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Hao Y, Xie F, Zhou Y, Li C, Zhang X, Shen J, Yao M, Sun X, Zhou J, Wen T, Peng W. Neoadjuvant therapy of sequential TACE, camrelizumab, and apatinib for single huge hepatocellular carcinoma (NEO-START): study protocol for a randomized controlled trial. Trials 2024; 25:490. [PMID: 39030637 PMCID: PMC11264851 DOI: 10.1186/s13063-024-08340-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Accepted: 07/15/2024] [Indexed: 07/21/2024] Open
Abstract
BACKGROUND The high recurrence rate after liver resection emphasizes the urgent need for neoadjuvant therapy in hepatocellular carcinoma (HCC) to enhance the overall prognosis for patients. Immune checkpoint inhibitors, camrelizumab combined with an anti-angiogenic tyrosine kinase inhibitor (TKI) apatinib, have emerged as a first-line treatment option for patients with unresectable HCC, yet its neoadjuvant application in combination with transarterial chemoembolization (TACE) in HCC remains unexplored. Therefore, this study aims to investigate the efficacy and safety of sequential TACE, camrelizumab, and apatinib as a neoadjuvant therapy for single, huge HCC. METHODS This multi-center, open-label randomized phase 3 trial will be conducted at 7 tertiary hospitals. Patients with single huge (≥ 10 cm in diameter), resectable HCC will be randomly assigned in a 1:1 ratio to arm of surgery alone or arm of neoadjuvant therapy followed by surgery. In the neoadjuvant therapy group, patients will receive TACE within 1 week after randomization, followed by camrelizumab (200 mg q2w, 4 cycles), along with apatinib (250 mg qd, 2 months). Patients will receive liver resection after neoadjuvant therapy unless the disease is assessed as progressive. The primary outcome is recurrence-free survival (RFS) at 1 year. The planned sample size of 60 patients will be calculated to permit the accumulation of sufficient RFS events in 1 year to achieve 80% power for the RFS primary endpoint. DISCUSSION Synergistic effects provided by multimodality therapy of locoregional treatment, TKI, and anti-programmed cell death 1 inhibitor significantly improved overall survival for patients with unresectable HCC. Our trial will investigate the efficacy and safety of the triple combination of TACE, camrelizumab, and apatinib as a neoadjuvant strategy for huge, resectable HCC. TRIAL REGISTRATION www.chitr.org.cn ChiCTR2300078086. Registered on November 28, 2023. Start recruitment: 1st January 2024. Expected completion of recruitment: 15th June 2025.
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MESH Headings
- Humans
- Carcinoma, Hepatocellular/therapy
- Carcinoma, Hepatocellular/pathology
- Carcinoma, Hepatocellular/mortality
- Carcinoma, Hepatocellular/drug therapy
- Liver Neoplasms/therapy
- Liver Neoplasms/pathology
- Liver Neoplasms/mortality
- Liver Neoplasms/drug therapy
- Chemoembolization, Therapeutic/adverse effects
- Chemoembolization, Therapeutic/methods
- Pyridines/therapeutic use
- Pyridines/administration & dosage
- Pyridines/adverse effects
- Antibodies, Monoclonal, Humanized/therapeutic use
- Antibodies, Monoclonal, Humanized/administration & dosage
- Antibodies, Monoclonal, Humanized/adverse effects
- Neoadjuvant Therapy/adverse effects
- Randomized Controlled Trials as Topic
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Antineoplastic Combined Chemotherapy Protocols/adverse effects
- Male
- Hepatectomy
- Adult
- Middle Aged
- Multicenter Studies as Topic
- Clinical Trials, Phase III as Topic
- Female
- Treatment Outcome
- China
- Aged
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Affiliation(s)
- Yun Hao
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Fei Xie
- Department of Hepatic Biliary Pancreatic Surgery, the First People's Hospital of Neijiang, Neijiang, China
| | - Yongjie Zhou
- Laboratory of Liver Transplantation, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, Chengdu, China
| | - Chuan Li
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaoyun Zhang
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Junyi Shen
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Minghong Yao
- Chinese Evidence-based Medicine Center, West China Hospital, Sichuan University, Chengdu, China
| | - Xin Sun
- Chinese Evidence-based Medicine Center, West China Hospital, Sichuan University, Chengdu, China
| | - Jin Zhou
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Tianfu Wen
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Wei Peng
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China.
- Chinese Evidence-based Medicine Center, West China Hospital, Sichuan University, Chengdu, China.
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Wei M, Jiang Y, Sun R, Fang L, Chu C, He H, Gou J, Yin T, Song Y, Tang X, Zhao F, Zhai Y, Zhang Y. Self-Assembly of a Linear-Dendritic Polymer Containing Cisplatin and Norcantharidin into Raspberry-like Multimicelle Clusters for the Efficient Chemotherapy of Liver Cancer. ACS APPLIED MATERIALS & INTERFACES 2023. [PMID: 36882938 DOI: 10.1021/acsami.2c21529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/18/2023]
Abstract
Combination chemotherapy has been proved to be an effective strategy in the clinic, and nanoformulations have drawn much attention in the field of drug delivery. However, conventional nanocarriers suffer from shortcomings such as inefficient coloading and undesired molar ratios of the combined drugs, preleakage of cargos during systemic circulation, and lack of cancer-selective drug release. To achieve tumor-specific codelivery of cisplatin (CDDP) and norcantharidin (NCTD) for synergistic treatment of liver cancer, a novel linear-dendritic polymer, termed as G1(PPDC)x, was designed and synthesized, where a prodrug consisting of cisplatin (CDDP) and norcantharidin (NCTD) was conjugated to PEG2000 via ester bonds to fabricate linear polymer-drug conjugates, and the conjugates were subsequently grafted to the terminal hydroxyls of a dendritic polycarbonate core. Benefiting from the hydrogen bond interactions, G1(PPDC)x could spontaneously self-assemble into a unique type of raspberry-like multimicelle clusters in solution (G1(PPDC)x-PMs). G1(PPDC)x-PMs possessed an optimal synergistic ratio of CDDP and NCTD, without obvious premature release or disassembly in biological environments. Intriguingly, upon extravasation into the interstitial tumor tissues, G1(PPDC)x-PMs (132 nm in diameter) could disassemble and reassemble into smaller micelles (40 nm in diameter) in response to the mildly acidic tumor microenvironment, which would enhance the deep tumor penetration and cellular accumulation of drugs. In vivo delivery of G1(PPDC)x-PMs led to a significantly prolonged blood circulation half-life, which is beneficial to achieve sufficient tumor accumulation through the enhanced permeability and retention (EPR) effect. G1(PPDC)x-PMs displayed the best antitumor activity in H22 tumor-bearing mice with a tumor inhibition rate of 78.87%. Meanwhile, G1(PPDC)x-PMs alleviated both myelosuppression toxicities of CDDP and vascular irritation of NCTD. Our results demonstrated that G1(PPDC)x-PMs could serve as an effective drug delivery system for codelivery of CDDP and NCTD to treat liver cancer efficiently.
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Affiliation(s)
- Mingli Wei
- Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Ying Jiang
- Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Rong Sun
- Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Liangyi Fang
- School of Life Science and Bio-Pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Chenxiao Chu
- Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Haibing He
- Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Jingxin Gou
- Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Tian Yin
- School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Yongbo Song
- School of Life Science and Bio-Pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Xing Tang
- Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Fan Zhao
- School of Life Science and Bio-Pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Yinglei Zhai
- Department of Biomedical Engineering, School of Medical Devices, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Yu Zhang
- Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
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Blanc JF, Debaillon-Vesque A, Roth G, Barbare JC, Baumann AS, Boige V, Boudjema K, Bouattour M, Crehange G, Dauvois B, Decaens T, Dewaele F, Farges O, Guiu B, Hollebecque A, Merle P, Selves J, Aparicio T, Ruiz I, Bouché O. Hepatocellular carcinoma: French Intergroup Clinical Practice Guidelines for diagnosis, treatment and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, AFEF, SIAD, SFR/FRI). Clin Res Hepatol Gastroenterol 2021; 45:101590. [PMID: 33780876 DOI: 10.1016/j.clinre.2020.101590] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Revised: 11/12/2020] [Accepted: 11/24/2020] [Indexed: 02/04/2023]
Abstract
INTRODUCTION This document is a summary of the French Intergroup guidelines regarding the management of hepatocellular carcinoma (HCC) published in March 2019. METHOD It is a collaborative work under the auspices of most of the French medical societies involved in the management of HCC. It is based on the previous guidelines published in 2017. Recommendations are graded in 3 categories according to the level of evidence of data found in the literature. RESULTS The diagnosis and staging of HCC is essentially based on clinical, biological and imaging features. A pathological analysis obtained by a biopsy of tumoral and non-tumoral liver is recommended. HCCs can be divided into 2 groups, taking into account not only the tumor stage, but also liver function. HCCs accessible to curative treatments are tumors that are in Milan criteria or with an AFP score ≤ 2, mainly treated by surgical resection, local ablation or liver transplantation. Intermediate and advanced HCCs with no liver insufficiency, accessible only to palliative treatments, benefit from TACE, SIRT or systemic therapy according to the presence or absence of macrovascular invasion or extrahepatic spread. CONCLUSION Such recommendations are in permanent optimization and each individual case must be discussed in a multidisciplinary expert board.
