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Huang J, Huang W, Guo Y, Cai M, Zhou J, Lin L, Zhu K. Risk Factors, Patterns, and Long-Term Survival of Recurrence After Radiofrequency Ablation With or Without Transarterial Chemoembolization for Hepatocellular Carcinoma. Front Oncol 2021; 11:638428. [PMID: 34123790 PMCID: PMC8191459 DOI: 10.3389/fonc.2021.638428] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2020] [Accepted: 04/13/2021] [Indexed: 12/12/2022] Open
Abstract
Objectives To classify hepatocellular carcinoma (HCC) recurrence patterns after radiofrequency ablation (RFA) or transarterial chemoembolization (TACE) combined with RFA (TACE-RFA) and analyze their risk factors and impacts on survival. Methods We retrospectively evaluated the medical records of HCC patients who underwent RFA or TACE-RFA from January 2006 to December 2016. HCC recurrences were classified into four patterns: local tumor progression (LTP), intra-segmental recurrence, extra-segmental recurrence, and aggressive recurrence. Risk factors, overall survival (OS), and post-recurrence survival of each pattern were evaluated. Results A total of 249 patients with a single, hepatitis-B virus (HBV)-related HCC ≤ 5.0 cm who underwent RFA (HCC ≤ 3.0 cm) or TACE-RFA (HCC of 3.1-5.0 cm) were included. During follow-up (median, 53 months), 163 patients experienced HCC recurrence: 40, 43, 62 and 18 patients developed LTP, intra-segmental recurrence, extra-segmental recurrence, and aggressive recurrence, respectively; the median post-recurrence survival was 49, 37, 25 and 15 months, respectively (P < .001); the median OS was 65, 56, 58 and 28 months, respectively (P < .001). Independent risk factors for each pattern were as follows: tumor sized 2.1-3.0 cm undergoing RFA alone and insufficient ablative margin for LTP, periportal tumor and non-smooth tumor margin for intra-segmental recurrence, HBV-DNA ≥ 2000 IU/mL for extra-segmental recurrence, and periportal tumor and α-fetoprotein ≥ 100 ng/mL for aggressive recurrence. Recurrence pattern (P < .001) and Child-Pugh class B (P = .025) were independent predictors for OS. Conclusions Based on our classification, each recurrence pattern had different recurrence risk factors, OS, and post-recurrence survival.
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Affiliation(s)
- Jingjun Huang
- Department of Minimally Invasive Interventional Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Wensou Huang
- Department of Minimally Invasive Interventional Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Yongjian Guo
- Department of Minimally Invasive Interventional Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Mingyue Cai
- Department of Minimally Invasive Interventional Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Jingwen Zhou
- Department of Minimally Invasive Interventional Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Liteng Lin
- Department of Minimally Invasive Interventional Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Kangshun Zhu
- Department of Minimally Invasive Interventional Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
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Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR, Zhu AX, Murad MH, Marrero JA. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 2018; 67:358-380. [PMID: 28130846 DOI: 10.1002/hep.29086] [Citation(s) in RCA: 2966] [Impact Index Per Article: 423.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2017] [Accepted: 01/10/2017] [Indexed: 12/07/2022]
Affiliation(s)
- Julie K Heimbach
- Division of Transplant Surgery, William J. von Liebig Transplant Center, Mayo Clinic, Rochester, MN
| | - Laura M Kulik
- Department of Medicine, Division of Gastroenterology and Hepatology, Northwestern University, Chicago, IL
| | - Richard S Finn
- Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine at the University of California, Los Angeles, Santa Monica Geffen School of Medicine at UCLA, Los Angeles, California
| | - Claude B Sirlin
- Liver Imaging Group, Department of Radiology, University of California, San Diego
| | | | - Lewis R Roberts
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Andrew X Zhu
- Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
| | - M Hassan Murad
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, MN
| | - Jorge A Marrero
- Digestive and Liver Diseases Division, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
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Bossé D, Ng T, Ahmad C, Alfakeeh A, Alruzug I, Biagi J, Brierley J, Chaudhury P, Cleary S, Colwell B, Cripps C, Dawson LA, Dorreen M, Ferland E, Galiatsatos P, Girard S, Gray S, Halwani F, Kopek N, Mahmud A, Martel G, Robillard L, Samson B, Seal M, Siddiqui J, Sideris L, Snow S, Thirwell M, Vickers M, Goodwin R, Goel R, Hsu T, Tsvetkova E, Ward B, Asmis T. Eastern Canadian Gastrointestinal Cancer Consensus Conference 2016. ACTA ACUST UNITED AC 2016; 23:e605-e614. [PMID: 28050151 DOI: 10.3747/co.23.3394] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2016 was held in Montreal, Quebec, 5-7 February. Experts in radiation oncology, medical oncology, surgical oncology, and infectious diseases involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics: ■ Follow-up and survivorship of patients with resected colorectal cancer■ Indications for liver metastasectomy■ Treatment of oligometastases by stereotactic body radiation therapy■ Treatment of borderline resectable and unresectable pancreatic cancer■ Transarterial chemoembolization in hepatocellular carcinoma■ Infectious complications of antineoplastic agents.
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Affiliation(s)
- D Bossé
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
| | - T Ng
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
| | - C Ahmad
- Newfoundland and Labrador: Dr. H. Bliss Murphy Cancer Centre, St. John's (Ahmad, Seal, Siddiqui)
| | - A Alfakeeh
- Quebec: Hôpital Charles-LeMoyne Cancer Centre, Greenfield Park (Samson); McGill University Health Centre, Montreal (Alfakeeh, Alruzug, Chaudhury, Kopek, Thirlwell, Ward); Sir Mortimer B. Davis Jewish General Hospital (Galiatsatos); Centre Hospitalier Pierre-Boucher (Ferland); Centre Hospitalier Universitaire de Montréal (Girard, Sideris)
| | - I Alruzug
- Quebec: Hôpital Charles-LeMoyne Cancer Centre, Greenfield Park (Samson); McGill University Health Centre, Montreal (Alfakeeh, Alruzug, Chaudhury, Kopek, Thirlwell, Ward); Sir Mortimer B. Davis Jewish General Hospital (Galiatsatos); Centre Hospitalier Pierre-Boucher (Ferland); Centre Hospitalier Universitaire de Montréal (Girard, Sideris)
| | - J Biagi
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
| | - J Brierley
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
| | - P Chaudhury
- Quebec: Hôpital Charles-LeMoyne Cancer Centre, Greenfield Park (Samson); McGill University Health Centre, Montreal (Alfakeeh, Alruzug, Chaudhury, Kopek, Thirlwell, Ward); Sir Mortimer B. Davis Jewish General Hospital (Galiatsatos); Centre Hospitalier Pierre-Boucher (Ferland); Centre Hospitalier Universitaire de Montréal (Girard, Sideris)
| | - S Cleary
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
| | - B Colwell
- Nova Scotia: QEII Health Sciences Centre, Halifax (Colwell, Dorreen, Snow)
| | - C Cripps
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
| | - L A Dawson
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
| | - M Dorreen
- Nova Scotia: QEII Health Sciences Centre, Halifax (Colwell, Dorreen, Snow)
| | - E Ferland
- Quebec: Hôpital Charles-LeMoyne Cancer Centre, Greenfield Park (Samson); McGill University Health Centre, Montreal (Alfakeeh, Alruzug, Chaudhury, Kopek, Thirlwell, Ward); Sir Mortimer B. Davis Jewish General Hospital (Galiatsatos); Centre Hospitalier Pierre-Boucher (Ferland); Centre Hospitalier Universitaire de Montréal (Girard, Sideris)
| | - P Galiatsatos
- Quebec: Hôpital Charles-LeMoyne Cancer Centre, Greenfield Park (Samson); McGill University Health Centre, Montreal (Alfakeeh, Alruzug, Chaudhury, Kopek, Thirlwell, Ward); Sir Mortimer B. Davis Jewish General Hospital (Galiatsatos); Centre Hospitalier Pierre-Boucher (Ferland); Centre Hospitalier Universitaire de Montréal (Girard, Sideris)
| | - S Girard
- Quebec: Hôpital Charles-LeMoyne Cancer Centre, Greenfield Park (Samson); McGill University Health Centre, Montreal (Alfakeeh, Alruzug, Chaudhury, Kopek, Thirlwell, Ward); Sir Mortimer B. Davis Jewish General Hospital (Galiatsatos); Centre Hospitalier Pierre-Boucher (Ferland); Centre Hospitalier Universitaire de Montréal (Girard, Sideris)
| | - S Gray
- New Brunswick: Saint John Regional Hospital, Saint John (Gray)
| | - F Halwani
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
| | - N Kopek
- Quebec: Hôpital Charles-LeMoyne Cancer Centre, Greenfield Park (Samson); McGill University Health Centre, Montreal (Alfakeeh, Alruzug, Chaudhury, Kopek, Thirlwell, Ward); Sir Mortimer B. Davis Jewish General Hospital (Galiatsatos); Centre Hospitalier Pierre-Boucher (Ferland); Centre Hospitalier Universitaire de Montréal (Girard, Sideris)
| | - A Mahmud
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
| | - G Martel
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
| | - L Robillard
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
| | - B Samson
- Quebec: Hôpital Charles-LeMoyne Cancer Centre, Greenfield Park (Samson); McGill University Health Centre, Montreal (Alfakeeh, Alruzug, Chaudhury, Kopek, Thirlwell, Ward); Sir Mortimer B. Davis Jewish General Hospital (Galiatsatos); Centre Hospitalier Pierre-Boucher (Ferland); Centre Hospitalier Universitaire de Montréal (Girard, Sideris)
| | - M Seal
- Newfoundland and Labrador: Dr. H. Bliss Murphy Cancer Centre, St. John's (Ahmad, Seal, Siddiqui)
| | - J Siddiqui
- Newfoundland and Labrador: Dr. H. Bliss Murphy Cancer Centre, St. John's (Ahmad, Seal, Siddiqui)
| | - L Sideris
- Quebec: Hôpital Charles-LeMoyne Cancer Centre, Greenfield Park (Samson); McGill University Health Centre, Montreal (Alfakeeh, Alruzug, Chaudhury, Kopek, Thirlwell, Ward); Sir Mortimer B. Davis Jewish General Hospital (Galiatsatos); Centre Hospitalier Pierre-Boucher (Ferland); Centre Hospitalier Universitaire de Montréal (Girard, Sideris)
| | - S Snow
- Nova Scotia: QEII Health Sciences Centre, Halifax (Colwell, Dorreen, Snow)
| | - M Thirwell
