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Zhang WZ, Chin KY, Zakaria R, Hassan NH. Strategies for Pain Management in Hepatocellular Carcinoma Patients Undergoing Transarterial Chemoembolisation: A Scoping Review of Current Evidence. Healthcare (Basel) 2025; 13:994. [PMID: 40361772 PMCID: PMC12071419 DOI: 10.3390/healthcare13090994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2025] [Revised: 04/08/2025] [Accepted: 04/08/2025] [Indexed: 05/15/2025] Open
Abstract
Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, with transarterial chemoembolisation (TACE) being a primary treatment for intermediate-stage disease. However, post-procedural pain remains a significant challenge due to inconsistent management practices and a lack of standardised protocols. This scoping review synthesises current evidence on pain management strategies in HCC patients undergoing TACE, evaluates their effectiveness, identifies practice gaps, and proposes optimisation strategies. Methods: A comprehensive database search according to the methodological approach given by Arksey and O'Malley with the aid of the PRISMA-ScR guidelines across Cochrane Library, Web of Science, CINAHL, PubMed, and Scopus was performed. The terms associated with pain, TACE, and liver cancer were included in the search strategy. Two independent researchers systematically screened study titles, abstracts, and full texts and extracted key study characteristics and approaches to pain management. Results: Of 1515 identified studies, 29 met the inclusion criteria. Most (72.7%) focused on pharmacological interventions, with dexamethasone and lidocaine being the most frequently investigated agents. Non-pharmacological approaches, including psychological interventions, physical therapies, music therapy, health education, and comprehensive nursing, were also reported. Pain was primarily assessed using the visual analogue scale (VAS) and numeric rating scale (NRS). Conclusions: Pharmacological interventions, particularly dexamethasone and lidocaine, remain the cornerstone of pain management in TACE, yet consensus on their optimal use is lacking. Non-pharmacological strategies provide complementary benefits. standardised, evidence-based pain management protocols integrating both approaches are needed. Future large-scale, multicentre trials are essential to establish the most effective strategies for optimising patient outcomes.
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Affiliation(s)
- Wei-Zheng Zhang
- Department of Nursing, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (W.-Z.Z.); (R.Z.)
| | - Kok-Yong Chin
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia;
| | - Roshaya Zakaria
- Department of Nursing, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (W.-Z.Z.); (R.Z.)
| | - Nor Haty Hassan
- Department of Nursing, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (W.-Z.Z.); (R.Z.)
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Peng Y, Shen S, Feng Y, Wen Z, Qin J, Lu W, Xiang B. Prognostic analysis and limited efficacy of adjuvant TACE in hepatocellular carcinoma following hepatectomy: a propensity score-matched study. Langenbecks Arch Surg 2025; 410:92. [PMID: 40053156 PMCID: PMC11889010 DOI: 10.1007/s00423-025-03663-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Accepted: 02/27/2025] [Indexed: 03/10/2025]
Abstract
BACKGROUND Postoperative adjuvant transarterial chemoembolization (PA-TACE) is proposed as a potentially effective treatment for hepatocellular carcinoma (HCC), but its benefits may be limited according to recent evidence. METHODS We analyzed clinicopathologic data from HCC patients who underwent hepatectomy between 2014 and 2019, categorizing them into two groups: surgery alone (non-PA-TACE) and PA-TACE. Propensity score matching (PSM) was used to adjust for selection bias. Cox proportional hazard models identified independent prognostic factors for overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meier estimates were used to compare RFS and OS rates between groups. RESULT PA-TACE was not an independent prognostic factor for RFS (entire cohort: hazard ratio [HR] 1.17, 95% confidence interval [CI] 0.92-1.50, p = 0.206; matched cohort: HR 1.10, 95% CI 0.79-1.54, p = 0.560) or OS (entire cohort: HR 1.15, 95% CI 0.87-1.52, p = 0.317; matched cohort: HR 0.96, 95% CI 0.68-1.36, p = 0.823). In the matched cohort, independent Predictors of worse OS included tumor diameter ≥ 5 cm, positive microvascular invasion (MVI), Edmondson-Steiner grade III-IV, pathological cirrhosis, and Barcelona Clinic Liver Cancer (BCLC) B/C stage. Predictors of worse RFS included tumor diameter ≥ 5 cm and Edmondson-Steiner grade III-IV. Only in the BCLC B/C stage subgroup, PA-TACE may improve OS compared to non-PA-TACE (HR 0.47, 95% CI 0.26-0.85, p = 0.011). CONCLUSION PA-TACE may not extend OS or RFS in HCC patients with BCLC 0/A stage, tumor diameter ≥ 5 cm, or MVI. PA-TACE should be administered with caution, even in HCC patients with BCLC B/C stage.
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Affiliation(s)
- Yi Peng
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
- Department of Gastrointestinal Surgery, Affiliated Nanhua Hospital, University of South China, Hengyang, China
| | - Shuang Shen
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Yifei Feng
- School of Basic Medical Sciences, Guangxi Medical University, Nanning, China
| | - Zhaochan Wen
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Jiayin Qin
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Wei Lu
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Bangde Xiang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China.
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Ministry of Education, Nanning, China.
- Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, China.
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Wei H, Zheng T, Zhang X, Zheng C, Jiang D, Wu Y, Lee JM, Bashir MR, Lerner E, Liu R, Wu B, Guo H, Chen Y, Yang T, Gong X, Jiang H, Song B. Deep learning-based 3D quantitative total tumor burden predicts early recurrence of BCLC A and B HCC after resection. Eur Radiol 2025; 35:127-139. [PMID: 39028376 PMCID: PMC11632001 DOI: 10.1007/s00330-024-10941-y] [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: 01/16/2024] [Revised: 05/15/2024] [Accepted: 06/16/2024] [Indexed: 07/20/2024]
Abstract
OBJECTIVES This study aimed to evaluate the potential of deep learning (DL)-assisted automated three-dimensional quantitative tumor burden at MRI to predict postoperative early recurrence (ER) of hepatocellular carcinoma (HCC). MATERIALS AND METHODS This was a single-center retrospective study enrolling patients who underwent resection for BCLC A and B HCC and preoperative contrast-enhanced MRI. Quantitative total tumor volume (cm3) and total tumor burden (TTB, %) were obtained using a DL automated segmentation tool. Radiologists' visual assessment was used to ensure the quality control of automated segmentation. The prognostic value of clinicopathological variables and tumor burden-related parameters for ER was determined by Cox regression analyses. RESULTS A total of 592 patients were included, with 525 and 67 patients assigned to BCLC A and B, respectively (2-year ER rate: 30.0% vs. 45.3%; hazard ratio (HR) = 1.8; p = 0.007). TTB was the most important predictor of ER (HR = 2.2; p < 0.001). Using 6.84% as the threshold of TTB, two ER risk strata were obtained in overall (p < 0.001), BCLC A (p < 0.001), and BCLC B (p = 0.027) patients, respectively. The BCLC B low-TTB patients had a similar risk for ER to BCLC A patients and thus were reassigned to a BCLC An stage; whilst the BCLC B high-TTB patients remained in a BCLC Bn stage. The 2-year ER rate was 30.5% for BCLC An patients vs. 58.1% for BCLC Bn patients (HR = 2.8; p < 0.001). CONCLUSIONS TTB determined by DL-based automated segmentation at MRI was a predictive biomarker for postoperative ER and facilitated refined subcategorization of patients within BCLC stages A and B. CLINICAL RELEVANCE STATEMENT Total tumor burden derived by deep learning-based automated segmentation at MRI may serve as an imaging biomarker for predicting early recurrence, thereby improving subclassification of Barcelona Clinic Liver Cancer A and B hepatocellular carcinoma patients after hepatectomy. KEY POINTS Total tumor burden (TTB) is important for Barcelona Clinic Liver Cancer (BCLC) staging, but is heterogenous. TTB derived by deep learning-based automated segmentation was predictive of postoperative early recurrence. Incorporating TTB into the BCLC algorithm resulted in successful subcategorization of BCLC A and B patients.
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Affiliation(s)
- Hong Wei
- Department of Radiology, Functional, and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
- Department of Radiology, Seoul National University Hospital, Seoul, 03080, Republic of Korea
| | - Tianying Zheng
- Department of Radiology, Functional, and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | | | - Chao Zheng
- Shukun Technology Co., Ltd, Beijing, 100102, China
| | - Difei Jiang
- Shukun Technology Co., Ltd, Beijing, 100102, China
| | - Yuanan Wu
- Big Data Research Center, University of Electronic Science and Technology of China, Chengdu, Sichuan, 610000, China
| | - Jeong Min Lee
- Department of Radiology, Seoul National University Hospital, Seoul, 03080, Republic of Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea
| | - Mustafa R Bashir
- Department of Radiology, Duke University Medical Center, Durham, NC, 27710, USA
- Center for Advanced Magnetic Resonance in Medicine, Duke University Medical Center, Durham, NC, 27705, USA
- Division of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, NC, 27710, USA
| | - Emily Lerner
- Department of Radiology, Duke University Medical Center, Durham, NC, 27710, USA
| | - Rongbo Liu
- Department of Radiology, Functional, and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Botong Wu
- Center for Biomedical Imaging Research, Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, 100102, China
| | - Hua Guo
- Center for Biomedical Imaging Research, Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, 100102, China
| | - Yidi Chen
- Department of Radiology, Functional, and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Ting Yang
- Department of Radiology, Functional, and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Xiaoling Gong
- Department of Radiology, Functional, and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Hanyu Jiang
- Department of Radiology, Functional, and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
| | - Bin Song
- Department of Radiology, Functional, and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
- Department of Radiology, Sanya People's Hospital, Sanya, Hainan, 572000, China.
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Huang J, Zhou Y, Wei S, Tang Y, Zhang Q, Tang Y, Huang W, Mo C, Dong X, Yang J. The impact of tumor burden score on prognosis in patients after radical resection of hepatocellular carcinoma: a single-center retrospective study. Front Oncol 2024; 14:1359017. [PMID: 39555448 PMCID: PMC11563962 DOI: 10.3389/fonc.2024.1359017] [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: 12/20/2023] [Accepted: 10/09/2024] [Indexed: 11/19/2024] Open
Abstract
Purpose This study examines the relationship between tumor burden score (TBS) and survival and recurrence following radical resection of hepatocellular carcinoma through a cohort study conducted in the Guangxi population of China. Methods This cohort study eventually recruited 576 HCC patients undergoing radical resection of HCC in the People's Hospital of Guangxi Zhuang Autonomous Region during 2013-2022. After determining the best threshold TBS, all cases were grouped to evaluate the relationship between TBS versus overall survival (OS) and cumulative recurrence. Using X-Tile software, the best threshold TBS to judge patient prognostic outcome following radical resection of HCC was 10.77. Results Kaplan-Meier curve analysis revealed that patients with high TBS showed considerably decreased OS relative to the control group, accompanied by an increased recurrence rate. According to multivariate Cox proportional regression, the patients with high TBS were associated with poorer OS (HR = 2.56, 95% CI 1.64-3.99, P < 0.001) and recurrence-free survival (RFS) (HR = 1.55, 95% CI 1.02-2.35, P < 0.001). Conclusion In patients undergoing radical resection for HCC, higher TBS was significantly related to shorter OS and RFS.