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Affiliation(s)
| | | | - Gaël Roth
- CHU Grenoble-Alpes, Grenoble, France
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Li C, Wang MD, Lu L, Wu H, Yu JJ, Zhang WG, Pawlik TM, Zhang YM, Zhou YH, Gu WM, Wang H, Chen TH, Han J, Xing H, Li ZL, Lau WY, Wu MC, Shen F, Yang T. Preoperative transcatheter arterial chemoembolization for surgical resection of huge hepatocellular carcinoma (≥ 10 cm): a multicenter propensity matching analysis. Hepatol Int 2019; 13:736-747. [PMID: 31486964 DOI: 10.1007/s12072-019-09981-0] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Accepted: 08/14/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Surgical resection for hepatocellular carcinoma (HCC) is potentially curative, but long-term survival remains unsatisfactory. There is currently no effective neoadjuvant or adjuvant therapy for HCC. We sought to evaluate the impact of preoperative transcatheter arterial chemoembolization (TACE) on long-term prognosis after surgical resection of huge HCCs (≥ 10 cm). METHODS Using a multicenter database, consecutive patients who underwent curative-intent resection for huge HCC without macrovascular invasion between 2004 and 2014 were identified. The association between preoperative TACE with perioperative outcomes, long-term overall survival (OS), and recurrence-free survival (RFS) was assessed before and after propensity score matching (PSM). RESULTS Among the 377 enrolled patients, 88 patients (23.3%) received preoperative TACE. The incidence of perioperative mortality and morbidity was comparable among patients who did and did not undergo preoperative TACE (3.4% vs. 2.4%, p= 0.704, and 33.0% vs. 31.1%, p= 0.749, respectively). PSM analysis created 84 matched pairs of patients. In examining the entire cohort as well as the PSM cohort, median OS (overall cohort: 32.8 vs. 22.3 months, p= 0.035, and PSM only: 32.8 vs. 18.1 months, p= 0.023, respectively) and RFS (12.9 vs. 6.4 months, p= 0.016, and 12.9 vs. 4.1 months, p= 0.009, respectively) were better among patients who underwent preoperative TACE vs. patients who did not. After adjustment for other confounding factors on multivariable analyses, preoperative TACE remained independently associated with a favorable OS and RFS after the resection of huge HCC. CONCLUSION Preoperative TACE did not increase perioperative morbidity or mortality, yet was associated with an improved OS and RFS after liver resection of huge HCC (≥ 10 cm).
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Affiliation(s)
- Chao Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), No. 225, Changhai Road, Shanghai, 200438, China
| | - Ming-Da Wang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), No. 225, Changhai Road, Shanghai, 200438, China
| | - Lun Lu
- Department of Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Han Wu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), No. 225, Changhai Road, Shanghai, 200438, China
| | - Jiong-Jie Yu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), No. 225, Changhai Road, Shanghai, 200438, China
| | - Wan-Guang Zhang
- Department of Hepatic Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Timothy M Pawlik
- Department of Surgery, Wexner Medical Center, Ohio State University, Columbus, OH, USA
| | - Yao-Ming Zhang
- The 2nd Department of Hepatobiliary Surgery, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital to Sun Yat-sen University, Meizhou, China
| | - Ya-Hao Zhou
- Department of Hepatobiliary Surgery, Pu'er People's Hospital, Yunnan, China
| | - Wei-Min Gu
- The 1st Department of General Surgery, The Fourth Hospital of Harbin, Heilongjiang, China
| | - Hong Wang
- Department of General Surgery, Liuyang People's Hospital, Hunan, China
| | - Ting-Hao Chen
- Department of General Surgery, Ziyang First People's Hospital, Sichuan, China
| | - Jun Han
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), No. 225, Changhai Road, Shanghai, 200438, China
| | - Hao Xing
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), No. 225, Changhai Road, Shanghai, 200438, China
| | - Zhen-Li Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), No. 225, Changhai Road, Shanghai, 200438, China
| | - Wan Yee Lau
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), No. 225, Changhai Road, Shanghai, 200438, China
- Faculty of Medicine the Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N.T.,, Hong Kong, SAR, China
| | - Meng-Chao Wu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), No. 225, Changhai Road, Shanghai, 200438, China
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), No. 225, Changhai Road, Shanghai, 200438, China.
| | - Tian Yang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), No. 225, Changhai Road, Shanghai, 200438, China.
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Kotewall CN, Cheung TT. Optimizing hepatectomy for hepatocellular carcinoma in Asia-patient selection and special considerations. Transl Gastroenterol Hepatol 2018; 3:75. [PMID: 30505962 DOI: 10.21037/tgh.2018.09.09] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2018] [Accepted: 09/05/2018] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a common affliction in Asia. The treatment of HCC depends on the tumor status as well as the underlying liver function. Resection is the cornerstone of surgical management of HCC. For those unfit to undergo resection, local ablative therapy is a viable alternative. For patients with multiple small unresectable HCCs, liver transplantation offers another option, having the simultaneous benefit of removing the cancer in addition to replacing the pre-malignant and cirrhotic liver together. However, the paucity of liver grafts limits the applicability of this operation. In assessing for the appropriate treatment, the traditional TNM staging is not widely applied to HCC. Conventionally, doctors in the West have relied on the Barcelona staging system. Asian surgeons, on the other hand, have long adopted a more aggressive approach for their patients. Borne out of the need for a system which better suited Asian patients, the Hong Kong guidelines have been established. For the surgical resection of HCC, considerations must take into account issues regarding the tumor, the underlying liver and the patient. For the tumor, the size, the presence vascular invasion and presence of extra-hepatic metastasis will determine operability. Another important issue is the liver function and, by extension, the estimated residual liver volume after resection. Thirdly, patient factors i.e., fitness to undergo general anesthesia must be properly assessed. With improved surgical technique and better patient selection, peri-operative morbidity and long-term survival results after operation have improved drastically over the past decades.
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Affiliation(s)
| | - Tan To Cheung
- Department of Surgery, The University of Hong Kong, Hong Kong, China
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Chen G, Zhang J, Sun J, Wei S, Chen J, Ren H, Zhou S. Revisiting Partial Hepatectomy of Large Hepatocellular Carcinoma in Older Patients. Sci Rep 2018; 8:14505. [PMID: 30266965 PMCID: PMC6162215 DOI: 10.1038/s41598-018-32798-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Accepted: 09/03/2018] [Indexed: 12/18/2022] Open
Abstract
Hepatectomy of large hepatocellular carcinomas (>10 cm) in over 70 year-old patients is presumed futile. We retrospectively reviewed 5970 patients with liver tumors Jan 2010 through Dec 2016 in our institute, of them, 37 older patients with large hepatocellular carcinomas staged I-III and Child-Pugh A liver functions receiving conservative treatments (conservative group, n = 37) and 16 older patients with large hepatocellular carcinomas staged I- III who underwent partial hepatectomy (resection group, n = 16) were included, the risk factors for poor survival were analyzed by univariate and multivariate analyses. Compared with the conservative treatments, Partial hepatectomy achieved better median survival time (25.5 months versus 11 months, log-rank = 0.0001) and better median performance status (1 versus 3, p = 0.023), there was different in Charlson comorbidity index (p = 0.019). For the conservative group, the 3-month, 1, 2, 3-year survival rate was 78.4%, 43.2%, 5.4%, 0%; for the resection group, The 3-month, 1, 2, 3-year survival rate was 100%, 93.7.2%, 56.3%, 12.5%; Multivariate Cox regression analysis showed the Charlson comorbidity index and the performance status associated with poor outcomes of those patients (p = 0.001, 0.018, respectively). Resections of large hepatocellular carcinomas in older patients can be performed safely to prolong life expectancy and improve life quality with or without cancer recurrence.
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Affiliation(s)
- Guoyong Chen
- Section 5 of Hepatopancreaticobiliary Surgery, Henan Provincial People's Hospital, Zhengzhou, Henan, 450003, China
| | - Jiabin Zhang
- Center of Hepatopancreaticobiliary Surgery and liver transplantation, 302 Hospital, Beijing, 100039, China
| | - Jianjun Sun
- Section 5 of Hepatopancreaticobiliary Surgery, Henan Provincial People's Hospital, Zhengzhou, Henan, 450003, China
| | - Sidong Wei
- Section 5 of Hepatopancreaticobiliary Surgery, Henan Provincial People's Hospital, Zhengzhou, Henan, 450003, China
| | - Jianbin Chen
- Section 5 of Hepatopancreaticobiliary Surgery, Henan Provincial People's Hospital, Zhengzhou, Henan, 450003, China
| | - Hui Ren
- Center of Hepatopancreaticobiliary Surgery and liver transplantation, 302 Hospital, Beijing, 100039, China.
| | - Shaotang Zhou
- Section 5 of Hepatopancreaticobiliary Surgery, Henan Provincial People's Hospital, Zhengzhou, Henan, 450003, China.
