/2023]
Abstract
Rapid identification of cancer cells is crucial for clinical treatment guidance. Laser tweezer Raman spectroscopy (LTRS) that provides biochemical characteristics of cells can be used to identify cell phenotypes through classification models in a non-invasive and label-free manner. However, traditional classification methods require extensive reference databases and clinical experience, which is challenging when sampling at inaccessible locations. Here, we describe a classification method combing LTRS with deep neural network (DNN) for differential and discriminative analysis of multiple liver cancer (LC) cells. By using LTRS, we obtained high-quality single-cell Raman spectra of normal hepatocytes (HL-7702) and liver cancer cell lines (SMMC-7721, Hep3B, HepG2, SK-Hep1 and Huh7). The tentative assignment of Raman peaks indicated that arginine content was elevated and phenylalanine, glutathione and glutamate content was decreased in liver cancer cells. Subsequently, we randomly selected 300 spectra from each cell line for DNN model analysis, achieving a mean accuracy of 99.2%, a mean sensitivity of 99.2% and a mean specificity of 99.8% for the identification and classification of multiple LC cells and hepatocyte cells. These results demonstrate the combination of LTRS and DNN is a promising method for rapid and accurate cancer cell identification at single cell level.
Collapse
Affiliation(s)
- Weng Shuyun
- Key Laboratory of Optoelectronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory of Photonics Technology, Fujian Normal University, Fuzhou, Fujian, 350117, China
| | - Fengjie Lin
- Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital Fuzhou, Fuzhou, 3500014, China
| | - Changbin Pan
- Key Laboratory of Optoelectronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory of Photonics Technology, Fujian Normal University, Fuzhou, Fujian, 350117, China
| | - Qiyi Zhang
- Key Laboratory of Optoelectronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory of Photonics Technology, Fujian Normal University, Fuzhou, Fujian, 350117, China
| | - Hong Tao
- Key Laboratory of Optoelectronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory of Photonics Technology, Fujian Normal University, Fuzhou, Fujian, 350117, China
| | - Min Fan
- Key Laboratory of Optoelectronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory of Photonics Technology, Fujian Normal University, Fuzhou, Fujian, 350117, China
| | - Luyun Xu
- Key Laboratory of Optoelectronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory of Photonics Technology, Fujian Normal University, Fuzhou, Fujian, 350117, China
| | - Kien Voon Kong
- Department of Chemistry, National Taiwan University, Taipei, Taiwan
| | - Yuanmei Chen
- Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital Fuzhou, Fuzhou, 3500014, China
| | - Duo Lin
- Key Laboratory of Optoelectronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory of Photonics Technology, Fujian Normal University, Fuzhou, Fujian, 350117, China.
| | - Shangyuan Feng
- Key Laboratory of Optoelectronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory of Photonics Technology, Fujian Normal University, Fuzhou, Fujian, 350117, China.
| |
Collapse
|
|
4
|
Lalisang ANL, Zacharia NJ, Jamtani I, Marbun VMG, Jeo WS, Lalisang TJM. Pedunculated hepatocellular carcinoma masquerading as a giant GIST: A case report. Int J Surg Case Rep 2023; 105:108102. [PMID: 37028187 PMCID: PMC10106485 DOI: 10.1016/j.ijscr.2023.108102] [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: 01/03/2023] [Revised: 03/24/2023] [Accepted: 03/24/2023] [Indexed: 04/03/2023] Open
Abstract
INTRODUCTION AND IMPORTANCE Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies in Indonesia and is well-known as a silent killer disease due to its mortality rate among males. Furthermore, a pedunculated HCC (P-HCC) is a rare subtype challenging to diagnose when presented as an extrahepatic mass. CASE PRESENTATION A 61-year-old man was admitted to our hospital due to abdominal pain with a palpable mass in the left upper abdomen after being referred from secondary health care. The laboratory results revealed values within normal ranges, except for reactive anti-HCV and anemia, with no evidence of liver abnormalities. CT scan detected a solid mass with a necrotic center and calcified component in the upper left hemiabdomen originating from the submucosa of the greater curvature of the stomach, which were suggestive of gastrointestinal stromal tumor (GIST). It was approximately 12.9 × 10.9 × 18.6 cm sized, multilobulated, well-defined, and infiltrating the splenic vein. CLINICAL DISCUSSION We did a laparotomy and resections consist of distal gastrectomy, liver metastasectomy (segment 2-3), distal pancreatectomy, and splenectomy. Our operative findings were still suggestive of neoplasm of the stomach, most likely a GIST. However, our histological examination revealed a moderate-poorly differentiated liver cell carcinoma, confirmed with immunohistochemical analysis. He was discharged on the seventh day after the operation without any complications. CONCLUSION This case illustrates challenges in diagnosing and treating a rare pedunculated hepatocellular carcinoma.
Collapse
Affiliation(s)
- Arnetta N L Lalisang
- Faculty of Medicine Universitas Indonesia, dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia; Division of Digestive Surgery, Department of Surgery, Faculty of Medicine Universitas Indonesia, dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia.
| | - Nathaniel J Zacharia
- Faculty of Medicine Universitas Indonesia, dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
| | - Indah Jamtani
- Faculty of Medicine Universitas Indonesia, dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia; Division of Digestive Surgery, Department of Surgery, Faculty of Medicine Universitas Indonesia, dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
| | - Vania M G Marbun
- Faculty of Medicine Universitas Indonesia, dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia; Division of Digestive Surgery, Department of Surgery, Faculty of Medicine Universitas Indonesia, dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
| | - Wifanto Saditya Jeo
- Faculty of Medicine Universitas Indonesia, dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia; Division of Digestive Surgery, Department of Surgery, Faculty of Medicine Universitas Indonesia, dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
| | - Toar Jean Maurice Lalisang
- Faculty of Medicine Universitas Indonesia, dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia; Division of Digestive Surgery, Department of Surgery, Faculty of Medicine Universitas Indonesia, dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
| |
Collapse
|
|
5
|
Lee AJL, Wu AGR, Yew KC, Shelat VG. Does size matter for resection of giant versus non-giant hepatocellular carcinoma? A meta-analysis. World J Gastrointest Surg 2023; 15:273-286. [PMID: 36896301 PMCID: PMC9988639 DOI: 10.4240/wjgs.v15.i2.273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 11/19/2022] [Accepted: 02/01/2023] [Indexed: 02/27/2023] Open
Abstract
BACKGROUND Research on long-term survival after resection of giant (≥ 10 cm) and non-giant hepatocellular carcinoma (HCC) (< 10 cm) has produced conflicting results. AIM This study aimed to investigate whether oncological outcomes and safety profiles of resection differ between giant and non-giant HCC. METHODS PubMed, MEDLINE, EMBASE, and Cochrane databases were searched. Studies designed to investigate the outcomes of giant vs non-giant HCC were included. The primary endpoints were overall survival (OS) and disease-free survival (DFS). The secondary endpoints were postoperative complications and mortality rates. All studies were assessed for bias using the Newcastle-Ottawa Scale. RESULTS 24 retrospective cohort studies involving 23747 patients (giant = 3326; non-giant = 20421) who underwent HCC resection were included. OS was reported in 24 studies, DFS in 17 studies, 30-d mortality rate in 18 studies, postoperative complications in 15 studies, and post-hepatectomy liver failure (PHLF) in six studies. The HR was significantly lower for non-giant HCC in both OS (HR 0.53, 95%CI: 0.50-0.55, P < 0.001) and DFS (HR 0.62, 95%CI: 0.58-0.84, P < 0.001). No significant difference was found for 30-d mortality rate (OR 0.73, 95%CI: 0.50-1.08, P = 0.116), postoperative complications (OR 0.81, 95%CI: 0.62-1.06, P = 0.140), and PHLF (OR 0.81, 95%CI: 0.62-1.06, P = 0.140). CONCLUSION Resection of giant HCC is associated with poorer long-term outcomes. The safety profile of resection was similar in both groups; however, this may have been confounded by reporting bias. HCC staging systems should account for the size differences.
Collapse
Affiliation(s)
- Aaron JL Lee
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
| | - Andrew GR Wu
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
| | - Kuo Chao Yew
- Department of Gastroenterology and Hepatology, Tan Tock Seng Hospital, Singapore 308433, Singapore
| | - Vishal G Shelat
- Department of Hepato-Pancreatico-Biliary Surgery, Tan Tok Seng Hospital, Singapore 308433, Singapore
| |
Collapse
|
|
6
|
Cui Y, Yun T, Zhao GG. Bioinformatics analysis of clinical significance of STMN1 gene in prognosis and immune infiltration in hepatocellular carcinoma. Shijie Huaren Xiaohua Zazhi 2022; 30:411-419. [DOI: 10.11569/wcjd.v30.i9.411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND STMN1 (stathmin1), a member of the microtubule destabilizing protein family, is transcriptionally repressed by the functional tumor suppressor protein p53. STMN1 was first identified as a cellular phosphorylated protein overexpressed in leukemia in 1983. STMN1 was found to be upregulated in a variety of cancers, such as non-small cell lung cancer, breast cancer, and gastric cancer, and it can induce cell differentiation, proliferation, and migration in solid tumors and is associated with a poor clinical prognosis. However, the role and mechanism of STMN1 in hepatocellular carcinoma remain unclear.
AIM To assess the expression of STMN1 gene in hepatocellular carcinoma and its relationship with the clinical characteristics and prognosis of patients, and to explore the molecular mechanism of STMN1 gene in this malignancy.