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Affiliation(s)
- Junzhang Huang
- Department of Hepatobiliary, Pancreas and Spleen Surgery, Guangxi Academy of Medical Sciences, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Ying Zhou
- Department of Hepatobiliary, Pancreas and Spleen Surgery, Guangxi Academy of Medical Sciences, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Suosu Wei
- Department of Scientific Cooperation of Guangxi Academy of Medical Sciences, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Yuntian Tang
- Department of Hepatobiliary, Pancreas and Spleen Surgery, Guangxi Academy of Medical Sciences, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Qiuhuan Zhang
- Department of Colorectal and Anal Surgery, People’s Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences, Nanning, China
| | - Yi Tang
- Department of Hepatobiliary, Pancreas and Spleen Surgery, Guangxi Academy of Medical Sciences, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Wei Huang
- Department of Hepatobiliary, Pancreas and Spleen Surgery, Guangxi Academy of Medical Sciences, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Chongde Mo
- Department of Hepatobiliary, Pancreas and Spleen Surgery, Guangxi Academy of Medical Sciences, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Xiaofeng Dong
- Department of Hepatobiliary, Pancreas and Spleen Surgery, Guangxi Academy of Medical Sciences, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Jianrong Yang
- Department of Hepatobiliary, Pancreas and Spleen Surgery, Guangxi Academy of Medical Sciences, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
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Zhu M, Li Y, Shen Q, Gong Z, Liu D. Sex hormone receptors, calcium-binding protein and Yap1 signaling regulate sex-dependent liver cell proliferation following partial hepatectomy. Dis Model Mech 2024; 17:dmm050900. [PMID: 39397390 PMCID: PMC11556313 DOI: 10.1242/dmm.050900] [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: 05/20/2024] [Accepted: 10/07/2024] [Indexed: 10/15/2024] Open
Abstract
Partial hepatectomy (PH) is commonly used to treat patients with hepatocellular carcinoma. The recovery of patients from PH depends on the initiation of liver regeneration, a process that mainly relies on liver cell proliferation. As sex affects the human liver regeneration progress, we investigated sex disparity in PH-induced liver regeneration in adult zebrafish. We found that, after PH, males began liver regeneration earlier than females in terms of liver cell proliferation and liver mass recovery, and this was associated with earlier activation of Yap1 signaling in male than female livers. We also found that androgen receptors regulated the sex-biased liver regeneration in a Yap1-dependent manner and that activated estrogen receptors are responsible for the later onset of female hepatocyte proliferation. Furthermore, we identified that S100A1, a calcium-binding protein, regulates the sex disparity in liver regeneration, as heterozygous S100A1 knockout inhibited Yap1 activity in male livers and delayed hepatocyte proliferation in males following PH. Thus, multiple pathways and/or their interplays contribute to the sex disparity in liver regeneration, suggesting that sex-biased therapeutic strategies are required for patients who have received PH-based therapies.
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Affiliation(s)
- Mingkai Zhu
- School of Life Science, Southern University of Science and Technology, Shenzhen 518055, China
- Department of Biological Sciences, National University of Singapore, Singapore 117558
| | - Yan Li
- Department of Biological Sciences, National University of Singapore, Singapore 117558
| | - Qiaosen Shen
- School of Life Science, Southern University of Science and Technology, Shenzhen 518055, China
| | - Zhiyuan Gong
- Department of Biological Sciences, National University of Singapore, Singapore 117558
| | - Dong Liu
- School of Life Science, Southern University of Science and Technology, Shenzhen 518055, China
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Wei X, Wang F, Liu Y, Li Z, Xue Z, Tang M, Chen X. A Machine Learning Model Based on Counterfactual Theory for Treatment Decision of Hepatocellular Carcinoma Patients. J Hepatocell Carcinoma 2024; 11:1675-1687. [PMID: 39229347 PMCID: PMC11370756 DOI: 10.2147/jhc.s470550] [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: 03/25/2024] [Accepted: 08/13/2024] [Indexed: 09/05/2024] Open
Abstract
Purpose To predict the efficacy of patients treated with hepatectomy and transarterial chemoembolization (TACE) based on machine learning models using clinical and radiomics features. Patients and Methods Patients with HCC whose first treatment was hepatectomy or TACE from June 2016 to July 2021 were collected in the retrospective cohort study. To ensure a causal effect of treatment effect and treatment modality, perfectly matched patients were obtained according to the principle of propensity score matching and used as an independent test cohort. Inverse probability of treatment weighting was used to control bias for unmatched patients, and the weighted results were used as the training cohort. Clinical characteristics were selected by univariate and multivariate analysis of cox proportional hazards regression, and radiomics features were selected using correlation analysis and random survival forest. The machine learning models (Deathhepatectomy and DeathTACE) were constructed to predict the probability of patient death after treatment (hepatectomy and TACE) by combining clinical and radiomics features, and an optimal treatment regimen was recommended. In addition, a prognostic model was constructed to predict the survival time of all patients. Results A total of 418 patients with HCC who received either hepatectomy (n=267, mean age, 58 years ± 11 [standard deviation]; 228 men) or TACE (n=151, mean age, 59 years ± 13 [standard deviation]; 127 men) were recruited. After constructing the machine learning models Deathhepatectomy and DeathTACE, patients were divided into the hepatectomy-preferred and TACE-preferred groups. In the hepatectomy-preferred group, hepatectomy had a significantly prolonged survival time than TACE (training cohort: P < 0.001; testing cohort: P < 0.001), and vise versa for the TACE-preferred group. In addition, the prognostic model yielded high predictive capability for overall survival. Conclusion The machine learning models could predict the outcomes difference between hepatectomy and TACE, and prognostic models could predict the overall survival for HCC patients.
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Affiliation(s)
- Xiaoqin Wei
- School of Medical Imaging, North Sichuan Medical College, Nanchong City, Sichuan Province, People’s Republic of China
| | - Fang Wang
- Department of Research and Development, Shanghai United Imaging Intelligence Co., Ltd, Shanghai, People’s Republic of China
| | - Ying Liu
- Department of Radiology, The First Affiliated Hospital of Chengdu Medical College, Chengdu City, Sichuan Province, People’s Republic of China
| | - Zeyong Li
- Department of Radiology, Bishan Hospital of Chongqing Medical University, ChongQing, People’s Republic of China
| | - Zhong Xue
- Department of Research and Development, Shanghai United Imaging Intelligence Co., Ltd, Shanghai, People’s Republic of China
| | - Mingyue Tang
- Department of Physics, School of Basic Medicine, North Sichuan Medical College, Nanchong, People’s Republic of China
| | - Xiaowen Chen
- School of Medical Imaging, North Sichuan Medical College, Nanchong City, Sichuan Province, People’s Republic of China
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Zhu M, Li Y, Liu D, Gong Z. Partial Hepatectomy Promotes the Development of KRASG12V-Induced Hepatocellular Carcinoma in Zebrafish. Cancers (Basel) 2024; 16:1793. [PMID: 38791872 PMCID: PMC11119731 DOI: 10.3390/cancers16101793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Revised: 04/30/2024] [Accepted: 05/04/2024] [Indexed: 05/26/2024] Open
Abstract
The purpose of this study was to investigate the effects of PH on the development of oncogenic krasG12V-induced HCC in zebrafish. The inducible HCC model in Tg(fabp10a:rtTA2s-M2; TRE2:EGFP-krasG12V) zebrafish was used. PH or sham surgery was performed before the induction of oncogenic krasG12V expression in the livers of transgenic zebrafish. Histological analysis was carried out to determine the progression of HCC and other HCC-associated features including hepatocyte proliferation, extracellular matrix production, and local oxidative stress. The similarity between the process of PH-induced liver regeneration and that of krasG12V-induced HCC development was further compared by RNA-Seq analysis. The results show that PH promotes the development of krasG12V-induced HCC in zebrafish possibly through enhancing neutrophil-mediated oxidative stress and promoting the upregulation of s100a1, and the downregulation of ribosome biogenesis.
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Affiliation(s)
- Mingkai Zhu
- Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore; (M.Z.); (Y.L.)
- School of Life Science, Southern University of Science and Technology, Shenzhen 518055, China
| | - Yan Li
- Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore; (M.Z.); (Y.L.)
| | - Dong Liu
- School of Life Science, Southern University of Science and Technology, Shenzhen 518055, China
| | - Zhiyuan Gong
- Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore; (M.Z.); (Y.L.)
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Hao X, Xu L, Lan X, Li B, Cai H. Impact of hepatic inflammation and fibrosis on the recurrence and long-term survival of hepatitis B virus-related hepatocellular carcinoma patients after hepatectomy. BMC Cancer 2024; 24:475. [PMID: 38622578 PMCID: PMC11017619 DOI: 10.1186/s12885-024-12187-9] [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: 12/03/2023] [Accepted: 03/26/2024] [Indexed: 04/17/2024] Open
Abstract
BACKGROUND Underlying liver disease is correlated with hepatocellular carcinoma (HCC) development in patients with hepatitis B virus (HBV) infection. However, the impact of hepatic inflammation and fibrosis on the patients' prognoses remains unclear. METHODS The clinicopathological data of 638 HBV-infected patients with early-stage HCC between 2017 and 2019 were prospectively collected. Hepatic inflammation and fibrosis were evaluated by experienced pathologists using the Scheuer score system. Survival analysis was analyzed using the Kaplan-Meier analysis. RESULTS Application of the Scheuer scoring system revealed that 50 (7.9%), 274 (42.9%), and 314 (49.2%) patients had minor, intermediate, and severe hepatic inflammation, respectively, and 125 (15.6%), 150 (23.5%), and 363 (56.9%) patients had minor fibrosis, advanced fibrosis, and cirrhosis, respectively. Patients with severe hepatitis tended to have a higher rate of HBeAg positivity, higher HBV-DNA load, elevated alanine aminotransferase (ALT) levels, and a lower proportion of capsule invasion (all Pp < 0.05). There were no significant differences in the recurrence-free and overall survival among the three groups (P = 0.52 and P = 0.66, respectively). Patients with advanced fibrosis or cirrhosis had a higher proportion of HBeAg positivity and thrombocytopenia, higher FIB-4, and larger tumor size compared to those with minor fibrosis (all P < 0.05). Patients with minor, advanced fibrosis, and cirrhosis had similar prognoses after hepatectomy (P = 0.48 and P = 0.70). The multivariate analysis results indicated that neither hepatic inflammation nor fibrosis was an independent predictor associated with prognosis. CONCLUSIONS For HBV-related HCC patients receiving antiviral therapy, hepatic inflammation and fibrosis had little impact on the post-hepatectomy prognosis.
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Affiliation(s)
- Xiangyong Hao
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, 610041, Chengdu, China
- Department of General Surgery, Gansu Provincial Hospital, 730000, Lanzhou, China
| | - Liangliang Xu
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, 610041, Chengdu, China
| | - Xiang Lan
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, 610041, Chengdu, China
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Chongqing Medical University, 400016, Chongqing, China
| | - Bo Li
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, 610041, Chengdu, China
| | - Hui Cai
- Department of General Surgery, Gansu Provincial Hospital, 730000, Lanzhou, China.