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Capussotti L, Ferrero A, Polastri R, Bouzari H, Vergara V, Amisano M, Ribero D, Muratore A. Hepatocellular Carcinoma on Cirrhosis: Resections. TUMORI JOURNAL 2018. [DOI: 10.1177/030089160108700428] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Affiliation(s)
- Lorenzo Capussotti
- Surgical Department, Ospedale Mauriziano “Umberto I”, Turin and Department of Surgical Oncology, Istituto per la Ricerca e la Cura del Cancro, Candiolo (To), Italy
| | - Alessandro Ferrero
- Surgical Department, Ospedale Mauriziano “Umberto I”, Turin and Department of Surgical Oncology, Istituto per la Ricerca e la Cura del Cancro, Candiolo (To), Italy
| | - Roberto Polastri
- Surgical Department, Ospedale Mauriziano “Umberto I”, Turin and Department of Surgical Oncology, Istituto per la Ricerca e la Cura del Cancro, Candiolo (To), Italy
| | - Hedayat Bouzari
- Surgical Department, Ospedale Mauriziano “Umberto I”, Turin and Department of Surgical Oncology, Istituto per la Ricerca e la Cura del Cancro, Candiolo (To), Italy
| | - Vincenzo Vergara
- Surgical Department, Ospedale Mauriziano “Umberto I”, Turin and Department of Surgical Oncology, Istituto per la Ricerca e la Cura del Cancro, Candiolo (To), Italy
| | - Marco Amisano
- Surgical Department, Ospedale Mauriziano “Umberto I”, Turin and Department of Surgical Oncology, Istituto per la Ricerca e la Cura del Cancro, Candiolo (To), Italy
| | - Dario Ribero
- Surgical Department, Ospedale Mauriziano “Umberto I”, Turin and Department of Surgical Oncology, Istituto per la Ricerca e la Cura del Cancro, Candiolo (To), Italy
| | - Andrea Muratore
- Surgical Department, Ospedale Mauriziano “Umberto I”, Turin and Department of Surgical Oncology, Istituto per la Ricerca e la Cura del Cancro, Candiolo (To), Italy
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Wakayama K, Kamiyama T, Yokoo H, Orimo T, Shimada S, Einama T, Kamachi H, Taketomi A. Huge hepatocellular carcinoma greater than 10 cm in diameter worsens prognosis by causing distant recurrence after curative resection. J Surg Oncol 2017; 115:324-329. [PMID: 28192617 DOI: 10.1002/jso.24501] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2016] [Accepted: 10/23/2016] [Indexed: 02/05/2023]
Abstract
BACKGROUND AND OBJECTIVES This study aimed to evaluate the impact of huge (≥10 cm) hepatocellular carcinoma (HCC) to the recurrence pattern and the prognosis after hepatectomy. METHODS 574 patients who underwent hepatectomy by 17 surgeons (Open 536 and Laparoscopic 38) for HCC without major vascular invasion from 1990 to 2013 at single institute were retrospectively analyzed. RESULTS Huge tumor, age, HCV, multiple tumors and microscopic portal invasion are independent risk factors for overall survival (OS), and huge tumor, ICGR15 ≥16%, multiple tumors, moderate/poor histology, microscopic portal invasion and a positive pathological margin are risk factors for relapse-free survival (RFS). The 5-year OS and RFS of patients with huge HCC (n = 53) (42.9 and 14.2%) were significantly worse than those of patients with HCC <10 cm (n = 521) (71.3 and 33.1%). Huge tumor is an independent risk factor for initial extra-hepatic recurrence (Hazard ratio 7.86, P < 0.0001). The 5-year OS of patients with initial extra-hepatic recurrence (n = 55) was significantly worse than patients with intra-hepatic recurrence (n = 338) (16.8 vs. 50.5%). CONCLUSIONS Huge HCC (≥10 cm) is an independent risk factor due to a high risk for initial extra-hepatic recurrence. Future systemic adjuvant therapy is needed for these patients. J. Surg. Oncol. 2017;115:324-329. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Kenji Wakayama
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Toshiya Kamiyama
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Hideki Yokoo
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Tatsuya Orimo
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Shingo Shimada
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Takahiro Einama
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Hirofumi Kamachi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Akinobu Taketomi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
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Tovoli F, Negrini G, Bolondi L. Comparative analysis of current guidelines for the treatment of hepatocellular carcinoma. Hepat Oncol 2016; 3:119-136. [PMID: 30191033 PMCID: PMC6095419 DOI: 10.2217/hep-2015-0006] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2015] [Accepted: 01/15/2016] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma is one of the most common malignancies and represents a unique challenge for physicians and patients. Treatment patterns are not uniform between areas despite efforts to promote a common protocol. Even if most hepatologists worldwide adopt the Barcelona Clinic Liver Cancer staging system, Asian and North American physicians are also independently making an effort to expand the indications of each treatment, combining therapies for better outcomes. Also, new therapeutic techniques have emerged and an increasing number of studies are trying to include these paradigm shifts into newer treatment guidelines. Controversial and diverging points in the current international guidelines are emphasized and discussed. Unanswered questions are also analyzed to identify the most needed and promising future perspectives.
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Affiliation(s)
- Francesco Tovoli
- Department of Medical & Surgical Sciences, Alma Mater Studiorum-University of Bologna, Via Massarenti 9, 40138 Bologna, Italy
| | - Giulia Negrini
- Department of Medical & Surgical Sciences, Alma Mater Studiorum-University of Bologna, Via Massarenti 9, 40138 Bologna, Italy
| | - Luigi Bolondi
- Department of Medical & Surgical Sciences, Alma Mater Studiorum-University of Bologna, Via Massarenti 9, 40138 Bologna, Italy
- *Author for correspondence:
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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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Survival Outcome Between Hepatic Resection and Transarterial Embolization for Hepatocellular Carcinoma More Than 10 cm: A Propensity Score Model. World J Surg 2015; 39:1510-8. [DOI: 10.1007/s00268-015-2975-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
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Cho CS. Prognostication systems as applied to primary and metastatic hepatic malignancies. Surg Oncol Clin N Am 2014; 24:41-56. [PMID: 25444468 DOI: 10.1016/j.soc.2014.09.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Staging systems are an attempt to incorporate the biology and therapy for cancer in a way that enables categorization and prediction of oncologic outcomes. Because of unusual disease biology and complexities related to treatment intervention, efforts to develop reliable staging systems for hepatic malignancies have been challenging. This article discusses the ways in which improved understanding of these diseases has informed the evolution of prognostication systems as applied to hepatocellular carcinoma, cholangiocarcinoma, and hepatic colorectal adenocarcinoma.
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Affiliation(s)
- Clifford S Cho
- Section of Surgical Oncology, Department of Surgery, University of Wisconsin School of Medicine and Public Health, J4/703 Clinical Sciences Center, 600 Highland Avenue, Madison, WI 53792, USA.
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Zhang H, Yuan SX, Dai SY, Zhang JM, Huang X, Lu CD, Lu JH, Wu FQ, Lau WY, Wu MC, Yang T, Shen F. Tumor size does not independently affect long-term survival after curative resection of solitary hepatocellular carcinoma without macroscopic vascular invasion. World J Surg 2014; 38:947-57. [PMID: 24258262 DOI: 10.1007/s00268-013-2365-2] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVE The aim of this study was to investigate the prognostic value of tumor size alone on long-term survival and recurrence after curative resection for solitary hepatocellular carcinoma (HCC) without macroscopic vascular invasion. METHODS A single-center cohort of 615 patients with solitary HCC (a single tumor, without macroscopic vascular invasion or distant metastasis) undergoing curative hepatic resection from 2002 to 2010 was retrospectively studied. Using 2.0, 3.0, 4.0, 5.0, 8.0, and 10.0 cm as cut-off values of tumor size, the overall survival (OS) and recurrence-free survival (RFS) rates were compared between the groups of patients with tumor size up to a certain cut-off value and the groups of patients with tumor size above that cut-off value. Thus, multiple comparisons were done. The prognostic factors of OS and RFS were evaluated using univariate and multivariate analyses. RESULTS The median tumor size of all HCCs was 4.0 cm (range 0.9-22.0 cm). The in-hospital mortality rate was 1.0 %, and the overall morbidity rate was 22.3 %. The 1-, 3-, and 5-year OS rates were 96.0, 79.8, and 69.9 %, and the corresponding RFS rates were 83.6, 72.7, and 57.2 %, respectively. On univariate analyses, the 1-, 3-, and 5-year OS and RFS rates were significantly different between the individual two groups of patients as divided by the aforementioned different cut-off values of tumor sizes (all p < 0.05). However, when tumor size was put as a continuous variable into multivariate analysis, it was no longer an independent prognostic factor of OS or RFS after curative resection. CONCLUSIONS Tumor size did not independently affect long-term survival and recurrence after curative resection of solitary HCC without macroscopic vascular invasion. Therefore, there is no size limit that precludes hepatic resection for solitary HCC, provided the tumor is resectable.
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Affiliation(s)
- Han Zhang
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No.225, Changhai Road, Shanghai, China
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Characteristics of combined hepatocelluar-cholangiocarcinoma and comparison with intrahepatic cholangiocarcinoma. Eur J Surg Oncol 2014; 40:976-81. [PMID: 24909336 DOI: 10.1016/j.ejso.2014.04.016] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2013] [Revised: 04/25/2014] [Accepted: 04/28/2014] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND The 7th American Joint Committee on Cancer (AJCC) currently classifies combined hepatocellular-cholangiocarcinoma (cHCC-CC) and intrahepatic cholangiocarcinoma (ICC) into one category. Study outcomes comparing the two carcinomas have shown contrary results. This study was designed to compare the survival and prognostic factors of both carcinomas. METHODS We retrospectively reviewed the medical records of 107 patients with cHCC-CC or ICC who underwent liver resection between January 2000 and December 2009. RESULTS Thirty patients (28%) were diagnosed with cHCC-CC, and 77 patients (72%) had ICC. Disease-free survival (DFS) was poorer in the cHCC-CC patients (six months), and the overall survival (OS) durations were similar (p = 0.477) between cHCC-CC (58 months) and ICC (45 months) patients. A tumor size larger than 5 cm, vascular invasion and lymph node (LN) metastasis were prognostic factors in all patients. However, tumor size and LN metastasis in cHCC-CC patients and carbohydrate antigen 19-9, differentiation and LN metastasis in ICC patients were found to be independent prognostic factors. CONCLUSIONS Patients with cHCC-CC showed poorer DFS and similar OS rates compared to those with ICC. Our study revealed different prognostic factors in cHCC-CC. To understand more accurately cHCC-CC's prognosis, difference of genetic characteristics and tumor biology should be further evaluated.
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Brouquet A, Andreou A, Shindoh J, Vauthey JN. Methods to improve resectability of hepatocellular carcinoma. Recent Results Cancer Res 2013; 190:57-67. [PMID: 22941013 DOI: 10.1007/978-3-642-16037-0_4] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Liver resection is associated with prolonged survival in selected patients with hepatocellular carcinoma (HCC). Surgical resection of HCC may be decided on an individual basis according to the extent of the tumor and the severity of chronic liver disease. In patients with compensated cirrhosis, the volume of the future liver remnant (FLR) is the most reliable factor for predicting postoperative liver function. Methods of increasing the FLR volume, including portal vein embolization and sequential transarterial chemoembolization in patients who are primarily not eligible for liver resection, have been shown to be safe and have contributed to the increase in the number of surgical candidates.
