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Zhang K, Wang W, Mu L, Xie L, Li M, Yang W, Jiang T. Therapeutic outcomes of thermal ablation versus repeated hepatic resection for recurrent hepatocellular carcinoma by using propensity score analysis: a multicenter real-world study. BMC Cancer 2025; 25:303. [PMID: 39972245 PMCID: PMC11841235 DOI: 10.1186/s12885-025-13660-9] [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: 10/05/2024] [Accepted: 02/05/2025] [Indexed: 02/21/2025] Open
Abstract
BACKGROUND The therapeutic value of thermal ablation (TA) versus repeat hepatic resection (RHR) for recurrent hepatocellular carcinoma (rHCC) after initial hepatic resection is uncertain. This study aimed to investigate the prognosis of TA and RHR. MATERIALS AND METHODS In this multicenter real-world retrospective study, 473 patients were enrolled between January 2015 and August 2023, with 340 in the TA group and 133 in the RHR group. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were employed to reduce selection bias. Local tumor progression (LTP), recurrence-free survival (RFS), and post-recurrence survival (PRS) were compared before and after PSM and IPTW. RESULTS A total of 473 patients (231 aged ≥ 60 years; 393 men) were evaluated. LTP, RFS, and PRS rates did not differ significantly between groups before (P = 0.940, P = 0.180, and P = 0.700) and after matching (P = 0.420, P = 0.680, and P = 0.810) and weighting (P = 0.940, P = 0.180, and P = 0.700). Multivariable Cox analysis identified tumor number (HR: 2.28; P < 0.001) and PLT (HR: 0.73; P = 0.038) as independent prognostic factors for RFS in the entire rHCC cohort. And tumor location, size, number, ascites, AST, and AFP (HR: 0.55-2.18; P = 0.004-0.046) were independent prognostic factors for PRS. Subgroup analysis showed both TA and RHR were effective treatments for rHCC, regardless of tumor size, number, subcapsular, or perivascular lesions. CONCLUSIONS The cumulative LTP, RFS, and PRS were not significantly different between TA and RHR for rHCC within the Milan criteria. TA may be a viable curative option for early-stage rHCC patients.
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Affiliation(s)
- Ke Zhang
- Department of Ultrasound Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Wenbo Wang
- Department of Ultrasound, Key Laboratory of Carcinogenesis and Translational Research, (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China
| | - Lei Mu
- Department of Ultrasound Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Liting Xie
- Department of Ultrasound Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Mengmeng Li
- Department of Ultrasound Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Wei Yang
- Department of Ultrasound, Key Laboratory of Carcinogenesis and Translational Research, (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China.
| | - Tianan Jiang
- Department of Ultrasound Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
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Matsumoto T, Kitano Y, Imai K, Ogawa D, Yumoto S, Takematsu T, Shiraishi Y, Itoyama R, Nakagawa S, Mima K, Okabe H, Nitta H, Hayashi H, Baba H. Prognostic impact of aspirin in patients with hepatocellular carcinoma after liver resection: propensity-score-matched analysis. Int J Clin Oncol 2025; 30:92-98. [PMID: 39438421 DOI: 10.1007/s10147-024-02646-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Accepted: 10/11/2024] [Indexed: 10/25/2024]
Abstract
BACKGROUND The association between aspirin and hepatocellular carcinoma (HCC) has been reported to prevent carcinogenesis caused by hepatitis B or C virus infection. The objective of this study was to investigate the prognostic impact of aspirin in patients who underwent liver resection for HCC. METHODS Data for 1032 patients who underwent primary resection for HCC between 2000 and 2019 were reviewed. There were 87 patients (8.4%) who took aspirin (aspirin group) and 945 (91.6%) who did not (non-aspirin group). Short-term outcomes, recurrence-free survival (RFS), and overall survival (OS) were compared between two groups in the matched cohort using propensity-score matching. RESULTS The median patient follow-up was 42.6 months (95% confidence interval 3.12-136.8 months). There was no significant difference in short-term outcomes, including bleeding events. RFS and OS after liver resection in the aspirin group were significantly better than those in the non-aspirin group in the unmatched cohort [5-year RFS rate: 50.3% vs 31.4%, hazard ratio (HR) 0.55, P = 0.0002; 5-year OS rate: 82.9% vs 70.2%, HR 0.46, P = 0.002]. In the matched cohort, RFS and OS after liver resection in the aspirin group were also significantly better than those in the non-aspirin group (5-year RFS rate: 50.3% vs 32.0%, HR 0.60, P = 0.003; 5-year OS rate: 82.9% vs 74.6%, HR 0.56, P = 0.03). CONCLUSION Use of aspirin was associated with better prognosis for patients who underwent primary resection for HCC.
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Affiliation(s)
- Takashi Matsumoto
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
| | - Yuki Kitano
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Katsunori Imai
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Daisuke Ogawa
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Shinsei Yumoto
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Toru Takematsu
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Yuta Shiraishi
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Rumi Itoyama
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Shigeki Nakagawa
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Kosuke Mima
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Hirohisa Okabe
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Hidetoshi Nitta
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Hiromitsu Hayashi
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
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Fuster-Anglada C, Mauro E, Ferrer-Fàbrega J, Caballol B, Sanduzzi-Zamparelli M, Bruix J, Fuster J, Reig M, Díaz A, Forner A. Histological predictors of aggressive recurrence of hepatocellular carcinoma after liver resection. J Hepatol 2024; 81:995-1004. [PMID: 38925272 DOI: 10.1016/j.jhep.2024.06.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Revised: 06/11/2024] [Accepted: 06/17/2024] [Indexed: 06/28/2024]
Abstract
BACKGROUND & AIMS Assessment of recurrence risk after liver resection (LR) is critical in hepatocellular carcinoma (HCC), particularly with the advent of effective adjuvant therapy. The aim of this study was to analyze the clinical and pathological factors associated with recurrence, aggressive recurrence, and survival after LR. METHOD We performed a retrospective study in which all single HCC (BCLC-0/A) patients treated with LR between February 2000 and November 2020 were included. The main clinical variables were recorded. Histological features were blindly evaluated by two independent pathologists. Aggressive recurrence was defined as those that exceeded the Milan criteria at 1st recurrence. RESULTS A total of 218 patients were included (30% BCLC 0 and 70% BCLC A), median (IQR) tumor size of 28 (19-42 mm). The prevalence of microvascular invasion and/or satellitosis (mVI/S) was 39%, with a kappa-index between both pathologists of 0.8. After a median follow-up of 49 (23-85) months, 61/218 (28%) patients died, 32/218 (15%) underwent liver transplantation, 127 (58%) developed HCC recurrence. The prevalence of aggressive recurrence was 35% (44/127 Milan-out, with 20 cases at advanced stage), and the 5-year survival rate was 81%. The presence of mVI/S was the only independent predictor of recurrence (hazard ratio [HR] 1.83, 95% CI 1.28-2.61, p <0.001), aggressive recurrence (HR 3.31, 95% CI 1.74-6.29, p <0.001) and mortality (HR 2.23, 95% CI 1.27-3.91, p = 0.005). The macrotrabecular-massive subtype was significantly associated with a higher prevalence of mVI/S, Edmonson Steiner grade III-IV, AFP values and vessels that encapsulate tumor clusters, but not with recurrence, aggressive recurrence, or overall survival. CONCLUSION The presence of mVI/S was the only independent risk factor for aggressive recurrence and mortality. This has important implications for early-stage patient management, especially in the setting of adjuvant immunotherapy or ab initio LT. IMPACT AND IMPLICATIONS Assessment of recurrence risk after liver resection is crucial in patients with hepatocellular carcinoma. Patients with a high risk of recurrence are candidates for liver transplantation as an ab initio indication or for the potential use of adjuvant therapy. Aggressive recurrences, defined as those exceeding the Milan criteria at first recurrence, have a significant impact on overall survival (OS). Fifty-eight percent of patients experienced hepatocellular carcinoma recurrence, with a prevalence of aggressive recurrence at the first occurrence standing at 35%. After a median follow-up of 49 (23-85) months, 61 (28%) patients died, and 32 (15%) underwent liver transplantation, resulting in a 5-year OS rate of 81%. Microvascular invasion and/or satellitosis was present in 39% of our cohort and was the only independent predictor of recurrence, aggressive recurrence, and OS on multivariate analysis. This is important as it could be used to guide therapeutic management.
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Affiliation(s)
- Carla Fuster-Anglada
- Pathology Department. CDB. Liver Oncology Unit. Hospital Clinic Barcelona. Barcelona. Spain; Barcelona Clinic Liver Cancer (BCLC) group. IDIBAPS. Barcelona. Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Ezequiel Mauro
- Barcelona Clinic Liver Cancer (BCLC) group. IDIBAPS. Barcelona. Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain; Liver Unit. Liver Oncology Unit. ICMDM. Hospital Clinic Barcelona. Barcelona, Spain
| | - Joana Ferrer-Fàbrega
- Barcelona Clinic Liver Cancer (BCLC) group. IDIBAPS. Barcelona. Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain; Hepatobiliopancreatic Surgery and Liver and Pancreatic Transplantation Unit, Department of Surgery. Liver Oncology Unit. ICMDM. Hospital Clinic Barcelona. Barcelona. Spain; Universitat de Barcelona, Barcelona, Spain
| | - Berta Caballol
- Liver Unit. Liver Oncology Unit. ICMDM. Hospital Clinic Barcelona. Barcelona, Spain
| | - Marco Sanduzzi-Zamparelli
- Barcelona Clinic Liver Cancer (BCLC) group. IDIBAPS. Barcelona. Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain; Liver Unit. Liver Oncology Unit. ICMDM. Hospital Clinic Barcelona. Barcelona, Spain
| | - Jordi Bruix
- Barcelona Clinic Liver Cancer (BCLC) group. IDIBAPS. Barcelona. Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain; Universitat de Barcelona, Barcelona, Spain; Liver Unit. Liver Oncology Unit. ICMDM. Hospital Clinic Barcelona. Barcelona, Spain
| | - Josep Fuster
- Barcelona Clinic Liver Cancer (BCLC) group. IDIBAPS. Barcelona. Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain; Hepatobiliopancreatic Surgery and Liver and Pancreatic Transplantation Unit, Department of Surgery. Liver Oncology Unit. ICMDM. Hospital Clinic Barcelona. Barcelona. Spain; Universitat de Barcelona, Barcelona, Spain
| | - María Reig
- Barcelona Clinic Liver Cancer (BCLC) group. IDIBAPS. Barcelona. Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain; Universitat de Barcelona, Barcelona, Spain; Liver Unit. Liver Oncology Unit. ICMDM. Hospital Clinic Barcelona. Barcelona, Spain
| | - Alba Díaz
- Pathology Department. CDB. Liver Oncology Unit. Hospital Clinic Barcelona. Barcelona. Spain; Barcelona Clinic Liver Cancer (BCLC) group. IDIBAPS. Barcelona. Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain; Universitat de Barcelona, Barcelona, Spain.
| | - Alejandro Forner
- Barcelona Clinic Liver Cancer (BCLC) group. IDIBAPS. Barcelona. Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain; Universitat de Barcelona, Barcelona, Spain; Liver Unit. Liver Oncology Unit. ICMDM. Hospital Clinic Barcelona. Barcelona, Spain.
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Ji J, Yan LL, Ma Y, Xu C, Zhou WZ, Lv PH. Transarterial chemoembolization combined with microwave ablation versus repeated resection for recurrent small hepatocellular carcinoma after resection: What is the better treatment? Clin Radiol 2024; 79:e1443-e1450. [PMID: 39299845 DOI: 10.1016/j.crad.2024.08.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2023] [Revised: 07/08/2024] [Accepted: 08/15/2024] [Indexed: 09/22/2024]
Abstract
PURPOSE This study aimed to compare the effectiveness of transcatheter arterial chemoembolization combined with microwave ablation (TACE-MWA) versus repeated hepatic resection (RHR) in patients with recurrent small hepatocellular carcinoma (sHCC) following primary resection. MATERIALS AND METHODS A total of 59 patients diagnosed with recurrent sHCC (≤3 cm) and treated with either TACE-MWA or RHR were recruited from two centers between June 2015 and October 2021. Patients were matched using propensity scores at a 1:1 ratio. Disease-free survival (DFS), overall survival (OS), and complications were assessed and compared between the two treatment groups. RESULTS After propensity score matching, 38 patients were included, with 19 in each group. Prior to matching, the 1-, 3-, and 5-year DFS rates for the TACE-MWA group were 68.1%, 46.6%, and 23.3%, respectively, and for the RHR group, they were 84.6%, 47.3%, and 47.3%, respectively. The corresponding 1-, 3-, and 5-year OS rates for TACE-MWA were 100.0%, 83.7%, and 47.8%, while for RHR, they were 100.0%, 95.0%, and 45.2%. After matching, the 1-, 3-, and 5-year DFS rates were 78.0%, 48.3%, and 24.1% for TACE-MWA, and 77.5%, 38.7%, and 38.7% for RHR. The 1-, 3-, and 5-year OS rates for TACE-MWA were 100.0%, 88.9%, and 54.9%, and for RHR, they were 100.0%, 93.3%, and 44.4%. Statistical analysis showed no significant differences in DFS rates (P=0.834 before matching, P=0.490 after matching) or OS rates (P=0.825 before matching, P=0.625 after matching) between the two groups. CONCLUSIONS TACE-MWA demonstrates comparable effectiveness to RHR in managing recurrent sHCC.
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Affiliation(s)
- J Ji
- Department of Interventional Radiology, Northern Jiangsu People's Hospital, 98 West Nantong Road, Yangzhou 225001, China.
| | - L-L Yan
- Department of Interventional Radiology, Northern Jiangsu People's Hospital, 98 West Nantong Road, Yangzhou 225001, China.
| | - Y Ma
- Department of Interventional Radiology, Northern Jiangsu People's Hospital, 98 West Nantong Road, Yangzhou 225001, China.
| | - C Xu
- Department of Interventional Radiology, Northern Jiangsu People's Hospital, 98 West Nantong Road, Yangzhou 225001, China.
| | - W-Z Zhou
- Department of Radiology, Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Gulou District, Nanjing 210029, China.
| | - P-H Lv
- Department of Interventional Radiology, Northern Jiangsu People's Hospital, 98 West Nantong Road, Yangzhou 225001, China.
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Chen ICY, Dungca LBP, Yong CC, Chen CL. Sequential living donor liver transplantation after liver resection optimizes outcomes for patients with high-risk hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 2024:S1499-3872(24)00127-9. [PMID: 39510903 DOI: 10.1016/j.hbpd.2024.10.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Accepted: 10/16/2024] [Indexed: 11/15/2024]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality. While liver transplantation (LT) provides the best long-term survival, it is constrained by organ scarcity and strict criteria. Liver resection (LR) is often the initial treatment for patients with solitary tumors and preserved liver function. The high recurrence rates associated with LR has prompted the exploration of sequential living donor liver transplantation (seqLDLT) after LR as a strategy for HCC patients with high-risk of recurrence. METHODS We analyzed data from 27 adult patients who underwent seqLDLT after LR for HCC at Kaohsiung Chang Gung Memorial Hospital (KCGMH) between June 1994 and December 2023. Patients were selected based on high-risk histopathological features post-LR or as part of downstaging strategy. Outcomes measured included overall survival (OS) and disease-free survival (DFS). RESULTS Among 765 HCC patients who underwent LDLT, 204 received LR before LDLT, and 27 underwent seqLDLT. Five patients (19%) underwent living donor liver transplantation (LDLT) following LR as a downstaging strategy while the rest received seqLDLT as a preemptive strategy. The median age was 53.5 years with 85% males. Chronic hepatitis B was the predominant underlying disease (74%). The 1-, 3-, and 5-year OS and DFS rates were 100%, 96.0%, 96.0% and 100%, 96.2%, 96.2%, respectively, with two patients experiencing HCC recurrence. One patient died from HCC recurrence. High-risk histopathological features included microvascular invasion (52%), satellite nodules (15%), multiple tumors (26%), tumors > 5 cm (19%), and a total tumor diameter > 10 cm (7%). CONCLUSIONS SeqLDLT offers a promising, tailored approach for managing HCC with adverse histopathologic features. Combining seqLDLT, downstaging strategies, and multidisciplinary treatments can achieve satisfactory OS and DFS in carefully selected patients, highlighting the need for refined criteria to identify the best candidates.
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Affiliation(s)
- Itsuko Chih-Yi Chen
- Liver Transplantation Center, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, Taiwan, China
| | - Leona Bettina P Dungca
- Liver Transplantation Center, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, Taiwan, China
| | - Chee-Chien Yong
- Liver Transplantation Center, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, Taiwan, China
| | - Chao-Long Chen
- Liver Transplantation Center, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, Taiwan, China.
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Yilma M, Houhong Xu R, Saxena V, Muzzin M, Tucker LY, Lee J, Mehta N, Mukhtar N. Survival Outcomes Among Patients With Hepatocellular Carcinoma in a Large Integrated US Health System. JAMA Netw Open 2024; 7:e2435066. [PMID: 39316399 PMCID: PMC11423175 DOI: 10.1001/jamanetworkopen.2024.35066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/25/2024] Open
Abstract
Importance Hepatocellular carcinoma (HCC) is the leading oncologic cause of death among patients with cirrhosis, but large studies examining mortality trends are lacking. Objective To evaluate survival among patients with HCC in one of the largest integrated health care systems in the US. Design, Setting, and Participants This retrospective cohort study included 3441 adult patients who received a diagnosis of HCC between January 1, 2006, and December 31, 2019, with end of follow-up on December 31, 2020. The study period was further categorized as era 1, defined as 2006 to 2012, and era 2, defined as 2013 to 2019. Statistical analysis was conducted from January 2021 to June 2024. Exposures Patient demographic characteristics and disease factors. Main Outcomes and Measures All-cause and HCC-specific mortality were used as primary end points, and survival probabilities were estimated using the Kaplan-Meier method. Cox proportional hazards regression analyses were adjusted for age at diagnosis, sex, race and ethnicity, cause of disease, Barcelona Clinic Liver Cancer (BCLC) stage, alpha-fetoprotein level, and treatment type. Results Of 3441 patients with HCC, 2581 (75.0%) were men, and the median age was 65 years (IQR, 58-73 years). A total of 1195 patients (34.7%) received curative treatment, 1374 (39.9%) received noncurative treatment, and 872 (25.3%) received no treatment. During the study period, 2500 patients (72.7%) experienced all-cause mortality, and 1809 (52.6%) had HCC-specific mortality. In multivariable analysis, being 70 years of age or older (adjusted hazard ratio [AHR], 1.39; 95% CI, 1.22-1.59), male sex (AHR, 1.20; 95% CI, 1.07-1.35), BCLC stage C or D (AHR, 2.40; 95% CI, 2.15-2.67), increasing alpha-fetoprotein level (vs <20 ng/mL; 20-99 ng/mL: AHR, 1.20; 95% CI, 1.04-1.38; ≥1000 ng/mL: AHR, 2.84; 95% CI, 2.45-3.25), noncurative treatment (AHR, 2.51; 95% CI, 2.16-2.90), and no treatment (AHR, 3.15; 95% CI, 2.64-3.76) were associated with higher all-cause mortality, while Asian or Other Pacific Islander race and ethnicity (vs non-Hispanic White; AHR, 0.76; 95% CI, 0.65-0.88) was associated with lower all-cause mortality. Survival improved in diagnosis era 2 (2013-2019; n = 2007) compared with diagnosis era 1 (2006-2012; n = 1434). Conclusions and Relevance This large, racially and ethnically diverse cohort study of patients with HCC found improving survival over time, especially among individuals with early-stage HCC receiving potentially curative treatments. This study highlights the importance of surveillance for detection of HCC at early stages, particularly among groups at risk for poorer outcomes.