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Fan ZQ, Serenari M, Lv X, Schwartz M, Qiu W, Pawlik TM, Chen Z, Zhou YH, Wang XM, Chen TH, Li J, Zhang CW, Wang H, Zhang YM, Gu WM, Liang YJ, Diao YK, Yao LQ, Li C, Cescon M, Wang MD, Sun XD, Lau WY, Shen F, Yang T, Lv G. Prognostic significance of nodular number in patients undergoing hepatectomy of intermediate-stage hepatocellular carcinoma. Br J Surg 2024; 111:znae047. [PMID: 38456676 DOI: 10.1093/bjs/znae047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 08/03/2023] [Accepted: 02/06/2024] [Indexed: 03/09/2024]
Affiliation(s)
- Zhong-Qi Fan
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Centre, First Hospital of Jilin University, Changchun, Jilin, China
| | - Matteo Serenari
- Hepatobiliary Surgery and Transplant Unit, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Sant'Orsola-Malpighi Hospital, Bologna, Italy
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Xing Lv
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Centre, First Hospital of Jilin University, Changchun, Jilin, China
| | - Myron Schwartz
- Liver Cancer Program, Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Wei Qiu
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Centre, First Hospital of Jilin University, Changchun, Jilin, China
| | - Timothy M Pawlik
- Department of Surgery, Ohio State University, Wexner Medical Center, Columbus, Ohio, USA
| | - Zhong Chen
- Department of Hepatobiliary Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
| | - Ya-Hao Zhou
- Department of Hepatobiliary Surgery, Pu'er People's Hospital, Pu'er, Yunnan, China
| | - Xian-Ming Wang
- Department of General Surgery, First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, China
| | - Ting-Hao Chen
- Department of General Surgery, Ziyang First People's Hospital, Ziyang, Sichuan, China
| | - Jie Li
- Department of Hepatobiliary Surgery, Fuyang People's Hospital, Fuyang, Anhui, China
| | - Cheng-Wu Zhang
- Department of General Surgery, Cancer Centre, Division of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Hong Wang
- Department of General Surgery, Liuyang People's Hospital, Liuyang, Hunan, China
| | - Yao-Ming Zhang
- The Second Department of Hepatobiliary Surgery, Meizhou People's Hospital, Meizhou, Guangdong, China
| | - Wei-Min Gu
- The First Department of General Surgery, The Fourth Hospital of Harbin, Harbin, Heilongjiang, China
| | - Ying-Jian Liang
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Yong-Kang Diao
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Centre, First Hospital of Jilin University, Changchun, Jilin, China
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Lan-Qing Yao
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Centre, First Hospital of Jilin University, Changchun, Jilin, China
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Chao Li
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Centre, First Hospital of Jilin University, Changchun, Jilin, China
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Matteo Cescon
- Hepatobiliary Surgery and Transplant Unit, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Sant'Orsola-Malpighi Hospital, Bologna, Italy
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Ming-Da Wang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Xiao-Dong Sun
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Centre, First Hospital of Jilin University, Changchun, Jilin, China
| | - 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, New Territories, Hong Kong SAR, China
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Tian Yang
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Centre, First Hospital of Jilin University, Changchun, Jilin, China
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Guoyue Lv
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Centre, First Hospital of Jilin University, Changchun, Jilin, China
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10
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Haber PK, Krenzien F, Sarıbeyoğlu K, Pratschke J, Schöning W. Integrating the new systemic treatment landscape and surgical therapy in hepatocellular carcinoma. Turk J Surg 2024; 40:1-10. [PMID: 39036000 PMCID: PMC11257723 DOI: 10.47717/turkjsurg.2024.6375] [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: 03/07/2024] [Accepted: 03/12/2024] [Indexed: 07/23/2024]
Abstract
The treatment landscape of hepatocellular carcinoma has evolved rapidly within the last decade. Minimally-invasive techniques have reached a new level of safety, affording surgeons to pursue more aggressive treatment strategies to ultimately improve oncological outcomes. These procedures have been increasingly applied to treat patients with more progressed tumors and in select case even patients with advanced stage disease confined to the liver. Concomitantly, a dramatic increase in research into immunotherapy has altered the treatment paradigm in advanced disease stages, where the emerging treatment regimens can provide durable responses in a subset of the patient population for whom prognosis is dramatically improved. These treatments are now tested in early-stage disease to address the pressing unmet need of high recurrence rates after resection and in intermediate stage to complement the proven efficacy of intraarterial embolization in delaying progression. This review provides an in-depth discussion of these trends and describes how the treatment landscape has already changed and which impediments remain.
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Affiliation(s)
| | - Felix Krenzien
- Department of Surgery, Charité University, Berlin, Germany
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11
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Lee HA, Lee M, Yoo JJ, Chun HS, Park Y, Kim HY, Kim TH, Seo YS, Sinn DH. Identification of patients with favorable prognosis after resection in intermediate-stage-hepatocellular carcinoma. Int J Surg 2024; 110:1008-1018. [PMID: 38016294 PMCID: PMC10871631 DOI: 10.1097/js9.0000000000000941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 11/11/2023] [Indexed: 11/30/2023]
Abstract
BACKGROUNDS It is unclear which patients benefit from resection in intermediate-stage-hepatocellular carcinoma (HCC). The authors aimed to identify high-risk patients for early recurrence among patients with resectable intermediate-stage HCC. METHODS This multicenter retrospective study included patients who underwent resection or trans-arterial chemoembolization (TACE) for intermediate-stage HCC (2008-2019). Multivariable Cox proportional analysis was performed to identify high-risk patients when treated with resection. A prediction score for 2-year recurrence-free survival (RFS) was developed using the training cohort and validated. The 2-year RFS in each risk group was compared with that in TACE group, after propensity score matching (PSM). RESULTS A total of 1686 patients were included (480 and 1206 patients in the resection and TACE groups). During a median follow-up of 31.4 months, the 2-year RFS was significantly higher in the resection (47.7%) than in the TACE group (19.8%) [adjusted hazard ratio (aHR)=1.471, 95% CI: 1.199-1.803, P <0.001). On multivariate analysis, alpha-fetoprotein ≥5.0 ng/ml (aHR=0.202), ALBI grade ≥2 (aHR=0.709), tumor number ≥3 (aHR=0.404), and maximal tumor size ≥5 cm (aHR=0.323) were significantly associated with the lower risk of 2-year RFS in the resection group. The newly developed Surgery Risk score in BCLC-B (SR-B score) with four significant risk factors showed an area under the curve of 0.801 for the 2-year RFS and was validated. Based on the SR-B score, low-risk patients had a significantly higher 2-year RFS (training: aHR=5.834; validation: aHR=5.675) than high-risk patients (all P <0.001) did. In a PSM cohort, a low-risk resection group had a significantly higher (aHR=3.891); a high-risk resection group had a comparable 2-year RFS to those treated with TACE (aHR=0.816). CONCLUSIONS Resection may be beneficial for resectable intermediate-stage HCC based on the SR-B score.
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Affiliation(s)
- Han Ah Lee
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University Medical Center
- The Korean Liver Cancer Association
| | - Minjong Lee
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University Medical Center
- The Korean Liver Cancer Association
| | - Jeong-Ju Yoo
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Ho Soo Chun
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University Medical Center
| | - Yewan Park
- Department of Internal Medicine, Kyung Hee University Hospital
| | - Hwi Young Kim
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University Medical Center
| | - Tae Hun Kim
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University Medical Center
| | - Yeon Seok Seo
- Department of Internal Medicine, Korea University College of Medicine, Seoul
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine
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12
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Lin S, Song Z, Shen S. Letter to the editor. Comment on: A novel nomogram based on preoperative parameters to predict posthepatectomy liver failure in patients with hepatocellular carcinoma. Surgery 2024; 175:568-569. [PMID: 38008604 DOI: 10.1016/j.surg.2023.10.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Accepted: 10/24/2023] [Indexed: 11/28/2023]
Affiliation(s)
- Shuirong Lin
- Center of Hepato-Pancreato-biliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Zimin Song
- Center of Hepato-Pancreato-biliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Shunli Shen
- Center of Hepato-Pancreato-biliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China.
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13
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Wei H, Fu F, Jiang H, Wu Y, Qin Y, Wei H, Yang T, Wang M, Song B. Development and validation of the OSASH score to predict overall survival of hepatocellular carcinoma after surgical resection: a dual-institutional study. Eur Radiol 2023; 33:7631-7645. [PMID: 37191923 PMCID: PMC10598081 DOI: 10.1007/s00330-023-09725-7] [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: 11/15/2022] [Revised: 02/17/2023] [Accepted: 03/26/2023] [Indexed: 05/17/2023]
Abstract
OBJECTIVE To develop and validate a risk score based on preoperative clinical-radiological parameters for predicting overall survival (OS) in patients undergoing surgical resection for hepatocellular carcinoma (HCC). METHODS From July 2010 to December 2021, consecutive patients with surgically-proven HCC who underwent preoperative contrast-enhanced MRI were retrospectively enrolled. A preoperative OS risk score was constructed in the training cohort using a Cox regression model and validated in a propensity score-matched internal validation cohort and an external validation cohort. RESULTS A total of 520 patients were enrolled, among whom 210, 210, and 100 patients were from the training, internal validation, and external validation cohorts, respectively. Independent predictors for OS included incomplete tumor "capsule," mosaic architecture, tumor multiplicity, and serum alpha-fetoprotein, which were incorporated into the "OSASH score." The C-index the OSASH score was 0.85, 0.81, and 0.62 in the training, internal, and external validation cohorts, respectively. Using 32 as the cutoff point, the OSASH score stratified patients into prognostically distinct low- and high-risk groups among all study cohorts and six subgroups (all p < 0.05). Furthermore, patients with BCLC stage B-C HCC and OSASH-low risk achieved comparable OS to that of patients with BCLC stage 0-A HCC and OSASH-high risk in the internal validation cohort (5-year OS rates, 74.7 vs. 77.8%; p = 0.964). CONCLUSION The OSASH score may help predict OS in HCC patients undergoing hepatectomy and identify potential surgical candidates among those with BCLC stage B-C HCC. CLINICAL RELEVANCE STATEMENT By incorporating three preoperative MRI features and serum AFP, the OSASH score may help predict postsurgical overall survival in patients with hepatocellular carcinoma and identify potential surgical candidates among those with BCLC stage B and C HCC. KEY POINTS • The OSASH score incorporating three MRI features and serum AFP can be used to predict OS in HCC patients who received curative-intent hepatectomy. • The score stratified patients into prognostically distinct low- and high-risk strata in all study cohorts and six subgroups. • Among patients with BCLC stage B and C HCC, the score identified a subgroup of low-risk patients who achieved favorable outcomes after surgery.