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Affiliation(s)
- Antoine Brouquet
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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17
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Cauchy F, Fuks D, Belghiti J. HCC: current surgical treatment concepts. Langenbecks Arch Surg 2012; 397:681-95. [DOI: 10.1007/s00423-012-0911-2] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2012] [Accepted: 01/17/2012] [Indexed: 12/28/2022]
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Vauthey JN, Dixon E, Abdalla EK, Helton WS, Pawlik TM, Taouli B, Brouquet A, Adams RB. Pretreatment assessment of hepatocellular carcinoma: expert consensus statement. HPB (Oxford) 2010; 12:289-99. [PMID: 20590901 PMCID: PMC2951814 DOI: 10.1111/j.1477-2574.2010.00181.x] [Citation(s) in RCA: 141] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Staging of hepatocellular carcinoma (HCC) is complex and relies on multiple factors including tumor extent and hepatic function. No single staging system is applicable to all patients with HCC. The staging of the American Joint Committee on Cancer / International Union for Cancer Control should be used to predict outcome following resection or liver transplantation. The Barcelona Clinic Liver Cancer scheme is appropriate in patients with advanced HCC not candidate for surgery. Dual phase computed tomography or magnetic resonance imaging can be used for pretreatment assessment of tumor extent but the accuracy of these methods remains poor to characterize < 1 cm lesions. Assessment of tumor response should not rely only on tumor size and new imaging methods are available to evaluate response to therapy in HCC patients. Liver volumetry is part of the preoperative assessment of patients with HCC candidate for resection as it reflects liver function. Preoperative portal vein embolization is indicated in patients with small future liver remnant (≤ 20% in normal liver; ≤ 40% in fibrotic or cirrhotic liver). Tumor size is not a contraindication to liver resection. Liver resection can be proposed in selected patients with multifocal HCC. Besides tumor extent, surgical resection of HCC may be performed in selected patients with chronic liver disease.
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Affiliation(s)
- Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer CenterHouston, TX, USA
| | - Elijah Dixon
- Department of Surgery, University of CalgaryCalgary, Canada
| | - Eddie K Abdalla
- Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer CenterHouston, TX, USA
| | - W Scott Helton
- Department of Surgery, Hospital of Saint RaphaelNew Haven, CT
| | - Timothy M Pawlik
- Department of Surgery, The Johns Hopkins University School of MedicineBaltimore, MD
| | - Bachir Taouli
- Department of Radiology, Mount Sinai School of MedicineNew York, NY
| | - Antoine Brouquet
- Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer CenterHouston, TX, USA
| | - Reid B Adams
- Department of Surgery, University of Virginia Health SystemCharlottesville, VA, USA
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Truty MJ, Vauthey JN. Surgical resection of high-risk hepatocellular carcinoma: patient selection, preoperative considerations, and operative technique. Ann Surg Oncol 2010; 17:1219-25. [PMID: 20405326 DOI: 10.1245/s10434-010-0976-5] [Citation(s) in RCA: 81] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2009] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma remains a leading cause of cancer death worldwide. There are an increasing number of patients that do not meet traditional criteria for surgical resection as a result of historically poor outcomes. We define these oncologically high-risk patients as those with either one of these risk factors or a combination of them: large (>5 cm) primary tumors, multinodular disease, and/or major vascular invasion. With appropriate selection and preparation, long-term survival is possible in this subset of patients after resection. This review focuses on the surgical treatment of these high-risk patients, focusing on our own institution's approach and methods as well as reviewing the literature pertinent to the support of our current practice.
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Affiliation(s)
- Mark J Truty
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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20
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Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma. Hepatol Int 2010; 4:439-74. [PMID: 20827404 DOI: 10.1007/s12072-010-9165-7] [Citation(s) in RCA: 831] [Impact Index Per Article: 55.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2009] [Accepted: 12/09/2009] [Indexed: 02/07/2023]
Abstract
INTRODUCTION The Asian Pacific Association for the Study of the Liver (APASL) convened an international working party on the management of hepatocellular carcinoma (HCC) in December 2008 to develop consensus recommendations. METHODS The working party consisted of expert hepatologist, hepatobiliary surgeon, radiologist, and oncologist from Asian-Pacific region, who were requested to make drafts prior to the consensus meeting held at Bali, Indonesia on 4 December 2008. The quality of existing evidence and strength of recommendations were ranked from 1 (highest) to 5 (lowest) and from A (strongest) to D (weakest), respectively, according to the Oxford system of evidence-based approach for developing the consensus statements. RESULTS Participants of the consensus meeting assessed the quality of cited studies and assigned grades to the recommendation statements. Finalized recommendations were presented at the fourth APASL single topic conference on viral-related HCC at Bali, Indonesia and approved by the participants of the conference.
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Omata M, Lesmana LA, Tateishi R, Chen PJ, Lin SM, Yoshida H, Kudo M, Lee JM, Choi BI, Poon RTP, Shiina S, Cheng AL, Jia JD, Obi S, Han KH, Jafri W, Chow P, Lim SG, Chawla YK, Budihusodo U, Gani RA, Lesmana CR, Putranto TA, Liaw YF, Sarin SK. Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma. Hepatol Int 2010. [PMID: 20827404 DOI: 10.1007/s12072-011-9165-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
INTRODUCTION The Asian Pacific Association for the Study of the Liver (APASL) convened an international working party on the management of hepatocellular carcinoma (HCC) in December 2008 to develop consensus recommendations. METHODS The working party consisted of expert hepatologist, hepatobiliary surgeon, radiologist, and oncologist from Asian-Pacific region, who were requested to make drafts prior to the consensus meeting held at Bali, Indonesia on 4 December 2008. The quality of existing evidence and strength of recommendations were ranked from 1 (highest) to 5 (lowest) and from A (strongest) to D (weakest), respectively, according to the Oxford system of evidence-based approach for developing the consensus statements. RESULTS Participants of the consensus meeting assessed the quality of cited studies and assigned grades to the recommendation statements. Finalized recommendations were presented at the fourth APASL single topic conference on viral-related HCC at Bali, Indonesia and approved by the participants of the conference.
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22
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Tsim NC, Frampton AE, Habib NA, Jiao LR. Surgical treatment for liver cancer. World J Gastroenterol 2010; 16:927-33. [PMID: 20180230 PMCID: PMC2828596 DOI: 10.3748/wjg.v16.i8.927] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2009] [Revised: 12/20/2009] [Accepted: 12/27/2009] [Indexed: 02/06/2023] Open
Abstract
Primary liver cancer is amongst the commonest tumors worldwide, particularly in parts of the developing world, and is increasing in incidence. Over the past three decades, surgical hepatic resection has evolved from a high risk, resource intensive procedure with limited application, to a safe and commonly performed operation with a range of indications. This article reviews the approach to surgical resection for malignancies such as hepatocellular cancer, metastatic liver deposits and neuroendocrine tumors. Survival data after resection is also reviewed, as well as indications for curative resection.
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Pandey D, Lee KH, Wai CT, Wagholikar G, Tan KC. Long term outcome and prognostic factors for large hepatocellular carcinoma (10 cm or more) after surgical resection. Ann Surg Oncol 2007; 14:2817-23. [PMID: 17690940 DOI: 10.1245/s10434-007-9518-1] [Citation(s) in RCA: 110] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2007] [Revised: 06/10/2007] [Accepted: 06/11/2007] [Indexed: 12/18/2022]
Abstract
BACKGROUND Surgical resection is the standard treatment for hepatocellular carcinoma (HCC). However, the role of surgery in treatment of large tumors (10 cm or more) is controversial. We have analyzed, in a single centre, the long-term outcome associated with surgical resection in patients with such large tumors. METHODS We retrospectively investigated 166 patients who had undergone surgical resection between July 1995 and December 2006 because of large (10 cm or more) HCC. Survival analysis was done using the Kaplan-Meier method. Prognostic factors were evaluated using univariate and multivariate analyses. RESULTS Of the 166 patients evaluated, 80% were associated with viral hepatitis and 48.2% had cirrhosis. The majority of patients underwent a major hepatectomy (48.2% had four or more segments resected and 9% had additional organ resection). The postoperative mortality was 3%. The median survival in our study was 20 months, with an actuarial 5-year and 10-year overall survival of 28.6% and 25.6%, respectively. Of these patients, 60% had additional treatment in the form of transarterial chemoembolization, radiofrequency ablation or both. On multivariate analysis, vascular invasion (P < 0.001), cirrhosis (P = 0.028), and satellite lesions/multicentricity (P = 0.006) were significant prognostic factors influencing survival. The patients who had none of these three risk factors had 5-year and 10-year overall survivals of 57.7% each, compared with 22.5% and 19.3%, respectively, for those with at least one risk factor (P < 0.001). CONCLUSIONS Surgical resection for those with large HCC can be safely performed with a reasonable long-term survival. For tumors with poor prognostic factors, there is a pressing need for effective adjuvant therapy.
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Affiliation(s)
- Durgatosh Pandey
- Hepatobiliary Surgery and Liver Transplantation, Asian Centre for Liver Diseases and Transplantation, Singapore, Singapore.
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25
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Capussotti L, Ferrero A, Viganò L, Polastri R, Tabone M. Liver resection for HCC with cirrhosis: surgical perspectives out of EASL/AASLD guidelines. Eur J Surg Oncol 2007; 35:11-5. [PMID: 17689043 DOI: 10.1016/j.ejso.2007.06.005] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2007] [Accepted: 06/20/2007] [Indexed: 02/06/2023] Open
Abstract
EASL/AASLD guidelines clearly define indications for liver surgery for HCC: patients with single HCC and completely preserved liver function without portal hypertension. These guidelines exclude from operation many patients that could benefit from radical resection and that are daily scheduled for hepatectomy in surgical centers. Patients with large tumors or with portal vein thrombosis cannot be transplanted or treated by interstitial treatments. In selected cases liver resection may obtain good long-term outcomes, significantly better than non-curative therapies. In cases of multinodular HCC, liver transplantation is the treatment of choice within Milan criteria; patients beyond these limits can benefit from liver resection, especially if only two nodules are diagnosed: even if they have a worse prognosis, survival results after liver surgery are better than those reported after TACE or conservative treatments. EASL/AASLD guidelines excluded from operating patients with portal hypertension but data about this topic are not conclusive and further studies are necessary. Selected patients with mild portal hypertension could probably be scheduled for liver resection and, considering the shortage of donors, listing for transplantation could be avoided. In conclusion, guidelines for HCC treatment should consider good results of liver resection for advanced HCC, and indications for hepatectomy should be expanded in order not to exclude from radical therapy patients that could benefit from it.