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Affiliation(s)
- Mignote Yilma
- General Surgery, University of California, San Francisco
- National Clinician Scholars Program, San Francisco, California
| | | | - Varun Saxena
- Department of Gastroenterology, Kaiser Permanente South San Francisco Medical Center, San Francisco, California
- Department of Medicine, University of California, San Francisco
| | - Monica Muzzin
- Department of Gastroenterology, Kaiser Permanente San Francisco Medical Center, San Francisco
| | - Lue-Yen Tucker
- Division of Research, Kaiser Permanente, Oakland, California
| | - Jeffrey Lee
- Division of Research, Kaiser Permanente, Oakland, California
- Department of Gastroenterology, Kaiser Permanente San Francisco Medical Center, San Francisco
| | - Neil Mehta
- Department of Medicine, University of California, San Francisco
| | - Nizar Mukhtar
- Department of Gastroenterology, Kaiser Permanente San Francisco Medical Center, San Francisco
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Hung HC, Lai Y, Lee JC, Wang YC, Cheng CH, Wu TH, Wu TJ, Chou HS, Chan KM, Lee WC, Lee CF. Optimal treatment strategy and prognostic analysis of salvage liver transplantation for patients with early hepatocellular carcinoma recurrence after hepatectomy. Hepatol Res 2024; 54:838-850. [PMID: 38451566 DOI: 10.1111/hepr.14033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 02/11/2024] [Accepted: 02/16/2024] [Indexed: 03/08/2024]
Abstract
AIM We aimed to investigate the prognostic factors for salvage liver transplant in patients with early hepatocellular carcinoma recurrence after hepatectomy. METHODS This retrospective analysis included 53 patients who underwent salvage living-donor liver transplantation between January 2007 and January 2018. There were 24 and 29 patients in the early (recurrence ≤24 months after primary liver resection) and the late recurrence groups, respectively. RESULTS In the multivariate Cox regression model, pre-liver transplant downstaging therapy, early recurrence (ER) after primary liver resection , and recurrence-to-liver-transplant ≥12 months were independent risks to predict recurrent hepatocellular carcinoma recurrence after salvage living-donor liver transplantation. Compared with the late recurrence group, the ER group showed lower disease-free survival rates (p < 0.001); however, the overall survival rates did not differ between the two groups (p = 0.355). The 1-, 3-, and 5-year disease-free survival rates were 83.3%, 70.6%, and 66.2%, and 96.0%, 91.6%, and 91.6% in the early and late recurrence groups, respectively. When stratified by recurrence-to-liver transplant time and pre-liver transplant downstaging therapy in the ER group, disease-free survival and overall survival rates were significantly different. CONCLUSION ER after primary liver resection with advanced tumor status and a longer period of recurrence-to-liver-transplant (≥12 months) have a negative impact on salvage liver transplant. Our findings provide novel recommendations for treatment strategies and eligibility for salvage liver transplant candidates.
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Affiliation(s)
- Hao-Chien Hung
- Division of Liver and Transplantation Surgery, Chang-Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
- Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Yin Lai
- Division of Liver and Transplantation Surgery, Chang-Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
| | - Jin-Chiao Lee
- Division of Liver and Transplantation Surgery, Chang-Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
- Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Yu-Chao Wang
- Division of Liver and Transplantation Surgery, Chang-Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
- Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Chih-Hsien Cheng
- Division of Liver and Transplantation Surgery, Chang-Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
- Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Tsung-Han Wu
- Division of Liver and Transplantation Surgery, Chang-Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
- Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Ting-Jung Wu
- Division of Liver and Transplantation Surgery, Chang-Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
- Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Hong-Shiue Chou
- Division of Liver and Transplantation Surgery, Chang-Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
- Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Kun-Ming Chan
- Division of Liver and Transplantation Surgery, Chang-Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
- Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Wei-Chen Lee
- Division of Liver and Transplantation Surgery, Chang-Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
- Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Chen-Fang Lee
- Division of Liver and Transplantation Surgery, Chang-Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
- Chang-Gung University College of Medicine, Taoyuan, Taiwan
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Naing C, Ni H, Aung HH. Tamoxifen for adults with hepatocellular carcinoma. Cochrane Database Syst Rev 2024; 8:CD014869. [PMID: 39132750 PMCID: PMC11318082 DOI: 10.1002/14651858.cd014869.pub2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/13/2024]
Abstract
RATIONALE Hepatocellular carcinoma is the most common type of liver cancer, accounting for 70% to 85% of individuals with primary liver cancer. Tamoxifen has been evaluated in randomised clinical trials in people with hepatocellular cancer. The reported results have been inconsistent. OBJECTIVES To evaluate the benefits and harms of tamoxifen or tamoxifen plus any other anticancer drugs compared with no intervention, placebo, any type of standard care, or alternative treatment in adults with hepatocellular carcinoma, irrespective of sex, administered dose, type of formulation, and duration of treatment. SEARCH METHODS We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, three other databases, and major trials registries, and handsearched reference lists up to 26 March 2024. ELIGIBILITY CRITERIA Parallel-group randomised clinical trials including adults (aged 18 years and above) diagnosed with advanced or unresectable hepatocellular carcinoma. Had we found cross-over trials, we would have included only the first trial phase. We did not consider data from quasi-randomised trials for analysis. OUTCOMES Our critical outcomes were all-cause mortality, serious adverse events, and health-related quality of life. Our important outcomes were disease progression, and adverse events considered non-serious. RISK OF BIAS We assessed risk of bias using the RoB 2 tool. SYNTHESIS METHODS We used standard Cochrane methods and Review Manager. We meta-analysed the outcome data at the longest follow-up. We presented the results of dichotomous outcomes as risk ratios (RR) and continuous data as mean difference (MD), with 95% confidence intervals (CI) using the random-effects model. We summarised the certainty of evidence using GRADE. INCLUDED STUDIES We included 10 trials that randomised 1715 participants with advanced, unresectable, or terminal stage hepatocellular carcinoma. Six were single-centre trials conducted in Hong Kong, Italy, and Spain, while three were conducted as multicentre trials in single countries (France, Italy, and Spain), and one trial was conducted in nine countries in the Asia-Pacific region (Australia, Hong Kong, Indonesia, Malaysia, Myanmar, New Zealand, Singapore, South Korea, and Thailand). The experimental intervention was tamoxifen in all trials. The control interventions were no intervention (three trials), placebo (six trials), and symptomatic treatment (one trial). Co-interventions were best supportive care (three trials) and standard care (one trial). The remaining six trials did not provide this information. The number of participants in the trials ranged from 22 to 496 (median 99), mean age was 63.7 (standard deviation 4.18) years, and mean proportion of men was 74.7% (standard deviation 42%). Follow-up was three months to five years. SYNTHESIS OF RESULTS Ten trials evaluated oral tamoxifen at five different dosages (ranging from 20 mg per day to 120 mg per day). All trials investigated one or more of our outcomes. We performed meta-analyses when at least two trials assessed similar types of tamoxifen versus similar control interventions. Eight trials evaluated all-cause mortality at varied follow-up points. Tamoxifen versus the control interventions (i.e. no treatment, placebo, and symptomatic treatment) results in little to no difference in mortality between one and five years (RR 0.99, 95% CI 0.92 to 1.06; 8 trials, 1364 participants; low-certainty evidence). In total, 488/682 (71.5%) participants died in the tamoxifen groups versus 487/682 (71.4%) in the control groups. The separate analysis results for one, between two and three, and five years were comparable to the analysis result for all follow-up periods taken together. The evidence is very uncertain about the effect of tamoxifen versus no treatment on serious adverse events at one-year follow-up (RR 0.44, 95% CI 0.19 to 1.06; 1 trial, 36 participants; very low-certainty evidence). A total of 5/20 (25.0%) participants in the tamoxifen group versus 9/16 (56.3%) participants in the control group experienced serious adverse events. One trial measured health-related quality of life at baseline and at nine months' follow-up, using the Spitzer Quality of Life Index. The evidence is very uncertain about the effect of tamoxifen versus no treatment on health-related quality of life (MD 0.03, 95% CI -0.45 to 0.51; 1 trial, 420 participants; very low-certainty evidence). A second trial found no appreciable difference in global health-related quality of life scores. No further data were provided. Tamoxifen versus control interventions (i.e. no treatment, placebo, or symptomatic treatment) results in little to no difference in disease progression between one and five years' follow-up (RR 1.02, 95% CI 0.91 to 1.14; 4 trials, 720 participants; low-certainty evidence). A total of 191/358 (53.3%) participants in the tamoxifen group versus 198/362 (54.7%) participants in the control group had progression of hepatocellular carcinoma. Tamoxifen versus control interventions (i.e. no treatment or placebo) may have little to no effect on adverse events considered non-serious during treatment, but the evidence is very uncertain (RR 1.17, 95% CI 0.45 to 3.06; 4 trials, 462 participants; very low-certainty evidence). A total of 10/265 (3.8%) participants in the tamoxifen group versus 6/197 (3.0%) participants in the control group had adverse events considered non-serious. We identified no trials with participants diagnosed with early stages of hepatocellular carcinoma. We identified no ongoing trials. AUTHORS' CONCLUSIONS Based on the low- and very low-certainty evidence, the effects of tamoxifen on all-cause mortality, disease progression, serious adverse events, health-related quality of life, and adverse events considered non-serious in adults with advanced, unresectable, or terminal stage hepatocellular carcinoma when compared with no intervention, placebo, or symptomatic treatment could not be established. Our findings are mostly based on trials at high risk of bias with insufficient power (fewer than 100 participants), and a lack of trial data on clinically important outcomes. Therefore, firm conclusions cannot be drawn. Trials comparing tamoxifen administered with any other anticancer drug versus standard care, usual care, or alternative treatment as control interventions were lacking. Evidence on the benefits and harms of tamoxifen in participants at the early stages of hepatocellular carcinoma was also lacking. FUNDING This Cochrane review had no dedicated funding. REGISTRATION Protocol available via DOI: 10.1002/14651858.CD014869.
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Affiliation(s)
- Cho Naing
- Division of Tropical Health and Medicine, James Cook University, Queensland, Australia
| | - Han Ni
- Department of Medicine, Newcastle University Medicine Malaysia, Johor, Malaysia
| | - Htar Htar Aung
- School of Medicine, IMU University, Kuala Lumpur, Malaysia
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Suddle A, Reeves H, Hubner R, Marshall A, Rowe I, Tiniakos D, Hubscher S, Callaway M, Sharma D, See TC, Hawkins M, Ford-Dunn S, Selemani S, Meyer T. British Society of Gastroenterology guidelines for the management of hepatocellular carcinoma in adults. Gut 2024; 73:1235-1268. [PMID: 38627031 PMCID: PMC11287576 DOI: 10.1136/gutjnl-2023-331695] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Accepted: 03/19/2024] [Indexed: 05/01/2024]
Abstract
Deaths from the majority of cancers are falling globally, but the incidence and mortality from hepatocellular carcinoma (HCC) is increasing in the United Kingdom and in other Western countries. HCC is a highly fatal cancer, often diagnosed late, with an incidence to mortality ratio that approaches 1. Despite there being a number of treatment options, including those associated with good medium to long-term survival, 5-year survival from HCC in the UK remains below 20%. Sex, ethnicity and deprivation are important demographics for the incidence of, and/or survival from, HCC. These clinical practice guidelines will provide evidence-based advice for the assessment and management of patients with HCC. The clinical and scientific data underpinning the recommendations we make are summarised in detail. Much of the content will have broad relevance, but the treatment algorithms are based on therapies that are available in the UK and have regulatory approval for use in the National Health Service.
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Affiliation(s)
- Abid Suddle
- King's College Hospital NHS Foundation Trust, London, UK
| | - Helen Reeves
- Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK
| | - Richard Hubner
- Department of Oncology, The Christie NHS Foundation Trust, Manchester, UK
| | | | - Ian Rowe
- University of Leeds, Leeds, UK
- St James's University Hospital, Leeds, UK
| | - Dina Tiniakos
- Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
| | - Stefan Hubscher
- Department of Pathology, University of Birmingham, Birmingham, UK
| | - Mark Callaway
- Division of Diagnostics and Therapies, University Hospitals Bristol NHS Trust, Bristol, UK
| | | | - Teik Choon See
- Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Maria Hawkins
- Department of Medical Physics and Biomedical Engineering, University College London, London, UK
| | | | - Sarah Selemani
- King's College Hospital NHS Foundation Trust, London, UK
| | - Tim Meyer
- Department of Oncology, University College, London, UK
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Naing C, Ni H, Aung HH, Htet NH, Nikolova D. Gene therapy for people with hepatocellular carcinoma. Cochrane Database Syst Rev 2024; 6:CD013731. [PMID: 38837373 PMCID: PMC11152182 DOI: 10.1002/14651858.cd013731.pub2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/07/2024]
Abstract
BACKGROUND Hepatocellular carcinoma is the most common type of liver cancer, accounting for 70% to 85% of individuals with primary liver cancer. Gene therapy, which uses genes to treat or prevent diseases, holds potential for treatment, especially for tumours. Trials on the effects of gene therapy in people with hepatocellular carcinoma have been published or are ongoing. OBJECTIVES To evaluate the benefits and harms of gene therapy in people with hepatocellular carcinoma, irrespective of sex, administered dose, and type of formulation. SEARCH METHODS We identified randomised clinical trials through electronic searches in The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index-Science. We searched five online clinical trial registries to identify unpublished or ongoing trials. We checked reference lists of the retrieved studies for further trials. The date of last search was 20 January 2023. SELECTION CRITERIA We aimed to include randomised clinical trials assessing any type of gene therapy in people diagnosed with hepatocellular carcinoma, irrespective of year, language of publication, format, or outcomes reported. DATA COLLECTION AND ANALYSIS We followed Cochrane methodology and used Review Manager to prepare the review. The primary outcomes were all-cause mortality/overall survival (whatever data were provided), serious adverse events during treatment, and health-related quality of life. The secondary outcomes were proportion of people with disease progression, adverse events considered non-serious, and proportion of people without improvement in liver function tests. We assessed risk of bias of the included trials using RoB 2 and the certainty of evidence using GRADE. We presented the results of time-to-event outcomes as hazard ratios (HR), dichotomous outcomes as risk ratios (RR), and continuous outcomes as mean difference (MD) with their 95% confidence intervals (CI). Our primary analyses were based on intention-to-treat and outcome data at the longest follow-up. MAIN RESULTS We included six randomised clinical trials with 364 participants. The participants had unresectable (i.e. advanced inoperable) hepatocellular carcinoma. We found no trials assessing the effects of gene therapy in people with operable hepatocellular carcinoma. Four trials were conducted in China, one in several countries (from North America, Asia, and Europe), and one in Egypt. The number of participants in the six trials ranged from 10 to 129 (median 47), median age was 55.2 years, and the mean proportion of males was 72.7%. The follow-up duration ranged from six months to five years. As the trials compared different types of gene therapy and had different controls, we could not perform meta-analyses. Five of the six trials administered co-interventions equally to the experimental and control groups. All trials assessed one or more outcomes of interest in this review. The certainty of evidence was very low in five of the six comparisons and low in the double-dose gene therapy comparison. Below, we reported the results of the primary outcomes only. Pexastimogene devacirepvec (Pexa-Vec) plus best supportive care versus best supportive care alone There is uncertainty about whether there may be little to no difference between the effect of Pexa-Vec plus best supportive care compared with best supportive care alone on overall survival (HR 1.19, 95% CI 0.78 to 1.82; 1 trial (censored observation at 20-month follow-up), 129 participants; very low-certainty evidence) and on serious adverse events (RR 1.42, 95% CI 0.60 to 3.33; 1 trial at 20 months after treatment, 129 participants; very low-certainty evidence). The trial reported quality of life narratively as "assessment of quality of life and time to symptomatic progression was confounded by the high patient dropout rate." Adenovirus-thymidine kinase with ganciclovir (ADV-TK/GCV) plus liver transplantation versus liver transplantation alone There is uncertainty about whether ADV-TK/GCV plus liver transplantation may benefit all-cause mortality at the two-year follow-up (RR 0.39, 95% CI 0.20 to 0.76; 1 trial, 45 participants; very low-certainty evidence). The trial did not report serious adverse events other than mortality or quality of life. Double-dose ADV-TK/GCV plus liver transplantation versus liver transplantation alone There is uncertainty about whether double-dose ADV-TK/GCV plus liver transplantation versus liver transplantation may benefit all-cause mortality at five-year follow-up (RR 0.40, 95% CI 0.22 to 0.73; 1 trial, 86 participants; low-certainty evidence). The trial did not report serious adverse events other than mortality or quality of life. Recombinant human adenovirus-p53 with hydroxycamptothecin (rAd-p53/HCT) versus hydroxycamptothecin alone There is uncertainty about whether there may be little to no difference between the effect of rAd-p53/HCT versus hydroxycamptothecin alone on the overall survival at 12-month follow-up (RR 3.06, 95% CI 0.16 to 60.47; 1 trial, 48 participants; very low-certainty evidence). The trial did not report serious adverse events or quality of life. rAd-p53/5-Fu (5-fluorouracil) plus transarterial chemoembolisation versus transarterial chemoembolisation alone The trial included 46 participants. We had insufficient data to assess overall survival. The trial did not report serious adverse events or quality of life. E1B-deleted (dl1520) adenovirus versus percutaneous ethanol injection The trial included 10 participants. It did not report data on overall survival, serious adverse events, or health-related quality of life. One trial did not provide any information on sponsorship; one trial received a national research grant, one trial by the Pedersen foundation, and three were industry-funded trials. We found five ongoing randomised clinical trials. AUTHORS' CONCLUSIONS The evidence is very uncertain about the effects of gene therapy on the studied outcomes because of high risk of bias and imprecision of outcome results. The trials were underpowered and lacked trial data on clinically important outcomes. There was only one trial per comparison, and we could not perform meta-analyses. Therefore, we do not know if gene therapy may reduce, increase, or have little to no effect on all-cause mortality or overall survival, or serious adverse events in adults with unresectable hepatocellular carcinoma. The impact of gene therapy on adverse events needs to be investigated further. Evidence on the effect of gene therapy on health-related quality of life is lacking.
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Affiliation(s)
- Cho Naing
- Division of Tropical Health and Medicine, James Cook University, Queensland, Australia
| | - Han Ni
- Department of Medicine, Newcastle University Medicine Malaysia, Johor, Malaysia
| | - Htar Htar Aung
- School of Medicine, IMU University, Kuala Lumpur, Malaysia
| | | | - Dimitrinka Nikolova
- Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital ─ Rigshospitalet, Copenhagen, Denmark
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Boros C, Sutter O, Cauchy F, Ganne-Carrié N, Nahon P, N'kontchou G, Ziol M, Grando V, Demory A, Blaise L, Dondero F, Durand F, Soubrane O, Lesurtel M, Laurent A, Seror O, Nault JC. Upfront multi-bipolar radiofrequency ablation for HCC in transplant-eligible cirrhotic patients with salvage transplantation in case of recurrence. Liver Int 2024; 44:1464-1473. [PMID: 38581233 DOI: 10.1111/liv.15900] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Revised: 01/13/2024] [Accepted: 03/04/2024] [Indexed: 04/08/2024]
Abstract
INTRODUCTION We aim to assess the long-term outcomes of percutaneous multi-bipolar radiofrequency (mbpRFA) as the first treatment for hepatocellular carcinoma (HCC) in transplant-eligible cirrhotic patients, followed by salvage transplantation for intrahepatic distant tumour recurrence or liver failure. MATERIALS AND METHODS We included transplant-eligible patients with cirrhosis and a first diagnosis of HCC within Milan criteria treated by upfront mbp RFA. Transplantability was defined by age <70 years, social support, absence of significant comorbidities, no active alcohol use and no recent extrahepatic cancer. Baseline variables were correlated with outcomes using the Kaplan-Meier and Cox models. RESULTS Among 435 patients with HCC, 172 were considered as transplantable with HCCs >2 cm (53%), uninodular (87%) and AFP >100 ng/mL (13%). Median overall survival was 87 months, with 75% of patients alive at 3 years, 61% at 5 years and 43% at 10 years. Age (p = .003) and MELD>10 (p = .01) were associated with the risk of death. Recurrence occurred in 118 patients within Milan criteria in 81% of cases. Local recurrence was observed in 24.5% of cases at 10 years and distant recurrence rates were observed in 69% at 10 years. After local recurrence, 69% of patients were still alive at 10 years. At the first tumour recurrence, 75 patients (65%) were considered transplantable. Forty-one patients underwent transplantation, mainly for distant intrahepatic tumour recurrence. The overall 5-year survival post-transplantation was 72%, with a tumour recurrence of 2.4%. CONCLUSION Upfront multi-bipolar RFA for a first diagnosis of early HCC on cirrhosis coupled with salvage liver transplantation had a favourable intention-to-treat long-term prognosis, allowing for spare grafts.
