|
1
|
Madani SP, Mirza-Aghazadeh-Attari M, Mohseni A, Pawlik T, Kamel IR. Diffuse infiltrative hepatocellular carcinoma: Multimodality imaging manifestations. J Surg Oncol 2023; 127:385-393. [PMID: 36374195 DOI: 10.1002/jso.27138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Accepted: 10/23/2022] [Indexed: 11/16/2022]
Abstract
Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer, being the third most common cause of cancer-related death globally. HCC most frequently develops in the context of hepatic cirrhosis. HCC can manifest as various morphologic subtypes. Each pattern exhibits distinct behaviors in terms of imaging features, disease progression, response to therapy, and prognosis. While the nodular pattern is the most frequent subtype, infiltrative HCC is the least prevalent and makes up about 8%-20% of all HCC cases. Infiltrative HCC manifests as small tumor nodules that often spread across the entire liver or across a hepatic segment/lobe and is not identified as a focal tumor. On ultrasonography, infiltrative HCC presents as a markedly heterogeneous area with ill-defined echotexture, making it difficult to distinguish from background hepatic cirrhosis. On magnetic resonance imaging (MRI), infiltrating HCC typically manifests as a mild, poorly defined hepatic region with heterogeneous or homogenous aberrant signal intensity. Specifically, on T1-weighted MRI scans, infiltrating HCC frequently appears as largely hypointense and typically homogenous and mildly to moderately hyperintense on T2-weighted imaging. Infiltrative HCC frequently lacks a clearly defined boundary on cross-sectional imaging and can consequently fade into the background of the cirrhotic liver. As a result, infiltrating HCC is frequently not discovered until an advanced stage and has an associated poor prognosis. Thus, understanding imaging features associated with infiltrative HCC diagnosis is crucial for abdominal radiologists to ensure effective and timely care. We herein review imaging characteristics of infiltrative HCC.
Collapse
Affiliation(s)
- Seyedeh Panid Madani
- Russell H. Morgan Department of Radiology and Radiological Science, School of Medicine, Johns Hopkins Hospital, Johns Hopkins University, Baltimore, Maryland, USA
| | - Mohammad Mirza-Aghazadeh-Attari
- Russell H. Morgan Department of Radiology and Radiological Science, School of Medicine, Johns Hopkins Hospital, Johns Hopkins University, Baltimore, Maryland, USA
| | - Alireza Mohseni
- Russell H. Morgan Department of Radiology and Radiological Science, School of Medicine, Johns Hopkins Hospital, Johns Hopkins University, Baltimore, Maryland, USA
| | - Timothy Pawlik
- Department of Surgery, Wexner Medical Center, The James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA
| | - Ihab R Kamel
- Russell H. Morgan Department of Radiology and Radiological Science, School of Medicine, Johns Hopkins Hospital, Johns Hopkins University, Baltimore, Maryland, USA
| |
Collapse
|
|
2
|
Beumer BR, de Wilde RF, Metselaar HJ, de Man RA, Polak WG, Ijzermans JNM. The Treatment Effect of Liver Transplantation versus Liver Resection for HCC: A Review and Future Perspectives. Cancers (Basel) 2021; 13:cancers13153730. [PMID: 34359629 PMCID: PMC8345205 DOI: 10.3390/cancers13153730] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 07/19/2021] [Accepted: 07/22/2021] [Indexed: 12/17/2022] Open
Abstract
For patients presenting with hepatocellular carcinoma within the Milan criteria, either liver resection or liver transplantation can be performed. However, to what extent either of these treatment options is superior in terms of long-term survival is unknown. Obviously, the comparison of these treatments is complicated by several selection processes. In this article, we comprehensively review the current literature with a focus on factors accounting for selection bias. Thus far, studies that did not perform an intention-to-treat analysis conclude that liver transplantation is superior to liver resection for early-stage hepatocellular carcinoma. In contrast, studies performing an intention-to-treat analysis state that survival is comparable between both modalities. Furthermore, all studies demonstrate that disease-free survival is longer after liver transplantation compared to liver resection. With respect to the latter, implications of recurrences for survival are rarely discussed. Heterogeneous treatment effects and logical inconsistencies indicate that studies with a higher level of evidence are needed to determine if liver transplantation offers a survival benefit over liver resection. However, randomised controlled trials, as the golden standard, are believed to be infeasible. Therefore, we suggest an alternative research design from the causal inference literature. The rationale for a regression discontinuity design that exploits the natural experiment created by the widely adopted Milan criteria will be discussed. In this type of study, the analysis is focused on liver transplantation patients just within the Milan criteria and liver resection patients just outside, hereby ensuring equal distribution of confounders.
Collapse
Affiliation(s)
- Berend R. Beumer
- Department of Surgery Division of HPB & Transplant Surgery, Erasmus MC Transplant Institute, Erasmus MC, University Medical Centre Rotterdam, 3015AA Rotterdam, The Netherlands; (B.R.B.); (R.F.d.W.); (W.G.P.)
| | - Roeland F. de Wilde
- Department of Surgery Division of HPB & Transplant Surgery, Erasmus MC Transplant Institute, Erasmus MC, University Medical Centre Rotterdam, 3015AA Rotterdam, The Netherlands; (B.R.B.); (R.F.d.W.); (W.G.P.)
| | - Herold J. Metselaar
- Department of Gastroenterology and Hepatology, Erasmus MC Transplant Institute, Erasmus MC, University Medical Centre Rotterdam, 3015AA Rotterdam, The Netherlands; (H.J.M.); (R.A.d.M.)
| | - Robert A. de Man
- Department of Gastroenterology and Hepatology, Erasmus MC Transplant Institute, Erasmus MC, University Medical Centre Rotterdam, 3015AA Rotterdam, The Netherlands; (H.J.M.); (R.A.d.M.)
| | - Wojciech G. Polak
- Department of Surgery Division of HPB & Transplant Surgery, Erasmus MC Transplant Institute, Erasmus MC, University Medical Centre Rotterdam, 3015AA Rotterdam, The Netherlands; (B.R.B.); (R.F.d.W.); (W.G.P.)
| | - Jan N. M. Ijzermans
- Department of Surgery Division of HPB & Transplant Surgery, Erasmus MC Transplant Institute, Erasmus MC, University Medical Centre Rotterdam, 3015AA Rotterdam, The Netherlands; (B.R.B.); (R.F.d.W.); (W.G.P.)
- Correspondence: ; Tel.: +31-010-7032396
| |
Collapse
|
|
3
|
Li ZL, Wu H, Wei YP, Zhong Q, Song JC, Yu JJ, Li C, Wang MD, Xu XF, Li JD, Han J, Xing H, Lau WY, Wu MC, Shen F, Yang T. Impact of Surveillance in Chronic Hepatitis B Patients on Long-Term Outcomes After Curative Liver Resection for Hepatocellular Carcinoma. J Gastrointest Surg 2020; 24:1987-1995. [PMID: 31388886 DOI: 10.1007/s11605-019-04295-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2019] [Accepted: 06/03/2019] [Indexed: 01/31/2023]
Abstract
BACKGROUND Clinical guidelines recommend surveillance in high-risk population to early detect hepatocellular carcinoma (HCC), when curative treatment such as liver resection can be applied. However, it is largely unknown whether surveillance would provide long-term survival benefits to these high-risk patients who have received curative liver resection for HCC. METHODS A prospectively maintained database on patients with chronic hepatitis B infection who underwent curative liver resection for HCC from 2003 to 2014 was reviewed. Patients' overall survival and recurrence were compared between the groups of patients whose HCCs were diagnosed by surveillance or non-surveillance, as well as between the groups of patients operated in the first (2003-2008) and second (2009-2014) 6-year periods. RESULTS Of 1075 chronic hepatitis B patients with HCC, 452 (42.0%) patients were diagnosed by preoperative surveillance. Compared with the non-surveillance group, the OS and RFS rates were significantly better in the surveillance group (both P < 0.001). Surveillance was associated with a 55% decrease in the overall survival risk and a 48% decrease in the recurrence risk (HR 0.45, 95% CI 0.38-0.53, and HR 0.52, 95% CI 0.44-0.61). Compared with the first period, a significant reduction of 12% and 19% in the overall death and recurrence risks, respectively, was observed in the second period (HR 0.88, 95% CI 0.78-0.97, and HR 0.81, 95% CI 0.70-0.95). CONCLUSION Surveillance for HCC was associated with favorable long-term overall and recurrence-free survival rates after curative liver resection of HCC in patients with chronic hepatitis B.
Collapse
Affiliation(s)
- Zhen-Li Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No 225, Changhai Road, Shanghai, 200438, China
| | - Han Wu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No 225, Changhai Road, Shanghai, 200438, China
| | - Yong-Peng Wei
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No 225, Changhai Road, Shanghai, 200438, China
| | - Qian Zhong
- Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jin-Chao Song
- Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jiong-Jie Yu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No 225, Changhai Road, Shanghai, 200438, China
| | - Chao Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No 225, Changhai Road, Shanghai, 200438, China
| | - Ming-Da Wang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No 225, Changhai Road, Shanghai, 200438, China
| | - Xin-Fei Xu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No 225, Changhai Road, Shanghai, 200438, China
| | - Ju-Dong Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No 225, Changhai Road, Shanghai, 200438, China
| | - Jun Han
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No 225, Changhai Road, Shanghai, 200438, China
| | - Hao Xing
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No 225, Changhai Road, Shanghai, 200438, China
| | - Wan Yee Lau
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No 225, Changhai Road, Shanghai, 200438, China
- Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, SAR, China
| | - Meng-Chao Wu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No 225, Changhai Road, Shanghai, 200438, China
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No 225, Changhai Road, Shanghai, 200438, China.
| | - Tian Yang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No 225, Changhai Road, Shanghai, 200438, China.
| |
Collapse
|
|
4
|
Meyerovich G, Goykhman Y, Nakache R, Nachmany I, Lahat G, Shibolet O, Menachem Y, Katchman H, Wolf I, Geva R, Klausner JM, Lubezky N. Resection vs Transplant Listing for Hepatocellular Carcinoma: An Intention-to-Treat Analysis. Transplant Proc 2019; 51:1867-1873. [PMID: 31399171 DOI: 10.1016/j.transproceed.2019.02.030] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2018] [Revised: 01/30/2019] [Accepted: 02/18/2019] [Indexed: 01/15/2023]
Abstract
BACKGROUND Liver transplantation (LT) and liver resection (LR) are curative treatment options for patients with hepatocellular carcinoma within the Milan criteria. Severe organ shortage dictates the preference for LR. Our aim was to provide an intention-to-treat retrospective comparison of survival between patients who were placed on waiting lists for LT and those who underwent LR. METHODS The medical records of patients with hepatocellular carcinoma within the Milan criteria treated by LR or listed for LT between 2007 and 2016 were reviewed. We performed intention-to-treat analyses of overall survival and recurrence. RESULTS There were 54 patients on the waiting list for LT, and 30 of them underwent LR. Thirteen of the 54 patients (24%) were not transplanted because of disease-related mortality or tumor progression. The median waiting time to transplantation was 304 days. The 90-day mortality was higher in transplanted patients (9.8% vs 3.3%, P = .003). Intention-to-treat survival was similar for the LT and LR groups (5-year survival, 47.8% vs 55%, respectively, P = .185). There was a trend toward improved 5-year disease-free survival for listed patients (56.2% vs 26.3% for patients undergoing LR, P = .15). CONCLUSION Intention-to-treat survival is similar in patients undergoing LR and those on waiting lists for LT. There is a 24% risk to drop from the transplant list. The higher perioperative mortality among patients undergoing LT is balanced by a higher tumor recurrence rate after LR.
