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Lanza C, Ascenti V, Amato GV, Pellegrino G, Triggiani S, Tintori J, Intrieri C, Angileri SA, Biondetti P, Carriero S, Torcia P, Ierardi AM, Carrafiello G. All You Need to Know About TACE: A Comprehensive Review of Indications, Techniques, Efficacy, Limits, and Technical Advancement. J Clin Med 2025; 14:314. [PMID: 39860320 PMCID: PMC11766109 DOI: 10.3390/jcm14020314] [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: 11/10/2024] [Revised: 12/17/2024] [Accepted: 12/28/2024] [Indexed: 01/27/2025] Open
Abstract
Transcatheter arterial chemoembolization (TACE) is a proven and widely accepted treatment option for hepatocellular carcinoma and it is recommended as first-line non-curative therapy for BCLC B/intermediate HCC (preserved liver function, multifocal, no cancer-related symptoms) in patients without vascular involvement. Different types of TACE are available nowadays, including TAE, c-TACE, DEB-TACE, and DSM-TACE, but at present there is insufficient evidence to recommend one TACE technique over another and the choice is left to the operator. This review then aims to provide a comprehensive overview of the current literature on indications, types of procedures, safety, and efficacy of different TACE treatments.
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Affiliation(s)
- Carolina Lanza
- Department of Diagnostic and Interventional Radiology, Foundation IRCCS Cà Granda—Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy; (C.L.); (P.B.); (S.C.); (P.T.); (A.M.I.); (G.C.)
| | - Velio Ascenti
- Postgraduate School in Radiodiagnostics, Università degli Studi di Milano, 20122 Milan, Italy; (V.A.); (G.V.A.); (G.P.); (S.T.); (J.T.)
| | - Gaetano Valerio Amato
- Postgraduate School in Radiodiagnostics, Università degli Studi di Milano, 20122 Milan, Italy; (V.A.); (G.V.A.); (G.P.); (S.T.); (J.T.)
| | - Giuseppe Pellegrino
- Postgraduate School in Radiodiagnostics, Università degli Studi di Milano, 20122 Milan, Italy; (V.A.); (G.V.A.); (G.P.); (S.T.); (J.T.)
| | - Sonia Triggiani
- Postgraduate School in Radiodiagnostics, Università degli Studi di Milano, 20122 Milan, Italy; (V.A.); (G.V.A.); (G.P.); (S.T.); (J.T.)
| | - Jacopo Tintori
- Postgraduate School in Radiodiagnostics, Università degli Studi di Milano, 20122 Milan, Italy; (V.A.); (G.V.A.); (G.P.); (S.T.); (J.T.)
| | - Cristina Intrieri
- Postgraduate School in Diangostic Imaging, Università degli Studi di Siena, 20122 Milan, Italy;
| | - Salvatore Alessio Angileri
- Department of Diagnostic and Interventional Radiology, Foundation IRCCS Cà Granda—Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy; (C.L.); (P.B.); (S.C.); (P.T.); (A.M.I.); (G.C.)
| | - Pierpaolo Biondetti
- Department of Diagnostic and Interventional Radiology, Foundation IRCCS Cà Granda—Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy; (C.L.); (P.B.); (S.C.); (P.T.); (A.M.I.); (G.C.)
| | - Serena Carriero
- Department of Diagnostic and Interventional Radiology, Foundation IRCCS Cà Granda—Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy; (C.L.); (P.B.); (S.C.); (P.T.); (A.M.I.); (G.C.)
| | - Pierluca Torcia
- Department of Diagnostic and Interventional Radiology, Foundation IRCCS Cà Granda—Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy; (C.L.); (P.B.); (S.C.); (P.T.); (A.M.I.); (G.C.)
| | - Anna Maria Ierardi
- Department of Diagnostic and Interventional Radiology, Foundation IRCCS Cà Granda—Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy; (C.L.); (P.B.); (S.C.); (P.T.); (A.M.I.); (G.C.)
| | - Gianpaolo Carrafiello
- Department of Diagnostic and Interventional Radiology, Foundation IRCCS Cà Granda—Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy; (C.L.); (P.B.); (S.C.); (P.T.); (A.M.I.); (G.C.)
- Faculty of Health Science, Università degli Studi di Milano, Via Festa del Perdono 7, 20122 Milan, Italy
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Wang A, Zhang Y, Lv X, Liang G. Therapeutic potential of targeting protein tyrosine phosphatases in liver diseases. Acta Pharm Sin B 2024; 14:3295-3311. [PMID: 39220870 PMCID: PMC11365412 DOI: 10.1016/j.apsb.2024.05.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 04/08/2024] [Accepted: 04/12/2024] [Indexed: 09/04/2024] Open
Abstract
Protein tyrosine phosphorylation is a post-translational modification that regulates protein structure to modulate demic organisms' homeostasis and function. This physiological process is regulated by two enzyme families, protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). As an important regulator of protein function, PTPs are indispensable for maintaining cell intrinsic physiology in different systems, as well as liver physiological and pathological processes. Dysregulation of PTPs has been implicated in multiple liver-related diseases, including chronic liver diseases (CLDs), hepatocellular carcinoma (HCC), and liver injury, and several PTPs are being studied as drug therapeutic targets. Therefore, given the regulatory role of PTPs in diverse liver diseases, a collated review of their function and mechanism is necessary. Moreover, based on the current research status of targeted therapy, we emphasize the inclusion of several PTP members that are clinically significant in the development and progression of liver diseases. As an emerging breakthrough direction in the treatment of liver diseases, this review summarizes the research status of PTP-targeting compounds in liver diseases to illustrate their potential in clinical treatment. Overall, this review aims to support the development of novel PTP-based treatment pathways for liver diseases.
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Affiliation(s)
- Ao Wang
- Department of Pharmacy and Institute of Inflammation, Zhejiang Provincial Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310014, China
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji 133002, China
| | - Yi Zhang
- Department of Pharmacy and Institute of Inflammation, Zhejiang Provincial Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310014, China
| | - Xinting Lv
- Department of Pharmacy and Institute of Inflammation, Zhejiang Provincial Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310014, China
| | - Guang Liang
- Department of Pharmacy and Institute of Inflammation, Zhejiang Provincial Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310014, China
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji 133002, China
- Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China
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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.
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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.
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Pei YX, Su CG, Liao Z, Li WW, Wang ZX, Liu JL. Comparative effectiveness of several adjuvant therapies after hepatectomy for hepatocellular carcinoma patients with microvascular invasion. World J Gastrointest Surg 2024; 16:554-570. [PMID: 38463369 PMCID: PMC10921205 DOI: 10.4240/wjgs.v16.i2.554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 12/24/2023] [Accepted: 01/18/2024] [Indexed: 02/25/2024] Open
Abstract
BACKGROUND For resectable hepatocellular carcinoma (HCC), radical hepatectomy is commonly used as a curative treatment. However, postoperative recurrence significantly diminishes the overall survival (OS) of HCC patients, especially with microvascular invasion (MVI) as an independent high-risk factor for recurrence. While some studies suggest that postoperative adjuvant therapy may decrease the risk of recurrence following liver resection in HCC patients, the specific role of adjuvant therapies in those with MVI remains unclear. AIM To conduct a network meta-analysis (NMA) to evaluate the efficacy of various adjuvant therapies and determine the optimal adjuvant regimen. METHODS A systematic literature search was conducted on PubMed, EMBASE, and Web of Science until April 6, 2023. Studies comparing different adjuvant therapies or comparing adjuvant therapy with hepatectomy alone were included. Hazard ratios (HRs) with 95% confidence intervals were used to combine data on recurrence free survival and OS in both pairwise meta-analyses and NMA. RESULTS Fourteen eligible trials (2268 patients) reporting five different therapies were included. In terms of reducing the risk of recurrence, radiotherapy (RT) [HR = 0.34 (0.23, 0.5); surface under the cumulative ranking curve (SUCRA) = 97.7%] was found to be the most effective adjuvant therapy, followed by hepatic artery infusion chemotherapy [HR = 0.52 (0.35, 0.76); SUCRA = 65.1%]. Regarding OS improvement, RT [HR: 0.35 (0.2, 0.61); SUCRA = 93.1%] demonstrated the highest effectiveness, followed by sorafenib [HR = 0.48 (0.32, 0.69); SUCRA = 70.9%]. CONCLUSION Adjuvant therapy following hepatectomy may reduce the risk of recurrence and provide a survival benefit for HCC patients with MVI. RT appears to be the most effective adjuvant regimen.
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Affiliation(s)
- Yin-Xuan Pei
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Chengde Medical University, Chengde 067000, Hebei Province, China
| | - Chen-Guang Su
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Chengde Medical University, Chengde 067000, Hebei Province, China
| | - Zheng Liao
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Chengde Medical University, Chengde 067000, Hebei Province, China
| | - Wei-Wei Li
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Chengde Medical University, Chengde 067000, Hebei Province, China
| | - Zi-Xiang Wang
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Chengde Medical University, Chengde 067000, Hebei Province, China
| | - Jin-Long Liu
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Chengde Medical University, Chengde 067000, Hebei Province, China
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Nakamura S, Tada T, Sue M, Matsuo Y, Murakami S, Muramatsu T, Morii K, Okada H. Clinical Outcomes of Next-Generation Microwave Thermosphere Ablation for Hepatocellular Carcinoma with Primarily Hepatitis-Related Etiology. J Clin Med 2023; 12:7577. [PMID: 38137645 PMCID: PMC10743866 DOI: 10.3390/jcm12247577] [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: 10/24/2023] [Revised: 12/04/2023] [Accepted: 12/06/2023] [Indexed: 12/24/2023] Open
Abstract
BACKGROUND AND AIM We investigated the clinical outcomes of patients with hepatocellular carcinoma (HCC) who underwent next-generation microwave thermosphere ablation (MTA). METHODS A total of 429 patients with 607 HCCs (maximum tumor diameter ≤40 mm) were included. We defined the following areas of the liver as those where MTA therapy is difficult to perform: caudate lobe and areas near the primary and secondary branches of the intrahepatic portal vein, inferior vena cava, gallbladder, heart, duodenum, abdominal esophagus, collateral veins around the liver, and spleen. Factors which predisposed patients to local tumor recurrence in the context of tumor location and complications were examined. RESULTS The primary etiologies of HCC were hepatitis-related: 259 (60.4%) cases of HCV, 31 (7.3%) cases of HBV, and two instances of both. Median maximum tumor diameter was 15.0 (interquartile range, 10.0-21.0) mm. There were 86 tumors in areas of the liver where MTA is difficult. The most common area was near the primary and secondary branches of the intrahepatic portal vein (26 nodules). The cumulative local tumor recurrence rates at 1, 2, and 3 years were 4.4%, 8.0%, and 8.5%, respectively. The cumulative local tumor recurrence rate differed significantly by tumor size group: 6.6%, 13.8%, and 29.4% at three years in the ≤20 mm group (n = 483), 20-30 mm group (n = 107), and ≥30 mm group (n = 17), respectively (p < 0.001). The cumulative local tumor recurrence rate was similar despite difficult-to-treat status (p = 0.169). In the multivariable analysis, tumor size (>15 mm) (hazard ratio [HR], 2.15; 95% confidence interval [CI], 1.11-4.16; p = 0.023) and ablative margin (<3 mm) (HR, 2.94; 95% CI, 1.52-5.71; p = 0.001) were significantly associated with local tumor recurrence. Only tumor size (>15 mm) (odds ratio, 3.41 95% CI, 1.53-7.84; p = 0.026) was significantly associated with complications. CONCLUSIONS MTA is a safe and effective local ablation therapy for HCC, even for tumors located in areas of the liver where local ablation therapy is difficult.
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Affiliation(s)
- Shinichiro Nakamura
- Department of Internal Medicine, Japanese Red Cross Society Himeji Hospital, 1-12-1 Shimoteno, Himeji 670-8540, Japan; (T.T.); (M.S.); (K.M.); (H.O.)