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Affiliation(s)
- Carina Boros
- Liver Unit, Avicenne Hospital, APHP, Paris Nord University, Bobigny, France
| | - Olivier Sutter
- Interventional Radiology Unit, Avicenne Hospital, APHP, Paris Nord University, Bobigny, France
| | - François Cauchy
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, University of Geneva, Geneva, Switzerland
| | - Nathalie Ganne-Carrié
- Liver Unit, Avicenne Hospital, APHP, Paris Nord University, Bobigny, France
- Cordeliers Research Center, Sorbonne Université, Inserm, Université de Paris, Team « Functional Genomics of Solid Tumors », Equipe labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, Paris, France
| | - Pierre Nahon
- Liver Unit, Avicenne Hospital, APHP, Paris Nord University, Bobigny, France
- Cordeliers Research Center, Sorbonne Université, Inserm, Université de Paris, Team « Functional Genomics of Solid Tumors », Equipe labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, Paris, France
| | - Gisele N'kontchou
- Liver Unit, Avicenne Hospital, APHP, Paris Nord University, Bobigny, France
| | - Marianne Ziol
- Cordeliers Research Center, Sorbonne Université, Inserm, Université de Paris, Team « Functional Genomics of Solid Tumors », Equipe labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, Paris, France
- Pathology Department, and Centre de ressources biologiques (BB-0033-00027) Hôpitaux Universitaires Paris-Seine-Saint-Denis, Avicenne Hospital, APHP, Université Paris Norr, Bobigny, France
| | - Véronique Grando
- Liver Unit, Avicenne Hospital, APHP, Paris Nord University, Bobigny, France
| | - Alix Demory
- Liver Unit, Avicenne Hospital, APHP, Paris Nord University, Bobigny, France
| | - Lorraine Blaise
- Liver Unit, Avicenne Hospital, APHP, Paris Nord University, Bobigny, France
| | - Fédérica Dondero
- Department of HPB Surgery and Liver Transplantation, APHP, Beaujon Hospital-University of Paris Cité, Paris, France
| | - François Durand
- Liver Unit, Beaujon Hospital, APHP, Beaujon Hospital-University of Paris Cité, Paris, France
| | - Olivier Soubrane
- Department of Digestive Surgery, Institut Mutualiste Montsouris, Paris, France
| | - Mickael Lesurtel
- Department of HPB Surgery and Liver Transplantation, APHP, Beaujon Hospital-University of Paris Cité, Paris, France
| | - Alexis Laurent
- Department of Digestive Surgery, Assistance Publique - Hôpitaux de Paris, Henri Mondor and Albert Chenevier Teaching Hospital, Université Paris Est Créteil, Créteil, France
| | - Oliver Seror
- Interventional Radiology Unit, Avicenne Hospital, APHP, Paris Nord University, Bobigny, France
- Cordeliers Research Center, Sorbonne Université, Inserm, Université de Paris, Team « Functional Genomics of Solid Tumors », Equipe labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, Paris, France
| | - Jean Charles Nault
- Liver Unit, Avicenne Hospital, APHP, Paris Nord University, Bobigny, France
- Cordeliers Research Center, Sorbonne Université, Inserm, Université de Paris, Team « Functional Genomics of Solid Tumors », Equipe labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, Paris, France
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Martinino A, Bucaro A, Cardella F, Wazir I, Frongillo F, Ardito F, Giovinazzo F. Liver transplantation vs liver resection in HCC: promoting extensive collaborative research through a survival meta-analysis of meta-analyses. Front Oncol 2024; 14:1366607. [PMID: 38567152 PMCID: PMC10986178 DOI: 10.3389/fonc.2024.1366607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Accepted: 02/13/2024] [Indexed: 04/04/2024] Open
Abstract
Background HCC is a major global health concern, necessitating effective treatment strategies. This study conducts a meta-analysis of meta-analyses comparing liver resection (LR) and liver transplantation (LT) for HCC. Methods The systematic review included meta-analyses comparing liver resection vs. liver transplantation in HCC, following PRISMA guidelines. Primary outcomes included 5-year overall survival (OS) and disease-free survival (DFS). AMSTAR-2 assessed study quality. Citation matrix and hierarchical clustering validated the consistency of the included studies. Results A search identified 10 meta-analyses for inclusion. The median Pearson correlation coefficient for citations was 0.59 (IQR 0.41-0.65). LT showed better 5-year survival and disease-free survival in all HCC (OR): 0.79; 95% CI: 0.67-0.93, I^2:57% and OR: 0.44; 95% CI: 0.25-0.75, I^2:96%). Five-year survival in early HCC and ITT was 0.63 (95% CI: 0.50-0.78, I^2:0%) and 0.60 (95% CI: 0.39-0.92, I^2:0%). Salvage LT vs. Primary LT did not differ between 5-year survival and disease-free survival (OR: 0.62; 95% CI: 0.33-1.15, I^2:0% and 0.93; 95% CI: 0.82-1.04, I^2:0%). Conclusion Overall, the study underscores the superior survival outcomes associated with LT over LR in HCC treatment, supported by comprehensive meta-analysis and clustering analysis. There was no difference in survival or recurrence rate between salvage LT and primary LT. Therefore, considering the organ shortage, HCC can be resected and transplanted in case of recurrence.
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Affiliation(s)
| | - Angela Bucaro
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Francesca Cardella
- Surgical Oncology of Gastrointestinal Tract Unit, Vanvitelli University, Naples, Italy
| | - Ishaan Wazir
- Vardhaman Mahavir Medical College & Safdarjung Hospital, New Delhi, India
| | - Francesco Frongillo
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Francesco Ardito
- Hepatobilairy and General Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Francesco Giovinazzo
- General Surgery and Liver Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
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Zhang C, Tao Y, Yang R, Wang Y, Yu Y, Zhou Y. Prediction of Non-Transplantable Recurrence After Liver Resection for Solitary Hepatocellular Carcinoma. J Hepatocell Carcinoma 2024; 11:229-240. [PMID: 38298271 PMCID: PMC10827633 DOI: 10.2147/jhc.s412933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Accepted: 12/29/2023] [Indexed: 02/02/2024] Open
Abstract
Purpose Using a combination model of preoperative imaging and clinical factors to predict non-transplantable recurrence (NTR) after liver resection and assist solitary hepatocellular carcinoma (HCC) patients in the selection of early treatment options. Patients and Methods A retrospective analysis was conducted on 253 solitary HCC patients who underwent radical resection and had preoperative MRI. NTR patients were defined as those exceeding the University of California, San Francisco (UCSF) criteria at the time of recurrence. Cox regression analysis was employed to identify preoperative factors associated with NTR based on clinical and tumor imaging characteristics. A risk scoring model (NTRScore) was developed and validated. Results Among the 253 patients, 86 (33.9%) experienced recurrence, and among those with recurrence, 34 patients (39.5%) developed NTR. In multivariate analysis, factors associated with NTR included alpha-fetoprotein (AFP) [>10 ng/mL] [HR: 3.42, 95% confidence interval (CI): 1.54-7.63, P: 0.003], arterial phase hyperenhancement (APHE) [HR: 2.23, 95% CI: 1.03-4.81, P: 0.041], washout[HR: 0.35, 95% CI: 0.15-0.84, P: 0.019], and capsule [HR: 0.44, 95% CI: 0.22-0.88, P: 0.021]. The β-coefficients of these variables were utilized to develop the weighted NTRScore(c-index 0.72, 95% CI: 0.65-0.79). The NTR occurrence increased across the three categories (low: 5.6%, medium: 13.6%, high: 35.1%, p < 0.001), and the Kaplan-Meier curves of recurrence-free survival(RFS) and overall survival(OS) show significant differences (p = 0.004 and p<0.001). Furthermore, the higher NTR categories may be associated with an increased risk of extrahepatic recurrence. Conclusion The NTRScore demonstrated strong discriminatory ability and may serve as a clinically useful tool to assist in risk stratification and potential to guide treatment and optimal surveillance for patients of solitary hepatocellular carcinoma within UCSF criteria.
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Affiliation(s)
- Chunhui Zhang
- Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150010, People’s Republic of China
| | - Yuqing Tao
- Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150010, People’s Republic of China
| | - Rui Yang
- Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150010, People’s Republic of China
| | - Yueqi Wang
- Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150010, People’s Republic of China
| | - Yanyan Yu
- Department of Radiology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150010, People’s Republic of China
| | - Yang Zhou
- Department of Radiology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150010, People’s Republic of China
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Pelizzaro F, Trevisani F, Simeon V, Vitale A, Cillo U, Piscaglia F, Missale G, Sangiovanni A, Foschi FG, Cabibbo G, Caturelli E, Di Marco M, Azzaroli F, Brunetto MR, Raimondo G, Vidili G, Guarino M, Gasbarrini A, Campani C, Svegliati-Baroni G, Giannini EG, Mega A, Masotto A, Rapaccini GL, Magalotti D, Sacco R, Nardone G, Farinati F. Predictors of non-transplantable recurrence in hepatocellular carcinoma patients treated with frontline liver resection. Liver Int 2023; 43:2762-2775. [PMID: 37753540 DOI: 10.1111/liv.15719] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Revised: 08/09/2023] [Accepted: 08/21/2023] [Indexed: 09/28/2023]
Abstract
BACKGROUND AND AIMS Hepatocellular carcinoma (HCC) recurrence is common in patients treated with liver resection (LR). In this study, we aimed to evaluate the incidence and preoperative predictors of non-transplantable recurrence in patients with single HCC ≤5 cm treated with frontline LR. METHODS From the Italian Liver Cancer (ITA.LI.CA) database, 512 patients receiving frontline LR for single HCC ≤5 cm were retrieved. Incidence and predictors of recurrence beyond Milan criteria (MC) and up-to-seven criteria were compared between patients with HCC <4 and ≥4 cm. RESULTS During a median follow-up of 4.2 years, the overall recurrence rate was 55.9%. In the ≥4 cm group, a significantly higher proportion of patients recurred beyond MC at first recurrence (28.9% vs. 14.1%; p < 0.001) and overall (44.4% vs. 25.2%; p < 0.001). Similar results were found considering recurrence beyond up-to-seven criteria. Compared to those with larger tumours, patients with HCC <4 cm had a longer recurrence-free survival and overall survival. HCC size ≥4 cm and high alpha-fetoprotein (AFP) level at the time of LR were independent predictors of recurrence beyond MC (and up-to-seven criteria). In the subgroup of patients with available histologic information (n = 354), microvascular invasion and microsatellite lesions were identified as additional independent risk factors for non-transplantable recurrence. CONCLUSIONS Despite the high recurrence rate, LR for single HCC ≤5 cm offers excellent long-term survival. Non-transplantable recurrence is predicted by HCC size and AFP levels, among pre-operatively available variables. High-risk patients could be considered for frontline LT or listed for transplantation even before recurrence.
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Affiliation(s)
- Filippo Pelizzaro
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
- Gastroenterology Unit, Azienda Ospedale-Università di Padova, Padova, Italy
| | - Franco Trevisani
- Unit of Semeiotics, Liver and Alcohol-related diseases, Department of Medical and Surgical Sciences, Università di Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Vittorio Simeon
- Medical Statistics Unit, Mental, Physical Health and Preventive Medicine, University of Campania 'Luigi Vanvitelli', Napoli, Italy
| | - Alessandro Vitale
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
- Hepatobiliary Surgery and Liver Transplantation Unit, Azienda Ospedale-Università di Padova, Padova, Italy
| | - Umberto Cillo
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
- Hepatobiliary Surgery and Liver Transplantation Unit, Azienda Ospedale-Università di Padova, Padova, Italy
| | - Fabio Piscaglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Gabriele Missale
- Department of Medicine and Surgery, Unit of Infectious Diseases and Hepatology, University of Parma, Parma, Italy
| | - Angelo Sangiovanni
- Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Francesco G Foschi
- Department of Internal Medicine, Ospedale per gli Infermi di Faenza, Faenza, Italy
| | - Giuseppe Cabibbo
- Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Italy
| | | | | | - Francesco Azzaroli
- Gastroenterology Unit, Department of Surgical and Medical Sciences, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Maurizia R Brunetto
- Department of Clinical and Experimental Medicine, Hepatology and Liver Physiopathology Laboratory and Internal Medicine Unit, University of Pisa, Pisa, Italy
| | - Giovanni Raimondo
- Department of Clinical and Experimental Medicine, Clinical and Molecular Hepatology Unit, University of Messina, Messina, Italy
| | - Gianpaolo Vidili
- Department of Medicine Surgery and Pharmacy, Centralized Day Hospital of the medical area, University of Sassari, Azienda Ospedaliero-Universitaria di Sassari, Sassari, Italy
| | - Maria Guarino
- Department of Clinical Medicine and Surgery, Diseases of the Liver and Biliary System Unit, University of Napoli 'Federico II', Napoli, Italy
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Claudia Campani
- Department of Experimental and Clinical Medicine, Internal Medicine and Hepatology Unit, University of Firenze, Firenze, Italy
| | | | - Edoardo G Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genova, IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - Andrea Mega
- Gastroenterology Unit, Bolzano Regional Hospital, Bolzano, Italy
| | - Alberto Masotto
- Gastroenterology Unit, Ospedale Sacro Cuore Don Calabria, Negrar, Italy
| | - Gian Ludovico Rapaccini
- Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Donatella Magalotti
- Division of Internal Medicine, Neurovascular and Hepatometabolic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Rodolfo Sacco
- Gastroenterology and Digestive Endoscopy Unit, Foggia University Hospital, Foggia, Italy
| | - Gerardo Nardone
- Department of Clinical Medicine and Surgery, Hepato-Gastroenterology Unit, University of Napoli 'Federico II', Napoli, Italy
| | - Fabio Farinati
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
- Gastroenterology Unit, Azienda Ospedale-Università di Padova, Padova, Italy
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15
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Kamal O, Horvat N, Arora S, Chaudhry H, Elmohr M, Khanna L, Nepal PS, Wungjramirun M, Nandwana SB, Shenoy-Bhangle AS, Lee J, Kielar A, Marks R, Elsayes K, Fung A. Understanding the role of radiologists in complex treatment decisions for patients with hepatocellular carcinoma. Abdom Radiol (NY) 2023; 48:3677-3687. [PMID: 37715846 PMCID: PMC11234513 DOI: 10.1007/s00261-023-04033-6] [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: 07/10/2023] [Revised: 08/18/2023] [Accepted: 08/20/2023] [Indexed: 09/18/2023]
Abstract
Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver and represents a significant global health burden. Management of HCC can be challenging due to multiple factors, including variable expectations for treatment outcomes. Several treatment options are available, each with specific eligibility and ineligibility criteria, and are provided by a multidisciplinary team of specialists. Radiologists should be aware of the types of treatment options available, as well as the criteria guiding the development of individualized treatment plans. This awareness enables radiologists to contribute effectively to patient-centered multidisciplinary tumor boards for HCC and play a central role in reassessing care plans when the treatment response is deemed inadequate. This comprehensive review aims to equip radiologists with an overview of HCC staging systems, treatment options, and eligibility criteria. The review also discusses the significance of imaging in HCC diagnosis, treatment planning, and monitoring treatment response. Furthermore, we highlight the crucial branch points in the treatment decision-making process that depend on radiological interpretation.
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Affiliation(s)
- Omar Kamal
- Department of Diagnostic Radiology, Oregon Health & Science University, Mail Code: L340, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.
| | - Natally Horvat
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | | | | | | | | | | | - Manida Wungjramirun
- Department of Diagnostic Radiology, Oregon Health & Science University, Mail Code: L340, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA
| | | | | | - James Lee
- University of Kentucky, Lexington, KY, USA
| | | | | | | | - Alice Fung
- Department of Diagnostic Radiology, Oregon Health & Science University, Mail Code: L340, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA
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16
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Famularo S, Cillo U, Lauterio A, Donadon M, Vitale A, Serenari M, Cipriani F, Fazio F, Giuffrida M, Ardito F, Dominioni T, Garancini M, Lai Q, Nicolini D, Molfino S, Perri P, Pinotti E, Conci S, Ferrari C, Zanello M, Patauner S, Zimmitti G, Germani P, Chiarelli M, Romano M, De Angelis M, La Barba G, Troci A, Ferraro V, Izzo F, Antonucci A, Belli A, Memeo R, Crespi M, Ercolani G, Boccia L, Zanus G, Tarchi P, Hilal MA, Frena A, Jovine E, Griseri G, Ruzzenente A, Zago M, Grazi G, Baiocchi GL, Vivarelli M, Rossi M, Romano F, Maestri M, Giuliante F, Valle RD, Ferrero A, Aldrighetti L, De Carlis L, Cescon M, Torzilli G. Survival benefit of second line therapies for recurrent hepatocellular carcinoma: repeated hepatectomy, thermoablation and second-line transplant referral in a real life national scenario. HPB (Oxford) 2023; 25:1223-1234. [PMID: 37357112 DOI: 10.1016/j.hpb.2023.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Revised: 05/05/2023] [Accepted: 06/10/2023] [Indexed: 06/27/2023]
Abstract
BACKGROUND Despite second-line transplant(SLT) for recurrent hepatocellular carcinoma(rHCC) leads to the longest survival after recurrence(SAR), its real applicability has never been reported. The aim was to compare the SAR of SLT versus repeated hepatectomy and thermoablation(CUR group). METHODS Patients were enrolled from the Italian register HE.RC.O.LE.S. between 2008 and 2021. Two groups were created: CUR versus SLT. A propensity score matching (PSM) was run to balance the groups. RESULTS 743 patients were enrolled, CUR = 611 and SLT = 132. Median age at recurrence was 71(IQR 6575) years old and 60(IQR 53-64, p < 0.001) for CUR and SLT respectively. After PSM, median SAR for CUR was 43 months(95%CI = 37 - 93) and not reached for SLT(p < 0.001). SLT patients gained a survival benefit of 9.4 months if compared with CUR. MilanCriteria(MC)-In patients were 82.7% of the CUR group. SLT(HR 0.386, 95%CI = 0.23 - 0.63, p < 0.001) and the MELD score(HR 1.169, 95%CI = 1.07 - 1.27, p < 0.001) were the only predictors of mortality. In case of MC-Out, the only predictor of mortality was the number of nodules at recurrence(HR 1.45, 95%CI= 1.09 - 1.93, p = 0.011). CONCLUSION It emerged an important transplant under referral in favour of repeated hepatectomy or thermoablation. In patients with MC-Out relapse, the benefit of SLT over CUR was not observed.