Collapse
Affiliation(s)
- Guy Meyerovich
- Department of Surgery, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Yaacov Goykhman
- Department of Surgery, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Richard Nakache
- Department of Surgery, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Ido Nachmany
- Department of Surgery, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Guy Lahat
- Department of Surgery, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Oren Shibolet
- Institute of Gastroenterology, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Yoram Menachem
- Institute of Gastroenterology, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Helena Katchman
- Institute of Gastroenterology, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Ido Wolf
- Institute of Oncology, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Ravit Geva
- Institute of Oncology, Tel Aviv Medical Center, Tel Aviv, Israel
| | | | - Nir Lubezky
- Department of Surgery, Tel Aviv Medical Center, Tel Aviv, Israel.
| |
Collapse
|
|
5
|
Li ZL, Yan WT, Zhang J, Zhao YJ, Lau WY, Mao XH, Zeng YY, Zhou YH, Gu WM, Wang H, Chen TH, Han J, Xing H, Wu H, Li C, Wang MD, Wu MC, Shen F, Yang T. Identification of Actual 10-Year Survival After Hepatectomy of HBV-Related Hepatocellular Carcinoma: a Multicenter Study. J Gastrointest Surg 2019; 23:288-296. [PMID: 30334177 DOI: 10.1007/s11605-018-4006-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2018] [Accepted: 10/05/2018] [Indexed: 01/31/2023]
Abstract
BACKGROUND Hepatitis B virus (HBV) infection is the leading cause of hepatocellular carcinoma (HCC) worldwide. The aim of the study was to identify the incidence and predictive factors of actual 10-year survival following liver resection of HBV-related HCC. METHODS A Chinese multicenter database of patients undergoing curative hepatectomy of HBV-related HCC was reviewed. Patients who survived ≥ 10 years and patients who died < 10 years after surgery were compared and analyzed. Univariable and multivariable regression analyses were performed to identify predictive factors associated with 10-year survival. RESULTS Among all enrolled 1016 patients, the actuarial 10-year survival rate was 24.1%, while the actual 10-year survival rate was 16.6%. There were 169 patients who survived at least 10 years after surgery and 688 who died within 10 years from surgery. These patients constituted the study population of this study. Multivariable regression analysis revealed that cirrhosis, preoperative HBV viral load > 104 copies/mL, maximum tumor size > 5 cm, multiple tumors, macroscopic and microscopic vascular invasion, postoperative HBV reactivation, and early recurrence (< 2 years after surgery) were independent risk factors associated with actual 10-year survival, while postoperative antiviral therapy, regular recurrence surveillance, and curative treatments for initial recurrence were independent protective factors. CONCLUSIONS The actual 10-year survival after curative resection of HBV-related HCC was calculated to be 16.6%. Postoperative antiviral therapy and regular recurrence surveillance were independent protective factors associated with actual 10-year survival after liver resection of HBV-related HCC.
Collapse
Affiliation(s)
- Zhen-Li Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No. 225, Changhai Road, Shanghai, 200438, China
| | - Wen-Tao Yan
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No. 225, Changhai Road, Shanghai, 200438, China
- Department of Clinical Medicine, Second Military Medical University, Shanghai, China
| | - Jin Zhang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No. 225, Changhai Road, Shanghai, 200438, China
| | - Yi-Jun Zhao
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No. 225, Changhai Road, Shanghai, 200438, China
| | - Wan Yee Lau
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No. 225, Changhai Road, Shanghai, 200438, China
- Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T, Hong Kong SAR
| | - Xian-Hai Mao
- Department of Hepatobiliary Surgery, The People's Hospital of Hunan Province, Changsha, Hunan, China
| | - Yong-Yi Zeng
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital, Fujian Medical University, Fuzhou, Fujian, China
| | - Ya-Hao Zhou
- Department of Hepatobiliary Surgery, Pu'er People's Hospital, Pu'er, Yunnan, China
| | - Wei-Min Gu
- The First Department of General Surgery, The Fourth Hospital of Harbin, Harbin, Heilongjiang, China
| | - Hong Wang
- Department of General Surgery, Liuyang People's Hospital, Liuyang, Hunan, China
| | - Ting-Hao Chen
- Department of General Surgery, Ziyang First People's Hospital, Ziyang, Sichuan, China
| | - Jun Han
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No. 225, Changhai Road, Shanghai, 200438, China
| | - Hao Xing
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No. 225, Changhai Road, Shanghai, 200438, China
| | - Han Wu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No. 225, Changhai Road, Shanghai, 200438, China
| | - Chao Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No. 225, Changhai Road, Shanghai, 200438, China
| | - Ming-Da Wang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No. 225, Changhai Road, Shanghai, 200438, China
| | - Meng-Chao Wu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No. 225, Changhai Road, Shanghai, 200438, China
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No. 225, Changhai Road, Shanghai, 200438, China.
| | - Tian Yang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No. 225, Changhai Road, Shanghai, 200438, China.
| |
Collapse
|
|
6
|
Duan X, Li T, Han X, Ren J, Chen P, Li H, Gong S. The antitumor effect of arsenic trioxide on hepatocellular carcinoma is enhanced by andrographolide. Oncotarget 2017; 8:90905-90915. [PMID: 29207612 PMCID: PMC5710893 DOI: 10.18632/oncotarget.18677] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2017] [Accepted: 06/02/2017] [Indexed: 12/25/2022] Open
Abstract
High concentrations of arsenic trioxide (As2O3) are used to treat acute promyelocytic leukemia and solid tumors, with negative side effects to normal cells. Andrographolide is a traditional Chinese medicine that exerts anti-cancer, anti-inflammatory, anti-virus, and anti-diabetic effects. Here, we tested the effects of combined andrographolide with As2O3 against hepatocellular carcinoma (HCC). We found that by increasing apoptosis, andrographolide synergistically enhanced the anti-tumor effects of As2O3 in HepG2 cells in vitro and in vivo. Furthermore, results from our microarray assays and experiments with mouse xenografts showed that EphB4 was downregulated by the combination of As2O3 plus andrographolide. These findings suggest that the combination of andrographolide and As2O3 could yield therapeutic benefits in the treatment of HCC.
Collapse
Affiliation(s)
- Xuhua Duan
- Department of Interventional Radiology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan Province, People's Republic of China
| | - Tengfei Li
- Department of Interventional Radiology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan Province, People's Republic of China
| | - Xinwei Han
- Department of Interventional Radiology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan Province, People's Republic of China
| | - Jianzhuang Ren
- Department of Interventional Radiology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan Province, People's Republic of China
| | - Pengfei Chen
- Department of Interventional Radiology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan Province, People's Republic of China
| | - Hao Li
- Department of Interventional Radiology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan Province, People's Republic of China
| | - Shaojun Gong
- Department of Interventional Radiology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan Province, People's Republic of China
| |
Collapse
|
|
7
|
Kutlu OC, Chan JA, Aloia TA, Chun YS, Kaseb AO, Passot G, Yamashita S, Vauthey JN, Conrad C. Comparative effectiveness of first-line radiofrequency ablation versus surgical resection and transplantation for patients with early hepatocellular carcinoma. Cancer 2017; 123:1817-1827. [PMID: 28085184 DOI: 10.1002/cncr.30531] [Citation(s) in RCA: 72] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2016] [Revised: 10/27/2016] [Accepted: 10/31/2016] [Indexed: 12/17/2022]
Abstract
BACKGROUND Significant controversy exists as to which treatment modality is most effective for small, solitary hepatocellular carcinomas (HCCs): radiofrequency ablation (RFA), surgical resection (RXN), or transplantation (TXP). Size cutoff values ranging from 20 to 50 mm have been proposed to achieve complete ablation. The current study compares outcomes between RFA, RXN, and TXP as first-line therapy for patients with HCC tumors measuring as large as 50 mm. METHODS The Surveillance, Epidemiology, and End Results database was queried for patients with HCC tumors measuring up to 50 mm who were treated with RFA, RXN, or TXP between 2004 and 2013. Overall survival (OS) and disease-specific survival (DSS) were examined in patients with tumors measuring ≤20 mm, 21 to 30 mm, or 31 to 50 mm. The impact of an increase in tumor size of only 5 mm beyond 30 mm was evaluated by also examining outcomes in patients with tumors measuring 31 to 35 mm. RESULTS Of 1894 cases, patients with HCC tumors measuring ≤20 mm and 21 to 30 mm demonstrated no difference in OS or DSS regardless of whether RFA and RXN was used. RFA was associated with a worse OS and DSS than TXP, whereas there was no difference in OS observed between RXN and TXP. In patients with tumors measuring 31 to 50 mm, OS and DSS were worse with RFA compared with RXN or TXP. Most important, the inferior DSS and OS noted with RFA were observed with only a 5-mm increase in tumors measuring >30 mm. CONCLUSIONS Although RFA frequently is used as first-line treatment of HCC tumors measuring as large as 50 mm, it is associated with worse results than RXN or TXP for tumors measuring >30 mm. To the best of the authors' knowledge, the results of the current study are the first to demonstrate that although RFA is an appropriate option for patients with HCC tumors measuring ≤30 mm, its use for tumors even slightly larger than 30 mm is associated with inferior outcomes. Cancer 2017;123:1817-1827. © 2017 American Cancer Society.