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Zheng L, Yang C, Sheng R, Rao S, Wu L, Zeng M, Dai Y. Characterization of Microvascular Invasion in Hepatocellular Carcinoma Using Computational Modeling of Interstitial Fluid Pressure and Velocity. J Magn Reson Imaging 2023; 58:1366-1374. [PMID: 36762823 DOI: 10.1002/jmri.28644] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2022] [Revised: 01/28/2023] [Accepted: 01/30/2023] [Indexed: 02/11/2023] Open
Abstract
BACKGROUND Most solid tumors show increased interstitial fluid pressure (IFP), and this increased IFP is an obstacle to treatment. A noninvasive model for measuring IFP in hepatocellular carcinoma (HCC) is an unresolved issue. PURPOSE To develop a noninvasive model to measure IFP and interstitial fluid velocity (IFV) in HCC and to characterize the microvascular invasion (MVI) status by using this model. STUDY TYPE Retrospective. POPULATION A total of 97 HCC patients (mean age 57.6 ± 10.9 years, 77.3% males), 53 of them with MVI and 44 of them without MVI. FIELD STRENGTH/SEQUENCE A 3-T, three-dimensional spoiled gradient-recalled echo. ASSESSMENT MVI was defined as microscopic vascular invasion of small vessels within the peritumoral liver tissue. The volumes of interest (VOIs) were manually delineated and enclosed the tumor lesion and healthy liver parenchyma, respectively. The extended Tofts model (ETM) was used to estimate permeability parameters from all the VOIs. Subsequently, the continuity partial differential equation (PDE) was implemented and IFP and IFV were acquired. STATISTICAL TESTS Wilcoxon signed-ranks tests, histogram analysis, Mann-Whitney U test, Fisher's exact test, least absolute shrinkage and selection operator (LASSO) logistic regression, receiver operating characteristic (ROC) curve analysis with the area under the curve (AUC), Youden index, DeLong test, and Benjamini-Hochberg correction. A P value <0.05 was considered statistically significant. RESULTS The HCC lesions exhibited elevated IFP and reduced IFV. There were no significant differences in any measured demographic and clinical features between the MVI-positive and MVI-negative groups, except for tumor size. Nine IFP histogram analysis-derived parameters and seven IFV histogram analysis-derived parameters could be used to characterize the MVI status. LASSO regression selected five features: IFP maximum, IFP 10th percentile, IFP 90th percentile, IFV SD, and IFV 10th percentile. The combination of these features showed the highest AUC (0.781) and specificity (77.3%). DATA CONCLUSION A noninvasive IFP and IFV measurement model for HCC was developed. Specific IFP- and IFV-derived parameters exhibited significant association with the MVI status. EVIDENCE LEVEL 3. TECHNICAL EFFICACY Stage 2.
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Affiliation(s)
- Liyun Zheng
- Shanghai Institute of Medical Imaging, Shanghai, China
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Chun Yang
- Shanghai Institute of Medical Imaging, Shanghai, China
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ruofan Sheng
- Shanghai Institute of Medical Imaging, Shanghai, China
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Shengxiang Rao
- Shanghai Institute of Medical Imaging, Shanghai, China
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Lifang Wu
- Shanghai Institute of Medical Imaging, Shanghai, China
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Mengsu Zeng
- Shanghai Institute of Medical Imaging, Shanghai, China
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yongming Dai
- School of Biomedical Engineering, ShanghaiTech University, Shanghai, China
- MR Collaboration, Central Research Institute, United Imaging Healthcare, Shanghai, China
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Chen Y, Yang X, Li X. Impact of radiation therapy and alpha-fetoprotein level on survival outcomes for patients with hepatocellular carcinoma: A population-based study. Clin Res Hepatol Gastroenterol 2023; 47:102196. [PMID: 37553066 DOI: 10.1016/j.clinre.2023.102196] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Accepted: 08/06/2023] [Indexed: 08/10/2023]
Abstract
BACKGROUND The use of radiation therapy (RT) in hepatocellular carcinoma (HCC) remains a matter for debate. Recently published research indicate that advanced RT techniques may improve survival in patients with HCC. This study aimed to evaluate this hypothesis in a large-scale retrospective cohort. The effect of alpha-fetoprotein (AFP) was taken into account because of its important role in the prognosis of HCC. METHODS The Surveillance, Epidemiology, and End Results (SEER) database was queried for adults patients diagnosed 2010-2019 with HCC (≥ 18 years). The study population was divided into four groups: Non-radiation & AFP-positive (reference), Non-radiation & AF-negative, Radiation & AFP-positive, Radiation & AFP-negative. Distant metastasis (DM) was used as a stratification factor. Differences in 5-year overall survival (OS) of the four groups were assessed using the Kaplan-Meier method. Univariate and multivariable Cox proportional hazards model were used to estimate unadjusted and adjusted hazard ratios (HR). RESULTS A total of 34,656 patients were eligible for this analysis, including 21,084 (60.8%), 8,449 (24.4%), 3,810 (11.0%) and 1,313 (3.8%) in the Non-radiation & AFP-positive, Non-radiation & AF-negative, Radiation & AFP-positive and Radiation & AFP-negative groups, respectively. Median OSs of the four groups were 3, 4, 5 and 11 months in the DM cohort, and 12, 28, 15, and 28 months in the Non-DM cohort. Patients in the Radiation & AFP - group had the best OS and patients in the Non-radiation & AFP + group had the worst OS (adjusted HR [95% confidence interval (CI)]: 0.497 [0.399-0.619] in the DM cohort, and 0.405 [0.372-0.441] in the Non-DM cohort). Radiation & AFP + also showed improved survival compared with the reference group (adjusted HR [95%CI]: 0.725 [0.657-0.801] in the DM cohort, and 0.630 [0.600-0.661] in the Non-DM cohort). CONCLUSIONS This population-based cohort study confirmed a significant improvement in overall survival with radiation therapy in HCC. AFP-negative patients benefit the most from RT. Superior OS of radiation therapy and AFP-negative status persisted even in patients with complex metastasis patterns. Our data suggest that radiation may provide an alternative modality for unresectable HCC.
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Affiliation(s)
- Yahong Chen
- Nursing Department, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Xueqing Yang
- Nursing Department, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Xiawei Li
- Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China.
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Aydin Y, Koksal AR, Thevenot P, Nunez K, Elgamal M, Koksal UI, Sandow T, Moehlen M, Regenstein F, Tahan V, Cohen A. The number of hepatocellular carcinoma foci as predictor of poor response to tumor-directed therapies in patients awaiting liver transplantation: a prospective cohort study. Eur J Gastroenterol Hepatol 2023; 35:1224-1229. [PMID: 37577793 DOI: 10.1097/meg.0000000000002631] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/15/2023]
Abstract
BACKGROUND AND AIMS Tumor-directed therapies (TDTs) are a constitutive part of hepatocellular carcinoma (HCC) treatment in patients awaiting liver transplantation (LT). While most patients benefit from TDTs as a bridge to LT, some patients drop out from the waiting list due to tumor progression. The study aimed to determine the risk factors for poor treatment outcome following TDTs among patients with HCC awaiting LT. METHODS A total of 123 patients with HCC were evaluated with 92 patients meeting Milan Criteria enrolled in the prospective cohort study. Tumor response was evaluated using the modified Response Evaluation Criteria for Solid Tumors for HCC 1 month after the procedure. The risk factors for progressive disease (PD) and dropout were evaluated. RESULTS After TDT, 55 patients (59.8%) achieved complete or partial response (44.6% and 15.2% respectively), 17 patients (18.5%) had stable disease, and 20 patients (21.7%) were assessed as PD. Multivariate analysis revealed a significant and independent association between the number of HCC foci and PD ( P = 0.03, OR = 2.68). There was no statistically significant association between treatment response and demographics, MELDNa score, pre-and post-treatment alpha-fetoprotein (AFP), cumulative tumor burden the largest tumor size, or TDT modality. PD was the major cause of dropout in our cohort. Pre-treatment AFP levels ≥200 ng/ml had a strong association with dropout after TDTs ( P = 0.0005). CONCLUSION This study demonstrated the presence of multifocal HCC is the sole prognostic factor for PD following TDTs in HCC patients awaiting LT. We recommend prioritizing patients with multifocal HCC within Milan criteria by exception points for LT to improve the dropout rate.
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Affiliation(s)
- Yucel Aydin
- Department of Medicine, Division of Gastroenterology and Hepatology, Tulane University Health Sciences Center
| | - Ali R Koksal
- Department of Medicine, Division of Gastroenterology and Hepatology, Tulane University Health Sciences Center
| | - Paul Thevenot
- Institute of Translational Research, Ochsner Clinic Foundation, New Orleans, Louisiana
| | - Kelley Nunez
- Institute of Translational Research, Ochsner Clinic Foundation, New Orleans, Louisiana
| | - Mohamed Elgamal
- Internal Medicine, Saint Mary`s Hospital, Waterbury, Connecticut
| | - Ulkuhan I Koksal
- Department of Medicine, Division of Hematology and Medical Oncology, Tulane University Health Sciences Center, New Orleans, Louisiana
| | - Tyler Sandow
- Institute of Translational Research, Ochsner Clinic Foundation, New Orleans, Louisiana
| | - Martin Moehlen
- Department of Medicine, Division of Gastroenterology and Hepatology, Tulane University Health Sciences Center
| | - Frederic Regenstein
- Department of Medicine, Division of Gastroenterology and Hepatology, Tulane University Health Sciences Center
| | - Veysel Tahan
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Missouri, Columbia, Missouri
| | - Ari Cohen
- Institute of Translational Research, Ochsner Clinic Foundation, New Orleans, Louisiana
- Multi-Organ Transplant Institute, Ochsner Clinic Foundation, New Orleans, Louisiana, USA
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Li W, Wan L. Cost-effectiveness analysis of adding transarterial chemoembolisation to lenvatinib as first-line treatment for advanced hepatocellular carcinoma in China. BMJ Open 2023; 13:e074245. [PMID: 37751954 PMCID: PMC10533713 DOI: 10.1136/bmjopen-2023-074245] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 09/03/2023] [Indexed: 09/30/2023] Open
Abstract
OBJECTIVE The objective of this study was to evaluate the comparative cost-effectiveness of lenvatinib (LEN) plus transarterial chemoembolisation (TACE) (LEN-TACE) and LEN alone to treat advanced hepatocellular carcinoma (HCC) from the perspective of the Chinese healthcare system. DESIGN A three-state partitioned survival model using clinical survival data from a phase III LAUNCH trial, a 5-year time horizon for costs and quality-adjusted life years (QALYs) was constructed to analyse the cost-effectiveness of LEN-TACE. Clinical inputs were extracted from the LAUNCH trial, with outcomes extrapolated using standard and flexible parametric survival models. Costs and utilities derived from published literature were discounted at an annual rate of 5%. Sensitivity analyses and scenario analyses were conducted to test the robustness of the model. SETTING The Chinese healthcare system perspective. PARTICIPANTS A hypothetical Chinese cohort of patients with advanced HCC. INTERVENTIONS TACE plus LEN versus LEN. PRIMARY OUTCOME MEASURE Costs, QALYs, incremental cost-effectiveness ratio (ICER). RESULTS Base-case analysis revealed that LEN-TACE would be cost-effective in China at the willingness-to-pay (WTP) threshold of $37 663 per QALYs, with improved effectiveness of 0.382 QALYs and additional cost of $12 151 (ICER: $31 808 per QALY). The probabilistic sensitivity analysis suggested that LEN-TACE had a 93.5% probability of cost-effectiveness at WTP threshold of three times gross domestic product per capital ($37 663). One-way deterministic sensitivity analysis indicated that the duration of LEN treatment in both two arms, utility of progression-free survival and the cost of TACE had a greater impact on the stability of ICER values. Scenario analyses results were in line with base-case analysis. CONCLUSIONS LEN-TACE might be a cost-effective strategy compared with LEN for the first-line treatment of patients with advanced HCC in China.