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Affiliation(s)
- L Capussotti
- Department of Surgery, Ospedale Mauriziano Umberto I, Largo Turati 62, Torino, Italy.
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Young AL, Malik HZ, Abu-Hilal M, Guthrie JA, Wyatt J, Prasad KR, Toogood GJ, Lodge JPA. Large hepatocellular carcinoma: time to stop preoperative biopsy. J Am Coll Surg 2007; 205:453-62. [PMID: 17765162 DOI: 10.1016/j.jamcollsurg.2007.04.033] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2007] [Revised: 04/23/2007] [Accepted: 04/24/2007] [Indexed: 02/07/2023]
Abstract
BACKGROUND In Western countries, hepatocellular carcinoma (HCC) often presents at a large size, which is seen as a contraindication to transplantation and often resection. Although diagnosis by imaging and alpha-fetoprotein is usually straightforward, nonspecialist units continue to use biopsy to prove the diagnosis before transfer for specialist surgical opinion. We have looked at the impact of this on our practice. STUDY DESIGN We retrospectively analyzed all large HCCs resected in our unit during the last 12 years. Survival data were calculated according to size and univariate and multivariate analyses were carried out to determine impact of preoperative, operative, and histologic factors affecting outcomes. RESULTS We identified 85 large HCCs (> 3 cm) and classified 42 as giant (> 10 cm). Overall survival at 1, 3, and 5 years was 76%, 54%, and 51%. Size did not influence survival, although more complex surgical techniques were required for giant tumors. Predictors of poorer disease-free survival were positive resection margin (p < 0.001), multiple tumors (p = 0.003), macroscopic vascular invasion (p = 0.015), and preoperative lesion biopsy (p = 0.027). CONCLUSIONS Our data shows excellent outcomes after resection for large HCC. This supports the management of such patients in large-volume units that are fully equipped and experienced in the management of these patients. Preoperative biopsy should be avoided, as this unnecessary maneuver appears to have worsened our longterm results.
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Affiliation(s)
- Alastair L Young
- Hepatobiliary and Transplant Unit, St James's University Hospital, Leeds, UK
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Abstract
In the absence of large randomized trials, the current treatment strategy for hepatocellular carcinoma (HCC) remains a matter of choice depending mostly on retrospective studies, experience of centers, and the technical therapeutic possibilities. In fact, treatment decisions must be based on HCC extension and liver function, which is dependent on underlying liver disease. Cirrhosis limits therapeutic choices, life expectancy, and tolerance to therapy. Surgical resection and/or local destruction are the most common curative treatments. Orthotopic liver transplantation is probably the best treatment for small HCC developed in cirrhosis because it treats tumor, cirrhosis, and preneoplastic lesions at the same time. However, this treatment method is feasible in fewer than 5% of cases. Adjuvant treatments include transarterial chemoembolization, chemotherapy, polyprenoic acid, interferon, adoptive immunotherapy, and intra-arterial radioactive lipiodol. Results from trials warrant confirmation in larger randomized trials to show a clear survival benefit on recurrence rate, secondary prevention, and overall survival. Chemoembolization is the only palliative treatment that has been proven to be active, unlike systemic chemotherapy, immunotherapy, and hormone therapy, whose activity is largely questionable and must all be restricted to clinical trials. Possible future therapeutic strategies include epidermal growth factor receptor inhibitors, antivascular endothelial growth factor therapies, cyclin D inhibitors, and HMG-CoA reductase inhibitors.
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Affiliation(s)
- Philippe Rougier
- Service d'Hépato-gastroentérologie, Hopital Ambroise Paré, 92100 Boulogne, France.
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Cillo U, Vitale A, Brolese A, Zanus G, Neri D, Valmasoni M, Bonsignore P, Grigoletto F, Burra P, Farinati F, D'Amico DF. Partial hepatectomy as first-line treatment for patients with hepatocellular carcinoma. J Surg Oncol 2007; 95:213-20. [PMID: 17066432 DOI: 10.1002/jso.20641] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Partial hepatectomy (PH) and liver transplantation (LT) compete as first-line treatment for hepatocellular carcinoma (HCC). A prospectively collected database was retrospectively reviewed to establish when PH can compete with LT. METHODS Between 1991 and 2002, PH was performed in 131 cases of HCC (Child-Pugh A-B, technically resectable tumor without metastases). To ascertain patient survival after PH, we compared this series with a group of 40 HCC patients (G1-G2 HCC with no gross vascular invasion or metastasis) enlisted for liver transplantation during the same period. RESULTS The 1-, 3-, and 5-year intention-to-treat survival rates were 75%, 52%, and 31% for resection and 89%, 71%, and 63% for transplantation. Two tumor-related variables (gross vascular invasion and histological grade) and three liver function parameters (Child-Pugh score, bilirubin, Okuda stage) proved to be independent predictors of survival after resection, whereas nodule size and number, and Milan criteria did not. The 5-year survival of the best candidates for resection (favorable tumor biology with very well preserved liver function, n = 52) was 58%. On a descriptive basis alone, this result did not differ significantly from the outcome in LT patients. PH patients with a poorly differentiated tumor and/or gross vascular invasion (n = 28) had the worst outcome, irrespective of their liver function parameters. CONCLUSIONS For technically resectable tumors without aggressive features (G3 or macroscopic vascular invasion), PH can only compete with LT, in terms of long-term survival, when patients with a well-preserved liver function are selected.
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Affiliation(s)
- Umberto Cillo
- Unità di chirurgia epatobiliare e trapianto di fegato, Dipartimento assistenziale di chirurgia generale e trapianti d'organo, University of Padua, School of Medicine, Padova, Italy
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Taieb J, Barbare JC, Rougier P. Medical treatments for hepatocellular carcinoma (HCC): what’s next? Ann Oncol 2006; 17 Suppl 10:x308-14. [PMID: 17018744 DOI: 10.1093/annonc/mdl279] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Affiliation(s)
- J Taieb
- Service d'Hépato-gastroentérologie, Groupe Hospitalier Pitié Salpétrière, Paris, France
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Cillo U, Vitale A, Navaglia F, Basso D, Montin U, Bassanello M, D'Amico F, Ciarleglio FA, Brolese A, Zanus G, De Pascale V, Plebani M, D'Amico DF. Role of blood AFP mRNA and tumor grade in the preoperative prognostic evaluation of patients with hepatocellular carcinoma. World J Gastroenterol 2006; 11:6920-5. [PMID: 16437593 PMCID: PMC4717031 DOI: 10.3748/wjg.v11.i44.6920] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM To explore the potential prognostic role of preoperative tumor grade and blood AFP mRNA in a cohort of patients with hepatocellular carcinoma (HCC) eligible for radical therapies according to a well-defined treatment algorithm not including nodule size and number as absolute selection criteria. METHODS Fifty patients with a diagnosis of HCC were prospectively enrolled in the study. Inclusion criteria were: (1) histological assessment of tumor grade by means of percutaneous biopsies; (2) determination of AFP mRNA status in the blood; (3) patient's eligibility for radical therapies. RESULTS At preoperative evaluation, 54% of the study group had a well-differentiated HCC, 42% had AFP mRNA in the blood, 40% had a tumor larger than 5 cm and 56% had more than one nodule. Surgery (resection or liver transplantation) was performed in 29 patients, while 21 had percutaneous ablation procedures. After a median follow-up of 28 mo, 12-, 24-, and 36-mo survival rates were 78%, 58%, and 51%, respectively. Surgical therapy, performance status and three tumor-related variables (AFP mRNA, HCC grade and gross vascular invasion) resulted as significant survival predictors at univariate analysis. Nodule size and number did not perform as significant prognosticators. Multivariate study selected only surgical therapy and a biologically early HCC profile (AFP mRNA negative and well-differentiated tumor without gross vascular invasion) as independent survival variables. CONCLUSION The preoperative determination of tumor grade and blood AFP mRNA status may potentially refine the prognostic evaluation of HCC patients and improve the selection process for radical therapies.
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Affiliation(s)
- Umberto Cillo
- Clinica Chirurgica I - Dipartimento di Scienze Chirurgiche e Gastroenterologiche - Università degli Studi di Padova - Via Giustiniani 2, Policlinico III piano, 35128 Padova, Italy
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31
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D'Ippolito G, Abreu Junior LD, Borri ML, Galvão Filho MDM, Hartmann LGC, Wolosker AMB, Ribeiro M, Salem MZ, Misiara A. Apresentações incomuns do hepatocarcinoma: ensaio iconográfico. Radiol Bras 2006. [DOI: 10.1590/s0100-39842006000200013] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
O objetivo deste trabalho foi descrever e ilustrar aspectos incomuns do hepatocarcinoma na tomografia computadorizada e ressonância magnética. A partir da análise retrospectiva de 100 casos de pacientes com hepatocarcinoma diagnosticado por análise combinada de exames de imagem, dosagem de alfa-feto-proteína, biópsia percutânea ou ressecção cirúrgica, selecionamos aqueles com apresentação atípica em um ou mais métodos de imagem ou aqueles com evolução não usual, ilustrando os seus principais aspectos de imagem. Entre os casos apresentados, escolhemos pacientes com hepatocarcinomas císticos, hemorrágicos, rotos e causando hemoperitônio, calcificados, com regressão espontânea, exofíticos, hipovasculares, gigantes e com disseminação não usual. O hepatocarcinoma é o tumor maligno mais comum do fígado e freqüentemente tem apresentação típica e associada à cirrose hepática. Porém, em alguns casos, apresentações atípicas podem retardar o seu diagnóstico.