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Affiliation(s)
- Hong Wei
- Department of Radiology, West China Hospital, Sichuan University, No. 37, GUOXUE Alley, Chengdu, 610041, Sichuan, China
| | - Fangfang Fu
- Department of Medical Imaging, Henan Provincial People's Hospital, No. 7, WEIWU Road, Zhengzhou, 450003, Henan, China
- Department of Medical Imaging, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Hanyu Jiang
- Department of Radiology, West China Hospital, Sichuan University, No. 37, GUOXUE Alley, Chengdu, 610041, Sichuan, China
| | - Yuanan Wu
- Big Data Research Center, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
| | - Yun Qin
- Department of Radiology, West China Hospital, Sichuan University, No. 37, GUOXUE Alley, Chengdu, 610041, Sichuan, China
| | - Huanhuan Wei
- Academy of Medical Sciences, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Ting Yang
- Department of Radiology, West China Hospital, Sichuan University, No. 37, GUOXUE Alley, Chengdu, 610041, Sichuan, China
| | - Meiyun Wang
- Department of Medical Imaging, Henan Provincial People's Hospital, No. 7, WEIWU Road, Zhengzhou, 450003, Henan, China.
- Department of Medical Imaging, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.
| | - Bin Song
- Department of Radiology, West China Hospital, Sichuan University, No. 37, GUOXUE Alley, Chengdu, 610041, Sichuan, China.
- Department of Radiology, Sanya People's Hospital, Sanya, Hainan, China.
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Chen L, Zhang N, Huang Y, Zhang Q, Fang Y, Fu J, Yuan Y, Chen L, Chen X, Xu Z, Li Y, Izawa H, Xiang C. Multiple Dimensions of using Mesenchymal Stem Cells for Treating Liver Diseases: From Bench to Beside. Stem Cell Rev Rep 2023; 19:2192-2224. [PMID: 37498509 DOI: 10.1007/s12015-023-10583-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/26/2023] [Indexed: 07/28/2023]
Abstract
Liver diseases impose a huge burden worldwide. Although hepatocyte transplantation has long been considered as a potential strategy for treating liver diseases, its clinical implementation has created some obvious limitations. As an alternative strategy, cell therapy, particularly mesenchymal stem cell (MSC) transplantation, is widely used in treating different liver diseases, including acute liver disease, acute-on-chronic liver failure, hepatitis B/C virus, autoimmune hepatitis, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, alcoholic liver disease, liver fibrosis, liver cirrhosis, and hepatocellular carcinoma. Here, we summarize the status of MSC transplantation in treating liver diseases, focusing on the therapeutic mechanisms, including differentiation into hepatocyte-like cells, immunomodulating function with a variety of immune cells, paracrine effects via the secretion of various cytokines and extracellular vesicles, and facilitation of homing and engraftment. Some improved perspectives and current challenges are also addressed. In summary, MSCs have great potential in the treatment of liver diseases based on their multi-faceted characteristics, and more accurate mechanisms and novel therapeutic strategies stemming from MSCs will facilitate clinical practice.
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Affiliation(s)
- Lijun Chen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, People's Republic of China
- Research Units of Infectious Disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou, Zhejiang, 310003, People's Republic of China
| | - Ning Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, People's Republic of China
- Research Units of Infectious Disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou, Zhejiang, 310003, People's Republic of China
| | - Yuqi Huang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, People's Republic of China
- Research Units of Infectious Disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou, Zhejiang, 310003, People's Republic of China
| | - Qi Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, People's Republic of China
- Research Units of Infectious Disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou, Zhejiang, 310003, People's Republic of China
| | - Yangxin Fang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, People's Republic of China
- Research Units of Infectious Disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou, Zhejiang, 310003, People's Republic of China
| | - Jiamin Fu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, People's Republic of China
- Research Units of Infectious Disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou, Zhejiang, 310003, People's Republic of China
| | - Yin Yuan
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, People's Republic of China
- Research Units of Infectious Disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou, Zhejiang, 310003, People's Republic of China
| | - Lu Chen
- Innovative Precision Medicine (IPM) Group, Hangzhou, Zhejiang, 311215, People's Republic of China
| | - Xin Chen
- Department of Hematology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310027, People's Republic of China
| | - Zhenyu Xu
- Innovative Precision Medicine (IPM) Group, Hangzhou, Zhejiang, 311215, People's Republic of China
| | - Yifei Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, People's Republic of China
- Research Units of Infectious Disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou, Zhejiang, 310003, People's Republic of China
| | - Hiromi Izawa
- Jingugaien Woman Life Clinic, Jingu-Gaien 3-39-5 2F, Shibuya-Ku, Tokyo, Japan
| | - Charlie Xiang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, People's Republic of China.
- Research Units of Infectious Disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou, Zhejiang, 310003, People's Republic of China.
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Li Z, Yu J, Li Y, Liu Y, Zhang M, Yang H, Du Y. Preoperative Radiomics Nomogram Based on CT Image Predicts Recurrence-Free Survival After Surgical Resection of Hepatocellular Carcinoma. Acad Radiol 2023; 30:1531-1543. [PMID: 36653278 DOI: 10.1016/j.acra.2022.12.039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 12/19/2022] [Accepted: 12/23/2022] [Indexed: 01/19/2023]
Abstract
RATIONALE AND OBJECTIVES To construct preoperative models based on CT radiomics, radiologic and clinical features to predict recurrence-free survival (RFS) after liver resection (LR) of BCLC 0 to B stage hepatocellular carcinoma (HCC) and to classify the prognosis. MATERIALS AND METHODS This study retrospectively analyzed 161 HCC patients who underwent radical LR. Two methods, the least absolute shrinkage and selection operator and random survival forest analysis, were performed for radiomics signature (RS) construction. Univariate and multivariate stepwise Cox regression analyses were performed to establish a combined nomogram (RCN) of RS and clinical parameters and a clinical nomogram (CN). The performance of the models was assessed comprehensively using Harrell's concordance index (C-index), the calibration curve, and decision curve analysis. The discrimination accuracy of the models was compared using integrated discrimination improvement index (IDI). The risk stratification effect was assessed with Kaplan-Meier survival analysis and subgroup analysis. RESULTS The RCN achieved a C-index of 0.792/0.758 in the training/validation set, which was higher than the CN, RS, and BCLC stage system. The discriminatory accuracy of the RCN was improved when compared to the CN, RS, and BCLC staging systems (IDI > 0). Decision curve analysis reflected the clinical net benefit of the RCN. The RCN allows risk stratification of patients in different clinical subgroups. CONCLUSION The integrated model combining RS and clinical factors can more effectively predict RFS after LR of BCLC 0 to B stage HCC patients and can effectively stratify the prognostic risk.
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Affiliation(s)
- Zeyong Li
- Department of Radiology, Bishan Hospital of Chongqing Medical University, Bishan, Chongqing, China
| | - Jialin Yu
- Department of Radiology, Xinqiao Hospital, Army Medical University (Third Military Medical University), Shapingba, Chongqing, China
| | - Yehan Li
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, 1 Maoyuan South Road, Nanchong, Sichuan, China, 637000
| | - Ying Liu
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, 1 Maoyuan South Road, Nanchong, Sichuan, China, 637000
| | - Manjing Zhang
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, 1 Maoyuan South Road, Nanchong, Sichuan, China, 637000
| | - Hanfeng Yang
- Department of Radiology and Interventional Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
| | - Yong Du
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, 1 Maoyuan South Road, Nanchong, Sichuan, China, 637000.
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Martin D, Smet H, Da Silva Costa AC, Halkic N, Uldry E, Tabrizian P, Schwartz M, Mahamid A, Goumard C, Scatton O, Perinel J, Adham M, Demartines N, Melloul E. Tumor burden in patients with early and intermediate-stage hepatocellular carcinoma undergoing liver resection: a retrospective multicenter study on clinical and oncological outcomes. HPB (Oxford) 2023; 25:836-844. [PMID: 37098458 DOI: 10.1016/j.hpb.2023.04.001] [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: 01/09/2023] [Revised: 03/31/2023] [Accepted: 04/03/2023] [Indexed: 04/27/2023]
Abstract
BACKGROUND According to the Barcelona Clinic Liver Cancer (BCLC) staging system, liver resection (LR) is recommended for early-stage (BCLC-A) hepatocellular carcinoma (HCC) but not for intermediate-stage (BCLC-B). This study aimed to assess the outcomes of LR in these patients using a subclassification tumour burden score (TBS). METHODS All consecutive patients that underwent LR for BCLC-A and BCLC-B HCC between 01/2010 and 12/2020 in 4 tertiary referral centers were included. Clinical outcomes and overall survival (OS) were assessed in relation to TBS and BCLC stages. RESULTS Among 612 patients included, 562 were classified as BCLC-A and 50 as BCLC-B. The incidence of overall postoperative complications (56.0 vs 41.5%, p = 0.053) and mortality (0 vs 1.6%, p = 1.000) were similar between BCLC-A and BCLC-B patients. OS was significantly higher for BCLC A/low TBS than BCLC B/low TBS (p = 0.009), while patients with medium and high TBS had similar OS, irrespective of BCLC stage (respectively p = 0.103 and p = 0.343). CONCLUSIONS Patients with medium and high TBS had comparable OS and DFS, irrespective of BCLC A or B stage, and postoperative morbidity was comparable. These results highlight the need for refinement of the BCLC staging system, and LR could be considered for selected intermediate stage (BCLC-B) according to the tumour burden.
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Affiliation(s)
- David Martin
- Department of Visceral Surgery, University Hospital CHUV, University of Lausanne (UNIL), Lausanne, Switzerland
| | - Héloïse Smet
- Department of Visceral Surgery, University Hospital CHUV, University of Lausanne (UNIL), Lausanne, Switzerland
| | - Ana Cristina Da Silva Costa
- Department of Visceral Surgery, University Hospital CHUV, University of Lausanne (UNIL), Lausanne, Switzerland
| | - Nermin Halkic
- Department of Visceral Surgery, University Hospital CHUV, University of Lausanne (UNIL), Lausanne, Switzerland
| | - Emilie Uldry
- Department of Visceral Surgery, University Hospital CHUV, University of Lausanne (UNIL), Lausanne, Switzerland
| | - Parissa Tabrizian
- Department of Liver Surgery, Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Myron Schwartz
- Department of Liver Surgery, Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Ahmad Mahamid
- Department of Liver Surgery, Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Claire Goumard
- Department of Hepatobiliary Surgery and Liver Transplantation, APHP Pitié-Salpêtrière Hospital, Sorbonne University, CRSA, Paris, France
| | - Olivier Scatton
- Department of Hepatobiliary Surgery and Liver Transplantation, APHP Pitié-Salpêtrière Hospital, Sorbonne University, CRSA, Paris, France
| | - Julie Perinel
- Department of Hepato-Biliary and Pancreatic Surgery, Edouard Herriot Hospital, Hospices Civils De Lyon, Lyon, France
| | - Mustapha Adham
- Department of Hepato-Biliary and Pancreatic Surgery, Edouard Herriot Hospital, Hospices Civils De Lyon, Lyon, France
| | - Nicolas Demartines
- Department of Visceral Surgery, University Hospital CHUV, University of Lausanne (UNIL), Lausanne, Switzerland
| | - Emmanuel Melloul
- Department of Visceral Surgery, University Hospital CHUV, University of Lausanne (UNIL), Lausanne, Switzerland.