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Affiliation(s)
- Wei Li
- Department of Pharmacy, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Li Wan
- Department of Pharmacy, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
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10
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Jeng LB, Li TC, Wang J, Teng CF. Increased plasma levels of monocyte chemoattractant protein-1 in patients with hepatitis B virus pre-S2 gene deletion mutation predict a higher risk of hepatocellular carcinoma recurrence after curative surgical resection. Cancer 2023; 129:2621-2636. [PMID: 37096803 DOI: 10.1002/cncr.34815] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 03/29/2023] [Accepted: 04/04/2023] [Indexed: 04/26/2023]
Abstract
BACKGROUND Despite resection surgery as a curative therapy for hepatocellular carcinoma (HCC), the high rate of postoperative HCC recurrence remains a big challenge for patient survival. Chronic hepatitis B virus (HBV) infection is the most important risk factor for HCC. Deletion mutation in the HBV pre-S2 gene leads to expression of an essential viral oncoprotein called pre-S2 mutant and represents an independent prognostic biomarker for HCC recurrence after curative surgical resection. Additionally, cytokines are multifunctional secreted proteins and implicated in all stages of HBV-related HCC tumorigenesis. METHODS This study aimed to identify the cytokines whose plasma levels were associated with pre-S2 gene deletion mutation and HCC recurrence and evaluate their potential to be combined with pre-S2 gene deletion mutation in predicting HCC recurrence. RESULTS Among a panel of 27 cytokines examined, plasma levels of monocyte chemoattractant protein-1 (MCP-1) were significantly upregulated in patients with pre-S2 gene deletion mutation or HCC recurrence. MCP-1 was validated as an independent prognostic biomarker for HCC recurrence. Moreover, patients with both the presence of pre-S2 gene deletion mutation and high levels of MCP-1 displayed a higher risk of HCC recurrence than patients with either one or none of these two biomarkers. The combination of pre-S2 gene deletion mutation and MCP-1 levels exhibited a better prognostic performance for HCC recurrence than each biomarker alone. CONCLUSIONS This study discovered that MCP-1 levels had a significance to be as a combination biomarker with pre-S2 gene deletion mutation providing an improved performance in predicting HCC recurrence after curative surgical resection.
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Affiliation(s)
- Long-Bin Jeng
- Organ Transplantation Center, China Medical University Hospital, Taichung, Taiwan
- Department of Surgery, China Medical University Hospital, Taichung, Taiwan
- Cell Therapy Center, China Medical University Hospital, Taichung, Taiwan
| | - Tsai-Chung Li
- Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan
- Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan
| | - John Wang
- Department of Pathology, China Medical University Hospital, Taichung, Taiwan
| | - Chiao-Fang Teng
- Organ Transplantation Center, China Medical University Hospital, Taichung, Taiwan
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
- Program for Cancer Biology and Drug Development, China Medical University, Taichung, Taiwan
- Research Center for Cancer Biology, China Medical University, Taichung, Taiwan
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11
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Combination of Hepatitis B Virus Pre-S2 Gene Deletion Mutation and Tumor-Node-Metastasis Stage Predicts Higher Hepatocellular Carcinoma Recurrence after Curative Surgical Resection. Biomedicines 2023; 11:biomedicines11030923. [PMID: 36979902 PMCID: PMC10045911 DOI: 10.3390/biomedicines11030923] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 03/09/2023] [Accepted: 03/15/2023] [Indexed: 03/19/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most frequent and life-threatening human cancers worldwide. Despite curative resection surgery, the high recurrence rate of HCC leads to poor patient survival. Chronic hepatitis B virus (HBV) infection is a major etiological factor for HCC. HBV pre-S2 gene deletion mutation leads to the expression of an important oncoprotein called a pre-S2 mutant. It represents an independent prognostic biomarker for HCC recurrence. This study aimed to identify other independent prognostic biomarkers from clinicopathological characteristics of 75 HBV-related HCC patients receiving resection surgery and to validate their potential to be combined with pre-S2 gene deletion mutation as a combination biomarker for HCC recurrence. Patients with both the presence of pre-S2 gene deletion mutation and tumor-node-metastasis (TNM) stage IIIA–IIIC had a higher HCC recurrence risk than patients with either one or none of these two factors. Moreover, the combination of pre-S2 gene deletion mutation and TNM stage exhibited better performance than either of these two factors alone in discriminating patients from patients without HCC recurrence. Collectively, this study proposed that the TNM stage held significance as a combination biomarker with pre-S2 gene deletion mutation with a greater performance in predicting HCC recurrence after curative surgical resection.
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12
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Yu SJ, Lee YB, Cho EJ, Lee JH, Kim HC, Chung JW, Yoon JH, Kim YJ. Use of doxorubicin-eluting bead transarterial chemoembolization for unresectable hepatocellular carcinoma with portal vein invasion: a prospective study. JOURNAL OF LIVER CANCER 2023; 23:166-176. [PMID: 37384028 PMCID: PMC10202235 DOI: 10.17998/jlc.2023.02.08] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 02/02/2023] [Accepted: 02/08/2023] [Indexed: 06/30/2023]
Abstract
Background/Aim To evaluate the applicability of transarterial chemoembolization (TACE) treatment with doxorubicin drug-eluting beads (DEBs) in advanced hepatocellular carcinoma (HCC) patients with portal vein invasion (PVI). Methods This prospective study was approved by the institutional review board and informed consent was obtained from all participants. A total of 30 HCC patients with PVI received DEB-TACE between 2015 and 2018. The following parameters were evaluated: complications during DEB-TACE, abdominal pain, fever, and laboratory outcomes, including liver function change. Overall survival (OS), time to progression (TTP), and adverse events were also analyzed and assessed. Results DEBs measuring 100-300 μm in diameter were loaded with doxorubicin (150 mg per procedure). There were no complications during DEB-TACE and no significant differences in the levels of prothrombin time, serum albumin, or total bilirubin at follow-up compared to baseline. The median TTP was 102 days (95% confidence interval [CI], 42-207 days) and the median OS was 216 days (95% CI, 160-336 days). Three patients (10%) had severe adverse reactions, including transient acute cholangitis (n=1), cerebellar infarction (n=1), and pulmonary embolism (n=1), but no treatment-related death occurred. Conclusions DEB-TACE may be a therapeutic option for advanced HCC patients with PVI.
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Affiliation(s)
- Su Jong Yu
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Yun Bin Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Eun Ju Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Hyo-Cheol Kim
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Jin Wook Chung
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Jung-Hwan Yoon
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Yoon Jun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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13
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Ding Z, Fang H, Huang M, Yu T. Laparoscopic versus open in right posterior sectionectomy: a systematic review and meta-analysis. Langenbecks Arch Surg 2023; 408:25. [PMID: 36637531 DOI: 10.1007/s00423-023-02764-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 11/17/2022] [Indexed: 01/14/2023]
Abstract
BACKGROUND Laparoscopic liver resection (LLR) is now widely adopted for the treatment of liver tumors due to its minimally invasive advantages. However, multicenter, large-sample population-based laparoscopic right posterior sectionectomy (LRPS) has rarely been reported. We aimed to assess the advantages and drawbacks of right posterior sectionectomy compared with laparoscopic and open surgery by meta-analysis. METHODS Relevant literature was searched using the PubMed, Embase, Cochrane, Ovid Medline, and Web of Science databases up to September 12, 2021. Quality assessment was performed based on a modified version of the Newcastle-Ottawa Scale (NOS). The data were analyzed by Review Manager 5.3. The data were calculated by odds ratio (OR) or mean difference (MD) with 95% confidence intervals (CI) for fixed-effects and random-effects models. RESULTS The meta-analysis included seven studies involving 739 patients. Compared with open right posterior sectionectomy (ORPS), the LRPS group had lower intraoperative blood loss (MD - 135.45; 95%CI - 170.61 to - 100.30; P < 0.00001) and shorter postoperative hospital stays (MD - 2.17; 95% CI - 3.03 to - 1.31; P < 0.00001). However, there were no statistically significant differences between LRPS and ORPS regarding operative time (MD 44.97; P = 0.11), pedicle clamping (OR 0.65; P = 0.44), clamping time (MD 2.72; P = 0.31), transfusion rate (OR 1.95; P = 0.25), tumor size (MD - 0.16; P = 0.13), resection margin (MD 0.08; P = 0.63), R0 resection (OR 1.49; P = 0.35), recurrence rate (OR 2.06; P = 0.20), 5-year overall survival (OR 1.44; P = 0.45), and 5-year disease-free survival (OR 1.07; P = 0.88). Furthermore, no significant difference was observed in terms of postoperative complications (P = 0.08), bile leakage (P = 0.60), ascites (P = 0.08), incisional infection (P = 0.09), postoperative bleeding (P = 0.56), and pleural effusion (P = 0.77). CONCLUSIONS LRPS has an advantage in the length of hospital stay and blood loss. LRPS is a very useful technology and feasible choice in patients with the right posterior hepatic lobe tumor.
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Affiliation(s)
- Zigang Ding
- Department of Hepatobiliary Pancreatic Surgery, The Jiujiang University Affiliated Hospital, No. 57, Xunyang East Road, Jiujiang, 332000, Jiangxi Province, China
| | - Hongcai Fang
- Department of Hepatobiliary Pancreatic Surgery, The Jiujiang University Affiliated Hospital, No. 57, Xunyang East Road, Jiujiang, 332000, Jiangxi Province, China
| | - Mingwen Huang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China
| | - Tao Yu
- Department of Hepatobiliary Pancreatic Surgery, The Jiujiang University Affiliated Hospital, No. 57, Xunyang East Road, Jiujiang, 332000, Jiangxi Province, China.
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14
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Peng Z, Fan W, Zhu B, Wang G, Sun J, Xiao C, Huang F, Tang R, Cheng Y, Huang Z, Liang Y, Fan H, Qiao L, Li F, Zhuang W, Peng B, Wang J, Li J, Kuang M. Lenvatinib Combined With Transarterial Chemoembolization as First-Line Treatment for Advanced Hepatocellular Carcinoma: A Phase III, Randomized Clinical Trial (LAUNCH). J Clin Oncol 2023; 41:117-127. [PMID: 35921605 DOI: 10.1200/jco.22.00392] [Citation(s) in RCA: 195] [Impact Index Per Article: 97.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
PURPOSE Lenvatinib (LEN) is a first-line therapy for patients with advanced hepatocellular carcinoma (HCC); however, it has shown modest survival benefits. Therefore, we aimed to compare clinical outcomes of LEN combined with transarterial chemoembolization (LEN-TACE) versus LEN monotherapy in patients with advanced HCC. MATERIALS AND METHODS This was a multicenter, randomized, open-label, parallel group, phase III trial. Patients with primary treatment-naive or initial recurrent advanced HCC after surgery were randomly assigned (1:1) to receive LEN plus on-demand TACE (LEN-TACE) or LEN monotherapy. LEN was initiated within 3 days after random assignment (initial dose: 12 mg once daily for patients ≥ 60 kg; 8 mg once daily for patients < 60 kg). TACE was initiated one day after LEN initiation. The primary end point was overall survival (OS). RESULTS Between June 2019 and July 2021, a total of 338 patients underwent random assignment at 12 centers in China: 170 to LEN-TACE and 168 to LEN. At a prespecified event-driven interim analysis after a median follow-up of 17.0 months, the median OS was significantly longer in the LEN-TACE group (17.8 v 11.5 months; hazard ratio, 0.45; P < .001). The median progression-free survival was 10.6 months in the LEN-TACE group and 6.4 months in the LEN group (hazard ratio, 0.43; P < .001). Patients in the LEN-TACE group had a higher objective response rate according to the modified RECIST (54.1% v 25.0%, P < .001). Multivariable analysis revealed that portal vein tumor thrombus and treatment allocation were independent risk factors for OS. CONCLUSION The addition of TACE to LEN improves clinical outcomes and is a potential first-line treatment for patients with advanced HCC.