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Affiliation(s)
- Simone Famularo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy; Surgical Data Science Team, Research Institute Against Digestive Cancer (IRCAD), Strasbourg, France.
| | - Umberto Cillo
- Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padova, Second General Surgical Unit, Padova Teaching Hospital, Padua, Italy
| | - Andrea Lauterio
- Department of General and Transplant Surgery, Grande Ospedale Metropolitano Niguarda, School of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
| | - Matteo Donadon
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Alessandro Vitale
- Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padova, Second General Surgical Unit, Padova Teaching Hospital, Padua, Italy
| | - Matteo Serenari
- Hepato-biliary Surgery and Transplant Unit, Policlinico Sant'Orsola IRCCS, Department of Medical and Surgical Sciences, University of Bologna, Italy
| | - Federica Cipriani
- Hepatobiliary Surgery Division, "Vita e Salute" University, Ospedale San Raffaele IRCCS, Milano, Italy
| | - Federico Fazio
- Department of General and Oncological Surgery, Mauriziano Hospital "Umberto I", Turin, Italy
| | - Mario Giuffrida
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Francesco Ardito
- Hepatobiliary Surgery Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Catholic University of the Sacred Heart, Rome, Italy
| | - Tommaso Dominioni
- Unit of General Surgery 1, University of Pavia and Foundation IRCCS Policlinico San Matteo, Pavia, Italy
| | - Mattia Garancini
- School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy
| | - Quirino Lai
- General Surgery and Organ Transplantation Unit, Sapienza University of Rome, Umberto I Polyclinic of Rome, Rome, Italy
| | - Daniele Nicolini
- HPB Surgery and Transplantation Unit, Department of Clinical and Experimental Medicine, Polytechnic University of Marche, Ancona, Italy
| | - Sarah Molfino
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Pasquale Perri
- Division of Hepatobiliarypancreatic Unit, IRCCS - Regina Elena National Cancer Institute, Rome, Italy
| | - Enrico Pinotti
- Department of Surgery, Ponte San Pietro Hospital, Bergamo, Italy
| | - Simone Conci
- Division of General and Hepatobiliary Surgery, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy
| | | | - Matteo Zanello
- Alma Mater Studiorum, University of Bologna, AOU Sant'Orsola Malpighi, IRCCS at Maggiore Hospital, Bologna, Italy
| | - Stefan Patauner
- Department of General and Pediatric Surgery, Bolzano Central Hospital, Bolzano, Italy
| | - Giuseppe Zimmitti
- Department of General Surgery, Poliambulanza Foundation Hospital, Brescia, Italy
| | - Paola Germani
- Division of General Surgery, Department of Medical and Surgical Sciences, ASUGI, Trieste, Italy
| | - Marco Chiarelli
- Department of Emergency and Robotic Surgery, ASST Lecco, Lecco, Italy
| | - Maurizio Romano
- Department of Surgical, Oncological and Gastroenterological Science (DISCOG), University of Padua, Hepatobiliary and Pancreatic Surgery Unit - Treviso Hospital, Italy
| | | | - Giuliano La Barba
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, Department of Medical and Surgical Sciences - University of Bologna Forlì, Italy
| | - Albert Troci
- Department of Surgery, L. Sacco Hospital, Milan, Italy
| | - Valentina Ferraro
- Department of Hepato-Pancreatic-Biliary Surgery, Miulli Hospital, Bari, Italy
| | - Francesco Izzo
- Division of Epatobiliary Surgical Oncology, Istituto Nazionale Tumori IRCCS Fondazione Pascale-IRCCS di Napoli, Naples, Italy
| | | | - Andrea Belli
- Division of Epatobiliary Surgical Oncology, Istituto Nazionale Tumori IRCCS Fondazione Pascale-IRCCS di Napoli, Naples, Italy
| | - Riccardo Memeo
- Department of Hepato-Pancreatic-Biliary Surgery, Miulli Hospital, Bari, Italy
| | | | - Giorgio Ercolani
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, Department of Medical and Surgical Sciences - University of Bologna Forlì, Italy
| | - Luigi Boccia
- Department of General Surgery, Ospedale Carlo Poma, Mantua, Italy
| | - Giacomo Zanus
- Department of Surgical, Oncological and Gastroenterological Science (DISCOG), University of Padua, Hepatobiliary and Pancreatic Surgery Unit - Treviso Hospital, Italy
| | - Paola Tarchi
- Division of General Surgery, Department of Medical and Surgical Sciences, ASUGI, Trieste, Italy
| | - Moh'd Abu Hilal
- Department of General Surgery, Poliambulanza Foundation Hospital, Brescia, Italy
| | - Antonio Frena
- Department of General and Pediatric Surgery, Bolzano Central Hospital, Bolzano, Italy
| | - Elio Jovine
- Alma Mater Studiorum, University of Bologna, AOU Sant'Orsola Malpighi, IRCCS at Maggiore Hospital, Bologna, Italy
| | - Guido Griseri
- HPB Surgical Unit, San Paolo Hospital, Savona, Italy
| | - Andrea Ruzzenente
- Division of General and Hepatobiliary Surgery, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy
| | - Mauro Zago
- Department of Surgery, Ponte San Pietro Hospital, Bergamo, Italy; Department of Emergency and Robotic Surgery, ASST Lecco, Lecco, Italy
| | - Gianluca Grazi
- Division of Hepatobiliarypancreatic Unit, IRCCS - Regina Elena National Cancer Institute, Rome, Italy
| | - Gian L Baiocchi
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Marco Vivarelli
- HPB Surgery and Transplantation Unit, Department of Clinical and Experimental Medicine, Polytechnic University of Marche, Ancona, Italy
| | - Massimo Rossi
- General Surgery and Organ Transplantation Unit, Sapienza University of Rome, Umberto I Polyclinic of Rome, Rome, Italy
| | - Fabrizio Romano
- School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy
| | - Marcello Maestri
- Unit of General Surgery 1, University of Pavia and Foundation IRCCS Policlinico San Matteo, Pavia, Italy
| | - Felice Giuliante
- Hepatobiliary Surgery Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Catholic University of the Sacred Heart, Rome, Italy
| | - Raffaele D Valle
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Alessandro Ferrero
- Department of General and Oncological Surgery, Mauriziano Hospital "Umberto I", Turin, Italy
| | - Luca Aldrighetti
- Hepatobiliary Surgery Division, "Vita e Salute" University, Ospedale San Raffaele IRCCS, Milano, Italy
| | - Luciano De Carlis
- Department of General and Transplant Surgery, Grande Ospedale Metropolitano Niguarda, School of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
| | - Matteo Cescon
- Hepato-biliary Surgery and Transplant Unit, Policlinico Sant'Orsola IRCCS, Department of Medical and Surgical Sciences, University of Bologna, Italy
| | - Guido Torzilli
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
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17
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Di Sandro S, Sposito C, Ravaioli M, Lauterio A, Magistri P, Bongini M, Odaldi F, De Carlis R, Botta F, Centonze L, Maroni L, Citterio D, Guidetti C, Bagnardi V, De Carlis L, Cescon M, Mazzaferro V, Di Benedetto F. Surgical Treatment of Hepatocellular Carcinoma: Multicenter Competing-risk Analysis of Tumor-related Death Following Liver Resection and Transplantation Under an Intention-to-treat Perspective. Transplantation 2023; 107:1965-1975. [PMID: 37022089 DOI: 10.1097/tp.0000000000004593] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/07/2023]
Abstract
BACKGROUND Early-stage hepatocellular carcinoma could benefit from upfront liver resection (LR) or liver transplantation (LT), but the optimal strategy in terms of tumor-related outcomes is still debated. We compared the oncological outcomes of LR and LT for hepatocellular carcinoma, stratifying the study population into a low-, intermediate-, and high-risk class according to the risk of death at 5-y predicted by a previously developed prognostic model. The impact of tumor pathology on oncological outcomes of low- and intermediate-risk patients undergoing LR was investigated as a secondary outcome. METHODS We performed a retrospective multicentric cohort study involving 2640 patients consecutively treated by LR or LT from 4 tertiary hepatobiliary and transplant centers between 2005 and 2015, focusing on patients amenable to both treatments upfront. Tumor-related survival and overall survival were compared under an intention-to-treat perspective. RESULTS We identified 468 LR and 579 LT candidates: 512 LT candidates underwent LT, whereas 68 (11.7%) dropped-out for tumor progression. Ninety-nine high-risk patients were selected from each treatment cohort after propensity score matching. Three and 5-y cumulative incidence of tumor-related death were 29.7% and 39.5% versus 17.2% and 18.3% for LR and LT group ( P = 0.039), respectively. Low-risk and intermediate-risk patients treated by LR and presenting satellite nodules and microvascular invasion had a significantly higher 5-y incidence of tumor-related death (29.2% versus 12.5%; P < 0.001). CONCLUSIONS High-risk patients showed significantly better intention-to-treat tumor-related survival after upfront LT rather than LR. Cancer-specific survival of low- and intermediate-risk LR patients was significantly impaired by unfavorable pathology, suggesting the application of ab-initio salvage LT in such scenarios.
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Affiliation(s)
- Stefano Di Sandro
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Carlo Sposito
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| | - Matteo Ravaioli
- Department of General Surgery and Transplantation, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Andrea Lauterio
- Department of General Surgery and Transplantation, Niguarda Ca' Granda Hospital, Milan, Italy
- School of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
| | - Paolo Magistri
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Marco Bongini
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy
| | - Federica Odaldi
- Department of General Surgery and Transplantation, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Riccardo De Carlis
- Department of General Surgery and Transplantation, Niguarda Ca' Granda Hospital, Milan, Italy
- PhD Course in Clinical and Experimental Sciences, Univeristy of Padua, Padua, Italy
| | - Francesca Botta
- Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy
| | - Leonardo Centonze
- Department of General Surgery and Transplantation, Niguarda Ca' Granda Hospital, Milan, Italy
- Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy
| | - Lorenzo Maroni
- Department of General Surgery and Transplantation, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Davide Citterio
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy
| | - Cristiano Guidetti
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Vincenzo Bagnardi
- Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy
| | - Luciano De Carlis
- Department of General Surgery and Transplantation, Niguarda Ca' Granda Hospital, Milan, Italy
- School of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
| | - Matteo Cescon
- Department of General Surgery and Transplantation, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Vincenzo Mazzaferro
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| | - Fabrizio Di Benedetto
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy
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18
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Liu YW, Moi SH, Li WF, Lin CC, Yong CC, Wang CC, Yen YH, Lin CY. A preoperative model for predicting early recurrence in patients undergoing resection for single hepatocellular carcinoma. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:1444-1449. [PMID: 36948970 DOI: 10.1016/j.ejso.2023.03.211] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 03/04/2023] [Accepted: 03/11/2023] [Indexed: 03/18/2023]
Abstract
BACKGROUND AND AIM The updated Barcelona Clinic Liver Cancer guidelines recommend liver resection (LR) for patients with single hepatocellular carcinoma (HCC) of any size. This study developed a preoperative model for predicting early recurrence in patients undergoing LR for single HCC. MATERIALS AND METHODS We identified 773 patients undergoing LR for single HCC between 2011 and 2017 from the cancer registry database of our institution. Multivariate Cox regression analyses were performed to construct a preoperative model for predicting early recurrence, i.e., recurrence within 2 years of LR. RESULTS Early recurrence was identified in 219 patients (28.3%). The final model of early recurrence included four predictive factors-alpha-fetoprotein level of ≥20 ng/mL, tumor size of >30 mm, Model for End-Stage Liver Disease score of >8, and cirrhosis. Preoperative application of this model provided three risk strata for recurrence-free survival (RFS): low risk, with 2-year RFS of 79.8% (95% confidence interval [CI]: 75.7-84.2%); intermediate risk, with 2-year RFS of 66.6% (95% CI: 61.1-72.6%); and high risk, with 2-year RFS of 51.1% (95% CI: 43.0-60.8%). CONCLUSION We developed a preoperative model for predicting early recurrence after LR for single HCC. This model provides useful information for clinical decision-making.
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Affiliation(s)
- Yueh-Wei Liu
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Sin-Hua Moi
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan
| | - Wei-Feng Li
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chih-Che Lin
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chee-Chien Yong
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chih-Chi Wang
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
| | - Yi-Hao Yen
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
| | - Chih-Yun Lin
- Biostatistics Center of Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
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Lu Y, Liang L, Lu WF, Cheng J, Yao WF, Xie YM, Wang DD, Xu FQ, Xiao ZQ, Zhang JG, Liu JW, Zhang CW, Huang DS. The prognosis of elderly patients with hepatocellular carcinoma after curative hepatectomy a multicenter competing risk analysis. Clin Res Hepatol Gastroenterol 2023; 47:102147. [PMID: 37245639 DOI: 10.1016/j.clinre.2023.102147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Revised: 05/25/2023] [Accepted: 05/25/2023] [Indexed: 05/30/2023]
Abstract
BACKGROUND Non-cancer-specific death (NCSD) is an important factor that needs to be considered in patients with malignancy, as it can affect their long-term prognosis. In particular, the effect of age on patients with hepatocellular carcinoma (HCC) after hepatectomy requires clarification. This study aims to examine the impact of age on patients with HCC after hepatectomy and to identify independent risk factors of survival. METHODS Patients with HCC that fell within the Milan Criteria and had undergone curative hepatectomy were included in this study. The patients were divided into two groups: young patients (age <70) and elderly patients (age ≥70). Perioperative complications, cancer-specific death (CSD), recurrence, and NCSD were all recorded and analyzed. Multivariate analyses were performed to identify independent risk factors of survival using Fine and Gray's competing-risk regression model. RESULTS Among 1,354 analytic patients, 1,068 (78.7%) were stratified into the young group and 286 (21.3%) into the elderly group. The elderly group had a higher 5-year cumulative incidence of NCSD (12.6% vs. 3.7% for the young group, P < 0.001), but lower 5-year cumulative incidences of recurrence (20.3% vs. 21.1% for the young group, P = 0.041) and CSD (14.3% vs. 15.5% for the young group, P = 0.066). Multivariate competing-risk regression analyses revealed that age was independently associated with NCSD (subdistribution hazard ratio (SHR) 3.003, 95%CI: 2.082-4.330, P < 0.001), but not with recurrence (SHR 0.837, 95%CI: 0.659-1.060, P = 0.120) or CSD (SHR 0.736, 95%CI: 0.537-1.020, P = 0.158). CONCLUSION For patients with early-stage HCC after hepatectomy, older age was independently associated with NCSD, but not recurrence and CSD.
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Affiliation(s)
- Yi Lu
- Department of Clinical Medicine, Medical College of Soochow University, Suzhou, China; General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Lei Liang
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.
| | - Wen Feng Lu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Jian Cheng
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Wei Feng Yao
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Ya Ming Xie
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Dong Dong Wang
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Fei Qi Xu
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Zun Qiang Xiao
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Jun Gang Zhang
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Jun Wei Liu
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Cheng Wu Zhang
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Dong Sheng Huang
- Department of Clinical Medicine, Medical College of Soochow University, Suzhou, China; General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China; Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, China.
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20
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Angelico R, Siragusa L, Serenari M, Scalera I, Kauffman E, Lai Q, Vitale A. Rescue liver transplantation after post-hepatectomy acute liver failure: A systematic review and pooled analysis. Transplant Rev (Orlando) 2023; 37:100773. [PMID: 37356212 DOI: 10.1016/j.trre.2023.100773] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2023] [Revised: 06/14/2023] [Accepted: 06/15/2023] [Indexed: 06/27/2023]
Abstract
BACKGROUND Post-hepatectomy liver failure is a severe complication after major liver resection and is associated with a high mortality rate. Nevertheless, there is no effective treatment for severe liver failure. In such a setting, rescue liver transplantation (LT) is used only in extraordinary cases with unclear results. This systematic review aims to define indication of LT in post-hepatectomy liver failure and post-LT outcomes, in terms of patient and disease-free survivals, to assess the procedure's feasibility and effectiveness. METHODS A systematic review of all English language full-text articles published until September 2022 was conducted. Inclusion criteria were articles describing patients undergoing LT for post-hepatectomy liver failure after liver resection, which specified at least one outcome of interest regarding patient/graft survival, postoperative complications, tumour recurrence and cause of death. A pseudo-individual participant data meta-analysis was performed to analyse data. Study quality was assessed with MINORS system. PROSPERO CRD42022349358. RESULTS Postoperative complication rate was 53.6%. All patients transplanted for benign indications survived. For malignant tumours, 1-, 3- and 5-year overall survival was 94.7%, 82.1% and 74.6%, respectively. The causes of death were tumour recurrence in 83.3% of cases and infection-related in 16.7% of LT recipients. At Cox regression, being transplanted for unconventional malignant indications (colorectal liver metastasis, cholangiocarcinoma) was a risk factor for death HR = 8.93 (95%CI = 1.04-76.63; P-value = 0.046). Disease-free survival differs according to different malignant tumours (P-value = 0.045). CONCLUSIONS Post-hepatectomy liver failure is an emergent indication for rescue LT, but it is not universally accepted. In selected patients, LT can be a life-saving procedure with low short-term risks. However, special attention must be given to long-term oncological prognosis before proceeding with rescue LT in an urgent setting, considering the severity of liver malignancy, organ scarcity, the country's organ allocation policies and the resource of living-related donation.
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Affiliation(s)
- Roberta Angelico
- Department of Surgical Sciences, Transplant and HPB Unit, University of Rome Tor Vergata, 00133 Rome, Italy.
| | - Leandro Siragusa
- Department of Surgical Sciences, Transplant and HPB Unit, University of Rome Tor Vergata, 00133 Rome, Italy
| | - Matteo Serenari
- General Surgery and Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Sant'Orsola-Malpighi Hospital, Bologna, Italy; Department of Medical and Surgical Sciences-DIMEC, Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Irene Scalera
- Unità di Chirurgia Epatobiliare e Trapianti di Fegato, Azienda Ospedaliero Universitaria -Consorziale Policlinico di Bari, Bari, Italy
| | - Emanuele Kauffman
- Division of General and Transplant Surgery, Pisa University, Pisa, Italy
| | - Quirino Lai
- General Surgery and Organ Transplantation Unit, Sapienza University of Rome, AUO Policlinico I of Rome, Rome, Italy
| | - Alessandro Vitale
- Department of Surgical Oncological and Gastroenterological Sciences, Padua University, Padua, Italy
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Wang L, Liu BX, Long HY. Ablative strategies for recurrent hepatocellular carcinoma. World J Hepatol 2023; 15:515-524. [PMID: 37206650 PMCID: PMC10190693 DOI: 10.4254/wjh.v15.i4.515] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 02/14/2023] [Accepted: 03/29/2023] [Indexed: 04/20/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is the fifth leading cause of cancer death worldwide and the third leading cause of all diseases worldwide. Liver transplantation, surgical resection and ablation are the three main curative treatments for HCC. Liver transplantation is the optimal treatment option for HCC, but its usage is limited by the shortage of liver sources. Surgical resection is considered the first choice for early-stage HCC, but it does not apply to patients with poor liver function. Therefore, more and more doctors choose ablation for HCC. However, intrahepatic recurrence occurs in up to 70% patients within 5 years after initial treatment. For patients with oligo recurrence after primary treatment, repeated resection and local ablation are both alternative. Only 20% patients with recurrent HCC (rHCC) indicate repeated surgical resection because of limitations in liver function, tumor location and intraperitoneal adhesions. Local ablation has become an option for the waiting period when liver transplantation is unavailable. For patients with intrahepatic recurrence after liver transplantation, local ablation can reduce the tumor burden and prepare them for liver transplantation. This review systematically describes the various ablation treatments for rHCC, including radiofrequency ablation, microwave ablation, laser ablation, high-intensity focused ultrasound ablation, cryablation, irreversible electroporation, percutaneous ethanol injection, and the combination of ablation and other treatment modalities.