Collapse
Affiliation(s)
- Onur C Kutlu
- Department of Surgery, Miller School of Medicine, University of Miami, Miami, Florida.,Division of Surgical Oncology, Medical University of South Carolina, Charleston, South Carolina
| | - Jennifer A Chan
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts
| | - Thomas A Aloia
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Yun S Chun
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Ahmed O Kaseb
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Guillaume Passot
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Suguru Yamashita
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Claudius Conrad
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| |
Collapse
|
|
8
|
Youssef MM, Tolba MF, Badawy NN, Liu AW, El-Ahwany E, Khalifa AE, Zada S, Abdel-Naim AB. Novel combination of sorafenib and biochanin-A synergistically enhances the anti-proliferative and pro-apoptotic effects on hepatocellular carcinoma cells. Sci Rep 2016; 6:30717. [PMID: 27470322 PMCID: PMC4965826 DOI: 10.1038/srep30717] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2015] [Accepted: 07/06/2016] [Indexed: 02/08/2023] Open
Abstract
Sorafenib (SOR) is the first-line treatment for hepatocellular carcinoma (HCC). However, its use is hindered by the recently expressed safety concerns. One approach for reducing SOR toxicity is to use lower doses in combination with other less toxic agents. Biochanin-A (Bio-A), a promising isoflavone, showed selective toxicity to liver cancer cells. We postulated that combining SOR and Bio-A could be synergistically toxic towards HCC cells. We further evaluated the underlying mechanism. Cytotoxicity assay was performed to determine the IC50 of Bio-A and SOR in HepG2, SNU-449 and Huh-7 cells. Then, combination index in HepG2 was evaluated using Calcusyn showing that the concurrent treatment with lower concentrations of SOR and Bio-A synergistically inhibited cell growth. Our combination induced significant arrest in pre-G and G0/G1 cell cycle phases and decrease in cyclin D1 protein level. Concomitantly, SOR/Bio-A reduced Bcl-2/Bax ratio. Furthermore, this co-treatment significantly increased caspase-3 & -9 apoptotic markers, while decreased anti-apoptotic and proliferative markers; survivin and Ki-67, respectively. Active caspase-3 in HepG2, SNU-449 and Huh-7 confirmed our synergism hypothesis. This study introduces a novel combination, where Bio-A synergistically enhanced the anti-proliferative and apoptotic effects of SOR in HCC cells, which could serve as a potential effective regimen for treatment.
Collapse
Affiliation(s)
- Mohieldin M Youssef
- The American University in Cairo, New Cairo, 11835 Egypt.,Okinawa Institute of Science and Technology Graduate University, OIST, Okinawa, 904-0495 Japan
| | - Mai F Tolba
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Ain-Shams University, Cairo, 11566 Egypt
| | - Noha N Badawy
- The American University in Cairo, New Cairo, 11835 Egypt
| | - Andrew W Liu
- Okinawa Institute of Science and Technology Graduate University, OIST, Okinawa, 904-0495 Japan
| | - Eman El-Ahwany
- Immunology Department, Theodor-Bilharz Research Institute (TBRI), Giza, 12411 Egypt
| | - Amani E Khalifa
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Ain-Shams University, Cairo, 11566 Egypt
| | - Suher Zada
- The American University in Cairo, New Cairo, 11835 Egypt
| | - Ashraf B Abdel-Naim
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Ain-Shams University, Cairo, 11566 Egypt
| |
Collapse
|
|
9
|
Spolverato G, Vitale A, Ejaz A, Kim Y, Maithel SK, Cosgrove DP, Pawlik TM. The relative net health benefit of liver resection, ablation, and transplantation for early hepatocellular carcinoma. World J Surg 2015; 39:1474-84. [PMID: 25665675 DOI: 10.1007/s00268-015-2987-7] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND There are no conclusive cost-effectiveness studies measuring the efficacy of salvage LT after liver resection (LR) and radiofrequency ablation (RFA) in patients with early hepatocellular carcinoma (HCC) and compensated cirrhosis. The aim of the present study is to compare liver transplantation (LT) versus locoregional therapy plus salvage LT (to treat tumor recurrence) in patients with early HCC and compensated cirrhosis. METHODS Reference case: 55-year old male with HCC within Milan criteria and Child-Pugh A cirrhosis. The analysis was performed in two geographical cost settings: USA and Italy. Survival benefit measured in quality-adjusted life years (QALYs), costs (C) in US$, incremental cost-effectiveness, willingness to pay, and net health benefit (NHB). RESULTS In the base-case analysis, NHB of LT vs. LR and RFA was -1.7 and -1.3 years for single tumor ≤3 cm, -1.2 and -0.7 for single nodules measuring 3.1-5 cm and -0.7 and -0.7 for multi-nodular tumor ≤3 cm in Italy. In USA, NHB of LT versus LR and RFA were -1.2 and -0.8 years for single tumor ≤3 cm, -0.9 and -0.5 for single nodules measuring 3.1-5 cm, and -0.5 and -0.4 for multi-nodular tumor ≤ 3 cm. On the Monte Carlo simulation, only young patients with multi-nodular HCC and short waiting list time had a positive NHB. Salvage LT proved to be an ineffective cost strategy after RFA or LR. CONCLUSION In patients with HCC within Milan criteria and Child-Pugh A cirrhosis, LR and RFA were more cost-effective than LT. Salvage LT was not cost-effective.
Collapse
Affiliation(s)
- Gaya Spolverato
- Department of Surgery, The Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock 688, Baltimore, MD, 21287, USA
| | | | | | | | | | | | | |
Collapse
|
|
10
|
The role of liver transplantation or resection for patients with early hepatocellular carcinoma. Tumour Biol 2015; 37:4193-201. [PMID: 26490991 DOI: 10.1007/s13277-015-4243-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2015] [Accepted: 10/12/2015] [Indexed: 12/14/2022] Open
Abstract
Liver resection (LR) and liver transplantation (LT) are curative treatments for early hepatocellular carcinoma (HCC), although their performance remains debated. We compared the survival of patients with HCC conforming to the Milan criteria (MC) after LT and LR and analyzed factors affecting clinical outcomes. Between January 2006 and January 2013, 65 and 184 patients received LT and LR for HCCs fulfilling the MC, respectively. Overall survival (OS) and disease-free survival (DFS) rates were compared between the two groups. To investigate effects of liver function and living donor liver transplantation (LDLT) on survival, two subgroup analyses were performed and associations with OS and DFS were examined. We found that OS rates were higher after LT than after LR since 3 years postoperatively. DFS rates were significantly better after LT than after LR. Performance of LR, vascular invasion, and tumor multiplicity were associated with poor DFS, and factors affecting OS included the presence of vascular invasions, liver cirrhosis, and tumor multiplicity. In conclusion, despite of the effects of tumor characteristics on clinical outcomes, LT, including LDLT, should be considered the treatment of choice for patients with HCCs who met the MC. The role of LR is to identify poor prognostic factors through pathological examination.
Collapse
|
|
11
|
Scatton O, Goumard C, Cauchy F, Fartoux L, Perdigao F, Conti F, Calmus Y, Boelle PY, Belghiti J, Rosmorduc O, Soubrane O. Early and resectable HCC: Definition and validation of a subgroup of patients who could avoid liver transplantation. J Surg Oncol 2015; 111:1007-15. [PMID: 25918872 DOI: 10.1002/jso.23916] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2014] [Accepted: 03/16/2015] [Indexed: 12/27/2022]
Abstract
BACKGROUND Liver transplantation (LT) remains the best curative option for early hepatocellular carcinoma (HCC) but is limited by the ongoing graft shortage. The present study aimed at defining the population in which primary liver resection (LR) could represent the best alternative to LT. METHODS An exploration set of 357 HCC patients (LR n = 221 and LT n = 136) operated between 2000-2012 was used in order to identify factors associated with survival following LR and define a good prognosis (GP) group for which LR may challenge the results of upfront LT. These factors were validated in an external validation set of 565 HCC patients operated at another center (LR n = 287 LR and LT n = 278). RESULTS In the exploration set, factors associated with survival on multivariate analysis were a solitary lesion, a diameter <50 mm, a well-moderately differentiated lesion, the absence of microvascular invasion, and preoperative AST level <2N. Thirty-nine patients (18%) displayed all these criteria and constituted the GP patients. Overall survivals at 1, 3, and 5 years did not significantly differ between GP resected patients, and the in Milan transplanted patients (93, 80.4, and 80.4% vs. 86.9, 82, and 78.8%, P = 0.79). In the validation cohort, patients with GP factors of survival still displayed better overall survivals than those without (P = 0.036) but also displayed better survivals than in Milan HCC transplanted patients (P = 0.005). CONCLUSION In a group of early HCC patients gathering all factors of GP, primary LR achieves at least similar survival as upfront LT and should be the approach of choice.
Collapse
Affiliation(s)
- Olivier Scatton
- Departments of Hepatobiliary Surgery and Liver Transplantation, Hôpital Pitié Salpêtrière, Assistance Publique Hopitaux de Paris, Paris, France. .,Université Pierre et Marie Curie, Paris 6.
| | - Claire Goumard
- Departments of Hepatobiliary Surgery and Liver Transplantation, Hôpital Pitié Salpêtrière, Assistance Publique Hopitaux de Paris, Paris, France
| | - Francois Cauchy
- Department of Hepatobiliary surgery and Liver Transplantation, Hopital Beaujon, Assistance Publique Hopitaux de Paris, Paris, France
| | - Laetitia Fartoux
- Université Pierre et Marie Curie, Paris 6.,Department of Hepatology, Hopital Pitié Salpêtrière, Assistance Publique Hopitaux de Paris, Paris, France
| | - Fabiano Perdigao
- Departments of Hepatobiliary Surgery and Liver Transplantation, Hôpital Pitié Salpêtrière, Assistance Publique Hopitaux de Paris, Paris, France
| | - Filomena Conti
- Université Pierre et Marie Curie, Paris 6.,Department of Pathology, Hopital Pitié Salpêtrière, Assistance Publique Hopitaux de Paris, Paris, France
| | - Yvon Calmus
- Université Pierre et Marie Curie, Paris 6.,Department of Pathology, Hopital Pitié Salpêtrière, Assistance Publique Hopitaux de Paris, Paris, France
| | - Pierre Yves Boelle
- Department of Biostatistics, Hopital Saint Antoine, Assistance Publique Hopitaux de Paris, Paris, France
| | - Jacques Belghiti
- Department of Hepatobiliary surgery and Liver Transplantation, Hopital Beaujon, Assistance Publique Hopitaux de Paris, Paris, France
| | - Olivier Rosmorduc
- Université Pierre et Marie Curie, Paris 6.,Department of Hepatology, Hopital Pitié Salpêtrière, Assistance Publique Hopitaux de Paris, Paris, France
| | - Olivier Soubrane
- Departments of Hepatobiliary Surgery and Liver Transplantation, Hôpital Pitié Salpêtrière, Assistance Publique Hopitaux de Paris, Paris, France.,Université Pierre et Marie Curie, Paris 6
| |
Collapse
|
|
12
|
Li D, Kang J, Golas BJ, Yeung VW, Madoff DC. Minimally invasive local therapies for liver cancer. Cancer Biol Med 2015; 11:217-36. [PMID: 25610708 PMCID: PMC4296086 DOI: 10.7497/j.issn.2095-3941.2014.04.001] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2014] [Accepted: 10/28/2014] [Indexed: 12/11/2022] Open
Abstract
Primary and metastatic liver tumors are an increasing global health problem, with hepatocellular carcinoma (HCC) now being the third leading cause of cancer-related mortality worldwide. Systemic treatment options for HCC remain limited, with Sorafenib as the only prospectively validated agent shown to increase overall survival. Surgical resection and/or transplantation, locally ablative therapies and regional or locoregional therapies have filled the gap in liver tumor treatments, providing improved survival outcomes for both primary and metastatic tumors. Minimally invasive local therapies have an increasing role in the treatment of both primary and metastatic liver tumors. For patients with low volume disease, these therapies have now been established into consensus practice guidelines. This review highlights technical aspects and outcomes of commonly utilized, minimally invasive local therapies including laparoscopic liver resection (LLR), radiofrequency ablation (RFA), microwave ablation (MWA), high-intensity focused ultrasound (HIFU), irreversible electroporation (IRE), and stereotactic body radiation therapy (SBRT). In addition, the role of combination treatment strategies utilizing these minimally invasive techniques is reviewed.