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Liau KH, Ruo L, Shia J, Padela A, Gonen M, Jarnagin WR, Fong Y, D'Angelica MI, Blumgart LH, DeMatteo RP. Outcome of partial hepatectomy for large (> 10 cm) hepatocellular carcinoma. Cancer 2005; 104:1948-55. [PMID: 16196045 DOI: 10.1002/cncr.21415] [Citation(s) in RCA: 108] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND Surgical resection for large (> 10 cm) hepatocellular carcinoma (HCC) is believed by many to be ineffective. The objective of the current study was to review the outcome of partial hepatectomy in patients with large HCC. METHODS Between 1985 and 2002, 193 consecutive patients who underwent partial hepatectomy for HCC were identified from a prospective database. The 82 patients with tumors > 10 cm were compared with the remaining 111 patients with < or = 10 cm tumors. Clinicopathologic features were analyzed and prognostic factors were evaluated by univariate and multivariate analysis. RESULTS The 5-year overall survival for patients with large HCC was 33% with a median of 32 months. Patients with < or = 10 cm tumors had similar survival. Furthermore, there was no significant difference between the groups in operative mortality (2% in large HCC vs. 6%) or recurrence rate. In patients with large HCC, vascular invasion by tumor and intraoperative blood loss > 2 liters predicted overall survival on multivariate analysis. CONCLUSIONS Partial hepatectomy is safe for patients with large HCC. In selected patients with large tumors, resection achieves similar overall survival and recurrence-free survival to that of patients with smaller tumors. Minimizing intraoperative blood loss appears to be critical for favorable long-term outcome in patients with large HCC.
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Affiliation(s)
- Kui-Hin Liau
- Hepatobiliary Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA
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Abstract
Surgery for hepatocellular carcinoma (HCC) includes partial liver resection (LR) and liver transplantation (LT). Although LT represents the most efficient treatment in patients with small HCC, <30% of patients are eligible for LT because of restrictive criteria (one nodule <5 cm or two to three nodules <3 cm without macroscopic vascular invasion), graft unavailability and the high cost of the procedure. For large HCC, LR remains the only potential curative treatment. LR is now safer, with a low rate of mortality. Selective preoperative morphological assessment, preoperative use of portal vein embolization for increasing future remnant liver volume and the improvement of surgical techniques such as the use of intermittent clamping and anterior approach are factors that improve the safety and tolerance of LR. In patients with small HCCs and a preserved liver function (Child-Pugh grade A), good long-term survival can be achieved after anatomical resection that removes the tumor(s) and its portal vein territory. These good results of LR for small HCC and the increasing duration of the waiting list for candidates of LT have renewed the place of LR as a bridge treatment before LT.
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Affiliation(s)
- Jacques Belghiti
- Department of Digestive Surgery and Transplantation, Beaujon Hospital, Clichy, France Assistance Publique-Hôpitaux de ParisFrance
| | - Reza Kianmanesh
- Department of Digestive Surgery and Transplantation, Beaujon Hospital, Clichy, France Assistance Publique-Hôpitaux de ParisFrance
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34
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35
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Ding X, Yang LY, Huang GW, Wang W, Lu WQ. ADAM17 mRNA expression and pathological features of hepatocellular carcinoma. World J Gastroenterol 2004; 10:2735-9. [PMID: 15309730 PMCID: PMC4572204 DOI: 10.3748/wjg.v10.i18.2735] [Citation(s) in RCA: 64] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: To study the expression of a disintegrin and metalloproteinase 17 (ADAM17) mRNA in hepatocellular carcinoma (HCC) and to evaluate the relationship between ADAM17 mRNA expression and clinicopathological features of HCC.
METHODS: Hepatocellular carcinomas (HCC) from 31 cases were divided into small HCC (SHCC), nodular HCC (NHCC) and solitary large HCC (SLHCC) according to tumor diameter and the number of nodes. ADAM17 mRNA expressions were compared among those groups by means of semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). The relationship between ADAM17 mRNA expression level and clinicopathological features of HCC was evaluated.
RESULTS: NHCC had lower differentiation and was more frequently of microvascular invasion (10/12) than SHCC (3/11) and SLHCC (3/8) (P < 0.05), but no statistical difference was observed between SHCC and SLHCC comparing their clinicopathological features. ADAM17 mRNA expression was detected in 77.4% (24/31) of HCC tissues and was significantly higher than that in paired non-cancerous liver tissues in which only 35.5% (11/31) of the samples were detected of the expression (P < 0.05). The expression of ADAM17 mRNA was much higher in NHCC than in SHCC and SLHCC (P < 0.05), while no significant difference was discovered between SHCC and SLHCC. The quantities of ADAM17 mRNA were significantly higher in poorly differentiated HCC than in well or moderately differentiated HCC, but no statistical difference was found concerning liver cirrhosis, tumor capsule formation or microvascular invasion of the cancer.
CONCLUSION: The increased expression of ADAM17 may play a key role in the development of HCC. The expression levels of ADAM17 mRNA varied among different pathological types of HCC. Lower mRNA expression of ADAM17 mRNA in SLHCC may be associated with the better molecular pathological features of SLHCC.
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Affiliation(s)
- Xiang Ding
- Liver Cancer Laboratory, Department of General Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
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36
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Yeh CN, Lee WC, Chen MF. Hepatic resection and prognosis for patients with hepatocellular carcinoma larger than 10 cm: two decades of experience at Chang Gung memorial hospital. Ann Surg Oncol 2004; 10:1070-6. [PMID: 14597446 DOI: 10.1245/aso.2003.03.072] [Citation(s) in RCA: 88] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Although screening programs in high-risk populations have facilitated the detection of small hepatocellular carcinoma (HCC), some HCC patients continue to present with advanced, large tumors. However, reports of hepatic resection for HCC larger than 10 cm (L-HCC) are limited. This study aims to determine the clinicopathologic factors that influence the prognosis of hepatic resection for L-HCC. METHODS The clinical features of 211 L-HCC patients undergoing hepatic resection were reviewed. Clinical features and factors influencing the outcome of 985 patients with HCC smaller than 10 cm (S-HCC) were used for comparison. RESULTS Of 1196 surgically resected HCCs, 211 (17.6%) were L-HCC. Multivariate logistic regression analysis showed that the presence of dull abdominal pain, a low indocyanine green retention rate value, a high percentage of alfa fetoprotein (AFP) >400 ng/mL, major hepatectomy, absence of tumor capsule formation, satellite lesions, and vascular invasion were the seven main independent factors differentiating L-HCC from S-HCC patients. Significantly worse overall survival was noted in L-HCC patients, especially those with tumor rupture, satellite lesions, AFP >400 ng/mL, and blood loss of >1 L during surgery. CONCLUSIONS Hepatic resection, when feasible, is safe and is the preferred treatment for L-HCC patients. However, overall and disease-free survival for L-HCC are worse than for S-HCC. Disease-free survival for L-HCC patients undergoing hepatic resection is significantly influenced by a high value of alkaline phosphatase and by AFP. Overall survival for L-HCC patients undergoing hepatic resection is significantly influenced by a high value of AFP, blood loss, tumor rupture, and satellite lesions.
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Affiliation(s)
- Chun-Nan Yeh
- Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan.
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37
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Capussotti L, Muratore A, Massucco P, Ferrero A, Polastri R, Bouzari H. Major liver resections for hepatocellular carcinoma on cirrhosis: early and long-term outcomes. Liver Transpl 2004; 10:S64-8. [PMID: 14762842 DOI: 10.1002/lt.20035] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Since the lack of donors, liver resections continue to be the treatment of choice for cirrhotic patients with good liver function and resectable hepatocellular carcinoma (HCC). Moreover, over the past 2 decades, an increasing number of major hepatic resections have been performed. The aim of this study is to evaluate short- and long-term outcomes of 55 cirrhotic patients undergoing major hepatic resection with particular attention to the survival of the patients with gross portal vein invasion or large size tumors. Twenty-two patients (40%) required intra- or post-operative blood transfusion. Medium tumor size was 66.6 +/- 29.2 mm; 7 patients had large size (>10 cm) HCCs. A single node was present in 38 cases (69.1%). There was a gross portal vein tumor thrombus (PVTT) in 13 patients (23.6%). Resection was non-curative in 4 cases. In-hospital mortality and morbidity rates were 5.5% and 30.9%, respectively. The overall and disease-free survival rates were 36.2% and 42.8%, respectively. Overall 5-year survival rates of patients with large size tumors was 17.1%. Ten patients with a gross PVTT had an R0 resection with a 26.6% 5-year survival rate. In conclusion, major hepatic resections for HCC can be performed with low mortality and morbidity rates. HCCs with PVTT or greater than 10 cm in size have very limited options of treatment; the favorable long-term results of our study suggest that they should undergo surgery if a radical resection can be achieved.
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Affiliation(s)
- Lorenzo Capussotti
- Department of Surgical Oncology, Istituto per la Ricerca e la Cura del Cancro, Turin, Italy.
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38
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Abstract
Hepatic resection and liver transplantation are considered the only curative treatments for hepatocellular carcinoma (HCC). Liver transplantation for HCCs < or =5 cm in diameter has been shown to produce favorable survival results, but its application is limited by the lack of donors. Hepatic resection remains the treatment of choice for patients who are not transplantation candidates because of large tumor, macroscopic vascular invasion, or advanced age. For small HCCs associated with Child's A cirrhosis, hepatic resection should still be considered the first-line treatment, but salvage transplantation for intrahepatic recurrence may be a feasible strategy. Recent improvement in surgical techniques and perioperative care has increased the safety and expanded the indication of hepatic resection for HCC to include large tumors that require extended hepatectomy in cirrhotic patients. Selection of appropriate candidates for hepatectomy depends on careful assessment of the tumor status and liver function reserve. Evaluation of the general fitness of patients is also critical because comorbid illness is an important cause of postoperative mortality, even if the patients have good liver function reserve. With careful patient selection and surgical expertise, the current operative mortality of hepatectomy for HCC is about 5% or less in major centers. Improved long-term survival results after resection of HCC have also been reported recently, with an overall 5-year survival rate of about 50%. The improved perioperative and long-term survival results have strengthened the role of hepatectomy as the mainstay of treatment for HCC despite the availability of a number of other treatment options for localized HCC.