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Affiliation(s)
- Lin Wang
- Department of Medical Ultrasound, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
| | - Bao-Xian Liu
- Department of Medical Ultrasound, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
| | - Hai-Yi Long
- Department of Medical Ultrasound, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
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22
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Wang D, Xiao M, Wan ZM, Lin X, Li QY, Zheng SS. Surgical treatment for recurrent hepatocellular carcinoma: Current status and challenges. World J Gastrointest Surg 2023; 15:544-552. [PMID: 37206072 PMCID: PMC10190723 DOI: 10.4240/wjgs.v15.i4.544] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 01/05/2023] [Accepted: 03/21/2023] [Indexed: 04/22/2023] Open
Abstract
Primary liver cancer is the sixth most commonly diagnosed cancer and was the third leading cause of cancer deaths worldwide in 2020. It includes hepatocellular carcinoma (HCC) (representing 75%-85% of cases), intrahepatic cholangiocarcinoma (representing 10%-15% of cases), and other rare types. The survival rate of patients with HCC has risen with improved surgical technology and perioperative management in recent years; however, high tumor recurrence rates continue to limit long-term survival, even after radical surgical resection (exceeding 50% recurrence). For resectable recurrent liver cancer, surgical removal [either salvage liver transplantation (SLT) or repeat hepatic resection] remains the most effective therapy that is potentially curative for recurrent HCC. Thus, here, we introduce surgical treatment for recurrent HCC. Areas Covered: A literature search was performed for recurrent HCC using Medline and PubMed up to August 2022. Expert commentary: In general, long-term survival after the re-resection of recurrent liver cancer is usually beneficial. SLT has equivalent outcomes to primary liver transplantation for unresectable recurrent illness in a selected group of patients; however, SLT is constrained by the supply of liver grafts. SLT seems to be inferior to repeat liver resection when considering operative and postoperative results but has the major advantage of disease-free survival. When considering the similar overall survival rate and the current situation of donor shortages, repeat liver resection remains an important option for recurrent HCC.
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Affiliation(s)
- Di Wang
- Division of Hepatobiliary and Pancreatic Surgery, Zhejiang Chinese Medical University, Hangzhou 310000, Zhejiang Province, China
- Division of Hepatobiliary and Pancreatic Surgery, Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250000, Shandong Province, China
| | - Min Xiao
- Division of Hepatobiliary and Pancreatic Surgery, Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250000, Shandong Province, China
- Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou 310000, Zhejiang Province, China
| | - Zhen-Miao Wan
- Division of Hepatobiliary and Pancreatic Surgery, Zhejiang Chinese Medical University, Hangzhou 310000, Zhejiang Province, China
- Division of Hepatobiliary and Pancreatic Surgery, Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250000, Shandong Province, China
| | - Xin Lin
- Division of Hepatobiliary and Pancreatic Surgery, Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250000, Shandong Province, China
- Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou 310000, Zhejiang Province, China
| | - Qi-Yong Li
- Division of Hepatobiliary and Pancreatic Surgery, Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250000, Shandong Province, China
- Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou 310000, Zhejiang Province, China
| | - Shu-Sen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250000, Shandong Province, China
- Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou 310000, Zhejiang Province, China
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23
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Lima HA, Moazzam Z, Endo Y, Alaimo L, Shaikh C, Munir MM, Resende V, Guglielmi A, Marques HP, Cauchy F, Lam V, Poultsides GA, Popescu I, Alexandrescu S, Martel G, Hugh T, Endo I, Kitago M, Shen F, Pawlik TM. TBS-Based Preoperative Score to Predict Non-transplantable Recurrence and Identify Candidates for Upfront Resection Versus Transplantation for Hepatocellular Carcinoma. Ann Surg Oncol 2023; 30:3363-3373. [PMID: 36820934 DOI: 10.1245/s10434-023-13273-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Accepted: 02/06/2023] [Indexed: 02/24/2023]
Abstract
BACKGROUND Recurrence following liver resection (LR) for hepatocellular carcinoma (HCC) can be as high as 50-70%. While salvage liver transplantation may be feasible, patients may develop a non-transplantable recurrence (NTR) (recurrence beyond Milan criteria). We sought to identify preoperative risk factors to predict NTR after resection. PATIENTS AND METHODS Patients who underwent curative-intent LR for HCC were identified from a multi-institutional database. Preoperative factors associated with NTR were identified and a risk score model (NTR score) was developed and validated. RESULTS Among 1620 patients, 842 (52.0%) developed recurrence; among patients with recurrence, NTR occurred in 341 (40.5%) with a median recurrence-free survival (RFS) of 30 months (24.7-35.3 months). On multivariable analysis, factors associated with NTR included alpha fetoprotein (AFP) > 400 ng/mL [hazard ratio (HR) 1.71, 95% confidence interval (CI) 1.33-2.19], albumin-bilirubin grade (ALBI) (referent low, medium ALBI: HR 1.41, 95% CI 1.10-1.81, high ALBI: HR 2.47, 95% CI 0.91-6.68), and tumor burden score (TBS) (referent low, high TBS: HR 2.55, 95% CI, 1.99-3.28). A simplified TBS-based NTR score was developed using the β-coefficients of each factor (C-index 0.68, 95% CI 0.65-0.71). Higher NTR score was associated with incrementally worse 5-year RFS (low 44.8%, medium 37.5%, high 24.5%) [area under the curve (AUC) 0.59] and increased incidence of NTR (low 13.7%, medium 25.4%, high 38.2%) (AUC 0.65) (both p < 0.001). Moreover, higher NTR score was associated with higher risk of extrahepatic recurrence (low 11.3%, medium 28.8%, high 37.5%) (p < 0.001). CONCLUSION NTR following curative-intent resection of HCC occurred in one in five patients. A simple TBS-based NTR score accurately predicted the risk of NTR and may help identify candidates for upfront resection versus transplantation.
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Affiliation(s)
- Henrique A Lima
- Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Health Services Management and Policy, Wexner Medical Center and James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.,Federal University of Minas Gerais School of Medicine, Belo Horizonte, Brazil
| | - Zorays Moazzam
- Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Health Services Management and Policy, Wexner Medical Center and James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
| | - Yutaka Endo
- Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Health Services Management and Policy, Wexner Medical Center and James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
| | - Laura Alaimo
- Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Health Services Management and Policy, Wexner Medical Center and James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
| | - Chanza Shaikh
- Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Health Services Management and Policy, Wexner Medical Center and James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
| | - Muhammad Musaab Munir
- Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Health Services Management and Policy, Wexner Medical Center and James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
| | - Vivian Resende
- Federal University of Minas Gerais School of Medicine, Belo Horizonte, Brazil
| | | | - Hugo P Marques
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | - François Cauchy
- Department of Hepatibiliopancreatic Surgery, APHP, Beaujon Hospital, Clichy, France
| | - Vincent Lam
- Department of Surgery, Westmead Hospital, Sydney, NSW, Australia
| | | | - Irinel Popescu
- Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania
| | | | | | - Tom Hugh
- Department of Surgery, School of Medicine, The University of Sydney, Sydney, NSW, Australia
| | - Itaru Endo
- Yokohama City University School of Medicine, Yokohama, Japan
| | - Minoru Kitago
- Department of Surgery, Keio University, Tokyo, Japan
| | - Feng Shen
- Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - Timothy M Pawlik
- Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Health Services Management and Policy, Wexner Medical Center and James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
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24
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Yang Y, Sun JH, Tan XY, Lu CD, Huang ZP, Zhu HD, Shi XT, Chen JX, Fang JZ. MTM-HCC at Previous Liver Resection as a Predictor of Overall Survival in Salvage Liver Transplantation. Dig Dis Sci 2023; 68:2768-2777. [PMID: 36790686 DOI: 10.1007/s10620-023-07857-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Accepted: 01/28/2023] [Indexed: 02/16/2023]
Abstract
OBJECTIVES Salvage liver transplantation (sLT) is considered an effective method to treat hepatocellular carcinoma (HCC) recurrence. This multicenter research aimed to identify the prognostic factors associated with recurrence-free survival (RFS) and overall survival (OS) after sLT. MATERIAL AND METHODS A retrospective analysis of 114 patients who had undergone sLT for recurrent HCC between February 2012 and September 2020 was performed. The baseline and clinicopathological data of the patients were collected. RESULTS The 1-, 3-, and 5-year RFS rates after sLT were 88.9%, 75.2%, and 69.2%, respectively, and the OS rates were 96.4%, 78.3%, and 70.8%. A time from liver resection (LR) to recurrence < 1 year, disease beyond the Milan criteria at sLT and macrotrabecular massive (MTM)-HCC were identified as risk factors for RFS and were further identified as independent risk factors. A time from LR to recurrence < 1 year, disease beyond the Milan criteria at sLT and MTM-HCC were also risk factors for OS and were further identified as independent risk factors. CONCLUSIONS Compared with primary liver transplantation (pLT), more prognostic factors are available from patients who had undergone LR. We suggest that in cases of HCC recurrence within 1 year after LR, disease beyond the Milan criteria at sLT and MTM-HCC patients, sLT should be used with caution.
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Affiliation(s)
- Yong Yang
- Department of Hepatopancreatobiliary Surgery, Ningbo Medical Centre Lihuili Hospital, Ningbo University, Ningbo, 315040, Zhejiang, China
| | - Ji-Han Sun
- Department of Hepatopancreatobiliary Surgery, Ningbo Medical Centre Lihuili Hospital, Ningbo University, Ningbo, 315040, Zhejiang, China
| | - Xiao-Yu Tan
- Department of Hepatopancreatobiliary Surgery, General Hospital of Southern Theater Command, Guangzhou, 315000, China
| | - Cai-De Lu
- Department of Hepatopancreatobiliary Surgery, Ningbo Medical Centre Lihuili Hospital, Ningbo University, Ningbo, 315040, Zhejiang, China
| | - Zhi-Ping Huang
- Department of Hepatopancreatobiliary Surgery, General Hospital of Southern Theater Command, Guangzhou, 315000, China
| | - Hong-Da Zhu
- Department of Hepatopancreatobiliary Surgery, Ningbo Medical Centre Lihuili Hospital, Ningbo University, Ningbo, 315040, Zhejiang, China
| | - Xiao-Ting Shi
- Department of Hepatopancreatobiliary Surgery, General Hospital of Southern Theater Command, Guangzhou, 315000, China
| | - Jian-Xiong Chen
- Department of Hepatopancreatobiliary Surgery, General Hospital of Southern Theater Command, Guangzhou, 315000, China
| | - Jiong-Ze Fang
- Department of Hepatopancreatobiliary Surgery, Ningbo Medical Centre Lihuili Hospital, Ningbo University, Ningbo, 315040, Zhejiang, China.
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25
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Nelson DW, Vauthey JN. Optimizing Treatment Strategies with Preoperative Assessment for Microvascular Invasion in Hepatocellular Carcinoma. Ann Surg Oncol 2023; 30:660-662. [PMID: 36310312 DOI: 10.1245/s10434-022-12746-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Accepted: 10/17/2022] [Indexed: 01/10/2023]
Affiliation(s)
- Daniel W Nelson
- Division of Surgical Oncology, Department of Surgery, William Beaumont Army Medical Center WBAMC, Uniformed Services University of the Health Sciences, Fort Bliss, TX, USA.
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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26
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Toubert C, Guiu B, Al Taweel B, Assenat E, Panaro F, Souche FR, Ursic-Bedoya J, Navarro F, Herrero A. Prolonged Survival after Recurrence in HCC Resected Patients Using Repeated Curative Therapies: Never Give Up! Cancers (Basel) 2022; 15:232. [PMID: 36612227 PMCID: PMC9818493 DOI: 10.3390/cancers15010232] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Revised: 12/18/2022] [Accepted: 12/26/2022] [Indexed: 01/04/2023] Open
Abstract
Surgical resection is the optimal treatment for HCC, despite a high risk of recurrence. Few data are available on patient’s survival after resection. This is a retrospective study of tumor recurrence occurring after hepatectomy for HCC from 2000 to 2016. Univariate and multivariate analyses were performed to identify prognostic factors of survival after recurrence (SAR). Among 387 patients, 226 recurred (58.4%) with a median SAR of 26 months. Curative treatments (liver transplantation, repeat hepatectomy, thermal ablation) were performed for 44.7% of patients. Independent prognostic factors for SAR were micro-vascular invasion on the primary surgical specimen, size of the initial tumor >5 cm, preoperative AFP, albumin and platelet levels, male gender, number, size and localization of tumors at recurrence, time to recurrence, Child−Pugh score and treatment at recurrence. In subgroup analysis, early recurrence (46%) was associated with a decrease in SAR, by contrast with late recurrence. However, the overall survival (OS) of patients with early recurrence and curative treatment did not significantly differ from that of non-recurring patients. For late recurrence, OS did not significantly differ from that of non-recurring patients, regardless of the proposed treatment. Aggressive and repeat treatments are therefore key to improve prognosis of patients with HCC.
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Affiliation(s)
- Cyprien Toubert
- Department of HBP Surgery and Liver Transplantation, Montpellier University Hospital, University of Montpellier, 34295 Montpellier, France
| | - Boris Guiu
- Department of Digestive Imaging, Montpellier University Hospital, University of Montpellier, 34295 Montpellier, France
| | - Bader Al Taweel
- Department of HBP Surgery and Liver Transplantation, Montpellier University Hospital, University of Montpellier, 34295 Montpellier, France
| | - Eric Assenat
- Department of Digestive Oncology, Montpellier University Hospital, University of Montpellier, 34295 Montpellier, France
| | - Fabrizio Panaro
- Department of HBP Surgery and Liver Transplantation, Montpellier University Hospital, University of Montpellier, 34295 Montpellier, France
| | - François-Regis Souche
- Department of Minimally Invasive and Oncologic Surgery, Montpellier University Hospital, University of Montpellier, 34295 Montpellier, France
| | - Jose Ursic-Bedoya
- Liver Transplantation Unit, Department of Hepatology, Montpellier University Hospital, University of Montpellier, 34295 Montpellier, France
| | - Francis Navarro
- Department of HBP Surgery and Liver Transplantation, Montpellier University Hospital, University of Montpellier, 34295 Montpellier, France
| | - Astrid Herrero
- Department of HBP Surgery and Liver Transplantation, Montpellier University Hospital, University of Montpellier, 34295 Montpellier, France
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27
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Tortajada P, Doamba R, Cano L, Ghallab M, Allard MA, Ciacio O, Pittau G, Salloum C, Cherqui D, Adam R, Sa Cunha A, Azoulay D, Pascale A, Vibert E, Golse N. Resectable and transplantable hepatocellular carcinoma: Integration of liver stiffness assessment in the decision-making algorithm. Surgery 2022; 172:1704-1711. [PMID: 36241470 DOI: 10.1016/j.surg.2022.08.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 08/08/2022] [Accepted: 08/09/2022] [Indexed: 11/07/2022]
Abstract
BACKGROUND Liver resection is a curative treatment for hepatocellular carcinoma (HCC) and an alternative to liver transplantation (LT). However, post-liver resection recurrence rates remain high. This study aimed to determine whether liver stiffness measurement (LSM) correlated with recurrence and to propose a method for predicting HCC recurrence exclusively using pre-liver resection criteria. METHODS This retrospective monocentric study included patients who had undergone LR liver resection for HCC between 2015 and 2018 and who had (1) preoperative alpha-fetoprotein scores indicating initial transplant viability and (2) available preoperative LSM data. We developed a predictive score for recurrence over time using Cox univariate regression and multivariate analysis with a combination plot before selecting the optimal thresholds (receiver operating characteristic curves + Youden test). RESULTS Sixty-six patients were included. After an average follow-up of 40 months, the recurrence rate was 45% (n = 30). Three-year overall survival was 88%. Four preoperative variables significantly impacted the time to recurrence: age ≥70 years, LSM ≥11 kPa, international normalized ratio (INR) ≥1.2, and maximum HCC diameter ≥3 cm. By assigning 1 point per positive item, patients with a score <2 (n = 22) demonstrated greater mean overall survival (69.7 vs 54.8 months, P = .02) and disease-free survival (52.2 vs 34.7 months, P = .02) than those with a score ≥2. Patients experiencing early recurrence (<1 year) presented a significantly higher preoperative LSM (P = .06). CONCLUSION We identified a simple preoperative score predictive of early hepatocellular carcinoma recurrence after liver resection, highlighting the role of liver stiffness. This score could help physicians select patients and make decisions concerning perioperative medical treatment.
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Affiliation(s)
- Pauline Tortajada
- Department of Surgery, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif, France.
| | - Rodrigue Doamba
- Department of Surgery, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif, France
| | - Luis Cano
- INSERM, Univ Rennes, INRAE, CHU Pontchaillou, UMR 1241 NUMECAN, Rennes, France
| | - Mohammed Ghallab
- Department of Surgery, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif, France; The Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - Marc Antoine Allard
- Department of Surgery, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif, France; INSERM, Physiopathogénèse et traitement des maladies du Foie, Université Paris-Saclay, UMRS 1193, FHU Hepatinov, Villejuif, France
| | - Oriana Ciacio
- Department of Surgery, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif, France
| | - Gabriella Pittau
- Department of Surgery, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif, France
| | - Chady Salloum
- Department of Surgery, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif, France
| | - Daniel Cherqui
- Department of Surgery, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif, France; INSERM, Physiopathogénèse et traitement des maladies du Foie, Université Paris-Saclay, UMRS 1193, FHU Hepatinov, Villejuif, France
| | - René Adam
- Department of Surgery, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif, France; Univ Paris-Sud, UMR-S 776, Villejuif, France
| | - Antonio Sa Cunha
- Department of Surgery, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif, France; INSERM, Physiopathogénèse et traitement des maladies du Foie, Université Paris-Saclay, UMRS 1193, FHU Hepatinov, Villejuif, France
| | - Daniel Azoulay
- Department of Surgery, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif, France; INSERM, Physiopathogénèse et traitement des maladies du Foie, Université Paris-Saclay, UMRS 1193, FHU Hepatinov, Villejuif, France
| | - Alina Pascale
- Department of Hepatology, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif, France
| | - Eric Vibert
- Department of Surgery, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif, France; INSERM, Physiopathogénèse et traitement des maladies du Foie, Université Paris-Saclay, UMRS 1193, FHU Hepatinov, Villejuif, France. https://twitter.com/Eric_Vibert
| | - Nicolas Golse
- Department of Surgery, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif, France; INSERM, Physiopathogénèse et traitement des maladies du Foie, Université Paris-Saclay, UMRS 1193, FHU Hepatinov, Villejuif, France
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Gozzo C, Hermida M, Herrero A, Panaro F, Cassinotto C, Mohamad AM, Assenat E, Guillot C, Allimant C, Schembri V, Basile A, Dharancy S, Ursic‐Bedoya J, Guiu B. Non-transplantable recurrence after percutaneous thermal ablation of ≤3-cm HCC: Predictors and implications for treatment allocation. Hepatol Commun 2022; 6:2975-2987. [PMID: 35932178 PMCID: PMC9512464 DOI: 10.1002/hep4.2063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 04/27/2022] [Accepted: 07/02/2022] [Indexed: 12/02/2022] Open
Abstract
Percutaneous thermal ablation (PTA), resection, and liver transplantation are the standard curative options for hepatocellular carcinoma (HCC). Liver transplantation yields the best long-term outcomes but is limited by graft shortage. Thus, patients with ≤3-cm HCC are primarily treated by PTA even though recurrence is frequent and may occur outside transplant criteria. Data on non-transplantable recurrence (NTR) following PTA are lacking, however. We therefore investigated the incidence and predictors of NTR among 213 potentially transplantable patients (cirrhosis, 93%; Child-Pugh A, 98.6%; alcohol-related disease, 62%) with ≤3-cm HCC(s) treated by PTA, to stratify them according to their NTR risk and to improve treatment allocation. During follow-up (median: 41.2 months), NTR occurred in 18.3% (alpha-fetoprotein [AFP] model) and 23% (Milan) patients. NTR prediction with competing-risk analysis and internal validation revealed AFP > 100 ng/ml (subdistribution hazard ratio: 7.28; p < 0.001) and prior HCC (subdistribution hazard ratio: 3.77; p = 0.002) as independent predictors (Harrell's C: 0.76). Based on this model using the AFP score (equally predictive within Milan criteria), patients were stratified into three NTR risk categories: HCC-naïve with AFP < 100 ng/ml (low risk, n = 108 of 213), non-HCC naïve with AFP < 100 ng/ml (intermediate risk, n = 92 of 213), AFP ≥ 100 ng/ml (high risk, n = 13 of 213), among whom 9.3% (3.7% [Milan]), 22.8% (25% [Milan]), and 61.5% (38/5% [Milan]) presented NTR (p < 0.001). Median recurrence-free survival was 4.6, 14.5, and 43.4 months, respectively, in high-risk, intermediate-risk, and low-risk categories (p < 0.001). Median overall survival, which was 19.1 months in high-risk patients, was not reached otherwise (p < 0.001). Conclusion: Overall, PTA of ≤3-cm HCC incurs a low NTR risk. Simple and noninvasive predictors (HCC naivety, AFP) accurately stratified patients' risk of NTR, and should help to improve treatment allocation. Patients with AFP ≥ 100 ng/ml have a high risk of NTR, poor recurrence-free survival, and overall survival. Further studies evaluating preemptive transplantation or adjuvant/neoadjuvant strategies are highly needed in this small patient subset.