METHODS Clinical information and high-throughput RNA-sequencing data of hepatocellular carcinoma patients were downloaded from The Cancer Genome Atlas (https://portal.gdc.cancer.gov, TCGA) database. R (v3.6.2) software was used to analyze the expression of STMN1 gene in hepatocellular carcinoma tissues, and its relationship with clinical characteristics of patients was analyzed. Univariate and multivariate Cox regression models were used to analyze the prognostic value of STMN1 in hepatocellular carcinoma. Gene enrichment analysis was used to analyze STMN1 expression-related pathway mechanisms. ssGSEA method was used to analyze the infiltration of 24 immune cell types in tumors, and to explore the relationship between STMN1 and immune cells.
RESULTS STMN1 was highly expressed in tumor tissues (P < 0.001). The diagnostic value of STMN1 was assessed by ROC curve analysis, and the area under the ROC curve (AUC) was 0.971. The predictive ability of STMN1 had high accuracy. Chi-square test or Fisher exact test revealed that STMN1 expression was significantly associated with overall survival rate (P = 0.013), T stage (P = 0.002), TNM stage (P = 0.008), age (P = 0.006), and tumor grade (P < 0.001). The overall survival rate, progression-free survival rate, and disease-specific survival rate of the high STMN1 gene expression group were lower than those of the low expression group (P < 0.01). Cox regression analysis showed that the high expression of STMN1 was an independent risk factor for the prognosis of patients with hepatocellular carcinoma (hazard ratio = 1.808, 95% confidence interval: 1.288-2.234, P = 0.014). GSEA analysis showed that STMN1 gene in hepatocellular carcinoma is mainly involved in cell cycle, oocyte meiosis, T cell receptor signaling pathway, natural killer cell-mediated cytotoxicity, and spliceosome. Immune infiltration analysis showed that STMN1 expression was positively correlated with helper T cells 2, follicular helper T cells, and helper T cells, and was negatively correlated with neutrophils, helper T cells 17, and dendritic cells.
CONCLUSION The expression of STMN1 gene is up-regulated in hepato-cellular carcinoma, which is associated with a poor prognosis of patients. It is an independent prognostic factor for hepatocellular carcinoma patients and is expected to become a potential molecular marker of this malignancy.
Collapse
Affiliation(s)
- Yu Cui
- Department of General Surgery, The Fifth Central Hospital of Tianjin, Tianjin 300450, China
| | - Tao Yun
- Department of General Surgery, The Fifth Central Hospital of Tianjin, Tianjin 300450, China
| | - Guo-Gang Zhao
- Department of General Surgery, The Fifth Central Hospital of Tianjin, Tianjin 300450, China
| |
Collapse
|
|
7
|
Hong SK, Lee KW, Lee S, Hong SY, Suh S, Han ES, Choi Y, Yi NJ, Suh KS. Impact of tumor size on hepatectomy outcomes in hepatocellular carcinoma: a nationwide propensity score matching analysis. Ann Surg Treat Res 2022; 102:193-204. [PMID: 35475226 PMCID: PMC9010965 DOI: 10.4174/astr.2022.102.4.193] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 02/19/2022] [Accepted: 02/22/2022] [Indexed: 11/30/2022] Open
Abstract
Purpose The aim of this study was to compare surgical outcomes after liver resection for hepatocellular carcinoma (HCC) according to tumor size using a large, nationwide cancer registry-based cohort and propensity score matching. Methods From 2008 to 2015, a total of 12,139 patients were diagnosed with liver cancer and registered in the Korean Primary Liver Cancer Registry. Patients without distant metastasis who underwent hepatectomy as a primary treatment were selected. We performed 1:1 propensity score matching between the small (<5 cm), large (≥5 cm and <10 cm), and huge (≥10 cm) groups. Results Overall, 265 patients in the small and large groups were compared, and 64 patients each in the large and huge groups were compared. The overall and progression-free survival rates were significantly lower in the large group than in the small group (P < 0.001 and P < 0.001, respectively). Overall survival tended to be poorer in the huge group than in the large group (P = 0.051). The progression-free survival rate was significantly lower in the huge group than in the large group (P = 0.002). Conclusion Although primary liver resection can be considered even in patients with huge HCC, greater caution with careful screening for recurrence is needed.
Collapse
Affiliation(s)
- Suk Kyun Hong
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Sola Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Su young Hong
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Sanggyun Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Eui Soo Han
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| |
Collapse
|
|
8
|
Song J, Zhou H, Gu D, Xu Y. Hepatocellular Carcinoma Differentiation: Research Progress in Mechanism and Treatment. Front Oncol 2022; 11:790358. [PMID: 35096588 PMCID: PMC8790246 DOI: 10.3389/fonc.2021.790358] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 12/20/2021] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. Although progress has been made in diagnosis and treatment, morbidity and mortality continue to rise. Chronic liver disease and liver cirrhosis are still the most important risk factors for liver cancer. Although there are many treatments, it can only be cured by orthotopic liver transplantation (OLT) or surgical resection. And the worse the degree of differentiation, the worse the prognosis of patients with liver cancer. Then it can be considered that restoring a better state of differentiation may improve the prognosis. The differentiation treatment of liver cancer is to reverse the dedifferentiation process of hepatocytes to liver cancer cells by means of drugs, improve the differentiation state of the tumor, and restore the normal liver characteristics, so as to improve the prognosis. Understanding the mechanism of dedifferentiation of liver cancer can provide ideas for drug design. Liver enrichment of transcription factors, imbalance of signal pathway and changes of tumor microenvironment can promote the occurrence and development of liver cancer, and restoring its normal level can inhibit the malignant behavior of tumor. At present, some drugs have been proved to be effective, but more clinical data are needed to support the effectiveness and reliability of drugs. The differentiation treatment of liver cancer is expected to become an important part of the treatment of liver cancer in the future.
Collapse
Affiliation(s)
- Jianning Song
- Department of Clinical Laboratory, Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen University, Shenzhen, China.,Guangzhou Medical University, Shenzhen, China
| | - Hongzhong Zhou
- Department of Clinical Laboratory, Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen University, Shenzhen, China.,Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
| | - Dayong Gu
- Department of Clinical Laboratory, Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen University, Shenzhen, China
| | - Yong Xu
- Department of Clinical Laboratory, Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen University, Shenzhen, China.,Guangzhou Medical University, Shenzhen, China
| |
Collapse
|
|
9
|
Samant H, Amiri HS, Zibari GB. Addressing the worldwide hepatocellular carcinoma: epidemiology, prevention and management. J Gastrointest Oncol 2021; 12:S361-S373. [PMID: 34422400 PMCID: PMC8343080 DOI: 10.21037/jgo.2020.02.08] [Citation(s) in RCA: 113] [Impact Index Per Article: 28.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2019] [Accepted: 01/22/2020] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world with rising incidence. Globally, there has been substantial variation in prevalence of risk factors for HCC over years, like control of viral hepatitis in developing countries but growing epidemic of fatty liver disease in developed world. Changing epidemiology of HCC is related to trends in these risk factors. HCC remains asymptomatic until it is very advanced which makes early detection by surveillance important in reducing HCC related mortality. Management of HCC. depends on stage of the tumor and severity of underlying liver disease. At present, resection and transplant are still the best curative options for small HCC, but recent advances in locoregional therapy and molecular targeted systemic therapy has changed the management for HCC at intermediate and advanced stages. This review is overview of global epidemiology, prevention, surveillance and emerging therapies for hepatocellular carcinoma.
Collapse
Affiliation(s)
- Hrishikesh Samant
- Division of Gastroenterology and Hepatology, LSU Health Science Center, Shreveport, LA, USA
| | - Hosein Shokouh Amiri
- John C McDonald Transplant Center, Willis Knighton Health System, Shreveport, LA, USA
| | - Gazi B. Zibari
- John C McDonald Transplant Center, Willis Knighton Health System, Shreveport, LA, USA
| |
Collapse
|
|
10
|
Han Y, Zhi WH, Xu F, Zhang CB, Huang XQ, Luo JF. Selection of first-line systemic therapies for advanced hepatocellular carcinoma: A network meta-analysis of randomized controlled trials. World J Gastroenterol 2021; 27:2415-2433. [PMID: 34040331 PMCID: PMC8130040 DOI: 10.3748/wjg.v27.i19.2415] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 03/10/2021] [Accepted: 04/21/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The majority of clinical trials of first-line systemic treatments for hepatocellular carcinoma (HCC) used placebo or sorafenib as comparators, and there are limited data providing a cross comparison of treatments in this setting, especially for newly-approved immune checkpoint inhibitor and vascular endothelial growth factor inhibitor combination treatments. AIM To systematically review and compare response rates, survival outcomes, and safety of first-line systemic therapies for advanced hepatocellular carcinoma. METHODS We searched PubMed, Science Direct, the Cochrane Database, Excerpta Medica Database, and abstracts from the American Society of Clinical Oncology 2020 annual congress. Eligible studies were randomized controlled trials of systemic therapy enrolling adults with advanced/unresectable HCC. Risk of bias was assessed with the Cochrane risk of bias tool for randomized controlled trials. A network meta-analysis was used to synthesize data and perform direct and indirect comparisons between treatments. P value, a frequentist analog to the surface under the cumulative ranking curve, was used to rank treatments. RESULTS In total, 1398 articles were screened and 27 included. Treatments compared were atezolizumab plus bevacizumab, brivanib, donafenib, dovitinib, FOLFOX4, lenvatinib, linifanib, nintedanib, nivolumab, sorafenib, sunitinib, vandetanib, 11 sorafenib combination therapies, and three other combination therapies. For overall response rate, lenvatinib ranked 1/19, followed by atezolizumab plus bevacizumab and nivolumab. For progression-free survival (PFS), atezolizumab + bevacizumab was ranked 1/15, followed by lenvatinib. With the exception of atezolizumab + bevacizumab [hazard ratios (HR)PFS = 0.90; 95% confidence interval (CI): 0.64-1.25], the estimated HRs for PFS for all included treatments vs lenvatinib were > 1; however, the associated 95%CI passed through unity for bevacizumab plus erlotinib, linifanib, and FOLFOX4. For overall survival, atezolizumab plus bevacizumab was ranked 1/25, followed by vandetanib 100 mg/d and donafinib, with lenvatinib ranked 6/25. Atezolizumab + bevacizumab was associated with a lower risk of death vs lenvatinib (HRos = 0.63; 95%CI: 0.44-0.89), while the HR for overall survival for most other treatments vs lenvatinib had associated 95%CIs that passed through unity. Vandetanib 300 mg/d and 100 mg/d were ranked 1/13 and 2/13, respectively, for the lowest incidence of treatment terminations due to adverse events, followed by sorafenib (5/13), lenvatinib (10/13), and atezolizumab + bevacizumab (13/13). CONCLUSION There is not one single first-line treatment for advanced HCC associated with superior outcomes across all outcome measurements. Therefore, first-line systemic treatment should be selected based on individualized treatment goals.