- Quebec: Hôpital Charles-LeMoyne Cancer Centre, Greenfield Park (Samson); McGill University Health Centre, Montreal (Alfakeeh, Alruzug, Chaudhury, Kopek, Thirlwell, Ward); Sir Mortimer B. Davis Jewish General Hospital (Galiatsatos); Centre Hospitalier Pierre-Boucher (Ferland); Centre Hospitalier Universitaire de Montréal (Girard, Sideris)
| | - M Vickers
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
| | - R Goodwin
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
| | - R Goel
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
| | - T Hsu
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
| | - E Tsvetkova
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
| | - B Ward
- Quebec: Hôpital Charles-LeMoyne Cancer Centre, Greenfield Park (Samson); McGill University Health Centre, Montreal (Alfakeeh, Alruzug, Chaudhury, Kopek, Thirlwell, Ward); Sir Mortimer B. Davis Jewish General Hospital (Galiatsatos); Centre Hospitalier Pierre-Boucher (Ferland); Centre Hospitalier Universitaire de Montréal (Girard, Sideris)
| | - T Asmis
- Ontario: The Ottawa Hospital Cancer Centre, Ottawa (Asmis, Bossé, Cripps, Goel, Goodwin, Halwani, Hsu, Martel, Ng, Robillard, Vickers); Queen's University and Cancer Centre of Southeastern Ontario, Kingston (Biagi); Princess Margaret Cancer Centre, Toronto (Brierley, Cleary, Dawson); Juravinski Cancer Centre, Hamilton (Tsvetkova); Cancer Centre of Southeastern Ontario, Kingston (Mahmud)
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Song MJ, Bae SH, Lee JS, Lee SW, Song DS, You CR, Choi JY, Yoon SK. Combination transarterial chemoembolization and radiofrequency ablation therapy for early hepatocellular carcinoma. Korean J Intern Med 2016; 31:242-252. [PMID: 26874512 PMCID: PMC4773726 DOI: 10.3904/kjim.2015.112] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2014] [Revised: 08/13/2014] [Accepted: 11/18/2015] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND/AIMS We compared the recurrence of hepatocellular carcinoma (HCC) and the survival of patients who received radiofrequency ablation (RFA) after transarterial chemoembolization (TACE) with patients treated with TACE or RFA alone. METHODS This study included 201 patients with HCC, who were consecutively enrolled at Seoul St. Mary's Hospital between December 2004 and February 2010. Inclusion criteria were a single HCC ≤ 5.0 cm or up to three HCCs ≤ 3.0 cm. We used a propensity score model to compare HCC patients (n = 87) who received RFA after TACE (TACE + RFA) with those who received TACE (n = 71) or RFA alone (n = 43). RESULTS The median follow-up period was 33.3 months (range, 6.8 to 80.9). The TACE + RFA group showed significantly lower local recurrence than the RFA or TACE groups (hazard ratio [HR], 0.309; 95% confidence interval [CI], 0.130 to 0.736; p = 0.008; and HR, 0.352; 95% CI, 0.158 to 0.787; p = 0.011, respectively). The overall survival was significantly better in the TACE + RFA group compared to the RFA group (HR, 0.422; 95% CI, 0.185 to 0.964; p = 0.041). However, the survival benefit was not different between the TACE + RFA and TACE groups (p = 0.124). Subgroup analysis showed that among patients with a tumor size < 3 cm, the TACE + RFA group had significantly better long-term survival than those in the TACE or RFA groups (p = 0.017, p = 0.004, respectively). CONCLUSIONS TACE + RFA combination treatment showed favorable local recurrence and better overall survival rates in early-stage HCC patients. Patients with tumors < 3 cm are likely to benefit more from TACE + RFA combination treatment. Additional studies are needed for the selection of suitable HCC patients for TACE + RFA treatment.
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Affiliation(s)
- Myeong Jun Song
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Si Hyun Bae
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - June Sung Lee
- Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Korea
| | - Sung Won Lee
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Do Seon Song
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Chan Ran You
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jong Young Choi
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Seung Kew Yoon
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Di Costanzo GG, Tortora R. Intermediate hepatocellular carcinoma: How to choose the best treatment modality? World J Hepatol 2015; 7:1184-1191. [PMID: 26019734 PMCID: PMC4438493 DOI: 10.4254/wjh.v7.i9.1184] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2014] [Revised: 10/16/2014] [Accepted: 02/11/2015] [Indexed: 02/06/2023] Open
Abstract
Intermediate stage, or stage B according to Barcelona Clinic Liver Cancer classification, of hepatocellular carcinoma (HCC) comprises a heterogeneous population with different tumor burden and liver function. This heterogeneity is confirmed by the large variability of treatment choice and disease-relate survival. The aim of this review was to highlight the existing evidences regarding this specific topic. In a multidisciplinary evaluation, patients with large (> 5 cm) solitary HCC should be firstly considered for liver resection (LR). When LR is unfeasible, locoregional treatments are evaluable therapeutic options, being transarterial chemoembolization (TACE), the most used procedure. Percutaneous ablation can be an evaluable treatment for large HCC. However, the efficacy of all ablative procedures decrease as tumor size increases over 3 cm. In clinical practice, a combination treatment strategy [TACE or transarterial radioembolization (TARE)-plus percutaneous ablation] is “a priori” preferred in a relevant percentage of these patients. On the other hands, sorafenib is the treatment of choice in patients who are unsuitable to surgery and/or with a contraindication to locoregional treatments. In multifocal HCC, TACE is the first-line treatment. The role of TARE is still undefined. Surgery may have also a role in the treatment of multifocal HCC in selected cases (patients with up to three nodules, multifocal HCC involving 2-3 adjacent liver segments). In some patients with bilobar disease the combination of LR and ablative treatment may be a valuable option. The choice of the best treatment in the patient with intermediate stage HCC should be “patient-tailored” and made by a multidisciplinary team.
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Adhoute X, Penaranda G, Castellani P, Perrier H, Bourliere M. Recommendations for the use of chemoembolization in patients with hepatocellular carcinoma: Usefulness of scoring system? World J Hepatol 2015; 7:521-31. [PMID: 25848475 PMCID: PMC4381174 DOI: 10.4254/wjh.v7.i3.521] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2014] [Revised: 10/02/2014] [Accepted: 11/27/2014] [Indexed: 02/06/2023] Open
Abstract
Several hepatocellular carcinoma (HCC) staging systems have been established, and a variety of country-specific treatment strategies are also proposed. The barcelona - clinic liver cancer (BCLC) system is the most widely used in Europe. The Hong Kong liver Cancer is a new prognostic staging system; it might become the reference system in Asia. Transarterial chemoembolization (TACE) is the most widely used treatment for HCC worldwide; but it showed a benefit only for intermediate stage HCC (BCLC B), and there is still no consensus concerning treatment methods and treatment strategies. In view of the highly diverse nature of HCC and practices, a scoring system designed to assist with decision making before the first TACE is performed or prior to repeating the procedure would be highly useful.
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Affiliation(s)
- Xavier Adhoute
- Xavier Adhoute, Paul Castellani, Herve Perrier, Marc Bourliere, Department of Hepatology, Hopital Saint-Joseph, 13285 Marseille, France
| | - Guillaume Penaranda
- Xavier Adhoute, Paul Castellani, Herve Perrier, Marc Bourliere, Department of Hepatology, Hopital Saint-Joseph, 13285 Marseille, France
| | - Paul Castellani
- Xavier Adhoute, Paul Castellani, Herve Perrier, Marc Bourliere, Department of Hepatology, Hopital Saint-Joseph, 13285 Marseille, France
| | - Herve Perrier
- Xavier Adhoute, Paul Castellani, Herve Perrier, Marc Bourliere, Department of Hepatology, Hopital Saint-Joseph, 13285 Marseille, France
| | - Marc Bourliere
- Xavier Adhoute, Paul Castellani, Herve Perrier, Marc Bourliere, Department of Hepatology, Hopital Saint-Joseph, 13285 Marseille, France
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Boily G, Villeneuve JP, Lacoursière L, Chaudhury P, Couture F, Ouellet JF, Lapointe R, Goulet S, Gervais N, Comité de l'évolution des pratiques en oncologie. Transarterial embolization therapies for the treatment of hepatocellular carcinoma: CEPO review and clinical recommendations. HPB (Oxford) 2015; 17:52-65. [PMID: 24961288 PMCID: PMC4266441 DOI: 10.1111/hpb.12273] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2014] [Accepted: 04/07/2014] [Indexed: 12/12/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is one of the most deadly cancers in the world and its incidence rate has consistently increased over the past 15 years in Canada. Although transarterial embolization therapies are palliative options commonly used for the treatment of HCC, their efficacy is still controversial. The objective of this guideline is to review the efficacy and safety of transarterial embolization therapies for the treatment of HCC and to develop evidence-based recommendations. METHOD A review of the scientific literature published up to October 2013 was performed. A total of 38 studies were included. RECOMMENDATIONS Considering the evidence available to date, the CEPO recommends the following: (i) transarterial chemoembolization therapy (TACE) be considered a standard of practice for the palliative treatment of HCC in eligible patients; (ii) drug-eluting beads (DEB)-TACE be considered an alternative and equivalent treatment to conventional TACE in terms of oncological efficacy (overall survival) and incidence of severe toxicities; (iii) the decision to treat with TACE or DEB-TACE be discussed in tumour boards; (iv) bland embolization (TAE) not be considered for the treatment of HCC; (v) radioembolization (TARE) not be considered outside of a clinical trial setting; and (vi) sorafenib combined with TACE not be considered outside of a clinical trial setting.