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Affiliation(s)
- Cecilia Gozzo
- Department of RadiologySt‐Eloi University HospitalMontpellierFrance
- Radiodiagnostic and Radiotherapy Unit, Department of Medical and Surgical Sciences and Advanced Technologies “GF Ingrassia”University of CataniaCataniaItaly
| | - Margaux Hermida
- Department of RadiologySt‐Eloi University HospitalMontpellierFrance
| | - Astrid Herrero
- Department of Liver SurgerySt‐Eloi University HospitalMontpellierFrance
| | - Fabrizio Panaro
- Division of HBP Surgery & Transplantation, Department of SurgeryMontpellier University HospitalMontpellierFrance
| | | | | | - Eric Assenat
- Department of OncologySt‐Eloi University HospitalMontpellierFrance
- Department of HepatologySt‐Eloi University HospitalMontpellierFrance
| | - Chloé Guillot
- Department of RadiologySt‐Eloi University HospitalMontpellierFrance
| | - Carole Allimant
- Department of RadiologySt‐Eloi University HospitalMontpellierFrance
| | | | - Antonio Basile
- Radiodiagnostic and Radiotherapy Unit, Department of Medical and Surgical Sciences and Advanced Technologies “GF Ingrassia”University of CataniaCataniaItaly
| | | | - José Ursic‐Bedoya
- Department of Liver SurgerySt‐Eloi University HospitalMontpellierFrance
| | - Boris Guiu
- Department of RadiologySt‐Eloi University HospitalMontpellierFrance
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29
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Sidali S, Trépo E, Sutter O, Nault J. New concepts in the treatment of hepatocellular carcinoma. United European Gastroenterol J 2022; 10:765-774. [PMID: 35975347 PMCID: PMC9486494 DOI: 10.1002/ueg2.12286] [Citation(s) in RCA: 56] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Accepted: 07/25/2022] [Indexed: 12/11/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death and occurs mainly in the context of chronic liver disease at cirrhosis stage. The Barcelona Clinic Liver Cancer classification, first established in 1999, is the most commonly used staging system for HCC in Western countries that link tumor burden, liver function and performance status with prognosis and therapeutic management. Since the first publication of this classification, it has been implemented in several clinical guidelines and recent major therapeutic advances in the management of HCC have modified the therapeutic landscape of HCC. Accordingly, an updated version was recently published in 2022, incorporating an expert clinical decision-making component and the concept of treatment stage migration. This update also introduces the positive results of recent randomized clinical trials, and introduces atezolizumab/bevacizumab (A/B) as a first-line combination regimen for patients with advanced HCC. Finally, the complexity of the management of patients with HCC highlights the need for a multidisciplinary approach including input from hepatology, surgery, radiology, medical oncology, and radiation oncology.
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Affiliation(s)
- Sabrina Sidali
- Université de ParisHôpitaux de Paris, Hôpital BeaujonService D’HépatologieDMU DIGESTClichyFrance
- Centre de Recherche des CordeliersSorbonne UniversitéInsermUniversité de ParisFunctional Genomics of Solid TumorsEquipe Labellisée Ligue Nationale Contre le CancerLabex OncoImmunologyParisFrance
| | - Eric Trépo
- Department of Gastroenterology, Hepatopancreatology and Digestive OncologyCUB Hôpital ErasmeUniversité Libre de BruxellesBrusselsBelgium
- Laboratory of Experimental GastroenterologyUniversité Libre de BruxellesBrusselsBelgium
| | - Olivier Sutter
- Interventional Radiology UnitHôpital AvicenneHôpitaux Universitaires Paris‐Seine‐Saint‐DenisAssistance‐Publique Hôpitaux de ParisBobignyFrance
| | - Jean‐Charles Nault
- Centre de Recherche des CordeliersSorbonne UniversitéInsermUniversité de ParisFunctional Genomics of Solid TumorsEquipe Labellisée Ligue Nationale Contre le CancerLabex OncoImmunologyParisFrance
- Liver UnitHôpital AvicenneHôpitaux Universitaires Paris‐Seine‐Saint‐DenisAssistance‐Publique Hôpitaux de ParisBobignyFrance
- Unité de Formation et de Recherche Santé Médecine et Biologie HumaineUniversité Paris 13Communauté D’Universités et Etablissements Sorbonne Paris CitéParisFrance
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30
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Zhang N, Zheng J, Wu Y, Lv J, Zhang S, Zhang Y, Jiang W, Song T, Kim V, Tohme S, Liu T, Zhang W, Gu J, Wang Z, Suo Y, Wang S, Li W, Zhang L, Xie Y, Zhou Y, Liu J, Qiu Y, Shen Z, Hao J, Geller D, Lu W. Comparison of the long-term outcomes of patients with hepatocellular carcinoma within the Milan criteria treated by ablation, resection, or transplantation. Cancer Med 2022; 12:2312-2324. [PMID: 36016484 PMCID: PMC9939228 DOI: 10.1002/cam4.5063] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 06/24/2022] [Accepted: 07/07/2022] [Indexed: 01/27/2023] Open
Abstract
BACKGROUND Liver transplantation (LT), resection (LR), and ablation (LA) are three curative-intent treatment options for patients with early hepatocellular carcinoma (HCC). We aimed to develop a prognostic calculator to compare the long-term outcomes following each of these therapies. METHODS A total of 976 patients with HCC within the Milan criteria who underwent LT, LR, and LA between 2009 and 2019 from four institutions were evaluated. Multistate competing risks prediction models for recurrence-free survival (RFS), recurrence within the Milan criteria (RWM), and HCC-specific survival (HSS) were derived to develop a prognostic calculator. RESULTS During a median follow-up of 51 months, 420 (43%) patients developed recurrence. In the multivariate analysis, larger tumor size, multinodularity, older age, male, higher alpha-fetoprotein (AFP), higher albumin-bilirubin (ALBI) grade, and the presence of portal hypertension were significantly associated with higher recurrence and decreased survival rates. The RFS and HSS were both significantly higher among patients treated by LT than by LR or LA and significantly higher between patients treated by LR than by LA (all p < 0.001). For multinodular HCC ≤3 cm, although LT had better RFS and HSS than LR or LA, LA was noninferior to LR. An online prognostic calculator was then developed based on the preoperative clinical factors that were independently associated with outcomes to evaluate RFS, RWM, and HSS at different time intervals for all three treatment options. CONCLUSIONS Although LT resulted in the best recurrence and survival outcomes, LR and LA also offered durable long-term alternatives. This prognostic calculator is a useful tool for clinicians to guide an informed and personalized discussion with patients based on their tumor biology and liver function.
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Affiliation(s)
- Ning‐Ning Zhang
- Department of Hepatobiliary Oncology, Liver Cancer Center, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for CancerTianjin Medical University Cancer Institute and Hospital, Tianjin Medical UniversityTianjinChina,Post‐Doctoral Research CenterNankai UniversityTianjinChina,Department of Hepatobiliary Surgery, Tianjin First Central Hospital, Tianjin Key Laboratory for Organ TransplantationTianjinChina
| | - Jian Zheng
- Department of SurgeryUniversity of Pittsburgh Medical CenterPittsburghPennsylvaniaUSA
| | - Ying Wu
- School of Statistics and Data ScienceNankai University, Key Laboratory for Medical Data Analysis and Statistical Research of TianjinTianjinChina
| | - Jia‐Yu Lv
- Department of HepatologyThe Third Central Hospital of TianjinTianjinChina
| | - Shu‐Wen Zhang
- Department of Hepatobiliary Oncology, Liver Cancer Center, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for CancerTianjin Medical University Cancer Institute and Hospital, Tianjin Medical UniversityTianjinChina
| | - Ya‐Min Zhang
- Department of Hepatobiliary Surgery, Tianjin First Central Hospital, Tianjin Key Laboratory for Organ TransplantationTianjinChina
| | - Wen‐Tao Jiang
- Department of Liver Transplantation, Tianjin First Center Hospital, NHC Key Laboratory for Critical Care Medicine, Key Laboratory of Transplantation, Chinese Academy of Medical SciencesTianjinChina
| | - Tian‐Qiang Song
- Department of Hepatobiliary Surgery, Liver Cancer CenterTianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, National Human Genetic Resources Sharing Service PlatformTianjin Medical UniversityTianjinChina
| | - Victoria Kim
- Department of SurgeryUniversity of Pittsburgh Medical CenterPittsburghPennsylvaniaUSA
| | - Samer Tohme
- Department of SurgeryUniversity of Pittsburgh Medical CenterPittsburghPennsylvaniaUSA
| | - Tian Liu
- Department of Hepatobiliary Oncology, Liver Cancer Center, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for CancerTianjin Medical University Cancer Institute and Hospital, Tianjin Medical UniversityTianjinChina
| | - Wei Zhang
- Department of Hepatobiliary Surgery, Liver Cancer CenterTianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, National Human Genetic Resources Sharing Service PlatformTianjin Medical UniversityTianjinChina
| | - Jie Gu
- Department of Hepatobiliary Oncology, Liver Cancer Center, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for CancerTianjin Medical University Cancer Institute and Hospital, Tianjin Medical UniversityTianjinChina
| | - Ze‐Yu Wang
- Department of Hepatobiliary Oncology, Liver Cancer Center, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for CancerTianjin Medical University Cancer Institute and Hospital, Tianjin Medical UniversityTianjinChina
| | - Yu‐Hong Suo
- Department of Hepatobiliary Oncology, Liver Cancer Center, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for CancerTianjin Medical University Cancer Institute and Hospital, Tianjin Medical UniversityTianjinChina
| | - Shuai Wang
- Department of Hepatobiliary Oncology, Liver Cancer Center, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for CancerTianjin Medical University Cancer Institute and Hospital, Tianjin Medical UniversityTianjinChina
| | - Wang Li
- Department of Hepatobiliary Oncology, Liver Cancer Center, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for CancerTianjin Medical University Cancer Institute and Hospital, Tianjin Medical UniversityTianjinChina
| | - Li Zhang
- Department of Liver Transplantation, Tianjin First Center Hospital, NHC Key Laboratory for Critical Care Medicine, Key Laboratory of Transplantation, Chinese Academy of Medical SciencesTianjinChina
| | - Yan Xie
- Department of Liver Transplantation, Tianjin First Center Hospital, NHC Key Laboratory for Critical Care Medicine, Key Laboratory of Transplantation, Chinese Academy of Medical SciencesTianjinChina
| | - Yong‐He Zhou
- Tianjin Second People’s Hospital, Tianjin Medical Research Institute of Liver DiseaseTianjinChina
| | - Jian‐Yong Liu
- Tianjin Second People’s Hospital, Tianjin Medical Research Institute of Liver DiseaseTianjinChina
| | - Yi‐Bo Qiu
- Department of Hepatobiliary Oncology, Liver Cancer Center, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for CancerTianjin Medical University Cancer Institute and Hospital, Tianjin Medical UniversityTianjinChina
| | - Zhong‐Yang Shen
- Department of Liver Transplantation, Tianjin First Center Hospital, NHC Key Laboratory for Critical Care Medicine, Key Laboratory of Transplantation, Chinese Academy of Medical SciencesTianjinChina
| | - Ji‐Hui Hao
- Department of Pancreatic CancerTianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and TherapyTianjinChina
| | - David Geller
- Department of SurgeryUniversity of Pittsburgh Medical CenterPittsburghPennsylvaniaUSA
| | - Wei Lu
- Department of Hepatobiliary Oncology, Liver Cancer Center, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for CancerTianjin Medical University Cancer Institute and Hospital, Tianjin Medical UniversityTianjinChina
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31
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Feng ZH, Wang MD, Chen Z, Sun LY, Xu X, Kong QY, Chen ZX, Zeng YY, Liang YJ, Chen ZY, Wang H, Zhou YH, Chen TH, Yao LQ, Li C, Pawlik TM, Lau WY, Shen F, Yang T. Risk factors and long-term prognosis of beyond-Milan recurrence after hepatectomy for BCLC stage 0/A hepatocellular carcinoma: A large-scale multicenter study. Surgery 2022; 172:1147-1155. [PMID: 35868902 DOI: 10.1016/j.surg.2022.05.023] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 05/18/2022] [Accepted: 05/20/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND Data on recurrence are important to inform surveillance and improve long-term surgical outcomes for patients with hepatocellular carcinoma. We sought to identify risk factors and long-term prognosis among patients who experienced beyond-Milan recurrence after hepatectomy for early-stage hepatocellular carcinoma. METHODS Patients who underwent hepatectomy for Barcelona Clinic Liver Cancer stage 0/A hepatocellular carcinoma were identified from a multi-institutional database. Predictors of beyond-Milan recurrence and risk factors associated with post-recurrence survival among patients with beyond-Milan recurrence were assessed using univariate and multivariate Cox regression analyses. RESULTS Among 753 patients (median follow-up, 51.8 months), 138 (18.3%) developed beyond-Milan recurrence. Regular surveillance (interval follow-up ≤3 months within 1 year and ≤6 months in subsequent years after surgery) was not carried out for 53 (38.4%) patients who developed beyond-Milan recurrence. On multivariate analysis, increased risk of beyond-Milan recurrence was independently associated with preoperative alpha-fetoprotein level >400 ng/mL, tumor size >5.0 cm, multifocal disease, microvascular invasion, and no/irregular recurrence surveillance. Median post-recurrence survival among patients with beyond-Milan recurrence was only 8.4 months (95% confidence interval: 7.0-9.8 months). Among patients who developed beyond-Milan recurrence, Child-Pugh grade B/C, early recurrence within 1 year after surgery, macrovascular invasion/distant metastasis, and noncurative treatment of recurrence were independent risk factors associated with worse post-recurrence survival. CONCLUSION Nearly 1 in 5 patients developed beyond-Milan recurrence after hepatectomy for early-stage hepatocellular carcinoma. Patients with beyond-Milan recurrence had a median survival of less than 1 year after diagnosis of the recurrence. Regular surveillance is an important and actionable measure to decrease beyond-Milan recurrence and, in turn, improve long-term survival among patients treated with hepatectomy for hepatocellular carcinoma.
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Affiliation(s)
- Zi-Han Feng
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China; Department of General Surgery, Cancer Center, Division of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, China; Department of Hepatobiliary Surgery, Affiliated Hospital of Nantong University, China
| | - Ming-Da Wang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Zhong Chen
- Department of Hepatobiliary Surgery, Affiliated Hospital of Nantong University, China
| | - Li-Yang Sun
- Department of General Surgery, Cancer Center, Division of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, China
| | - Xiao Xu
- Department of Hepatobiliary Surgery, Affiliated Hospital of Nantong University, China
| | - Qing-Yu Kong
- Department of Hepatobiliary Surgery, Affiliated Hospital of Nantong University, China
| | - Zi-Xiang Chen
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Yong-Yi Zeng
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital, Fujian Medical University, Fuzhou, China
| | - Ying-Jian Liang
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Harbin Medical University, China
| | - Zhi-Yu Chen
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Hong Wang
- Department of General Surgery, Liuyang People's Hospital, China
| | - Ya-Hao Zhou
- Department of Hepatobiliary Surgery, Pu'er People's Hospital, China
| | - Ting-Hao Chen
- Department of General Surgery, Ziyang First People's Hospital, China
| | - Lan-Qing Yao
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Chao Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Timothy M Pawlik
- Department of Surgery, Ohio State University, Wexner Medical Center, Columbus, OH
| | - Wan Yee Lau
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China; Faculty of Medicine, the Chinese University of Hong Kong, Shatin, Hong Kong, SAR, China
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China; Eastern Hepatobiliary Clinical Research Institute, Third Affiliated Hospital of Navy Medical University, Shanghai, China.
| | - Tian Yang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China; Department of General Surgery, Cancer Center, Division of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, China; Eastern Hepatobiliary Clinical Research Institute, Third Affiliated Hospital of Navy Medical University, Shanghai, China.
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Guerrini GP, Esposito G, Olivieri T, Magistri P, Ballarin R, Di Sandro S, Di Benedetto F. Salvage versus Primary Liver Transplantation for Hepatocellular Carcinoma: A Twenty-Year Experience Meta-Analysis. Cancers (Basel) 2022; 14:3465. [PMID: 35884526 PMCID: PMC9320001 DOI: 10.3390/cancers14143465] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 07/04/2022] [Accepted: 07/12/2022] [Indexed: 02/04/2023] Open
Abstract
(1) Background: Primary liver transplantation (PLT) for HCC represents the ideal treatment. However, since organ shortage increases the risk of drop-out from the waiting list for tumor progression, a new surgical strategy has been developed: Salvage Liver Transplantation (SLT) can be offered as an additional curative strategy for HCC recurrence after liver resection. The aim of this updated meta-analysis is to compare surgical and long-term outcomes of SLT versus PLT for HCC. (2) Materials and Methods: A systematic review and meta-analysis was conducted using the published papers comparing SLT and PLT up to January 2022. (3) Results: 25 studies describing 11,275 patients met the inclusion criteria. The meta-analysis revealed no statistical difference in intraoperative blood loss, overall vascular complications, retransplantation rate, and hospital stay in the SLT group compared with the PLT group. However, the SLT group showed a slightly significant lower 5-year OS rate and 5-year disease-free survival rate. (4) Conclusion: meta-analysis advocates the relative safety and feasibility of both Salvage LT and Primary LT strategies. Specifically, SLT seems to have comparable surgical outcomes but slightly poorer long-term survival than PLT.
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Affiliation(s)
- Gian Piero Guerrini
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, Policlinico Modena Hospital, Azienda Ospedaliero Universitaria di Modena, Via del Pozzo 71, 41125 Modena, Italy; (G.E.); (T.O.); (P.M.); (R.B.); (S.D.S.); (F.D.B.)
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Ji J, Yang W, Shi HB, Liu S, Zhou WZ. Transcatheter arterial chemoembolization alone versus combined with microwave ablation for recurrent small hepatocellular carcinoma after resection: a retrospective comparative study. BMC Gastroenterol 2022; 22:321. [PMID: 35768773 PMCID: PMC9241260 DOI: 10.1186/s12876-022-02387-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Accepted: 06/13/2022] [Indexed: 11/30/2022] Open
Abstract
Purpose To compare the efficacy and safety of transcatheter arterial chemoembolization combined with microwave ablation (TACE–MWA) versus TACE alone for the treatment of recurrent small hepatocellular carcinoma (sHCC) after resection. Materials and methods From June 2015 to January 2020, a total of 45 patients with recurrent sHCC (size ≤ 3 cm) treated by TACE–MWA or TACE were included in this study. The radiological response at 1-, 3-, 6-month after initial treatment [modified Response Evaluation Criteria in Solid Tumors (mRECIST)], progression-free survival (PFS), overall survival (OS), and complications were evaluated. Results The TACE–MWA group showed better 1-, 3-, 6-month tumor response rates than TACE group. The corresponding 1-, 3-, and 5-year PFS rates were 76.5%, 70.6%, and 70.6% for the TACE–MWA group, and 56.1%, 15.0%, and 15.0% for the TACE group (P = 0.003). The 1-, 3-, and 5-year OS rates were 100.0%, 82.1%, and 61.5% for the TACE–MWA group, and 89.0%, 58.1%, and 50.8% for the TACE group (P = 0.389), respectively. Moreover, no major complications related to treatment were observed in either of the groups. Compared with the TACE group, the TACE–MWA group had a significantly lower number of re-TACE sessions (P = 0.003). Conclusions Although TACE alone provides equivalent effectiveness for recurrent sHCC in terms of OS rates, TACE–MWA had better 1-, 3-, 6-month tumor response rates and may prolong tumor PFS time.