Collapse
Affiliation(s)
- Yue Han
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Wei-Hua Zhi
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Fei Xu
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Chen-Bo Zhang
- Department of Biostatistics, School of Public Health, Fudan University, Shanghai 200034, China
| | - Xiao-Qian Huang
- Department of Biostatistics, School of Public Health, Fudan University, Shanghai 200034, China
| | - Jian-Feng Luo
- Department of Biostatistics, School of Public Health, Fudan University, Shanghai 200034, China
| |
Collapse
|
|
11
|
Omer DM, Dozier J, Cao Z, Zhu H, McCain DA. A case report on a large, peduncular intra-abdominal hepatocellular carcinoma extending into the retroperitoneum. Clin Case Rep 2021; 9:1288-1291. [PMID: 33768828 PMCID: PMC7981764 DOI: 10.1002/ccr3.3751] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2020] [Revised: 10/11/2020] [Accepted: 10/13/2020] [Indexed: 11/18/2022] Open
Abstract
Here, we discuss a relatively uncommon presentation of a hepatocellular carcinoma and discuss its preoperative planning and surgical intervention required to reach complete resection.
Collapse
Affiliation(s)
- Dana M. Omer
- Hackensack University Medical CenterHackensackNJUSA
| | | | - Zongxian Cao
- Hackensack University Medical CenterHackensackNJUSA
| | - Hongfa Zhu
- Hackensack University Medical CenterHackensackNJUSA
| | | |
Collapse
|
|
12
|
Karahaliloglu Z, Kilicay E, Hazer B. PLinaS-g-PEG coated magnetic nanoparticles as a contrast agent for hepatocellular carcinoma diagnosis. JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION 2020; 31:1580-1603. [PMID: 32460649 DOI: 10.1080/09205063.2020.1764183] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Among many different types of fabricated nanoparticles, magnetic iron oxide nanoparticles (MNPs) have unique physical and chemical properties and have been widely used due to theirs enhanced permeability and retention effect for biomedical applications. The incorporated theranostic MNPs into biopolymer coatings are currently particular interest to investigators in the fields of nanobiomedicine because of efficiently delivering of various drugs, genes and providing imaging properties. Hepatocellular carcinoma (HCC) is the most prevalent reason of cancer-related deaths, makes it one of the worst malignant tumors in the world. Because, there is a lack of effective treatment methods for HCC, aforementioned magnetic carrier technology with recent innovations could be a promising tool in HCC diagnosis and treatment. Therefore, this study proposes a novel fatty-acid-based polymeric magnetic nanoprobe for diagnosis of hepatocellular tumors using polyethylene glycol (PEG)-terminated polystyrene (PS)-linoleic copolymer coated magnetic iron oxide nanoparticles. MNPs were synthesized by a co-precipitation method and were subsequently coated with a copolymer containing PEG group as termini. Fifty-nanometer-sized MNPs were incorporated into the core of PLinaS-g-PEG nanoparticles. The morphology and size distribution of the bare and magnetic PLinaS-g-PEG were determined by transmission electron microscopy (TEM), and dynamic light scattering (DLS), respectively. MTT and flow cytometry assays showed that PLinaS-g-PEG MNPs demonstrated ultrasentive apoptotic behavior against cancerous cell line, i.e. HepG2 in the culture plate when the fatty acid-containing polymer coated MNPs showed no adverse effect on L929 cell growth. The localization, and accumulation in hepatocytes of PLinaS-g-PEG MNPs without specific targeting ligand was confirmed by fluorescence and confocal microscopy. Therefore, PLinaS-g-PEG MNPs may be potentially used as a unique candidate for diagnosis of hepatocellular carcinomas.
Collapse
Affiliation(s)
| | - Ebru Kilicay
- Vocational High School of Eldivan Health Care Services, Karatekin University, Cankiri, Turkey
| | - Baki Hazer
- Department of Aircraft Airframe Engine Maintenance, Kapadokya University, Nevşehir, Turkey.,Department of Chemistry, Bülent Ecevit University, Zonguldak, Turkey.,Department of Nanotechnology Engineering, Bülent Ecevit University, Zonguldak, Turkey
| |
Collapse
|
|
13
|
Health economic evaluation of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma: a systematic review. COST EFFECTIVENESS AND RESOURCE ALLOCATION 2020; 18:1. [PMID: 31938024 PMCID: PMC6954573 DOI: 10.1186/s12962-019-0198-z] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Accepted: 12/30/2019] [Indexed: 02/07/2023] Open
Abstract
Stereotactic body radiotherapy (SBRT) is a novel noninvasive treatment for hepatocellular carcinoma. SBRT can achieve effective local control, but it requires a relatively high input of resources; this systematic review was performed to assess the cost effectiveness of SBRT in the treatment of hepatocellular carcinoma to provide a basis for government pricing and medical insurance decision-making. The PubMed, EMBASE, Cochrane Library, CNKI, Wanfang and SinoMed databases were searched to collect economic evaluations of SBRT for the treatment of hepatocellular carcinoma from the date of database inception through December 31, 2018. Two reviewers independently screened the studies, extracted the data and performed a descriptive analysis of the basic characteristics, methods of economic evaluation and main results, as well as the quality and heterogeneity of the reports. A total of 5 studies were included. Among them, the level of heterogeneity was relatively acceptable, with a median score of 90%. Four studies were cost-utility analyses (CUAs), and 1 was a cost-effectiveness analysis (CEA). The incremental cost effectiveness ratio (ICER) for sorafenib compared to SBRT was US $114,795 per quality-adjusted life year gained (cost/QALY) in patients with advanced hepatocellular carcinoma. The ICER for proton beam therapy compared to SBRT was US $6465 in patients with inoperable advanced hepatocellular carcinoma. The ICER for SBRT compared to RFA was US $164,660 for patients with unresectable colorectal cancer (CRC) with liver metastases and US $56,301 for patients with early-stage hepatocellular carcinoma. For patients with inoperable localized hepatocellular carcinoma, compared with RFA–SBRT therapy, the ICERs for SBRT–SBRT and SBRT–RFA were US $558,679 and US $2197,000, respectively; RFA–RFA was dominated. In conclusion, there is limited evidence suggesting that SBRT could be cost-effective for highly specific subpopulations of HCC patients, and further economic evaluations based on randomized controlled trials (RCTs) or cohort studies are needed.
Collapse
|
|
14
|
Fang Q, Xie QS, Chen JM, Shan SL, Xie K, Geng XP, Liu FB. Long-term outcomes after hepatectomy of huge hepatocellular carcinoma: A single-center experience in China. Hepatobiliary Pancreat Dis Int 2019; 18:532-537. [PMID: 31543313 DOI: 10.1016/j.hbpd.2019.09.001] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Accepted: 08/26/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Currently, hepatectomy remains the first-line therapy for hepatocellular carcinoma (HCC). However, surgery for patients with huge (>10 cm) HCCs is controversial. This retrospective study aimed to explore long-term survival after hepatectomy for patients with huge HCC. METHODS The records of 188 patients with pathologically confirmed HCC who underwent curative hepatectomy between 2007 and 2017 were reviewed; patients were divided into three groups according to tumor size: huge (>10 cm; n = 84), large (5-10 cm; n = 51) and small (<5 cm; n = 53) HCC. Kaplan-Meier analysis was used to assess overall survival (OS) and disease-free survival (DFS), and log-rank analysis was performed for pairwise comparisons among the three groups. Risk factors for survival and recurrence were analyzed using the Cox proportional hazard model. RESULTS The median follow-up period was 20 months. Although the prognosis of small HCC was better than that of huge and large HCC, OS and DFS were not significantly different between huge and large HCC (P = 0.099 and P = 0.831, respectively). A family history of HCC, poor Child-Pugh class, vascular invasion, diolame, pathologically positive margins, and operative time ≥240 min were identified as independent risk factors for OS and DFS in a multivariate model. Tumor size (>10 cm) had significant effect on OS, and postoperative antiviral therapy and postoperative complications also had significant effects on DFS. CONCLUSIONS Huge HCC is not a contraindication of hepatectomy. Although most of these patients experienced recurrence after surgery, OS and DFS were not significantly different from those of patients with large HCC after resection.