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Affiliation(s)
- Gino Boily
- Institut national d'excellence en santé et en services sociauxQuébec, QC, Canada
| | | | - Luc Lacoursière
- Hôtel-Dieu de Lévis (CSSS Alphonse-Desjardins)Lévis, QC, Canada
| | | | - Félix Couture
- Hôtel-Dieu de Québec (CHU de Québec)Québec, QC, Canada
| | | | | | - Stéphanie Goulet
- Institut national d'excellence en santé et en services sociauxQuébec, QC, Canada
| | - Normand Gervais
- Centre hospitalier régional du Grand-Portage (CSSS de Rivière-du-Loup)Rivière-du-Loup, QC, Canada,Correspondence, Normand Gervais, Centre hospitalier régional du Grand-Portage (CSSS de Rivière-du-Loup), 75 rue St-Henri, Rivière-du-Loup, QC, Canada G5R 2A4. Tel:+1 418 868 1000. Fax: +1 418 868 3336. E-mail:
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8
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Masaki T, Morishita A, Kurokohchi K, Kuriyama S. Multidisciplinary treatment of patients with hepatocellular carcinoma. Expert Rev Anticancer Ther 2014; 6:1377-84. [PMID: 17069523 DOI: 10.1586/14737140.6.10.1377] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Hepatocellular carcinoma is one of the most common malignancies in the world. When it is diagnosed, patients can choose from among several potentially curative treatments, such as surgical resection, transplantation, ablation therapy and transcatheter arterial chemoembolization. This review will give an overview of the present management of hepatocellular carcinoma. Liver transplantation is considered the best curative option, achieving a high rate of complete response, especially in patients with small hepatocellular carcinoma and good residual liver function. However, a shortage of donor livers restricts the availability of transplantation. In addition, only a minority of patients with hepatocellular carcinoma can be treated surgically, owing to impaired hepatic reserve, multiple intrahepatic lesions, extrahepatic lesions and the inability to obtain an optimal tumor-free margin. Therefore, for most patients, other types of interventions (transcatheter arterial chemoembolization, percutaneous ethanol injection and radiofrequency ablation) have been developed. Among them, two local ablative modalities, percutaneous ethanol injection and percutaneous radiofrequency ablation, have been accepted as the only potentially curative nonsurgical treatments for hepatocellular carcinoma. Radiofrequency ablation may become a standard nonsurgical treatment option for patients with early hepatocellular carcinoma.
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Affiliation(s)
- Tsutomu Masaki
- Kagawa Medical University, Third Department of Internal Medicine, 1750-1 Ikenobe Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
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9
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Weis S, Franke A, Mössner J, Jakobsen JC, Schoppmeyer K. Radiofrequency (thermal) ablation versus no intervention or other interventions for hepatocellular carcinoma. Cochrane Database Syst Rev 2013; 2013:CD003046. [PMID: 24357457 PMCID: PMC11931681 DOI: 10.1002/14651858.cd003046.pub3] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Hepatocellular carcinoma is the fifth most common cancer worldwide. Percutaneous interventional therapies, such as radiofrequency (thermal) ablation (RFA), have been developed for early hepatocellular carcinoma. RFA competes with other interventional techniques such as percutaneous ethanol injection, surgical resection, and liver transplantation. The potential benefits and harms of RFA compared with placebo, no intervention, chemotherapy, hepatic resection, liver transplantation, or other interventions are unclear. OBJECTIVES To assess the beneficial and harmful effects of RFA versus placebo, no intervention, or any other therapeutic approach in patients with hepatocellular carcinoma. SEARCH METHODS We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and ISI Web of Science to September 2012. We handsearched meeting abstracts from ASCO, ESMO, AASLD, EASL, APASL, and references of articles. We also contacted researchers in the field (last search September 2012). SELECTION CRITERIA We considered for inclusion randomised clinical trials investigating the effects of RFA versus placebo, no intervention, or any other therapeutic approach on hepatocellular carcinoma patients regardless of blinding, language, and publication status. DATA COLLECTION AND ANALYSIS Two review authors independently performed the selection of trials, assessment of risk of bias, and data extraction. We contacted principal investigators for missing information. We analysed hazard ratios (HR) as relevant effect measures for overall survival, two-year survival, event-free survival, and local recurrences with 95% confidence intervals (CI). In addition, we analysed dichotomous survival outcomes using risk ratios (RR). We used trial sequential analysis to control the risk of random errors ('play of chance'). MAIN RESULTS We identified no trials comparing RFA versus placebo, no intervention, or liver transplantation. We identified and included 11 randomised clinical trials with 1819 participants that included four comparisons: RFA versus hepatic resection (three trials, 578 participants); RFA versus percutaneous ethanol injection (six trials, 1088 participants) including one three-armed trial that also investigated RFA versus acetic acid injection; RFA versus microwave ablation (one trial, 72 participants); and RFA versus laser ablation (one trial, 81 participants). Ten of the eleven included trials reported on the primary outcome of this review, overall survival. Rates of major complications or procedure-related deaths were reported in 10 trials. The overall risk of bias was considered low in five trials and high in six trials. For a subgroup analysis, we included only low risk of bias trials. Regarding the comparison RFA versus hepatic resection, there was moderate-quality evidence from two low risk of bias trials that hepatic resection seems more effective than RFA regarding overall survival (HR 0.56; 95% CI 0.40 to 0.78) and two-year survival (HR 0.38; 95% CI 0.17 to 0.84). However, if we included a third trial with high risk of bias, the difference became insignificant (overall survival: HR 0.71; 95% CI 0.44 to 1.15). With regards to the outcomes event-free survival and local progression, hepatic resection also yielded better results than RFA. However, the number of complications was higher in surgically treated participants (odds ratio (OR) 8.24; 95% CI 2.12 to 31.95). RFA seemed superior to percutaneous ethanol or acetic acid injection regarding overall survival (HR 1.64; 95% CI 1.31 to 2.07). The RR for mortality was also in favour of RFA, but did not reach statistical significance (150/490 (30.6%) people in the percutaneous ethanol or acetic acid group versus 119/496 (24.0%) people in the RFA group; RR 1.76; 95% CI 0.97 to 3.22). The proportion of adverse events did not differ significantly between RFA and percutaneous ethanol or acetic acid injection (HR 0.70; 95% CI 0.33 to 1.48). Trial sequential analyses revealed that the number of participants in the included trials was insufficient and that more trials are needed to assess the effects of RFA versus other interventions. AUTHORS' CONCLUSIONS The effects of RFA versus no intervention, chemotherapeutic treatment, or liver transplantation are unknown. We found moderate-quality evidence that hepatic resection is superior to RFA regarding survival. However, RFA might be associated with fewer complications and a shorter hospital stay than hepatic resection. We found moderate-quality evidence showing that RFA seems superior to percutaneous ethanol injection regarding survival. There were too sparse data to recommend or refute ablation achieved by techniques other than RFA. More randomised clinical trials with low risk of bias and low risks of random errors assessing the effect of RFA are needed.
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Affiliation(s)
- Sebastian Weis
- University of LeipzigDivision of Gastroenterology and Rheumatology Department of Internal Medicine, Neurology and DermatologyLiebigstrasse 20LeipzigGermany04103
| | - Annegret Franke
- Universität LeipzigZentrum für Klinische Studien (ZKS) LeipzigHaertelstrasse 16‐18LeipzigGermany04107
| | - Joachim Mössner
- University of LeipzigDivision of Gastroenterology and Rheumatology Department of Internal Medicine, Neurology and DermatologyLiebigstrasse 20LeipzigGermany04103
| | - Janus C Jakobsen
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, RigshospitaletThe Cochrane Hepato‐Biliary GroupBlegdamsvej 9CopenhagenSjællandDenmarkDK‐2100
| | - Konrad Schoppmeyer
- Euregio‐Klinik GmbHInternal MedicineAlbert‐Schweitzer‐Str. 10NordhornGermany48529
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10
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Bolondi L, Cillo U, Colombo M, Craxì A, Farinati F, Giannini EG, Golfieri R, Levrero M, Pinna AD, Piscaglia F, Raimondo G, Trevisani F, Bruno R, Caraceni P, Ciancio A, Coco B, Fraquelli M, Rendina M, Squadrito G, Toniutto P. Position paper of the Italian Association for the Study of the Liver (AISF): the multidisciplinary clinical approach to hepatocellular carcinoma. Dig Liver Dis 2013; 45:712-723. [PMID: 23769756 DOI: 10.1016/j.dld.2013.01.012] [Citation(s) in RCA: 141] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2012] [Accepted: 01/16/2013] [Indexed: 12/11/2022]
Abstract
Patients with hepatocellular carcinoma should be managed with a multidisciplinary approach framed in a network where all the diagnostic techniques and therapeutic resources are available in order to provide the optimal level of care. Given this assumption, the Coordinating Committee of the Italian Association for the Study of the Liver nominated a panel of experts to elaborate practical recommendations for the multidisciplinary management of hepatocellular carcinoma aiming to provide: (1) homogeneous and efficacious diagnostic and staging work-up, and (2) the best treatment choice tailored to patient status and tumour stage at diagnosis. The 2010 updated American Association for the Study of Liver Disease Guidelines for hepatocellular carcinoma were selected as the reference document. For each management issue, the American Association for the Study of Liver Disease recommendations were briefly summarised and discussed, according to both the scientific evidence published after their release and the clinical expertise of the Italian centres taking care of these patients. The Italian Association for the Study of the Liver expert panel recommendations are finally reported.
