|
1
|
Gu X, Lu H, Wang W, Zhao Z, Zhang W, Lu X. miR-130a-5p/TFPI2 axis promotes invasion of hepatocellular carcinoma by altering epithelial-to-mesenchymal transition. Discov Oncol 2025; 16:546. [PMID: 40244374 PMCID: PMC12006631 DOI: 10.1007/s12672-025-02296-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2025] [Accepted: 04/02/2025] [Indexed: 04/18/2025] Open
Abstract
BACKGROUND MicroRNAs (miRNAs), particularly miR-130a-5p, play pivotal roles in the tumorigenesis and progression of hepatocellular carcinoma (HCC) by participating in diverse biological processes. The objective of this study was to elucidate the mechanistic basis by which miR-130a-5p regulates the expression of tissue factor pathway inhibitor-2 (TFPI2) and to demonstrate the subsequent impact of the miR-130a-5p/TFPI2 axis on HCC invasion. METHODS Expression levels of miR-130a-5p and TFPI2 were quantified in HepG2 cell lines using quantitative real-time PCR (qRT-PCR). Western blot and qRT-PCR were employed to assess the expression of TFPI2 and epithelial-to-mesenchymal transition (EMT)-related proteins in both cancer cells and tissues. miR-130a-5p knockdown and TFPI2 overexpression were achieved through transfection of HepG2 cells with short hairpin RNA (shRNA) and synthetic overexpression plasmids, respectively. A dual luciferase reporter assay was conducted to verify the binding of miR-130a-5p to TFPI2. Migration and invasion capabilities of cancer cells were evaluated using Transwell migration and invasion assays. A mouse xenograft tumor model was established to investigate tumor growth in vivo. Immunohistochemical (IHC) staining was utilized to examine the expression of EMT-related proteins in tumor tissues. RESULTS The dual-luciferase reporter assay confirmed that miR-130a-5p binds to the 3' untranslated region (3'UTR) of TFPI2 mRNA, inhibiting its luciferase activity. Western blot analysis revealed that miR-130a-5p negatively regulates TFPI2 protein expression and promotes EMT molecular events by targeting TFPI2 in HCC cells. Transwell assays demonstrated that downregulation of miR-130a-5p and upregulation of TFPI2 inhibited the migration and invasion abilities of HCC cells in vitro. Silencing of miR-130a-5p was found to retard the growth of HCC xenografts in vivo, decrease TFPI2 expression, and alter the EMT process. CONCLUSIONS miR-130a-5p binds to TFPI2 mRNA and promotes HCC cell migration, invasion, and xenograft tumor growth by regulating the EMT process. These findings suggest that the miR-130a-5p/TFPI2 axis may represent a promising therapeutic target for the treatment of HCC.
Collapse
Affiliation(s)
- Xiaoyuan Gu
- Department of Oncology, Shibei Hospital of Shanghai, Jing'an District, No. 4500, Gonghexin Road, Shanghai, China
| | - Hongmin Lu
- Department of Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 145, Shandong Middle Road, Shanghai, 200127, China
| | - Wei Wang
- Department of Oncology, Shibei Hospital of Shanghai, Jing'an District, No. 4500, Gonghexin Road, Shanghai, China
| | - Zijun Zhao
- Department of Oncology, Shibei Hospital of Shanghai, Jing'an District, No. 4500, Gonghexin Road, Shanghai, China
| | - Weiqiang Zhang
- Department of Oncology, Shibei Hospital of Shanghai, Jing'an District, No. 4500, Gonghexin Road, Shanghai, China.
| | - Xinyuan Lu
- Department of Pathology, Shanghai Baoshan District Wusong Central Hospital (Wusong Branch, Zhongshan Hospital Affiliated to Fudan University), Shanghai, 200940, China.
| |
Collapse
|
|
2
|
Kim DW, Park JH, Hong SK, Jung MH, Pyeon JO, Lee JY, Suh KS, Yi NJ, Choi Y, Lee KW, Kim YJ. Exploring methylation signatures for high de novo recurrence risk in hepatocellular carcinoma. Clin Mol Hepatol 2025; 31:563-576. [PMID: 40241383 PMCID: PMC12016632 DOI: 10.3350/cmh.2024.0899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Revised: 12/23/2024] [Accepted: 01/07/2025] [Indexed: 04/18/2025] Open
Abstract
BACKGROUND/AIMS Hepatocellular carcinoma (HCC) exhibits high de novo recurrence rates post-resection. Current post-surgery recurrence prediction methods are limited, emphasizing the need for reliable biomarkers to assess recurrence risk. We aimed to develop methylation-based markers for classifying HCC patients and predicting their risk of de novo recurrence post-surgery. METHODS In this retrospective cohort study, we analyzed data from HCC patients who underwent surgical resection in Korea, excluding those with recurrence within one year post-surgery. Using the Infinium Methylation EPIC array on 140 samples in the discovery cohort, we classified patients into low- and high-risk groups based on methylation profiles. Distinctive markers were identified through random forest analysis. These markers were validated in the cancer genome atlas (n=217), Validation cohort 1 (n=63) and experimental Validation using a methylation-sensitive high-resolution melting (MS-HRM) assay in Validation cohort 1 and Validation cohort 2 (n=63). RESULTS The low-risk recurrence group (methylation group 1; MG1) showed a methylation average of 0.73 (95% confidence interval [CI] 0.69-0.77) with a 23.5% recurrence rate, while the high-risk group (MG2) had an average of 0.17 (95% CI 0.14-0.20) with a 44.1% recurrence rate (P<0.03). Validation confirmed the applicability of methylation markers across diverse populations, showing high accuracy in predicting the probability of HCC recurrence risk (area under the curve 96.8%). The MS-HRM assay confirmed its effectiveness in predicting de novo recurrence with 95.5% sensitivity, 89.7% specificity, and 92.2% accuracy. CONCLUSION Methylation markers effectively classified HCC patients by de novo recurrence risk, enhancing prediction accuracy and potentially offering personalized management strategies.
Collapse
Affiliation(s)
- Da-Won Kim
- Interdisciplinary Program of Integrated OMICS for Biomedical Science, Yonsei University, Seoul, Korea
- R&D center, LepiDyne Inc, Seoul, Korea
| | - Jin Hyun Park
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Suk Kyun Hong
- Department of Surgery, Seoul National University Hospital, Seoul, Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Min-Hyeok Jung
- R&D center, LepiDyne Inc, Seoul, Korea
- Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea
| | | | - Jin-Young Lee
- Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University Hospital, Seoul, Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University Hospital, Seoul, Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University Hospital, Seoul, Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University Hospital, Seoul, Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Young-Joon Kim
- R&D center, LepiDyne Inc, Seoul, Korea
- Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea
| |
Collapse
|
|
3
|
Kong Y, Huang X, Cao X, Tang F, Zhou X. Early Recurrence of Colorectal Liver Metastasis (Number ≤ 5 and Largest Diameter ≤ 3 cm) after Resection or Thermal Ablation: a Multi-center Study of Patterns, Safety, Survival and Risk Factors. J Gastrointest Cancer 2025; 56:77. [PMID: 40072796 DOI: 10.1007/s12029-025-01200-4] [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] [Accepted: 03/02/2025] [Indexed: 03/14/2025]
Abstract
OBJECTIVE To compare early recurrence patterns, safety, survival and investigate the clinical risk factors of early recurrence (ER) after liver resection or thermal ablation (TA) for patients with colorectal liver metastases (CRLM) with number ≤ 5 and largest diameter ≤ 3 cm. MATERIALS AND METHODS This retrospective study included patients with CRLM who underwent liver resection or TA between January 2016 and December 2021 at two hospitals in China. The Kaplan-Meier method and log-rank test were used to assess recurrence-free survival (RFS) and overall survival (OS). Risk factors for ER were analysed using univariate and multivariate Cox regression analyses. RESULTS 303 patients with 632 liver metastases were enrolled. The most common early recurrence pattern was intrahepatic recurrence (IHR) in resection group and TA group. There was no significant difference in 6-month RFS rate (65.81% vs 66.23%) and median OS (P = 0.10) between two groups. Patients without ER had better OS than those with ER (P < 0.05). The incidence of serious complications (P = 0.013), length of hospitalization (P < 0.01), and albumin-bilirubin (ALBI) score (P = 0.038) in TA group were significantly better than resection group. The diameter of liver metastases (HR: 4.89, 95% CI: 1.16-20.60; P = 0.031) and clinical risk score (CRS) (HR: 1.86, 95% CI: 1.06-3.25; P = 0.029) were independent risk factors for ER. CONCLUSION For CRLM with largest diameter ≤ 3 cm and number ≤ 5, the efficacy of receiving resection or TA is comparable, and the safety of TA is better. TA may be considered as the first-line local treatment option for patients with CRLM.
Collapse
Affiliation(s)
- Yaqing Kong
- Department of Interventional Therapy, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Xiaoyu Huang
- Department of Interventional Therapy, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Xiaojing Cao
- Department of Interventional Therapy, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Fan Tang
- Department of Interventional Therapy, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Xiang Zhou
- Department of Interventional Therapy, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
| |
Collapse
|
|
4
|
Zhang Y, Ma H, Lei P, Li Z, Yan Z, Wang X. Prediction of early postoperative recurrence of hepatocellular carcinoma by habitat analysis based on different sequence of contrast-enhanced CT. Front Oncol 2025; 14:1522501. [PMID: 39830646 PMCID: PMC11739309 DOI: 10.3389/fonc.2024.1522501] [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: 11/04/2024] [Accepted: 12/10/2024] [Indexed: 01/22/2025] Open
Abstract
Aim To develop a habitat imaging method for preoperative prediction of early postoperative recurrence of hepatocellular carcinoma. Methods A retrospective cohort study was conducted to collect data on 344 patients who underwent liver resection for HCC. The internal subregion of the tumor was objectively delineated and the clinical features were also analyzed to construct clinical models. Radiomics feature extraction was performed on tumor subregions of arterial and portal venous phase images. Machine learning classification models were constructed as a fusion model combining the three different models, and the models were assessed. Results A comprehensive retrospective analysis was conducted on a cohort of 344 patients who underwent hepatic cancer resection at one of the two centers. it was found that the combined SVM model yielded superior results after comparing various metrics, such as the AUC, accuracy, sensitivity, specificity, and DCA. Conclusions Habitat analysis of sequential CT images can delineate distinct subregions within a tumor, offering valuable insights for early prediction of postoperative HCC recurrence.
Collapse
Affiliation(s)
- Yubo Zhang
- Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, Yinchuan, China
- School of Clinical Medicine, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Hongyan Ma
- School of Clinical Medicine, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Peng Lei
- Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Zhiyuan Li
- School of Clinical Medicine, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Zhao Yan
- School of Clinical Medicine, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Xinqing Wang
- Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, Yinchuan, China
| |
Collapse
|
|
5
|
Yugawa K, Maeda T, Tsuji K, Shimokawa M, Sakai A, Yamaguchi S, Konishi K, Hashimoto K. Mac-2 binding protein glycosylation isomer as a novel predictor of early recurrence after resection for hepatocellular carcinoma. Surg Today 2025; 55:62-69. [PMID: 38937354 DOI: 10.1007/s00595-024-02885-z] [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: 07/31/2023] [Accepted: 05/20/2024] [Indexed: 06/29/2024]
Abstract
PURPOSE Hepatocellular carcinoma (HCC) frequently recurs after radical resection, resulting in a poor prognosis. This study assessed the prognostic value of Mac-2 binding protein glycosylation isomer (M2BPGi) for early recurrence (ER) in patients with HCC. METHODS Patients who underwent radical resection for HCC between 2015 and 2021. HCC recurrence within one year after curative resection was defined as ER. RESULTS The 150 patients were divided into two groups: non-ER (116, 77.3%) and ER (34, 22.7%). The ER group had a lower overall survival rate (p < 0.0001) and significantly higher levels of M2BPGi (1.06 vs. 2.74 COI, p < 0.0001) than the non-ER group. High M2BPGi levels (odds ratio [OR] 1.78, 95% confidence interval [CI] 1.31-2.41, p < 0.0001) and a large tumor size (OR 1.31, 95% CI, 1.05-1.63; p = 0.0184) were identified as independent predictors of ER. M2BPGi was the best predictor of ER according to a receiver operating characteristic (ROC) analysis (area under the ROC curve 0.82, p < 0.0001). CONCLUSIONS M2BPGi can predict ER after surgery and is useful for risk stratification in patients with HCC.
Collapse
Affiliation(s)
- Kyohei Yugawa
- Department of Surgery, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, Hiroshima, 730-0052, Japan
| | - Takashi Maeda
- Department of Surgery, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, Hiroshima, 730-0052, Japan.
| | - Keiji Tsuji
- Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, Hiroshima, Japan
| | - Mototsugu Shimokawa
- Department of Biostatistics, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan
| | - Akihiro Sakai
- Department of Surgery, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, Hiroshima, 730-0052, Japan
| | - Shohei Yamaguchi
- Department of Surgery, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, Hiroshima, 730-0052, Japan
| | - Kozo Konishi
- Department of Surgery, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, Hiroshima, 730-0052, Japan
| | - Kenkichi Hashimoto
- Department of Surgery, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, Hiroshima, 730-0052, Japan
| |
Collapse
|
|
6
|
Cai Y, Wang W, Jiao Q, Hu T, Ren Y, Su X, Li Z, Feng M, Liu X, Wang Y. Nanotechnology for the Diagnosis and Treatment of Liver Cancer. Int J Nanomedicine 2024; 19:13805-13821. [PMID: 39735328 PMCID: PMC11681781 DOI: 10.2147/ijn.s490661] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Accepted: 12/04/2024] [Indexed: 12/31/2024] Open
Abstract
Liver cancer has become a major global health challenge due to its high incidence, high rate of late diagnosis and limited treatment options. Although there are many clinical treatments available for liver cancer, the cure rate is still very low, and now researchers have begun to explore new aspects of liver cancer treatment, and nanotechnology has shown great potential for improving diagnostic accuracy and therapeutic efficacy and is therefore a promising treatment option. In diagnosis, nanomaterials such as gold nanoparticles, magnetic nanoparticles, and silver nanoparticles can realize highly sensitive and specific detection of liver cancer biomarkers, supporting diagnosis and real-time monitoring of the disease process. In terms of treatment, nanocarriers can realize precise targeted delivery of drugs, improve the bioavailability of liver cancer therapeutic drugs and reduce systemic toxic side effects. In addition, advanced technologies such as nanoparticle-based photothermal therapy and photodynamic therapy provide innovative solutions to overcome drug resistance and local tumor ablation. Therefore, in this paper, we will introduce nanotechnology for hepatocellular carcinoma in terms of tumor marker detection, targeted drug delivery, and synergistic PDT/CDT therapy.
Collapse
Affiliation(s)
- Yuxuan Cai
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China
| | - Weiwei Wang
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China
| | - Qinlian Jiao
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China
| | - Tangbin Hu
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China
| | - Yidan Ren
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China
| | - Xin Su
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250033, People’s Republic of China
| | - Zigan Li
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250033, People’s Republic of China
| | - Maoxiao Feng
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China
| | - Xiaoyan Liu
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China
| | - Yunshan Wang
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China
| |
Collapse
|
|
7
|
Gu K, Min JH, Lee JH, Shin J, Jeong WK, Kim YK, Kim H, Baek SY, Kim JM, Choi GS, Rhu J, Ha SY. Prognostic significance of MRI features in patients with solitary large hepatocellular carcinoma following surgical resection. Eur Radiol 2024; 34:7002-7012. [PMID: 38767659 DOI: 10.1007/s00330-024-10780-x] [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: 11/03/2023] [Revised: 02/22/2024] [Accepted: 03/17/2024] [Indexed: 05/22/2024]
Abstract
OBJECTIVE To assess the prognostic impact of preoperative MRI features on outcomes for single large hepatocellular carcinoma (HCC) (≥ 8 cm) after surgical resection. MATERIAL AND METHODS This retrospective study included 151 patients (mean age: 59.2 years; 126 men) with a single large HCC who underwent gadoxetic acid-enhanced MRI and surgical resection between 2008 and 2020. Clinical variables, including tumor markers and MRI features (tumor size, tumor margin, and the proportion of hypovascular component on hepatic arterial phase (AP) (≥ 50% vs. < 50% tumor volume) were evaluated. Cox proportional hazards model analyzed overall survival (OS), recurrence-free survival (RFS), and associated factors. RESULTS Among 151 HCCs, 37.8% and 62.2% HCCs were classified as ≥ 50% and < 50% AP hypovascular groups, respectively. The 5- and 10-year OS and RFS rates in all patients were 62.0%, 52.6% and 41.4%, 38.5%, respectively. Multivariable analysis revealed that ≥ 50% AP hypovascular group (hazard ratio [HR] 1.7, p = 0.048), tumor size (HR 1.1, p = 0.006), and alpha-fetoprotein ≥ 400 ng/mL (HR 2.6, p = 0.001) correlated with poorer OS. ≥ 50% AP hypovascular group (HR 1.9, p = 0.003), tumor size (HR 1.1, p = 0.023), and non-smooth tumor margin (HR 2.1, p = 0.009) were linked to poorer RFS. One-year RFS rates were lower in the ≥ 50% AP hypovascular group than in the < 50% AP hypovascular group (47.4% vs 66.9%, p = 0.019). CONCLUSION MRI with ≥ 50% AP hypovascular component and larger tumor size were significant factors associated with poorer OS and RFS after resection of single large HCC (≥ 8 cm). These patients require careful multidisciplinary management to determine optimal treatment strategies. CLINICAL RELEVANCE STATEMENT Preoperative MRI showing a ≥ 50% arterial phase hypovascular component and larger tumor size can predict worse outcomes after resection of single large hepatocellular carcinomas (≥ 8 cm), underscoring the need for tailored, multidisciplinary treatment strategies. KEY POINTS MRI features offer insights into the postoperative prognosis for large hepatocellular carcinoma. Hypovascular component on arterial phase ≥ 50% and tumor size predicted poorer overall survival and recurrence-free survival. These findings can assist in prioritizing aggressive and multidisciplinary approaches for patients at risk for poor outcomes.