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Affiliation(s)
- Zhenwei Peng
- Cancer Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Clinical Trials Unit, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Wenzhe Fan
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Bowen Zhu
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Guoying Wang
- Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Junhui Sun
- Division of Hepatobiliary and Pancreatic Surgery, Hepatobiliary and Pancreatic Interventional Treatment Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Chengjiang Xiao
- Department of Interventional Radiology, Guangdong Second Provincial General Hospital, Guangzhou, China
| | - Fuxi Huang
- Department of Medical Oncology, Guangzhou Panyu Central Hospital, Guangzhou, China
| | - Rong Tang
- Department of Hepatopancreatobiliary Surgery, Hainan General Hospital, Haikou, China
| | - Yu Cheng
- Department of Hepatobiliary Surgery, Huizhou Municipal Central Hospital, Huizhou, China
| | - Zhen Huang
- Department of Interventional Angiology, Huizhou First People's Hospital, Huizhou, China
| | - Yuchuang Liang
- Department of Interventional Medicine, Jiangmen Central Hospital, Jiangmen, China
| | - Huishuang Fan
- Interventional Department, Dongguan People's Hospital, Dongguan, China
| | - Liangliang Qiao
- Department of Interventional Oncology, Jinshazhou Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Fuliang Li
- Hepatobiliary Surgical Department, Gaozhou People's Hospital, Gaozhou, China
| | - Wenquan Zhuang
- Department of Interventional Radiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Baogang Peng
- Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jiping Wang
- Division of Surgical Oncology, Hepatobiliary Cancer, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Jiaping Li
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Ming Kuang
- Cancer Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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15
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Sabeti S, Ternifi R, Larson NB, Olson MC, Atwell TD, Fatemi M, Alizad A. Morphometric analysis of tumor microvessels for detection of hepatocellular carcinoma using contrast-free ultrasound imaging: A feasibility study. Front Oncol 2023; 13:1121664. [PMID: 37124492 PMCID: PMC10134399 DOI: 10.3389/fonc.2023.1121664] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Accepted: 03/21/2023] [Indexed: 05/02/2023] Open
Abstract
Introduction A contrast-free ultrasound microvasculature imaging technique was evaluated in this study to determine whether extracting morphological features of the vascular networks in hepatic lesions can be beneficial in differentiating benign and malignant tumors (hepatocellular carcinoma (HCC) in particular). Methods A total of 29 lesions from 22 patients were included in this work. A post-processing algorithm consisting of clutter filtering, denoising, and vessel enhancement steps was implemented on ultrasound data to visualize microvessel structures. These structures were then further characterized and quantified through additional image processing. A total of nine morphological metrics were examined to compare different groups of lesions. A two-sided Wilcoxon rank sum test was used for statistical analysis. Results In the malignant versus benign comparison, six of the metrics manifested statistical significance. Comparing only HCC cases with the benign, only three of the metrics were significantly different. No statistically significant distinction was observed between different malignancies (HCC versus cholangiocarcinoma and metastatic adenocarcinoma) for any of the metrics. Discussion Obtained results suggest that designing predictive models based on such morphological characteristics on a larger sample size may prove helpful in differentiating benign from malignant liver masses.
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Affiliation(s)
- Soroosh Sabeti
- Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine and Science, Rochester, MN, United States
| | - Redouane Ternifi
- Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine and Science, Rochester, MN, United States
| | - Nicholas B. Larson
- Department of Quantitative Health Sciences, Mayo Clinic College of Medicine and Science, Rochester, MN, United States
| | - Michael C. Olson
- Department of Radiology, Mayo Clinic College of Medicine and Science, Rochester, MN, United States
| | - Thomas D. Atwell
- Department of Radiology, Mayo Clinic College of Medicine and Science, Rochester, MN, United States
| | - Mostafa Fatemi
- Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine and Science, Rochester, MN, United States
| | - Azra Alizad
- Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine and Science, Rochester, MN, United States
- Department of Radiology, Mayo Clinic College of Medicine and Science, Rochester, MN, United States
- *Correspondence: Azra Alizad,
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16
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Charonpongsuntorn C, Tanasanvimon S, Korphaisarn K, Payapwattanawong S, Siripoon T, Pakvisal N, Juengsamarn J, Phaibulvatanapong E, Chindaprasirt J, Prasongsook N, Udomdamrongkul K, Ngamphaiboon N, Sirachainan E. Efficacy, Safety, and Patient-Reported Outcomes of Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma in Thailand: A Multicenter Prospective Study. JCO Glob Oncol 2022; 8:e2200205. [PMID: 36455172 PMCID: PMC10166432 DOI: 10.1200/go.22.00205] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
PURPOSE Atezolizumab plus bevacizumab treatment is a first-line therapy for unresectable hepatocellular carcinoma (HCC) worldwide. The efficacy, safety, and patient-reported outcomes (PROs) of HCC in Thailand have not yet been reported. This study aimed to evaluate the efficacy, safety, and PROs of atezolizumab plus bevacizumab. MATERIALS AND METHODS From September 2020 to August 2021, 30 patients with unresectable HCC who met the inclusion criteria of atezolizumab plus bevacizumab as first-line treatment were enrolled. Analysis was assessed for progression-free survival, overall survival, adverse events (AEs), and quality of life (QoL). RESULTS The median progression-free survival and overall survival periods were 6.7 and 10.2 months, respectively. The disease control rate was 63.3%. The frequent AEs were proteinuria, hypertension, and hepatitis. Serious AEs included gastrointestinal bleeding, but none of the patients died from serious AEs. The discontinuation rate was 23.3%, and the median number of treatment cycles was 10.5 cycles. In total, 23.3% of the patients continued treatment after 1 year of therapy. The global health status/QoL and physical function scores showed less deterioration at baseline than at 3 and 6 months (median scores = 76.7, 71.6, and 64.1 in QoL and 84.7, 79.6, and 79.0 in physical function, respectively). The HCC18 symptom score index data showed a slow progression of symptom scores from baseline to 3 and 6 months (12.7, 19.6, and 22.3, respectively). CONCLUSION This study demonstrates that atezolizumab plus bevacizumab is effective and has a safety profile comparable with that of previous studies as first-line therapy for unresectable HCC in a real-world setting and in Thai populations. Data on PROs also demonstrate benefits in terms of patients' QoL and symptoms.
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Affiliation(s)
- Chanchai Charonpongsuntorn
- Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Srinakharinwirot University, Nakhon Nayok, Thailand
| | - Suebpong Tanasanvimon
- Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Krittiya Korphaisarn
- Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Siriraj Hospital Mahidol University, Bangkok, Thailand
| | - Songwit Payapwattanawong
- Oncology Unit, Department of Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, Lak Hok, Thailand
| | - Teerada Siripoon
- Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Ramathibodi Hospital Mahidol University, Bangkok, Thailand
| | - Nussara Pakvisal
- Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Jitlada Juengsamarn
- Oncology Unit, Department of Medicine, Sunpasitthiprasong Hospital, Ubon Ratchathani, Thailand
| | | | - Jarin Chindaprasirt
- Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Naiyarat Prasongsook
- Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Phramongkutklao University, Bangkok, Thailand
| | | | - Nuttapong Ngamphaiboon
- Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Ramathibodi Hospital Mahidol University, Bangkok, Thailand
| | - Ekaphop Sirachainan
- Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Ramathibodi Hospital Mahidol University, Bangkok, Thailand
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17
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Advances in novel systemic therapies for advanced hepatocellular carcinoma. Future Med Chem 2022; 14:1455-1470. [PMID: 35997677 DOI: 10.4155/fmc-2022-0045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) represents the most frequent type of primary liver tumor. Most HCC patients present with advanced disease at diagnosis and the recurrence rate after surgery remains high. Treatment options for advanced HCC are limited, with sorafenib representing the only systemic agent approved for treatment of advanced HCC in more than a decade. However, in recent years new molecular targeted therapies and immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced HCC. In particular, combinations of ICIs with antiangiogenic drugs, or with other ICIs, represent one of the most promising strategies. Herein we provide a comprehensive overview of the main therapeutic advances in the systemic treatment of HCC, focusing on the most relevant ongoing clinical trials.
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18
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Canesin G, Feldbrügge L, Wei G, Janovicova L, Janikova M, Csizmadia E, Ariffin J, Hedblom A, Herbert ZT, Robson SC, Celec P, Swanson KD, Nasser I, Popov YV, Wegiel B. Heme oxygenase-1 mitigates liver injury and fibrosis via modulation of LNX1/Notch1 pathway in myeloid cells. iScience 2022; 25:104983. [PMID: 36093061 PMCID: PMC9450142 DOI: 10.1016/j.isci.2022.104983] [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: 01/24/2022] [Revised: 07/01/2022] [Accepted: 08/16/2022] [Indexed: 01/12/2023] Open
Abstract
Activation of resident macrophages (Mϕ) and hepatic stellate cells is a key event in chronic liver injury. Mice with heme oxygenase-1 (HO-1; Hmox1)-deficient Mϕ (LysM-Cre:Hmox1 flfl ) exhibit increased inflammation, periportal ductular reaction, and liver fibrosis following bile duct ligation (BDL)-induced liver injury and increased pericellular fibrosis in NASH model. RiboTag-based RNA-sequencing profiling of hepatic HO-1-deficient Mϕ revealed dysregulation of multiple genes involved in lipid and amino acid metabolism, regulation of oxidative stress, and extracellular matrix turnover. Among these genes, ligand of numb-protein X1 (LNX1) expression is strongly suppressed in HO-1-deficient Mϕ. Importantly, HO-1 and LNX1 were expressed by hepatic Mϕ in human biliary and nonbiliary end-stage cirrhosis. We found that Notch1 expression, a downstream target of LNX1, was increased in LysM-Cre:Hmox1 flfl mice. In HO-1-deficient Mϕ treated with heme, transient overexpression of LNX1 drives M2-like Mϕ polarization. In summary, we identified LNX1/Notch1 pathway as a downstream target of HO-1 in liver fibrosis.
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Affiliation(s)
- Giacomo Canesin
- Department of Surgery, Division of Surgical Sciences, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
| | - Linda Feldbrügge
- Charité – Universitätsmedizin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, 13353 Berlin, Germany,Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
| | - Guangyan Wei
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA,Department of Radiation Oncology, First Affiliated Hospital, Sun Yat-sen University, 510080 Guangzhou, China
| | - Lubica Janovicova
- Department of Surgery, Division of Surgical Sciences, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA,Institute of Molecular Biomedicine, Comenius University in Bratislava, 811 08 Bratislava, Slovakia
| | - Monika Janikova
- Department of Surgery, Division of Surgical Sciences, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA,Institute of Molecular Biomedicine, Comenius University in Bratislava, 811 08 Bratislava, Slovakia
| | - Eva Csizmadia
- Department of Surgery, Division of Surgical Sciences, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
| | - Juliana Ariffin
- Department of Surgery, Division of Surgical Sciences, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
| | - Andreas Hedblom
- Department of Surgery, Division of Surgical Sciences, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
| | - Zachary T. Herbert
- Molecular Biology Core Facilities, Dana-Farber Cancer Institute, Boston, MA 02215, USA
| | - Simon C. Robson
- Department of Anesthesia, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
| | - Peter Celec
- Institute of Molecular Biomedicine, Comenius University in Bratislava, 811 08 Bratislava, Slovakia
| | - Kenneth D. Swanson
- Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
| | - Imad Nasser
- Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
| | - Yury V. Popov
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA,Corresponding author
| | - Barbara Wegiel
- Department of Surgery, Division of Surgical Sciences, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA,Corresponding author
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19
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Wu CH, Lee YH, Liang PC, Hu RH, Shih TTF, Ho MC. Predictors of changes in preoperative tumor stage between dynamic computed tomography and gadoxetate disodium-enhanced magnetic resonance imaging for hepatocellular carcinoma. J Formos Med Assoc 2022; 121:1550-1559. [PMID: 35033411 DOI: 10.1016/j.jfma.2021.12.026] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Revised: 08/27/2021] [Accepted: 12/28/2021] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND/PURPOSE Gadoxetate disodium-enhanced magnetic resonance imaging (EOB-MRI) has a higher diagnostic accuracy for hepatocellular carcinoma (HCC) than computed tomography (CT). However, indications for performing EOB-MRI after dynamic CT are not well defined. Therefore, we investigated the clinical factors associated with changes in the preoperative tumor stage between dynamic CT and EOB-MRI. METHODS A prospective cohort was conducted from January 2014 to December 2017. 156 adult patients with clinical suspicion of HCC before liver resection were enrolled and we retrospectively reviewed the images. The tumor staging was evaluated by dynamic CT and then EOB-MRI subsequently according to the TNM staging system. The changes in tumor stage between two modalities were identified, and the associated clinical factors were analyzed. RESULTS A total of 99 patients were analyzed after excluding 57 patients. 20 patients (20.2%) had changes in tumor stage between dynamic CT and EOB-MRI. The change occurred only in early stage (T1 and T2 lesions) based on dynamic CT initially. Furthermore, in univariate and multivariate analyses, albumin-bilirubin (ALBI) grade 2 and log alpha-fetoprotein (AFP) levels were associated with changes in tumor staging by EOB-MRI than those without (50% vs. 9.9%, p < 0.001 and 2.04 ± 1.35 vs. 1.40 ± 1.16, p = 0.038, respectively). Patients with changes in tumor stage also exhibited higher 1-year recurrence rate and shorter recurrence-free survival. CONCLUSION Changes in preoperative tumor stage between dynamic CT and EOB-MRI were associated with CT-defined early stage, ALBI grades, higher log AFP levels, and early recurrence.
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Affiliation(s)
- Chih-Horng Wu
- Department of Medical Imaging, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Radiology, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yu-Hsin Lee
- Department of Surgery, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Po-Chin Liang
- Department of Medical Imaging, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Radiology, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Rey-Heng Hu
- Department of Surgery, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Tiffany Ting-Fang Shih
- Department of Medical Imaging, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Radiology, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Ming-Chih Ho
- Department of Surgery, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan; Center for Functional Image and Interventional Image, National Taiwan University, Taipei, Taiwan; Department of Surgery, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan.