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11
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Kobayashi T, Ishiyama K, Ohdan H. Prevention of recurrence after curative treatment for hepatocellular carcinoma. Surg Today 2012; 43:1347-54. [PMID: 23271667 DOI: 10.1007/s00595-012-0473-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2012] [Accepted: 10/26/2012] [Indexed: 12/22/2022]
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12
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Ablative zone size created by radiofrequency ablation with and without chemoembolization in small hepatocellular carcinomas. Jpn J Radiol 2012; 30:553-9. [PMID: 22610876 DOI: 10.1007/s11604-012-0087-2] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2012] [Accepted: 04/27/2012] [Indexed: 12/12/2022]
Abstract
PURPOSE We retrospectively evaluated whether combined use of chemoembolization expands ablative zone sizes created by radiofrequency (RF) ablation in patients with small hepatocellular carcinomas (HCCs). MATERIALS AND METHODS Fifty-seven patients treated with single RF ablation for solitary HCC measuring ≤2 cm were assessed. RF ablation alone was done in nine patients and in 48 patients following chemoembolization, with an interval of 0 days in 6, 1-14 days in 27, 15-28 days in 6, and ≥4 weeks in 9. Ablative zone sizes, disappearance of tumor enhancement, and creation of sufficient ablative margins (>5 mm) were evaluated on contrast-enhanced computed tomography (CT) images. RESULTS Both mean long-axis (4.2-4.7 vs. 3.6 ± 0.4 cm, p < 0.04) and short-axis (3.3-3.8 vs. 2.3 ± 0.5 cm, p < 0.03) diameters were expanded significantly when RF ablation was done until 4 weeks after chemoembolization than with RF ablation alone. Tumor enhancement disappeared in all patients. Frequency of achieving sufficient ablative margins was significantly higher when RF ablation was done until 4 weeks after chemoembolization than with RF ablation alone (74.0-83.3 vs. 22.2 %, p < 0.05). CONCLUSION Ablative zones created by RF ablation with chemoembolization become larger than RF ablation alone, leading to secure ablative margins.
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13
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Forner A, Llovet JM, Bruix J. Chemoembolization for intermediate HCC: is there proof of survival benefit? J Hepatol 2012; 56:984-6. [PMID: 22008737 DOI: 10.1016/j.jhep.2011.08.017] [Citation(s) in RCA: 94] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2011] [Accepted: 08/21/2011] [Indexed: 12/11/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) results in more than 600,000 deaths per year. Transarterial embolisation(TAE) and transarterial chemoembolisation (TACE) have become standard loco-regional treatments for unresectable HCC. OBJECTIVES To assess the beneficial and harmful effects of TACE or TAE. SEARCH STRATEGY We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Cancer Network register,The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and The Latin American Caribbean Health Sciences Literature(LILACS) from dates of inceptions up to September 2010. SELECTION CRITERIA We considered for inclusion all randomised trials that compared TACE or TAE versus placebo, sham, or no intervention.Co-interventions were allowed if comparable between intervention groups. Trials with inadequate randomisation were excluded. DATA COLLECTION AND ANALYSIS For all-cause mortality, we calculated the log hazard ratio (HR) with standard error as point estimate and pooled them for meta-analysis using the inverse variance method. Sub-group analyses were performed regarding intervention regimen, trial truncation, or co-interventions. We validated the results with trial sequential analyses. We used random-effects model in all meta-analyses in anticipation of statistical heterogeneity among the trials. MAIN RESULTS We included nine trials with 645 participants. Six trials assessed TACE versus control and three trials assessed TAE versus control. Seven trials had low risk of selection bias based on adequate generation of allocation sequence and concealment – but all these trials had other risks of bias. Three trials were stopped early due to interim inspections and one due to slow accrual. For all-cause mortality,statistical heterogeneity between trials was low to moderate(I2) = 30%). Meta-analysis of trials with low risk of selection bias showed that TACE or TAE versus control does not significantly increase survival (HR 0.88; 95% CI 0.71–1.10). Two trials with low risk of selection bias, no early stopping, and no co-intervention did not establish any significant effect of TACE or TAE on overall survival(hazard ratio 1.22, 95% confidence interval 0.82–1.83; P = 0.33). Trials equential analysis confirmed the absence of evidence for a beneficial effect of TACE or TAE on survival indicating the need for future randomisation of up to 383 additional participants. Substantial differences in criteria for assessing tumor response did not allow quantitative analyses. One trial investigated quality of life but did not detect any significant differences between the intervention groups. A range of adverse events including post-embolisation syndrome and serious complications were reported. AUTHORS’ CONCLUSIONS There is no firm evidence to support or refute TACE or TAE for patients with unresectable HCC. More adequately powered and bias-protected trials are needed.
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Affiliation(s)
- Alejandro Forner
- Barcelona Clinic Liver Cancer (BCLC) group, Liver Unit, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Spain
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14
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Ray CE, Haskal ZJ, Geschwind JFH, Funaki BS. The use of transarterial chemoembolization in the treatment of unresectable hepatocellular carcinoma: a response to the Cochrane Collaboration review of 2011. J Vasc Interv Radiol 2011; 22:1693-6. [PMID: 22035882 PMCID: PMC4332810 DOI: 10.1016/j.jvir.2011.09.014] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2011] [Accepted: 09/06/2011] [Indexed: 02/07/2023] Open
Abstract
This commentary is written in response to a recent Cochrane Collaboration review published in March 2011 (1). The authors of this commentary would like to express their concerns over the conclusions of the Cochrane review, which state, "There is no firm evidence to support or refute transarterial chemoembolization (TACE) or transarterial embolization (TAE) for patients with unresectable hepatocellular carcinoma (HCC)."
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MESH Headings
- Antineoplastic Agents/administration & dosage
- Carcinoma, Hepatocellular/drug therapy
- Carcinoma, Hepatocellular/mortality
- Chemoembolization, Therapeutic/adverse effects
- Chemoembolization, Therapeutic/methods
- Chemoembolization, Therapeutic/mortality
- Embolization, Therapeutic/adverse effects
- Embolization, Therapeutic/methods
- Embolization, Therapeutic/mortality
- Evidence-Based Medicine
- Humans
- Infusions, Intra-Arterial/adverse effects
- Infusions, Intra-Arterial/methods
- Liver Neoplasms/drug therapy
- Liver Neoplasms/mortality
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Affiliation(s)
- Charles E Ray
- University of Colorado, Department of Radiology, Aurora, CO 80045, USA.
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15
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Meza-Junco J, Montano-Loza AJ, Liu DM, Sawyer MB, Bain VG, Ma M, Owen R. Locoregional radiological treatment for hepatocellular carcinoma; Which, when and how? Cancer Treat Rev 2011; 38:54-62. [PMID: 21726960 DOI: 10.1016/j.ctrv.2011.05.002] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2011] [Revised: 04/27/2011] [Accepted: 05/03/2011] [Indexed: 12/11/2022]
Abstract
Hepatocellular carcinoma (HCC) is one of the most frequent and deadliest cancers worldwide. Liver transplantation, surgical resection or local ablation offer the best survival advantages but most patients either present when the tumor is in an advanced stage or the degree of underlying liver disease precludes these options. Several therapies have been proposed for these patients with proven survival benefits. These therapies comprise the locoregional treatment for HCC, and include percutaneous ethanol injection (PEI), radiofrequency ablation (RFA), transarterial chemoembolization (TACE), transarterial radioembolization (TARE), and drug-eluting bead (DEB). PEI and RFA are considered curative treatments for early stage HCC; whereas TACE is a standard of care for intermediate stages. Additionally, evaluation of response to locoregional treatment in HCC is important, as objective response may become a surrogate marker for improved survival. Currently, there are several criteria for response assessment, including the World Health Organization (WHO), the Response Evaluation Criteria in Solid Tumors (RECIST), the European Association for the Study of the Liver Criteria (EASL), and the modified RECIST (mRECIST); however, there has been poor correlation between the clinical benefit provided by locoregional interventional therapies and conventional methods of response assessment. The aim of our study was to review and analyze the current evidence for radiological interventions in HCC, and to propose evidence based recommendations to improve the management of these patients.