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Affiliation(s)
- Ronnie Tung-Ping Poon
- Centre for the Study of Liver Disease and Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, China
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39
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Marín-Hargreaves G, Azoulay D, Bismuth H. Hepatocellular carcinoma: surgical indications and results. Crit Rev Oncol Hematol 2003; 47:13-27. [PMID: 12853096 DOI: 10.1016/s1040-8428(02)00213-5] [Citation(s) in RCA: 63] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a tumour of increasing incidence that usually arises in cirrhotic liver. Untreated, the prognosis is grim and the only curative treatment is surgical resection. The practical application of segmental surgery to the liver together with the use of ultrasound and other imaging techniques, patient selection criteria and improvements in perioperative technique and postoperative care have contributed to better results in hepatic surgery. Today, less than 10% mortality for resection of cirrhotic livers, with up to 50% 5-year survival rates are to be expected. However, the limits of resection for cure: intrahepatic recurrence makes stringent follow-up necessary. In this way the available modalities of treatment can be applied so as to improve survival. Herein, a current 'state-of-the-art' of surgical indications and results for HCC is given.
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Affiliation(s)
- Guillermo Marín-Hargreaves
- Centre Hépato-Biliaire, Hôpital Paul Brousse, Villejuif et Université Paris-Sud, 12 avenue Paul Vaillant Couturier, 94800 Villejuif, Paris, France
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40
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De Carlis L, Giacomoni A, Pirotta V, Lauterio A, Slim AO, Sammartino C, Cardillo M, Forti D. Surgical treatment of hepatocellular cancer in the era of hepatic transplantation. J Am Coll Surg 2003; 196:887-97. [PMID: 12788425 DOI: 10.1016/s1072-7515(03)00140-6] [Citation(s) in RCA: 64] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
BACKGROUND This study compares liver resection (LR) or transplantation (LTx) in an attempt to reevaluate the indications for treatment. STUDY DESIGN One hundred fifty-four LRs and 121 LTxs performed from 1985 to 1999 were considered. Survival and recurrence rate, together with age, gender, liver disease, Child-Pugh classification, alpha-fetoprotein (AFP), tumor capsule, vascular invasion, size, number of nodules, histologic grade, and pTNM were considered. Followup was completed in all cases (mean +/- SD = 3.2 +/- 2.9 years). RESULTS The 5- and 10-year actuarial survival rates were 61.7% and 59.8% in LTx and 46.9% and 28.0% in LR (p = 0.08). Recurrence-free survival was 85.9% and 85.9%, respectively, in LTx and 42.8% and 30.7% in LR (p < 0.0001). In both groups, size, capsule, AFP, vascular invasion, grade, pTNM, Child-Pugh classification, and age were all significantly related to survival and cancer recurrence. pTNM, AFP, Child-Pugh classification, and age, in LR, and capsule, AFP, and viral cirrhosis, in LTx, were significant independent variables in Cox's regression model for survival. Only AFP, vascular invasion, and grade were significant in both groups for recurrence. CONCLUSIONS LTx offers better recurrence freedom than LR, but longterm survival is not significantly different in the two series. A strict selection should be made to optimize graft allocation. Size and multifocality should not be considered absolute contraindications for LTx. AFP, vascular invasion, and grade are more likely to reflect the risk of recurrence of the disease. LR should be considered in patients who do not fulfill transplant criteria and also in some categories of patients with certain tumor characteristics (small resectable tumors in well-compensated cirrhosis).
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Affiliation(s)
- Luciano De Carlis
- Division of General Surgery and Abdominal Transplantation, Niguarda Hospital, Milan, Italy
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41
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Abstract
AIM: To evaluate the value of right trisectionectomy, previously named right trisegmentectomy, in the treatment of primary liver cancer by summarizing our 13-year experience for this procedure.
METHODS: Thirty three primary liver cancer patients undergoing right trisectionectomy from Apr. 1987 to Dec. 1999 were investigated retrospectively. The impacts in survival of patients by cancerous biological behavior, such as tumor thrombi and satellite nodules, were discussed respectively. All right trisectionectomies were performed under normothermic interruption of porta hepatis at single time. Ultrasonic dissector (CUSA system 200) was used in dissection of hepatic parenchyma from Nov. 1992, instead of finger fracture.
RESULTS: 1-, 3- and 5-year survival rates were 71.9%, 40.6% and 34.4%, respectively. The longest survival term with free cancer was 150 months (alive). There were no significant differences in survival curves between cases with and without tumor thrombi (right branch of portal vein) and satellite nodules. Operative mortality was 3.0% (1/33). Main surgical complications occurred in 5 cases.
CONCLUSION: Right trisectionectomy should be regarded as an effective and safe procedure for huge primary liver cancers and is worth using more widely.
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Affiliation(s)
- Jing-An Rui
- Department of General Surgery, Peking Union Medical College Hospital, Beijing 100032, China
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42
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Abstract
AIM To evaluate the value of right trisectionectomy, previously named right trisegmentectomy, in the treatment of primary liver cancer by summarizing our 13-year experience for this procedure. METHODS Thirty three primary liver cancer patients undergoing right trisectionectomy from Apr. 1987 to Dec. 1999 were investigated retrospectively. The impacts in survival of patients by cancerous biological behavior, such as tumor thrombi and satellite nodules, were discussed respectively. All right trisectionectomies were performed under normothermic interruption of porta hepatis at single time. Ultrasonic dissector (CUSA system 200) was used in dissection of hepatic parenchyma from Nov. 1992, instead of finger fracture. RESULTS 1-, 3- and 5-year survival rates were 71.9 %, 40.6 % and 34.4 %, respectively. The longest survival term with free cancer was 150 months (alive). There were no significant differences in survival curves between cases with and without tumor thrombi (right branch of portal vein) and satellite nodules. Operative mortality was 3.0 % (1/33). Main surgical complications occurred in 5 cases. CONCLUSION Right trisectionectomy should be regarded as an effective and safe procedure for huge primary liver cancers and is worth using more widely.
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Affiliation(s)
- Jing-An Rui
- Department of General Surgery, Peking Union Medical College Hospital, Beijing 100032, China
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De Carlis L, Giacomoni A, Lauterio A, Slim A, Sammartino C, Pirotta V, Colella G, Forti D. Liver transplantation for hepatocellular cancer: should the current indication criteria be changed? Transpl Int 2003; 16:115-122. [PMID: 12595973 DOI: 10.1111/j.1432-2277.2003.tb00272.x] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2001] [Revised: 05/14/2002] [Accepted: 07/20/2002] [Indexed: 11/09/2023]
Abstract
Liver transplantation (LTx) is the best treatment for hepatocellular carcinoma (HCC), but should be offered only to selected patients. The usual procedure is to transplant only for small and unilobular tumors. The aim of this paper is to verify whether the actual indication criteria are still justified. The details of 121 patients with HCC who were submitted to LTx from 1985 to 2000 were analyzed. Age, gender, liver disease, Child class, alpha-fetoprotein (AFP) level, presence of tumor capsule, vascular invasion, size and number of nodules, histological grade, and pTNM were considered. The 5- and 10-year actuarial survival rates were 61.7% and 53.1%. Freedom from recurrence was 85.9% and 85.9%, respectively. At univariate analysis, size, presence of capsule, AFP levels, vascular invasion, grade, pTNM, transarterial chemoembolization (TACE), Child class, and age were all significantly related to survival and/or cancer recurrence. Presence of capsule, AFP levels, and viral cirrhosis were independent variables in Cox's analysis for survival, whereas histological grade, AFP levels, and vascular invasion were significant independent variables for recurrence. In conclusion, a strict selection should be made to optimize graft allocation while size and multifocality should probably no longer be considered a contraindication for LTx. Histological grade, AFP levels, and vascular invasion, as indicator of tumor behavior, more likely reflect the risk of recurrence.
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Affiliation(s)
- Luciano De Carlis
- Department of Surgery and Abdominal Transplantation, Niguarda Hospital, 20162 Milan, Italy.
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44
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Kianmanesh R, Regimbeau JM, Belghiti J. Selective approach to major hepatic resection for hepatocellular carcinoma in chronic liver disease. Surg Oncol Clin N Am 2003; 12:51-63. [PMID: 12735129 DOI: 10.1016/s1055-3207(02)00090-x] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
For large HCCs, partial liver resection remains the best therapeutic option for cure because neither liver transplantation nor percutaneous treatments are indicated. In specialized centers, a better selection of at-risk patients and technical procedures, including the use of intermittent inflow occlusion and the anterior approach, have contributed to improve dramatically the outcome of major liver resection for HCC in CLD. In addition, portal vein embolization has become an important tool to hypertrophy the future liver remnant before major liver resection in cirrhotic patients with apparently normal liver function.