Collapse
Affiliation(s)
- Kyowon Gu
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Ji Hye Min
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
| | - Jeong Hyun Lee
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jaeseung Shin
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Woo Kyoung Jeong
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Young Kon Kim
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Honsoul Kim
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Sun-Young Baek
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Gyu Seong Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jinsoo Rhu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Sang Yun Ha
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| |
Collapse
|
|
8
|
Altaf A, Munir MM, Endo Y, Khan MMM, Rashid Z, Khalil M, Guglielmi A, Aldrighetti L, Bauer TW, Marques HP, Martel G, Lam V, Weiss MJ, Fields RC, Poultsides G, Maithel SK, Endo I, Pawlik TM. Development of an artificial intelligence-based model to predict early recurrence of neuroendocrine liver metastasis after resection. J Gastrointest Surg 2024; 28:1828-1837. [PMID: 39197678 DOI: 10.1016/j.gassur.2024.08.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 08/12/2024] [Accepted: 08/21/2024] [Indexed: 09/01/2024]
Abstract
PURPOSE We sought to develop an artificial intelligence (AI)-based model to predict early recurrence (ER) after curative-intent resection of neuroendocrine liver metastases (NELMs). METHODS Patients with NELM who underwent resection were identified from a multi-institutional database. ER was defined as recurrence within 12 months of surgery. Different AI-based models were developed to predict ER using 10 clinicopathologic factors. RESULTS Overall, 473 patients with NELM were included. Among 284 patients with recurrence (60.0%), 118 patients (41.5%) developed an ER. An ensemble AI model demonstrated the highest area under receiver operating characteristic curves of 0.763 and 0.716 in the training and testing cohorts, respectively. Maximum diameter of the primary neuroendocrine tumor, NELM radiologic tumor burden score, and bilateral liver involvement were the factors most strongly associated with risk of NELM ER. Patients predicted to develop ER had worse 5-year recurrence-free survival and overall survival (21.4% vs 37.1% [P = .002] and 61.6% vs 90.3% [P = .03], respectively) than patients not predicted to recur. An easy-to-use tool was made available online: (https://altaf-pawlik-nelm-earlyrecurrence-calculator.streamlit.app/). CONCLUSION An AI-based model demonstrated excellent discrimination to predict ER of NELM after resection. The model may help identify patients who can benefit the most from curative-intent resection, risk stratify patients according to prognosis, as well as guide tailored surveillance and treatment decisions including consideration of nonsurgical treatment options.
Collapse
Affiliation(s)
- Abdullah Altaf
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, United States
| | - Muhammad Musaab Munir
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, United States
| | - Yutaka Endo
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, United States
| | - Muhammad Muntazir M Khan
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, United States
| | - Zayed Rashid
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, United States
| | - Mujtaba Khalil
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, United States
| | | | | | - Todd W Bauer
- Department of Surgery, University of Virginia School of Medicine, Charlottesville, VA, United States
| | - Hugo P Marques
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | - Guillaume Martel
- Department of Surgery, University of Ottawa, Ottawa, Ontario, Canada
| | - Vincent Lam
- Department of Surgery, Westmead Hospital, Sydney, New South Wales, Australia
| | - Mathew J Weiss
- Department of Surgery, Johns Hopkins Medicine, Baltimore, MD, United States
| | - Ryan C Fields
- Department of Surgery, Washington University in Saint Louis School of Medicine, Saint Louis, MO, United States
| | - George Poultsides
- Department of Surgery, Stanford University School of Medicine, Stanford, CA, United States
| | - Shishir K Maithel
- Department of Surgery, Emory University School of Medicine, Atlanta, GA, United States
| | - Itaru Endo
- Department of Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, United States.
| |
Collapse
|
|
9
|
Huang K, Qian T, Chen W, Lao M, Li H, Lin WC, Chen BW, Bai X, Gao S, Ma T, Liang T. The role of adjuvant transcatheter arterial chemoembolization following repeated curative resection/ablation for hepatocellular carcinoma with early recurrence: a propensity score matching analysis. BMC Cancer 2024; 24:620. [PMID: 38773564 PMCID: PMC11110442 DOI: 10.1186/s12885-024-12396-2] [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: 01/30/2024] [Accepted: 05/16/2024] [Indexed: 05/24/2024] Open
Abstract
BACKGROUND The role of adjuvant transcatheter arterial chemoembolization (TACE) following repeated resection/ablation for recurrent hepatocellular carcinoma (HCC) remains uncertain. The aim of this study was to assess the effectiveness of adjuvant TACE following repeated resection or ablation in patients with early recurrent HCC. METHODS Information for patients who underwent repeated surgery or radiofrequency ablation (RFA) for early recurrent HCCs (< 2 years) at our institution from January 2017 to December 2020 were collected. Patients were divided into adjuvant TACE and observation groups according to whether they received adjuvant TACE or not. The recurrence-free survival (RFS) and overall survival (OS) were compared between the two groups before and after propensity score matching (PSM). RESULTS Of the 225 patients enrolled, the median time of HCC recurrence was 11 months (IQR, 6-16 months). After repeated surgery or radiofrequency ablation (RFA) for recurrent tumors, 45 patients (20%) received adjuvant TACE while the remaining 180 (80%) didn't. There were no significant differences in RFS (P = 0.325) and OS (P = 0.072) between adjuvant TACE and observation groups before PSM. There were also no significant differences in RFS (P = 0.897) and OS (P = 0.090) between the two groups after PSM. Multivariable analysis suggested that multiple tumors, liver cirrhosis, and RFA were independent risk factors for the re-recurrence of HCC. CONCLUSION Adjuvant TACE after repeated resection or ablation for early recurrent HCCs was not associated with a long-term survival benefit in this single-center cohort.
Collapse
Affiliation(s)
- Kaiquan Huang
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Tao Qian
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Wen Chen
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Mengyi Lao
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Huiliang Li
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Wei-Chiao Lin
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Bryan Wei Chen
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Xueli Bai
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Shunliang Gao
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Tao Ma
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China.
| | - Tingbo Liang
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China.
- Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou, China.
- Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China.
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China.
- Cancer Center, Zhejiang University, Hangzhou, China.
| |
Collapse
|
|
10
|
Lu Y, Xing F, Peng S. The effect of CXCL12 on survival outcomes of patients with viral hepatitis-associated hepatocellular carcinoma after hepatectomy. Heliyon 2024; 10:e30782. [PMID: 38756575 PMCID: PMC11096947 DOI: 10.1016/j.heliyon.2024.e30782] [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: 10/06/2023] [Revised: 05/05/2024] [Accepted: 05/06/2024] [Indexed: 05/18/2024] Open
Abstract
Background The CXCL12-CXCR4/CXCR7 axis is garnering growing attention. But the comprehension of its function in the progression of HCC remains controversial. The purpose of this study was to investigate the effects of CXCL12 and its receptor on the prognosis of patients with viral hepatitis-associated HCC after hepatectomy. Methods A total of 86 patients had been enrolled who had undergone hepatectomy for HCC and followed up to July 31, 2019, and their clinicopathological and follow-up data were recorded. Tumor and peritumoral tissues were obtained to detect the expression of CXCL12, CXCR4, and CXCR7 using immunohistochemistry. Real-time polymerase chain reaction was utilized to detect hepatitis B or C virus loads, while survival analysis was performed using the Kaplan-Meier method. Furthermore, the Cox proportional hazards regression model was employed to analyze the factors affecting the prognosis. Results The results revealed that the CXCL12, CXCR4, and CXCR7 expression in tumor tissues was lower than in the corresponding non-tumor tissues in 20.93 %, 22.09 %, and 23.26 % of the patients, respectively, and that only CXCL12 was found to be related to the extrahepatic invasion of HCC. The survival analysis and Cox regression showed that only CXCL12 was associated with the postoperative survival of patients with HCC, and that it was an independent prognostic risk factor in the CXCL12-CXCR4/CXCR7 axis. The CXCL12low group represented shorter progression-free survival and lower overall survival rates. However, the subgroup analysis displayed that the survival difference associated with CXCL12 was only manifested in patients with higher expression of CXCR4 or CXCR7 in HCC, as compared to the surrounding tissues. Conclusions Our findings suggest that, when assessing the prognostic significance of CXCL12 in HCC, it is essential to consider the expression level of its receptor. Nevertheless, CXCL12 can potentially serve as a promising prognostic marker for HCC.
Collapse
Affiliation(s)
- Yan Lu
- the Department of Hospital Infection Control and Public Health Management, the Seventh Affiliated Hospital, Sun Yat-sen University, No. 628 Zhenyuan Road, Guangming District, Shenzhen, 518107, China
| | - Fei Xing
- the Department of Oncology, the Shengjing Hospital of China Medical University, Shenyang, No. 36 Sanhao Street, Heping District, 110004, China
| | - Songlin Peng
- the Department of General Surgery, the Seventh Affiliated Hospital, Sun Yat-sen University, No. 628 Zhenyuan Road, Guangming District, Shenzhen, 518107, China
| |
Collapse
|
|
11
|
Yu Y, Wang XH, Hu WJ, Chen DH, Hu ZL, Li SQ. Patterns, Risk Factors, and Outcomes of Recurrence After Hepatectomy for Hepatocellular Carcinoma with and without Microvascular Invasion. J Hepatocell Carcinoma 2024; 11:801-812. [PMID: 38737385 PMCID: PMC11088842 DOI: 10.2147/jhc.s438850] [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: 09/06/2023] [Accepted: 04/24/2024] [Indexed: 05/14/2024] Open
Abstract
Purpose The patterns and risk factors of postsurgical recurrence of patient with hepatocellular carcinoma (HCC) with microvascular invasion (MVI) are not clarified. This study aimed to decipher and compare the postoperative recurrent patterns and the risk factors contributing to recurrence between MVI positive (MVI(+)) and MVI negative (MVI(-)) HCC after hepatectomy. Patients and methods Patients with HCC who underwent hepatectomy in three Chinese academic hospitals between January 1, 2009, and December 31, 2018, were enrolled. Recurrent patterns included early (≤2 years) or late (>2 years) recurrence, recurrent sites and number, and risk factors of recurrence were compared between the MVI(+)and MVI(-) groups by propensity score-matching (PSM). Results Of 1756 patients included, 581 (33.1%) were MVI(+), and 875 (49.8%) patients developed early recurrence. Compared with the MVI(-) group, the MVI(+) group had a higher 2-year recurrence rate in the PSM cohort (hazard ratio [HR], 1.82; 95% confidence interval [CI], 1.59-2.10; P < 0.001), and more patients with multiple tumor recurrence. Patients with early recurrence in the MVI(+) group had a worse overall survival (OS) than those in the MVI(-) group (HR, 1.24; 95% CI, 1.02-1.50; P = 0.034). Resection margin (RM) ≤1.0 cm is a surgical predictor of early recurrence for the MVI(+) group (HR, 0.68; 95% CI, 0.54-0.87; P = 0.002), but not for the MVI(-) group. Conclusion Compared to MVI(-) HCC, MVI(+) HCC tends to be early, multiple recurrence and lung and lymph node metastasis after resection. RM ≤1.0 cm is a surgical risk factor of early recurrence for patient with MVI.
Collapse
Affiliation(s)
- Yang Yu
- Hepatic Pancreatobiliary Surgery Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China
| | - Xiao-Hui Wang
- Department of Hepatobiliary Surgery, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University) Changsha, Hunan Province, 410005, People’s Republic of China
| | - Wen-Jie Hu
- Hepatic Pancreatobiliary Surgery Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China
| | - De-Hua Chen
- Hepatic Pancreatobiliary Surgery Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China
| | - Zi-Li Hu
- Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangdong, 510060, Guangzhou, People’s Republic of China
| | - Shao-Qiang Li
- Hepatic Pancreatobiliary Surgery Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China
| |
Collapse
|
|
12
|
Vaghiri S, Prassas D, Mustafov O, Kalmuk S, Knoefel WT, Lehwald-Tywuschik N, Alexander A, Dizdar L. Which factors predict tumor recurrence and survival after curative hepatectomy in hepatocellular carcinoma? Results from a European institution. BMC Surg 2024; 24:101. [PMID: 38589847 PMCID: PMC11003056 DOI: 10.1186/s12893-024-02399-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: 02/22/2024] [Accepted: 03/28/2024] [Indexed: 04/10/2024] Open
Abstract
BACKGROUND High tumor recurrence and dismal survival rates after curative intended resection for hepatocellular carcinoma (HCC) are still concerning. The primary goal was to assess predictive factors associated with disease-free (DFS) and overall survival (OS) in a subset of patients with HCC undergoing hepatic resection (HR). METHODS Between 08/2004-7/2021, HR for HCC was performed in 188 patients at our institution. Data allocation was conducted from a prospectively maintained database. The prognostic impact of clinico-pathological factors on DFS and OS was assessed by using uni- and multivariate Cox regression analyses. Survival curves were generated with the Kaplan Meier method. RESULTS The postoperative 1-, 3- and 5- year overall DFS and OS rates were 77.9%, 49.7%, 41% and 72.7%, 54.7%, 38.8%, respectively. Tumor diameter ≥ 45 mm [HR 1.725; (95% CI 1.091-2.727); p = 0.020], intra-abdominal abscess [HR 3.812; (95% CI 1.859-7.815); p < 0.0001], and preoperative chronic alcohol abuse [HR 1.831; (95% CI 1.102-3.042); p = 0.020] were independently predictive for DFS while diabetes mellitus [HR 1.714; (95% CI 1.147-2.561); p = 0.009), M-Stage [HR 2.656; (95% CI 1.034-6.826); p = 0.042], V-Stage [HR 1.946; (95% CI 1.299-2.915); p = 0.001, Sepsis [HR 10.999; (95% CI 5.167-23.412); p < 0.0001], and ISGLS B/C [HR 2.008; (95% CI 1.273-3.168); p = 0.003] were significant determinants of OS. CONCLUSIONS Despite high postoperative recurrence rates, an acceptable long-term survival in patients after curative HR could be achieved. The Identification of parameters related to OS and DFS improves patient-centered treatment and surveillance strategies.
Collapse
Affiliation(s)
- Sascha Vaghiri
- Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, Bldg. 12.46, 40225, Duesseldorf, Germany
| | - Dimitrios Prassas
- Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, Bldg. 12.46, 40225, Duesseldorf, Germany
- Department of Surgery, Katholisches Klinikum Essen, Philippusstift, Teaching Hospital of Duisburg-Essen University, Huelsmannstrasse 17, 45355, Essen, Germany
| | - Onur Mustafov
- Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, Bldg. 12.46, 40225, Duesseldorf, Germany
| | - Sinan Kalmuk
- Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, Bldg. 12.46, 40225, Duesseldorf, Germany
| | - Wolfram Trudo Knoefel
- Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, Bldg. 12.46, 40225, Duesseldorf, Germany.
| | - Nadja Lehwald-Tywuschik
- Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, Bldg. 12.46, 40225, Duesseldorf, Germany
| | - Andrea Alexander
- Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, Bldg. 12.46, 40225, Duesseldorf, Germany
| | - Levent Dizdar
- Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, Bldg. 12.46, 40225, Duesseldorf, Germany
| |
Collapse
|
|
13
|
Cho WR, Wang CC, Tsai MJ, Lin CC, Yen YH, Chen CH, Kuo YH, Yao CC, Hung CH, Huang PY, Liu AC, Tsai MC. Smoking as a Risk Factor for Very Late Recurrence in Surgically Resected Early-Stage Primary Hepatocellular Carcinoma. Clin Med Insights Oncol 2024; 18:11795549241228232. [PMID: 38450293 PMCID: PMC10916494 DOI: 10.1177/11795549241228232] [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: 06/22/2023] [Accepted: 01/07/2024] [Indexed: 03/08/2024] Open
Abstract
Background The risk of first recurrence of hepatocellular carcinoma (HCC) within years 5 to 10 after curative hepatectomy remains unknown. We aimed to assess the incidence and prognostic factors for very late recurrence among patients who achieved 5 years' recurrence-free survival (RFS) after primary resection. Methods We retrospectively analyzed 337 patients with early-stage HCC underwent primary tumor resection and achieved more than 5 years' RFS. Results A total of 77 patients (22.8%) developed very late recurrence. The cumulative very late recurrence rate increased from 6.9% and 11.7% to 16.6% at 6, 7, and 8 years, respectively. Patients stopped smoking had a higher rate of very late RFS. Conclusions The high rates of very late recurrence in HCC indicate that patients warrant continued surveillance, even after 5 recurrence-free years. Moreover, smoking is a risk factor for very late HCC recurrence, and quitting smoking may reduce the risk of very late recurrence.