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Bogdanovic A, Djokic Kovac J, Zdujic P, Djindjic U, Dugalic V. Liver resection versus transarterial chemoembolisation for the treatment of intermediate hepatocellular carcinoma: a systematic review and meta-analysis. Int J Surg 2023; 109:1439-1446. [PMID: 37222718 PMCID: PMC10389385 DOI: 10.1097/js9.0000000000000344] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 03/09/2023] [Indexed: 05/25/2023]
Abstract
BACKGROUND Transarterial chemoembolisation (TACE) is the primary treatment for intermediate-stage hepatocellular carcinoma (HCC), according to the updated Barcelona Clinic Liver Cancer (BCLC) staging system. Although growing evidence favours liver resection (LR) over TACE for intermediate-stage HCC, the best treatment option remains controversial. This meta-analysis aimed to compare the overall survival (OS) after LR versus TACE for intermediate-stage HCC. METHODS A comprehensive literature review of PubMed, Embase, Cochrane Library, and Web of Science was performed. Studies that compared the efficacy of LR and TACE in patients with intermediate (BCLC stage B) HCC were selected. According to the recent updated BCLC classification, intermediate stage of HCC was defined as follows: (a) four or more HCC nodules of any size, or (b) two or three nodules, but if at least one tumour is larger than 3 cm. The main outcome was OS, expressed as the hazard ratio. RESULTS Nine eligible studies of 3355 patients were included in the review. The OS of patients who underwent LR was significantly longer than that of patients who underwent TACE (hazard ratio=0.52; 95% CI: 0.39-0.69; I2=79%). Prolonged survival following LR was confirmed after sensitivity analysis of five studies using propensity score matching (HR=0.45; 95% CI: 0.34-0.59; I2=55%). CONCLUSION Patients with intermediate-stage HCC who underwent LR had a longer OS that those who underwent TACE. The role of LR in patients with BCLC stage B should be clarified in future randomised controlled trials.
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Affiliation(s)
- Aleksandar Bogdanovic
- Clinic for Digestive Surgery
- School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Jelena Djokic Kovac
- Center for Radiology and Magnetic Resonance Imaging, University Clinical Center of Serbia
- School of Medicine, University of Belgrade, Belgrade, Serbia
| | | | | | - Vladimir Dugalic
- Clinic for Digestive Surgery
- School of Medicine, University of Belgrade, Belgrade, Serbia
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Huang J, Wei S, Tang Y, Zhang Q, Luo H, Tang Z, Tang Y, Liu H, Huang W, Dong X, Yang J. Sex Differences in the Impact of Metabolic Dysfunction-associated Fatty Liver Disease on the of Patients with Hepatocellular Carcinoma After Radical Resection. J Cancer 2023; 14:1107-1116. [PMID: 37215444 PMCID: PMC10197934 DOI: 10.7150/jca.83779] [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: 02/23/2023] [Accepted: 04/08/2023] [Indexed: 05/24/2023] Open
Abstract
Background: International experts have put forward a new definition for metabolic dysfunction-associated fatty liver disease (MAFLD). Nonetheless, sex differences in MAFLD function in hepatocellular carcinoma (HCC) survival is still unknown. Therefore, the current work focused on exploring the gender-specific association of MAFLD effect on prognosis after radical resection of liver cancer. Methods: The long-term prognostic outcomes of 642 HCC patients undergoing hepatectomy were analyzed retrospectively. To calculate overall survival (OS) and recurrence-free survival (RFS), Kaplan-Meier (KM) curve was plotted. Further, using Cox proportional model to explore the prognostic factors. Sensitivity analysis was performed using propensity score matching (PSM) to balance the confounding bias. Results: For MAFLD patients, median OS and RFS times were 6.8 years and 6.1 years, respectively, compared to 8.5 years and 2.9 years in non-MAFLD patients. KM curve shown that compare with non-MAFLD patients, MAFLD patients had a higher survival rate in men, but had a lower survival rate in women (P<0.05). Multivariate analysis showed that MAFLD was significantly risk factor with mortality in the female (HR = 5.177, 95%CI: 1.475-18.193). However, MAFLD was not related to RFS This correlation was consistent after PSM analysis. Conclusions: MAFLD can improve the mortality of women undergoing radical resection for liver cancer, which independently estimate disease prognosis but is not related to recurrence-free survival.
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Affiliation(s)
- Junzhang Huang
- Department of Hepatobiliary, Pancreas and Spleen Surgery, Guangxi Academy of Medical Sciences, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi, China
| | - Suosu Wei
- Department of Scientific Cooperation of Guangxi Academy of Medical Sciences, People' s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi, China
| | - Yuntian Tang
- Department of Hepatobiliary, Pancreas and Spleen Surgery, Guangxi Academy of Medical Sciences, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi, China
| | - Qiuhuan Zhang
- Department of Colorectal and Anal Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region & Guangxi Academy of Medical Sciences, Guangxi, China
| | - Honglin Luo
- Institute of Oncology, Guangxi Academy of Medical Sciences, the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, People's Republic of China
| | - Zhenyong Tang
- Department of Hepatobiliary, Pancreas and Spleen Surgery, Guangxi Academy of Medical Sciences, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi, China
| | - Yi Tang
- Department of Hepatobiliary, Pancreas and Spleen Surgery, Guangxi Academy of Medical Sciences, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi, China
| | - Hongjun Liu
- Department of Hepatobiliary, Pancreas and Spleen Surgery, Guangxi Academy of Medical Sciences, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi, China
| | - Wei Huang
- Department of Hepatobiliary, Pancreas and Spleen Surgery, Guangxi Academy of Medical Sciences, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi, China
| | - Xiaofeng Dong
- Department of Hepatobiliary, Pancreas and Spleen Surgery, Guangxi Academy of Medical Sciences, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi, China
| | - Jianrong Yang
- Department of Hepatobiliary, Pancreas and Spleen Surgery, Guangxi Academy of Medical Sciences, People's Hospital of Guangxi Zhuang Autonomous Region, No.6 Taoyuan Road, Qingxiu District, Nanning 530021, Guangxi, China
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Wong JK, Lim HJ, Tam VC, Burak KW, Dawson LA, Chaudhury P, Abraham RJ, Meyers BM, Sapisochin G, Valenti D, Samimi S, Ramjeesingh R, Mujoomdar A, Martins I, Dixon E, Segedi M, Liu DM. Clinical consensus statement: Establishing the roles of locoregional and systemic therapies for the treatment of intermediate-stage hepatocellular carcinoma in Canada. Cancer Treat Rev 2023; 115:102526. [PMID: 36924644 DOI: 10.1016/j.ctrv.2023.102526] [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: 12/09/2022] [Revised: 02/12/2023] [Accepted: 02/14/2023] [Indexed: 03/06/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) a leading cause of cancer mortality worldwide and approximately one-third of patients present with intermediate-stage disease. The treatment landscape of intermediate-stage HCC is rapidly evolving due to developments in local, locoregional and systemic therapies. Treatment recommendations focused on this heterogenous disease stage and that take into account the Canadian reality are lacking. To address this gap, a pan-Canadian group of experts in hepatology, transplant, surgery, radiation therapy, nuclear medicine, interventional radiology, and medical oncology came together to develop consensus recommendations on management of intermediate-stage HCC relevant to the Canadian context. METHODS A modified Delphi framework was used to develop consensus statements with strengths of recommendation and supporting levels of evidence graded using the AHA/ACC classification system. Tentative consensus statements were drafted based on a systematic search and expert input in a series of iterative feedback cycles and were then circulated via online survey to assess the level of agreement. RESULTS & CONCLUSION The pre-defined ratification threshold of 80 % agreement was reached for all statements in the areas of multidisciplinary treatment (n = 4), intra-arterial therapy (n = 14), biologics (n = 5), radiation therapy (n = 3), surgical resection and transplantation (n = 7), and percutaneous ablative therapy (n = 4). These generally reflected an expansion in treatment options due to developments in previously established or emergent techniques, introduction of new and more active therapies and increased therapeutic flexibility. These developments have allowed for greater treatment tailoring and personalization as well as a paradigm shift toward strategies with curative intent in a wider range of disease settings.
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Affiliation(s)
- Jason K Wong
- University of Calgary, 2500 University Dr NW, Calgary, AB T2N 1N4, Canada.
| | - Howard J Lim
- BC Cancer Agency, 600 West 10th Avenue, Vancouver, BC V5Z 4E6, Canada.
| | - Vincent C Tam
- Tom Baker Cancer Centre, University of Calgary, 1331 29 St NW, Calgary, AB T2N 4N2, Canada.
| | - Kelly W Burak
- University of Calgary, 2500 University Dr NW, Calgary, AB T2N 1N4, Canada.
| | - Laura A Dawson
- Princess Margaret Cancer Centre, University of Toronto, 610 University Ave, Toronto, ON M5G 2C1, Canada.
| | | | - Robert J Abraham
- Department of Diagnostic Radiology, Dalhousie University, 6299 South St, Halifax, NS B3H 4R2, Canada.
| | - Brandon M Meyers
- Juravinski Cancer Centre, 699 Concession St, Hamilton, ON L8V 5C2, Canada.
| | | | - David Valenti
- McGill University, 845 Rue Sherbrooke O, Montréal, QC H3A 0G4, Canada.
| | - Setareh Samimi
- Hopital Sacre-Coeur de Montreal, University of Montreal, 5400 Boul Gouin O, Montréal, QC H4J 1C5, Canada.
| | - Ravi Ramjeesingh
- Department of Medicine, Dalhousie University, 6299 South St, Halifax, NS B3H 4R2, Canada.
| | - Amol Mujoomdar
- Western University, 1151 Richmond Street, London, ON N6A 5B9, Canada.
| | - Ilidio Martins
- Kaleidoscope Strategic, Inc. 1 King Street W, Suite 4800 - 117, Toronto, ON M5H 1A1, Canada.
| | - Elijah Dixon
- University of Calgary, 2500 University Dr NW, Calgary, AB T2N 1N4, Canada.
| | - Maja Segedi
- Department of Surgery, Vancouver General Hospital, Jim Pattison Pavilion, 899 W 12th Ave, Vancouver, BC V5Z 1M9, Canada.
| | - David M Liu
- School of Biomedical Engineering, University of British Columbia, 2329 West Mall Vancouver, BC V6T 1Z4, Canada.