Collapse
Affiliation(s)
- David Li
- 1 Department of Radiology, Division of Interventional Radiology, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10065, USA ; 2 Department of Medicine, NYU Langone Medical Center, New York, NY 10016, USA ; 3 Flushing Radiation Oncology Services, Flushing, New York, NY 11354, USA ; 4 Department of Surgery, Division of Surgical Oncology, New York-Presbyterian Hospital/Weill Cornell Medical Center New York, New York, NY 10065, USA
| | - Josephine Kang
- 1 Department of Radiology, Division of Interventional Radiology, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10065, USA ; 2 Department of Medicine, NYU Langone Medical Center, New York, NY 10016, USA ; 3 Flushing Radiation Oncology Services, Flushing, New York, NY 11354, USA ; 4 Department of Surgery, Division of Surgical Oncology, New York-Presbyterian Hospital/Weill Cornell Medical Center New York, New York, NY 10065, USA
| | - Benjamin J Golas
- 1 Department of Radiology, Division of Interventional Radiology, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10065, USA ; 2 Department of Medicine, NYU Langone Medical Center, New York, NY 10016, USA ; 3 Flushing Radiation Oncology Services, Flushing, New York, NY 11354, USA ; 4 Department of Surgery, Division of Surgical Oncology, New York-Presbyterian Hospital/Weill Cornell Medical Center New York, New York, NY 10065, USA
| | - Vincent W Yeung
- 1 Department of Radiology, Division of Interventional Radiology, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10065, USA ; 2 Department of Medicine, NYU Langone Medical Center, New York, NY 10016, USA ; 3 Flushing Radiation Oncology Services, Flushing, New York, NY 11354, USA ; 4 Department of Surgery, Division of Surgical Oncology, New York-Presbyterian Hospital/Weill Cornell Medical Center New York, New York, NY 10065, USA
| | - David C Madoff
- 1 Department of Radiology, Division of Interventional Radiology, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10065, USA ; 2 Department of Medicine, NYU Langone Medical Center, New York, NY 10016, USA ; 3 Flushing Radiation Oncology Services, Flushing, New York, NY 11354, USA ; 4 Department of Surgery, Division of Surgical Oncology, New York-Presbyterian Hospital/Weill Cornell Medical Center New York, New York, NY 10065, USA
| |
Collapse
|
|
13
|
Leoni S, Piscaglia F, Serio I, Terzi E, Pettinari I, Croci L, Marinelli S, Benevento F, Golfieri R, Bolondi L. Adherence to AASLD guidelines for the treatment of hepatocellular carcinoma in clinical practice: experience of the Bologna Liver Oncology Group. Dig Liver Dis 2014; 46:549-55. [PMID: 24630947 DOI: 10.1016/j.dld.2014.02.012] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2013] [Revised: 01/30/2014] [Accepted: 02/14/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND Few data exist on real-life adherence to international guidelines for the treatment of hepatocellular carcinoma. We analysed the rate of adherence to American Association for the Study of Liver Diseases guidelines, to identify reasons for discrepancy with treatments performed in our centre. METHODS 227 consecutive cirrhotics with a first hepatocellular carcinoma diagnosis (2005-2010) were retrospectively evaluated and stratified based on Barcelona Clinic Liver Cancer system: 126 early, 50 intermediate, 40 advanced, and 11 end stage. RESULTS Early hepatocellular carcinomas were theoretically eligible for resection (n=27), liver transplantation (n=36), and percutaneous treatment (n=63). In practice, 15/27 (55.5%), 31/36 (86.1%), and 22/63 (34.9%) respectively were treated as recommended. Reasons for discrepancy were age/comorbidity, tumour location, ultrasound visibility, surgical contraindications. Transarterial chemoembolisation was performed in 25/126 early hepatocellular carcinomas (19.8%), resection in 11/63 early hepatocellular carcinomas eligible for percutaneous treatment (17.5%). Transarterial chemoembolisation was excluded in 16/50 intermediate hepatocellular carcinomas (32%). Resection or transarterial chemoembolisation was performed in 6/40 advanced hepatocellular carcinomas (15%). CONCLUSION Overall, 60% of patients were treated according to American Association for the Study of Liver Diseases guidelines. Approximately 28% of hepatocellular carcinomas were "under-treated" and 7% treated more aggressively than recommended. Peculiarities of individual patients can lead the multidisciplinary team to personalise real-life treatments.
Collapse
Affiliation(s)
- Simona Leoni
- Division of Internal Medicine, Department of Medical and Surgical Sciences, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.
| | - Fabio Piscaglia
- Division of Internal Medicine, Department of Medical and Surgical Sciences, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy
| | - Ilaria Serio
- Division of Internal Medicine, Department of Medical and Surgical Sciences, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy
| | - Eleonora Terzi
- Division of Internal Medicine, Department of Medical and Surgical Sciences, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy
| | - Irene Pettinari
- Division of Internal Medicine, Department of Medical and Surgical Sciences, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy
| | - Luca Croci
- Division of Internal Medicine, Department of Medical and Surgical Sciences, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy
| | - Sara Marinelli
- Division of Internal Medicine, Department of Medical and Surgical Sciences, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy
| | - Francesca Benevento
- Division of Internal Medicine, Department of Medical and Surgical Sciences, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy
| | - Rita Golfieri
- Division of Radiology, Department of Digestive Diseases and Internal Medicine, Sant'Orsola-Malpighi Hospital, Bologna, Italy
| | - Luigi Bolondi
- Division of Internal Medicine, Department of Medical and Surgical Sciences, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy
| |
Collapse
|
|
14
|
Xu XS, Liu C, Qu K, Song YZ, Zhang P, Zhang YL. Liver transplantation versus liver resection for hepatocellular carcinoma: a meta-analysis. Hepatobiliary Pancreat Dis Int 2014; 13:234-41. [PMID: 24919605 DOI: 10.1016/s1499-3872(14)60037-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Liver transplantation (LT) and liver resection (LR) are currently considered the standard treatment of patients with hepatocellular carcinoma (HCC). However, the outcomes of LT and LR are still inconclusive. DATA SOURCES MEDLINE, EMBASE, and Cochrane Library were searched for relevant studies. Surgical safety indices such as treatment-related morbidity and mortality, and efficacy indices such as overall and tumor-free survival outcomes were evaluated. Weighted mean differences and odds ratios (ORs) were calculated using a random-effects model. RESULTS Seventeen studies were included in this meta-analysis. LT achieved significantly higher rates of surgery-related morbidity (OR=1.47; 95% CI: 1.02-2.13) and mortality (OR=2.12; 95% CI: 1.11-4.05). Likewise, the 1-year survival rate was lower in LT (OR=0.86; 95% CI: 0.61-1.20). However, the 3- and 5-year survival rates were significantly higher in LT than in LR and the ORs were 1.12 (95% CI: 0.96-1.30) in 3 years and 1.84 (95% CI: 1.49-2.28) in 5 years. Furthermore, the tumor-free survival rate in LT was significantly higher than that in LR in 1, 3, 5 years after surgery, with the ORs of 1.72 (95% CI: 1.24-2.41), 3.75 (95% CI: 2.94-4.78) and 5.64 (95% CI: 4.35-7.31), respectively. CONCLUSIONS One-year morbidity and mortality are higher in LT than in LR for patients with HCC. However, long-term survival and tumor-free survival rates are higher in patients treated with LT than those treated with LR.
Collapse
Affiliation(s)
- Xin-Sen Xu
- Department of Hepatobiliary Surgery, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
| | | | | | | | | | | |
Collapse
|
|
15
|
Li D, Kang J, Madoff DC. Locally ablative therapies for primary and metastatic liver cancer. Expert Rev Anticancer Ther 2014; 14:931-45. [PMID: 24746315 DOI: 10.1586/14737140.2014.911091] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Locally ablative therapies have an increasing role in the effective multidisciplinary approach towards the treatment of both primary and metastatic liver tumors. In patients who are not considered surgical candidates and have low volume disease, these therapies have now become established into consensus practice guidelines. A large range of therapeutic options exist including percutaneous ethanol injection (PEI), radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation, percutaneous laser ablation (PLA), irreversible electroporation (IRE), stereotactic body radiation therapy (SBRT) and high intensity focused ultrasound (HIFU); each having benefits and drawbacks. The greatest body of evidence supporting clinical utility in the liver currently exists for RFA, with PEI having fallen out of favor. MWA, IRE, SBRT and HIFU are relatively nascent technologies, and outcomes data supporting their use is promising. Future directions of ablative therapies include tandem approaches to improve efficacy in the treatment of liver tumors.
Collapse
Affiliation(s)
- David Li
- Department of Radiology, Division of Interventional Radiology, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY, USA
| | | | | |
Collapse
|
|
16
|
Liver transplantation versus liver resection in the treatment of hepatocellular carcinoma: a meta-analysis of observational studies. Transplantation 2014; 97:227-34. [PMID: 24142034 DOI: 10.1097/tp.0b013e3182a89383] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND A number of cohort studies have compared the outcomes of liver transplantation (LT) and liver resection (LR) in hepatocellular carcinoma (HCC) patients. However, the effects of LT versus LR remain unclear. We searched electronic databases and reference lists for relevant articles published before February 2013. METHODS The primary endpoints were pooled using random-effects models to model potential heterogeneity, including overall survival (OS), disease-free survival, and recurrence rate. RESULTS We found similar 1-year OS (odds ratio [OR], 1.08; 95% confidence interval [CI], 0.81-1.43; P=0.61) yet significantly better 3-year OS (OR, 1.47; 95% CI, 1.18-1.84; P<0.001) and 5-year OS (OR, 1.77; 95% CI, 1.45-2.16; P<0.001) after LT compared with LR with relative risk differences of 9% (P<0.001) and 14% (P<0.001), respectively. The 1-, 3-, and 5-year difference-free survival were 13%, 29%, and 39% higher (P<0.001 in all) in LT recipients than LR patients. Additionally, recurrence rate was 30% less (P<0.001) in LT than LR. Furthermore, better 5-year difference-free survival (P<0.001) and recurrence rates (P<0.05) were yielded after LT when patients from the entire HCC population were included. CONCLUSIONS When including all the 62 previous studies comparing LT and resection, LT provides increased survival and lower recurrence rates than LR for HCC patients. These results of disease-free survival and recurrence rate are similar among early HCC patients with Child-Turcotte-Pugh class A cirrhosis. However, summary ORs and risk differences cannot be interpreted as causal effects of LT versus LR.