Collapse
Affiliation(s)
- Wei-Ru Cho
- Department of Hepato-Gastroenterology, Chang Gung Memorial Hospital, Yunlin
| | - Chih-Chi Wang
- Division of General Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
| | - Mu-Jung Tsai
- Kaohsiung Municipal Kaohsiung Senior High School, Kaohsiung
| | - Chih-Che Lin
- Division of General Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
| | - Yi-Hao Yen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
| | - Chien Hung Chen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
| | - Yuan-Hung Kuo
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
| | - Chih-Chien Yao
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
| | - Chao-Hung Hung
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
| | - Pao-Yuan Huang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
| | - An-Che Liu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
| | - Ming-Chao Tsai
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
- School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung
| |
Collapse
|
|
14
|
Hosoda K, Umemura K, Shimizu A, Kubota K, Notake T, Kitagawa N, Sakai H, Hayashi H, Yasukawa K, Soejima Y. The platelet-to-lymphocyte ratio is a complementary prognostic factor to tumor markers in predicting early recurrence of hepatocellular carcinoma after hepatectomy. J Surg Oncol 2024; 129:765-774. [PMID: 38105473 DOI: 10.1002/jso.27564] [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: 08/24/2023] [Accepted: 12/03/2023] [Indexed: 12/19/2023]
Abstract
BACKGROUND The usefulness of inflammation-based prognostic scores for early recurrence (ER) after hepatectomy for hepatocellular carcinoma has rarely been reported. This study aimed to evaluate the potential of inflammation-based prognostic scores as predictors of ER and their relationship with tumor markers. METHODS We enrolled 338 patients who underwent hepatectomy for hepatocellular carcinoma between January 2007 and December 2021. Clinicopathological factors were compared between patients who developed ER (ER group) and those who did not develop ER (non-ER group). The association between inflammation-based prognostic scores and ER status was evaluated. These scores were compared with those of well-established tumor markers. RESULTS The platelet-to-lymphocyte ratio (PLR) correlated with ER of hepatocellular carcinoma, with an area under the curve (AUC) value of 0.70, sensitivity of 68.1%, and specificity of 67.7%. In patients with low tumor marker levels, the PLR showed a strong correlation with ER of hepatocellular carcinoma, with an AUC value of 0.851, sensitivity of 100%, and specificity of 76.2%. Multivariate analysis revealed that the PLR was an independent prognostic factor for ER. CONCLUSIONS The PLR is useful and complementary to tumor markers for predicting ER after hepatectomy for hepatocellular carcinoma.
Collapse
Affiliation(s)
- Kiyotaka Hosoda
- Department of Surgery, Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Kentaro Umemura
- Department of Surgery, Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Akira Shimizu
- Department of Surgery, Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Koji Kubota
- Department of Surgery, Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Tsuyoshi Notake
- Department of Surgery, Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Noriyuki Kitagawa
- Department of Surgery, Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Hiroki Sakai
- Department of Surgery, Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Hikaru Hayashi
- Department of Surgery, Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Koya Yasukawa
- Department of Surgery, Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Yuji Soejima
- Department of Surgery, Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| |
Collapse
|
|
15
|
Harimoto N, Tsukagoshi M, Seki T, Hoshino K, Hagiwara K, Ishii N, Igarashi T, Araki K, Haruki K, Ikegami T, Shirabe K. Predictors for early recurrence beyond up-to-7 or distant metastasis after hepatocellular carcinoma resection: proposal for borderline resectable HCC. Int J Clin Oncol 2024; 29:195-204. [PMID: 38227089 DOI: 10.1007/s10147-023-02434-7] [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: 05/24/2023] [Accepted: 11/01/2023] [Indexed: 01/17/2024]
Abstract
BACKGROUND The recurrence rate after curative resection for hepatocellular carcinoma (HCC) reaches over 70% after 5 years and early recurrence (within 1 year) is now recognized as having a poor prognosis and has limited treatment options. METHODS We retrospectively reviewed 184 consecutive patients who underwent curative hepatic resection for HCC. Severe early recurrence was defined as multiple (beyond up-to-7) liver recurrence or distant metastasis after hepatic resection within 1 year. We divided the participants into two groups according to severe early recurrence and analyzed clinicopathological and long-term outcomes. RESULTS Among the patients with multiple or distant metastasis (n = 59), 49 patients (83%) had recurrence within 1 year. Overall survival (OS) and recurrence-free survival (RFS) were significantly worse in the severe early recurrence group than in the others group. Logistic regression analysis revealed that severe early recurrence was significantly associated with macroscopic vascular invasion (MVI), tumor burden score (TBS) > 4.70, and ALBI grade 2. In patients with scores of 2 and 3 (the sum of the three factors), OS and RFS rates were significantly poorer than those of patients with scores of 0 or 1. Positive predictive value and negative predictive value for severe early recurrence was 68.4% and 84.2%, respectively. Furthermore, a validation study demonstrated that cases with these factors were at high risk of severe early recurrence and had poor prognosis. CONCLUSIONS In this retrospective analysis, MVI, TBS, and ALBI could predict severe early recurrence after hepatic resection for HCC, and patients with these risk factors had a poor prognosis.
Collapse
Affiliation(s)
- Norifumi Harimoto
- Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, Graduate School of Medicine, Gunma University, 3-39-22, Showamachi, Maebashi, 371-8511, Japan.
| | - Mariko Tsukagoshi
- Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, Graduate School of Medicine, Gunma University, 3-39-22, Showamachi, Maebashi, 371-8511, Japan
| | - Takaomi Seki
- Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, Graduate School of Medicine, Gunma University, 3-39-22, Showamachi, Maebashi, 371-8511, Japan
| | - Kouki Hoshino
- Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, Graduate School of Medicine, Gunma University, 3-39-22, Showamachi, Maebashi, 371-8511, Japan
| | - Kei Hagiwara
- Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, Graduate School of Medicine, Gunma University, 3-39-22, Showamachi, Maebashi, 371-8511, Japan
| | - Norihiro Ishii
- Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, Graduate School of Medicine, Gunma University, 3-39-22, Showamachi, Maebashi, 371-8511, Japan
| | - Takamichi Igarashi
- Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, Graduate School of Medicine, Gunma University, 3-39-22, Showamachi, Maebashi, 371-8511, Japan
| | - Kenichiro Araki
- Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, Graduate School of Medicine, Gunma University, 3-39-22, Showamachi, Maebashi, 371-8511, Japan
| | - Koichiro Haruki
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan
| | - Toru Ikegami
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan
| | - Ken Shirabe
- Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, Graduate School of Medicine, Gunma University, 3-39-22, Showamachi, Maebashi, 371-8511, Japan
| |
Collapse
|
|
16
|
Shi S, Zhao YX, Fan JL, Chang LY, Yu DX. Development and External Validation of a Nomogram Including Body Composition Parameters for Predicting Early Recurrence of Hepatocellular Carcinoma After Hepatectomy. Acad Radiol 2023; 30:2940-2953. [PMID: 37798207 DOI: 10.1016/j.acra.2023.05.022] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 05/20/2023] [Accepted: 05/21/2023] [Indexed: 10/07/2023]
Abstract
RATIONALE AND OBJECTIVES Body composition, including adipose and muscle tissues, evaluated by computer tomography is correlated with the prognosis of hepatocellular carcinoma (HCC). However, its relationship with early recurrence (ER) remains unclear. This study aimed at establishing and validating a nomogram based on body composition and clinicopathological indices to predict ER of HCC. MATERIALS AND METHODS One hundred ninety-five patients from institution A formed the training cohort and internal validation cohort, and 50 patients from institution B formed the external validation cohort. Independent predictors of ER were identified using LASSO and Cox regression analyses. The performance of nomogram was evaluated using the calibration curve, concordance index (C-index), area under the curve (AUC), and decision curve analysis (DCA). RESULTS After data screening, the nomogram was constructed using eight independent predictors of ER, including the tumor size, alpha fetoprotein, body mass index, Edmondson Steiner grade, visceral adipose tissue radiodensity, intermuscular adipose tissue index, intramuscular adipose tissue content, and skeletal muscle area. The calibration curve exhibited excellent concordances, with C-indices of 0.808 (95%CI: 0.771-0.860), 0.802 (95%CI: 0.747-0.942), and 0.804 (95%CI: 0.701-0.861) in training, internal validation, and external validation cohorts, respectively. In addition, compared to conventional staging systems and pure clinical model, the nomogram exhibited a higher AUC and wider range of threshold probabilities in DCA, which indicated better discriminative ability and greater clinical benefit. Finally, patients with nomogram scores of <183.07, 183.07-243.09, and >243.09 were considered to have low, moderate, and high risks of ER, respectively. CONCLUSION The nomogram exhibits excellent ER predictive ability for patients with HCC who underwent hepatectomy.
Collapse
Affiliation(s)
- Shuo Shi
- Department of Radiology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China
| | - Yu-Xuan Zhao
- Department of Radiology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China
| | - Jin-Lei Fan
- Department of Radiology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China
| | - Ling-Yu Chang
- Department of Radiology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China
| | - De-Xin Yu
- Department of Radiology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China.
| |
Collapse
|
|
17
|
Endo Y, Munir MM, Woldesenbet S, Katayama E, Ratti F, Marques HP, Cauchy F, Lam V, Poultsides GA, Kitago M, Popescu I, Alexandrescu S, Martel G, Workneh A, Guglielmi A, Gleisner A, Hugh T, Aldrighetti L, Shen F, Endo I, Pawlik TM. Impact of Surgical Margin Width on Prognosis Following Resection of Hepatocellular Carcinoma Varies on the Basis of Preoperative Alpha-Feto Protein and Tumor Burden Score. Ann Surg Oncol 2023; 30:6581-6589. [PMID: 37432523 DOI: 10.1245/s10434-023-13825-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Accepted: 06/14/2023] [Indexed: 07/12/2023]
Abstract
BACKGROUND We sought to examine the prognostic impact of margin width at time of hepatocellular carcinoma (HCC) resection relative to the alpha-feto protein tumor burden score (ATS). PATIENTS AND METHODS Patients who underwent curative-intent hepatectomy for HCC between 2000 and 2020 were identified from a multi-institutional database. The impact of margin width on overall survival and recurrence-free survival was examined relative to ATS using univariable and multivariable analyses. RESULTS Among 782 patients with HCC who underwent resection, median ATS was 6.5 [interquartile range (IQR) 4.3-10.2]. Most patients underwent R0 resection (n = 613, 78.4%); among patients who had an R0 resection, 325 (41.6%) had a margin width > 5 mm while 288 (36.8%) had a 0-5 mm margin width. Among patients with high ATS, an increasing margin width was associated with incrementally better overall and recurrence-free survival. In contrast, among patients with low ATS, margin width was not associated with long-term outcomes. On multivariable Cox regression analysis, each unit increase in ATS was independently associated with a 7% higher risk of death [hazard ratio (HR) 1.07; 95% confidence interval (CI) 1.03-1.11, p < 0.001]. While the incidence of early recurrence was not associated with margin width among patients with low ATS, wider margin width was associated with an incrementally lower incidence of early recurrence among patients with high ATS. CONCLUSION ATS, an easy-to-use composite tumor-related metric, was able to risk stratify patients following resection of HCC relative to overall survival and recurrence-free survival. The therapeutic impact of resection margin width had a variable impact on long-term outcomes relative to ATS.
Collapse
Affiliation(s)
- Yutaka Endo
- Department of Surgery, Wexner Medical Center and James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
| | - Muhammad Musaab Munir
- Department of Surgery, Wexner Medical Center and James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
| | - Selamawit Woldesenbet
- Department of Surgery, Wexner Medical Center and James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
| | - Erryk Katayama
- Department of Surgery, Wexner Medical Center and James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
| | | | - Hugo P Marques
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | - François Cauchy
- Department of Hepatobiliopancreatic Surgery, APHP, Beaujon Hospital, Clichy, France
| | - Vincent Lam
- Department of Surgery, Westmead Hospital, Sydney, NSW, Australia
| | | | - Minoru Kitago
- Department of Surgery, Keio University, Tokyo, Japan
| | - Irinel Popescu
- Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania
| | | | | | - Aklile Workneh
- Department of Surgery, University of Ottawa, Ottawa, ON, Canada
| | | | - Ana Gleisner
- Department of Surgery, University of Colorado, Denver, CO, USA
| | - Tom Hugh
- Department of Surgery, School of Medicine, The University of Sydney, Sydney, NSW, Australia
| | | | - Feng Shen
- Department of Hepatic Surgery IV, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Itaru Endo
- Yokohama City University School of Medicine, Yokohama, Japan
| | - Timothy M Pawlik
- Department of Surgery, Wexner Medical Center and James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
| |
Collapse
|
|
18
|
Akimoto S, Tahara H, Yanagawa S, Ide K, Tanaka Y, Kobayashi T, Ohdan H. Heterophile carbohydrate antigen N-glycolylneuraminic acid as a potential biomarker in patients with hepatocellular carcinoma. Cancer Rep (Hoboken) 2023; 6:e1831. [PMID: 37265054 PMCID: PMC10432449 DOI: 10.1002/cnr2.1831] [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: 01/25/2023] [Revised: 03/31/2023] [Accepted: 04/29/2023] [Indexed: 06/03/2023] Open
Abstract
BACKGROUND AND OBJECTIVES Hepatocellular carcinoma (HCC) has a high recurrence rate even after radical hepatectomy. More optimal biomarkers may help improve recurrence and prognosis. METHODS We investigated whether the oncological properties of N-glycolylneuraminic acid (NeuGc) can participate in the prognosis of HCC. We evaluated the NeuGc antigen (Ag) expression in the HCC tissues and measured the preoperative anti-NeuGc IgG antibodies (Abs) in the sera of the patients with HCC. We compared the clinical characteristics and survival rate in the hepatectomized patients (initial; n = 66, recurrent; n = 34) with and without the NeuGc Ag or Abs. RESULTS Multivariate analyses showed positive expression of NeuGc Ag in HCC tissues (Odds ratio; initial = 6.3, recurrent = 14.0) and higher titers of preoperative anti-NeuGc Ab (Odds ratio; initial = 4.9; recurrent = 3.8), which could be the predictive factors related to early recurrence. Both the NeuGc Ag-positive and Ab-positive groups in the initial hepatectomized patients exhibited significantly shorter recurrent free survival compared to those in the negative groups. CONCLUSIONS Our findings suggested that anti-NeuGc Ab titers and NeuGc Ag expression in the HCC tissues can be used as the predictive factors for the postoperative recurrence and prognosis of HCC.
Collapse
Affiliation(s)
- Shuji Akimoto
- Department of Gastroenterological and Transplant SurgeryGraduate School of Biomedical & Health Sciences, Hiroshima UniversityHiroshimaJapan
| | - Hiroyuki Tahara
- Department of Gastroenterological and Transplant SurgeryGraduate School of Biomedical & Health Sciences, Hiroshima UniversityHiroshimaJapan
| | - Senichiro Yanagawa
- Department of Gastroenterological and Transplant SurgeryGraduate School of Biomedical & Health Sciences, Hiroshima UniversityHiroshimaJapan
| | - Kentaro Ide
- Department of Gastroenterological and Transplant SurgeryGraduate School of Biomedical & Health Sciences, Hiroshima UniversityHiroshimaJapan
| | - Yuka Tanaka
- Department of Gastroenterological and Transplant SurgeryGraduate School of Biomedical & Health Sciences, Hiroshima UniversityHiroshimaJapan
| | - Tsuyoshi Kobayashi
- Department of Gastroenterological and Transplant SurgeryGraduate School of Biomedical & Health Sciences, Hiroshima UniversityHiroshimaJapan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant SurgeryGraduate School of Biomedical & Health Sciences, Hiroshima UniversityHiroshimaJapan
| |
Collapse
|
|
19
|
Shindoh J, Matsumura M, Kobayashi M, Akabane M, Okubo S, Hashimoto M. Disease-Free Interval and Tumor Stage Complementarily Predict the Biological Behavior of Recurrent Hepatocellular Carcinoma. Ann Surg Oncol 2023; 30:3402-3410. [PMID: 36808590 DOI: 10.1245/s10434-023-13228-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 01/21/2023] [Indexed: 02/21/2023]
Abstract
BACKGROUND Currently used treatment algorithms were originally established based on the clinical outcomes of the initial treatment for primary hepatocellular carcinoma (HCC), and no strong evidence exists yet to suggest if these algorithms could also be applicable to patients with recurrent HCC after surgery. As such, this study sought to explore an optimal risk stratification method for cases of recurrent HCC for better clinical management. METHODS Among the 1616 patients who underwent curative resection for HCC, the clinical features and survival outcomes of 983 patients who developed recurrence were examined in detail. RESULTS Multivariate analysis confirmed that both the disease-free interval (DFI) from the previous surgery and tumor stage at recurrence were significant prognostic factors. However, the prognostic impact of DFI seemed different according to the tumor stages at recurrence. While curative-intent treatment showed strong influence on survival [hazard ratio (HR), 0.61; P < 0.001] regardless of the DFI in patients with stage 0 or stage A disease at recurrence, early recurrence (< 6 months) was a poor prognostic marker in patients with stage B disease. The prognosis of patients with stage C disease was exclusively influenced by the tumor distribution or choice of treatment than by the DFI. CONCLUSIONS The DFI complementarily predicts the oncological behavior of recurrent HCC, with its predictive value differing depending on the tumor stage at recurrence. These factors should be considered for selection of the optimal treatment in patients with recurrent HCC after curative-intent surgery.
Collapse
Affiliation(s)
- Junichi Shindoh
- Hepatobiliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo, Japan.