Collapse
Affiliation(s)
- Qiang Fang
- Division of General Surgery, First Affiliated Hospital, Anhui Medical University, Hefei 230022, China
| | - Qing-Song Xie
- Division of General Surgery, First Affiliated Hospital, Anhui Medical University, Hefei 230022, China
| | - Jiang-Ming Chen
- Division of General Surgery, First Affiliated Hospital, Anhui Medical University, Hefei 230022, China
| | - Shen-Liang Shan
- Division of General Surgery, First Affiliated Hospital, Anhui Medical University, Hefei 230022, China
| | - Kun Xie
- Division of General Surgery, First Affiliated Hospital, Anhui Medical University, Hefei 230022, China
| | - Xiao-Ping Geng
- Division of General Surgery, First Affiliated Hospital, Anhui Medical University, Hefei 230022, China
| | - Fu-Bao Liu
- Division of General Surgery, First Affiliated Hospital, Anhui Medical University, Hefei 230022, China.
| |
Collapse
|
|
15
|
Prognostic Factors and Survival Outcomes of Surgical Resection of Huge Hepatocellular Carcinomas. J Gastrointest Cancer 2019; 51:250-253. [PMID: 31054105 DOI: 10.1007/s12029-019-00240-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
INTRODUCTION The aim of the study was to analyze the various prognostic factors that influence survival and clinical outcomes in patients undergoing liver resection for huge hepatocellular carcinomas. MATERIALS AND METHODS The records of patients who underwent curative surgery between 1991 and 2011 for huge hepatocellular carcinoma were analyzed. Various prognostic factors that influenced the survival were studied. The patients were followed up till November 2016. RESULTS The number of patients who underwent liver resection with huge hepatocellular carcinoma during the study period was 17; this included 14 males and 3 females. The median age of the study population was 52 years. The median serum AFP in the study population was 132.3 ng/ml (range 2 to 187,000 ng/ml). 41.2% of the patients were hepatitis B positive. The overall morbidity was 6%. The mortality rate was nil. The mean size of the resected specimen was 13.9 cm ± 3.6 cm. The overall recurrence rate was 76.5%. The local recurrence rate was 29.4%. The median time to recurrence was 8 months. The 5-year disease-free survival and overall survival of the study group were 26% and 32%, respectively. The factors that predicted an adverse survival outcome after the log-rank test for univariate analysis using life-table method were presence of lymphovascular invasion (p = 0.047), age ≤ 55 years (p = 0.021), and raised serum AFP (p = 0.041). CONCLUSION The factors that predict an adverse outcome after surgery in patients with huge hepatocellular carcinomas were the presence of lymphovascular invasion, raised serum AFP, and age ≤ 55 years.
Collapse
|
|
16
|
Gans JH, Lipman J, Golowa Y, Kinkhabwala M, Kaubisch A. Hepatic Cancers Overview: Surgical and Chemotherapeutic Options, How Do Y-90 Microspheres Fit in? Semin Nucl Med 2019; 49:170-181. [DOI: 10.1053/j.semnuclmed.2019.01.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
|
|
17
|
miR-330-5p targets SPRY2 to promote hepatocellular carcinoma progression via MAPK/ERK signaling. Oncogenesis 2018; 7:90. [PMID: 30464168 PMCID: PMC6249243 DOI: 10.1038/s41389-018-0097-8] [Citation(s) in RCA: 63] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Revised: 09/24/2018] [Accepted: 10/18/2018] [Indexed: 12/03/2022] Open
Abstract
MicroRNAs (miRNAs) have been identified as critical modulators of cell proliferation and growth, which are the major causes of cancer progression including hepatocellular carcinoma (HCC). Our previous miRNA microarray data have shown that miR-330-5p was always upregulated in HCC. However, the accurate role of miR-330-5p in HCC is still uncertain. Here, we report that miR-330-5p expression is upregulated in HCC tissues and cell lines, and is associated with tumor size, tumor nodule number, capsule formation and Tumor Node Metastasis (TNM) stage in HCC patients. Overexpression of miR-330-5p promotes proliferation and growth of HCC cells in vitro and in vivo, while miR-330-5p knockdown has the inverse effect. Moreover, using miRNA databases and dual luciferase report assay, we find miR-330-5p directly binds to the 3′-untranslated region (3′-UTR) of Sprouty2 (SPRY2). Then we find the novel biofunctional role of SPRY2 inactivation in promoting HCC progression. Finally, we confirm that miR-330-5p suppresses SPRY2 to promote proliferation via mitogen-activated protein kinases (MAPK)/extracellular regulated kinase (ERK) signaling in HCC. Taken together, our findings demonstrate the critical role of miR-330-5p in promoting HCC progression via targeting SPRY2 to activate MAPK/ERK signaling, which may provide a novel and promising prognostic marker and therapeutic target for HCC.
Collapse
|
|
18
|
Kamarajah SK. Fibrosis score impacts survival following resection for hepatocellular carcinoma (HCC): A Surveillance, End Results and Epidemiology (SEER) database analysis. Asian J Surg 2018; 41:551-561. [DOI: 10.1016/j.asjsur.2018.01.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2017] [Revised: 11/03/2017] [Accepted: 01/08/2018] [Indexed: 02/09/2023] Open
|
|
19
|
Chen G, Zhang J, Sun J, Wei S, Chen J, Ren H, Zhou S. Revisiting Partial Hepatectomy of Large Hepatocellular Carcinoma in Older Patients. Sci Rep 2018; 8:14505. [PMID: 30266965 PMCID: PMC6162215 DOI: 10.1038/s41598-018-32798-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Accepted: 09/03/2018] [Indexed: 12/18/2022] Open
Abstract
Hepatectomy of large hepatocellular carcinomas (>10 cm) in over 70 year-old patients is presumed futile. We retrospectively reviewed 5970 patients with liver tumors Jan 2010 through Dec 2016 in our institute, of them, 37 older patients with large hepatocellular carcinomas staged I-III and Child-Pugh A liver functions receiving conservative treatments (conservative group, n = 37) and 16 older patients with large hepatocellular carcinomas staged I- III who underwent partial hepatectomy (resection group, n = 16) were included, the risk factors for poor survival were analyzed by univariate and multivariate analyses. Compared with the conservative treatments, Partial hepatectomy achieved better median survival time (25.5 months versus 11 months, log-rank = 0.0001) and better median performance status (1 versus 3, p = 0.023), there was different in Charlson comorbidity index (p = 0.019). For the conservative group, the 3-month, 1, 2, 3-year survival rate was 78.4%, 43.2%, 5.4%, 0%; for the resection group, The 3-month, 1, 2, 3-year survival rate was 100%, 93.7.2%, 56.3%, 12.5%; Multivariate Cox regression analysis showed the Charlson comorbidity index and the performance status associated with poor outcomes of those patients (p = 0.001, 0.018, respectively). Resections of large hepatocellular carcinomas in older patients can be performed safely to prolong life expectancy and improve life quality with or without cancer recurrence.
Collapse
Affiliation(s)
- Guoyong Chen
- Section 5 of Hepatopancreaticobiliary Surgery, Henan Provincial People's Hospital, Zhengzhou, Henan, 450003, China
| | - Jiabin Zhang
- Center of Hepatopancreaticobiliary Surgery and liver transplantation, 302 Hospital, Beijing, 100039, China
| | - Jianjun Sun
- Section 5 of Hepatopancreaticobiliary Surgery, Henan Provincial People's Hospital, Zhengzhou, Henan, 450003, China
| | - Sidong Wei
- Section 5 of Hepatopancreaticobiliary Surgery, Henan Provincial People's Hospital, Zhengzhou, Henan, 450003, China
| | - Jianbin Chen
- Section 5 of Hepatopancreaticobiliary Surgery, Henan Provincial People's Hospital, Zhengzhou, Henan, 450003, China
| | - Hui Ren
- Center of Hepatopancreaticobiliary Surgery and liver transplantation, 302 Hospital, Beijing, 100039, China.
| | - Shaotang Zhou
- Section 5 of Hepatopancreaticobiliary Surgery, Henan Provincial People's Hospital, Zhengzhou, Henan, 450003, China.
| |
Collapse
|
|
20
|
Koh YX, Tan HL, Lye WK, Kam JH, Chiow AKH, Tan SS, Choo SP, Chung AYF, Goh BKP. Systematic review of the outcomes of surgical resection for intermediate and advanced Barcelona Clinic Liver Cancer stage hepatocellular carcinoma: A critical appraisal of the evidence. World J Hepatol 2018; 10:433-447. [PMID: 29988922 PMCID: PMC6033716 DOI: 10.4254/wjh.v10.i6.433] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Revised: 02/10/2018] [Accepted: 03/03/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To perform a systematic review to determine the survival outcomes after curative resection of intermediate and advanced hepatocellular carcinomas (HCC). METHODS A systematic review of the published literature was performed using the PubMed database from 1st January 1999 to 31st Dec 2014 to identify studies that reported outcomes of liver resection as the primary curative treatment for Barcelona Clinic Liver Cancer (BCLC) stage B or C HCC. The primary end point was to determine the overall survival (OS) and disease free survival (DFS) of liver resection of HCC in BCLC stage B or C in patients with adequate liver reserve (i.e., Child's A or B status). The secondary end points were to assess the morbidity and mortality of liver resection in large HCC (defined as lesions larger than 10 cm in diameter) and to compare the OS and DFS after surgical resection of solitary vs multifocal HCC. RESULTS We identified 74 articles which met the inclusion criteria and were analyzed in this systematic review. Analysis of the resection outcomes of the included studies were grouped according to (1) BCLC stage B or C HCC, (2) Size of HCC and (3) multifocal tumors. The median 5-year OS of BCLC stage B was 38.7% (range 10.0-57.0); while the median 5-year OS of BCLC stage C was 20.0% (range 0.0-42.0). The collective median 5-year OS of both stages was 27.9% (0.0-57.0). In examining the morbidity and mortality following liver resection in large HCC, the pooled RR for morbidity [RR (95%CI) = 1.00 (0.76-1.31)] and mortality [RR (95%CI) = 1.15 (0.73-1.80)] were not significant. Within the spectrum of BCLC B and C lesions, tumors greater than 10 cm were reported to have median 5-year OS of 33.0% and multifocal lesions 54.0%. CONCLUSION Indication for surgical resection should be extended to BCLC stage B lesions in selected patients. Further studies are needed to stratify stage C lesions for resection.