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Liu Y, Wei X, Zhang X, Pang C, Xia M, Du Y. CT radiomics combined with clinical variables for predicting the overall survival of hepatocellular carcinoma patients after hepatectomy. Transl Oncol 2022; 26:101536. [PMID: 36115077 PMCID: PMC9483805 DOI: 10.1016/j.tranon.2022.101536] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 08/29/2022] [Accepted: 09/04/2022] [Indexed: 11/18/2022] Open
Abstract
PURPOSE To establish a model for assessing the overall survival (OS) of the hepatocellular carcinoma (HCC) patients after hepatectomy based on the clinical and radiomics features. METHODS This study recruited a total of 267 patients with HCC, which were randomly divided into the training (N = 188) and validation (N = 79) cohorts. In the training cohort, radiomic features were selected with the intra-reader and inter-reader correlation coefficient (ICC), Spearman's correlation coefficient, and the least absolute shrinkage and selection operator (LASSO). The radiomics signatures were built by COX regression analysis and compared the predictive potential in the different phases (arterial, portal, and double-phase) and regions of interest (tumor, peritumor 3 mm, peritumor 5 mm). A clinical-radiomics model (CR model) was established by combining the radiomics signatures and clinical risk factors. The validation cohort was used to validate the proposed models. RESULTS A total of 267 patients 86 (45.74%) and 37 (46.84%) patients died in the training and validation cohorts, respectively. Among all the radiomics signatures, those based on the tumor and peritumor (5 mm) (AP-TP5-Signature) showed the best prognostic potential (training cohort 1-3 years AUC:0.774-0.837; validation cohort 1-3 years AUC:0.754-0.810). The CR model showed better discrimination, calibration, and clinical applicability as compared to the clinical model and radiomics features. In addition, the CR model could perform risk-stratification and also allowed for significant discrimination between the Kaplan-Meier curves in most of the subgroups. CONCLUSIONS The CR model could predict the OS of the HCC patients after hepatectomy.
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Affiliation(s)
- Ying Liu
- School of Medical Imaging, North Sichuan Medical College, Nanchong City 637000, Sichuan Province, China
| | - Xiaoqin Wei
- School of Medical Imaging, North Sichuan Medical College, Nanchong City 637000, Sichuan Province, China
| | - Xinrui Zhang
- School of Medical Imaging, North Sichuan Medical College, Nanchong City 637000, Sichuan Province, China
| | - Caifeng Pang
- School of Medical Imaging, North Sichuan Medical College, Nanchong City 637000, Sichuan Province, China
| | - Mingkai Xia
- School of Medical Imaging, North Sichuan Medical College, Nanchong City 637000, Sichuan Province, China
| | - Yong Du
- Department of Radiology, the Affiliated Hospital of North Sichuan Medical College, Nanchong City 637000, Sichuan Province, China.
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21
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Labgaa I. Editorial: The impact of liquid biopsies in the management of liver cancer. Front Oncol 2022; 12:1083355. [DOI: 10.3389/fonc.2022.1083355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 11/17/2022] [Indexed: 11/30/2022] Open
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22
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Hu XS, Yang HY, Leng C, Zhang ZW. Postoperative outcomes and recurrence patterns of intermediate-stage hepatocellular carcinoma dictated by the sum of tumor size and number. World J Gastroenterol 2022; 28:6271-6281. [PMID: 36504552 PMCID: PMC9730440 DOI: 10.3748/wjg.v28.i44.6271] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2022] [Revised: 10/09/2022] [Accepted: 11/09/2022] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND The selection criteria for Barcelona Clinic Liver Cancer (BCLC) intermediate-stage hepatocellular carcinoma (HCC) patients who would truly benefit from liver resection (LR) remain undefined.
AIM To identify BCLC-B HCC patients more suitable for LR.
METHODS We included patients undergoing curative LR for BCLC stage A or B multi-nodular HCC (MNHCC) and stratified BCLC-B patients by the sum of tumor size and number (N + S). Overall survival (OS), recurrence-free survival (RFS), recur-rence-to-death survival (RTDS), recurrence patterns, and treatments after recurrence in BCLC-B patients in each subgroup were compared with those in BCLC-A patients.
RESULTS In total, 143 patients who underwent curative LR for MNHCC with BCLC-A (n = 25) or BCLC-B (n = 118) were retrospectively analyzed. According to the N + S, patients with BCLC-B HCC were divided into two subgroups: BCLC-B1 (N + S ≤ 10, n = 83) and BCLC-B2 (N + S > 10, n = 35). Compared with BCLC-B2 patients, those with BCLC-B1 had a better OS (5-year OS rate: 67.4% vs 33.6%; P < 0.001), which was comparable to that in BCLC-A patients (5-year OS rate: 67.4% vs 74.1%; P = 0.250), and a better RFS (median RFS: 19 mo vs 7 mo; P < 0.001), which was worse than that in BCLC-A patients (median RFS: 19 mo vs 48 mo; P = 0.022). Further analysis of patients who developed recurrence showed that both BCLC-B1 and BCLC-A patients had better RTDS (median RTDS: Not reached vs 49 mo; P = 0.599), while the RTDS in BCLC-B2 patients was worse (median RTDS: 16 mo vs not reached, P < 0.001; 16 mo vs 49 mo, P = 0.042). The recurrence patterns were similar between BCLC-B1 and BCLC-A patients, but BCLC-B2 patients had a shorter recurrence time and a higher proportion of patients had recurrence with macrovascular invasion and/or extrahepatic metastasis, both of which were independent risk factors for RTDS.
CONCLUSION BCLC-B HCC patients undergoing hepatectomy with N + S ≤ 10 had mild recurrence patterns and excellent OS similar to those in BCLC-A MNHCC patients, and LR should be considered in these patients.
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Affiliation(s)
- Xin-Sheng Hu
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Hui-Yuan Yang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Chao Leng
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Zhi-Wei Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
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Yi PS, Liu JN, Li Y, Wu B, Li JS. The priority of liver resection compared with transarterial chemoembolization in hepatocellular carcinoma at BCLC B1 stage: A single-center experience. Front Surg 2022; 9:920976. [PMID: 36439533 PMCID: PMC9681909 DOI: 10.3389/fsurg.2022.920976] [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: 04/15/2022] [Accepted: 10/17/2022] [Indexed: 08/30/2023] Open
Abstract
BACKGROUND This study aimed to compare the efficacy of liver resection (LR) and transarterial chemoembolization (TACE) in the treatment of Barcelona Clinic Liver Cancer B1 (BCLC B1) hepatocellular carcinoma. METHODS A total of 65 patients with BCLC B1 were divided into the radical (LR group) and TACE groups. Survival analysis was performed using the Kaplan-Meier method. Univariate and multivariate analyses were carried out, and the prognostic factors for survival outcomes were identified using Cox proportional analysis. RESULTS The 1-, 3-, and 5-year survival rates and the 1-, 3-, and 5-year progression-free survival (PFS) rates in the LR group (P = 0.036) were significantly higher than those in the TACE group (P = 0.027). Results of the multivariate analysis demonstrated that tumor distribution (both lobes vs. semi-liver) and treatment strategy (LR vs. TACE) were independent risk factors for the overall survival (OS) [hazard ratios (HRs): 3.926 and 0.479; P < 0.05] and PFS (HR: 3.336 and 0.465, P < 0.05). LR was associated with increased OS and PFS compared with TACE in patients with BCLC B1 hepatocellular carcinoma.
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Affiliation(s)
- Peng-Sheng Yi
- Department of Hepato-Biliary-Pancreas II, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
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Zhou Y, Gu H, Shao B, Zhang S, Pall H, Peixoto RD, Mok SRS, Zhu G. Glycolysis-related gene dihydrolipoamide acetyltransferase promotes poor prognosis in hepatocellular carcinoma through the Wnt/β-catenin and PI3K/Akt signaling pathways. ANNALS OF TRANSLATIONAL MEDICINE 2022; 10:1240. [PMID: 36544660 PMCID: PMC9761179 DOI: 10.21037/atm-22-5272] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Accepted: 11/17/2022] [Indexed: 11/30/2022]
Abstract
Background Recent research suggests that dihydrolipoamide acetyltransferase (DLAT), which is a copper-induced cell death-related gene, is involved in multiple biological events in tumors. This study sought to investigate the relationship between DLAT and hepatocellular carcinoma (HCC). Methods In the Cancer Genome Atlas (TCGA) database, we first identified the differentially expressed gene (i.e., DLAT), then confirmed DLAT expression, and found a link between it and the prognosis of HCC patients. An internal validation nomogram was built based on a multivariate Cox regression analysis. Data from the Tumor Immune Estimation Resource (TIMER) database was used to examine the association between DLT and immunological cells. A gene set enrichment analysis (GSEA) was conducted to investigate the probable mechanism of action. Finally, in vitro cytological research was conducted to further examin the involvement of DLAT in HCC-related unfavorable biological events. Results The database screenings showed that DLAT was a differentially expressed molecule; that is, DLAT was more highly expressed in the cancer tissues than normal tissues. TCGA results and Kaplan-Meier-plotter data sets showed that HCC patients with reduced DLAT expression had greater disease-specific survival (DSS), overall survival (OS), and progression-free interval (PFI). The prediction model had a concordance index of 0.659 (0.614-0.704), which indicates high accuracy. According to the TIMER database, tumor cells in the HCC microenvironment may be able to bypass the immune system due to the expression of DLAT. The in vitro cytological tests showed that DLAT knockdown significantly decreased the proliferation and invasion of the HCC cells. It also inhibited the activity of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (Akt) and Wnt/β-catenin signaling pathways. Conclusions Decreased DLAT expression significantly prolongs the OS, PFI, and DSS of HCC patients. DLAT may be employed as a new predictive biomarker for HCC, and may be linked to the immune system in HCC patients. The tumor microenvironment (TME) may have a significant effect on the ability of tumor cells to evade the immune system. The PI3K/Akt and Wnt/β-catenin signaling pathways may affect the prognosis of HCC by interfering with DLAT. Given these findings, HCC may be an ideal target for the development of anti-cancer therapies.
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Affiliation(s)
- Yuan Zhou
- Department of Hepatobiliary Surgery, Tumor Hospital Affiliated to Nantong University, Nantong Tumor Hospital, Nantong, China;,Southeast University School of Medicine, Nanjing, China
| | - Haijuan Gu
- Department of Pharmacy, Tumor Hospital Affiliated to Nantong University, Nantong Tumor Hospital, Nantong, China
| | - Bingfeng Shao
- Department of Hepatobiliary Surgery, Tumor Hospital Affiliated to Nantong University, Nantong Tumor Hospital, Nantong, China
| | - Suqing Zhang
- Department of Hepatobiliary Surgery, Tumor Hospital Affiliated to Nantong University, Nantong Tumor Hospital, Nantong, China
| | - Harpreet Pall
- Department of Pediatrics, Hackensack Meridian School of Medicine, Hackensack Meridian K. Hovnanian Children’s Hospital, Jersey Shore University Medical Center, Neptune, NJ, USA
| | | | - Shaffer R. S. Mok
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL, USA
| | - Guodong Zhu
- Department of Hepatobiliary Surgery, Affiliated Nantong Hospital 3 of Nantong University, Nantong, China
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Sortilin 1 Promotes Hepatocellular Carcinoma Cell Proliferation and Migration by Regulating Immune Cell Infiltration. JOURNAL OF ONCOLOGY 2022; 2022:6509028. [PMID: 35847356 PMCID: PMC9286884 DOI: 10.1155/2022/6509028] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Accepted: 05/24/2022] [Indexed: 12/17/2022]
Abstract
Objectives Recent evidence suggests that Sort1 promotes carcinogenesis and tumor progression in multiple types of cancers. This study investigates the role of Sort1 in hepatocellular carcinoma (HCC). Methods The differentially expressed gene was screened through GEO and TCGA databases. The Sort1 gene was identified and its expression was then verified by TCGA and HCCDB (a database of hepatocellular carcinoma expression atlas) databases. The Human Protein Atlas database was used to assess the gene expression in tissues. The TCGA and KM-plotter databases were used to study the relationship between Sort1 and HCC. The correlation between Sort1 and immune cells was evaluated through the TIMER database. GO and KEGG enrichment analysis was used to investigate the possible mechanism. The role of Sort1 in cell proliferation and invasion of HCC was further explored through in vitro experiments. Result The differentially expressed molecule obtained from database screening was Sort1. Its expression was higher in cancer tissues than in paracancerous ones, and it was mainly located in the cytoplasm. The TCGA, KM-plotter databases, and our study data showed that low expression of Sort1 in HCC patients had better overall survival (OS), progression-free survival (PFI), and disease-specific survival (DSS). Further analysis indicated a significant correlation between Sort1 expression and immune cell infiltration. The gene set enrichment analysis (GSEA) analysis showed that Sort1 affected the biological events of HCC by participating in the WNT, TGF-BETA, JAK, STAT, and CALCIUM signaling pathways. In vitro, cytological experiments demonstrated reduced expression of PCNA, Ki-67, Vimentin, N-cadherin, and MMP-9 mRNA after knocking down Sort1, although E-cadherin expression was promoted. Overall, these processes reduced the ability of proliferation and invasion of HCC cells. Conclusion Downregulation of Sort1 can prolong the OS, PFI, and DSS of HCC patients. Furthermore, due to its link with immune cell infiltration, the Sort1 gene represents a potentially novel predictive biomarker of HCC. The growth of HCC can be significantly inhibited by interfering with Sort1; therefore, these results provide a potential target for developing anticancer strategies for HCC.