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Affiliation(s)
- Jie Ji
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Gulou District, Nanjing, 210029, China
| | - Wei Yang
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Gulou District, Nanjing, 210029, China
| | - Hai-Bin Shi
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Gulou District, Nanjing, 210029, China
| | - Sheng Liu
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Gulou District, Nanjing, 210029, China
| | - Wei-Zhong Zhou
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Gulou District, Nanjing, 210029, China.
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Hatzidakis A, Müller L, Krokidis M, Kloeckner R. Local and Regional Therapies for Hepatocellular Carcinoma and Future Combinations. Cancers (Basel) 2022; 14:cancers14102469. [PMID: 35626073 PMCID: PMC9139740 DOI: 10.3390/cancers14102469] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Revised: 05/10/2022] [Accepted: 05/11/2022] [Indexed: 02/08/2023] Open
Abstract
Simple Summary Percutaneous interventional radiological techniques offer many alternatives for treatment of Hepatocellular Carcinoma (HCC) using local anesthesia and sedation. These methods aim to destroy the malignant tumors locally without affecting the non-malignant liver. In this way, complications are kept low and patient recovery is quick. Indications depend on tumor size, type and stage, as well as patient’s condition, liver function and co-morbidities. In recent years, a lot of research has been made in combining such approaches with immune therapy, but there is still much work to be done. This manuscript tries to analyze where we stand today and explain, using a comprehensive algorithm, the treatment options for each different clinical condition. Abstract Background: Hepatocellular carcinoma (HCC) can be treated by local and regional methods of percutaneous interventional radiological techniques. Indications depend on tumor size, type and stage, as well as patient’s condition, liver function and co-morbidities. According to international classification systems such as Barcelona Clinic Liver Cancer (BCLC) classification, very early, early or intermediate staged tumors can be treated either with ablative methods or with transarterial chemoembolization (TACE), depending on tumor characteristics. The combination of both allows for individualized forms of treatment with the ultimate goal of improving response and survival. In recent years, a lot of research has been carried out in combining locoregional approaches with immune therapy. Although recent developments in systemic treatment, especially immunotherapy, seem quite promising and have expanded possible combined treatment options, there is still not enough evidence in their favor. The aim of this review is to provide a comprehensive up-to-date overview of all these techniques, explaining indications, contraindications, technical problems, outcomes, results and complications. Moreover, combinations of percutaneous treatment with each other or with immunotherapy and future options will be discussed. Use of all those methods as down-staging or bridging solutions until surgery or transplantation are taken into consideration will also be reviewed. Conclusion: Local and regional therapies remain a mainstay of curative and palliative treatment of patients with HCC. Currently, evidence on potential combination of the local and regional treatment options with each other as well as with other treatment modalities is growing and has the potential to further individualize HCC therapy. To identify the most suitable treatment option out of these new various options, a repeated interdisciplinary discussion of each case by the tumor board is of utmost importance.
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Affiliation(s)
- Adam Hatzidakis
- Department of Radiology, AHEPA University Hospital of Thessaloniki, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
- Correspondence:
| | - Lukas Müller
- Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany; (L.M.); (R.K.)
| | - Miltiadis Krokidis
- 1st Department of Radiology, Areteion Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece;
| | - Roman Kloeckner
- Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany; (L.M.); (R.K.)
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35
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Zhang XF, Xue F, Bagante F, Ratti F, Marques HP, Silva S, Soubrane O, Lam V, Poultsides GA, Popescu I, Grigorie R, Alexandrescu S, Martel G, Workneh A, Guglielmi A, Hugh T, Aldrighetti L, Lv Y, Pawlik TM. Non-transplantable Recurrence After Resection for Transplantable Hepatocellular Carcinoma: Implication for Upfront Treatment Choice. J Gastrointest Surg 2022; 26:1021-1029. [PMID: 34797558 DOI: 10.1007/s11605-021-05206-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Accepted: 11/13/2021] [Indexed: 01/31/2023]
Abstract
OBJECTIVES To identify the preoperative risk factors for prediction of non-transplantable recurrence (NTR) after tumor resection for early-stage hepatocellular carcinoma (HCC) to assist in patient selection relative to upfront liver resection (LR) versus liver transplantation (LT). METHODS Patients who underwent curative resection for transplantable HCC and chronic liver disease were identified from an international multi-institutional database. NTR was defined as recurrence beyond the Milan or UCSF criteria, and the preoperative risk factors of NTR were investigated. RESULTS Among 293 patients with transplantable HCC within Milan criteria and 320 within UCSF criteria, 113 (38.6%) and 131 (40.9%) patients developed tumor recurrence, respectively. Among patients who recurred, NTR was present in 32 (28.3%) patients within Milan and 35 (26.7%) within UCSF criteria. When either Milan or UCSF criteria was adopted, three preoperative risk factors including liver cirrhosis, tumor size > 3 cm, and multiple lesions were consistently identified as risk factors associated with NTR after curative resection. By summing up the three factors, a scoring model was established and the incidence of NTR among patients with 0, 1 or ≥ 2 risk factors incrementally increased from 4.5%, 13.3% to 20.5% when Milan criteria was used, and from 4.5%, 12.4% to 33.9% when UCSF criteria was adopted. The model demonstrated very good discriminatory power on internal validation (n = 5,000) (c-index 0.689 for Milan criteria, and 0.715 for UCSF criteria). CONCLUSIONS Whereas surgical resection may be optimal first-line treatment for patients with no or one risk factor, patients with ≥ 2 risk factors should be considered for upfront liver transplantation.
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Affiliation(s)
- Xu-Feng Zhang
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.,Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, 395 W. 12th Ave., Suite 670, Columbus, OH, USA
| | - Feng Xue
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Fabio Bagante
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, 395 W. 12th Ave., Suite 670, Columbus, OH, USA.,Department of Surgery, University of Verona, Verona, Italy
| | | | - Hugo P Marques
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | - Silvia Silva
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | - Olivier Soubrane
- Department of Hepatobiliopancreatic Surgery, APHP, Beaujon Hospital, Clichy, France
| | - Vincent Lam
- Department of Surgery, Westmead Hospital, Sydney, Australia
| | | | - Irinel Popescu
- Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania
| | - Razvan Grigorie
- Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania
| | | | | | - Aklile Workneh
- Department of Surgery, University of Ottawa, Ottawa, Canada
| | | | - Tom Hugh
- Department of Surgery, School of Medicine, The University of Sydney, Sydney, Australia
| | | | - Yi Lv
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Timothy M Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, 395 W. 12th Ave., Suite 670, Columbus, OH, USA.
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36
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Reig M, Forner A, Rimola J, Ferrer-Fàbrega J, Burrel M, Garcia-Criado Á, Kelley RK, Galle PR, Mazzaferro V, Salem R, Sangro B, Singal AG, Vogel A, Fuster J, Ayuso C, Bruix J. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol 2022; 76:681-693. [PMID: 34801630 DOI: 10.1016/j.jhep.2021.11.018hxqeanni] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 11/15/2021] [Accepted: 11/17/2021] [Indexed: 01/29/2024]
Abstract
There have been major advances in the armamentarium for hepatocellular carcinoma (HCC) since the last official update of the Barcelona Clinic Liver Cancer prognosis and treatment strategy published in 2018. Whilst there have been advances in all areas, we will focus on those that have led to a change in strategy and we will discuss why, despite being encouraging, data for select interventions are still too immature for them to be incorporated into an evidence-based model for clinicians and researchers. Finally, we describe the critical insight and expert knowledge that are required to make clinical decisions for individual patients, considering all of the parameters that must be considered to deliver personalised clinical management.
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Affiliation(s)
- Maria Reig
- BCLC Group, Liver Unit, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain.
| | - Alejandro Forner
- BCLC Group, Liver Unit, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
| | - Jordi Rimola
- BCLC Group, Radiology Department, CDI, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Joana Ferrer-Fàbrega
- BCLC Group, Surgery Department, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Marta Burrel
- BCLC Group, Vascular Department, CDI, Hospital Clinic of Barcelona, Barcelona University, University of Barcelona, Barcelona, Spain
| | - Ángeles Garcia-Criado
- BCLC Group, Radiology Department, CDI, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Robin K Kelley
- Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA
| | - Peter R Galle
- Department of Internal Medicine, Mainz University Medical Center, Mainz, Germany
| | - Vincenzo Mazzaferro
- Department of Oncology, University of Milan and HPB Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Riad Salem
- Department of Radiology, Section of Interventional Radiology, Northwestern University, Chicago, IL, USA
| | - Bruno Sangro
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain; Liver Unit, Clinica Universidad de Navarra, Pamplona, Spain
| | - Amit G Singal
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Arndt Vogel
- Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Germany
| | - Josep Fuster
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain; BCLC Group, Surgery Department, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Carmen Ayuso
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain; BCLC Group, Radiology Department, CDI, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Jordi Bruix
- BCLC Group, Liver Unit, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain.
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37
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Reig M, Forner A, Rimola J, Ferrer-Fàbrega J, Burrel M, Garcia-Criado Á, Kelley RK, Galle PR, Mazzaferro V, Salem R, Sangro B, Singal AG, Vogel A, Fuster J, Ayuso C, Bruix J. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol 2022; 76:681-693. [PMID: 34801630 DOI: 10.1016/j.jhep.2021.11.018'||'] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 11/15/2021] [Accepted: 11/17/2021] [Indexed: 01/29/2024]
Abstract
There have been major advances in the armamentarium for hepatocellular carcinoma (HCC) since the last official update of the Barcelona Clinic Liver Cancer prognosis and treatment strategy published in 2018. Whilst there have been advances in all areas, we will focus on those that have led to a change in strategy and we will discuss why, despite being encouraging, data for select interventions are still too immature for them to be incorporated into an evidence-based model for clinicians and researchers. Finally, we describe the critical insight and expert knowledge that are required to make clinical decisions for individual patients, considering all of the parameters that must be considered to deliver personalised clinical management.
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Affiliation(s)
- Maria Reig
- BCLC Group, Liver Unit, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain.
| | - Alejandro Forner
- BCLC Group, Liver Unit, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
| | - Jordi Rimola
- BCLC Group, Radiology Department, CDI, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Joana Ferrer-Fàbrega
- BCLC Group, Surgery Department, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Marta Burrel
- BCLC Group, Vascular Department, CDI, Hospital Clinic of Barcelona, Barcelona University, University of Barcelona, Barcelona, Spain
| | - Ángeles Garcia-Criado
- BCLC Group, Radiology Department, CDI, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Robin K Kelley
- Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA
| | - Peter R Galle
- Department of Internal Medicine, Mainz University Medical Center, Mainz, Germany
| | - Vincenzo Mazzaferro
- Department of Oncology, University of Milan and HPB Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Riad Salem
- Department of Radiology, Section of Interventional Radiology, Northwestern University, Chicago, IL, USA
| | - Bruno Sangro
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain; Liver Unit, Clinica Universidad de Navarra, Pamplona, Spain
| | - Amit G Singal
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Arndt Vogel
- Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Germany
| | - Josep Fuster
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain; BCLC Group, Surgery Department, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Carmen Ayuso
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain; BCLC Group, Radiology Department, CDI, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Jordi Bruix
- BCLC Group, Liver Unit, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain.
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38
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Reig M, Forner A, Rimola J, Ferrer-Fàbrega J, Burrel M, Garcia-Criado Á, Kelley RK, Galle PR, Mazzaferro V, Salem R, Sangro B, Singal AG, Vogel A, Fuster J, Ayuso C, Bruix J. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol 2022; 76:681-693. [PMID: 34801630 DOI: 10.1016/j.jhep.2021.11.018%' and 2*3*8=6*8 and 'nh7h'!='nh7h%] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 11/15/2021] [Accepted: 11/17/2021] [Indexed: 01/29/2024]
Abstract
There have been major advances in the armamentarium for hepatocellular carcinoma (HCC) since the last official update of the Barcelona Clinic Liver Cancer prognosis and treatment strategy published in 2018. Whilst there have been advances in all areas, we will focus on those that have led to a change in strategy and we will discuss why, despite being encouraging, data for select interventions are still too immature for them to be incorporated into an evidence-based model for clinicians and researchers. Finally, we describe the critical insight and expert knowledge that are required to make clinical decisions for individual patients, considering all of the parameters that must be considered to deliver personalised clinical management.
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Affiliation(s)
- Maria Reig
- BCLC Group, Liver Unit, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain.
| | - Alejandro Forner
- BCLC Group, Liver Unit, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
| | - Jordi Rimola
- BCLC Group, Radiology Department, CDI, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Joana Ferrer-Fàbrega
- BCLC Group, Surgery Department, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Marta Burrel
- BCLC Group, Vascular Department, CDI, Hospital Clinic of Barcelona, Barcelona University, University of Barcelona, Barcelona, Spain
| | - Ángeles Garcia-Criado
- BCLC Group, Radiology Department, CDI, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Robin K Kelley
- Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA
| | - Peter R Galle
- Department of Internal Medicine, Mainz University Medical Center, Mainz, Germany
| | - Vincenzo Mazzaferro
- Department of Oncology, University of Milan and HPB Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Riad Salem
- Department of Radiology, Section of Interventional Radiology, Northwestern University, Chicago, IL, USA
| | - Bruno Sangro
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain; Liver Unit, Clinica Universidad de Navarra, Pamplona, Spain
| | - Amit G Singal
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Arndt Vogel
- Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Germany
| | - Josep Fuster
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain; BCLC Group, Surgery Department, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Carmen Ayuso
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain; BCLC Group, Radiology Department, CDI, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Jordi Bruix
- BCLC Group, Liver Unit, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain.
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39
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Reig M, Forner A, Rimola J, Ferrer-Fàbrega J, Burrel M, Garcia-Criado Á, Kelley RK, Galle PR, Mazzaferro V, Salem R, Sangro B, Singal AG, Vogel A, Fuster J, Ayuso C, Bruix J. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol 2022; 76:681-693. [PMID: 34801630 DOI: 10.1016/j.jhep.2021.11.018' and 2*3*8=6*8 and 'b5hw'='b5hw] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 11/15/2021] [Accepted: 11/17/2021] [Indexed: 01/29/2024]
Abstract
There have been major advances in the armamentarium for hepatocellular carcinoma (HCC) since the last official update of the Barcelona Clinic Liver Cancer prognosis and treatment strategy published in 2018. Whilst there have been advances in all areas, we will focus on those that have led to a change in strategy and we will discuss why, despite being encouraging, data for select interventions are still too immature for them to be incorporated into an evidence-based model for clinicians and researchers. Finally, we describe the critical insight and expert knowledge that are required to make clinical decisions for individual patients, considering all of the parameters that must be considered to deliver personalised clinical management.
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Affiliation(s)
- Maria Reig
- BCLC Group, Liver Unit, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain.
| | - Alejandro Forner
- BCLC Group, Liver Unit, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
| | - Jordi Rimola
- BCLC Group, Radiology Department, CDI, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Joana Ferrer-Fàbrega
- BCLC Group, Surgery Department, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Marta Burrel
- BCLC Group, Vascular Department, CDI, Hospital Clinic of Barcelona, Barcelona University, University of Barcelona, Barcelona, Spain
| | - Ángeles Garcia-Criado
- BCLC Group, Radiology Department, CDI, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Robin K Kelley
- Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA
| | - Peter R Galle
- Department of Internal Medicine, Mainz University Medical Center, Mainz, Germany
| | - Vincenzo Mazzaferro
- Department of Oncology, University of Milan and HPB Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Riad Salem
- Department of Radiology, Section of Interventional Radiology, Northwestern University, Chicago, IL, USA
| | - Bruno Sangro
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain; Liver Unit, Clinica Universidad de Navarra, Pamplona, Spain
| | - Amit G Singal
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Arndt Vogel
- Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Germany
| | - Josep Fuster
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain; BCLC Group, Surgery Department, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Carmen Ayuso
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain; BCLC Group, Radiology Department, CDI, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Jordi Bruix
- BCLC Group, Liver Unit, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain.
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40
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Reig M, Forner A, Rimola J, Ferrer-Fàbrega J, Burrel M, Garcia-Criado Á, Kelley RK, Galle PR, Mazzaferro V, Salem R, Sangro B, Singal AG, Vogel A, Fuster J, Ayuso C, Bruix J. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol 2022; 76:681-693. [PMID: 34801630 DOI: 10.1016/j.jhep.2021.11.018" and 2*3*8=6*8 and "xwlv"="xwlv] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 11/15/2021] [Accepted: 11/17/2021] [Indexed: 01/29/2024]
Abstract
There have been major advances in the armamentarium for hepatocellular carcinoma (HCC) since the last official update of the Barcelona Clinic Liver Cancer prognosis and treatment strategy published in 2018. Whilst there have been advances in all areas, we will focus on those that have led to a change in strategy and we will discuss why, despite being encouraging, data for select interventions are still too immature for them to be incorporated into an evidence-based model for clinicians and researchers. Finally, we describe the critical insight and expert knowledge that are required to make clinical decisions for individual patients, considering all of the parameters that must be considered to deliver personalised clinical management.
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Affiliation(s)
- Maria Reig
- BCLC Group, Liver Unit, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain.
| | - Alejandro Forner
- BCLC Group, Liver Unit, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
| | - Jordi Rimola
- BCLC Group, Radiology Department, CDI, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Joana Ferrer-Fàbrega
- BCLC Group, Surgery Department, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Marta Burrel
- BCLC Group, Vascular Department, CDI, Hospital Clinic of Barcelona, Barcelona University, University of Barcelona, Barcelona, Spain
| | - Ángeles Garcia-Criado
- BCLC Group, Radiology Department, CDI, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Robin K Kelley
- Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA
| | - Peter R Galle
- Department of Internal Medicine, Mainz University Medical Center, Mainz, Germany
| | - Vincenzo Mazzaferro
- Department of Oncology, University of Milan and HPB Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Riad Salem
- Department of Radiology, Section of Interventional Radiology, Northwestern University, Chicago, IL, USA
| | - Bruno Sangro
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain; Liver Unit, Clinica Universidad de Navarra, Pamplona, Spain
| | - Amit G Singal
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Arndt Vogel
- Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Germany
| | - Josep Fuster
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain; BCLC Group, Surgery Department, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Carmen Ayuso
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain; BCLC Group, Radiology Department, CDI, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Jordi Bruix
- BCLC Group, Liver Unit, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain.
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Reig M, Forner A, Rimola J, Ferrer-Fàbrega J, Burrel M, Garcia-Criado Á, Kelley RK, Galle PR, Mazzaferro V, Salem R, Sangro B, Singal AG, Vogel A, Fuster J, Ayuso C, Bruix J. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol 2022; 76:681-693. [PMID: 34801630 DOI: 10.1016/j.jhep.2021.11.018'"] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 11/15/2021] [Accepted: 11/17/2021] [Indexed: 01/29/2024]
Abstract
There have been major advances in the armamentarium for hepatocellular carcinoma (HCC) since the last official update of the Barcelona Clinic Liver Cancer prognosis and treatment strategy published in 2018. Whilst there have been advances in all areas, we will focus on those that have led to a change in strategy and we will discuss why, despite being encouraging, data for select interventions are still too immature for them to be incorporated into an evidence-based model for clinicians and researchers. Finally, we describe the critical insight and expert knowledge that are required to make clinical decisions for individual patients, considering all of the parameters that must be considered to deliver personalised clinical management.