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20
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Association of Increased Programmed Death Ligand 1 Expression and Regulatory T Cells Infiltration with Higher Hepatocellular Carcinoma Recurrence in Patients with Hepatitis B Virus Pre-S2 Mutant after Curative Surgical Resection. Viruses 2022; 14:v14061346. [PMID: 35746817 PMCID: PMC9229682 DOI: 10.3390/v14061346] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Revised: 06/03/2022] [Accepted: 06/18/2022] [Indexed: 01/27/2023] Open
Abstract
Although surgical resection is available as a potentially curative therapy for hepatocellular carcinoma (HCC), high recurrence of HCC after surgery remains a serious obstacle for long-term patient survival. Therefore, the discovery of valuable prognostic biomarkers for HCC recurrence is urgently needed. Pre-S2 mutant is a mutant form of hepatitis B virus (HBV) large surface protein which is expressed from the HBV surface gene harboring deletion mutations spanning the pre-S2 gene segment. Pre-S2 mutant-positive HCC patients have been regarded as a high-risk population of HCC recurrence after resection surgery and display increased immune checkpoint programmed death ligand 1 (PD-L1) expression and pro-tumor regulatory T cells (Tregs) infiltration in tumor tissues. In this study, the association of higher levels of PD-L1 expression and Tregs infiltration in tumor tissues with post-operative HCC recurrence in pre-S2 mutant-positive HCC patients was evaluated. We found that patients with pre-S2 mutant in combination with higher levels of PD-L1 expression and Tregs infiltration in tumor tissues were independently associated with a higher risk of HCC recurrence (hazard ratio, 4.109; p value = 0.0011) and poorer recurrence-free survival (median, 8.2 versus 18.0 months; p value = 0.0004) than those of patients with either one or two of these three biomarkers. Furthermore, a combination of pre-S2 mutant, intra-tumoral PD-L1 expression, and tumor-infiltrating Tregs exhibited superior performance in identifying patients at a higher risk of HCC recurrence (area under the receiver operating characteristic curve, 0.8400). Collectively, this study suggests that higher levels of PD-L1 expression and Tregs infiltration in tumor tissues predicted a higher risk of HCC recurrence in pre-S2 mutant-positive HCC patients after curative surgical resection.
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21
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Di Federico A, Rizzo A, Carloni R, De Giglio A, Bruno R, Ricci D, Brandi G. Atezolizumab-bevacizumab plus Y-90 TARE for the treatment of hepatocellular carcinoma: preclinical rationale and ongoing clinical trials. Expert Opin Investig Drugs 2021; 31:361-369. [PMID: 34798793 DOI: 10.1080/13543784.2022.2009455] [Citation(s) in RCA: 70] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
INTRODUCTION The treatment algorithm of advanced hepatocellular carcinoma (HCC) has evolved since the introduction of immunotherapy. The IMbrave150 trial set atezolizumab-bevacizumab as a new standard-of-care first-line treatment for unresectable HCC patients. However, for patients with intermediate or advanced stage with portal vein thrombosis but without distant metastases, 90Yttrium transarterial radioembolization (90Y-TARE) is considered the treatment of choice. AREAS COVERED We discuss the main evidence regarding the use of 90Y-TARE in HCC, the recent progress of immunotherapy in this tumor, and the preclinical rationale of combining VEGF blockade with the other two treatment strategies. EXPERT OPINION HCC has an extremely heterogeneous tumor immune microenvironment. This may explain the inconsistent outcomes obtained with immune-checkpoint inhibitors. The identification of patients who could benefit most from immunotherapy is crucial; however, reliable markers of response are lacking. Radiation therapy and VEGF inhibition have an established synergism with immunotherapy, mainly linked to enhanced antigen presentation and reduced immunosuppressive immune infiltrate. Combining an immune-checkpoint inhibitor with VEGF blockade and 90Y-TARE might hence overcome primary resistances observed when each of these treatments is administerd alone.
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Affiliation(s)
- Alessandro Di Federico
- Division of Medical Oncology, Irccs Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy.,Department of Specialized, Experimental and Diagnostic Medicine, University of Bologna, Bologna, Italy
| | - Alessandro Rizzo
- Division of Medical Oncology, Irccs Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy.,Department of Specialized, Experimental and Diagnostic Medicine, University of Bologna, Bologna, Italy
| | - Riccardo Carloni
- Division of Medical Oncology, Irccs Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy.,Department of Specialized, Experimental and Diagnostic Medicine, University of Bologna, Bologna, Italy
| | - Andrea De Giglio
- Division of Medical Oncology, Irccs Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy.,Department of Specialized, Experimental and Diagnostic Medicine, University of Bologna, Bologna, Italy
| | - Riccardo Bruno
- Department of Specialized, Experimental and Diagnostic Medicine, University of Bologna, Bologna, Italy.,Department of Radiology, Irccs Azienda Ospedaliero Universitaria Di Bologna, Bologna, Italia
| | - Dalia Ricci
- Division of Medical Oncology, Irccs Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy.,Department of Specialized, Experimental and Diagnostic Medicine, University of Bologna, Bologna, Italy
| | - Giovanni Brandi
- Division of Medical Oncology, Irccs Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy.,Department of Specialized, Experimental and Diagnostic Medicine, University of Bologna, Bologna, Italy
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22
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Tada T, Kumada T, Toyoda H, Nakamura S, Endo Y, Kaneoka Y, Hiraoka A, Joko K, Hirooka M, Hiasa Y. A validation study of combined resection and ablation therapy for multiple hepatocellular carcinoma. Clin Radiol 2021; 77:114-120. [PMID: 34789396 DOI: 10.1016/j.crad.2021.10.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Accepted: 10/15/2021] [Indexed: 11/26/2022]
Abstract
AIM To validate the utility of hepatic resection combined with complementary radiofrequency ablation (RFA) compared with resection alone for patients with multiple hepatocellular carcinoma (HCC), and to compare these results with those of a previous report. MATERIALS AND METHODS A total of 78 HCC patients with multiple (≤5) tumours who were initially treated with hepatic resection only (Resection group) or with combined hepatic resection and RFA (Combination group) were included. Overall and disease-free survival were analysed. RESULTS There were 21 women and 57 men with a median age of 72.5 (64.3-76.8) years. Fifty-three patients were treated with resection alone and 25 received combination therapy. The 3-, 5-, and 7-year cumulative overall survival rates were 81.2%, 68.2%, and 57.1%, respectively, in the Resection group, and 81.3%, 59.6%, and 42.4%%, respectively, in the Combination group (hazard ratio [HR], 1.462; 95% confidence interval [CI], 0.682-3.136; p=0.329). The 1-, 3-, and 5-year cumulative disease-free survival rates were 61.4%, 45.7%, and 39.8%, respectively, in the Resection group, and 53.1%, 18.6%, and 0%, respectively, in the Combination group (HR, 2.080; 95% CI, 1.157-3.737; p=0.014). The overall survival rate was not significantly different between the Resection and Combination groups in patients within the up-to-seven HCC criteria (n=56; HR, 2.101; 95% CI, 0.805-5.486; p=0.130) or those beyond these criteria (n=22; HR, 0.804; 95% CI, 0.197-3.286; p=0.761). CONCLUSIONS The combination of hepatic resection and RFA therapy may be an effective strategy for HCC patients with multiple tumours.
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Affiliation(s)
- T Tada
- Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan; Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan.
| | - T Kumada
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - H Toyoda
- Faculty of Nursing, Gifu Kyoritsu University, Ogaki, Japan
| | - S Nakamura
- Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan
| | - Y Endo
- Department of Surgery, Japanese Red Cross Himeji Hospital, Himeji, Japan
| | - Y Kaneoka
- Department of Surgery, Ogaki Municipal Hospital, Ogaki, Japan
| | - A Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - K Joko
- Hepato-biliary Center, Japanese Red Cross Matsuyama Hospital, Matsuyama, Japan
| | - M Hirooka
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Y Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
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23
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Cucchetti A, Gramenzi A, Johnson P, Giannini EG, Tovoli F, Rapaccini GL, Marra F, Cabibbo G, Caturelli E, Gasbarrini A, Svegliati-Baroni G, Sacco R, Zoli M, Morisco F, Di Marco M, Mega A, Foschi FG, Biasini E, Masotto A, Nardone G, Raimondo G, Azzaroli F, Vidili G, Brunetto MR, Farinati F, Trevisani F. Material deprivation affects the management and clinical outcome of hepatocellular carcinoma in a high-resource environment. Eur J Cancer 2021; 158:133-143. [PMID: 34666215 DOI: 10.1016/j.ejca.2021.09.018] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Revised: 08/31/2021] [Accepted: 09/14/2021] [Indexed: 02/07/2023]
Abstract
AIM This study investigated how material deprivation in Italy influences the stage of hepatocellular carcinoma (HCC) at diagnosis and the chance of cure. METHODS 4114 patients from the Italian Liver Cancer database consecutively diagnosed with HCC between January 2008 and December 2018 were analysed about severe material deprivation (SMD) rate tertiles of the region of birth and region of managing hospitals, according to the European Statistics on Income and Living Conditions. The main outcomes were HCC diagnosis modalities (during or outside surveillance), treatment adoption and overall survival. RESULTS In more deprived regions, HCC was more frequently diagnosed during surveillance, while the incidental diagnosis was prevalent in the least deprived. Tumour characteristics did not differ among regions. The proportion of patients undergoing potentially curative treatments progressively decreased as the SMD worsened. Consequently, overall survival was better in less deprived regions. Patients who moved from most deprived to less deprived regions increased their probability of receiving potentially curative treatments by 1.11 times (95% CI 1.03 to 1.19), decreasing their mortality likelihood (hazard ratio 0.78 95% CI 0.67 to 0.90). CONCLUSIONS Socioeconomic status measured through SMD does not seem to influence HCC features at diagnosis but brings a negative effect on the chance of receiving potentially curative treatments. Patient mobility from the most deprived to the less deprived regions increased the access to curative therapies, with the ultimate result of improving survival.
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Affiliation(s)
- Alessandro Cucchetti
- Department of Medical and Surgical Sciences, University of Bologna, Italy; Morgagni-Pierantoni Hospital, Forlì, Italy.
| | - Annagiulia Gramenzi
- Department of Medical and Surgical Sciences, Semeiotica Medica Unit, University of Bologna, Italy.
| | - Philip Johnson
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, UK.
| | - Edoardo G Giannini
- Department of Internal Medicine, Gastroenterology Unit, IRCCS Policlinico San Martino, University of Genova, Italy.
| | - Francesco Tovoli
- Internal Medicine Unit, S. Orsola-Malpighi Hospital, Bologna, Italy.
| | - Gian Ludovico Rapaccini
- Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario "A. Gemelli", IRCCS, Roma, Italy.
| | - Fabio Marra
- Department of Experimental and Clinical Medicine, University of Firenze, Italy.
| | - Giuseppe Cabibbo
- Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties (PROMISE), Section of Gastroenterology and Hepatology, University of Palermo, Italy.
| | | | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology Unit, Fondazione Policlinico Universitario "A. Gemelli", IRCCS, Roma, Italy.
| | | | - Rodolfo Sacco
- Gastroenterology and Digestive Endoscopy, Foggia University Hospital, Foggia, Italy.
| | - Marco Zoli
- Department of Medical and Surgical Sciences, Internal Medicine Unit, University of Bologna, Italy.
| | - Filomena Morisco
- Department of Medicine and Surgery, Gastroenterology Unit, University of Napoli "Federico II", Italy.
| | | | - Andrea Mega
- Gastroenterology Unit, Bolzano Regional Hospital, Bolzano, Italy.
| | - Francesco G Foschi
- Department of Internal Medicine, Ospedale per gli Infermi di Faenza, Italy.
| | - Elisabetta Biasini
- Infectious Diseases and Hepatology Unit, Azienda Ospedaliero-Universitaria di Parma, Italy.
| | - Alberto Masotto
- Gastroenterology Unit, Ospedale Sacro Cuore Don Calabria, Negrar, Italy.
| | - Gerardo Nardone
- Department of Clinical Medicine and Surgery, Hepato-Gastroenterology Unit, University of Napoli "Federico II", Italy.
| | - Giovanni Raimondo
- Department of Clinical and Experimental Medicine, Clinical and Molecular Hepatology Unit, University of Messina, Italy.
| | - Francesco Azzaroli
- Department of Medical and Surgical Sciences, Gastroenterology Unit, University of Bologna, Italy.
| | - Gianpaolo Vidili
- Department of Medical, Surgical and Experimental Sciences, Clinica Medica Unit, University of Sassari, Italy.
| | - Maurizia R Brunetto
- Department of Clinical and Experimental Medicine, Hepatology and Liver Physiopathology Laboratory and Internal Medicine, University of Pisa, Italy.
| | - Fabio Farinati
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Italy.
| | - Franco Trevisani
- Department of Medical and Surgical Sciences, Semeiotica Medica Unit, University of Bologna, Italy.