- Okinaka Memorial Institute for Medical Disease, Tokyo, Japan.
| | - Masaru Matsumura
- Hepatobiliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo, Japan
| | - Masahiro Kobayashi
- Hepatobiliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo, Japan
| | - Miho Akabane
- Hepatobiliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo, Japan
| | - Satoshi Okubo
- Hepatobiliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo, Japan
| | - Masaji Hashimoto
- Hepatobiliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo, Japan
| |
Collapse
|
|
20
|
Bosi C, Rimini M, Casadei-Gardini A. Understanding the causes of recurrent HCC after liver resection and radiofrequency ablation. Expert Rev Anticancer Ther 2023; 23:503-515. [PMID: 37060290 DOI: 10.1080/14737140.2023.2203387] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/16/2023]
Abstract
INTRODUCTION Surgical resection and radiofrequency ablation are preferred options for early-stage disease, with 5-year recurrence rates as high as 70% when patients are treated according to guidelines. With increasing availability of therapeutic options, including but not limited to, immune-checkpoint inhibitors (ICI), tyrosine kinase inhibitors, antiangiogenics, and adoptive cell therapies, understanding the causes of recurrence and identifying its predictors should be priorities in the hepatocellular carcinoma (HCC) research agenda. AREAS COVERED Current knowledge of HCC predictors of recurrence is reviewed, and recent insights about its underlying mechanisms are presented. In addition, results from recent clinical trials investigating treatment combinations are critically appraised. EXPERT OPINION HCC recurrence is either due to progressive growth of microscopic residual disease, or to de novo cancer development in the context of a diseased liver, each occurring in an early (<2years) vs. late (≥2 years) fashion. Collectively, morphological, proteomic, and transcriptomic data suggest vascular invasion and angiogenesis as key drivers of HCC recurrence. Agents aimed at blocking either of these two hallmarks should be prioritized at the moment of early-stage HCC clinical trial design. Emerging results from clinical trials testing ICI in early-stage HCC underscore the importance of defining the best treatment sequence and the most appropriate combination strategies. Lastly, as different responses to systemic therapies are increasingly defined according to the HCC etiology, patient enrolment into clinical trials should take into account the biological characteristics of their inherent disease.
Collapse
Affiliation(s)
- Carlo Bosi
- Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy
- Vita-Salute San Raffaele University School of Medicine, Milan, 20132, Italy
| | - Margherita Rimini
- Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy
- Vita-Salute San Raffaele University School of Medicine, Milan, 20132, Italy
| | - Andrea Casadei-Gardini
- Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy
- Vita-Salute San Raffaele University School of Medicine, Milan, 20132, Italy
| |
Collapse
|
|
21
|
Villalba-López F, Sáenz-Mateos LF, Sánchez-Lorencio MI, De La Orden-García V, Alconchel-Gago F, Cascales-Campos PA, García-Bernardo C, Noguera-Velasco JA, Baroja-Mazo A, Ramírez-Romero P. Usefulness of PIVKA-II for monitoring after liver transplantation in patients with hepatocellular carcinoma. Sci Rep 2023; 13:5621. [PMID: 37024609 PMCID: PMC10079651 DOI: 10.1038/s41598-023-32879-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Accepted: 04/04/2023] [Indexed: 04/08/2023] Open
Abstract
The high morbidity and mortality of hepatocellular carcinoma (HCC) has encouraged the search for new biomarkers to be used alongside alpha-foetoprotein (AFP) and imaging tests. The aim of this study was to evaluate the clinical contribution of protein induced by vitamin K absence or antagonist-II (PIVKA-II) for HCC monitoring after liver transplantation (LT) and compare it with AFP, a routinely used tumour marker. A total of 46 HCC patients (Milan criteria) were enrolled in this study. Serum levels of PIVKA-II and AFP were measured before and after transplantation. Clinical features were determined for all the patients that were included. Significant correlations were found between PIVKA-II expression levels and some clinicopathological features, such as tumour size and number of pre-transplant transarterial chemoembolizations (TACEs). Serum levels of PIVKA-II and AFP decreased significantly after LT and increased in patients with tumour recurrence. Serum PIVKA-II levels may play an important role in predicting disease severity. Furthermore, monitoring PIVKA-II levels in HCC transplant recipients reflects the tumor early recurrence after transplantation and could be used, complementing AFP and imaging tests, as a novel biomarker of this pathology.
Collapse
Affiliation(s)
| | | | | | | | - Felipe Alconchel-Gago
- Liver Transplant Unit, University Hospital Virgen de la Arrixaca, 30120, Murcia, Spain
| | | | | | | | | | - Pablo Ramírez-Romero
- Liver Transplant Unit, University Hospital Virgen de la Arrixaca, 30120, Murcia, Spain
| |
Collapse
|
|
22
|
Deep learning model based on contrast-enhanced ultrasound for predicting early recurrence after thermal ablation of colorectal cancer liver metastasis. Eur Radiol 2023; 33:1895-1905. [PMID: 36418624 DOI: 10.1007/s00330-022-09203-6] [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: 05/18/2022] [Revised: 09/19/2022] [Accepted: 09/25/2022] [Indexed: 11/27/2022]
Abstract
OBJECTIVES To develop and validate a deep learning (DL) model based on quantitative analysis of contrast-enhanced ultrasound (CEUS) images that predicts early recurrence (ER) after thermal ablation (TA) of colorectal cancer liver metastasis (CRLM). METHODS Between January 2010 and May 2019, a total of 207 consecutive patients with CRLM with 13,248 slice images at three dynamic phases who received CEUS within 2 weeks before TA were retrospectively enrolled in two centres (153 for the training cohort (TC), 32 for the internal test cohort (ITC), and 22 for the external test cohort (ETC)). Clinical and CEUS data were used to develop and validate the clinical model, DL model, and DL combining with clinical (DL-C) model to predict ER after TA. The performance of these models was compared by the receiver operating characteristic curve (ROC) with the DeLong test. RESULTS After a median follow-up of 56 months, 49% (99/207) of patients experienced ER. Three key clinical features (preoperative chemotherapy (PC), lymph node metastasis of the primary colorectal cancer (LMPCC), and T stage) were used to develop the clinical model. The DL model yielded better performance than the clinical model in the ETC (AUC: 0.67 for the clinical model, 0.76 for the DL model). The DL-C model significantly outperformed the clinical model and DL model (AUC: 0.78 for the DL-C model in the ETC; both, p < 0.001). CONCLUSIONS The model based on CEUS can achieve satisfactory prediction and assist physicians during the therapeutic decision-making process in clinical practice. KEY POINTS • This is an exploratory study in which ablation-related contrast-enhanced ultrasound (CEUS) data from consecutive patients with colorectal cancer liver metastasis (CRLM) were collected simultaneously at multiple institutions. • The deep learning combining with clinical (DL-C) model provided desirable performance for the prediction of early recurrence (ER) after thermal ablation (TA). • The DL-C model based on CEUS provides guidance for TA indication selection and making therapeutic decisions.
Collapse
|
|
23
|
Nevola R, Ruocco R, Criscuolo L, Villani A, Alfano M, Beccia D, Imbriani S, Claar E, Cozzolino D, Sasso FC, Marrone A, Adinolfi LE, Rinaldi L. Predictors of early and late hepatocellular carcinoma recurrence. World J Gastroenterol 2023; 29:1243-1260. [PMID: 36925456 PMCID: PMC10011963 DOI: 10.3748/wjg.v29.i8.1243] [Citation(s) in RCA: 98] [Impact Index Per Article: 49.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 01/06/2023] [Accepted: 01/30/2023] [Indexed: 02/28/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most frequent liver neoplasm, and its incidence rates are constantly increasing. Despite the availability of potentially curative treatments (liver transplantation, surgical resection, thermal ablation), long-term outcomes are affected by a high recurrence rate (up to 70% of cases 5 years after treatment). HCC recurrence within 2 years of treatment is defined as "early" and is generally caused by the occult intrahepatic spread of the primary neoplasm and related to the tumor burden. A recurrence that occurs after 2 years of treatment is defined as "late" and is related to de novo HCC, independent of the primary neoplasm. Early HCC recurrence has a significantly poorer prognosis and outcome than late recurrence. Different pathogenesis corresponds to different predictors of the risk of early or late recurrence. An adequate knowledge of predictive factors and recurrence risk stratification guides the therapeutic strategy and post-treatment surveillance. Patients at high risk of HCC recurrence should be referred to treatments with the lowest recurrence rate and when standardized to combined or adjuvant therapy regimens. This review aimed to expose the recurrence predictors and examine the differences between predictors of early and late recurrence.
Collapse
Affiliation(s)
- Riccardo Nevola
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
- Internal Medicine and Hepatology Unit, Ospedale Evangelico Betania, Naples 80147, Italy
| | - Rachele Ruocco
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Livio Criscuolo
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Angela Villani
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Maria Alfano
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Domenico Beccia
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Simona Imbriani
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Ernesto Claar
- Internal Medicine and Hepatology Unit, Ospedale Evangelico Betania, Naples 80147, Italy
| | - Domenico Cozzolino
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Ferdinando Carlo Sasso
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Aldo Marrone
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Luigi Elio Adinolfi
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Luca Rinaldi
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| |
Collapse
|
|
24
|
Qin YL, Wang S, Chen F, Liu HX, Yue KT, Wang XZ, Ning HF, Dong P, Yu XR, Wang GZ. Prediction of outcomes by diffusion kurtosis imaging in patients with large (≥5 cm) hepatocellular carcinoma after liver resection: A retrospective study. Front Oncol 2022; 12:939358. [DOI: 10.3389/fonc.2022.939358] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 10/18/2022] [Indexed: 11/18/2022] Open
Abstract
PurposeTo evaluate preoperative diffusion kurtosis imaging (DKI) in predicting the outcomes of large hepatocellular carcinoma (HCC) after liver resection (LR).Materials and methodsFrom January 2015 to December 2017, patients with a large (≥5cm) HCC who underwent preoperative DKI were retrospectively reviewed. The correlations of the mean kurtosis (MK), mean diffusivity (MD), and apparent diffusion coefficient (ADC) with microvascular invasion (MVI) or histological grade were analyzed. Cox regression analyses were performed to identify the predictors of recurrence-free survival (RFS) and overall survival (OS). A nomogram to predict RFS was established. P<0.05 was considered as statistically significant.ResultsA total of 97 patients (59 males and 38 females, 56.0 ± 10.9 years) were included in this study. The MK, MD, and ADC values were correlated with MVI or histological grade (P<0.01). With a median follow-up time of 41.2 months (range 12-69 months), 67 patients (69.1%) experienced recurrence and 41 patients (42.3%) were still alive. The median RFS and OS periods after LR were 29 and 45 months, respectively. The 1-, 3-, and 5-year RFS and OS rates were 88.7%, 41.2%, and 21.7% and 99.0%, 68.3%, and 25.6%, respectively. MK (P<0.001), PVT (P<0.001), and ADC (P=0.033) were identified as independent predictor factors for RFS. A nomogram including the MK value for RFS showed the best performance, and the C-index was 0.895.ConclusionThe MK value obtained from DKI is a potential predictive factor for recurrence and poor survival, which could provide valuable information for guiding the efficacy of LR in patients with large HCC.
Collapse
|
|
25
|
Giuffrè M, Zuliani E, Visintin A, Tarchi P, Martingano P, Pizzolato R, Bonazza D, Masutti F, Moretti R, Crocè LS. Predictors of Hepatocellular Carcinoma Early Recurrence in Patients Treated with Surgical Resection or Ablation Treatment: A Single-Center Experience. Diagnostics (Basel) 2022; 12:diagnostics12102517. [PMID: 36292205 PMCID: PMC9600725 DOI: 10.3390/diagnostics12102517] [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: 09/16/2022] [Revised: 10/07/2022] [Accepted: 10/15/2022] [Indexed: 01/27/2023] Open
Abstract
Introduction: Hepatocellular carcinoma (HCC) is the sixth most diagnosed malignancy and the fourth leading cause of cancer-related death worldwide, with poor overall survival despite available curative treatments. One of the most crucial factors influencing survival in HCC is recurrence. The current study aims to determine factors associated with early recurrence of HCC in patients with BCLC Stage 0 or Stage A treated with surgical resection or local ablation. Materials and Methods: We retrospectively enrolled 58 consecutive patients diagnosed with HCC within BCLC Stage 0 or Stage A and treated either by surgical resection or local ablation with maximum nodule diameter < 50 mm. In the first year of follow-up after treatment, imaging was performed regularly one month after treatment and then every three months. Each case was discussed collectively by the Liver Multidisciplinary Group to decide diagnosis, treatment, follow-up, and disease recurrence. Variables resulting in statistically significant difference were then studied by Cox regression analysis; univariately and then multivariately based on forward stepwise Cox regression. Results are represented in hazard ratio (H.R.) with 95% confidence interval (C.I.). Results: There was no statistically significant difference in recurrence rates (34.8 vs. 45.7%, log-rank test, p = 0.274) between patients undergoing surgical resection and local ablation, respectively. Early recurrence was associated with male gender (HR 2.5, 95% C.I. 1.9−3.1), nodule diameter > 20 mm (HR 4.5, 95% C.I. 3.9−5.1), platelet count < 125 × 103 cell/mm3 (HR 1.6, 95% C.I. 1.2−1.9), platelet-lymphocyte ratio < 95 (HR 2.1, 95% C.I. 1.7−2.6), lymphocyte-monocyte ratio < 2.5 (HR 1.9, 95% C.I. 1.4−2.5), and neutrophil-lymphocyte ratio > 2 (HR 2.7, 95% C.I. 2.2−3.3). Discussion and Conclusions: Our results are in line with the current literature. Male gender and tumor nodule dimension are the main risk factors associated with early HCC recurrence. Platelet count and other combined scores can be used as predictive tools for early HCC recurrence, although more studies are needed to define cut-offs.
Collapse
Affiliation(s)
- Mauro Giuffrè
- Department of Medical, Surgical and Health Sciences, University of Trieste, 341349 Trieste, Italy
- Correspondence:
| | - Enrico Zuliani
- Department of Medical, Surgical and Health Sciences, University of Trieste, 341349 Trieste, Italy
| | - Alessia Visintin
- Liver Clinic, University Hospital of Trieste (Azienda Sanitaria Giuliano-Isontina), 34149 Trieste, Italy
| | - Paola Tarchi
- Surgical Clinic, University Hospital of Trieste (Azienda Sanitaria Giuliano-Isontina), 34149 Trieste, Italy
| | - Paola Martingano
- Diagnostic and Interventional Radiology, University Hospital of Trieste (Azienda Sanitaria Giuliano-Isontina), 34149 Trieste, Italy
| | - Riccardo Pizzolato
- Diagnostic and Interventional Radiology, University Hospital of Trieste (Azienda Sanitaria Giuliano-Isontina), 34149 Trieste, Italy
| | - Deborah Bonazza
- Anatomic Pathology and Histology, University Hospital of Trieste (Azienda Sanitaria Giuliano-Isontina), 34149 Trieste, Italy
| | - Flora Masutti
- Liver Clinic, University Hospital of Trieste (Azienda Sanitaria Giuliano-Isontina), 34149 Trieste, Italy
| | - Rita Moretti
- Department of Medical, Surgical and Health Sciences, University of Trieste, 341349 Trieste, Italy
| | - Lory Saveria Crocè
- Department of Medical, Surgical and Health Sciences, University of Trieste, 341349 Trieste, Italy
- Liver Clinic, University Hospital of Trieste (Azienda Sanitaria Giuliano-Isontina), 34149 Trieste, Italy
| |
Collapse
|
|
26
|
Li W, Zhuang BW, Qiao B, Zhang N, Hu HT, Li C, Xie XH, Kuang M, Lu MD, Xie XY, Wang W. Circulating tumour cell counts and ultrasomics signature-based nomogram for preoperative prediction of early recurrence of hepatocellular carcinoma after radical treatment. Br J Radiol 2022; 95:20211137. [PMID: 36165329 PMCID: PMC9793480 DOI: 10.1259/bjr.20211137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 08/15/2022] [Accepted: 08/30/2022] [Indexed: 01/27/2023] Open
Abstract
METHODS Between December 2017 and December 2018, 153 HCC patients (134 males and 19 females; mean age, 56.0 ± 10.2 years; range, 28-78 years) treated with radical therapy were enrolled in our retrospective study and were divided into a training cohort (n = 107) and a validation cohort (n = 46). All patients underwent preoperative CTC tests and CEUS examinations before treatment. The ultrasomics signature was extracted and built from CEUS images. Univariate and multivariate logistic regression analyses were used to identify the significant variables related to ER, which were then combined to build a predictive nomogram. The performance of the nomogram was evaluated by its discrimination, calibration and clinical utility. The predictive model was further evaluated in the internal validation cohort. RESULTS HBV DNA, serum AFP level, CTC status, tumour size and ultrasomics score were identified as independent predictors associated with ER (all p < 0.05). Multivariable logistic regression analysis showed that the CTC status (OR = 7.02 [95% CI, 2.07 to 28.38], p = 0.003) and ultrasomics score (OR = 148.65 [95% CI, 25.49 to 1741.72], p < 0.001) were independent risk factors for ER. The nomogram based on ultrasomics score, CTC status, serum AFP level and tumour size exhibited C-indexes of 0.933 (95% CI, 0.878 to 0.988) and 0.910 (95% CI, 0.765 to 1.055) in the training and validation cohorts, respectively, fitting well in calibration curves. Decision curve analysis further confirmed the clinical usefulness of the nomogram. CONCLUSION The nomogram incorporating CTC, ultrasomics features and independent clinical risk factors achieved satisfactory preoperative prediction of ER in HCC patients after radical treatment. ADVANCES IN KNOWLEDGE 1. CTC status and ultrasomics score were identified as independent predictors associated with ER of HCC after radical treatment. 2. The nomogram constructed by ultrasomics score generated by 17 ultrasomics features, combined with CTCs and independent clinical risk factors such as AFP and tumour size. 3. The nomogram exhibited satisfactory discriminative power, and could be clinically useful in the preoperative prediction of ER after radical treatment in HCC patients.