Collapse
|
|
17
|
Nathan H, Herlong HF, Gurakar A, Li Z, Koteish AA, Bridges JF, Pawlik TM. Clinical Decision-Making by Gastroenterologists and Hepatologists for Patients with Early Hepatocellular Carcinoma. Ann Surg Oncol 2014; 21:1844-51. [DOI: 10.1245/s10434-014-3536-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2013] [Indexed: 12/15/2022]
|
|
18
|
Lei JY, Yan LN, Wang WT. Transplantation vs resection for hepatocellular carcinoma with compensated liver function after downstaging therapy. World J Gastroenterol 2013; 19:4400-4408. [PMID: 23885153 PMCID: PMC3718910 DOI: 10.3748/wjg.v19.i27.4400] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2013] [Revised: 04/27/2013] [Accepted: 06/19/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: Our study aimed to compare the results of liver transplantation (LT) and liver resection (LR) in patients with hepatocellular carcinoma (HCC) that met the Milan criteria after successful downstaging therapy.
METHODS: From February 2004 to August 2010, a consecutive series of 102 patients were diagnosed with advanced-stage HCC that met the modified UCSF down-staging protocol inclusion criteria. All of the patients accepted various down-staging therapies. The types and numbers of treatments were tailored to each patient according to the tumor characteristics, location, liver function and response. After various downstaging therapies, 66 patients had tumor characteristics that met the Milan criteria; 31 patients accepted LT in our center, and 35 patients accepted LR. The baseline characteristics, down-staging protocols, postoperative complications, overall survival and tumor free survival rate, and tumor recurrence rate were compared between the two groups. Kaplan-Meier analyses were used to estimate the long-term overall survival and tumor-free survival rate. Meanwhile, a Cox proportional hazards model was used for the multivariate analyses of overall survival and disease-free survival rate.
RESULTS: No significant difference was observed between the LT and LR groups with respect to the down-staging protocol, target tumor characteristics, and baseline patient characteristics. Fifteen patients suffered various complications after LT, and 8 patients had complications after LR. The overall complication rate for the LT group was 48.4%, which was significantly higher than the LR group (22.9%) (P = 0.031). The overall in-hospital mortality in hospital for the LT group was 12.9% vs 2.9% for the LR group (P = 0.172). The overall patient survival rates at 1-, 3- and 5-years were 87.1%, 80.6% and 77.4%, respectively, after LT and 91.4%, 77.1% and 68.6%, respectively, after LR (P = 0.498). The overall 1-, 3- and 5-year tumor recurrence-free rates were also comparable (P = 0.656). Poorer tumor differentiation (P = 0.041) and a higher post-downstage alpha-fetoprotein (AFP) level (> 400 ng/mL) (P = 0.015) were the two independent risk factors for tumor recurrence in the LT and LR patients who accepted successful down-staging therapy.
CONCLUSION: Due to the higher postoperative morbidity and similar survival and tumor recurrence-free rates, LR might offer better or similar outcome over LT, but a larger number and further randomized studies may be needed in the future for drawing any positive conclusions.
Collapse
|
|
19
|
Lee YH, Hsu CY, Huang YH, Su CW, Lin HC, Hsia CY, Huo TI. α-fetoprotein-to-total tumor volume ratio predicts post-operative tumor recurrence in hepatocellular carcinoma. J Gastrointest Surg 2013. [PMID: 23188220 DOI: 10.1007/s11605-012-2081-5] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND/AIMS Serum α-fetoprotein (AFP) and total tumor volume (TTV) are important factors linked with post-operative tumor recurrence in hepatocellular carcinoma (HCC) patients. We investigated the role of a new prognostic marker, AFP-to-TTV ratio, in predicting HCC recurrence. METHODS A total of 655 HCC patients undergoing resection were analyzed. RESULTS In the multivariate logistic model, serum AFP level [odds ratio (OR) 32.459, p = 0.012] and TTV (OR 0.006, p = 0.01) were independently associated with a higher AFT/TTV ratio. The 1-, 3-, and 5-year tumor recurrence rates were 29 %, 55 %, and 68 %, respectively. In the Cox proportional hazards model, alcoholism (hazard ratio [HR], 1.354, p = 0.028), international normalized ratio of prothrombin time ≥1.01 (HR, 1.349, p < 0.001), multiple nodules (HR, 1.381, p = 0.004), main tumor diameter ≥4 cm (HR, 1.535, p = 0.001), macrovascular invasion (HR, 1.362, p = 0.016), and AFP/TTV ratio ≥1.5 (HR, 1.49, p < 0.001) were independently associated with tumor recurrence. In subgroup analysis, a higher AFP/TTV ratio was significantly associated with tumor recurrence in patients characterized by macrovascular invasion, TTV ≥ 40 cm(3), or main tumor diameter ≥4cm (all p = 0.001). CONCLUSION The AFP/TTV ratio, a newly proposed marker for predicting post-operative tumor recurrence in HCC, is a feasible surrogate and may be useful in selecting super-high-risk patients for tumor recurrence.
Collapse
Affiliation(s)
- Yun-Hsuan Lee
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | | | | | | | | | | | | |
Collapse
|
|
20
|
Sogawa H, Shrager B, Jibara G, Tabrizian P, Roayaie S, Schwartz M. Resection or transplant-listing for solitary hepatitis C-associated hepatocellular carcinoma: an intention-to-treat analysis. HPB (Oxford) 2013; 15:134-41. [PMID: 23036070 PMCID: PMC3719920 DOI: 10.1111/j.1477-2574.2012.00548.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2012] [Accepted: 06/08/2012] [Indexed: 12/12/2022]
Abstract
OBJECTIVES The relative roles of liver resection (LR) and liver transplantation (LT) in the treatment of a solitary hepatocellular carcinoma (HCC) remain unclear. This study was conducted to provide a retrospective intention-to-treat comparison of these two curative therapies. METHODS Records maintained at the study centre for all patients treated with LR or listed for LT for hepatitis C-associated HCC between January 2002 and December 2007 were reviewed. Inclusion criteria required: (i) an initial diagnosis of a solitary HCC lesion measuring ≤ 5 cm, and (ii) Child-Pugh class A or B cirrhosis. The primary endpoint analysed was intention-to-treat survival. RESULTS A total of 75 patients were listed for transplant (LT-listed group) and 56 were resected (LR group). Of the 75 LT-listed patients, 23 (30.7%) were never transplanted because they were either removed from the waiting list (n = 13) or died (n = 10). Intention-to-treat median survival was superior in the LR group compared with the LT-listed group (61.8 months vs. 30.6 months), but the difference did not reach significance. Five-year recurrence was higher in the LR group than in the 52 LT patients (71.5% vs. 30.5%; P < 0.001). CONCLUSIONS In the context of limited donor organ availability, partial hepatectomy represents an efficacious primary approach in properly selected patients with hepatitis C-associated HCC.
Collapse
Affiliation(s)
- Hiroshi Sogawa
- Recanati/Miller Transplantation Institute, Mount Sinai Medical CenterNew York, NY, USA
| | - Brian Shrager
- Division of Surgical Oncology, Department of Surgery, Mount Sinai Medical CenterNew York, NY, USA
| | - Ghalib Jibara
- Division of Surgical Oncology, Department of Surgery, Mount Sinai Medical CenterNew York, NY, USA
| | - Parissa Tabrizian
- Division of Surgical Oncology, Department of Surgery, Mount Sinai Medical CenterNew York, NY, USA
| | - Sasan Roayaie
- Division of Surgical Oncology, Department of Surgery, Mount Sinai Medical CenterNew York, NY, USA
| | - Myron Schwartz
- Recanati/Miller Transplantation Institute, Mount Sinai Medical CenterNew York, NY, USA
- Division of Surgical Oncology, Department of Surgery, Mount Sinai Medical CenterNew York, NY, USA
| |
Collapse
|
|
21
|
Groeschl RT, Clark Gamblin T, Turaga KK. Surgical resection in hepatocellular carcinoma patients with minimal background fibrosis: a strategy in the era of organ shortage. Ann Surg Oncol 2013; 20:2043-8. [PMID: 23334253 DOI: 10.1245/s10434-012-2857-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2012] [Indexed: 12/18/2022]
Abstract
BACKGROUND Surgical therapies for hepatocellular carcinoma (HCC) represent the potentially curative approaches and provide patients the greatest survival advantage. We sought to examine the outcomes of patients with HCC treated with surgical resection, transplantation, and local ablation. METHODS The Surveillance, Epidemiology, and End Results database was queried for all patients with nonmetastatic HCC from 2004 to 2007 who underwent local ablation (LA), segmental resection (SR), hemihepatectomy or extended resection (ER), or transplantation (TP). RESULTS Of 16,209 patients with HCC, 3,989 (24.6 %) met criteria for inclusion and received therapies: 1,550 LA (39 %), 703 SR (18 %), 619 ER (16 %), and 1,117 TP (28 %). AFP was elevated in 69 % (2,026 of 2,921), and fibrosis grade 0-4 was noted in 32 % (368 of 1,156). The 3-year survival by procedure was 34 % (LA), 50 % (SR), 54 % (ER), and 74 % (TP), p = .001. In patients with minimal fibrosis, 1-year survival for patients undergoing resection was similar to TP (85 vs. 92 %, p = .346), but greater than LA (69 %, p = .001). DISCUSSION Survival after surgical resection for HCC patients without extensive fibrosis appears to be superior to ablation and non-inferior to transplantation. In an era of organ shortage, transplantation may be better reserved for patients with cirrhosis and/or unresectable disease.
Collapse
Affiliation(s)
- Ryan T Groeschl
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA.
| | | | | |
Collapse
|
|
22
|
Levitsky J, Oniscu GC. Meeting report of the International Liver Transplantation Society's 18th annual international congress: Hilton San Francisco Hotel, San Francisco, CA, May 16-19, 2012. Liver Transpl 2013; 19:27-35. [PMID: 23239473 DOI: 10.1002/lt.23562] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2012] [Accepted: 09/26/2012] [Indexed: 12/14/2022]
Abstract
From May 16-19, 2012, the International Liver Transplantation Society held its annual congress in San Francisco, CA. More than 1300 registrants attended the meeting, which included a premeeting conference entitled Balancing Risk in Liver Transplantation, focused topic sessions, and a variety of oral and poster presentations. This report is not all-inclusive and focuses on specific research abstracts on key topics in liver transplantation. As always, the new data herein are presented in the context of the published literature to further enhance knowledge in the field.