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Affiliation(s)
- Maria Reig
- BCLC Group, Liver Unit, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain.
| | - Alejandro Forner
- BCLC Group, Liver Unit, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
| | - Jordi Rimola
- BCLC Group, Radiology Department, CDI, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Joana Ferrer-Fàbrega
- BCLC Group, Surgery Department, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Marta Burrel
- BCLC Group, Vascular Department, CDI, Hospital Clinic of Barcelona, Barcelona University, University of Barcelona, Barcelona, Spain
| | - Ángeles Garcia-Criado
- BCLC Group, Radiology Department, CDI, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Robin K Kelley
- Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA
| | - Peter R Galle
- Department of Internal Medicine, Mainz University Medical Center, Mainz, Germany
| | - Vincenzo Mazzaferro
- Department of Oncology, University of Milan and HPB Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Riad Salem
- Department of Radiology, Section of Interventional Radiology, Northwestern University, Chicago, IL, USA
| | - Bruno Sangro
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain; Liver Unit, Clinica Universidad de Navarra, Pamplona, Spain
| | - Amit G Singal
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Arndt Vogel
- Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Germany
| | - Josep Fuster
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain; BCLC Group, Surgery Department, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Carmen Ayuso
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain; BCLC Group, Radiology Department, CDI, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Jordi Bruix
- BCLC Group, Liver Unit, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain.
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42
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Reig M, Forner A, Rimola J, Ferrer-Fàbrega J, Burrel M, Garcia-Criado Á, Kelley RK, Galle PR, Mazzaferro V, Salem R, Sangro B, Singal AG, Vogel A, Fuster J, Ayuso C, Bruix J. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol 2022; 76:681-693. [PMID: 34801630 DOI: 10.1016/j.jhep.2021.11.018����%2527%2522\'\"] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 11/15/2021] [Accepted: 11/17/2021] [Indexed: 01/29/2024]
Abstract
There have been major advances in the armamentarium for hepatocellular carcinoma (HCC) since the last official update of the Barcelona Clinic Liver Cancer prognosis and treatment strategy published in 2018. Whilst there have been advances in all areas, we will focus on those that have led to a change in strategy and we will discuss why, despite being encouraging, data for select interventions are still too immature for them to be incorporated into an evidence-based model for clinicians and researchers. Finally, we describe the critical insight and expert knowledge that are required to make clinical decisions for individual patients, considering all of the parameters that must be considered to deliver personalised clinical management.
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Affiliation(s)
- Maria Reig
- BCLC Group, Liver Unit, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain.
| | - Alejandro Forner
- BCLC Group, Liver Unit, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
| | - Jordi Rimola
- BCLC Group, Radiology Department, CDI, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Joana Ferrer-Fàbrega
- BCLC Group, Surgery Department, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Marta Burrel
- BCLC Group, Vascular Department, CDI, Hospital Clinic of Barcelona, Barcelona University, University of Barcelona, Barcelona, Spain
| | - Ángeles Garcia-Criado
- BCLC Group, Radiology Department, CDI, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Robin K Kelley
- Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA
| | - Peter R Galle
- Department of Internal Medicine, Mainz University Medical Center, Mainz, Germany
| | - Vincenzo Mazzaferro
- Department of Oncology, University of Milan and HPB Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Riad Salem
- Department of Radiology, Section of Interventional Radiology, Northwestern University, Chicago, IL, USA
| | - Bruno Sangro
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain; Liver Unit, Clinica Universidad de Navarra, Pamplona, Spain
| | - Amit G Singal
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Arndt Vogel
- Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Germany
| | - Josep Fuster
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain; BCLC Group, Surgery Department, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Carmen Ayuso
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain; BCLC Group, Radiology Department, CDI, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Jordi Bruix
- BCLC Group, Liver Unit, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain.
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Reig M, Forner A, Rimola J, Ferrer-Fàbrega J, Burrel M, Garcia-Criado Á, Kelley RK, Galle PR, Mazzaferro V, Salem R, Sangro B, Singal AG, Vogel A, Fuster J, Ayuso C, Bruix J. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol 2022; 76:681-693. [PMID: 34801630 PMCID: PMC8866082 DOI: 10.1016/j.jhep.2021.11.018] [Citation(s) in RCA: 2314] [Impact Index Per Article: 771.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 11/15/2021] [Accepted: 11/17/2021] [Indexed: 02/06/2023]
Abstract
There have been major advances in the armamentarium for hepatocellular carcinoma (HCC) since the last official update of the Barcelona Clinic Liver Cancer prognosis and treatment strategy published in 2018. Whilst there have been advances in all areas, we will focus on those that have led to a change in strategy and we will discuss why, despite being encouraging, data for select interventions are still too immature for them to be incorporated into an evidence-based model for clinicians and researchers. Finally, we describe the critical insight and expert knowledge that are required to make clinical decisions for individual patients, considering all of the parameters that must be considered to deliver personalised clinical management.
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Affiliation(s)
- Maria Reig
- BCLC Group, Liver Unit, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain.
| | - Alejandro Forner
- BCLC Group, Liver Unit, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
| | - Jordi Rimola
- BCLC Group, Radiology Department, CDI, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Joana Ferrer-Fàbrega
- BCLC Group, Surgery Department, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Marta Burrel
- BCLC Group, Vascular Department, CDI, Hospital Clinic of Barcelona, Barcelona University, University of Barcelona, Barcelona, Spain
| | - Ángeles Garcia-Criado
- BCLC Group, Radiology Department, CDI, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Robin K Kelley
- Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA
| | - Peter R Galle
- Department of Internal Medicine, Mainz University Medical Center, Mainz, Germany
| | - Vincenzo Mazzaferro
- Department of Oncology, University of Milan and HPB Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Riad Salem
- Department of Radiology, Section of Interventional Radiology, Northwestern University, Chicago, IL, USA
| | - Bruno Sangro
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain; Liver Unit, Clinica Universidad de Navarra, Pamplona, Spain
| | - Amit G Singal
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Arndt Vogel
- Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Germany
| | - Josep Fuster
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain; BCLC Group, Surgery Department, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Carmen Ayuso
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain; BCLC Group, Radiology Department, CDI, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Jordi Bruix
- BCLC Group, Liver Unit, ICMDM, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain.
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Treatment Strategy for Post-hepatectomy Recurrent Hepatocellular Carcinoma Within the Milan Criteria: Repeat Resection, Local Ablative Therapy or Transarterial Chemoembolization? Indian J Surg 2022. [DOI: 10.1007/s12262-022-03343-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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Preoperative predictors of non-transplantable recurrence after resection for early-stage hepatocellular carcinoma: application in an East Asian cohort. Updates Surg 2022; 74:891-897. [PMID: 35023038 DOI: 10.1007/s13304-021-01220-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Accepted: 12/06/2021] [Indexed: 10/19/2022]
Abstract
A French study found that three preoperative factors (i.e. alpha-fetoprotein (AFP) > 100 ng/ml, image-diagnosed tumor number > 1, and cirrhosis) could predict non-transplantable recurrence (NTR) after liver resection (LR) for early-stage hepatocellular carcinoma (HCC). We aimed to evaluate whether this model could be applicable in an East Asian cohort from a country in which the majority of patients undergo living donor liver transplantation (LT). This retrospective study enrolled consecutive patients who underwent LR for transplantable HCC between 2011 and 2018 in our institution. The occurrence of NTR after LR was analyzed in a competing risks analysis, with death and transplantable recurrence as competing events. A total of 309 patients were included. The five-year overall survival and recurrence-free survival were 79.0% and 51.4%, respectively (median follow-up: 32.0 months). Recurrence was noted in 94 (30.4%) patients. NTR was noted in 35 (11.3%) patients. Univariate analysis showed that cirrhosis (sub-distribution hazard ratio (SHR) = 2.301, 95% CI = 1.046-5.065; p = 0.038) and image-diagnosed tumor number > 1 (SHR = 2.32; 95% CI = 1.11-4.86; p = 0.026) were associated with NTR, whereas AFP > 100 ng/ml (SHR = 1.56; 95% CI = 0.59-4.10; p = 0.37) was not associated with NTR. In the presence of 0, 1, and 2 factors (i.e. cirrhosis or image-diagnosed tumor number > 1), the NTR rates were 7.2%, 10.8%, and 29.0%, respectively. The results showed that the French model was applicable to our cohort. In the presence of two factors (i.e. cirrhosis and image-diagnosed tumor number > 1), risks and benefits of upfront LT could be discussed with the patient and the living donor.
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Li L, Su Q, Yang H. Preoperative prediction of microvascular invasion in hepatocellular carcinoma: a radiomic nomogram based on MRI. Clin Radiol 2021; 77:e269-e279. [PMID: 34980458 DOI: 10.1016/j.crad.2021.12.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Accepted: 12/08/2021] [Indexed: 11/18/2022]
Abstract
AIM To develop a reliable model to predict microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC) by combining a large number of clinical and imaging examinations, especially the radiomic features of magnetic resonance imaging (MRI). MATERIALS AND METHODS Three hundred and one consecutive patients from two centres were enrolled. Least absolute shrinkage and selection operator (LASSO) regression was used to shrink the feature size, and logistic regression was used to construct a predictive radiomic signature. The ability of the nomogram to discriminate MVI in patients with HCC was evaluated using area under the curve (AUC) of receiver operating characteristics (ROC), accuracy, and calibration curves. RESULTS The radiomic signature showed a significant association with MVI (p<0.001 for all data sets). Other useful predictors of MVI included non-smooth tumour margin, internal arteries, and the alpha-fetoprotein (AFP) level. The nomogram demonstrated a strong prognostic capability in the training set and both validation sets, providing AUCs of 0.914 (95% confidence interval [CI] 0.853-0.956), 0.872 (95% CI: 0.757-0.946), and 0.881 (95% CI: 0.806-0.934), respectively. CONCLUSIONS The preoperative radiomic nomogram, incorporating clinical risk factors and a radiomic signature, could predict MVI in patients with HCC. The MRI-based radiomic-clinical model predicted the MVI of HCC effectively and was more efficient compared with the radiomic model or clinical model alone.
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Affiliation(s)
- L Li
- Department of Hepatobiliary Surgery, The People's Hospital of Qijiang, Chongqing, China
| | - Q Su
- Department of Hepatopancreatobiliary Surgery, The Affiliated Calmette Hospital of Kunming Medical University, The First People's Hospital of Kunming, Calmette Hospital Kunming, Yunnan Province, China.
| | - H Yang
- Department of Hepatobiliary Surgery, The People's Hospital of Qijiang, Chongqing, China.
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Why may citrate sodium significantly increase the effectiveness of transarterial chemoembolization in hepatocellular carcinoma? Drug Resist Updat 2021; 59:100790. [PMID: 34924279 DOI: 10.1016/j.drup.2021.100790] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 09/01/2021] [Accepted: 09/04/2021] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma (HCC) represents the third cause of cancer death in men worldwide, and its increasing incidence can be explained by the increasing occurrence of non-alcoholic steatohepatitis (NASH). HCC prognosis is poor, as its 5-year overall survival is approximately 18 % and most cases are diagnosed at an inoperable advanced stage. Moreover, tumor sensitivity to conventional chemotherapeutics (particularly to cisplatin-based regimen), trans-arterial chemoembolization (cTACE), tyrosine kinase inhibitors, anti-angiogenic molecules and immune checkpoint inhibitors is limited. Oncogenic signaling pathways, such as HIF-1α and RAS/PI3K/AKT, may provoke drug resistance by enhancing the aerobic glycolysis ("Warburg effect") in cancer cells. Indeed, this metabolism, which promotes cancer cell development and aggressiveness, also induces extracellular acidity. In turn, this acidity promotes the protonation of drugs, hence abrogating their internalization, since they are most often weakly basic molecules. Consequently, targeting the Warburg effect in these cancer cells (which in turn would reduce the extracellular acidification) could be an effective strategy to increase the delivery of drugs into the tumor. Phosphofructokinase-1 (PFK1) and its activator PFK2 are the main regulators of glycolysis, and they also couple the enhancement of glycolysis to the activation of key signaling cascades and cell cycle progression. Therefore, targeting this "Gordian Knot" in HCC cells would be of crucial importance. Here, we suggest that this could be achieved by citrate administration at high concentration, because citrate is a physiologic inhibitor of PFK1 and PFK2. As shown in various in vitro studies, including HCC cell lines, administration of high concentrations of citrate inhibits PFK1 and PFK2 (and consequently glycolysis), decreases ATP production, counteracts HIF-1α and PI3K/AKT signaling, induces apoptosis, and sensitizes cells to cisplatin treatment. Administration of high concentrations of citrate in animal models (including Ras-driven tumours) has been shown to effectively inhibit cancer growth, reverse cell dedifferentiation, and neutralize intratumor acidity, without apparent toxicity in animal studies. Citrate may also induce a rapid secretion of pro-inflammatory cytokines by macrophages, and it could favour the destruction of cancer stem cells (CSCs) sustaining tumor recurrence. Consequently, this "citrate strategy" could improve the tumor sensitivity to current treatments of HCC by reducing the extracellular acidity, thus enhancing the delivery of chemotherapeutic drugs into the tumor. Therefore, we propose that this strategy should be explored in clinical trials, in particular to enhance cTACE effectiveness.
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Involvement of Kynurenine Pathway in Hepatocellular Carcinoma. Cancers (Basel) 2021; 13:cancers13205180. [PMID: 34680327 PMCID: PMC8533819 DOI: 10.3390/cancers13205180] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 10/08/2021] [Accepted: 10/13/2021] [Indexed: 12/11/2022] Open
Abstract
Simple Summary The kynurenine pathway (KP) is a biochemical pathway that synthesizes the vital coenzyme, nicotinamide adenine dinucleotide (NAD+). In cancer, the KP is significantly activated, leading to tryptophan depletion and the production of downstream metabolites, which skews the immune response towards tumour tolerance. More specifically, advanced stage cancers that readily metastasize evidence the most dysregulation in KP enzymes, providing a clear link between the KP and cancer morbidity. Consequently, this provides the rationale for an attractive new drug discovery opportunity for adjuvant therapeutics targeting KP-mediated immune tolerance, which would greatly complement current pharmacological interventions. In this review, we summarize recent developments in the roles of the KP and clinical trials examining KP inhibition in liver cancer. Abstract As the second and third leading cancer-related death in men and the world, respectively, primary liver cancer remains a major concern to human health. Despite advances in diagnostic technology, patients with primary liver cancer are often diagnosed at an advanced stage. Treatment options for patients with advanced hepatocarcinoma (HCC) are limited to systemic treatment with multikinase inhibitors and immunotherapy. Furthermore, the 5-year survival rate for these late-stage HCC patients is approximately 12% worldwide. There is an unmet need to identify novel treatment options and/or sensitive blood-based biomarker(s) to detect this cancer at an early stage. Given that the liver harbours the largest proportion of immune cells in the human body, understanding the tumour–immune microenvironment has gained increasing attention as a potential target to treat cancer. The kynurenine pathway (KP) has been proposed to be one of the key mechanisms used by the tumour cells to escape immune surveillance for proliferation and metastasis. In an inflammatory environment such as cancer, the KP is elevated, suppressing local immune cell populations and enhancing tumour growth. In this review, we collectively describe the roles of the KP in cancer and provide information on the latest research into the KP in primary liver cancer.
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Xia W, Peng T, Guan R, Zhou Y, Zeng C, Lin Y, Wu Z, Tan H. Development of a novel prognostic nomogram for the early recurrence of liver cancer after curative hepatectomy. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:1541. [PMID: 34790747 PMCID: PMC8576734 DOI: 10.21037/atm-21-4837] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Accepted: 10/22/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is one of the most common malignant cancers worldwide. Curative resection is an effective treatment but HCC recurrence rates remain high. This study aimed to establish a novel prognostic nomogram to assess the risk of recurrence in patients following curative resection. METHODS A total of 410 patients undergoing HCC curative resection were recruited from the Guangdong Provincial People's Hospital (GDPH). The cohort was divided into a training group (n=291) and a validation group (n=97). The risk factors for HCC early recurrence within 1 year of curative hepatectomy were identified. Finally, a multivariate prognostic nomogram was developed and validated. RESULTS Age, tumor number, tumor capsule, portal vein tumor thrombi, pathological grade, vascular tumor emboli, activated partial thromboplastin time (APTT), and tumor size were identified as independent prognostic risk factors for HCC early recurrence within 1 year of curative hepatectomy. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.806 [95% confidence interval (CI): 0.755 to 0.857; P<0.001], and no AUC/ROC statistical difference was detected between the training and validation sets. CONCLUSIONS The nomogram effectively predicted postoperative HCC recurrence within 1 year after curative hepatectomy, which may be a useful tool for the postoperative treatment or follow up for HCC patients.
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Affiliation(s)
- Wuzheng Xia
- Department of Organ Transplant, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Tianyi Peng
- Department of Hepatobiliary Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Shantou University Medical College, Shantou, China
| | - Renguo Guan
- Department of Hepatobiliary Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Yu Zhou
- Department of Pancreatic Surgery, Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Cong Zeng
- Department of General Practice, Hospital of South China Normal University, Guangzhou, China
| | - Ye Lin
- Department of Hepatobiliary Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Zhongshi Wu
- Department of Hepatobiliary Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Hongmei Tan
- Day Operating Room, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
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Kim M, Kim T, Lee HY, Hong SY, Wang HJ, Kim BW. Risk Factors for Beyond Milan Recurrence After Hepatic Resection for Single Hepatocellular Carcinoma No Larger Than 5 Centimeters. Liver Transpl 2021; 27:1116-1129. [PMID: 33835642 DOI: 10.1002/lt.26070] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 03/29/2021] [Accepted: 03/30/2021] [Indexed: 12/22/2022]
Abstract
Hepatic resection (HR) is considered a treatment of choice for a single hepatocellular carcinoma (HCC) ≤5 cm in patients with preserved liver function. However, it is possible for these patients to develop a severe form of recurrence (beyond Milan recurrence [BMR] criteria). This recurrence could have been avoided if liver transplantation (LT) was performed primarily, as LT is believed to yield a more favorable oncological outcome compared with HR. The aim of this study was to determine the risk factors for BMR after HR and to verify whether primary LT can provide a more favorable outcome in patients with BMR risk factors. Data from 493 patients who underwent HR for HCC ≤5 cm between 1995 and 2016 were analyzed. Among them, 74 patients (15%) experienced BMR. The 10-year survival rate of patients with BMR was significantly low compared with that of patients without BMR (22.6% versus 79.8%; P < 0.01). In multivariate analysis, calculated hepatic venous pressure gradient ≥7 mm Hg and microvascular invasion were identified as the risk factors for BMR (P < 0.05). During the same period, 63 eligible patients underwent LT as a primary treatment for HCC ≤5 cm. No significant difference in long-term survival rate was observed when no risk factor for BMR was present in the HR and LT groups (85.5% versus 100%; P = 0.39). However, 10-year survival was poorer in the HR group in the presence of risk factors for BMR (60.6% versus 91.8%; P < 0.001). Among the patients with HCCs ≤5 cm, which are resectable and transplantable, LT is indicated when calculated hepatic venous pressure gradient ≥7 mm Hg and/or microvascular invasion is present.
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Affiliation(s)
- Mina Kim
- Department of Liver Transplantation and Hepatobiliary Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Taegyu Kim
- Department of Liver Transplantation and Hepatobiliary Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Hyun Young Lee
- Clinical Trial Center, Ajou University School of Medicine, Suwon, Korea
| | - Sung Yeon Hong
- Department of Liver Transplantation and Hepatobiliary Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Hee-Jung Wang
- Department of Liver Transplantation and Hepatobiliary Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Bong-Wan Kim
- Department of Liver Transplantation and Hepatobiliary Surgery, Ajou University School of Medicine, Suwon, Korea
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