Collapse
Affiliation(s)
- Wei Li
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Bo-Wen Zhuang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Bin Qiao
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Nan Zhang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Hang-Tong Hu
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Cong Li
- Forevergen Biosciences Co., Ltd., Guangzhou, China
| | - Xiao-Hua Xie
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | | | | | - Xiao-Yan Xie
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Wei Wang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| |
Collapse
|
|
27
|
Zhang H, Huo F. Prediction of early recurrence of HCC after hepatectomy by contrast-enhanced ultrasound-based deep learning radiomics. Front Oncol 2022; 12:930458. [PMID: 36248986 PMCID: PMC9554932 DOI: 10.3389/fonc.2022.930458] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 09/07/2022] [Indexed: 12/07/2022] Open
Abstract
Objective This study aims to evaluate the predictive model based on deep learning (DL) and radiomics features from contrast-enhanced ultrasound (CEUS) to predict early recurrence (ER) in patients with hepatocellular carcinoma (HCC). Methods One hundred seventy-two patients with HCC who underwent hepatectomy and followed up for at least 1 year were included in this retrospective study. The data were divided according to the 7:3 ratios of training and test data. The ResNet-50 architecture, CEUS-based radiomics, and the combined model were used to predict the early recurrence of HCC after hepatectomy. The receiver operating characteristic (ROC) curve and calibration curve were drawn to evaluate its diagnostic efficiency. Results The CEUS-based radiomics ROCs of the “training set” and “test set” were 0.774 and 0.763, respectively. The DL model showed increased prognostic value, the ROCs of the “training set” and “test set” were 0.885 and 0.834, respectively. The combined model ROCs of the “training set” and “test set” were 0.943 and 0.882, respectively. Conclusion The deep learning radiomics model integrating DL and radiomics features from CEUS was used to predict ER and achieve satisfactory performance. Its diagnostic efficiency is significantly better than that of the single model.
Collapse
Affiliation(s)
- Hui Zhang
- Department of Ultrasound, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College (University), Nanchong, Sichuan, China
| | - Fanding Huo
- Department of Medical Ultrasound, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
- Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China
- *Correspondence: Fanding Huo,
| |
Collapse
|
|
28
|
Tay BWR, Huang DQ, Mark M, Thong NW, Guan Huei L, Gee LS, Cheng LH, Mei LY, Thurairajah P, Chen LJ, Ng CH, Lim WH, Tan DJH, Maureen DC, Alfred KWC, Ganpathi IS, Seng TP, Young DY. Comparable Outcomes in Early Hepatocellular Carcinomas Treated with Trans-Arterial Chemoembolization and Radiofrequency Ablation. Biomedicines 2022; 10:2361. [PMID: 36289623 PMCID: PMC9598932 DOI: 10.3390/biomedicines10102361] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 09/15/2022] [Accepted: 09/18/2022] [Indexed: 11/30/2022] Open
Abstract
The guidelines recommend radiofrequency ablation (RFA) for early hepatocellular carcinomas that are less than 3 cm and trans-arterial chemoembolization (TACE) for intermediate-stage tumors. Real-world patient and tumor factors commonly limit strict adherence to the guidelines. We aimed to compare the clinical outcomes for TACE and RFA in early HCC. All consecutive patients from 2010 to 2014 that were treated with locoregional therapy at our institution were enrolled. The decision for TACE or RFA was based on tumor location, stage and technical accessibility for ablation. A subgroup analysis was performed for patients with tumors less than 3 cm. A total of 168 patients underwent TACE while 56 patients underwent RFA. Patients treated with TACE and RFA had 1- and 5-year survival rates of 84.7% and 39.8% versus 91.5% and 51.5%, respectively (p = 0.28). In tumors less than 3 cm, there was no significant difference in overall survival (p = 0.69), time to progression (p = 0.55), or number of treatment sessions required (p = 0.12). Radiofrequency ablation had a significantly higher chance of a complete response (p = 0.004). In conclusion, TACE may be selectively considered for early-stage hepatocellular carcinoma in patients unsuitable for other modalities.
Collapse
Affiliation(s)
- Benjamin Wei Rong Tay
- Division of Gastroenterology and Hepatology, National University Health System, Singapore 119228, Singapore
| | - Daniel Q. Huang
- Division of Gastroenterology and Hepatology, National University Health System, Singapore 119228, Singapore
- Department of Medicine, Yong Loo Yin School of Medicine, National University of Singapore, Singapore 119077, Singapore
| | - Muthiah Mark
- Division of Gastroenterology and Hepatology, National University Health System, Singapore 119228, Singapore
| | - Neo Wee Thong
- Department of Diagnostic Imaging, National University Health System, Singapore 119228, Singapore
| | - Lee Guan Huei
- Division of Gastroenterology and Hepatology, National University Health System, Singapore 119228, Singapore
- Department of Medicine, Yong Loo Yin School of Medicine, National University of Singapore, Singapore 119077, Singapore
| | - Lim Seng Gee
- Division of Gastroenterology and Hepatology, National University Health System, Singapore 119228, Singapore
- Department of Medicine, Yong Loo Yin School of Medicine, National University of Singapore, Singapore 119077, Singapore
| | - Low How Cheng
- Division of Gastroenterology and Hepatology, National University Health System, Singapore 119228, Singapore
| | - Lee Yin Mei
- Division of Gastroenterology and Hepatology, National University Health System, Singapore 119228, Singapore
| | - Prem Thurairajah
- Division of Gastroenterology and Hepatology, National University Health System, Singapore 119228, Singapore
| | - Lim Jia Chen
- Division of Gastroenterology and Hepatology, National University Health System, Singapore 119228, Singapore
| | - Cheng Han Ng
- Department of Medicine, Yong Loo Yin School of Medicine, National University of Singapore, Singapore 119077, Singapore
| | - Wen Hui Lim
- Department of Medicine, Yong Loo Yin School of Medicine, National University of Singapore, Singapore 119077, Singapore
| | - Darren Jun Hao Tan
- Department of Medicine, Yong Loo Yin School of Medicine, National University of Singapore, Singapore 119077, Singapore
| | - Da Costa Maureen
- Division of Hepatobiliary Surgery, National University Health System, Singapore 119228, Singapore
| | - Kow Wei Chieh Alfred
- Division of Hepatobiliary Surgery, National University Health System, Singapore 119228, Singapore
| | - Iyer Shridar Ganpathi
- Division of Hepatobiliary Surgery, National University Health System, Singapore 119228, Singapore
| | - Tan Poh Seng
- Division of Gastroenterology and Hepatology, National University Health System, Singapore 119228, Singapore
| | - Dan Yock Young
- Division of Gastroenterology and Hepatology, National University Health System, Singapore 119228, Singapore
- Department of Medicine, Yong Loo Yin School of Medicine, National University of Singapore, Singapore 119077, Singapore
| |
Collapse
|
|
29
|
Liu H, Yan Y, Lin J, He C, Liao H, Li H, Zhou Z, Wang J, Mao K, Xiao Z. Circular RNA circSFMBT2 downregulation by HBx promotes hepatocellular carcinoma metastasis via the miR-665/TIMP3 axis. MOLECULAR THERAPY. NUCLEIC ACIDS 2022; 29:788-802. [PMID: 36159591 PMCID: PMC9463182 DOI: 10.1016/j.omtn.2022.08.008] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 08/02/2022] [Indexed: 04/30/2023]
Abstract
Hepatitis B virus X protein (HBx) is considered as an oncogene in tumorigenesis and progression of hepatocellular carcinoma (HCC). In recent years, the important role of circular RNAs (circRNAs) in HCC has been increasingly demonstrated. However, the regulatory mechanisms of HBx on circRNAs remains largely unknown. In this study, we identified that a novel circRNA, circSFMBT2, was markedly downregulated by HBx. Low expression of circSFMBT2 was correlated with poor prognosis and vascular invasion. Functionally, overexpression of circSFMBT2 significantly inhibited HCC metastasis both in vitro and in vivo. The mechanism of circSFMBT2 was to as a sponge of miR-665, which is a negative regulator of tissue inhibitor of metalloproteinases 3 (TIMP3). However, HBx downregulated circSFMBT2 via the interaction with DExH-box helicase 9 (DHX9), which binds to flanking circRNA-forming introns. In conclusion, circSFMBT2, which is downregulated by HBx, acts as a tumor suppressor to inhibit tumor metastasis through the miR-665/TIMP3 axis. Our study suggests that circSFMBT2 could be a potential prognostic biomarker and therapeutic target for HCC.
Collapse
Affiliation(s)
- Haohan Liu
- Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
| | - Yongcong Yan
- Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
- Corresponding author Yongcong Yan, Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Yanjiang West Road #107, Guangzhou 510120, China.
| | - Jianhong Lin
- Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
| | - Chuanchao He
- Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
| | - Hao Liao
- Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
| | - Huoming Li
- Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
| | - Zhenyu Zhou
- Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
| | - Jie Wang
- Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
| | - Kai Mao
- Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
- Department of General Surgery, Shenshan Medical Center, Memorial Hospital of Sun Yat-Sen University, Shanwei 516600, China
- Corresponding author Kai Mao, Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Yanjiang West Road #107, Guangzhou 510120, China.
| | - Zhiyu Xiao
- Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
- Department of General Surgery, Shenshan Medical Center, Memorial Hospital of Sun Yat-Sen University, Shanwei 516600, China
- Corresponding author Zhiyu Xiao, Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Yanjiang West Road #107, Guangzhou 510120, China.
| |
Collapse
|
|
30
|
Wang Y, Xue R, Xing W, Li Q, Gei L, Yan F, Mai D, Zeng W, Yan Y, Chen D. Intraoperative low-dose dopamine is associated with worse survival in patients with hepatocellular carcinoma: A propensity score matching analysis. Front Oncol 2022; 12:947172. [PMID: 36091153 PMCID: PMC9452952 DOI: 10.3389/fonc.2022.947172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Accepted: 07/26/2022] [Indexed: 01/27/2023] Open
Abstract
Background Dopamine is widely used in patients during surgery. We evaluated the association between intraoperative low-dose dopamine administration and recurrence-free survival (RFS) and overall survival (OS) in patients with hepatocellular carcinoma (HCC). Methods Consecutive patients with nonmetastatic HCC who underwent radical hepatectomy were enrolled between 2008 and 2010. Univariate and multivariate logistic regression analyses were used to evaluate the prognostic factors for RFS and OS. Survival outcomes were evaluated using Kaplan–Meier analyses with the log-rank test. A one-to-one propensity score matching (PSM) analysis was performed to reduce confounding bias. Results A total of 805 HCC patients, including 699 patients who did not receive dopamine consumption and 106 patients who received low-dose dopamine during the operation, were retrospectively analyzed. The patients who were assigned low-dose dopamine had worse RFS (p = 0.009) and OS (p = 0.041) than those who did not receive dopamine. Multivariate regression analysis showed that the intraoperative administration of low-dose dopamine was an independent unfavorable predictor for RFS (p = 0.004) but not for OS (p = 0.059). After PSM, the low-dose dopamine-treated group still had significantly poorer RFS (p = 0.003) and OS (p = 0.002). When stratified by time of recurrence, patients with low-dose dopamine use had a significantly greater chance of recurrence within 2 years (p = 0.007) but not after 2 years (p = 0.186). Conclusions Intraoperative low-dose dopamine use has a negative impact on RFS and OS in HCC patients who have undergone radical hepatectomy. Further prospective studies are required to assess the effects of low-dose dopamine on surgical outcomes in HCC patients.
Collapse
Affiliation(s)
- Yan Wang
- Department of Anesthesiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Ruifeng Xue
- Department of Anesthesiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Wei Xing
- Department of Anesthesiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Qiang Li
- Department of Anesthesiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Liba Gei
- Department of Anesthesiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Anesthesiology, Inner Mongolia Autonomous Region Cancer Hospital, Affiliated People’s Hospital of Inner Mongolia Medical University, Hohhot, China
| | - Fang Yan
- Department of Anesthesiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Dongmei Mai
- Department of Anesthesiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Weian Zeng
- Department of Anesthesiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- *Correspondence: Weian Zeng, ; Yan Yan, ; Dongtai Chen,
| | - Yan Yan
- Department of Anesthesiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Anesthesiology, Huizhou Municipal Central Hospital, Huizhou, China
- *Correspondence: Weian Zeng, ; Yan Yan, ; Dongtai Chen,
| | - Dongtai Chen
- Department of Anesthesiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- *Correspondence: Weian Zeng, ; Yan Yan, ; Dongtai Chen,
| |
Collapse
|
|
31
|
Cheng CH, Lai Y, Hung HC, Lee JC, Wang YC, Wu TH, Lee CF, Wu TJ, Chou HS, Chan KM, Lee WC. Recurrence Patterns After Hepatectomy With Very Narrow Resection Margins for Hepatocellular Carcinoma. Front Surg 2022; 9:926728. [PMID: 35910466 PMCID: PMC9330627 DOI: 10.3389/fsurg.2022.926728] [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: 04/23/2022] [Accepted: 06/20/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND The extent of hepatic resection In HCC depends on the remnant liver reserve or the proximity of the tumor to major vessels. In this study, we evaluated the effects of very close resection margins on postoperative recurrence. METHODS Consecutive LR for HCC between 2003 and 2009 were studied. Patients were divided into groups with very narrow (≤1 mm) or wider (>1 mm) resection margins. Propensity score matching (PSM) was used to balance demographic, surgical, and pathological factors. RESULTS 983 patients were included in the study. After PSM, 173 patients were analyzed in each group. 5-year tumor recurrence and survival rates were comparable. Most recurrences were multiple intrahepatic. Section margin recurrences were similar in both groups. By multivariate analysis, tumor size >5 cm was associated with a very narrow resection margin, whereas low platelet count and tumor macrovascular invasion were significant factors related to tumor recurrence. CONCLUSIONS Patients with very narrow surgical margins showed outcomes comparable to those with wider surgical margins. Most recurrences were multiple intrahepatic and associated with the degree of portal hypertension and adverse tumor biology. Although wide surgical margins should be aimed whenever possible, a narrow tumor-free margin resection still represents an effective therapeutic strategy.
Collapse
Affiliation(s)
- Chih-Hsien Cheng
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Yin Lai
- Department of General Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Hao-Chien Hung
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Jin-Chiao Lee
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Yu-Chao Wang
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Tsung-Han Wu
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Chen-Fang Lee
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Ting-Jung Wu
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Hong-Shiue Chou
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Kun-Ming Chan
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Wei-Chen Lee
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
| |
Collapse
|
|
32
|
Wu C, Yu S, Zhang Y, Zhu L, Chen S, Liu Y. CT-Based Radiomics Nomogram Improves Risk Stratification and Prediction of Early Recurrence in Hepatocellular Carcinoma After Partial Hepatectomy. Front Oncol 2022; 12:896002. [PMID: 35875140 PMCID: PMC9302642 DOI: 10.3389/fonc.2022.896002] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Accepted: 06/17/2022] [Indexed: 01/27/2023] Open
Abstract
Objectives To develop and validate an intuitive computed tomography (CT)-based radiomics nomogram for the prediction and risk stratification of early recurrence (ER) in hepatocellular carcinoma (HCC) patients after partial hepatectomy. Methods A total of 132 HCC patients treated with partial hepatectomy were retrospectively enrolled and assigned to training and test sets. Least absolute shrinkage and selection operator and gradient boosting decision tree were used to extract quantitative radiomics features from preoperative contrast-enhanced CT images of the HCC patients. The radiomics features with predictive value for ER were used, either alone or in combination with other predictive features, to construct predictive models. The best performing model was then selected to develop an intuitive, simple-to-use nomogram, and its performance in the prediction and risk stratification of ER was evaluated using the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). Results The radiomics model based on the radiomics score (Rad-score) achieved AUCs of 0.870 and 0.890 in the training and test sets, respectively. Among the six predictive models, the combined model based on the Rad-score, Edmondson grade, and tumor size had the highest AUCs of 0.907 in the training set and 0.948 in the test set and was used to develop an intuitive nomogram. Notably, the calibration curve and DCA for the nomogram showed good calibration and clinical application. Moreover, the risk of ER was significantly different between the high- and low-risk groups stratified by the nomogram (p <0.001). Conclusions The CT-based radiomics nomogram developed in this study exhibits outstanding performance for ER prediction and risk stratification. As such, this intuitive nomogram holds promise as a more effective and user-friendly tool in predicting ER for HCC patients after partial hepatectomy.