Collapse
Affiliation(s)
- Ye Xin Koh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore 169608, Singapore.
| | - Hwee Leong Tan
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore 169608, Singapore
| | - Weng Kit Lye
- Center for Quantitative Medicine, Duke-NUS Graduate Medical School, Singapore 169857, Singapore
| | - Juinn Huar Kam
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore 169608, Singapore
| | - Adrian Kah Heng Chiow
- Department of General Surgery, Hepatopancreatobiliary Service, Changi General Hospital, Singapore 529889, Singapore
| | - Siong San Tan
- Department of General Surgery, Hepatopancreatobiliary Service, Changi General Hospital, Singapore 529889, Singapore
| | - Su Pin Choo
- Department of Medical Oncology, National Cancer Centre Singapore, Singapore 169610, Singapore
| | - Alexander Yaw Fui Chung
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore 169608, Singapore
| | - Brian Kim Poh Goh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore 169608, Singapore
| |
Collapse
|
|
21
|
Abstract
Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. In select patients, surgical treatment in the form of either resection or transplantation offers a curative option. The aims of this review are to (1) review the current American Association for the Study of Liver Diseases/European Association for the Study of the Liver guidelines on the surgical management of HCC and (2) review the proposed changes to these guidelines and analyze the strength of evidence underlying these proposals. Three authors identified the most relevant publications in the literature on liver resection and transplantation for HCC and analyzed the strength of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification. In the United States, the liver allocation system provides priority for liver transplantation to patients with HCC within the Milan criteria. Current evidence suggests that liver transplantation may also be indicated in certain patient groups beyond Milan criteria, such as pediatric patients with large tumor burden or adult patients who are successfully downstaged. Patients with no underlying liver disease may also benefit from liver transplantation if the HCC is unresectable. In patients with no or minimal (compensated) liver disease and solitary HCC ≥2 cm, liver resection is warranted. If liver transplantation is not available or contraindicated, liver resection can be offered to patients with multinodular HCC, provided that the underlying liver disease is not decompensated. Many patients may benefit from surgical strategies adapted to local resources and policies (hepatitis B prevalence, organ availability, etc). Although current low-quality evidence shows better overall survival with aggressive surgical strategies, this approach is limited to select patients. Larger and well-designed prospective studies are needed to better define the benefits and limits of such approach.
Collapse
Affiliation(s)
- Daniel Zamora-Valdes
- 1 Divisions of Transplantation Surgery, William J. von Liebig Transplant Center, Mayo Clinic, Rochester, MN, USA
| | - Timucin Taner
- 1 Divisions of Transplantation Surgery, William J. von Liebig Transplant Center, Mayo Clinic, Rochester, MN, USA
| | | |
Collapse
|
|
22
|
Zainal N, Hasbullah HH. Prolonged survival of metastatic hepatocellular carcinoma: a case report. J Gastrointest Oncol 2018; 9:E6-E8. [PMID: 29755781 DOI: 10.21037/jgo.2018.01.04] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
Management of hepatocellular carcinoma (HCC) generally follows EASL-EORTC clinical practise guideline. We report a case of a 50-year-old man who had multinodular HCC with lung metastases, whose management had deviated from the standard guideline but still survive 5 years after initial diagnosis.
Collapse
Affiliation(s)
- Nadiah Zainal
- Oncology and Radiotherapy, Hospital Kuala Lumpur, Malaysia
| | | |
Collapse
|
|
23
|
Lu J, Wang J, Ling D. Surface Engineering of Nanoparticles for Targeted Delivery to Hepatocellular Carcinoma. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2018; 14:1702037. [PMID: 29251419 DOI: 10.1002/smll.201702037] [Citation(s) in RCA: 61] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/15/2017] [Revised: 10/24/2017] [Indexed: 05/20/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-associated deaths worldwide. There is a lack of efficient therapy for HCC; the only available first-line systemic drug, sorafenib, can merely improve the average survival by two months. Among the efforts to develop an efficient therapy for HCC, nanomedicine has drawn the most attention, owing to its unique features such as high drug-loading capacity, intrinsic anticancer activities, integrated diagnostic and therapeutic functionalities, and easy surface engineering with targeting ligands. Despite its tremendous advantages, no nanomedicine can be effective unless it successfully targets the tumor site, which is a challenging task. In this review, the features of HCC are described, and the physiological hurdles that prevent nanoparticles from targeting HCC are discussed. Then, the surface physicochemical factors of nanoparticles that can influence targeting efficiency are discussed. Finally, a thorough description of the physiological barriers that nanomedicine must conquer before uptake by HCC cells if possible is provided, as well as the surface engineering approaches to nanomedicine to achieve targeted delivery to HCC cells. The physiological hurdles and corresponding solutions summarized in this review provide a general guide for the rational design of HCC targeting nanomedicine systems.
Collapse
Affiliation(s)
- Jingxiong Lu
- Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, and Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, 310058, China
| | - Jin Wang
- Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, and Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, 310058, China
| | - Daishun Ling
- Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, and Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, 310058, China
| |
Collapse
|
|
24
|
Wang L, Liu Z, Liu X, Zeng Y, Liu J. The hepatectomy efficacy of huge hepatocellular carcinoma and its risk factors: A meta analysis. Medicine (Baltimore) 2017; 96:e9226. [PMID: 29384907 PMCID: PMC6392948 DOI: 10.1097/md.0000000000009226] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2017] [Revised: 11/04/2017] [Accepted: 11/21/2017] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND There has always been a controversy on the hepatectomy for huge hepatocellular carcinoma (HCC). Therefore, we aim to explore the hepatectomy efficacy of huge HCC and its risk factors. METHODS A systematic research was performed using PubMed, MedLine, Web of Knowledge, and Cochrane Library from their establishment to August 2017. The major endpoints were overall survival (OS) rate and recurrence-free survival (RFS) rate, and the secondary ones were the morbidity of complications and mortality of hepatectomy. RESULTS About 13 studies with a total of 7609 patients were included in this meta-analysis. The hepatectomy efficacy of huge HCC was inferior to non-huge HCC both in OS (hazard ratio [HR] = 2.18, 95% confidence interval [CI] = 1.90-2.50, P < .00001; I = 66%, P = .003) and RFS (HR = 1.97, 95% CI = 1.76-2.19, P < .00001; I = 74%, P = .0001). However, the risk difference[RD] of the 1-year, 3-year and 5-year OS tended to be acceptable (RD = -0.05, 95% CI = -0.11-0.00, P = .05; RD = -0.13, 95% CI = -0.21--0.05, P = .002; RD = -0.10, 95% CI = -0.19--0.01, P = .03; respectively). Moreover, there were also no significant differences between huge HCC and non-huge HCC in the morbidity of complication and mortality of hepatectomy (RD = 0.07, 95% CI = -0.09-0.23, P = .38; RD = -0.01, 95% CI = -0.00--0.03, P = .06; respectively). Related risk factors were measured to explore the differences, and the results showed that the level of alpha fetal protein (AFP) and the margin-positive rate were higher (standard mean difference [SMD] = 0.57, 95% CI = 0.26-0.88, P = .0003; odd radio[OR] = 32.52, 95% CI = 1.02-6.22, P = .04; respectively), the characteristic of huge HCC tended to be worse such as lower clinical or pathological stage, incomplete capsule and incorporate satellite metastases (OR = 2.91, 95% CI = 1.68-5.04, P = .001; OR = 3.99, 95% CI = 3.40-4.67, P < .00001; OR = 2.52, 95% CI = 1.66-3.83, P < .0001; respectively), and the rate of micorvascular invasion (MVI) including portal vein tumor thrombus (PVTT) were higher (OR = 3.36, 95% CI = 1.61-7.02, P = .001; OR = 2.75, 95% CI = 2.29-3.31, P < .00001; respectively) in the huge HCC. CONCLUSION The hepatectomy efficacy of huge HCC was inferior to non-huge HCC, but its survival benefits and feasibility were confirmed in this meta-analysis. In addition, higher level of AFP, positive margin, lower clinical or pathological stage, incomplete capsule, incorporate satellite metastasis and MVI were significantly correlated with poor OS.
Collapse
Affiliation(s)
- Lei Wang
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University
- The Liver Center of Fujian Province, Fujian Medical University
| | - Zhiqiang Liu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University
- The Liver Center of Fujian Province, Fujian Medical University
| | - Xiaolong Liu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University
- The Liver Center of Fujian Province, Fujian Medical University
| | - Yongyi Zeng
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University
- The Liver Center of Fujian Province, Fujian Medical University
| | - Jingfeng Liu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University
- The Liver Center of Fujian Province, Fujian Medical University
- Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, P. R. China
| |
Collapse
|
|
25
|
Ettorre GM, Levi Sandri GB, Colasanti M, Mascianà G, de Werra E, Santoro R, Lepiane P, Montalbano M, Antonini M, Vennarecci G. Liver resection for hepatocellular carcinoma ≥5 cm. Transl Gastroenterol Hepatol 2017; 2:22. [PMID: 28447057 PMCID: PMC5388623 DOI: 10.21037/tgh.2017.03.13] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2017] [Accepted: 03/10/2017] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Management of hepatocellular carcinoma (HCC) larger than 5 cm is still debated. The aim of our study was to compare morbidity and mortality after the surgical resection of HCC according to the nodule size. METHODS Since 2001, 429 liver resections for HCC were performed in our institution. We divided the cohort into two groups, 88 patients in group 1 patients with HCC diameter from 5 to 10 cm and 39 patients in group 2 with HCC diameter ≥10 cm. RESULTS In 30.7% of cases in the first group and in 35.9% of cases in the second group the HCC grew into a healthy liver. A major liver resection was performed in 36.3% of cases in group 1 vs. 66.6% in group 2 (P=0.001). In two cases for the first group and in ten cases in the second group a laparoscopic approach was performed. Median operative time was higher in group 2 (P=0.001). The median post-operative hospital stay was similar in the two groups (P=0.897). The post-operative morbidity was not different between the two groups (P=0.595). CONCLUSIONS The tumour size does not contraindicate a surgical resection of HCC even in patient with HCC ≥10 cm.