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Partial hepatectomy vs. transcatheter arterial chemoembolization for multiple hepatocellular carcinomas of BCLC-B stage: A meta-analysis of high-quality studies. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 48:1685-1691. [PMID: 35545472 DOI: 10.1016/j.ejso.2022.04.017] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Revised: 03/15/2022] [Accepted: 04/22/2022] [Indexed: 12/17/2022]
Abstract
BACKGROUND/AIM The Barcelona Clinic Liver Cancer (BCLC) recommends that transcatheter arterial chemoembolization (TACE) are indicated in patients with multiple hepatocellular carcinomas (HCCs) of BCLC-B stage. However, partial hepatectomy (PH) has increasely performed in these patients. The purpose of this meta-analyses is to illustrate the comparative survival benefits of PH and TACE for patients with multiple HCCs of BCLC-B stage. METHOD Electronic databases were systematically searched for eligible studies that compared PH and TACE performed in patients with multiple HCCs of BCLC-B stage. Studies that met the inclusion criteria were reviewed systematically. The reported data were aggregated statistically using the RevMan5.3 software. Primary endpoint was overall survival (OS), and secondary endpoint were the 1-, 3-, and 5-year survival rates, postoperative 30-day mortality and postoperative complications. RESULTS A total of seven high-quality studies (one randomized controlled trial [RCT], six propensity-score matching (PSM) nonrandomized comparative trials [non-RCTs] that met the inclusion criteria, which comprised of 2487 patients (1245 PH and 1242 TACE) in the meta-analysis. When compared with the TACE group, the PH group had a significantly higher OS (HR, 1.65; 95% CI, 1.48-1.84; P = 0.26; I2 = 22%) and 1-, 3-, 5-year survival rates (OR, 1.96; 95% CI, 1.59-2.41; P = 0.0005; I2 = 75%; P < 0.00001; OR, 2.92; 95% CI, 1.94-4.42; P = 0.0001; I2 = 78%; P < 0.00001; OR, 2.60; 95% CI, 2.17-3.11; P = 0.13; I2 = 44%; P < 0.00001; respectively). Survival benefits persisted across sensitivity and subgroup analyses; High heterogeneity remained after sensitivity and subgroup analyses for 3-year survival rates. CONCLUSION PH can provide more survival benefit for patients with multiple HCCs of BCLC-B stage compared with TACE.
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Xu L, Chen L, Zhang W. Neoadjuvant treatment strategies for hepatocellular carcinoma. World J Gastrointest Surg 2021; 13:1550-1566. [PMID: 35070063 PMCID: PMC8727178 DOI: 10.4240/wjgs.v13.i12.1550] [Citation(s) in RCA: 6] [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: 04/19/2021] [Revised: 06/27/2021] [Accepted: 11/30/2021] [Indexed: 02/06/2023] Open
Abstract
The incidence of hepatocellular carcinoma (HCC) remains high globally. Surgical treatment is the best treatment for improving the prognosis of patients with HCC. Neoadjuvant therapy plays a key role in preventing tumor progression and even downstaging HCC. The liver transplantation rate and resectability rate have increased for neoadjuvant therapy. Neoadjuvant therapy is effective in different stages of HCC. In this review, we summarized the definition, methods, effects, indications and contraindications of neoadjuvant therapy in HCC, which have significance for guiding treatment.
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Affiliation(s)
- Lei Xu
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Lin Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Wei Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
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Shen J, Qi W, Dai J, Leng S, Jiang K, Zhang Y, Ran S, Li C, Wen T. Tenofovir vs. entecavir on recurrence of hepatitis B virus-related hepatocellular carcinoma beyond Milan criteria after hepatectomy. Chin Med J (Engl) 2021; 135:301-308. [PMID: 34958539 PMCID: PMC8812695 DOI: 10.1097/cm9.0000000000001864] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Indexed: 01/27/2023] Open
Abstract
BACKGROUND Hepatectomy for hepatocellular carcinoma (HCC) beyond the Milan criteria is shown to be beneficial. However, a high rate of post-operative HCC recurrence hinders the long-term survival of the patients. This study aimed to investigate and compare the impacts of tenofovir (TDF) and entecavir (ETV) on the recurrence of hepatitis B viral (HBV)-related HCC beyond the Milan criteria. METHODS Data pertaining to 1532 patients who underwent hepatectomy and received antiviral therapy between January 2014 and January 2019 were collected from five centers. Recurrence-free survival (RFS) analysis was performed using the Kaplan-Meier method. Cox proportional hazards regression analysis was performed to determine prognostic factors for HCC recurrence. RESULTS The analysis incorporates 595 HBV-related HCC patients. The overall 5-year RFS was 21.3%. Among them, 533 and 62 patients received ETV and TDF treatment, respectively. The 1-, 3-, and 5-year RFS rates were 46.3%, 27.4%, and 19.6%, respectively, in the ETV group compared with 65.1%, 41.8%, and 37.2%, respectively, in the TDF group (P < 0.001). Multivariate analysis showed that TDF treatment (hazard ratio [HR]: 0.604, P = 0.005), cirrhosis (HR: 1.557, P = 0.004), tumor size (HR: 1.037, P = 0.008), microvascular invasion (MVI) (HR: 1.403, P = 0.002), portal vein tumor thrombus (PVTT) (HR: 1.358, P = 0.012), capsular invasion (HR: 1.228, P = 0.040), and creatinine levels (CREA) (HR: 0.993, P = 0.031) were statistically significant prognostic factors associated with RFS. CONCLUSIONS Patients with HCC beyond the Milan criteria exhibited a high rate of HCC recurrence after hepatectomy. Compared to the ETV therapy, TDF administration significantly lowered the risk of HCC recurrence.
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Affiliation(s)
- Junyi Shen
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
- Laboratory of Liver Transplantation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
- Institute of Clinical Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Weili Qi
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Junlong Dai
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Shusheng Leng
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Chengdu University, Chengdu, Sichuan 610072, China
| | - Kangyi Jiang
- Department of Hepatobiliary and Pancreatic Surgery, The People's Hospital of Leshan, Leshan, Sichuan 614700, China
| | - Yu Zhang
- Department of Hepatobiliary Surgery, Sichuan Provincial People's Hospital, Chinese Academy of Sciences, Chengdu, Sichuan 610072, China
| | - Shun Ran
- Department of Hepatobiliary Surgery, Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, Guizhou 550000, China
| | - Chuan Li
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
- Laboratory of Liver Transplantation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Tianfu Wen
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
- Laboratory of Liver Transplantation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
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Hu S, Gan W, Qiao L, Ye C, Wu D, Liao B, Yang X, Jiang X. A New Prognostic Algorithm Predicting HCC Recurrence in Patients With Barcelona Clinic Liver Cancer Stage B Who Received PA-TACE. Front Oncol 2021; 11:742630. [PMID: 34745962 PMCID: PMC8566809 DOI: 10.3389/fonc.2021.742630] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 09/27/2021] [Indexed: 01/05/2023] Open
Abstract
Background Postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) is effective in preventing the recurrence of hepatocellular carcinoma (HCC) in patients treated with surgery. However, there is a lack of reports studying the risk factors associated with recurrence in HCC patients who received PA-TACE. In this study, we identified the independent risk factors for recurrence of HCC patients who received PA-TACE. We also developed a novel, effective, and valid nomogram to predict the individual probability of recurrence, 1, 3, and 5 years after PA-TACE. Methods A retrospective study was performed to identify the independent risk factors for recurrence of HCC in a group of 502 patients diagnosed in stage B based on the Barcelona Clinic Liver Cancer (BCLC) evaluation system for HCC that underwent curative resections. Then, subgroup analysis was performed for 184 patients who received PA-TACE, who were included in the training cohort. The other 147 HCC patients were included in a validation cohort. A recurrence-free survival (RFS)-predicting nomogram was constructed, and results were assessed using calibration and decision curves and a time-dependent AUC diagram. Results PA-TACE was shown to be a significant independent prognostic value for patients with BCLC stage B [p < 0.001, hazard ratio (HR) = 0.508, 95% CI = 0.375–0.689 for OS, p = 0.002; HR = 0.670, 95%CI = 0.517–0.868 for RFS]. Alpha fetoprotein (AFP), tumor number, tumor size, microvascular invasion (MVI), and differentiation were considered as independent risk factors for RFS in the training cohort, and these were further confirmed in the validation cohort. Next, a nomogram was constructed to predict RFS. The C-index for RFS in the nomogram was 0.721 (95% CI = 0.718–0.724), which was higher than SNACOR, HAP, and CHIP scores (0.587, 0.573, and 0.607, respectively). Calibration and decision curve analyses and a time-dependent AUC diagram were used. Our nomogram showed stronger performance than these other nomograms in both the training and validation cohorts. Conclusions HCC patients diagnosed as stage B according to BCLC may benefit from PA-TACE after surgery. The RFS nomogram presented here provides an accurate and reliable prognostic model to monitor recurrence. Patients with a high recurrence score based on the nomogram should receive additional high-end imaging exams and shorter timeframes in between follow-up visits.