Collapse
Affiliation(s)
- Cuiyun Wu
- Cancer Center, Department of Radiology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, China
| | - Shufeng Yu
- Cancer Center, Department of Radiology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, China
| | - Yang Zhang
- Cancer Center, Department of Radiology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, China
| | - Li Zhu
- Cancer Center, Department of Ultrasound Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, China
| | - Shuangxi Chen
- Cancer Center, Department of Ultrasound Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, China
| | - Yang Liu
- Cancer Center, Department of Ultrasound Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, China
- Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, China
- *Correspondence: Yang Liu,
| |
Collapse
|
|
33
|
Zeng G, Zou B, Li Y, Lin E, Liu X, Li P, Chen J, Zhang B, Jia Y, Cai C, Li J. Efficacy of Adjuvant Transarterial Chemoembolization after Radical Hepatectomy in Solitary Hepatocellular Carcinoma Patients: A Retrospective Study. J INVEST SURG 2022; 35:1208-1216. [PMID: 35078386 DOI: 10.1080/08941939.2021.2021334] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 12/11/2021] [Accepted: 12/15/2021] [Indexed: 12/24/2022]
Abstract
Background: More and more studies have suggested that hepatocellular carcinoma (HCC) patients with high-risk recurrence factors can benefit the most from postoperative adjuvant transarterial chemoembolization (PA-TACE) for its potential effect in delaying cancer recurrence. However, it remains unclear if solitary HCC (SHCC) patients particularly those without high-risk recurrence factors should also receive PA-TACE. This study aimed to analyze the efficacy of PA-TACE in them. Methods: Retrospectively, we enrolled 123 SHCC patients who either received radical hepatectomy alone (No TACE group, n = 39) or followed by PA-TACE (PA-TACE group, n = 84) in our institution. Prognostic risk factors, disease-free survival (DFS), and overall survival (OS) were analyzed using the Cox proportional hazard regression model, the Kaplan-Meier method, and the log-rank test. Results: Liver cirrhosis was the only independent risk factor for SHCC patients. Overall, the PA-TACE group had no improved OS (P = 0.977) but worse DFS compared with the No TACE group (P = 0.045). Consistently, in subgroup analysis, SHCC patients with negative microvascular invasion (MVI), tumor size ≤ 5 cm and preoperative alpha-fetoprotein (AFP) < 400 ng/ml had similar OS (P = 0.466, P = 0.864, P = 0.488, respectively) but even worse DFS (P = 0.035, P = 0.040, P = 0.019, respectively) than those in the No TACE group. Besides, there was no significant difference in DFS and OS between the two groups of SHCC patients with liver cirrhosis (P = 0.342, P = 0.941, respectively). Conclusions: PA-TACE may not improve the long-term survival of SHCC patients, but may even potentially promote their postoperative tumor recurrence, especially for those with MVI-negative, tumor size ≤ 5 cm, and preoperative AFP < 400 ng/ml.
Collapse
Affiliation(s)
- Guifang Zeng
- Department of Hepatobiliary Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People's Republic of China
| | - Baojia Zou
- Department of Hepatobiliary Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People's Republic of China
| | - Yongliang Li
- Department of Pathology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People's Republic of China
| | - En Lin
- Department of Hepatobiliary Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People's Republic of China
| | - Xialei Liu
- Department of Hepatobiliary Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People's Republic of China
| | - Peiping Li
- Department of Hepatobiliary Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People's Republic of China
| | - Jiafan Chen
- Department of Hepatobiliary Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People's Republic of China
| | - Baimeng Zhang
- Department of Hepatobiliary Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People's Republic of China
| | - Yingbin Jia
- Department of Hepatobiliary Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People's Republic of China
| | - Chaonong Cai
- Department of Hepatobiliary Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People's Republic of China
| | - Jian Li
- Department of Hepatobiliary Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People's Republic of China
| |
Collapse
|
|
34
|
Yan W, Han Q, Gong L, Zhan X, Li W, Guo Z, Zhao J, Li T, Bai Z, Wu J, Huang Y, Lv L, Zhao H, Cai H, Huang S, Diao X, Chen Y, Gong W, Xia Q, Man J, Chen L, Dai G, Zhou T. MBD3 promotes hepatocellular carcinoma progression and metastasis through negative regulation of tumour suppressor TFPI2. Br J Cancer 2022; 127:612-623. [PMID: 35501390 PMCID: PMC9381593 DOI: 10.1038/s41416-022-01831-5] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 04/03/2022] [Accepted: 04/14/2022] [Indexed: 12/24/2022] Open
Abstract
Background The mechanism of recurrence and metastasis of hepatocellular carcinoma (HCC) is complex and challenging. Methyl-CpG binding domain protein 3 (MBD3) is a key epigenetic regulator involved in the progression and metastasis of several cancers, but its role in HCC remains unknown. Methods MBD3 expression in HCC was detected by immunohistochemistry and its association with clinicopathological features and patient’s survival was analysed. The effects of MBD3 on hepatoma cells growth and metastasis were investigated, and the mechanism was explored. Results MBD3 is significantly highly expressed in HCC, associated with the advanced tumour stage and poor prognosis in HCC patients. MBD3 promotes the growth, angiogenesis and metastasis of HCC cells by inhibiting the tumour suppressor tissue factor pathway inhibitor 2 (TFPI2). Mechanistically, MBD3 can inhibit the TFPI2 transcription via the Nucleosome Remodeling and Deacetylase (NuRD) complex-mediated deacetylation, thus reactivating the activity of matrix metalloproteinases (MMPs) and PI3K/AKT signaling pathway, leading to the progression and metastasis of HCC Conclusions Our results unravel the novel regulatory function of MBD3 in the progression and metastasis of HCC and identify MBD3 as an independent unfavourable prognostic factor for HCC patients, suggesting its potential as a promising therapeutic target as well.
Collapse
Affiliation(s)
- Weiwei Yan
- State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 100850, Beijing, China.,Department of Radiation Oncology, 5th Medical Center of Chinese PLA General Hospital, 100853, Beijing, China
| | - Qiuying Han
- State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 100850, Beijing, China.,Nanhu Laboratory, 314002, Jiaxing, Zhejiang Province, China
| | - Lin Gong
- Department of Hepatobiliary Surgery, PLA navy No. 971 Hospital, 266071, Qingdao, Shandong Province, China
| | - Xiaoyan Zhan
- State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 100850, Beijing, China
| | - Wanjin Li
- State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 100850, Beijing, China
| | - Zenglin Guo
- State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 100850, Beijing, China
| | - Jiangman Zhao
- State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 100850, Beijing, China
| | - Tingting Li
- State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 100850, Beijing, China
| | - Zhaofang Bai
- Department of Liver Disease, 5th Medical Center of Chinese PLA General Hospital, 100039, Beijing, China
| | - Jin Wu
- State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 100850, Beijing, China
| | - Yan Huang
- State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 100850, Beijing, China
| | - Luye Lv
- State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 100850, Beijing, China
| | - Haixin Zhao
- State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 100850, Beijing, China
| | - Hong Cai
- State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 100850, Beijing, China
| | - Shaoyi Huang
- State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 100850, Beijing, China
| | - Xinwei Diao
- State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 100850, Beijing, China
| | - Yuan Chen
- State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 100850, Beijing, China
| | - Weili Gong
- State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 100850, Beijing, China
| | - Qing Xia
- State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 100850, Beijing, China
| | - Jianghong Man
- State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 100850, Beijing, China
| | - Liang Chen
- State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 100850, Beijing, China. .,Nanhu Laboratory, 314002, Jiaxing, Zhejiang Province, China.
| | - Guanghai Dai
- Department of Oncology, 5th Medical Center of Chinese PLA General Hospital, 100853, Beijing, China.
| | - Tao Zhou
- State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 100850, Beijing, China. .,Nanhu Laboratory, 314002, Jiaxing, Zhejiang Province, China.
| |
Collapse
|
|
35
|
Bae BK, Park HC, Yoo GS, Choi MS, Oh JH, Yu JI. The Significance of Systemic Inflammation Markers in Intrahepatic Recurrence of Early-Stage Hepatocellular Carcinoma after Curative Treatment. Cancers (Basel) 2022; 14:2081. [PMID: 35565210 PMCID: PMC9102776 DOI: 10.3390/cancers14092081] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 04/11/2022] [Accepted: 04/18/2022] [Indexed: 12/21/2022] Open
Abstract
Systemic inflammatory markers (SIMs) are known to be associated with carcinogenesis and prognosis of hepatocellular carcinoma (HCC). We evaluated the significance of SIMs in intrahepatic recurrence (IHR) of early-stage HCC after curative treatment. This study was performed using prospectively collected registry data of newly diagnosed, previously untreated HCC between 2005 and 2017 at a single institution. Inclusion criteria were patients with Barcelona Clinic Liver Cancer stage 0 or A, who underwent curative treatment. Pre-treatment and post-treatment values of platelet, neutrophil, lymphocyte, monocyte, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and lymphocyte/monocyte ratio (LMR) were analyzed with previously well-known risk factors of HCC to identify factors associated with IHR-free survival (IHRFS), early IHR, and late IHR. Of 4076 patients, 2142 patients (52.6%) experienced IHR, with early IHR in 1018 patients (25.0%) and late IHR in 1124 patients (27.6%). Pre-treatment platelet count and PLR and post-treatment worsening of NLR, PLR, and LMR were independently associated with IHRFS. Pre-treatment platelet count and post-treatment worsening of NLR, PLR, and LMR were significantly related to both early and late IHR. Pre-treatment values and post-treatment changes in SIMs were significant factors of IHR in early-stage HCC, independent of previously well-known risk factors of HCC.
Collapse
Affiliation(s)
- Bong Kyung Bae
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (B.K.B.); (G.S.Y.)
| | - Hee Chul Park
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (B.K.B.); (G.S.Y.)
| | - Gyu Sang Yoo
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (B.K.B.); (G.S.Y.)
| | - Moon Seok Choi
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (M.S.C.); (J.H.O.)
| | - Joo Hyun Oh
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (M.S.C.); (J.H.O.)
| | - Jeong Il Yu
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (B.K.B.); (G.S.Y.)
| |
Collapse
|
|
36
|
Shimagaki T, Yoshizumi T, Itoh S, Iseda N, Tomiyama T, Morinaga A, Wang H, Kurihara T, Nagao Y, Toshima T, Harada N, Kinjo N, Maeda T, Mori M. The ratio of serum des-gamma-carboxy prothrombin to tumor volume as a new biomarker for early recurrence of resected hepatocellular carcinoma. Hepatol Res 2022; 52:381-389. [PMID: 35089647 DOI: 10.1111/hepr.13750] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 12/24/2021] [Accepted: 01/17/2022] [Indexed: 02/08/2023]
Abstract
BACKGROUND Early recurrence (ER) of hepatocellular carcinoma (HCC) (within 1 year after resection) is known to be a poor prognostic factor. The aim was to identify the risk factors associated with ER after HCC resection. METHODS Data were analyzed retrospectively from patients who underwent primary resection for HCC from two hospitals. For cross-validation, HCC resection cases were divided into the training and testing cohort. The clinicopathological factors between the ER and non-ER groups and factors for predicting ER and prognosis after HCC resection were compared. RESULTS Out of 173 patients in the training dataset, 33 patients had ER and the ER group showed larger tumor size, more intrahepatic metastasis (IM), and a higher ratio of serum des-gamma-carboxy prothrombin (DCP) to tumor volume (TV) (DCP/TV) than the non-ER group. Out of 203 patients in the testing dataset, 30 patients had ER and the ER group demonstrated larger tumor size, more IM, and higher serum alpha-fetoprotein, AFP/TV, DCP/TV, AFP/tumor maximum diameter (TMD), and DCP/TMD than the non-ER group. The patients were divided into high and low DCP/TV groups and high serum DCP/TV was associated with unfavorable overall survival in the training and testing dataset. Multivariate analysis confirmed that high serum DCP/TV and IM were independently associated with ER. CONCLUSION Preoperative high serum DCP/TV may be useful for stratifying patients at risk of early HCC recurrence after curative resection.
Collapse
Affiliation(s)
- Tomonari Shimagaki
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.,Department of Surgery, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Shinji Itoh
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Norifumi Iseda
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takahiro Tomiyama
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Akinari Morinaga
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Huanlin Wang
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takeshi Kurihara
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yoshihiro Nagao
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takeo Toshima
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Noboru Harada
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Nao Kinjo
- Department of Surgery, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Takashi Maeda
- Department of Surgery, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Masaki Mori
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| |
Collapse
|
|
37
|
Margonis GA, Andreatos N, Wang J, Weiss MJ, Wolfgang CL. Lessons learned from hepatocellular carcinoma may cause a paradigm shift in intraductal papillary mucinous neoplasms: a narrative review and discussion of conceptual similarities in tumor progression and recurrence. JOURNAL OF PANCREATOLOGY 2022; 5:36-40. [PMID: 39640535 PMCID: PMC11619816 DOI: 10.1097/jp9.0000000000000083] [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] [Indexed: 11/27/2022] Open
Abstract
Although the natural history of recurrence/progression in patients with intraductal papillary mucinous neoplasms (IPMN) of the pancreas has not been studied thoroughly, the three principal mechanisms have been identified: (a) presence of residual disease at the transection margin, (b) presence of intraductal/intraparenchymal metastases and (c) development of new primary lesions. Mechanisms (a) and (b) result in metastatic lesions that are genetically related to the primary, while new primary lesions (mechanism c) are genetically distinct. Interestingly, recurrence/progression in IPMN displays conceptual parallels with the well-established paradigm of disease recurrence in patients with hepatocellular carcinoma (HCC). Specifically, patients with HCC may also develop recurrent tumors due to microscopic residual disease/intrahepatic metastasis which are genetically similar to the primary while the development of genetically unrelated, de novo HCC after curative-intent resection is also common. The latter has been attributed to the presence of a widespread genetic abnormality ("field defect") in the liver (ie, cirrhosis). Given the conceptual similarities between IPMN and HCC, a pancreatic "field defect"may also be hypothesized to exist. This review does not suggest that HCC and IPMN have identical pathogeneses, but rather that they have conceptual similarities in tumor recurrence/progression; thus, lessons learned from HCC could be applied to IPMN research and subsequent management. Conceptual similarities in tumor progression and recurrence may also be observed between IPMN and other malignancies. However, HCC was selected because it is well studied and can serve as a paradigm.
Collapse
Affiliation(s)
| | - Nikolaos Andreatos
- Department of Internal Medicine and Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH
| | - Jane Wang
- Department of Surgery, University of California San Francisco, San Francisco, CA
| | - Matthew J. Weiss
- Department of Surgery, Northwell Health Cancer Institute and Zucker School of Medicine at Hofstra, Lake Success
| | | |
Collapse
|
|
38
|
Xin Z, Li J, Zhang H, Zhou Y, Song J, Chen P, Bai L, Chen H, Zhou J, Chen J, Ying B. Cancer Genomic Alterations Can Be Potential Biomarkers Predicting Microvascular Invasion and Early Recurrence of Hepatocellular Carcinoma. Front Oncol 2022; 12:783109. [PMID: 35155229 PMCID: PMC8828586 DOI: 10.3389/fonc.2022.783109] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Accepted: 01/03/2022] [Indexed: 02/05/2023] Open
Abstract
Background High recurrence incidence and poor survival after hepatectomy are enormous threats to hepatocellular carcinoma (HCC) patients, which can be caused by microvascular invasion (MVI). However, it is difficult to predict preoperative MVI status. In this study, we focus on cancer genomic alterations to comprehensively explore potential MVI and early recurrence biomarkers and provide clues to the mechanisms of HCC invasion and metastasis. Methods Forty-one patients with initially suspected HCC who were undergoing hepatectomy were finally enrolled. High-throughput targeted sequencing was performed on genomic alterations in their preoperative plasma and surgical fresh tumor tissues utilizing the 1,021-gene panel. Results HCC patients without MVI had longer RFS than MVI ones (p < 0.0001). The mutant incidence of genes like KEAP1, TP53, HIST1H3D, NFKBIA, PIK3CB, and WRN was higher in both MVI and early-recurrence patients than their counterparts. Besides, the alteration rates of Rap1 and Ras signaling pathways were significantly higher in MVI patients than NMVI ones (p < 0.05), and a similar trend of differences was also found in early-recurrence/non-recurrence comparison. The maximal variant allele frequency (VAF) of circulating tumor DNA (ctDNA) was statistically higher in MVI patients than NMVI ones (0.038 vs. 0.012, p = 0.0048). With the cutoff value of 0.018, ctDNA maximal VAF could potentially predict the presence of MVI with an AUC of 0.85 (95% CI 0.693–0.998, p = 0.0062). Conclusion The integration of a panel containing specific mutated genes and ctDNA maximal VAF for predicting MVI and early recurrence of HCC may achieve better performance.