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Affiliation(s)
- Judith Meza-Junco
- Department of Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada
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16
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Oliveri RS, Wetterslev J, Gluud C. Transarterial (chemo)embolisation for unresectable hepatocellular carcinoma. Cochrane Database Syst Rev 2011:CD004787. [PMID: 21412886 DOI: 10.1002/14651858.cd004787.pub2] [Citation(s) in RCA: 148] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) results in more than 600,000 deaths per year. Transarterial embolisation (TAE) and transarterial chemoembolisation (TACE) have become standard loco-regional treatments for unresectable HCC. OBJECTIVES To assess the beneficial and harmful effects of TACE or TAE. SEARCH STRATEGY We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Cancer Network register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and The Latin American Caribbean Health Sciences Literature (LILACS) from dates of inceptions up to September 2010. SELECTION CRITERIA We considered for inclusion all randomised trials that compared TACE or TAE versus placebo, sham, or no intervention. Co-interventions were allowed if comparable between intervention groups. Trials with inadequate randomisation were excluded. DATA COLLECTION AND ANALYSIS For all-cause mortality, we calculated the log hazard ratio (HR) with standard error as point estimate and pooled them for meta-analysis using the inverse variance method. Sub-group analyses were performed regarding intervention regimen, trial truncation, or co-interventions. We validated the results with trial sequential analyses. We used random-effects model in all meta-analyses in anticipation of statistical heterogeneity among the trials. MAIN RESULTS We included nine trials with 645 participants. Six trials assessed TACE versus control and three trials assessed TAE versus control. Seven trials had low risk of selection bias based on adequate generation of allocation sequence and concealment - but all these trials had other risks of bias. Three trials were stopped early due to interim inspections and one due to slow accrual. For all-cause mortality, statistical heterogeneity between trials was low to moderate (I(2)= 30%). Meta-analysis of trials with low risk of selection bias showed that TACE or TAE versus control does not significantly increase survival (HR 0.88; 95% CI 0.71 to 1.10). Two trials with low risk of selection bias, no early stopping, and no co-intervention did not establish any significant effect of TACE or TAE on overall survival (hazard ratio 1.22, 95% confidence interval 0.82 to 1.83; P = 0.33). Trial sequential analysis confirmed the absence of evidence for a beneficial effect of TACE or TAE on survival indicating the need for future randomisation of up to 383 additional participants. Substantial differences in criteria for assessing tumour response did not allow quantitative analyses. One trial investigated quality of life but did not detect any significant differences between the intervention groups. A range of adverse events including post-embolisation syndrome and serious complications were reported. AUTHORS' CONCLUSIONS There is no firm evidence to support or refute TACE or TAE for patients with unresectable HCC. More adequately powered and bias-protected trials are needed.
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MESH Headings
- Antineoplastic Agents/administration & dosage
- Carcinoma, Hepatocellular/drug therapy
- Carcinoma, Hepatocellular/mortality
- Chemoembolization, Therapeutic/adverse effects
- Chemoembolization, Therapeutic/methods
- Chemoembolization, Therapeutic/mortality
- Embolization, Therapeutic/adverse effects
- Embolization, Therapeutic/methods
- Embolization, Therapeutic/mortality
- Humans
- Infusions, Intra-Arterial/adverse effects
- Infusions, Intra-Arterial/methods
- Liver Neoplasms/drug therapy
- Liver Neoplasms/mortality
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Affiliation(s)
- Roberto S Oliveri
- Department of Oncology, The Finsen Centre, section 5073, Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark, DK-2100
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17
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Abstract
BACKGROUND Locoregional treatments of hepatocellular carcinoma (HCC) have evolved over the past 20 years. Interventional radiologists have developed an important role in the palliative and curative treatment of the disease. This review summarizes commonly used interventional radiological treatment protocols to assist practitioners in understanding the techniques used to treat HCC. METHODS Various searches were performed to evaluate recent publications regarding systemic treatments of HCC as well as transplant/surgery, chemoembolization, yttrium-90 radioembolization, percutaneous radiofrequency ablation (RFA), cryoablation, and percutaneous ethanol injection (PEI). RESULTS No standard for chemoembolization was found. Two studies evaluating survival with chemoembolization vs medical therapy found benefits with the former. PEI offers favorable outcomes in small HCC but has increased recurrence and decreased long-term survival compared with RFA. Local recurrence, response rates, and mortality from RFA rival surgical resection in HCC less than 3 cm. Cryoablation appears to be effective, and yttrium-90 radioembolization is an additional tool. CONCLUSIONS Chemoembolization improves survival and offers improved tumor response compared to systemic treatment. More studies are needed to standardize chemoembolization preparations and techniques. RFA provides better results than PEI but has not been compared with cryoablation. Radioembolization appears to be as effective as chemoembolization, but the preprocedure evaluation and costs may limit its use.
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Affiliation(s)
- Cliff R Davis
- Tampa General Hospital, Radiology Association of Tampa/Department of Interventional Radiology, Tampa, FL 33606, USA.
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18
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Andreana L, Burroughs AK. Treatment of early hepatocellular carcinoma: How to predict and prevent recurrence. Dig Liver Dis 2010; 42 Suppl 3:S249-57. [PMID: 20547311 DOI: 10.1016/s1590-8658(10)60513-0] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Early and very early stage hepatocellular cancers (HCC) when staged clinically, if they are coincident with histological early HCC, have the best outcome in terms of recurrence rates and survival after potential curative therapy. This is because predictors of HCC recurrence such as microscopic vascular invasion and satellite metastases, are rarely present in histological early HCC. Other predictors of HCC recurrence are size of the principal lesion, numbers of lesions, histological grade, several gene signature patterns that are promising for future clinical practice, and other less constantly predictive features such as high alpha-fetoprotein and transaminase concentrations, and cellular aneuploidia. Adjuvant and neo-adjuvant therapies have been proposed to reduce the risk of HCC recurrence after potentially curative treatments. These preventative therapies are focused on extra-tumoural therapies, such as retinoids or interferon, possibly effective in preventing late recurrence by influencing the premalignant field in cirrhosis, and on tumour related therapies, by utilising several procedures able to downstage tumours, such as neo-adjuvant and "bridge to transplant" therapies, which influence mainly early recurrence. Both strategies have been combined for example with using sorafenib which may treat both the patient's premalignant liver and malignant liver cells themselves.
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Affiliation(s)
- Lorenzo Andreana
- The Sheila Sherlock Liver Centre and University Department of Surgery, Royal Free Hospital, London, UK
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19
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Seinstra BA, van Delden OM, van Erpecum KJ, van Hillegersberg R, Mali WPTM, van den Bosch MAAJ. Minimally invasive image-guided therapy for inoperable hepatocellular carcinoma: What is the evidence today? Insights Imaging 2010; 1:167-81. [PMID: 23100194 PMCID: PMC3288853 DOI: 10.1007/s13244-010-0027-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2010] [Revised: 05/23/2010] [Accepted: 05/28/2010] [Indexed: 02/08/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a primary malignant tumor of the liver that accounts for an important health problem worldwide. Only 10-15% of HCC patients are suitable candidates for hepatic resection and liver transplantation due to the advanced stage of the disease at time of diagnosis and shortage of donors. Therefore, several minimally invasive image-guided therapies for locoregional treatment have been developed. Tumor ablative techniques are either based on thermal tumor destruction, as in radiofrequency ablation, cryoablation, microwave ablation, laser ablation and high-intensity focused ultrasound, or chemical tumor destruction, as in percutaneous ethanol injection. Image-guided catheter-based techniques rely on intra-arterial delivery of embolic, chemoembolic or radioembolic agents. These minimally invasive image-guided therapies have revolutionized the management of inoperable HCC. This review provides a description of all minimally invasive image-guided therapies currently available, an up-to-date overview of the scientific evidence for their clinical use, and thoughts for future directions.
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Affiliation(s)
- Beatrijs A. Seinstra
- Department of Radiology, University Medical Center Utrecht, Room E.01.132, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
| | - Otto M. van Delden
- Department of Radiology, Academic Medical Center Amsterdam, Amsterdam, The Netherlands
| | - Karel J. van Erpecum
- Department of Gastroenterology, University Medical Center Utrecht, Utrecht, The Netherlands
| | | | - Willem P. Th. M. Mali
- Department of Radiology, University Medical Center Utrecht, Room E.01.132, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
| | - Maurice A. A. J. van den Bosch
- Department of Radiology, University Medical Center Utrecht, Room E.01.132, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
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20
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Padma S, Martinie JB, Iannitti DA. Liver tumor ablation: percutaneous and open approaches. J Surg Oncol 2010; 100:619-34. [PMID: 20017157 DOI: 10.1002/jso.21364] [Citation(s) in RCA: 82] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The global incidence of liver cancer is greater than a million cases a year. Surgical resection where applicable is still the standard of care for these patients. Various liver-directed regional therapies have been developed in an effort to treat the vast majority of unresectable liver tumors. This article reviews the principles behind various ablation therapies currently available for malignant liver tumors and their outcomes.
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Affiliation(s)
- Srikanth Padma
- Section of Hepato-Pancreatico-Biliary Surgery, Division of GI & Minimally Invasive Surgery, Department of Surgery, Carolinas Medical Center, Charlotte, North Carolina 28203, USA
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21
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Hsu CY, Huang YH, Su CW, Lin HC, Chiang JH, Lee PC, Lee FY, Huo TI, Lee SD. Renal failure in patients with hepatocellular carcinoma and ascites undergoing transarterial chemoembolization. Liver Int 2010; 30:77-84. [PMID: 19818004 DOI: 10.1111/j.1478-3231.2009.02128.x] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Ascites is often present in patients with hepatocellular carcinoma (HCC) with cirrhosis. Advanced cirrhosis may predispose to renal dysfunction. Acute renal failure (ARF) may occur after transarterial chemoembolization (TACE) for HCC because of radiocontrast agents. This study aimed to investigate the incidence and risk factors of ARF and prognostic predictors in HCC patients with ascites undergoing TACE. METHODS A total of 591 HCC patients receiving TACE were enrolled. RESULTS In a mean follow-up duration of 19+/-17 months, 239 (40.4%) patients undergoing TACE died. Ascites, which was present in 91 (15.4%) patients at entry, independently predicted a poor prognosis in the Cox proportional hazard model [risk ratio (RR): 1.71, P=0.002]. Of these, 11 (12.6%) of 87 patients with complete follow-up developed ARF after TACE. Serum albumin level <3.3 g/dl (odds ratio: 7.3, P=0.009) was the only independent risk factor associated with ARF in the logistic regression analysis. ARF (RR: 2.17, P=0.036), alpha-fetoprotein >400 ng/ml (RR: 1.84, P=0.04), multiple tumours (RR: 2.11, P=0.013), tumour size > or = 5 cm (RR: 2.32, P=0.006) and serum sodium level <139 mmol/L (RR: 2.4, P=0.005) were independent poor prognostic predictors for HCC patients with ascites receiving TACE. CONCLUSIONS Pre-existing ascites is associated with increased mortality in HCC patients receiving TACE. In HCC patients with ascites, hypoalbuminaemia is associated with the occurrence of post-TACE ARF. Post-TACE ARF is a poor prognostic predictor in this subset of HCC patients.