Collapse
Affiliation(s)
- Josh Levitsky
- Division of Gastroenterology and Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
| | | |
Collapse
|
|
23
|
Dhir M, Lyden ER, Smith LM, Are C. Comparison of outcomes of transplantation and resection in patients with early hepatocellular carcinoma: a meta-analysis. HPB (Oxford) 2012; 14:635-45. [PMID: 22882201 PMCID: PMC3461390 DOI: 10.1111/j.1477-2574.2012.00500.x] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES Surgical decision making for patients with early hepatocellular carcinoma (HCC) and well-compensated cirrhosis remains controversial. The aim of the current study was to conduct a meta-analysis of published reports to compare survival outcomes after transplantation and resection, respectively, in patients with early HCC [i.e. HCC falling within the Milan Criteria (a solitary lesion measuring ≤5 cm or fewer than three lesions with a largest diameter of ≤3 cm, and absence of macroscopic vascular invasion or extrahepatic disease)] and well-compensated cirrhosis. METHODS A total of 990 abstracts were identified through a PubMed-based search. Ten articles comparing transplantation and resection in patients with early HCC were included in the meta-analysis. Meta-analysis was performed using stata 9.2 statistical software. RESULTS Outcomes were analysed for a total of 1763 patients with early HCC. The 5-year overall survival (OS) for all patients was 58% (transplantation: 63%; resection: 53%). Meta-analysis of all 10 studies revealed a survival advantage for transplantation [odds ratio (OR) 0.581, 95% confidence interval (CI) 0.359-0.939; P = 0.027]. Analysis of only those reports that utilized an 'intention-to-treat' strategy failed to demonstrate a survival advantage for either treatment approach (OR 0.600, 95% CI 0.291-1.237; P = 0.166). CONCLUSIONS The current study demonstrates a favourable outcome in patients with early HCC treated by either transplantation or resection. Although transplantation was noted to have a survival advantage in some settings, resection continues to be a viable treatment approach.
Collapse
Affiliation(s)
- Mashaal Dhir
- Department of Surgery, Division of Surgical Oncology, Eppley Cancer CenterOmaha, NE, USA
| | - Elizabeth R Lyden
- Department of Epidemiology and Biostatistics, College of Public HealthOmaha, NE, USA
| | - Lynette M Smith
- Department of Epidemiology and Biostatistics, College of Public HealthOmaha, NE, USA
| | - Chandrakanth Are
- Department of Surgery, Division of Surgical Oncology, Eppley Cancer CenterOmaha, NE, USA,Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical CenterOmaha, NE, USA
| |
Collapse
|
|
24
|
Nathan H, Segev DL, Bridges JFP, Massie AB, Cameron AM, Hirose K, Schulick RD, Choti MA, Pawlik TM. Influence of Nonclinical Factors on Choice of Therapy for Early Hepatocellular Carcinoma. Ann Surg Oncol 2012; 20:448-56. [DOI: 10.1245/s10434-012-2619-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2012] [Indexed: 12/19/2022]
|
|
25
|
Kneuertz PJ, Demirjian A, Firoozmand A, Corona-Villalobos C, Bhagat N, Herman J, Cameron A, Gurakar A, Cosgrove D, Choti MA, Geschwind JFH, Kamel IR, Pawlik TM. Diffuse infiltrative hepatocellular carcinoma: assessment of presentation, treatment, and outcomes. Ann Surg Oncol 2012; 19:2897-907. [PMID: 22476754 DOI: 10.1245/s10434-012-2336-0] [Citation(s) in RCA: 76] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2011] [Indexed: 12/18/2022]
Abstract
BACKGROUND Data on infiltrating hepatocellular carcinoma (HCC) are limited. We sought to define treatment and outcome of patients treated with infiltrating HCC compared with patients who had advanced multifocal HCC. METHODS Between January 2000 and July 2011, a total of 147 patients with advanced HCC were identified from the Johns Hopkins Hospital database (infiltrative, n = 75; multifocal, n = 72). Clinicopathologic data were compared by HCC subtype. RESULTS Patients with infiltrating HCC had higher alfa-fetoprotein levels (median infiltrative, 326.5 ng/mL vs. multifocal, 27.0 ng/mL) and larger tumors (median size, infiltrating, 9.2 cm vs. multifocal, 5.5 cm) (P < 0.05). Imaging failed to reveal a discrete lesion in 42.7 % of patients with infiltrating HCC. Most infiltrating HCC lesions presented as hypointense on T1-weighted images (55.7 %) and hyperintense on T2-weighted images (80.3 %). Among patients with infiltrating HCC, most (64.0 %) were treated with intra-arterial therapy (IAT), and periprocedural morality was 2.7 %. Patients treated with IAT had longer survival versus patients receiving best support care (median survival, IAT, 12 months vs. best supportive care, 3 months; P = 0.001). Survival after IAT was similar among patients treated with infiltrating HCC versus multifocal HCC (hazard ratio 1.29, 95 % confidence interval 0.82-2.03; P = 0.27). Among infiltrating HCC patients, pretreatment bilirubin >2 mg/dL and alfa-fetoprotein >400 ng/mL were associated with worse survival after IAT (P < 0.05). Patients with progressive disease after IAT had higher risk of death versus patients who had stable/responsive disease (hazard ratio 3.53, 95 % confidence interval 1.49-8.37; P = 0.004). CONCLUSIONS Patients with infiltrative HCC often present without a discrete lesion on imaging. IAT for infiltrative HCC was safe and was associated with survival comparable to IAT outcomes for patients with multifocal HCC. Infiltrative HCC morphology is not a contraindication to IAT therapy in select patients.
Collapse
Affiliation(s)
- Peter J Kneuertz
- Department of Surgery, Liver Tumor Center, Johns Hopkins University School of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
26
|
Qiu JL, Huang PZ, You JH, Zou RH, Wang L, Hong J, Li BK, Zhou K, Yuan YF. LIN28 expression and prognostic value in hepatocellular carcinoma patients who meet the Milan criteria and undergo hepatectomy. CHINESE JOURNAL OF CANCER 2012; 31:223-32. [PMID: 22429493 PMCID: PMC3777525 DOI: 10.5732/cjc.011.10426] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Stem cell marker LIN28, related closely with SOX2 and OCT4, has been studied as a biomarker for the maintainance of pluripotent cells in several malignancies. Our previous study showed that SOX2 and OCT4 were negative predictors for hepatocellular carcinoma (HCC). However, the predictive value of LIN28 in HCC outcome is still undetermined. We hypothesized that LIN28 may also play a role as a biomarker for HCC. To test this hypothesis, we examined the expression of LIN28 in 129 radically resected HCC tissues using reverse transcription-polymerase chain reaction and analyzed the association of LIN28 expression with clinicopathologic features and prognosis. Our study showed that LIN28 was expressed at a higher frequency in tumor tissues than in non-HCC tissues (45.0% vs. 21.7%, P = 0.020). Moreover, LIN28 expression was significantly increased in cases with large tumor size (P = 0.010). Univariate analysis did not reveal a significant correlation between LIN28 expression and overall survival or recurrence-free survival. For HCC patients who met the Milan criteria, stratified analysis revealed shorter overall survival (P = 0.007) and recurrence-free survival (P < 0.001) in those with detectable LIN28 expression compared to those with no detectable LIN28 expression. Furthermore, multivariate analysis revealed that LIN28 was a negative independent predictor for both overall survival (hazard ratio= 7.093, P = 0.017) and recurrence-free survival (hazard ratio=5.518, P = 0.004) in patients who met the Milan criteria. Taken together, our results suggest that LIN28 identifies low-risk and high-risk subsets of HCC patients meeting the Milan criteria who undergo hepatectomy.
Collapse
Affiliation(s)
- Ji-Liang Qiu
- State Key Laboratory of Oncology in South China, Guangzhou, Guangdong 510060, PR China
| | | | | | | | | | | | | | | | | |
Collapse
|
|
27
|
Chow PKH. Resection for hepatocellular carcinoma: is it justifiable to restrict this to the American Association for the Study of the Liver/Barcelona Clinic for Liver Cancer criteria? J Gastroenterol Hepatol 2012; 27:452-7. [PMID: 22142283 DOI: 10.1111/j.1440-1746.2011.07034.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Hepatocellular carcinoma (HCC) is an important cancer worldwide. The main curative treatment modality is surgical resection although only a minority of afflicted patients are amendable because of poor liver function reserve or extensive disease at the time of diagnosis. The selection criteria for surgical resection, however, are variable and frequently appear to be center-specific. Further, they are influenced by rapidly evolving data on the outcomes of surgical resection and other emerging modalities of treatment. Recently, two major international practice guidelines on the management of HCC were published at about the same time, namely those of the American Association for the Study of the Liver (AASLD), and of the Asia-Pacific Association for the Study of the Liver (APASL). These two practice guidelines differ significantly in philosophy and practice with regards to surgical resection. In fact, they reflect the two extremes of a spectrum of existing consensus opinions. The AASLD Guidelines have evolved from the guidelines of the Barcelona Clinic for Liver Cancer (BCLC), and are significantly more conservative with regard to surgical resection compared with the APASL Guidelines. The scientific basis for these major differences in criteria with regard to surgical resection for HCC is reviewed here, particularly with regard to the situation in the Asia-Pacific region where HCC is especially common.
Collapse
|
|
28
|
N'Kontchou G, Aout M, Laurent A, Nahon P, Ganne-Carrié N, Grando V, Baghad I, Roulot D, Trinchet JC, Sellier N, Cherqui D, Vicaut E, Beaugrand M, Seror O. Survival after radiofrequency ablation and salvage transplantation in patients with hepatocellular carcinoma and Child-Pugh A cirrhosis. J Hepatol 2012; 56:160-6. [PMID: 21703186 DOI: 10.1016/j.jhep.2011.03.026] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2010] [Revised: 02/28/2011] [Accepted: 03/25/2011] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS In patients with hepatocellular carcinoma (HCC) within the Milan criteria, liver transplantation (LT) may be the best therapeutic option. However, the shortage of grafts, leads to attempt liver resection (LR) or radiofrequency ablation (RFA) as a first-line treatment for patients with Child-Pugh A cirrhosis. METHODS We report results, obtained between 2000 and 2007 from a single center, involving 67 patients (mean age: 57 years) eligible for LT, who were treated with RFA, followed by LT if there was recurrence or liver failure. RESULTS Eighty three tumors were treated (mean size: 29±9 mm; 16 binodular forms). RFA achieved complete ablation in 96% of nodules. No mortality occurred. During a post-RFA median follow-up of 48 months, 38 patients experienced recurrence, corresponding to a 5-year recurrence rate of 58%. Of these, 14 patients did not receive a transplant because they fell outside the Milan criteria, 21 were transplanted, and 3 were treated by RFA after refusing LT. Binodularity (95% CI HR=2, 1.0-4.0; p=0.049) was the unique risk factor for recurrence. By the study's end-point, 24 patients had undergone LT (21 for HCC recurrence and three for liver failure). No HCC recurrence occurred after LT. Among the 43 non-transplant patients, 12 died due to HCC progression, and 27 were alive without detectable viable tumor. The probability rates for 5-year overall and tumor-free survival were 74% and 69%, respectively. CONCLUSIONS First line RFA followed by salvage LT allows survival figures that are at least as good as a first-line LT, while limiting the number of grafts.