Collapse
Affiliation(s)
- Zhaodan Xin
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.,Med+ Molecular Diagnostics Institute of West China Hospital/West China School of Medicine, Chengdu, China.,West China School of Medicine, Sichuan University, Chengdu, China
| | - Jin Li
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.,Med+ Molecular Diagnostics Institute of West China Hospital/West China School of Medicine, Chengdu, China
| | - Haili Zhang
- West China School of Medicine, Sichuan University, Chengdu, China.,Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yi Zhou
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.,Med+ Molecular Diagnostics Institute of West China Hospital/West China School of Medicine, Chengdu, China
| | - Jiajia Song
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.,Med+ Molecular Diagnostics Institute of West China Hospital/West China School of Medicine, Chengdu, China
| | - Piaopiao Chen
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.,Med+ Molecular Diagnostics Institute of West China Hospital/West China School of Medicine, Chengdu, China
| | - Ling Bai
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.,Med+ Molecular Diagnostics Institute of West China Hospital/West China School of Medicine, Chengdu, China
| | - Hao Chen
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.,Med+ Molecular Diagnostics Institute of West China Hospital/West China School of Medicine, Chengdu, China
| | - Juan Zhou
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.,Med+ Molecular Diagnostics Institute of West China Hospital/West China School of Medicine, Chengdu, China
| | - Jie Chen
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.,Med+ Molecular Diagnostics Institute of West China Hospital/West China School of Medicine, Chengdu, China
| | - Binwu Ying
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.,Med+ Molecular Diagnostics Institute of West China Hospital/West China School of Medicine, Chengdu, China
| |
Collapse
|
|
39
|
Kim SJ, Kim JM, Yi NJ, Choi GS, Lee KW, Suh KS, Joh JW. Validation for models for tumor recurrence after liver transplantation in hepatectomy patients. Ann Surg Treat Res 2022; 102:131-138. [PMID: 35317356 PMCID: PMC8914523 DOI: 10.4174/astr.2022.102.3.131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 01/13/2022] [Accepted: 01/18/2022] [Indexed: 11/30/2022] Open
Affiliation(s)
- Sung Joon Kim
- Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Gyu-Seong Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Jae-Won Joh
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| |
Collapse
|
|
40
|
Jeon D, Choi WM, Kim JS, Jung Y, Lee SY, Seo HR, Kim KM. Serum Sorbitol Dehydrogenase as a Novel Prognostic Factor for Hepatocellular Carcinoma after Surgical Resection. Cancers (Basel) 2021; 13:6143. [PMID: 34885252 PMCID: PMC8657083 DOI: 10.3390/cancers13236143] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2021] [Revised: 12/02/2021] [Accepted: 12/03/2021] [Indexed: 12/12/2022] Open
Abstract
The majority of patients with hepatocellular carcinoma (HCC) undergoing curative resection experience tumor recurrence. To examine the association between preoperative serum sorbitol dehydrogenase (SORD), a liver-derived enzyme that reflects liver damage, and recurrence of HCC after curative resection, 92 patients were randomly selected who underwent curative resection for HCC between 2011 and 2012 from a prospective registry. Recurrence-free survival (RFS) was compared based on serum SORD levels. Cox proportional hazard models were used to investigate prognostic factors for RFS. During a median follow-up duration of 57.1 months, 43 patients experienced HCC recurrence. Patients with serum SORD ≥15 ng/mL (HR, 3.46; 95% CI, 1.76-6.81; p < 0.001) had worse RFS compared with patients with serum SORD <15 ng/mL. Serum AFP and SORD levels were two independent prognostic factors for RFS. When patients were stratified by baseline serum SORD and AFP levels, patients with serum AFP levels ≥400 ng/mL and serum SORD levels ≥15 ng/mL had a distinctly poor prognosis with the lowest RFS rates (HR, 22.08; 95% CI, 6.91-70.50; p < 0.001). Baseline serum SORD is an effective prognostic factor for HCC after resection. It may help guide patient selection for surgery, especially when combined with serum AFP levels.
Collapse
Affiliation(s)
- Dongsub Jeon
- Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; (D.J.); (W.-M.C.); (J.-S.K.); (Y.J.)
| | - Won-Mook Choi
- Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; (D.J.); (W.-M.C.); (J.-S.K.); (Y.J.)
| | - Jin-Sun Kim
- Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; (D.J.); (W.-M.C.); (J.-S.K.); (Y.J.)
| | - Yusun Jung
- Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; (D.J.); (W.-M.C.); (J.-S.K.); (Y.J.)
| | - Su-Yeon Lee
- Advanced Biomedical Research Laboratory, Institut Pasteur Korea, Seongnam-si 13488, Korea;
| | - Haeng Ran Seo
- Advanced Biomedical Research Laboratory, Institut Pasteur Korea, Seongnam-si 13488, Korea;
| | - Kang Mo Kim
- Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; (D.J.); (W.-M.C.); (J.-S.K.); (Y.J.)
| |
Collapse
|
|
41
|
Fu Y, Wei X, Han Q, Le J, Ma Y, Lin X, Xu Y, Liu N, Wang X, Kong X, Gu J, Tong Y, Wu H. Identification and characterization of a 25-lncRNA prognostic signature for early recurrence in hepatocellular carcinoma. BMC Cancer 2021; 21:1165. [PMID: 34717566 PMCID: PMC8556945 DOI: 10.1186/s12885-021-08827-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 09/30/2021] [Indexed: 02/06/2023] Open
Abstract
Background Early recurrence is the major cause of poor prognosis in hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) are deeply involved in HCC prognosis. In this study, we aimed to establish a prognostic lncRNA signature for HCC early recurrence. Methods The lncRNA expression profile and corresponding clinical data were retrieved from total 299 HCC patients in TCGA database. LncRNA candidates correlated to early recurrence were selected by differentially expressed gene (DEG), univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses. A 25-lncRNA prognostic signature was constructed according to receiver operating characteristic curve (ROC). Kaplan-Meier and multivariate Cox regression analyses were used to evaluate the performance of this signature. ROC and nomogram were used to evaluate the integrated models based on this signature with other independent clinical risk factors. Gene set enrichment analysis (GSEA) was used to reveal enriched gene sets in the high-risk group. Tumor infiltrating lymphocytes (TILs) levels were analyzed with single sample Gene Set Enrichment Analysis (ssGSEA). Immune therapy response prediction was performed with TIDE and SubMap. Chemotherapeutic response prediction was conducted by using Genomics of Drug Sensitivity in Cancer (GDSC) pharmacogenomics database. Results Compared to low-risk group, patients in high-risk group showed reduced disease-free survival (DFS) in the training (p < 0.0001) and validation cohort (p = 0.0132). The 25-lncRNA signature, AFP, TNM and vascular invasion could serve as independent risk factors for HCC early recurrence. Among them, the 25-lncRNA signature had the best predictive performance, and combination of those four risk factors further improves the prognostic potential. Moreover, GSEA showed significant enrichment of “E2F TARGETS”, “G2M CHECKPOINT”, “MYC TARGETS V1” and “DNA REPAIR” pathways in the high-risk group. In addition, increased TILs were observed in the low-risk group compared to the high-risk group. The 25-lncRNA signature negatively associates with the levels of some types of antitumor immune cells. Immunotherapies and chemotherapies prediction revealed differential responses to PD-1 inhibitor and several chemotherapeutic drugs in the low- and high-risk group. Conclusions Our study proposed a 25-lncRNA prognostic signature for predicting HCC early recurrence, which may guide postoperative treatment and recurrence surveillance in HCC patients. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-021-08827-z.
Collapse
Affiliation(s)
- Yi Fu
- Affiliated Zhoupu Hospital, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China.,Shanghai Key Laboratory of Molecular Imaging, Collaborative Innovation Center for Biomedicines, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China.,School of Medical Instruments, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China
| | - Xindong Wei
- Nanjing University of Traditional Chinese Medicine, Nanjing, 210000, China
| | - Qiuqin Han
- Affiliated Zhoupu Hospital, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China.,Shanghai Key Laboratory of Molecular Imaging, Collaborative Innovation Center for Biomedicines, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China
| | - Jiamei Le
- Affiliated Zhoupu Hospital, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China.,Shanghai Key Laboratory of Molecular Imaging, Collaborative Innovation Center for Biomedicines, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China
| | - Yujie Ma
- Shanghai Key Laboratory of Molecular Imaging, Collaborative Innovation Center for Biomedicines, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China
| | - Xinjie Lin
- Shanghai Key Laboratory of Molecular Imaging, Collaborative Innovation Center for Biomedicines, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China
| | - Yuhui Xu
- Graduate School of Art and Sciences, Columbia University, New York, NY, 10027, USA
| | - Ning Liu
- Department of Clinical Oncology, Taian City Central Hospital, Taian, 271000, Shandong, China
| | - Xuan Wang
- Department of General Surgery, Nanjing General Hospital of Nanjing Military Command, Nanjing, 210000, China
| | - Xiaoni Kong
- Institute of Clinical Immunology, Department of Liver Diseases, Central Laboratory, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200021, China
| | - Jinyang Gu
- Department of Transplantation, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
| | - Ying Tong
- Department of Liver Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
| | - Hailong Wu
- Affiliated Zhoupu Hospital, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China. .,Shanghai Key Laboratory of Molecular Imaging, Collaborative Innovation Center for Biomedicines, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China.
| |
Collapse
|
|
42
|
Different Risk Factors for Early and Late Recurrence After Curative Resection of Hepatocellular Carcinoma. World J Surg 2021; 46:197-206. [PMID: 34533588 DOI: 10.1007/s00268-021-06308-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/28/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND Factors of early and late recurrence after curative resection of hepatocellular carcinoma (HCC) may be different. The aim of this study was to identify clinical factors, including liver stiffness measurement (LSM), which are associated with HCC recurrence after curative resection. METHODS Patients who underwent preoperative LSM and primary curative resection for HCC between October 2015 and May 2018 were retrospectively reviewed, with 1 year as the cut-off between early and late recurrence. RESULTS Recurrence was observed in 42/149 (28.2%) patients over a median follow-up of 38.3 months (early recurrence: 10 [6.7%] patients; late recurrence: 32 [21.5%] patients). Multivariate analysis identified LSM (P = 0.026) and tumor size (P = 0.010) as the only factors that were significantly associated with recurrence-free survival. Compared with patients without recurrence, those with early recurrence had larger tumor size (P = 0.035) and those with late recurrence had higher LSM (P = 0.024). Receiver-operating characteristic analysis indicated that the optimal LSM cut-off value for predicting HCC recurrence was 7.4 kPa. CONCLUSION Tumor size was associated with early HCC recurrence after curative resection and LSM was associated with late recurrence. LSM cut-off of 7.4 kPa is recommended in predicting recurrence.
Collapse
|
|
43
|
Lin SY, Chang TT, Steffen JD, Chen S, Jain S, Song W, Lin YJ, Su YH. Detection of CTNNB1 Hotspot Mutations in Cell-Free DNA from the Urine of Hepatocellular Carcinoma Patients. Diagnostics (Basel) 2021; 11:1475. [PMID: 34441409 PMCID: PMC8393790 DOI: 10.3390/diagnostics11081475] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 07/30/2021] [Accepted: 08/11/2021] [Indexed: 11/16/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. The beta-catenin gene, CTNNB1, is among the most frequently mutated in HCC tissues. However, mutational analysis of HCC tumors is hampered by the difficulty of obtaining tissue samples using traditional biopsy. Here, we explored the feasibility of detecting tumor-derived CTNNB1 mutations in cell-free DNA (cfDNA) extracted from the urine of HCC patients. Using a short amplicon qPCR assay targeting HCC mutational hotspot CTNNB1 codons 32-37 (exon 3), we detected CTNNB1 mutations in 25% (18/73) of HCC tissues and 24% (15/62) of pre-operative HCC urine samples in two independent cohorts. Among the CTNNB1-mutation-positive patients with available matched pre- and post-operative urine (n = 13), nine showed apparent elimination (n = 7) or severalfold reduction (n = 2) of the mutation in urine following tumor resection. Four of the seven patients with no detectable mutations in postoperative urine remained recurrence-free within five years after surgery. In contrast, all six patients with mutation-positive in post-operative urine recurred, including the two with reduced mutation levels. This is the first report of association between the presence of CTNNB1 mutations in pre- and post-operative urine cfDNA and HCC recurrence with implications for minimum residual disease detection.
Collapse
Affiliation(s)
- Selena Y. Lin
- JBS Science, Inc., Doylestown, PA 18902, USA; (S.Y.L.); (J.D.S.); (S.C.); (S.J.); (W.S.)
| | - Ting-Tsung Chang
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan;
| | - Jamin D. Steffen
- JBS Science, Inc., Doylestown, PA 18902, USA; (S.Y.L.); (J.D.S.); (S.C.); (S.J.); (W.S.)
| | - Sitong Chen
- JBS Science, Inc., Doylestown, PA 18902, USA; (S.Y.L.); (J.D.S.); (S.C.); (S.J.); (W.S.)
| | - Surbhi Jain
- JBS Science, Inc., Doylestown, PA 18902, USA; (S.Y.L.); (J.D.S.); (S.C.); (S.J.); (W.S.)
| | - Wei Song
- JBS Science, Inc., Doylestown, PA 18902, USA; (S.Y.L.); (J.D.S.); (S.C.); (S.J.); (W.S.)
| | - Yih-Jyh Lin
- Department of Surgery, National Cheng Kung University Medical College and Hospital, Tainan 701, Taiwan
| | - Ying-Hsiu Su
- The Baruch S. Blumberg Research Institute, Doylestown, PA 18902, USA
| |
Collapse
|
|
44
|
Kim HS, Yi NJ, Kim JM, Joh JW, Lee KW, Suh KS. Clinical impact of the treatment modality on small, solitary, recurrent intrahepatic hepatocellular carcinomas after primary liver resection. Ann Surg Treat Res 2021; 101:85-92. [PMID: 34386457 PMCID: PMC8331554 DOI: 10.4174/astr.2021.101.2.85] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 04/13/2021] [Accepted: 05/04/2021] [Indexed: 02/07/2023] Open
Abstract
Purpose The aim of this study was to determine the survival benefit based on different treatment strategies in patients with small, solitary, recurring intrahepatic hepatocellular carcinomas (HCCs) that were defined as recurred Barcelona Clinic Liver Cancer stage O (reBCLC-O). Methods Among the 917 patients with HCC recurrence after primary hepatic resection, 394 patients with reBCLC-O were selected. Of these, 150 patients underwent curative treatment (re-resection, radiofrequency ablation, and liver transplantation) and 203 underwent transarterial chemoembolization (TACE) group for recurrent HCC. After propensity score matching (PSM), both the groups were well balanced (89 patients in each group). Results Before PSM, the 1-, 3-, and 5-year overall survival (OS) rates of patients in the curative treatment group (96.7%, 78.6%, and 70.5%, respectively) were significantly better than those in the TACE treatment group (95.6%, 53.7%, and 44.2%, respectively) (P < 0.001). After PSM, the 1-, 3-, and 5-year OS rates also differed significantly (92.0%, 79.6%, and 71.1% in the curative treatment group vs. 88.8%, 65.6%, and 57.9% in the TACE group) (P = 0.005). The independent predictors of worse OS were tumor number at the time of resection and treatment modality for the recurrence, time interval to recurrence, and prothrombin time international normalized ratio and alpha-fetoprotein levels at the time of recurrence. Conclusion The OS of patients in the curative treatment group was better than that in the non-curative treatment group after PSM. Based on our results, curative treatment should be strongly recommended in the patients with reBCLC-O recurrence for better survival.
Collapse
Affiliation(s)
- Hyo-Sin Kim
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.,Department of Surgery, Chonnam National University Medical School, Gwangju, Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jae-Won Joh
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| |
Collapse
|
|
45
|
Yang Y, Xin Y, Ye F, Liu N, Zhang X, Wang Y, Li X, Fan Q, Zhou X, Chen Y. Early recurrence after radiofrequency ablation for hepatocellular carcinoma: a multicenter retrospective study on definition, patterns and risk factors. Int J Hyperthermia 2021; 38:437-446. [PMID: 33724137 DOI: 10.1080/02656736.2020.1849828] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
OBJECTIVE To define an optimal cutoff time to distinguish early and late recurrence in hepatocellular carcinoma (HCC) patients after radiofrequency ablation (RFA), and to determine the risk factors and patterns of early recurrence. MATERIALS AND METHODS This retrospective study included HCC patients who developed recurrence after RFA as the primary therapy at three Chinese hospitals from January 2011 to December 2016. The best cutoff time to define early and late recurrence was determined based on differences in post recurrence survival (PRS). The clinical variables were assessed by univariate and multivariate logistic regression analyses. RESULTS A total of 279 eligible patients were included. The optimal cutoff time interval after RFA to differentiate early and late recurrence was identified as 12 months (p = 0.029). The independent risk factors of early recurrence were multiple tumors, alpha fetoprotein (AFP) levels, gamma-glutamyl transferase (γ-GT), and serum albumin (ALB) levels. A well-discriminated nomogram was constructed to predict risk of early recurrence. The incidence of intrahepatic distant recurrence (IDR) alone and IDR + extrahepatic recurrence (ER) in early recurrence group was significantly higher than those in late recurrence group (80.73% vs. 66.47%, p = 0.009). CONCLUSION Twelve months was determined as the optimal cutoff time for differentiating early and late recurrence after RFA for HCC patients. The factors affecting early recurrence after RFA were multiple tumors, AFP levels, ALB level, and γ-GT level. Patients in early recurrence cohort were more likely to develop IDR alone or IDR + ER.