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Affiliation(s)
- Chia-Yang Hsu
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
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22
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Yu Y, Lang Q, Chen Z, Li B, Yu C, Zhu D, Zhai X, Ling C. The efficacy for unresectable hepatocellular carcinoma may be improved by transcatheter arterial chemoembolization in combination with a traditional Chinese herbal medicine formula: a retrospective study. Cancer 2009; 115:5132-8. [PMID: 19672999 DOI: 10.1002/cncr.24567] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Transcatheter arterial chemoembolization (TACE) is the most widely used primary treatment for unresectable hepatocellular carcinoma (HCC) because of its survival benefit, although its clinical effect is still far from satisfactory. In China, there has been a long history of using traditional Chinese medicine in the treatment of liver cancer and other malignancies. In this study, the authors evaluated the effect of combined therapy with TACE and JDF granule preparation (a traditional Chinese herbal medicine formula) in the treatment of patients with unresectable HCC on survival. Clinical data, including baseline, performance status change, and survival time of 165 patients with unresectable HCC seen between January 2002 and December 2007 were retrospectively analyzed. Among the 165 patients, 80 patients (study group) received combined therapy consisting of TACE and a long-term maintenance treatment with oral JDF granule preparation, and 85 patients (control group) received TACE alone. The survival rate of both groups was calculated by the Kaplan-Meier method. Factors possibly affecting survival were assessed by multivariate analysis in the Cox proportional hazard model. The median overall survival was 9.2 months (95% confidence interval [95% CI], 6.94-1.46) in the study group versus 5.87 months (95% CI, 4.21-7.52) in the control group. In the study group (TACE + JDF), 1-year, 2-year, and 3-year survival rates were 41.2%, 18.4%, and 9.6%, respectively. The Cox regression analysis revealed the therapy model to be an independent predictor of patient prognosis. Current study data demonstrated that TACE combined with JDF granule preparation could improve the prognosis of patients. TACE combined with JDF granule preparation may prolong survival of patients with unresectable HCC.
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Affiliation(s)
- Yang Yu
- Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai, China
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23
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Kirikoshi H, Saito S, Yoneda M, Fujita K, Mawatari H, Uchiyama T, Higurashi T, Goto A, Takahashi H, Abe Y, Inamori M, Kobayashi N, Kubota K, Sakaguchi T, Ueno N, Nakajima A. Outcome of transarterial chemoembolization monotherapy, and in combination with percutaneous ethanol injection, or radiofrequency ablation therapy for hepatocellular carcinoma. Hepatol Res 2009; 39:553-62. [PMID: 19527484 DOI: 10.1111/j.1872-034x.2009.00490.x] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
AIM Hepatocellular carcinoma (HCC) is one of the most commonly occurring malignances worldwide. Curative therapies such as resection, percutaneous ethanol injection (PEI) and radiofrequency ablation (RFA) have been applied to patients with early-stage HCC. Patients with more advanced cancers require local or systemic therapies. We present the results of our retrospective review conducted to evaluate whether transarterial chemoembolization (TACE) alone and combined TACE with percutaneous ablation for HCC exhibited superior efficacy to palliative treatment. METHODS The effects of TACE and of the combined therapies (TACE + PEI or TACE + RFA) on the long-term survival rates were evaluated in 268 untreated HCC patients by various statistical analyses. RESULTS The cumulative survival rates in the TACE alone group were significantly superior to those in the palliative treatment group. Further, the cumulative survival rates in the combined TACE + PEI/RFA group were significantly superior to those in the TACE alone group. When the comparison among the groups was restricted to patients with two or three tumors fulfilling the Milan criteria, significantly greater prolongation of survival was observed in the combined TACE + PEI/RFA group than in the PEI/RFA alone group. CONCLUSIONS The aforementioned treatment modalities yielded greater improvements of the survival rate and survival duration as compared to palliative treatment in HCC patients. Furthermore, in terms of the effect on the survival period, combined TACE + PEI/RFA therapy was more effective than TACE monotherapy, and also more effective than PEI or RFA monotherapy in cases with multiple tumors fulfilling the Milan criteria.
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Affiliation(s)
- Hiroyuki Kirikoshi
- Division of Gastroenterology, Yokohama City University School of Medicine, Yokohama, Japan
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24
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Pleguezuelo M, Marelli L, Misseri M, Germani G, Calvaruso V, Xiruochakis E, Manousou P, Burroughs AK. TACE versus TAE as therapy for hepatocellular carcinoma. Expert Rev Anticancer Ther 2009; 8:1623-41. [PMID: 18925854 DOI: 10.1586/14737140.8.10.1623] [Citation(s) in RCA: 63] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Transarterial chemoembolization (TACE) improves survival in cirrhotic patients with hepatocellular carcinoma (HCC). The optimal schedule, best anticancer agent and best technique are still unclear. TACE may not be better than transarterial embolization (TAE). HCC is very chemoresistant, thus embolization may be more important than chemotherapy. Lipiodol cannot be considered as an embolic agent and there are no data to show that it can release chemotherapeutic agents slowly. It can mask residual vascularity on CT imaging and its use is not recommended. Both TACE and TAE result in hypoxia, which stimulates angiogenesis, promoting tumor growth; thus combination of TACE with antiangiogenic agents may improve current results. To date, there is no evidence that TACE pre-liver transplantation or resection helps to expand current selection criteria for patients with HCC, nor results in less recurrence after surgery. Combination with other techniques, such as radiofrequency ablation and drugs, may enhance the effect of TACE. New trials are being conducted to clarify these issues.
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Affiliation(s)
- Maria Pleguezuelo
- Department of Surgery & Liver Transplantation, The Royal Free Sheila Sherlock Liver Centre, Royal Free Hospital, Hampstead Heath, London, UK.
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25
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Multimodal approaches to the treatment of hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol 2009; 6:159-69. [DOI: 10.1038/ncpgasthep1357] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2008] [Accepted: 12/17/2008] [Indexed: 02/16/2023]
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26
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Takaki H, Yamakado K, Uraki J, Nakatsuka A, Fuke H, Yamamoto N, Shiraki K, Yamada T, Takeda K. Radiofrequency ablation combined with chemoembolization for the treatment of hepatocellular carcinomas larger than 5 cm. J Vasc Interv Radiol 2008; 20:217-24. [PMID: 19097810 DOI: 10.1016/j.jvir.2008.10.019] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2008] [Revised: 10/21/2008] [Accepted: 10/21/2008] [Indexed: 12/11/2022] Open
Abstract
PURPOSE To evaluate survival, recurrence-free survival, technical success, technique effectiveness, and safety of radiofrequency (RF) ablation combined with chemoembolization in patients with hepatocellular carcinomas (HCCs) larger than 5 cm. MATERIALS AND METHODS Patients with Child-Pugh class A or B cirrhosis and three or fewer HCCs with a maximum tumor diameter of 5.1-10 cm were included. Twenty patients with 32 HCCs were included. There were 16 men and four women with mean age of 69 years +/- 7.4 (range, 46-79 years).The maximum mean tumor diameter was 6.2 cm (range, 5.1-9.5 cm). RF ablation was performed under computed tomographic (CT) fluoroscopic guidance 1-2 weeks after chemoembolization. The primary endpoint of this study was survival. RESULTS RF electrodes were placed in the planned sites, and RF ablation was completed with a planned protocol (technical success rate, 100%). Tumor enhancement was eradicated in all patients after 32 RF sessions. The primary and secondary technique effectiveness rates were 40% and 100%, respectively. There were two major complications in the 32 RF sessions (6%)--hepatic abscess and diaphragm perforation. Local tumor progression developed in five of the 20 patients (25%) during the mean follow-up of 30 months. The overall and recurrence-free survival rates were, respectively, 100% and 74% at 1 year, 62% and 28% at 3 years, and 41% and 14% at 5 years. The serum bilirubin level of 1.0 mg/dL (17.1 micromol/L) or less was a significantly better prognostic factor in the univariate analysis. CONCLUSIONS This combination therapy may enhance survival in patients with HCCs larger than 5 cm.
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Affiliation(s)
- Haruyuki Takaki
- Department of Radiology, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
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27
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Pleguezuelo M, Germani G, Marelli L, Xiruochakis E, Misseri M, Manousou P, Arvaniti V, Burroughs AK. Evidence-based diagnosis and locoregional therapy for hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol 2008; 2:761-84. [PMID: 19090737 DOI: 10.1586/17474124.2.6.761] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Early identification of hepatocellular carcinoma (HCC) is crucial to improving the results of therapy and for patients to be eligible for liver transplantation. Recent advances in noninvasive imaging technology include various techniques of harmonic ultrasound, new ultrasound contrast agents, multislice helical computed tomography and rapid high-quality magnetic resonance. The imaging diagnosis relies on the hallmark of arterial hypervascularity with portal venous washout. Since the use of better radiological techniques has improved the accuracy of noninvasive diagnosis, the role of liver biopsy in the diagnosis of HCC has declined. With recent advances in genomics and proteomics, a great number of potential markers have been identified and developed as new candidate markers for HCC. Locoregional therapies currently constitute the best options for early nonsurgical treatment of HCC. Percutaneous ethanol injection shows similar results to resection surgery for single tumors less than 3 cm in diameter. Radiofrequency ablation is superior to percutaneous ethanol injection in terms of local recurrence. Transarterial chemoembolization is currently the most common approach for the management of HCC without curative options since it improves patient survival, but the optimal embolizing agent, length of interval between sessions and whether the chemotherapeutic agent has any effect have not yet been determined. Combining transarterial chemoembolization with antiangiogenic agents, as well as with other techniques, such as radiofrequency ablation, may improve the results. Injection of radioisotopes such as yttrium-90, via the hepatic artery, may be particularly useful in patients with portal vein thrombosis. Comparisons with other transarterial techniques are needed.