Collapse
Affiliation(s)
- Giuseppe Maria Ettorre
- Division of General Surgery and Liver Transplantation, S. Camillo Hospital, Rome, Lazio, Italy
| | | | - Marco Colasanti
- Division of General Surgery and Liver Transplantation, S. Camillo Hospital, Rome, Lazio, Italy
| | - Gianluca Mascianà
- Division of General Surgery and Liver Transplantation, S. Camillo Hospital, Rome, Lazio, Italy
| | - Edoardo de Werra
- Division of General Surgery and Liver Transplantation, S. Camillo Hospital, Rome, Lazio, Italy
| | - Roberto Santoro
- Division of General Surgery and Liver Transplantation, S. Camillo Hospital, Rome, Lazio, Italy
| | - Pasquale Lepiane
- Division of General Surgery and Liver Transplantation, S. Camillo Hospital, Rome, Lazio, Italy
| | - Marzia Montalbano
- Hepatology and Infectious Diseases Unit, National Institute for Infectious Disease “L. Spallanzani”, Rome, Italy
| | - Mario Antonini
- Anesthesiology and Intensive Care Unit, National Institute for Infectious Disease “L. Spallanzani”, Rome, Italy
| | - Giovanni Vennarecci
- Division of General Surgery and Liver Transplantation, S. Camillo Hospital, Rome, Lazio, Italy
| |
Collapse
|
|
26
|
|
|
27
|
Zhong JH, Torzilli G, Xing H, Li C, Han J, Liang L, Zhang H, Dai SY, Li LQ, Shen F, Yang T. Controversies and evidence of hepatic resection for hepatocellular carcinoma. BBA CLINICAL 2016; 6:125-130. [PMID: 27761414 PMCID: PMC5067978 DOI: 10.1016/j.bbacli.2016.10.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/13/2016] [Revised: 10/06/2016] [Accepted: 10/10/2016] [Indexed: 02/07/2023]
Abstract
Symptoms of early hepatocellular carcinoma (HCC) often go unnoticed, so more than half of patients with primary HCC are diagnosed after their disease has already reached an intermediate or advanced stage, or after portal hypertension has appeared. While hepatic resection is widely recognized as a first-line therapy to treat very early or early HCC, its use in treating intermediate or advanced HCC or HCC involving portal hypertension remains controversial. Here we review PubMed-indexed literature covering the use of hepatic resection for such patients. The available evidence strongly suggests that, as a result of improvements in surgical techniques and perioperative care, hepatic resection can benefit many patients with intermediate or advanced HCC or with HCC associated with portal hypertension.
Collapse
Affiliation(s)
- Jian-Hong Zhong
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Guido Torzilli
- Department of Surgery, Division of Hepatobiliary and General Surgery, Humanitas University, Humanitas Research Hospital-IRCCS, Rozzano, Milan, Italy
| | - Hao Xing
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Chao Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jun Han
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Lei Liang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Han Zhang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Shu-Yang Dai
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Le-Qun Li
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Tian Yang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| |
Collapse
|
|
28
|
Balogh J, Victor D, Asham EH, Burroughs SG, Boktour M, Saharia A, Li X, Ghobrial RM, Monsour HP. Hepatocellular carcinoma: a review. J Hepatocell Carcinoma 2016; 3:41-53. [PMID: 27785449 PMCID: PMC5063561 DOI: 10.2147/jhc.s61146] [Citation(s) in RCA: 798] [Impact Index Per Article: 88.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is a leading cause of cancer-related death worldwide. In the United States, HCC is the ninth leading cause of cancer deaths. Despite advances in prevention techniques, screening, and new technologies in both diagnosis and treatment, incidence and mortality continue to rise. Cirrhosis remains the most important risk factor for the development of HCC regardless of etiology. Hepatitis B and C are independent risk factors for the development of cirrhosis. Alcohol consumption remains an important additional risk factor in the United States as alcohol abuse is five times higher than hepatitis C. Diagnosis is confirmed without pathologic confirmation. Screening includes both radiologic tests, such as ultrasound, computerized tomography, and magnetic resonance imaging, and serological markers such as α-fetoprotein at 6-month intervals. Multiple treatment modalities exist; however, only orthotopic liver transplantation (OLT) or surgical resection is curative. OLT is available for patients who meet or are downstaged into the Milan or University of San Francisco criteria. Additional treatment modalities include transarterial chemoembolization, radiofrequency ablation, microwave ablation, percutaneous ethanol injection, cryoablation, radiation therapy, systemic chemotherapy, and molecularly targeted therapies. Selection of a treatment modality is based on tumor size, location, extrahepatic spread, and underlying liver function. HCC is an aggressive cancer that occurs in the setting of cirrhosis and commonly presents in advanced stages. HCC can be prevented if there are appropriate measures taken, including hepatitis B virus vaccination, universal screening of blood products, use of safe injection practices, treatment and education of alcoholics and intravenous drug users, and initiation of antiviral therapy. Continued improvement in both surgical and nonsurgical approaches has demonstrated significant benefits in overall survival. While OLT remains the only curative surgical procedure, the shortage of available organs precludes this therapy for many patients with HCC.
Collapse
Affiliation(s)
- Julius Balogh
- Sherrie and Alan Conover Center for Liver Disease and Transplantation
- Division of Transplantation, Department of Surgery
| | - David Victor
- Sherrie and Alan Conover Center for Liver Disease and Transplantation
- Department of Gastroenterology and Transplant Hepatology
- Department of Medicine, Houston Methodist Hospital, Houston, TX, USA
| | - Emad H Asham
- Sherrie and Alan Conover Center for Liver Disease and Transplantation
- Division of Transplantation, Department of Surgery
| | - Sherilyn Gordon Burroughs
- Sherrie and Alan Conover Center for Liver Disease and Transplantation
- Division of Transplantation, Department of Surgery
| | - Maha Boktour
- Sherrie and Alan Conover Center for Liver Disease and Transplantation
- Division of Transplantation, Department of Surgery
| | - Ashish Saharia
- Sherrie and Alan Conover Center for Liver Disease and Transplantation
- Division of Transplantation, Department of Surgery
| | - Xian Li
- Sherrie and Alan Conover Center for Liver Disease and Transplantation
- Division of Transplantation, Department of Surgery
| | - R Mark Ghobrial
- Sherrie and Alan Conover Center for Liver Disease and Transplantation
- Division of Transplantation, Department of Surgery
| | - Howard P Monsour
- Sherrie and Alan Conover Center for Liver Disease and Transplantation
- Department of Gastroenterology and Transplant Hepatology
- Department of Medicine, Houston Methodist Hospital, Houston, TX, USA
| |
Collapse
|
|
29
|
Chang YJ, Chung KP, Chang YJ, Chen LJ. Long-term survival of patients undergoing liver resection for very large hepatocellular carcinomas. Br J Surg 2016; 103:1513-20. [PMID: 27550624 DOI: 10.1002/bjs.10196] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2015] [Revised: 03/08/2016] [Accepted: 03/16/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND This study aimed to assess long-term survival after liver resection for huge hepatocellular carcinoma (HCC). METHODS Patients with stage I-III HCC who underwent hepatectomy from 2002 to 2010 were identified retrospectively from prospective national databases and followed until December 2012. Patients were assigned into four groups according to tumour size: less than 3·0 cm (small), 3·0-4·9 cm (medium), 5·0-10·0 cm (large) and over 10·0 cm (huge). The primary endpoint was overall survival. The Kaplan-Meier method and Cox proportional hazards model were used for survival analysis. RESULTS A total of 11 079 patients with HCC (mean(s.d.) age 59·7 (12·0) years) were eligible for this study. Median follow-up was 72·5 months. Patients with huge HCC had the worst prognosis; overall survival rates for patients with small, medium, large and huge HCC were 72·0, 62·1, 50·8 and 35·0 per cent respectively at 5 years, and 52·6, 41·8, 35·8 and less than 20·0 per cent at 10 years (P < 0·001). Multivariable analysis showed that tumour size affected long-term survival (hazard ratio (HR) 1·31, 1·55 and 2·38 for medium, large and huge HCC respectively versus small HCC). Prognostic factors for huge HCC were surgical margin larger than 0·2 cm (HR 0·70; P = 0·025), poor differentiation (HR 1·34; P = 0·004), multiple tumours (HR 1·64; P < 0·001), vascular invasion (HR 1·52; P = 0·008), cirrhosis (HR 1·37; P = 0·013) and the use of nucleoside analogues (HR 0·69; P = 0·004). CONCLUSION Huge HCCs have a worse prognosis than smaller HCCs after liver resection. A wide resection margin and antiviral therapy with nucleoside analogues may be associated with favourable long-term survival.