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24
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Anti-Hepatocellular Carcinoma Biomolecules: Molecular Targets Insights. Int J Mol Sci 2021; 22:ijms221910774. [PMID: 34639131 PMCID: PMC8509806 DOI: 10.3390/ijms221910774] [Citation(s) in RCA: 59] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 09/25/2021] [Accepted: 09/26/2021] [Indexed: 12/15/2022] Open
Abstract
This report explores the available curative molecules directed against hepatocellular carcinoma (HCC). Limited efficiency as well as other drawbacks of existing molecules led to the search for promising potential alternatives. Understanding of the cell signaling mechanisms propelling carcinogenesis and driven by cell proliferation, invasion, and angiogenesis can offer valuable information for the investigation of efficient treatment strategies. The complexity of the mechanisms behind carcinogenesis inspires researchers to explore the ability of various biomolecules to target specific pathways. Natural components occurring mainly in food and medicinal plants, are considered an essential resource for discovering new and promising therapeutic molecules. Novel biomolecules normally have an advantage in terms of biosafety. They are also widely diverse and often possess potent antioxidant, anti-inflammatory, and anti-cancer properties. Based on quantitative structure-activity relationship studies, biomolecules can be used as templates for chemical modifications that improve efficiency, safety, and bioavailability. In this review, we focus on anti-HCC biomolecules that have their molecular targets partially or completely characterized as well as having anti-cancer molecular mechanisms that are fairly described.
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25
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Jeng LB, Li TC, Hsu SC, Chan WL, Teng CF. Association of Low Serum Albumin Level with Higher Hepatocellular Carcinoma Recurrence in Patients with Hepatitis B Virus Pre-S2 Mutant after Curative Surgical Resection. J Clin Med 2021; 10:jcm10184187. [PMID: 34575311 PMCID: PMC8464848 DOI: 10.3390/jcm10184187] [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: 08/24/2021] [Revised: 09/11/2021] [Accepted: 09/14/2021] [Indexed: 12/17/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is, globally, one of the most prevalent and deadly human cancers; despite curative surgical resection, its high recurrence rate after surgery remains a large threat, resulting in poor patient survival. The hepatitis B virus (HBV) pre-S2 mutant that harbors deletions spanning the pre-S2 gene segment has emerged as an important oncoprotein for HCC development and a valuable prognostic biomarker for HCC recurrence; however, its relationship with clinicopathological factors is largely unexplored. In this study, the correlation of the deletion spanning the pre-S2 gene segment with clinicopathological factors and the association of such correlation with HCC recurrence after curative surgical resection were examined in HBV-related HCC patients. Inverse correlation between serum albumin level and the deletion spanning the pre-S2 gene segment was identified. HCC patients with the presence of the deletion spanning the pre-S2 gene segment and a low serum albumin level were associated with higher HCC recurrence than patients with either factor alone or neither factor were. Moreover, a combination of the serum albumin level and the deletion spanning the pre-S2 gene segment exhibited better performance than that of either factor alone in predicting HCC recurrence. Collectively, this study shows an association of low serum albumin level with pre-S2 mutant-positive HCC patients, and validates the prognostic value of this association in identifying patients with higher HCC recurrence after curative surgical resection.
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Affiliation(s)
- Long-Bin Jeng
- Organ Transplantation Center, China Medical University Hospital, Taichung City 404, Taiwan; (L.-B.J.); (S.-C.H.)
- Department of Surgery, China Medical University Hospital, Taichung City 404, Taiwan
- School of Medicine, China Medical University, Taichung City 404, Taiwan
| | - Tsai-Chung Li
- Department of Public Health, College of Public Health, China Medical University, Taichung City 404, Taiwan;
- Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung City 404, Taiwan
| | - Shih-Chao Hsu
- Organ Transplantation Center, China Medical University Hospital, Taichung City 404, Taiwan; (L.-B.J.); (S.-C.H.)
- Department of Surgery, China Medical University Hospital, Taichung City 404, Taiwan
- School of Medicine, China Medical University, Taichung City 404, Taiwan
| | - Wen-Ling Chan
- Department of Bioinformatics and Medical Engineering, Asia University, Taichung City 404, Taiwan;
- Epigenome Research Center, China Medical University Hospital, Taichung City 404, Taiwan
| | - Chiao-Fang Teng
- Organ Transplantation Center, China Medical University Hospital, Taichung City 404, Taiwan; (L.-B.J.); (S.-C.H.)
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung City 404, Taiwan
- Research Center for Cancer Biology, China Medical University, Taichung City 404, Taiwan
- Correspondence: ; Tel.: +886-4-2205-2121; Fax: +886-4-2202-9083
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26
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Li Z, Yu Q, Lu X, Liu Y, Ji B. Efficacy of radiofrequency ablation versus laparoscopic liver resection for hepatocellular carcinoma in China: a comprehensive meta-analysis. Wideochir Inne Tech Maloinwazyjne 2021; 16:455-471. [PMID: 34691297 PMCID: PMC8512513 DOI: 10.5114/wiitm.2021.105377] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 01/08/2021] [Indexed: 11/17/2022] Open
Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) has been the second leading cause of cancer-related death in China. Radiofrequency ablation is a relatively novel treatment that may improve the treatment of HCC. AIM To evaluate and compare the efficacy and safety of radiofrequency ablation (RFA) versus laparoscopic liver resection (LLR) in the treatment of HCC. MATERIAL AND METHODS We searched for relevant published studies in English (PubMed, Cochrane Library, EMBASE) and in Chinese (CBM, CNKI and Wanfang) from their inception until September 23, 2019. The quality of included studies was evaluated by the Newcastle-Ottawa Scale. RESULTS A total of 19 retrospective studies including 2038 patients were eligible for the meta-analysis. The results of the meta-analysis demonstrated that LLR was superior to RFA in terms of 3-year overall survival rate (OR = 0.62), 1 to 3-year disease-free survival rates (OR = 0.57; OR = 0.41, respectively) and local recurrence rates (OR = 2.71). CONCLUSIONS The meta-analysis demonstrates that laparoscopic liver resection should be preferred in tumors of size 3-5 cm, while for < 3 cm the long term results are equal.
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Affiliation(s)
- Zhijun Li
- Department of Hepatobiliary and Pancreatic Surgery, the First Hospital, Jilin University, Changchun, China
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Qiong Yu
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Xiaozheng Lu
- Department of Hepatobiliary and Pancreatic Surgery, the First Hospital, Jilin University, Changchun, China
| | - Yahui Liu
- Department of Hepatobiliary and Pancreatic Surgery, the First Hospital, Jilin University, Changchun, China
| | - Bai Ji
- Department of Hepatobiliary and Pancreatic Surgery, the First Hospital, Jilin University, Changchun, China
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27
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Elfadaly AN, Tsilimigras DI, Hyer JM, Paro A, Bagante F, Ratti F, Marques HP, Soubrane O, Lam V, Poultsides GA, Popescu I, Alexandrescu S, Martel G, Workneh A, Guglielmi A, Hugh T, Aldrighetti L, Endo I, Pawlik TM. Impact of Tumor Burden Score on Conditional Survival after Curative-Intent Resection for Hepatocellular Carcinoma: A Multi-Institutional Analysis. World J Surg 2021; 45:3438-3448. [PMID: 34341844 DOI: 10.1007/s00268-021-06265-3] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/23/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND The impact of tumor burden score (TBS) on conditional survival (CS) among patients undergoing curative-intent resection of hepatocellular carcinoma (HCC) has not been examined to date. METHODS Patients who underwent liver resection of HCC between 2000 and 2017 were identified from a multi-institutional database. The impact of TBS and other clinicopathologic factors on 3-year conditional survival (CS3) was examined. RESULTS Among 1,040 patients, 263 (25.3%) patients had low TBS, 668 (64.2%) had medium TBS and 109 (10.5%) had high TBS. TBS was strongly associated with OS; 5-year OS was 39.0% among patients with high TBS compared with 61.1% and 79.4% among patients with medium and low TBS, respectively (p < 0.001). While actuarial survival decreased as time elapsed from resection, CS increased over time irrespective of TBS. The largest differences between 3-year actuarial survival and CS3 were noted among patients with high TBS (5-years postoperatively; CS3: 78.7% vs. 3-year actuarial survival: 30.7%). The effect of adverse clinicopathologic factors including high TBS, poor/undifferentiated tumor grade, microvascular invasion, liver capsule involvement, and positive margins on prognosis decreased over time. CONCLUSIONS CS rates among patients who underwent resection for HCC increased as patients survived additional years, irrespective of TBS. CS estimates can be used to provide important dynamic information relative to the changing survival probability after resection of HCC.
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Affiliation(s)
- Ahmed N Elfadaly
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | | | - J Madison Hyer
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Alessandro Paro
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Fabio Bagante
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA.,Department of Surgery, University of Verona, Verona, Italy
| | | | - Hugo P Marques
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | - Olivier Soubrane
- Department of Hepatobiliopancreatic Surgery, APHP, Beaujon Hospital, Clichy, France
| | - Vincent Lam
- Department of Surgery, Westmead Hospital, Sydney, Australia
| | | | - Irinel Popescu
- Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania
| | | | | | - Aklile Workneh
- Department of Surgery, University of Ottawa, Ottawa, Canada
| | | | - Tom Hugh
- Department of Surgery, School of Medicine, The University of Sydney, Sydney, Australia
| | | | - Itaru Endo
- Yokohama City University School of Medicine, Yokohama, Japan
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
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Wu CH, Liang PC, Su TH, Lin MC, Chang YH, Shih TTF, Kao JH. Iodized oil computed tomography versus ultrasound-guided radiofrequency ablation for early hepatocellular carcinoma. Hepatol Int 2021; 15:1247-1257. [PMID: 34338971 DOI: 10.1007/s12072-021-10236-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Accepted: 07/15/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND AND PURPOSE Radiofrequency ablation (RFA) is the standard of care for early stage hepatocellular carcinoma (HCC). However, the clinical outcomes of iodized oil computed tomography (IoCT) versus ultrasound (US)-guided RFA for HCC remain unclear. METHODS We retrospectively analyzed consecutive treatment-naïve patients who received curative RFA for HCC within Milan criteria from January 2016 to December 2018. Patients who underwent either IoCT-guided RFA (IoCT group) or US-guided RFA (US group) were included. Various clinical factors, including tumor location, were adjusted with a 1:1 propensity score matching. Subsequently, the cumulative incidence rates for recurrence and hazard ratios for survival were calculated. RESULTS We included 184 (37.9%) and 301 (62.1%) patients who received IoCT- and US-guided RFA, respectively. Before propensity score matching, IoCT guidance was significantly associated with multiple tumors, higher body mass index, lower albumin level, and tumors located at S8. After matching, the 1-, 2-, and 3-year local tumor progression rates of the IoCT group were significantly lower than those of the US group (4.4%, 6.9%, and 7.5% vs. 14.4%, 16.3%, and 16.3%, respectively, at p = 0.002, 0.009, and 0.016, respectively). In univariate analyses and multivariate analyses that adjusted for clinical and tumor location-related parameters, the IoCT group had better recurrence-free survival (hazard ratio = 0.581, 95% confidence interval 0.375-0.899) than those with US guidance but not overall survival. CONCLUSION IoCT-guided RFA had a lower local tumor progression rate and better recurrence-free survival than did US-guided RFA for HCC within the Milan criteria. CT-guide RFA is a safe and effective alternative to US-guided with similar overall survival. IoCT-guided RFA might have a better local tumor control than US-guided. IoCT-guided RFA may be more suitable for male patients, aged < 70 years, a single tumor measuring 2-5 cm, and a tumor located at the subdiaphragmatic/subcardiac region.