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Affiliation(s)
- Maria Pleguezuelo
- The Royal Free Sheila Sherlock Liver Centre, Royal Free Hospital, Pond Street, London, NW3 2QG, UK.
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28
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Seror O, N'Kontchou G, Ibraheem M, Ajavon Y, Barrucand C, Ganne N, Coderc E, Trinchet JC, Beaugrand M, Sellier N. Large (>or=5.0-cm) HCCs: multipolar RF ablation with three internally cooled bipolar electrodes--initial experience in 26 patients. Radiology 2008; 248:288-96. [PMID: 18483229 DOI: 10.1148/radiol.2481071101] [Citation(s) in RCA: 104] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
PURPOSE To prospectively evaluate the safety and effectiveness of percutaneous multipolar radiofrequency (RF) ablation for the treatment of large (>or=5.0 cm in diameter) hepatocellular carcinomas (HCCs). MATERIALS AND METHODS Twenty-six patients (four women, 22 men; median age, 72 years) with cirrhosis (Child-Pugh class A disease, 22 patients; Child-Pugh class B disease, four patients) and at least one 5.0-9.0-cm-diameter HCC without invasion of the portal trunk or main portal branches were treated with multipolar RF ablation performed by a single operator. The procedure was performed with three separate bipolar linear internally cooled electrodes with ultrasonographic guidance. Twenty-seven of the 33 tumors treated had a diameter of 5.0 cm or greater (median diameter, 5.7 cm; range, 5.0-8.5 cm); 12 of these 27 tumors were infiltrative, and four invaded segmental portal vein branches. Ten patients had a serum alpha-fetoprotein level higher than 400 microg/L. Results were assessed by using computed tomography. Primary effectiveness, complications, tumor progression, and survival rates were recorded. Probabilities of survival were calculated by using the Kaplan-Meier method. RESULTS One to two RF ablation procedures per patient (mean, 1.15 +/- 0.43 [standard deviation]) led to the complete ablation of 22 (81%) of the 27 tumors (18 tumors after one and four tumors after two procedures), including three tumors that showed segmental portal vein invasion. All patients experienced postablation syndrome, and one experienced subcapsular hematoma and a segmental liver infarct, but no major complication occurred. After a mean follow-up of 14 months (range, 3-34 months), local and distant tumor progression and actual survival rates were 14% (three of 22), 24% (five of 21), and 65% (17 of 26), respectively. The probabilities of 1- and 2-year survival, respectively, were 68% (95% confidence interval: 49%, 86%) and 56% (95% confidence interval: 51%, 81%). CONCLUSION HCCs larger than 5.0 cm (but smaller than 9.0 cm)--even those that are infiltrative and those that involve a segmental portal vein--can be completely and safely ablated with multipolar RF ablation.
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Affiliation(s)
- Olivier Seror
- Department of Radiology, Centre Hôspitalo-Universitaire Jean Verdier, Assistance Publique-Hôpitaux de Paris, avenue du 14 Juillet, 93140 Bondy, France.
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29
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McGrane S, McSweeney SE, Maher MM. Which patients will benefit from percutaneous radiofrequency ablation of colorectal liver metastases? Critically appraised topic. ACTA ACUST UNITED AC 2008; 33:48-53. [PMID: 17874263 DOI: 10.1007/s00261-007-9313-2] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
In clinical radiology, there are numerous examples of new techniques that were initially enthusiastically promoted and then subsequently abandoned when early promise was not realized in routine patient care. Appropriateness of new or established interventional radiology techniques to specific clinical conditions must be determined from clinical experience, from communication with experts in the field and/or careful review of available medical literature, and on an individual patient basis by means of review of clinical notes and diagnostic imaging studies. For patients with liver neoplasms, regional techniques such as radiofrequency ablation (RFA) have been developed and are now the subject of ongoing research. This article describes the utilization of Evidence-Based Practice (EBP) techniques as a means of deciding the appropriateness of percutaneous RFA in treating colorectal liver metastases (CLM).
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Affiliation(s)
- Siobhán McGrane
- Department of Radiology, Cork University Hospital, University College Cork, Cork, Ireland
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30
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Abstract
The incidence of hepatocellular carcinoma (HCC) is predicted to continue to increase over the next 30 years. Surgical intervention, including resection and orthotopic liver transplantation (OLT) is offered to a limited number of patients. Novel approaches to the treatment of patients with HCC are needed. This article aims to review emerging approaches in the care of the HCC patient including systemic treatment, selection of appropriate candidates for OLT, improved imaging to follow treatment response, and management pre-OLT and post-OLT.
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Affiliation(s)
- Laura M Kulik
- Division of Hepatology, Departments of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
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31
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Watanabe Y, Horiuchi A, Yoshida M, Yamamoto Y, Sugishita H, Kumagi T, Hiasa Y, Kawachi K. Significance of laparoscopic splenectomy in patients with hypersplenism. World J Surg 2007; 31:549-55. [PMID: 17308852 DOI: 10.1007/s00268-006-0504-8] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE This study was aimed at investigating the efficacy and safety of minimally invasive laparoscopic splenectomy in patients with hypersplenism secondary to cirrhosis. BACKGROUND While advances have been made in the treatment of liver cancer and chronic hepatitis, certain treatments such as radio frequency ablation (RFA) must often be discontinued due to thrombocytopenia caused by hypersplenism. Laparoscopic splenectomy is performed to treat diseases as idiopathic thrombocytopenic purpura, but is contraindicated for hypersplenism in many institutions. Few studies have thus examined the safety and efficacy of this approach. METHODS Efficacy and safety were retrospectively analyzed for laparoscopic splenectomies starting from January 2003. Relationships between postoperative increases in platelet count and thrombopoietin, platelet-associated immunoglobulin, excised spleen weight, and serum parameters were examined. Perioperative data of open splenectomies starting from January 1990 were compared with those of laparoscopic splenectomies. RESULTS No laparoscopic cases were converted to open surgery in this series. Mean operative times of open and laparoscopic splenectomy were 205 and 173 min respectively. Mean blood losses were 750 and 359 ml (P < 0.05) and the mean weights of excised spleen were 460 and 525 g respectively. Postoperatively, no changes in liver function were noted, and platelet and leukocyte counts were significantly increased. Compared with preoperative platelet count, degree of increase at 2 weeks postoperatively did not correlate with preoperative thrombopoietin levels, but significantly correlated with levels of platelet-associated immunoglobulin and spleen volume (P < 0.05). Postoperative portal or splenic vein thrombosis (PSVT) was seen in 3 patients and these patients did not exhibit any clinical symptoms. CONCLUSIONS Laparoscopic splenectomy is a safe technique for the treatment of hypersplenism and contributes to postoperative increases in platelet counts. Postoperative increases in platelet count seem to depend on platelet-associated immunoglobulin level and spleen weight, which may be valuable prognosticators.
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Affiliation(s)
- Yuji Watanabe
- Department of Surgery II, School of Medicine, Ehime University, Shitsukawa, Toon-Shi, 791-0295, Ehime, Japan.
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32
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Liver embolizations in oncology: A review. Med Oncol 2007; 25:1-11. [DOI: 10.1007/s12032-007-0039-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2007] [Accepted: 05/20/2007] [Indexed: 02/08/2023]
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Takaki H, Yamakado K, Nakatsuka A, Fuke H, Murata K, Shiraki K, Takeda K. Radiofrequency Ablation Combined with Chemoembolization for the Treatment of Hepatocellular Carcinomas 5 cm or Smaller: Risk Factors for Local Tumor Progression. J Vasc Interv Radiol 2007; 18:856-61. [PMID: 17609444 DOI: 10.1016/j.jvir.2007.04.022] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
PURPOSE To investigate the risk factors for local tumor progression after radiofrequency (RF) ablation combined with chemoembolization for the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS A total of 255 HCC lesions 5 cm or less in maximum diameter were treated by RF ablation in 173 patients within 2 weeks after chemoembolization was performed. Therapeutic response was evaluated by contrast medium-enhanced computed tomography studies. The disappearance of tumor enhancement was considered to indicate complete necrosis. Local tumor progression was defined by the appearance of enhanced tumor adjacent to the zone of ablation. The risk factors for local tumor progression after RF ablation were retrospectively assessed by univariate and multivariate analyses. RESULTS All tumors showed complete necrosis after RF ablation. Local tumor progression was found in 18 of the 255 lesions (7%) during a mean follow-up period of 23 months (range, 1-63 months). The cumulative local tumor progression rate was 12% at 5 years. Larger tumor (3.1-5 cm), infiltrating tumor, and previous treatments were found to increase the risk of local tumor progression in univariate and multivariate analyses. CONCLUSIONS The combination of chemoembolization with RF ablation is an effective treatment to control HCC lesions. The factors identified in the present study may help to predict the therapeutic response.
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Affiliation(s)
- Haruyuki Takaki
- Department of Radiology, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie, Japan.