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Affiliation(s)
- Shuyang Hu
- Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Wei Gan
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.,Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, Key Laboratory for Carcinogenesis & Cancer Invasion, The Chinese Ministry of Education, Shanghai, China
| | - Liang Qiao
- Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Cheng Ye
- Medical Center of Fudan University, Shanghai, China
| | - Demin Wu
- Department of Health Physical Examination, Shanghai Electric Power Hospital, Shanghai, China
| | - Boyi Liao
- Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Xiaoyu Yang
- Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Xiaoqing Jiang
- Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
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Chen QF, Dai L, Wu Y, Huang Z, Chen M, Zhao M. Surveillance Strategy for Barcelona Clinic Liver Cancer B Hepatocellular Carcinoma Achieving Complete Response: An Individualized Risk-Based Machine Learning Study. Front Bioeng Biotechnol 2021; 9:667641. [PMID: 34540812 PMCID: PMC8447402 DOI: 10.3389/fbioe.2021.667641] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Accepted: 06/30/2021] [Indexed: 12/30/2022] Open
Abstract
Background: For patients with complete response (CR) of Barcelona Clinical Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC), there is no consensus regarding the monitoring strategy. Optimal surveillance strategies that can detect early progression of HCC within a limited visit after treatment have not yet been investigated. A retrospective, real-world study was conducted to investigate surveillance strategies for BCLC stage B HCC (BBHCC) patients with CR after curative treatment to support clinical decision making. Methods: From January 2007 to December 2019, 546 BBHCC patients with CR after radical treatment were collected at Sun Yat-sen University Cancer Center. Seventy percent of patients were subjected to the train cohort randomly; the remaining patients comprised the validation cohort to verify the proposed arrangements. The random survival forest method was applied to calculate the disease progression hazard per month, and follow-up schedules were arranged to maximize the capability of progression detection at each visit. The primary endpoint of the study was the delayed-detection months for disease progression. Results: The cumulative 1, 2, and 3-years risk-adjusted probabilities for the train/validation cohorts were 32.8%/33.7%, 54.0%/56.3%, and 64.0%/67.4%, respectively, with peaks around approximately the 9th month. The surveillance regime was primarily concentrated in the first year posttreatment. The delayed-detection months gradually decreased when the total follow-up times increased from 6 to 11. Compared with controls, our schedule reduced delayed detection. Typically, the benefits of our surveillance regimes were obvious when the patients were followed seven times according to our schedule. The optional schedules were 5, 7, 9, 11, 17, 23, and 30 months. Conclusion: The proposed new surveillance schedule may provide a new perspective concerning follow-up for BBHCC patients with CR.
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Affiliation(s)
- Qi-Feng Chen
- Department of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, China.,State Key Laboratory of Oncology in South China, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Lin Dai
- Cancer Prevention Center, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Ying Wu
- Department of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, China.,State Key Laboratory of Oncology in South China, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Zilin Huang
- Department of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Minshan Chen
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Ming Zhao
- Department of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, China
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Liu S, Xu Z, Fang Z, Zhang D, Qin Z, Fan L, Duan J, Yin H, Zhang Y, Pang Q, Tan Y. The Combination of Age, International Standardized Ratio, Albumin and γ-Glutamyl Transpeptidase (AIAG), Tumor Size and Alpha Fetoprotein (AFP) Stage as the Prognostic Model for Hepatitis B-Related Hepatocellular Carcinoma. Int J Gen Med 2021; 14:4291-4301. [PMID: 34408472 PMCID: PMC8364385 DOI: 10.2147/ijgm.s323293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 07/26/2021] [Indexed: 12/09/2022] Open
Abstract
Background Advanced liver fibrosis can lead to cirrhosis, portal hypertension and liver failure. Besides, advanced liver fibrosis and cirrhosis are the major risk factors for hepatocellular carcinoma (HCC). Almost all patients with HCC also have liver cirrhosis. This study aims to predict the survival rate of hepatitis B-related hepatocellular carcinoma (HCC) by age, international standardized ratio, albumin and γ-glutamyl transpeptidase (AIAG), an indicator measuring the degree of cirrhosis. Methods A total of 501 hepatitis B-related HCC patients experiencing radical surgery were analyzed, retrospectively. General data about demographics and labs were collected at the date of diagnosis to calculate AIAG [age, international standardized ratio (INR), albumin and gamma-glutamyl transferase (GGT)]. The Kaplan–Meier curves and Cox analysis were used to evaluate overall survival (OS) and recurrence-free survival (RFS). The C-index was calculated in R software (version 4.0.3) to evaluate the accuracy of the prognostic model. Results During a median follow-up period of 30 months, 31.1% (156/501) of the patients died, and 34.3% (172/501) experienced the recurrence of HCC. Compared with patients with lower AIAG score, patients with higher AIAG score had higher Child-Pugh grade and were at higher Barcelona Clinic Liver Cancer (BCLC) stage (both P<0.05). Multivariate analysis suggested that GGT, alpha fetoprotein (AFP), tumor size, BCLC stage and AIAG grade were independent predictors of OS and RFS. Furthermore, the combined use of tumor size, AFP and AIAG stage could predict survival significantly better (C-index=0.710, 95% CI: 0.669–0.751) than BCLC stage. Conclusion AIAG is significantly associated with survival of HCC patients, and provides additional prognostic information for patients with HCC. Our findings suggest that the combination of AIAG, tumor size and AFP stage has a better predictive value for the prognosis of patients with hepatitis B-related hepatocellular carcinoma. However, it is necessary for more external evidences to determine clinical utility.
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Affiliation(s)
- Shuangchi Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, Anhui, People's Republic of China
| | - Zhiduan Xu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, Anhui, People's Republic of China
| | - Zhuling Fang
- Department of Medical Laboratory, Bengbu Medical College, Bengbu, Anhui, 233000, People's Republic of China
| | - Dengyong Zhang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, Anhui, People's Republic of China
| | - Zhongqiang Qin
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, Anhui, People's Republic of China
| | - Longfei Fan
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, Anhui, People's Republic of China
| | - Jiakang Duan
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, Anhui, People's Republic of China
| | - Hongxiang Yin
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, Anhui, People's Republic of China
| | - Yigang Zhang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, Anhui, People's Republic of China
| | - Qing Pang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, Anhui, People's Republic of China.,Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China
| | - Yi Tan
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, Anhui, People's Republic of China
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Chen HY, Kee KM, Lu SN, Wang JH, Chen CH, Hung CH, Yen YH, Kuo YH. Incorporating albumin-bilirubin grade and up-to-seven criteria to predict outcomes of patients with intermediate stage hepatocellular carcinoma after transarterial (chemo)embolization. J Formos Med Assoc 2021; 121:778-786. [PMID: 34303584 DOI: 10.1016/j.jfma.2021.07.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Revised: 05/15/2021] [Accepted: 07/05/2021] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND/PURPOSE This study is to use albumin-bilirubin (ALBI) grade and up-to-7 (UT7) criteria to assess outcomes of patients with intermediate stage hepatocellular carcinoma (HCC) after transarterial (chemo)embolization (TA(C)E). METHODS Between January 2012 and January 2019, newly diagnosed intermediate HCC patients underwent TA(C)E were enrolled and analyzed. The demographics, clinical characteristics and survival were obtained from medical chart reviews. RESULTS A total of 359 patients were enrolled and 30.4% of them were within UT7 criteria (UT7 (-)). There were 36.5%, 59.3%, and 4.2% of the patients with ALBI grade I, II, and III, respectively. Beyond UT7 (UT7 (+)) and ALBI grade II/III were associated with overall mortality in multivariate analysis. Based on ALBI grade I/II/III and UT7 -/+, patients were classified into six groups as ALBI grade I plus UT7 (-), II plus UT7 (-), III plus UT7 (-), I plus UT7 (+), II plus UT7 (+), and III plus UT7(+). Distributions of median survival were 47.5, 32.9, 15, 34.3, 16.7 and 14.3 months, respectively. Patients with statistically insignificant survivals were further combined. Patients with ALBI grade I plus UT7 (-) were reclassified as ALBI-U class I, whereas ALBI grade II plus UT7 (-) and I plus UT7 (+) were ALBI-U class II, and the others were ALBI-U class III. There were 8.4%, 48.7%, and 42.9% of patients in ALBI-U class I, II, and III, respectively. The 5-year survival rate was 48.8%, 22.5%, and 13.7% in ALBI-U class I, II, and III, respectively (p < 0.01). CONCLUSION ALBI-U classification was useful in predicting outcomes of patient with intermediate stage HCC after TA(C)E.
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Affiliation(s)
- Hsin-Yeh Chen
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung City, Taiwan
| | - Kwong-Ming Kee
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung City, Taiwan
| | - Sheng-Nan Lu
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung City, Taiwan
| | - Jing-Houng Wang
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung City, Taiwan
| | - Chien-Hung Chen
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung City, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung City, Taiwan
| | - Yi-Hao Yen
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung City, Taiwan
| | - Yuan-Hung Kuo
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung City, Taiwan.
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Romano F, Chiarelli M, Garancini M, Scotti M, Zago M, Cioffi G, De Simone M, Cioffi U. Rethinking the Barcelona clinic liver cancer guidelines: Intermediate stage and Child-Pugh B patients are suitable for surgery? World J Gastroenterol 2021; 27:2784-2794. [PMID: 34135554 PMCID: PMC8173387 DOI: 10.3748/wjg.v27.i21.2784] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Revised: 02/24/2021] [Accepted: 04/29/2021] [Indexed: 02/06/2023] Open
Abstract
According to Barcelona Clinic Liver Cancer recommendations, intermediate stage hepatocellular carcinomas (stage B) are excluded from liver resection and are referred to palliative treatment. Moreover, Child-Pugh B patients are not usually candidates for liver resection. However, many hepatobiliary centers in the world manage patients with intermediate stage hepatocellular carcinoma or Child-Pugh B cirrhosis with liver resection, maintaining that hepatic resection is not contraindicated in selected patients with non-early-stage hepatocellular carcinoma and without normal liver function. Several studies demonstrate that resection provides the best survival benefit for selected patients in very early/early and even in intermediate stages of Barcelona Clinic Liver Cancer classification, and this treatment gives good results in the setting of multinodular, large tumors in patients with portal hypertension and/or Child-Pugh B cirrhosis. In this review we explore this controversial topic, and we show through the literature analysis how liver resection may improve the short- and long-term survival rate of carefully selected Barcelona Clinic Liver Cancer B and Child-Pugh B hepatocellular carcinoma patients. However, other large clinical studies are needed to clarify which patients with intermediate stage hepatocellular carcinoma are most likely to benefit from liver resection.
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Affiliation(s)
- Fabrizio Romano
- Department of Surgery, School of Medicine and Surgery, University of Milano-Bicocca, Monza 20900, Italy
| | - Marco Chiarelli
- Emergency and Robotic Surgery, A. Manzoni Hospital, ASST Lecco, Lecco 23900, Italy
| | - Mattia Garancini
- Department of General Surgery, San Gerardo Hospital, Monza 20900, Italy
| | - Mauro Scotti
- Department of General Surgery, San Gerardo Hospital, Monza 20900, Italy
| | - Mauro Zago
- Emergency and Robotic Surgery, A. Manzoni Hospital, ASST Lecco, Lecco 23900, Italy
| | - Gerardo Cioffi
- Department of Sciences and Technologies, Università degli Studi del Sannio di Benevento, Benevento 82100, Italy
| | | | - Ugo Cioffi
- Department of Surgery, University of Milan, Milano 20122, Italy
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