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Affiliation(s)
- Chih-Horng Wu
- Department of Medical Imaging and Radiology, National Taiwan University Hospital and College of Medicine, National Taiwan University, 7 Chung-Shan South Road, Taipei, 10002, Taiwan.,Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Po-Chin Liang
- Department of Medical Imaging and Radiology, National Taiwan University Hospital and College of Medicine, National Taiwan University, 7 Chung-Shan South Road, Taipei, 10002, Taiwan
| | - Tung-Hung Su
- Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Ming-Chi Lin
- Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan
| | - Yu-Hsuan Chang
- Department of Medical Imaging and Radiology, National Taiwan University Hospital and College of Medicine, National Taiwan University, 7 Chung-Shan South Road, Taipei, 10002, Taiwan
| | - Tiffany Ting-Fang Shih
- Department of Medical Imaging and Radiology, National Taiwan University Hospital and College of Medicine, National Taiwan University, 7 Chung-Shan South Road, Taipei, 10002, Taiwan.
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. .,Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
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Zeng J, Wang C, Wang Y, Luo Z, Zhang Y, Luo X. Sorafenib plus partial splenic embolism for treatment of hepatocellular carcinoma Barcelona stage C combined with hypersplenism: a case series. J Int Med Res 2021; 49:3000605211023351. [PMID: 34139869 PMCID: PMC8216376 DOI: 10.1177/03000605211023351] [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] [Indexed: 11/24/2022] Open
Abstract
Background Sorafenib is mainly used to treat patients with hepatocellular carcinoma (HCC) Barcelona Clinic Liver Cancer (BCLC) stage C, many of whom also have severe cirrhosis. However, hypersplenism and digestive tract hemorrhage are common complications of cirrhosis, which increase the risk and difficulty of treatment. Methods Nineteen patients with HCC BCLC stage C with hypersplenism were treated with sorafenib plus partial splenic embolism at Chongqing University Cancer Hospital, Chongqing, China, between January 2015 and June 2018. We analyzed the therapeutic effect and clinical safety of this treatment in these patients. Result Hypersplenism was rectified in all patients. The incidence rates of hemorrhage and myelosuppression were 0%, and the mean survival time was 11.2 months. Conclusion Sorafenib plus partial splenic embolism could relieve hypersplenism and prolong survival in patients with BCLC stage C HCC.
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Affiliation(s)
- Jianting Zeng
- Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), Chongqing University Cancer Hospital, Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing, China
| | - Chunmei Wang
- Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), Chongqing University Cancer Hospital, Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing, China
| | - Yu Wang
- Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), Chongqing University Cancer Hospital, Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing, China
| | - Zhenhua Luo
- Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), Chongqing University Cancer Hospital, Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing, China
| | - Yanlin Zhang
- Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), Chongqing University Cancer Hospital, Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing, China
| | - Xianzhang Luo
- Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), Chongqing University Cancer Hospital, Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing, China
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Qu C, Li XQ, Li C, Xia F, Feng K, Ma K. The Short-Term Efficacy of Novel No-Touch Combined Directional Perfusion Radiofrequency Ablation in the Treatment of Small Hepatocellular Carcinoma with Cirrhosis. J INVEST SURG 2021; 35:880-887. [PMID: 34085878 DOI: 10.1080/08941939.2021.1931575] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND No-touch combined directed perfusion radiofrequency ablation (NTDP-RFA) is a new technique for the treatment of hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the short-term efficacy of this new technique for the treatment of small HCC with cirrhosis. METHODS From January 2017 to March 2018, 56 consecutive patients treated with NTDP-RFA at our center were enrolled in this retrospective study. All NTDP-RFA procedures involved the use of internally cooled wet electrodes with a directional injection function, which can perform both intraelectrode cooling and extraelectrode saline perfusion. Survival curves were analyzed using Kaplan-Meier methods, and Cox proportional hazards regression analyses were used to assess predictors of tumor progression and overall survival. Operative characteristics and complications were also assessed. RESULTS No technical failure occurred, and the complete ablation rate after single NTDP-RFA treatment was 98.2%. The median tumor diameter and ablation time were 26 (18.0 - 28.0) mm and 8 (6 - 8) min, respectively. Mild complications occurred in five patients (8.9%) postoperatively, and the median hospital stay was 4 (4 - 5) days. In the 18 patients (32.1%) with poor liver function reserve (indocyanine green retention rate at 15 min > 15%, their liver function returned to normal on the third day after the postoperation. The 1- and 2-year local and distant progression rates were 1.7%, 7.1%, 3.5% and 10.7%, respectively. CONCLUSIONS NTDP-RFA in the treatment of small HCC with cirrhosis has a low incidence of complications and provides a high survival rate without local tumor progression.
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Affiliation(s)
- Chengming Qu
- Insitute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, P.R. China
| | - Xin-Qian Li
- Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, P.R. China
| | - Changfeng Li
- Insitute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, P.R. China
| | - Feng Xia
- Insitute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, P.R. China
| | - Kai Feng
- Insitute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, P.R. China
| | - Kuansheng Ma
- Insitute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, P.R. China
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The Role of Fibroblast Growth Factor 19 in Hepatocellular Carcinoma. THE AMERICAN JOURNAL OF PATHOLOGY 2021; 191:1180-1192. [PMID: 34000282 DOI: 10.1016/j.ajpath.2021.04.014] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Revised: 04/09/2021] [Accepted: 04/22/2021] [Indexed: 12/12/2022]
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common type of cancer and the third leading cause of cancer-related deaths worldwide. Liver resection or liver transplantation is the most effective therapy for HCC because drugs approved by the US Food and Drug Administration to treat patients with unresectable HCC have an unfavorable overall survival rate. Therefore, the development of biomarkers for early diagnosis and effective therapy strategies are still necessary to improve patient outcomes. Fibroblast growth factor (FGF) 19 was amplified in patients with HCC from various studies, including patients from The Cancer Genome Atlas. FGF19 plays a syngeneic function with other signaling pathways in primary liver cancer development, such as epidermal growth factor receptor, Wnt/β-catenin, the endoplasmic reticulum-related signaling pathway, STAT3/IL-6, RAS, and extracellular signal-regulated protein kinase, among others. The current review presents a comprehensive description of the FGF19 signaling pathway involved in liver cancer development. The use of big data and bioinformatic analysis can provide useful clues for further studies of the FGF19 pathway in HCC, including its application as a biomarker, targeted therapy, and combination therapy strategies.
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Sirohi B, Shrikhande SV, Gaikwad V, Patel A, Patkar S, Goel M, Bal M, Sharma A, Shrimali RK, Bhatia V, Kulkarni S, Srivastava DN, Kaur T, Dhaliwal RS, Rath GK. Indian Council of Medical Research consensus document on hepatocellular carcinoma. Indian J Med Res 2021; 152:468-474. [PMID: 33707388 PMCID: PMC8157895 DOI: 10.4103/ijmr.ijmr_404_20] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
This document aims to assist oncologists in making clinical decisions encountered while managing their patients with hepatocellular carcinoma (HCC), specific to Indian practice, based on consensus among experts. Most patients are staged by Barcelona Clinic Liver Cancer (BCLC) staging system which comprises patient performance status, Child-Pugh status, number and size of nodules, portal vein invasion and metastasis. Patients should receive multidisciplinary care. Surgical resection and transplant forms the mainstay of curative treatment. Ablative techniques are used for small tumours (<3 cm) in patients who are not candidates for surgical resection (Child B and C). Patients with advanced (HCC should be assessed on an individual basis to determine whether targeted therapy, interventional radiology procedures or best supportive care should be provided. In advanced HCC, immunotherapy, newer targeted therapies and modern radiation therapy have shown promising results. Patients should be offered regular surveillance after completion of curative resection or treatment of advanced disease.
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Affiliation(s)
- Bhawna Sirohi
- Department of Medical Oncology, Apollo Proton Cancer Centre, Chennai, India
| | - Shailesh V Shrikhande
- Department of Gastrointestinal & Hepato-Pancreato-biliary Service, Tata Memorial Centre, Mumbai, Maharashtra, India
| | - Vinay Gaikwad
- Department of Gastrointestinal & Hepato-Pancreato-biliary Service, Paras Hospital, Gurugram, Haryana, India
| | - Amol Patel
- Department of Medical Oncology, Army Hospital Research & Referral, New Delhi, India
| | - Shraddha Patkar
- Department of Gastrointestinal & Hepato-Pancreato-biliary Service, Tata Memorial Centre, Mumbai, Maharashtra, India
| | - Mahesh Goel
- Department of Gastrointestinal & Hepato-Pancreato-biliary Service, Tata Memorial Centre, Mumbai, Maharashtra, India
| | - Munita Bal
- Department of Pathology, Tata Memorial Centre, Mumbai, Maharashtra, India
| | - Atul Sharma
- Department of Medical Oncology, Dr. B.R.A Institute-Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
| | - Raj Kumar Shrimali
- Department of Radiation Oncology, Tata Medical Centre, Kolkata, West Bengal, India
| | - Vikram Bhatia
- Department of Gastroenterology, Institute of Liver & Biliary Sciences, New Delhi, India
| | - Suyash Kulkarni
- Department of Interventional Radiology, Tata Memorial Centre, Mumbai, Maharashtra, India
| | - Deep Narayan Srivastava
- Department of Radiodiagnosis, Dr. B.R.A Institute-Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
| | - Tanvir Kaur
- Division of Non-Communicable Diseases, Indian Council of Medical Research, New Delhi, India
| | - R S Dhaliwal
- Division of Non-Communicable Diseases, Indian Council of Medical Research, New Delhi, India
| | - Goura Kishor Rath
- Department of Radiation Oncology, Dr. B.R.A Institute-Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
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Identification of prognostic and metastasis-related alternative splicing signatures in hepatocellular carcinoma. Biosci Rep 2021; 40:225701. [PMID: 32627826 PMCID: PMC7364508 DOI: 10.1042/bsr20201001] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2020] [Revised: 06/23/2020] [Accepted: 06/30/2020] [Indexed: 02/07/2023] Open
Abstract
As the most common neoplasm in digestive system, hepatocellular carcinoma (HCC) is one of the most important leading cause of cancer deaths worldwide. Its high-frequency metastasis and relapse rate lead to the poor survival of HCC patients. However, the mechanism of HCC metastasis is still unclear. Alternative splicing events (ASEs) have a great effect in cancer development, progression and metastasis. We downloaded RNA sequencing and seven types of ASEs data of HCC samples, in order to explore the mechanism of ASEs underlying tumorigenesis and metastasis of HCC. The data were taken from the The Cancer Genome Atlas (TCGA) and TCGASpliceSeq databases. Univariate Cox regression analysis was used to determine a total of 3197 overall survival-related ASEs (OS-SEs). And based on five OS-SEs screened by Lasso regression, we constructed a prediction model with the Area Under Curve of 0.765. With a good reliability of the model, the risk score was also proved to be an independent predictor. Among identified 390 candidate SFs, Y-box protein 3 (YBX3) was significantly correlated with OS and metastasis. Among 177 ASEs, ATP-binding cassette subfamily A member 6 (ABCA6)-43162-AT and PLIN5-46808-AT were identified both associated with OS, bone metastasis and co-expressed with SFs. Then we identified primary bile acid biosynthesis as survival-related (KEGG) pathway by Gene Set Variation Analysis (GSVA) and univariate regression analysis, which was correlated with ABCA6-43162-AT and PLIN5-46808-AT. Finally, we proposed that ABCA6-43162-AT and PLIN5-46808-AT may contribute to HCC poor prognosis and metastasis under the regulation of aberrant YBX3 through the pathway of primary bile acid biosynthesis.
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Cheung TT, Ma KW, She WH. A review on radiofrequency, microwave and high-intensity focused ultrasound ablations for hepatocellular carcinoma with cirrhosis. Hepatobiliary Surg Nutr 2021; 10:193-209. [PMID: 33898560 DOI: 10.21037/hbsn.2020.03.11] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Importance Hepatocellular carcinoma (HCC) is usually accompanied by liver cirrhosis, which makes treatment of this disease challenging. Liver transplantation theoretically provides an ultimate solution to the disease, but the maximal surgical stress and the scarcity of liver graft make this treatment option impossible for some patients. In an ideal situation, a treatment that is safe and effective should provide a better outcome for patients with the dilemma. Objective This article aims to give a comprehensive review of various types of loco-ablative treatment for HCC. Evidence Review Loco-ablative treatment bridges the gap between surgical resection and transarterial chemotherapy. Various types of ablative therapy have their unique ability, and evidence-based outcome analysis is the most important key to assisting clinicians to choose the most suitable treatment modality for their patients. Findings Radiofrequency ablation (RFA) has a relatively longer history and more evidence to support its effectiveness. Microwave ablation (MWA) is gaining momentum because of its shorter ablation time and consistent ablation zone. High-intensity focused ultrasound (HIFU) ablation is a relatively new technology that provides non-invasive treatment for patients with HCC. It has been carried out at centers of excellence and it is a safe and effective treatment option for selected patients with HCC and liver cirrhosis. Conclusion and Relevance Selective use of different loco-ablative therapies will enhance clinicians' treatment options for treatment of HCC.