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Affiliation(s)
- Reza Kianmanesh
- Department of Surgery, Beaujon Hospital, 100 Boulevard du Gal Leclerc, F-92110 Clichy, France
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45
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Extended hepatic resection for hepatocellular carcinoma in patients with cirrhosis: is it justified? Ann Surg 2002. [PMID: 12409666 DOI: 10.1097/01.sla.0000033038.38956.5e] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To evaluate the perioperative outcomes and long-term survival of extended hepatic resection for hepatocellular carcinoma (HCC) in patients with cirrhosis. SUMMARY BACKGROUND DATA Hepatic resection is a well-established treatment for HCC in cirrhotic patients with preserved liver function and limited disease. However, the role of extended hepatic resection (more than four segments) for HCC in cirrhotic patients has not been elucidated. METHODS Between 1993 and 2000, 45 consecutive patients with histologically confirmed cirrhosis underwent right or left extended hepatectomy for HCC (group A). Perioperative outcomes and long-term survival of these patients were compared with 161 patients with HCC and cirrhosis who underwent hepatic resection of a lesser extent in the same period (group B). All clinicopathologic and follow-up data were collected prospectively. RESULTS Group A patients had significantly higher intraoperative blood loss, longer operation time, and longer hospital stay than group B. However, the two groups were similar in overall morbidity and hospital mortality. There were no significant differences in the incidence of liver failure or other complications. The resection margin width was similar between the two groups. Despite significantly larger tumor size in group A compared with group B, long-term survival was comparable between the two groups. CONCLUSIONS Extended hepatic resection for HCC can be performed in selected cirrhotic patients with acceptable morbidity, mortality, and long-term survival that are comparable to those of lesser hepatic resection. Extended hepatectomy for large HCC extending from one lobe to the other or central HCC critically related to the hepatic veins is justifiable in cirrhotic patients with preserved liver function and adequate liver remnant.
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46
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Poon RTP, Fan ST, Lo CM, Liu CL, Lam CM, Yuen WK, Yeung C, Wong J. Extended hepatic resection for hepatocellular carcinoma in patients with cirrhosis: is it justified? Ann Surg 2002; 236:602-11. [PMID: 12409666 PMCID: PMC1422618 DOI: 10.1097/00000658-200211000-00010] [Citation(s) in RCA: 151] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVE To evaluate the perioperative outcomes and long-term survival of extended hepatic resection for hepatocellular carcinoma (HCC) in patients with cirrhosis. SUMMARY BACKGROUND DATA Hepatic resection is a well-established treatment for HCC in cirrhotic patients with preserved liver function and limited disease. However, the role of extended hepatic resection (more than four segments) for HCC in cirrhotic patients has not been elucidated. METHODS Between 1993 and 2000, 45 consecutive patients with histologically confirmed cirrhosis underwent right or left extended hepatectomy for HCC (group A). Perioperative outcomes and long-term survival of these patients were compared with 161 patients with HCC and cirrhosis who underwent hepatic resection of a lesser extent in the same period (group B). All clinicopathologic and follow-up data were collected prospectively. RESULTS Group A patients had significantly higher intraoperative blood loss, longer operation time, and longer hospital stay than group B. However, the two groups were similar in overall morbidity and hospital mortality. There were no significant differences in the incidence of liver failure or other complications. The resection margin width was similar between the two groups. Despite significantly larger tumor size in group A compared with group B, long-term survival was comparable between the two groups. CONCLUSIONS Extended hepatic resection for HCC can be performed in selected cirrhotic patients with acceptable morbidity, mortality, and long-term survival that are comparable to those of lesser hepatic resection. Extended hepatectomy for large HCC extending from one lobe to the other or central HCC critically related to the hepatic veins is justifiable in cirrhotic patients with preserved liver function and adequate liver remnant.
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Affiliation(s)
- Ronnie Tung Ping Poon
- Centre for the Study of Liver Disease & Department of Surgery, University of Hong Kong Medical Centre, Queen Mary Hospital, Hong Kong, China.
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47
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Roberts DA, Rosen MA, Clark TWI, Mondschein J, Soulen MC, Siegelman E, Leigh JS. Chemical-shift MR imaging of acetic acid during percutaneous chemical ablation therapy: preliminary work. J Vasc Interv Radiol 2002; 13:1055-9. [PMID: 12397130 DOI: 10.1016/s1051-0443(07)61874-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
Abstract
The purpose of this study was to test the hypothesis that chemical-shift magnetic resonance (MR) imaging may be used to map the distribution of acetic acid during percutaneous chemical ablation procedures. Chemical-shift MR imaging was performed with use of standard methods on a 1.5-T scanner. Phantom and ex-vivo data demonstrated focal increases in the observed signal in chemical-shift MR imaging that correlate well with the site of injection. Preliminary study in a patient with hepatoma revealed focal signal at the injection site. These preliminary results suggest that chemical-shift MR imaging may be used to visualize acetic acid distribution during percutaneous chemical ablation procedures.
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Affiliation(s)
- David A Roberts
- Department of Radiology, University of Pennsylvania Medical Center, 3400 Spruce Street, Philadelphia, Pennsylvania 19104-4283, USA.
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Poon RTP, Fan ST, Wong J. Selection criteria for hepatic resection in patients with large hepatocellular carcinoma larger than 10 cm in diameter. J Am Coll Surg 2002; 194:592-602. [PMID: 12022599 DOI: 10.1016/s1072-7515(02)01163-8] [Citation(s) in RCA: 133] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND The role of hepatic resection for large hepatocellular carcinoma (HCC) larger than 10 cm remains unclear. STUDY DESIGN Perioperative and longterm outcomes of 120 patients with HCC larger than 10 cm who underwent resection (group A) were compared with 368 patients with smaller HCC (group B). The prognostic factors in group A were analyzed. RESULTS A higher proportion of patients underwent major hepatic resection in group A than in group B (90% versus 57.6%, p = 0.001), but the hospital mortality was similar (5.0% versus 4.6%, p = 0.874). Group A had worse longterm overall survival (median 18.8 months versus 62.8 months, p < 0.001) and disease-free survival (median 5.5 months versus 25.4 months, p < 0.001) than group B. Macroscopic residual tumor, macroscopic venous invasion, and multiple tumors were identified as independent prognostic factors in group A. The median survival of patients with residual tumor and those with curative resection was 7.7 months and 20.8 months, respectively. The median survival of patients with curative resection of solitary HCC larger than 10cm without macroscopic venous invasion was 38.0 months; that of patients with both macroscopic venous invasion and multiple tumors was only 10.5 months. CONCLUSIONS Hepatic resection is a safe and effective treatment for HCC larger than 10cm when liver function reserve is satisfactory and when curative resection can be expected. Patients with solitary HCC larger than 10cm without macroscopic venous invasion can enjoy longterm survival after surgery, and we propose hepatic resection as a standard treatment for this group of patients.
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Affiliation(s)
- Ronnie Tung-Ping Poon
- Centre for the Study of Liver Disease and the Department of Surgery, University of Hong Kong Medical Centre, Queen Mary Hospital, China
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Farges O, Denys A. [Portal vein embolization prior to hepatectomy. Techniques, indications and results]. ANNALES DE CHIRURGIE 2001; 126:836-44. [PMID: 11760573 DOI: 10.1016/s0003-3944(01)00617-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Postoperative liver failure is a severe complication of major hepatectomies, in particular in patients with a chronic underlying liver disease. Preoperative interruption of the portal flow in the liver territories planned to be removed, induces their atrophy and the compensatory hypertrophy of the segments spared by the resection. This interruption can be induced by the surgical ligation of the portal branches or by the percutaneous intraportal injection, under ultrasound guidance, of glues or sclerosing agents. Preoperative portal vein embolisation is usually indicated when the remnant liver accounts for less than 25-40% of the total liver volume. Feasibility is close to 100% and the risk comparable to that of a percutaneous liver biopsy. It is well tolerated and the biological impact is minimal in patients without liver failure. Compensatory hypertrophy of the non-embolised segments is maximal during the first 2 weeks and persists, although to a lesser extent during approximately 6 weeks. The magnitude of hypertrophy is correlated with the volume of parenchyma embolised, and is reduced in diabetic or jaundiced patients or when there is an active chronic liver disease. Liver resection is performed 2 to 6 weeks after embolisation. Retrospective studies and one prospective study suggest that patients so prepared have a reduced perioperative risk and that their long term carcinologic results are not impaired.
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Affiliation(s)
- O Farges
- Service de chirurgie digestive, hôpital Beaujon, université Paris VII, 100, boulevard du Général-Leclerc, 92118 Clichy, France.
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Poon RT, Ng IO, Fan ST, Lai EC, Lo CM, Liu CL, Wong J. Clinicopathologic features of long-term survivors and disease-free survivors after resection of hepatocellular carcinoma: a study of a prospective cohort. J Clin Oncol 2001; 19:3037-44. [PMID: 11408499 DOI: 10.1200/jco.2001.19.12.3037] [Citation(s) in RCA: 128] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
PURPOSE This study aims to clarify the clinicopathologic features of long-term survivors and disease-free survivors after resection of hepatocellular carcinoma (HCC). PATIENTS AND METHODS The clinicopathologic features of 5-year survivors and disease-free survivors were elucidated in a cohort of 230 patients prospectively observed for > 5 years (64 to 192 months) after curative resection of HCC. RESULTS The incidence of 5-year overall and disease-free survivors were 37% (85 of 230) and 20% (45 of 230), respectively. Clinicopathologic features associated with 5-year survivors included female sex (P =.024), preoperative serum albumin > or= 40 g/L (P =.033), AST < 50 u/L (P =.001), tumor < 5 cm (P =.001), solitary tumor (P =.035), encapsulated tumor (P =.021), no venous invasion (P =.001), no microsatellite nodule (P =.001), and early pathologic tumor-node-metastasis (pTNM) stage (I or II, P <.001). Features favoring 5-year disease-free survivors were preoperative serum AST < 50 u/L (P =.007), tumor < 5 cm (P =.005), encapsulated tumor (P =.007), no venous invasion (P <.001), no microsatellite nodule (P =.001), and early pTNM stage (I or II, P <.001). By multivariate analysis, pTNM stage was the only significant predictive factor for both overall and disease-free survival. CONCLUSION This study shows that long-term disease-free survival > 5 years after resection of HCC can be achieved in patients with favorable tumor characteristics. Early pTNM stage was the most reliable predictor of both long-term overall and disease-free survivors.
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Affiliation(s)
- R T Poon
- Center for Study of Liver Disease, Department of Surgery, University of Hong Kong Medical Center, Queen Mary Hospital, Hong Kong, China.
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