Collapse
Affiliation(s)
- Gisèle N'Kontchou
- Department of Hepatogastroenterology, Hôpital Jean Verdier (Assistance Publique-Hôpitaux de Paris), Bondy, France
| | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
29
|
Hong YJ, Kim SH, Choi GH, Kim KS, Choi JS. Long-term outcome after liver resection and clinicopathological features in patients with small hepatocellular carcinoma. KOREAN JOURNAL OF HEPATO-BILIARY-PANCREATIC SURGERY 2011; 15:199-205. [PMID: 26421040 PMCID: PMC4582469 DOI: 10.14701/kjhbps.2011.15.4.199] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/19/2011] [Revised: 10/05/2011] [Accepted: 10/18/2011] [Indexed: 01/08/2023]
Abstract
Backgrounds/Aims Surveillance programs and imaging modality developments have increased the detection rate of small hepatocellular carcinoma (HCC). In particular, liver transplantation produces good results and is now regarded an alternative to liver resection. However, optimal treatment for small HCC is still debated, and thus, the authors designed this study to document clinicopathological characteristics, to identify the prognostic factors of small HCC, and to determine the effectiveness of surgery. Methods A total of 507 patients underwent curative liver resection for HCC between January 1996 and August 2006 in our institution. One hundred and thirty four of these patients with a single HCC of less than 3 cm and no gross vascular invasion were enrolled. Results Major resection was performed in 32 (23.9%) patients; there was no postoperative mortality. Fifty-eight (43.3%) patients experienced recurrence, 53 developed intrahepatic recurrence alone, and 50 (94.3%) of 53 had tumors within the Milan criteria. Five-year disease-free and overall survival rates were 51.0% and 77.3%, respectively. Microscopic vascular invasion, positivity for hepatitis B surface antigen or antibody to hepatitis C, and an indocyanine green retention test at 15 minutes of more than 10% were found to be significantly correlated with disease-free overall survival. A platelet count of less than 100,000/mm3 was the only independent prognostic factors of overall survival identified. Conclusions This study showed favorable outcome comparable to the survival after liver transplantation, thus that liver resection appears to be the primary treatment option for small HCC, even in cases with poor prognostic factors.
Collapse
Affiliation(s)
- Young Ju Hong
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Sung Hoon Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Gi Hong Choi
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Kyung Sik Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Jin Sub Choi
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| |
Collapse
|
|
30
|
Demirjian A, Peng P, Geschwind JFH, Cosgrove D, Schutz J, Kamel IR, Pawlik TM. Infiltrating hepatocellular carcinoma: seeing the tree through the forest. J Gastrointest Surg 2011; 15:2089-97. [PMID: 21725699 PMCID: PMC3580771 DOI: 10.1007/s11605-011-1614-7] [Citation(s) in RCA: 61] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2011] [Accepted: 06/20/2011] [Indexed: 01/31/2023]
Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. It is traditionally difficult to cure, especially when discovered at later stages, making early diagnosis and intervention of paramount importance. HCC typically arises in the background of chronic liver disease and can have various morphologic appearances. One of the most difficult of these to recognize on early surveillance imaging is the infiltrative subtype, which can account for up to 13% of all HCC cases, and may be more closely associated with background hepatitis B infection. DISCUSSION Certain imaging characteristics can provide vital clues, including differing signal intensity on the T1 and T2 sequences of magnetic resonance imaging (MRI) and the presence/appearance of portal vein thrombus. Owing to the diffuse and infiltrating properties of this tumor, surgical resection and transplantation are rarely if ever viable therapeutic options. Other forms of liver-directed therapy have been attempted with limited success, having minimal efficacy and high morbidity. To date, there is no data available to determine if the various HCC subtypes respond to systemic therapy differently, so this may be the most reasonable approach. Left untreated, observed patients commonly progress to hepatic failure fairly rapidly. CONCLUSION Infiltrative HCC can be extremely subtle, and therefore difficult to detect, especially in the background of cirrhosis. Providers caring for patients with hepatitis, chronic liver disease, and cirrhosis must be extremely vigilant in the evaluation of surveillance imaging in order to potentially discover this HCC subtype as early as possible and initiate a multidisciplinary treatment plan.
Collapse
Affiliation(s)
- Aram Demirjian
- Department of Surgery, The Johns Hopkins University School of Medicine, 600 N Wolfe St., Harvey 611, Baltimore, MD 21287, USA
| | - Peter Peng
- Department of Surgery, The Johns Hopkins University School of Medicine, 600 N Wolfe St., Harvey 611, Baltimore, MD 21287, USA
| | - Jean-Francois H. Geschwind
- Department of Interventional Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - David Cosgrove
- Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Jacob Schutz
- Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Ihab R. Kamel
- Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Timothy M. Pawlik
- Department of Surgery, The Johns Hopkins University School of Medicine, 600 N Wolfe St., Harvey 611, Baltimore, MD 21287, USA
| |
Collapse
|
|
31
|
Rhee H, Kim MJ, Park YN, Choi JS, Kim KS. Gadoxetic acid-enhanced MRI findings of early hepatocellular carcinoma as defined by new histologic criteria. J Magn Reson Imaging 2011; 35:393-8. [PMID: 21990116 DOI: 10.1002/jmri.22828] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2011] [Accepted: 09/06/2011] [Indexed: 12/18/2022] Open
Abstract
PURPOSE To describe the imaging features of early hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced MRI (Gd-EOB-MRI) in comparison with multidetector computed tomography (MDCT) examinations. MATERIALS AND METHODS We analyzed imaging findings of 19 pathologically proven early HCC lesions in 15 patients who underwent both MDCT and Gd-EOB-MRI at 3.0 Tesla (T) units before surgery. MRI included in-phase and out-of-phase T1-weighted dual-echo gradient-recalled-echo sequences, dynamic T1-weighted images before and after bolus injection of gadoxetic acid disodium, fat-saturated T2-weighted fast spin-echo sequences, and T1-weighted hepatobiliary phase images 20 min after contrast injection. Two radiologists retrospectively evaluated the signal intensities and enhancement features on MRI and MDCT. RESULTS None of the lesions displayed arterial enhancement and washout on MDCT. On Gd-EOB-MRI, six (32%) lesions showed T2-hyperintensity, five (26%) lesions showed signal drop on opposed-phase. Three lesions (16%) showed arterial enhancement and washout. Twelve (63%), 13 (68%), and 15 (79%) lesions were hypointense on hepatic venous, equilibrium, and hepatobiliary phase, respectively. CONCLUSION Most early HCCs did not show arterial enhancement and washout pattern on both MDCT and Gd-EOB-MRI. Gd-EOB-MRI may provide several ancillary findings for diagnosis of early HCC such as decreased hepatobiliary uptake, T2 hyperintensity and signal drop in opposed phase.
Collapse
Affiliation(s)
- Hyungjin Rhee
- Department of Radiology, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea
| | | | | | | | | |
Collapse
|
|
32
|
Fan ST, Poon RTP, Yeung C, Lam CM, Lo CM, Yuen WK, Ng KKC, Liu CL, Chan SC. Outcome after partial hepatectomy for hepatocellular cancer within the Milan criteria. Br J Surg 2011; 98:1292-300. [PMID: 21656513 DOI: 10.1002/bjs.7583] [Citation(s) in RCA: 87] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/07/2011] [Indexed: 01/04/2023]
Abstract
BACKGROUND There is a trend to offer liver transplantation to patients with hepatocellular carcinoma (HCC) with tumour status within the Milan criteria but with preserved liver function. This study aimed to evaluate the outcome of such patients following partial hepatectomy as primary treatment. METHODS A retrospective analysis was performed on all adult patients with HCC and tumour status within the Milan criteria undergoing partial hepatectomy at a single centre from 1995 to 2008. Their outcomes were compared with those of similar patients having right-lobe living donor liver transplantation (LDLT) as primary treatment. RESULTS A total of 408 patients with HCC were enrolled. Some 384 patients with a solitary tumour 5 cm or less in diameter had a better 5-year survival rate than 24 patients with oligonodular tumours (2-3 nodules, each 3 cm or less in size) (70·7 versus 46 per cent; P = 0·025). Multivariable analysis identified younger age (65 years or less), lack of postoperative complications, negative resection margin, absent microvascular invasion and non-cirrhotic liver as predictors of favourable overall survival. The 5-year survival rate of 287 younger patients with chronic liver disease and R0 hepatectomy was 72·8 per cent, comparable to that of 81 per cent in 50 similar patients treated by LDLT (P = 0·093). CONCLUSION Partial hepatectomy for patients with HCC and tumour status within the Milan criteria achieved a satisfactory 5-year survival rate, particularly in younger patients with solitary tumours and R0 hepatectomy. Patients with oligonodular tumours have a worse survival and might benefit from liver transplantation.
Collapse
Affiliation(s)
- S T Fan
- Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Pokfulam, 102 Pok Fu Lam Road, Hong Kong, China.
| | | | | | | | | | | | | | | | | |
Collapse
|
|
33
|
Resection of a Transplantable Single-Nodule Hepatocellular Carcinoma in Child-Pugh Class A Cirrhosis: Factors Affecting Survival and Recurrence. World J Surg 2011; 35:1055-62. [DOI: 10.1007/s00268-011-1000-3] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
|
|
34
|
Soong RS, Yu MC, Chan KM, Chou HS, Wu TJ, Lee CF, Wu TH, Lee WC. Analysis of the recurrence risk factors for the patients with hepatocellular carcinoma meeting University of California San Francisco criteria after curative hepatectomy. World J Surg Oncol 2011; 9:9. [PMID: 21269525 PMCID: PMC3041689 DOI: 10.1186/1477-7819-9-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2010] [Accepted: 01/27/2011] [Indexed: 01/07/2023] Open
Affiliation(s)
- Ruey-Shyang Soong
- Chang-Gung Transplantation Institute, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University Medical School, Taipei, Taiwan
| | - Ming-Chin Yu
- Chang-Gung Transplantation Institute, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University Medical School, Taipei, Taiwan
| | - Kun-Ming Chan
- Chang-Gung Transplantation Institute, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University Medical School, Taipei, Taiwan
| | - Hong-Shiue Chou
- Chang-Gung Transplantation Institute, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University Medical School, Taipei, Taiwan
| | - Ting-Jung Wu
- Chang-Gung Transplantation Institute, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University Medical School, Taipei, Taiwan
| | - Chen-Fang Lee
- Chang-Gung Transplantation Institute, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University Medical School, Taipei, Taiwan
| | - Tsung-Han Wu
- Chang-Gung Transplantation Institute, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University Medical School, Taipei, Taiwan
| | - Wei-Chen Lee
- Chang-Gung Transplantation Institute, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University Medical School, Taipei, Taiwan
| |
Collapse
|
|
35
|
Prognostic impact of underlying liver fibrosis and cirrhosis after curative resection of hepatocellular carcinoma. World J Surg 2011; 34:2442-51. [PMID: 20544346 DOI: 10.1007/s00268-010-0655-5] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND In the case of hepatocellular carcinoma (HCC), underlying liver pathology may not only determine the feasibility of surgery but may also affect the postsurgical outcome. We report our experience after curative liver resection for HCC in patients with normal liver, liver fibrosis, and liver cirrhosis. METHODS A total of 72 patients after liver resection with curative intention were analyzed. Histopathologic findings of tumor-unaffected liver tissue were used for retrospective classification: group A (normal liver); group B (liver fibrosis); group C (liver cirrhosis). The groups were compared for differences in short-term surgical results, total survival, and recurrence-free survival. RESULTS The rate of major complications was 34.7% and did not significantly differ among groups. The overall perioperative mortality rate was 9.7%, with one patient dying in group A and three patients dying in each of the other two groups. Including perioperative mortality, the median overall survival for the whole group was 37.3 months (95% confidence interval 29.3-45.2 months). The respective 1-, 2-, and 5-year survival rates for group A (n = 21) were 86%, 71%, and 50% and for group C (n = 24) 62%, 50%, and 17%. The overall survival of group B (n = 27) was intermediate (log-rank, P = 0.032). The respective recurrence-free survival rates were 76%, 42%, and 20% for group A and 39%, 13%, and 4% for group C, with group B being intermediate (log-rank, P = 0.016). CONCLUSIONS Our data demonstrate that liver resection in the presence of compensated liver cirrhosis is feasible but associated with a significantly impaired prognosis for overall and recurrence-free survival. The management of cirrhotic patients with compensated liver function and HCC therefore also requires the opportunity for transplantation.