Collapse
Affiliation(s)
- Y J Chang
- Department of General Surgery, National Taiwan University Hospital, Taipei, Taiwan.,Department of General Surgery, Zhong-Xing Branch, Taipei City Hospital, Taipei, Taiwan
| | - K P Chung
- Graduate Institute of Health Policy and Management, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Y J Chang
- Department of Surgery, Taipei Branch, Buddhist Tzu Chi General Hospital, Taipei, Taiwan.,School of Medicine, Buddhist Tzu Chi University, Hualien, Taiwan
| | - L J Chen
- Graduate Institute of Health Policy and Management, College of Public Health, National Taiwan University, Taipei, Taiwan. .,Department of Ophthalmology, Heping Fuyou Branch, Taipei City Hospital, Taipei, Taiwan.
| |
Collapse
|
|
30
|
Glantzounis GK, Tokidis E, Basourakos SP, Ntzani EE, Lianos GD, Pentheroudakis G. The role of portal vein embolization in the surgical management of primary hepatobiliary cancers. A systematic review. Eur J Surg Oncol 2016; 43:32-41. [PMID: 27283892 DOI: 10.1016/j.ejso.2016.05.026] [Citation(s) in RCA: 88] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2016] [Revised: 05/17/2016] [Accepted: 05/23/2016] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Primary liver and biliary cancers are very aggressive tumors. Surgical treatment is the main option for cure or long term survival. The main purpose of this systematic review is to underline the indications for portal vein embolization (PVE), in patients with inadequate future liver remnant (FLR) and to analyze other parameters such as resection rate, morbidity, mortality, survival after PVE and hepatectomy for primary hepatobiliary tumors. Also the role of trans-arterial chemoembolization (TACE) before PVE, is investigated. METHODS A systematic search of the literature was performed in Pub Med and the Cochrane Library from 01.01.1990 to 30.09.2015. RESULTS Forty articles were selected, including 2144 patients with a median age of 61 years. The median excision rate was 90% for hepatocellular carcinomas (HCCs) and 86% for hilar cholangiocarcinomas (HCs). The main indications for PVE in patients with HCC and presence of liver fibrosis or cirrhosis was FLR <40% when liver function was good (ICGR15 < 10%) and FLR < 50% when liver function was affected (ICGR15:10-20%). The combination of TACE and PVE increased hypertrophy rate and was associated with better overall survival and disease free survival and should be considered in advanced HCC tumors with inadequate FLR. In patients with HCs PVE was performed, after preoperative biliary drainage, when FLR was <40%, in the majority of studies, with very good post-operative outcome. However indications should be refined. CONCLUSION PVE before major hepatectomy allows resection in a patient group with advanced primary hepato-biliary tumors and inadequate FLR, with good long term survival.
Collapse
Affiliation(s)
- G K Glantzounis
- Department of Surgery, School of Medicine, University of Ioannina, Ioannina, Greece.
| | - E Tokidis
- Department of Surgery, School of Medicine, University of Ioannina, Ioannina, Greece
| | - S-P Basourakos
- Department of Surgery, School of Medicine, University of Ioannina, Ioannina, Greece
| | - E E Ntzani
- Evidence-based Medicine Unit, Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece
| | - G D Lianos
- Department of Surgery, School of Medicine, University of Ioannina, Ioannina, Greece
| | - G Pentheroudakis
- Department of Medical Oncology, School of Medicine, University of Ioannina, Ioannina, Greece
| |
Collapse
|
|
31
|
Guo R, Feng X, Xiao S, Yan J, Xia F, Ma K, Li X. Short- and long-term outcomes of hepatectomy with or without radiofrequency-assist for the treatment of hepatocellular carcinomas: a retrospective comparative cohort study. Biosci Trends 2015; 9:65-72. [PMID: 25787911 DOI: 10.5582/bst.2014.01142] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
The objective of this study was to compare the short- and long-term outcomes of radiofrequency-assisted liver resection (RFLR) and conventional clamp-crushing liver resection (CCLR) and to evaluate the safety and efficiency of RFLR. Between January 2008 and December 2012, a total of 597 patients with hepatocellular carcinoma (HCC) who underwent curative hepatectomy were identified. A total of 272 patients underwent RFLR, and 325 patients received CCLR. The short- and long-term outcomes were compared. The patients in the RFLR and CCLR groups showed similar baseline characteristics. The RFLR group showed less intraoperative blood loss (485.5 vs. 763.2 mL, p = 0.003), a lower transfusion requirement rate (19.1 vs. 31.7%, p ≤ 0.01), shorter surgery duration (211 vs. 296 min, p ≤ 0.01) and a lower vascular inflow occlusion rate (25.7 vs. 33.8%, p = 0.032). No significant postoperative changes in bilirubin or liver enzymes were observed in the two groups. The degree of postoperative complications and morbidity did not significantly differ between the two groups. There were no significant differences in the 1-, 2- and 3-year overall survival rates (73.8%, 58.5%, and 55.7% vs. 80.8%, 65.8%, and 56.2%, respectively) or disease-free rates (51.9%, 47.2%, and 46.0% vs. 54.5%, 44.9%, and 38.5%, respectively) between the RFLR and CCLR groups. These results suggested RFLR was a safe and efficient method for patients with HCC. RFLR was associated with decreased blood loss, fewer blood transfusions, shorter surgery times and less vascular inflow occlusion application. The RFLR group did not show increased liver injury or postoperative morbidity or mortality.
Collapse
Affiliation(s)
- Rui Guo
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University
| | | | | | | | | | | | | |
Collapse
|
|
32
|
Zhang TT, Zhao XQ, Liu Z, Mao ZY, Bai L. Factors affecting the recurrence and survival of hepatocellular carcinoma after hepatectomy: a retrospective study of 601 Chinese patients. Clin Transl Oncol 2015; 18:831-40. [PMID: 26577107 DOI: 10.1007/s12094-015-1446-0] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2015] [Accepted: 11/03/2015] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Indications for resection of hepatocellular carcinoma (HCC) remain controversial. This study aimed to identify prognostic factors that affect overall survival (OS) and disease-free survival (DFS) in patients with HCC after hepatectomy. METHODS From 2004 to 2010, 601 patients with HCC who underwent resection were enrolled. Factors stratified into the host, biochemical, surgical treatment and tumor-related features in terms of recurrence and overall survival were analyzed. Prognostic factors were evaluated by univariate and multivariate analyses, with Kaplan-Meier survival analyses and Cox proportional hazard model. RESULTS The overall survival rates of 1-, 3- and 5- year were 79, 62, and 54 %, and the corresponding DFS rates were 51, 38 and 31 %, respectively. In a multivariate analysis, Child-Pugh, serum AFP level, ALT level, time for hepatic resection, tumor differentiation, maximum size of tumors, local necrosis, portal vein tumor thrombus, and TNM Stage were correlated significantly with patients' OS. Gender (P = 0.046), cigarette smoking (P = 0.007), serum AFP level (P = 0.001), GGT level (P = 0.002), maximum size of tumors (P = 0.009), liver cirrhosis (P = 0.025), portal vein tumor thrombus (P = 0.022), microvascular tumor thrombus (P = 0.007) and TNM Stage (P = 0.001) were significantly affected DFS. CONCLUSION Preoperative AFP level, maximum size of tumors, portal vein tumor thrombus and TNM Stage were revealed as important prognostic factors for OS and DFS through follow-up of a relatively large cohort of Chinese HCC patients.
Collapse
Affiliation(s)
- T T Zhang
- Department of Oncology, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing, 100853, People's Republic of China
| | - X Q Zhao
- Department of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing, People's Republic of China
| | - Z Liu
- Department of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing, People's Republic of China
| | - Z Y Mao
- Department of Oncology, Air Force General Hospital of Chinese PLA, Beijing, People's Republic of China
| | - L Bai
- Department of Oncology, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing, 100853, People's Republic of China.
| |
Collapse
|
|
33
|
Zhu SL, Zhong JH, Ke Y, Ma L, You XM, Li LQ. Efficacy of hepatic resection vs transarterial chemoembolization for solitary huge hepatocellular carcinoma. World J Gastroenterol 2015; 21:9630-9637. [PMID: 26327771 PMCID: PMC4548124 DOI: 10.3748/wjg.v21.i32.9630] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2015] [Revised: 03/29/2015] [Accepted: 07/08/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To compare the efficacy of hepatic resection (HR) and transarterial chemoembolization (TACE) for patients with solitary huge (≥ 10 cm) hepatocellular carcinoma (HCC). METHODS Records were retrospectively analyzed of 247 patients with solitary huge HCC, comprising 180 treated by HR and 67 by TACE. Long-term overall survival (OS) was compared between the two groups using the Kaplan-Meier method, and independent predictors of survival were identified by multivariate analysis. These analyses were performed using all patients in both groups and/or 61 pairs of propensity score-matched patients from the two groups. RESULTS OS at 5 years was significantly higher in the HR group than the TACE group, across all patients (P = 0.002) and across propensity score-matched pairs (36.4% vs 18.2%, P = 0.039). The two groups showed similar postoperative mortality and morbidity. Multivariate analysis identified alpha-fetoprotein ≥ 400 ng/mL, presence of vascular invasion and TACE treatment as independent predictors of poor OS. CONCLUSION Our findings suggest that HR can be safe and more effective than TACE for patients with solitary huge HCC.