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Sato S, Miyake T, Mishiro T, Furuta K, Azumi T, Oshima N, Takahashi Y, Rumi MAK, Ishihara S, Adachi K, Amano Y, Kinoshita Y. Kinetics of indocyanine green removal from blood can be used to predict the size of the area removed by radiofrequency ablation of hepatic nodules. J Gastroenterol Hepatol 2006; 21:1714-9. [PMID: 16984595 DOI: 10.1111/j.1440-1746.2006.04417.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIM The size of radiofrequency ablation (RFA) in the liver can be negatively influenced by the surrounding blood flow. The indocyanine green (ICG) test can be used to evaluate the effective blood flow in the liver, and distance from the hilus can affect local blood flow. The aim of this study was to assess whether the ICG test or distance from the hilus could be used to predict the size of the ablated area in liver by RFA treatment of hepatocellular carcinoma (HCC) nodules. METHODS The RFA measurements of 44 HCC nodules in 39 patients were retrospectively studied. Cases were included if they met the following criteria: (i) no catheter treatment before RFA; (ii) no movement of the RFA device; (iii) strict ablation time; and (iv) only one ablation. In all patients, ICG-R15 testing was done immediately before RFA and the initial therapeutic efficacy was evaluated by dynamic computed tomography scanning 2-5 days after RFA. The correlation between the maximum size of the RFA area and the ICG test results or the distance of the target area from the hilus (site of first portal vein divergence) were analyzed statistically. RESULTS The ICG-R15 result was significantly correlated with the maximum diameter of the ablated area both in 2 cm-electrode tip length (R2 = 0.35, P = 0.0012), and in 3 cm-tip length (R2 = 0.26, P = 0.0377). Multiple-regression analysis showed that the electrode tip length (P = 0.0010) and ICG-R15 (P = 0.0046) were independent factors that could predict the maximum diameter of the RFA area. CONCLUSION The results of ICG testing can be used to predict the size of the area that will be ablated at a target liver site before RFA treatment.
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Affiliation(s)
- Shuichi Sato
- Department of Gastroenterology and Hepatology, Shimane University School of Medicine, Izumo, Shimane, Japan.
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Marelli L, Stigliano R, Triantos C, Senzolo M, Cholongitas E, Davies N, Yu D, Meyer T, Patch DW, Burroughs AK. Treatment outcomes for hepatocellular carcinoma using chemoembolization in combination with other therapies. Cancer Treat Rev 2006; 32:594-606. [PMID: 17045407 DOI: 10.1016/j.ctrv.2006.08.002] [Citation(s) in RCA: 71] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2006] [Accepted: 08/20/2006] [Indexed: 12/30/2022]
Abstract
BACKGROUND Although transarterial chemoembolization (TACE) improves survival in patients with hepatocellular carcinoma (HCC), it is not known if TACE combined with other treatments is beneficial. AIM To evaluate the evidence for improved outcomes in HCC with a multimodal treatment approach involving TACE. METHOD PubMed search for all cohort and randomized trials (n=84) evaluating TACE combined with other therapies; meta-analysis performed where appropriate. RESULTS A meta-analysis involving 4 RCTs showed a significant decrease in mortality favouring combination treatment (TACE plus percutaneous ablation) compared to monotherapy in patients with either small (<3cm) or large HCC nodules (>3cm) (OR, 0.534; 95% CI, 0.288-0.990; p=0.046). TACE combined with local radiotherapy improved survival in patients with tumour thrombosis of the portal vein in 7 non-randomized studies. Two RCTs and 13 non-randomized studies showed that TACE prior to hepatic resection does not improve survival nor tumour recurrence. Conversely, 2 RCTs and 5 comparative studies showed that transarterial injection of chemotherapeutic drugs mixed with lipiodol (TOCE) following hepatectomy confers survival benefit and less tumour recurrence. TACE before liver transplantation is safe and reduces drop-out rate from the waiting list, but there is no current evidence of improvement in subsequent survival or recurrence rate. CONCLUSIONS A combined approach involving TACE and percutaneous ablation improves survival. Adjuvant TOCE improves outcome after hepatectomy. TACE is useful to control tumours burden while on the waiting list for OLT. Multimodal treatment seems to be the best way to optimize TACE outcomes in HCC.
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Affiliation(s)
- Laura Marelli
- Liver Transplantation and Hepatobiliary Medicine Unit, Royal Free Hospital, Pond Street, NW3 2QG London, UK.
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Morioka D, Tanaka K, Matsuo KI, Takeda K, Ueda M, Sugita M, Nagano Y, Endo I, Sekido H, Togo S, Shimada H. Applicability of the Milan Criteria for Determining Liver Transplantation as a First-Line Treatment for Hepatocellular Carcinoma. Ann Surg Oncol 2006; 13:1500-10. [PMID: 17009137 DOI: 10.1245/s10434-006-9204-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2006] [Revised: 07/18/2006] [Accepted: 07/20/2006] [Indexed: 12/14/2022]
Abstract
BACKGROUND To determine whether or not the Milan criteria (MC) should be used to determine the applicability of liver transplantation (LT) as a first-line treatment for patients with cirrhosis with hepatocellular carcinoma (HCC) who are able to endure hepatectomy. METHODS Retrospective analysis of 82 patients with cirrhosis with HCC who were treated by hepatectomy without LT at our institution between 1990 and 2003. RESULTS Of these 82 patients, 48 met the MC. Proportional hazard regression analyses to determine the independent prognostic factors for postoperative cumulative patient and disease-free survival showed that meeting the MC is the strongest prognostic factor for both patient and disease-free survival. The cumulative patient and disease-free survival rates were 76.7% and 28.9%, respectively, at 5 years in patients who met the MC. The cumulative disease-free survival was markedly inferior to those in previously reported series of LT for HCC who met the MC, but the cumulative patient survival was comparable to those in the previously reported series. A comparison of cumulative postoperative survival between patients who met the MC and fulfilled all five factors listed below and patients who met the MC but did not fulfill any of the five factors demonstrated that the latter patients showed statistically significantly worse postoperative patient survival than the former. The five factors included: Model for End-Stage Liver Disease score < 10, indocyanine green retention rate at 15 minutes < 20%, absence of microscopic fibrous capsular invasion and microscopic intrahepatic metastases, and earlier grade (T1 or T2) of American Joint Committee on Cancer tumor classification. CONCLUSIONS The MC should not be used to determine the applicability of LT as a first-line treatment for patients with HCC considered able to endure hepatectomy. However, modifying MC with some clinicopathological factors could satisfy the appropriate criteria for applying LT as a first-line treatment for these patients.
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Affiliation(s)
- Daisuke Morioka
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, 3-9, Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
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Lopez PM, Villanueva A, Llovet JM. Systematic review: evidence-based management of hepatocellular carcinoma--an updated analysis of randomized controlled trials. Aliment Pharmacol Ther 2006; 23:1535-47. [PMID: 16696801 DOI: 10.1111/j.1365-2036.2006.02932.x] [Citation(s) in RCA: 267] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The treatment strategy of hepatocellular carcinoma applied following scientific guidelines is only supported by 77 randomized controlled trials published so far, a figure that clearly pinpoints hepatocellular carcinoma as an 'orphan' cancer in terms of clinical research when compared with other high-prevalent cancers worldwide. A systematic review analysing 61 randomized controlled trials (1978-2002) showed a modest survival benefit from chemoembolization in patients with intermediate tumours, and the lack of an effective first-line treatment option for patients with advanced disease. These conclusions have been endorsed by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases. The present updated evidence-based approach includes 16 randomized controlled trials published from 2002 to 2005 assessing percutaneous ablation (seven), other loco-regional therapies (three) and systemic therapies (six). Eight showed high-quality methodological profiles. Four randomized controlled trials demonstrated a better local hepatocellular carcinoma control in tumours larger than 2 cm treated by radiofrequency ablation compared with ethanol injection. No survival advantages were obtained from systemic treatments in patients with advanced hepatocellular carcinoma, an area that is an unmet need. Therefore, there is an urgent request to conduct well-designed phase III investigations in hepatocellular carcinoma patients.
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Affiliation(s)
- P M Lopez
- Mount Sinai Liver Cancer Program, Division of Liver Diseases, Mount Sinai School of Medicine, New York, NY 10029, USA
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Cerwenka H, Bacher H, Mischinger HJ. Primary hepatoma – guidelines for interdisciplinary treatment. Eur Surg 2006; 38:94-99. [DOI: 10.1007/s10353-006-0227-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
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Pereira P, Boss A, Clasen S, Gouttefangeas C, Schmidt D, Claussen CD. Radiofrequency ablation: the percutaneous approach. Recent Results Cancer Res 2006; 167:39-52. [PMID: 17044295 DOI: 10.1007/3-540-28137-1_3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/12/2023]
Affiliation(s)
- Philippe Pereira
- Division of Local Therapy, Hoppe-Seyler-Str.3, Tübingen, Germany
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Yoshida H, Yoshida H, Shiina S, Omata M. Early liver cancer: concepts, diagnosis, and management. Int J Clin Oncol 2005; 10:384-90. [PMID: 16369741 DOI: 10.1007/s10147-005-0537-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2005] [Indexed: 12/15/2022]
Abstract
Hepatocellular carcinoma is a major health problem worldwide. The prognosis of patients depends on the stage when the disease is diagnosed. For the early detection of these tumors, both the selection of patients at high risk and effective surveillance programs are important. When the tumor is diagnosed early, patients can choose potentially curative treatment, including surgical resection, transplantation, and ablation therapy. Here, we give an overview of the present management of hepatocellular carcinoma. Further studies in diagnosis, treatment, and prevention are required to achieve the best clinical management of this disease.
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Affiliation(s)
- Hideo Yoshida
- Department of Gastroenterology, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
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