Collapse
|
|
36
|
Nathan H, Bridges JFP, Schulick RD, Cameron AM, Hirose K, Edil BH, Wolfgang CL, Segev DL, Choti MA, Pawlik TM. Understanding surgical decision making in early hepatocellular carcinoma. J Clin Oncol 2011; 29:619-25. [PMID: 21205759 DOI: 10.1200/jco.2010.30.8650] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
PURPOSE The choice between liver transplantation (LT), liver resection (LR), and radiofrequency ablation (RFA) as initial therapy for early hepatocellular carcinoma (HCC) is controversial, yet little is known about how surgeons choose therapy for individual patients. We sought to quantify the impact of both clinical factors and surgeon specialty on surgical decision making in early HCC by using conjoint analysis. METHODS Surgeons with an interest in liver surgery were invited to complete a Web-based survey including 10 case scenarios. Choice of therapy was then analyzed by using regression models that included both clinical factors and surgeon specialty (non-LT v LT). RESULTS When assessing early HCC occurrences, non-LT surgeons (50% LR; 41% LT; 9% RFA) made significantly different recommendations compared with LT surgeons (63% LT; 31% LR; 6% RFA; P < .001). Clinical factors, including tumor number and size, type of resection required, and platelet count, had significant effects on the choice between LR, LT, and RFA. After adjusting for clinical factors, non-LT surgeons remained more likely than LT surgeons to choose LR compared with LT (relative risk ratio [RRR], 2.67). When the weight of each clinical factor was allowed to vary by surgeon specialty, the residual independent effect of surgeon specialty on the decision between LR and LT was negligible (RRR, 0.93). CONCLUSION The impact of surgeon specialty on choice of therapy for early HCC is stronger than that of some clinical factors. However, the influence of surgeon specialty does not merely reflect an across-the-board preference for one therapy over another. Rather, certain clinical factors are weighed differently by surgeons in different specialties.
Collapse
Affiliation(s)
- Hari Nathan
- The Johns Hopkins Hospital, 600 N Wolfe St, Harvey 611, Baltimore, MD 21287, USA
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
37
|
Merchant N, David CS, Cunningham SC. Early Hepatocellular Carcinoma: Transplantation versus Resection: The Case for Liver Resection. Int J Hepatol 2011; 2011:142085. [PMID: 21994848 PMCID: PMC3170737 DOI: 10.4061/2011/142085] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2011] [Accepted: 02/27/2011] [Indexed: 12/11/2022] Open
Abstract
The optimal surgical treatment of hepatocellular carcinoma on well-compensated cirrhosis is controversial. Advocates of liver transplantation cite better long-term survival, lower risk of recurrence, and the ability of transplantation to treat both the HCC and the underlying liver cirrhosis. Transplantation, however, is not universally available to all appropriate-risk candidates because of a lack of sufficient organ donors and in addition suffers from the disadvantages of requiring a more complex pre- and postoperative management associated with risks of inaccessibility, noncompliance, and late complications. Resection, by contrast, is much more easily and widely available, avoids many of those risks, is by many accounts as effective at achieving similar long-term survival, and still allows for safe, subsequent liver transplantation in cases of recurrence. Here, arguments are made in favor of resection being easier, safer, simpler, and comparably effective in the treatment of HCC relative to transplantation, and therefore being the optimal initial treatment in cases of hepatocellular carcinoma on well-compensated cirrhosis.
Collapse
Affiliation(s)
- Nishant Merchant
- Department of Surgery, Saint Agnes Hospital, 900 Caton Avenue, Mailbox #207, Baltimore, MD 21229, USA
| | - Calvin S. David
- Department of Surgery, Saint Agnes Hospital, 900 Caton Avenue, Mailbox #207, Baltimore, MD 21229, USA
| | - Steven C. Cunningham
- Department of Surgery, Saint Agnes Hospital, 900 Caton Avenue, Mailbox #207, Baltimore, MD 21229, USA,*Steven C. Cunningham:
| |
Collapse
|
|
38
|
Chanyaputhipong J, Low SCA, Chow PKH. Gadoxetate Acid-Enhanced MR Imaging for HCC: A Review for Clinicians. Int J Hepatol 2011; 2011:489342. [PMID: 21994860 PMCID: PMC3170825 DOI: 10.4061/2011/489342] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2011] [Revised: 02/28/2011] [Accepted: 03/31/2011] [Indexed: 12/19/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is increasingly being detected at an earlier stage, owing to the screening programs and regular imaging follow-up in high-risk populations. Small HCCs still pose diagnostic challenges on imaging due to decreased sensitivity and increased frequency of atypical features. Differentiating early HCC from premalignant or benign nodules is important as management differs and has implications on both the quality of life and the overall survival for the patients. Gadoxetate acid (Gd-EOB-DTPA, Primovist(®), Bayer Schering Pharma) is a relatively new, safe and well-tolerated liver-specific contrast agent for magnetic resonance (MR) imaging of the liver that has combined perfusion- and hepatocyte-specific properties, allowing for the acquisition of both dynamic and hepatobiliary phase images. Its high biliary uptake and excretion improves lesion detection and characterization by increasing liver-to-lesion conspicuity in the added hepatobiliary phase imaging. To date, gadoxetate acid-enhanced MRI has been mostly shown to be superior to unenhanced MRI, computed tomography, and other types of contrast agents in the detection and characterization of liver lesions. This review article focuses on the evolving role of gadoxetate acid in the characterization of HCC, differentiating it from other mimickers of HCC.
Collapse
Affiliation(s)
| | - Su-Chong Albert Low
- Department of Diagnostic Radiology, Singapore General Hospital, Outram Road, 169608, Singapore,*Su-Chong Albert Low:
| | - Pierce K. H. Chow
- Department of General Surgery, Singapore General Hospital, 169608, Singapore ,Duke-NUS Graduate Medical School, 169857, Singapore
| |
Collapse
|
|
39
|
Rossi L, Zoratto F, Papa A, Iodice F, Minozzi M, Frati L, Tomao S. Current approach in the treatment of hepatocellular carcinoma. World J Gastrointest Oncol 2010; 2:348-59. [PMID: 21160806 PMCID: PMC2999141 DOI: 10.4251/wjgo.v2.i9.348] [Citation(s) in RCA: 70] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2010] [Revised: 08/24/2010] [Accepted: 08/31/2010] [Indexed: 02/05/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common malignant hepatobiliary disease; it is responsible for about 1 million deaths per year. Risk factors include hepatitis B and C, hepatic cirrhosis, including alcohol related hepatitis, metabolic and nutritional hepatic damage. The main modality of diffusion is intrahepatic in the natural course of the disease. There are two leading types of treatment: local and systemic. Surgical resection and liver transplantation constitute the most appropriate local treatments and are considered the only real possibility for recovery. Other local approaches include: radiofrequency ablation, percutaneous ethanol ablation, hepatic endoarterial chemoembolization and intrahepatic radiotherapy (SIRT: selective internal radiation therapy). These last treatments are used to control the disease when surgery or transplantation is not achievable; in some cases they are able to prolong survival while they constitute mainly a palliative treatment. Systemic treatments include: chemotherapy, immunological and hormonal therapies and, more recently, the introduction of new specific molecular target drugs. At the moment, in this group, the only drug that has given positive results during phase III trials (SHARP study) is Sorafenib. Sorafenib represents the only primary systemic therapy that has demonstrated, unlike the other treatments previously described, an increase in survival rate in patients affected with advanced HCC. Currently, other studies are taking place that are further developing the potential of this drug. These studies, including phase III trials, are directed in order to test the activity and safety of new emerging drugs with targeted activity. Examples of these new agents are: Sunitinib, Gefitinib, Cetuximab, Bevacizumab and Erlotinib.
Collapse
Affiliation(s)
- Luigi Rossi
- Luigi Rossi, Federica Zoratto, Anselmo Papa, Marina Minozzi, Luigi Frati, Silverio Tomao, Department of Experimental Medicine, University of Rome "Sapienza", Viale Regina Elena 324, 00161 Rome, Italy
| | | | | | | | | | | | | |
Collapse
|
|
40
|
Thomas MB, Jaffe D, Choti MM, Belghiti J, Curley S, Fong Y, Gores G, Kerlan R, Merle P, O'Neil B, Poon R, Schwartz L, Tepper J, Yao F, Haller D, Mooney M, Venook A. Hepatocellular carcinoma: consensus recommendations of the National Cancer Institute Clinical Trials Planning Meeting. J Clin Oncol 2010; 28:3994-4005. [PMID: 20679622 DOI: 10.1200/jco.2010.28.7805] [Citation(s) in RCA: 315] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Hepatocelluar carcinoma (HCC) is the most common primary malignancy of the liver in adults and the third most common cause of cancer death worldwide. The incidence of HCC in the United States is rising steadily because of the prevalence of hepatitis C viral infection and other causes of hepatic cirrhosis. The majority of patients have underlying hepatic dysfunction, which complicates patient management and the search for safe and effective therapies. The Clinical Trials Planning Meeting (CTPM) in HCC was convened by the National Cancer Institute's Gastrointestinal Cancer Steering Committee to identify the key knowledge gaps in HCC and define clinical research priorities. The CTPM structured its review according to current evidence-based treatment modalities in HCC and prioritized the recommendations on the basis of the patient populations representing the greatest unmet medical need.
Collapse
Affiliation(s)
- Melanie B Thomas
- Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA.
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|