Collapse
|
|
34
|
Yang J, Li C, Wen TF, Yan LN, Li B, Wang WT, Yang JY, Xu MQ. Is hepatectomy for huge hepatocellular carcinoma (≥ 10 cm in diameter) safe and effective? A single-center experience. Asian Pac J Cancer Prev 2015; 15:7069-77. [PMID: 25227793 DOI: 10.7314/apjcp.2014.15.17.7069] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND This retrospective study aimed to validate the safety and effectiveness of hepatectomy for huge hepatocellular carcinoma (HCC). MATERIALS AND METHODS Data of patients who underwent hepatectomy for HCC between January 2006 and December 2012 were reviewed. The patients were divided into three groups: huge HCC(≥ 10 cm in diameter), large HCC(≥ 5 but<10 cm in diameter) and small HCC(<5 cm in diameter). RESULTS Characteristics of pre-operative patients in all three groups were homogeneously distributed except for alpha fetal protein (AFP)(p<0.001).The 30, 60, 90-day post-operative mortality rates were not different among the three groups (p=0.785, p=0.560, and p=0.549). Laboratory data at 1, 3, and 7 days after surgery also did not vary. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) rates in the huge and large HCC groups were lower than that of the small HCC group (OS: 32.5% vs 36.3% vs 71.2%, p=0.000; DFS: 20.0% vs 24.8% vs 40.7%, p=0.039), but there was no difference between the huge and large HCC groups (OS: 32.5% vs 36.3%, p=0.667; DFS: 20.0% vs 24.8%, p=0.540). In multivariate analysis, five independent poor prognostic factors that affected OS were significantly associated with worse survival (p<0.05), namely, AFP level, macrovascular invasion, Edmondsone Steiner grade, surgical margin and Ishak score. AFP level, macrovascular invasion, microvascular invasion, and surgical margin influenced disease-free survival independently (p<0.05). CONCLUSIONS The safety of hepatectomy for huge HCC is similar to that for large and small HCC; and this approach for huge HCC may achieve similar long-term survival and disease-free survival as for large HCC.
Collapse
Affiliation(s)
- Jian Yang
- Department of Liver Surgery and Liver Transplantation, West China Hospital, Sichuan University, Chengdu, China E-mail :
| | | | | | | | | | | | | | | |
Collapse
|
|
35
|
Tejeda-Maldonado J, García-Juárez I, Aguirre-Valadez J, González-Aguirre A, Vilatobá-Chapa M, Armengol-Alonso A, Escobar-Penagos F, Torre A, Sánchez-Ávila JF, Carrillo-Pérez DL. Diagnosis and treatment of hepatocellular carcinoma: An update. World J Hepatol 2015; 7:362-376. [PMID: 25848464 PMCID: PMC4381163 DOI: 10.4254/wjh.v7.i3.362] [Citation(s) in RCA: 88] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2014] [Revised: 12/11/2014] [Accepted: 12/31/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignancies leading to high mortality rates in the general population; in cirrhotic patients, it is the primary cause of death. The diagnosis is usually delayed in spite of at-risk population screening recommendations, i.e., patients infected with hepatitis B or C virus. Hepatocarcinogenesis hinges on a great number of genetic and molecular abnormalities that lead to tumor angiogenesis and foster their dissemination potential. The diagnosis is mainly based on imaging studies such as computed tomography and magnetic resonance, in which lesions present a characteristic classical pattern of early arterial enhancement followed by contrast medium “washout” in late venous phase. On occasion, when imaging studies are not conclusive, biopsy of the lesion must be performed to establish the diagnosis. The Barcelona Clinic Liver Cancer staging method is the most frequently used worldwide and recommended by the international guidelines of HCC management. Currently available treatments include tumor resection, liver transplant, sorafenib and loco-regional therapies (alcoholization, radiofrequency ablation, chemoembolization). The prognosis of hepatocarcinoma is determined according to the lesion’s stage and in cirrhotic patients, on residual liver function. Curative treatments, such as liver transplant, are sought in patients diagnosed in early stages; patients in more advanced stages, were not greatly benefitted by chemotherapy in terms of survival until the advent of target molecules such as sorafenib.
Collapse
|
|
36
|
Zhong JH, Rodríguez AC, Ke Y, Wang YY, Wang L, Li LQ. Hepatic resection as a safe and effective treatment for hepatocellular carcinoma involving a single large tumor, multiple tumors, or macrovascular invasion. Medicine (Baltimore) 2015; 94:e396. [PMID: 25621684 PMCID: PMC4602643 DOI: 10.1097/md.0000000000000396] [Citation(s) in RCA: 107] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Revised: 11/25/2014] [Accepted: 11/26/2014] [Indexed: 01/27/2023] Open
Abstract
This systematic review examined whether the available evidence justifies using hepatic resection (HR) during later stages of hepatocellular carcinoma (HCC), which contravenes treatment guidelines but is current practice at many medical centers.Official guidelines and retrospective studies recommend different roles for HR for patients with large/multinodular HCC or with HCC involving macrovascular invasion (MVI).Several databases were systematically searched for studies examining the safety and efficacy of HR for treating HCC involving a single large tumor (>5 cm) or multiple tumors, or for treating HCC involving MVI.We identified 50 studies involving 14, 808 patients that investigated the use of HR to treat large/multinodular HCC, and 24 studies with 4389 patients that investigated HR to treat HCC with MVI. Median in-hospital mortality for patients with either type of HCC was significantly lower in Asian studies (2.7%) than in non-Asian studies (7.3%, P < 0.001). Median overall survival (OS) was significantly higher for all Asian patients with large/multinodular HCC than for all non-Asian patients at both 1 year (81% vs 65%, P < 0.001) and 5 years (42% vs 32%, P < 0.001). Similar results were obtained for median disease-free survival at 1 year (61% vs 50%, P < 0.001) and 5 years (26% vs 24%, P < 0.001). However, median OS was similar for Asian and non-Asian patients with HCC involving MVI at 1 year (50% vs 52%, P = 0.45) and 5 years (18% vs 14%, P = 0.94). There was an upward trend in 5-year OS in patients with either type of HCC.HR is reasonably safe and effective at treating large/multinodular HCC and HCC with MVI. The available evidence argues for expanding the indications for HR in official treatment guidelines.
Collapse
Affiliation(s)
- Jian-Hong Zhong
- From the Department of Hepatobiliary Surgery (J-HZ, ACR, Y-YW, L-QL), Affiliated Tumor Hospital of Guangxi Medical University, Nanning; Department of Research (ACR), Creaducate Enterprises Ltd, Kowloon, Hong Kong; and Department of Hepatobiliary Surgery (YK, LW), The Second Affiliated Hospital of Kunming Medical University, Kunming, PR China
| | | | | | | | | | | |
Collapse
|
|
37
|
Zhang XY, Luo Y, Wen TF, Jiang L, Li C, Zhong XF, Zhang JY, Ling WW, Yan LN, Zeng Y, Wu H. Contrast-enhanced ultrasound: Improving the preoperative staging of hepatocellular carcinoma and guiding individual treatment. World J Gastroenterol 2014; 20:12628-12636. [PMID: 25253968 PMCID: PMC4168101 DOI: 10.3748/wjg.v20.i35.12628] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2014] [Revised: 06/01/2014] [Accepted: 06/14/2014] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the clinical role of contrast-enhanced ultrasound (CEUS) combined with contrast-enhanced computed tomography (CE-CT) or magnetic resonance imaging to improve the preoperative staging of hepatocellular carcinoma (HCC) and guide surgical decision-making. METHODS Sixty-nine patients who underwent liver resection for HCC in our center were enrolled prospectively in the study. CEUS and CE-CT/MRI were performed before surgery. Intraoperative ultrasound (IOUS) was carried out after liver mobilization. Lesions depicted by each imaging modality were counted and mapped. To investigate the impact of tumor size on the study, we divided the patients into two groups, the "Smaller group"(S-group, ≤ 5 cm in diameter) and the "Larger-group" (L-group, > 5 cm in diameter). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of CE-CT/MRI, CEUS, IOUS, CEUS+CE-CT/MRI and the tumor node metastasis staging of tumors were calculated and compared. Changes in the surgical strategy as a result of CEUS and IOUS were analyzed. RESULTS One hundred and twenty-seven nodules, comprising 94 HCCs confirmed by histopathology and 33 benign lesions confirmed by histopathology and follow-up, were identified in 69 patients. The overall diagnostic sensitivity rates of CE-CT/MRI, CEUS, IOUS and CEUS+ CE-CT/MRI were 78.7%, 89.4%, 89.4% and 89.4%, respectively. There was a significant difference between CEUS + CE-CT/MRI and CE-CT/MRI (P = 0.046). Combining CEUS with CT or MRI increased, the diagnostic specificity compared with CT/MRI, CEUS and IOUS, and this difference was statistically significant (100%, 72.7%, 97.0%, and 69.7%, P = 0.004, P = 0.002, P = 0.002, respectively). The diagnostic accuracy was significantly higher for CEUS + CT/MRI compared with CT/MRI (92.1% vs 77.2%, P = 0.001). The TNM staging of tumors based on CEUS + CE-CT/MRI approximated to the final pathological TNM staging (P = 0.977). There was a significant difference in the accuracy of TNM staging when comparing CEUS + CE-CT/MRI with CE-CT/MRI (P = 0.002). Before surgery, strategies were changed in 15.9% (11/69) of patients as a result of CEUS. Finally, only 5.7% (4/69) of surgical strategies were changed because of IOUS findings. In the S-group, CEUS revealed 12 false positive lesions, including seven false positive lesions that were diagnosed by preoperative imaging examinations and five by IOUS. In contrast, in the L-group, IUOS revealed eight new malignant lesions; six of these lesions were true HCCs that were also identified by preoperative CEUS. CONCLUSION CEUS combined with CT or MRI improves the accuracy of preoperative staging for hepatocellular carcinoma and may help to guide individualized treatment for patients with HCC. CEUS may better identify non-malignant lesions in patients with small tumors and discover new malignant lesions in patients with large tumors.
Collapse
|