Collapse
Affiliation(s)
- Yi Yang
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yujing Xin
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Feng Ye
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ning Liu
- Department of Computer Science and Technology, Tsinghua University, Beijing, China
| | - Xinyuan Zhang
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yanan Wang
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiao Li
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qingsheng Fan
- Department of Oncology, Capital Medical University Affiliated Beijing Hospital of Traditional Chinese Medicine, Beijing, China
| | - Xiang Zhou
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yi Chen
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Department of Interventional Radiology, First Hospital of Shanxi Medical University, Taiyuan, China
| |
Collapse
|
|
46
|
Sun YF, Wu L, Liu SP, Jiang MM, Hu B, Zhou KQ, Guo W, Xu Y, Zhong Y, Zhou XR, Zhang ZF, Liu G, Liu S, Shi YH, Ji Y, Du M, Li NN, Li GB, Zhao ZK, Huang XY, Xu LQ, Yu QC, Peng DH, Qiu SJ, Sun HC, Dean M, Wang XD, Chung WY, Dennison AR, Zhou J, Hou Y, Fan J, Yang XR. Dissecting spatial heterogeneity and the immune-evasion mechanism of CTCs by single-cell RNA-seq in hepatocellular carcinoma. Nat Commun 2021; 12:4091. [PMID: 34215748 PMCID: PMC8253833 DOI: 10.1038/s41467-021-24386-0] [Citation(s) in RCA: 128] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Accepted: 06/14/2021] [Indexed: 02/07/2023] Open
Abstract
Little is known about the transcriptomic plasticity and adaptive mechanisms of circulating tumor cells (CTCs) during hematogeneous dissemination. Here we interrogate the transcriptome of 113 single CTCs from 4 different vascular sites, including hepatic vein (HV), peripheral artery (PA), peripheral vein (PV) and portal vein (PoV) using single-cell full-length RNA sequencing in hepatocellular carcinoma (HCC) patients. We reveal that the transcriptional dynamics of CTCs were associated with stress response, cell cycle and immune-evasion signaling during hematogeneous transportation. Besides, we identify chemokine CCL5 as an important mediator for CTC immune evasion. Mechanistically, overexpression of CCL5 in CTCs is transcriptionally regulated by p38-MAX signaling, which recruites regulatory T cells (Tregs) to facilitate immune escape and metastatic seeding of CTCs. Collectively, our results reveal a previously unappreciated spatial heterogeneity and an immune-escape mechanism of CTC, which may aid in designing new anti-metastasis therapeutic strategies in HCC.
Collapse
Affiliation(s)
- Yun-Fan Sun
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China
| | - Liang Wu
- BGI-Shenzhen, Shenzhen, Beishan Industrial Zone, Shenzhen, China
- BGI Education Center, University of Chinese Academy of Sciences (UCAS), Shenzhen, China
- Shenzhen Key Laboratory of Single-cell Omics, BGI-Shenzhen, Shenzhen, China
| | - Shi-Ping Liu
- BGI-Shenzhen, Shenzhen, Beishan Industrial Zone, Shenzhen, China
- Shenzhen Key Laboratory of Single-cell Omics, BGI-Shenzhen, Shenzhen, China
| | - Miao-Miao Jiang
- BGI-Shenzhen, Shenzhen, Beishan Industrial Zone, Shenzhen, China
- State Key Laboratory of Bioelectronics, Southeast University, Nanjing, China
- School of Biological Science and Medical Engineering, Southeast University, Nanjing, China
| | - Bo Hu
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China
| | - Kai-Qian Zhou
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China
| | - Wei Guo
- Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Yang Xu
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China
| | - Yu Zhong
- BGI-Shenzhen, Shenzhen, Beishan Industrial Zone, Shenzhen, China
- Shenzhen Key Laboratory of Single-cell Omics, BGI-Shenzhen, Shenzhen, China
| | - Xiao-Rui Zhou
- BGI-Shenzhen, Shenzhen, Beishan Industrial Zone, Shenzhen, China
- BGI Education Center, University of Chinese Academy of Sciences (UCAS), Shenzhen, China
| | - Ze-Fan Zhang
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China
| | - Geng Liu
- BGI-Shenzhen, Shenzhen, Beishan Industrial Zone, Shenzhen, China
| | - Sheng Liu
- BGI-Shenzhen, Shenzhen, Beishan Industrial Zone, Shenzhen, China
- BGI Education Center, University of Chinese Academy of Sciences (UCAS), Shenzhen, China
| | - Ying-Hong Shi
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China
| | - Yuan Ji
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Min Du
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Nan-Nan Li
- BGI-Shenzhen, Shenzhen, Beishan Industrial Zone, Shenzhen, China
- Shenzhen Key Laboratory of Single-cell Omics, BGI-Shenzhen, Shenzhen, China
| | - Gui-Bo Li
- BGI-Shenzhen, Shenzhen, Beishan Industrial Zone, Shenzhen, China
- Shenzhen Key Laboratory of Single-cell Omics, BGI-Shenzhen, Shenzhen, China
| | - Zhi-Kun Zhao
- BGI-Shenzhen, Shenzhen, Beishan Industrial Zone, Shenzhen, China
| | - Xiao-Yun Huang
- BGI-Shenzhen, Shenzhen, Beishan Industrial Zone, Shenzhen, China
| | - Li-Qin Xu
- BGI-Shenzhen, Shenzhen, Beishan Industrial Zone, Shenzhen, China
- Shenzhen Key Laboratory of Single-cell Omics, BGI-Shenzhen, Shenzhen, China
| | - Qi-Chao Yu
- BGI-Shenzhen, Shenzhen, Beishan Industrial Zone, Shenzhen, China
- Shenzhen Key Laboratory of Single-cell Omics, BGI-Shenzhen, Shenzhen, China
| | | | - Shuang-Jian Qiu
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China
| | - Hui-Chuan Sun
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China
| | - Michael Dean
- Laboratory of Translational Genomics, Division of Cancer Epidemiology & Genetics, National Cancer Institute Gaithersburg, Rockville, MD, USA
| | - Xiang-Dong Wang
- Zhongshan Hospital Institute of Clinical Science, Shanghai Institute of Clinical Bioinformatics, Fudan University Center for Clinical Bioinformatics, Shanghai, China
| | - Wen-Yuan Chung
- Department of Hepatobiliary and Pancreatic Surgery, University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Ashley R Dennison
- Department of Hepatobiliary and Pancreatic Surgery, University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Jian Zhou
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China
- Zhong-Hua Precision Medical Center, Zhongshan Hospital, Fudan University-BGI, Shanghai, People's Republic of China
| | - Yong Hou
- Zhong-Hua Precision Medical Center, Zhongshan Hospital, Fudan University-BGI, Shanghai, People's Republic of China.
| | - Jia Fan
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China.
- Zhong-Hua Precision Medical Center, Zhongshan Hospital, Fudan University-BGI, Shanghai, People's Republic of China.
| | - Xin-Rong Yang
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China.
| |
Collapse
|
|
47
|
Dai H, Lu M, Huang B, Tang M, Pang T, Liao B, Cai H, Huang M, Zhou Y, Chen X, Ding H, Feng ST. Considerable effects of imaging sequences, feature extraction, feature selection, and classifiers on radiomics-based prediction of microvascular invasion in hepatocellular carcinoma using magnetic resonance imaging. Quant Imaging Med Surg 2021; 11:1836-1853. [PMID: 33936969 PMCID: PMC8047362 DOI: 10.21037/qims-20-218] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Accepted: 12/02/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Microvascular invasion (MVI) has a significant effect on the prognosis of hepatocellular carcinoma (HCC), but its preoperative identification is challenging. Radiomics features extracted from medical images, such as magnetic resonance (MR) images, can be used to predict MVI. In this study, we explored the effects of different imaging sequences, feature extraction and selection methods, and classifiers on the performance of HCC MVI predictive models. METHODS After screening against the inclusion criteria, 69 patients with HCC and preoperative gadoxetic acid-enhanced MR images were enrolled. In total, 167 features were extracted from the MR images of each sequence for each patient. Experiments were designed to investigate the effects of imaging sequence, number of gray levels (Ng), quantization algorithm, feature selection method, and classifiers on the performance of radiomics biomarkers in the prediction of HCC MVI. We trained and tested these models using leave-one-out cross-validation (LOOCV). RESULTS The radiomics model based on the images of the hepatobiliary phase (HBP) had better predictive performance than those based on the arterial phase (AP), portal venous phase (PVP), and pre-enhanced T1-weighted images [area under the receiver operating characteristic (ROC) curve (AUC) =0.792 vs. 0.641/0.634/0.620, P=0.041/0.021/0.010, respectively]. Compared with the equal-probability and Lloyd-Max algorithms, the radiomics features obtained using the Uniform quantization algorithm had a better performance (AUC =0.643/0.666 vs. 0.792, P=0.002/0.003, respectively). Among the values of 8, 16, 32, 64, and 128, the best predictive performance was achieved when the Ng was 64 (AUC =0.792 vs. 0.584/0.697/0.677/0.734, P<0.001/P=0.039/0.001/0.137, respectively). We used a two-stage feature selection method which combined the least absolute shrinkage and selection operator (LASSO) and recursive feature elimination (RFE) gradient boosting decision tree (GBDT), which achieved better stability than and outperformed LASSO, minimum redundancy maximum relevance (mRMR), and support vector machine (SVM)-RFE (stability =0.967 vs. 0.837/0.623/0.390, respectively; AUC =0.850 vs. 0.792/0.713/0.699, P=0.142/0.007/0.003, respectively). The model based on the radiomics features of HBP images using the GBDT classifier showed a better performance for the preoperative prediction of MVI compared with logistic regression (LR), SVM, and random forest (RF) classifiers (AUC =0.895 vs. 0.850/0.834/0.884, P=0.558/0.229/0.058, respectively). With the optimal combination of these factors, we established the best model, which had an AUC of 0.895, accuracy of 87.0%, specificity of 82.5%, and sensitivity of 93.1%. CONCLUSIONS Imaging sequences, feature extraction and selection methods, and classifiers can have a considerable effect on the predictive performance of radiomics models for HCC MVI.
Collapse
Affiliation(s)
- Houjiao Dai
- Medical AI Lab, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, China
- Shenzhen University Clinical Research Center for Neurological Diseases, Shenzhen University General Hospital, Shenzhen, China
| | - Minhua Lu
- School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, China
| | - Bingsheng Huang
- Medical AI Lab, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, China
- Shenzhen University Clinical Research Center for Neurological Diseases, Shenzhen University General Hospital, Shenzhen, China
| | - Mimi Tang
- Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Tiantian Pang
- School of Computer Science and Software Engineering, Jilin University, Changchun, China
| | - Bing Liao
- Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Huasong Cai
- Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Mengqi Huang
- Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yongjin Zhou
- School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, China
- Marshall Laboratory of Biomedical Engineering, Shenzhen, China
| | - Xin Chen
- School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, China
| | - Huijun Ding
- School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, China
| | - Shi-Ting Feng
- Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| |
Collapse
|
|
48
|
Shin J, Lee S, Kim SS, Chung YE, Choi JY, Park MS, Kim MJ. Characteristics and Early Recurrence of Hepatocellular Carcinomas Categorized as LR-M: Comparison with Those Categorized as LR-4 or 5. J Magn Reson Imaging 2021; 54:1446-1454. [PMID: 33891790 DOI: 10.1002/jmri.27650] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 04/06/2021] [Accepted: 04/06/2021] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND According to the Liver Imaging Reporting and Data System (LI-RADS), the LI-RADS category M (LR-M), which are probably or definitely malignant but are not specific for hepatocellular carcinomas (HCCs), does not exclude HCCs. A gap in knowledge remains, including their characteristics and recurrence of HCCs categorized as LR-M. PURPOSE To compare the characteristics of HCCs categorized as LR-M with HCCs categorized as LR-4 or LR-5 (LR-4/5) using the LI-RADS version 2018 and evaluate the relationship of these categories with the risk of early recurrence after curative resections of single HCCs. STUDY TYPE Retrospective. SUBJECTS Two hundred and eighty-one patients (mean age, 57 years; 191 men and 90 women) who underwent curative resections for single HCCs and preoperative contrast-enhanced MRI between 2015 and 2017. FIELD STRENGTH/SEQUENCE 3T Dual gradient-echo T1 WI with in- and opposed-phase, turbo spin-echo T2 WI, diffusion-weighted echo-planar images, and three-dimensional gradient-echo T1 WI before and after administration of contrast agent. ASSESSMENT MRI features according to the LI-RADS version 2018 were evaluated and LI-RADS category were assigned for each observation. Clinical, imaging, and histopathological features were compared based on LI-RADS categorization. Early recurrence rates (<2 years) and associated factors were also evaluated. STATISTICAL TESTS Fisher's exact test, two-sample t test after satisfying assumption of normality through Shapiro-Wilk test, Fleiss κ coefficient, Cox proportional hazards regression analysis, Kaplan-Meier method, and log-rank test. RESULTS Forty-one HCCs (14.6%) were categorized as LR-M and 240 HCCs (85.4%) were categorized as LR-4/5. LR-M HCCs showed poorer differentiation than LR-4/5 HCCs. In the multivariate analysis, the LR-M category was an independent predictor for early recurrence (hazard ratio, 1.904; 95% confidence interval, 1.024-3.542; P < 0.05). Early recurrence rates were significantly higher in patients with LR-M HCCs than in patients with LR-4/5 HCCs (32.0% vs. 18.4%, respectively, P < 0 05). DATA CONCLUSION Compared to LR-4/5 HCCs, LR-M HCCs were associated with poorer tumor differentiation and higher early recurrence rates after curative resections of single HCCs. LEVEL OF EVIDENCE 3 Technical Efficacy Stage: 2.
Collapse
Affiliation(s)
- Jaeseung Shin
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sunyoung Lee
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Seung-Seob Kim
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yong Eun Chung
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jin-Young Choi
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Mi-Suk Park
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Myeong-Jin Kim
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| |
Collapse
|
|
49
|
Abstract
OBJECTIVE To evaluate the long-term outcomes of surgery for recurrent hepatocellular carcinoma (HCC). BACKGROUND HCC recurs with high incidence after liver resection. Little is known about long-term outcomes of patients undergoing surgery for recurrent HCC. METHODS Among 989 patients who underwent R0/R1 liver resection for HCC between 1995 and 2014, 676 patients who exhibited recurrence were included. Repeat surgery was performed in 128 patients (RS group), and not in the remaining 548 patients (NS group). Prognostic value after repeat surgery was evaluated by comparing survival after recurrence (SAR) between the RS and NS groups. Subgroup analyses according to the 3 recurrence patterns [intrahepatic recurrence (IHR), extrahepatic recurrence (EHR), and intra plus extrahepatic recurrence (IHR + EHR)] were performed. RESULTS Seventy-three of 430 patients (17.0%) with IHR, 17 of 57 patients (29.8%) with EHR, and 38 of 189 patients (20.1%) with IH + EHR underwent repeat surgery. Compared with the NS group, the RS group had better liver function and their time to recurrence was significantly longer (16.5 vs 11.4 months; P < 0.001). In the overall and 3 recurrence patterns, the 5-year SAR rate was better in the RS group compared with the NS group (RS vs NS group; overall, 53.0% vs 25.7%; IHR, 73.8% vs 37.2%; EHR, 30.0% vs 0%; IHR + EHR, 34.1% vs 10.6%; all P < 0.001, respectively). On multivariate analysis, repeat surgery was identified as an independent factor for better SAR (P < 0.001). CONCLUSION Surgery for recurrent HCC may yield long-term survival for not only IHR but also for EHR in selected patients.
Collapse
|
|
50
|
Ahmed A, Stauffer JA, LeGout JD, Burns J, Croome K, Paz-Fumagalli R, Frey G, Toskich B. The use of neoadjuvant lobar radioembolization prior to major hepatic resection for malignancy results in a low rate of post hepatectomy liver failure. J Gastrointest Oncol 2021; 12:751-761. [PMID: 34012663 DOI: 10.21037/jgo-20-507] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Background Neoadjuvant yttrium-90 transarterial radioembolization (TARE) is increasingly being used as a strategy to facilitate resection of otherwise unresectable tumors due to its ability to generate both tumor response and remnant liver hypertrophy. Perioperative outcomes after the use of neoadjuvant lobar TARE remain underinvestigated. Methods A single center retrospective review of patients who underwent lobar TARE prior to major hepatectomy for primary or metastatic liver cancer between 2007 and 2018 was conducted. Baseline demographics, radioembolization parameters, pre- and post-radioembolization volumetrics, intra-operative surgical data, adverse events, and post-operative outcomes were analyzed. Results Twenty-six patients underwent major hepatectomy after neoadjuvant lobar TARE. The mean age was 58.3 years (17-88 years). 62% of patients (n=16) had primary liver malignancies while the remainder had metastatic disease. Liver resection included right hepatectomy or trisegmentectomy, left or extended left hepatectomy, and sectorectomy/segmentectomy in 77% (n=20), 8% (n=2), and 15% (n=4) of patients, respectively. The mean length of stay was 8.3 days (range, 3-33 days) and there were no grade IV morbidities or 90-day mortalities. The incidence of post hepatectomy liver failure (PHLF) was 3.8% (n=1). The median time to progression after resection was 4.5 months (range, 3.3-10 months). Twenty-three percent (n=6) of patients had no recurrence. The median survival was 28.9 months (range, 16.9-46.8 months) from major hepatectomy and 37.6 months (range, 25.2-53.1 months) from TARE. Conclusions Major hepatectomy after neoadjuvant lobar radioembolization is safe with a low incidence of PHLF.
Collapse
Affiliation(s)
- Altan Ahmed
- Department of Radiology, Mayo Clinic, Jacksonville, FL, USA.,Department of Radiology, Moffitt Cancer Center, Tampa, FL, USA
| | | | | | - Justin Burns
- Department of Transplantation, Mayo Clinic, Jacksonville, FL, USA
| | | | | | - Gregory Frey
- Department of Radiology, Mayo Clinic, Jacksonville, FL, USA
| | - Beau Toskich
- Department of Radiology, Mayo Clinic, Jacksonville, FL, USA
| |
Collapse
|