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Affiliation(s)
- Tan To Cheung
- Department of Surgery, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China
| | - Ka Wing Ma
- Department of Surgery, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China
| | - Wong Hoi She
- Department of Surgery, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China
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Tong J, Liu P, Ji M, Wang Y, Xue Q, Yang JJ, Zhou CM. Machine Learning Can Predict Total Death After Radiofrequency Ablation in Liver Cancer Patients. CLINICAL MEDICINE INSIGHTS-ONCOLOGY 2021; 15:11795549211000017. [PMID: 33854400 PMCID: PMC8013536 DOI: 10.1177/11795549211000017] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Accepted: 02/07/2021] [Indexed: 01/10/2023]
Abstract
Objective: Over 1 million new cases of hepatocellular carcinoma (HCC) are diagnosed worldwide every year. Its prognosis remains poor, and the 5-year survival rate in all disease stages is estimated to be between 10% and 20%. Radiofrequency ablation (RFA) has become an important local treatment for liver cancer, and machine learning (ML) can provide many shortcuts for liver cancer medical research. Therefore, we explore the role of ML in predicting the total mortality of liver cancer patients undergoing RFA. Methods: This study is a secondary analysis of public database data from 578 liver cancer patients. We used Python for ML to establish the prognosis model. Results: The results showed that the 5 most important factors were platelet count (PLT), Alpha-fetoprotein (AFP), age, tumor size, and total bilirubin, respectively. Results of the total death model for liver cancer patients in test group: among the 5 algorithm models, the highest accuracy rate was that of gbm (0.681), followed by the Logistic algorithm (0.672); among the 5 algorithms, area under the curve (AUC) values, from high to low, were Logistic (0.738), DecisionTree (0.723), gbm (0.717), GradientBoosting (0.714), and Forest (0.693); Among the 5 algorithms, gbm had the highest precision rate (0.721), followed by the Logistic algorithm (0.714). Among the 5 algorithms, DecisionTree had the highest recall rate (0.642), followed by the GradientBoosting algorithm (0.571). Conclusion: Machine learning can predict total death after RFA in liver cancer patients. Therefore, ML research has great potential for both personalized treatment and prognosis of liver cancer.
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Affiliation(s)
- Jianhua Tong
- Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Panmiao Liu
- Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Muhuo Ji
- Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Ying Wang
- Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Qiong Xue
- Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jian-Jun Yang
- Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Cheng-Mao Zhou
- Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Choi HJ, Park JH, Kim OH, Kim KH, Hong HE, Seo H, Kim SJ. Combining Everolimus and Ku0063794 Promotes Apoptosis of Hepatocellular Carcinoma Cells via Reduced Autophagy Resulting from Diminished Expression of miR-4790-3p. Int J Mol Sci 2021; 22:ijms22062859. [PMID: 33799789 PMCID: PMC7998287 DOI: 10.3390/ijms22062859] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 03/09/2021] [Accepted: 03/09/2021] [Indexed: 11/16/2022] Open
Abstract
It is challenging to overcome the low response rate of everolimus in the treatment of patients with hepatocellular carcinoma (HCC). To overcome this challenge, we combined everolimus with Ku0063794, the inhibitor of mTORC1 and mTORC2, to achieve higher anticancer effects. However, the precise mechanism for the synergistic effects is not clearly understood yet. To achieve this aim, the miRNAs were selected that showed the most significant variation in expression according to the mono- and combination therapy of everolimus and Ku0063794. Subsequently, the roles of specific miRNAs were determined in the processes of the treatment modalities. Compared to individual monotherapies, the combination therapy significantly reduced viability, increased apoptosis, and reduced autophagy in HepG2 cells. The combination therapy led to significantly lower expression of miR-4790-3p and higher expression of zinc finger protein225 (ZNF225)—the predicted target of miR-4790-3p. The functional study of miR-4790-3p and ZNF225 revealed that regarding autophagy, miR-4790-3p promoted it, while ZNF225 inhibited it. In addition, regarding apoptosis, miR-4790-3p inhibited it, while ZNF225 promoted it. It was also found that HCC tissues were characterized by higher expression of miR-4790-3p and lower expression of ZNF225; HCC tissues were also characterized by higher autophagic flux. We, thus, conclude that the potentiated anticancer effect of the everolimus and Ku0063794 combination therapy is strongly associated with reduced autophagy resulting from diminished expression of miR-4790-3p, as well as higher expression of ZNF225.
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Affiliation(s)
- Ho Joong Choi
- Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (O.-H.K.); (H.E.H.); (H.S.); (S.-J.K.)
- Correspondence:
| | - Jung Hyun Park
- Department of Surgery, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 03312, Korea;
| | - Ok-Hee Kim
- Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (O.-H.K.); (H.E.H.); (H.S.); (S.-J.K.)
- Catholic Central Laboratory of Surgery, Institute of Biomedical Industry, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea;
| | - Kee-Hwan Kim
- Catholic Central Laboratory of Surgery, Institute of Biomedical Industry, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea;
- Department of Surgery, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 11765, Korea
| | - Ha Eun Hong
- Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (O.-H.K.); (H.E.H.); (H.S.); (S.-J.K.)
- Catholic Central Laboratory of Surgery, Institute of Biomedical Industry, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea;
| | - Haeyeon Seo
- Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (O.-H.K.); (H.E.H.); (H.S.); (S.-J.K.)
- Catholic Central Laboratory of Surgery, Institute of Biomedical Industry, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea;
| | - Say-June Kim
- Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (O.-H.K.); (H.E.H.); (H.S.); (S.-J.K.)
- Catholic Central Laboratory of Surgery, Institute of Biomedical Industry, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea;
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Liver Imaging and Data System (LI-RADS) Version 2018 and Other Imaging Features in Intrahepatic Cholangiocarcinoma in Chinese Adults with vs. without Chronic Hepatitis B Viral Infection. Can J Gastroenterol Hepatol 2021; 2021:6639600. [PMID: 33748033 PMCID: PMC7952186 DOI: 10.1155/2021/6639600] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Revised: 02/08/2021] [Accepted: 02/20/2021] [Indexed: 12/14/2022] Open
Abstract
PURPOSE To describe liver imaging reporting and data system (LI-RADS) version 2018 and other MRI imaging features in intrahepatic mass-forming cholangiocarcinoma (iCCA) in Chinese adults with vs. without chronic hepatitis B viral (HBV) infection. METHODS We retrospectively enrolled 89 patients with pathologically proven iCCA after multiphase imaging performed between 2004 and 2017 at a tertiary medical center in southern China. Based on whether patients had chronic HBV, iCCA was divided into two subgroups: HBV-positive (n = 50 patients, including 9 with cirrhosis) vs. HBV-negative (n = 39 patients, including 14 with hepatolithiasis and 25 with no identifiable risk factor for iCCA; none had cirrhosis). Two independent abdominal radiologists in consensus reviewed the largest mass in each patient to assign LI-RADS v2018 features; they also scored each observation's shape and location. Imaging features were compared using chi-square or Fisher's exact tests. RESULTS Most iCCAs in HBV-positive (88% (44/50)) and HBV-negative (97% (38/39)) patients had at least one LR-M feature. Compared to iCCAs in HBV-negative patients, iCCAs in HBV-positive patients were more likely to have at least one major feature of HCC (46% (23/50) vs. 8% (3/39), P < 0.001) and more likely to be smooth (42% (21/50) vs. 10% (4/39), P = 0.001). Six of 50 (12%) iCCAs in HBV-positive patients and 1/39 (3%) iCCAs in HBV-negative patients had at least one major feature of HCC without any LR-M feature. CONCLUSIONS In this retrospective single-center study in Chinese adults, iCCAs in HBV-positive patients were more likely to resemble HCCs than iCCAs in HBV-negative patients.
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Chen R, Zhang J, Kong D, Lou Q, Lu F. Fast calculation of 3D radiofrequency ablation zone based on a closed-form solution of heat conduction equation fitted by ex vivo measurements. Phys Med Biol 2021; 66:055022. [PMID: 33503590 DOI: 10.1088/1361-6560/abe052] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Fast calculation or simulation of the ablation zone induced by radiofrequency ablation (RFA) has a critical role in hepatic RFA planning and therapy. However, it remains challenging to approximate the ablation zone in real time, especially when more than one probe is involved in one ablation session. This paper presents a novel computational technique to calculate the 3D ablation zone of one probe RFA and two-probe switching RFA. The main idea is to get an approximate solution of the temperature distribution from a simplified Pennes bioheat equation, and further fit the solution to the coagulation measurements on ex vivo porcine liver. With a closed-form solution of temperature distribution, the calculation of the ablation zone is as simple as the commonly used ellipsoidal model, but it allows a more realistic prediction of combined ablation zones with different inter-probe spacing. The new approximation technique could potentially replace the original ellipsoidal model in the intervention planning step.
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Affiliation(s)
- Rendong Chen
- School of Mathematical Sciences, Qufu Normal University, Qufu 273165, People's Republic of China
| | - Jianfeng Zhang
- School of Mathematical Sciences, Zhejiang University, Hangzhou 310027, People's Republic of China
| | - Dexing Kong
- School of Mathematical Sciences, Zhejiang University, Hangzhou 310027, People's Republic of China
| | - Qiong Lou
- Department of Mathematics, School of Sciences, Zhejiang University of Science and Technology, Hangzhou 310023, People's Republic of China
| | - Fang Lu
- Department of Mathematics, School of Sciences, Zhejiang University of Science and Technology, Hangzhou 310023, People's Republic of China
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Ghafouri-Fard S, Honarmand Tamizkar K, Hussen BM, Taheri M. MicroRNA signature in liver cancer. Pathol Res Pract 2021; 219:153369. [PMID: 33626406 DOI: 10.1016/j.prp.2021.153369] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 01/31/2021] [Accepted: 02/02/2021] [Indexed: 12/24/2022]
Abstract
Liver cancer is the 7th utmost frequent neoplasm and the 4th principal source of cancer deaths. This malignancy is linked with several environmental and lifestyle-related factors emphasizing the role of epigenetics in its pathogenesis. MicroRNAs (miRNAs) have been regarded as potent epigenetic mechanisms partaking in the pathogenesis of liver cancer. Dysregulation of miRNAs has been related with poor outcome of patients with liver cancer. In the current manuscript, we provide a concise review of the results of recent studies about the role of miRNAs in the progression of liver cancer and their diagnostic and prognostic utility.
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Affiliation(s)
- Soudeh Ghafouri-Fard
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Bashdar Mahmud Hussen
- Pharmacognosy Department, College of Pharmacy, Hawler Medical University, Erbil, Iraq
| | - Mohammad Taheri
- Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Predictors of Complete Response in Patients with Hepatocellular Carcinoma Treated with Trans-Arterial Radioembolization. Curr Oncol 2021; 28:965-977. [PMID: 33617513 PMCID: PMC7985772 DOI: 10.3390/curroncol28010095] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Revised: 02/02/2021] [Accepted: 02/12/2021] [Indexed: 12/12/2022] Open
Abstract
Background: Trans-arterial radioembolization (TARE) has shown promising results in treating hepatocellular carcinoma (HCC). We identified independent predictors of radiological complete response (CR) in patients with intrahepatic HCC who were treated with TARE. Methods: Patients with intrahepatic HCC treated with TARE between 2011 and 2017 were recruited. CR was defined according to the modified Response Evaluation Criteria in Solid Tumors. Cox regression analysis was used to determine independent predictors of CR. Results: The median age of study participants (83 men and 19 women) was 64.3 years. The mean survival after TARE was 55.5 months, and 21 (20.6%) patients died during the study period. Patients who achieved CR (14 patients, 13.7%) had significantly higher serum albumin level (median 4.1 vs. 3.9 g/dL), lower total bilirubin level (median 0.6 vs. 0.7 mg/dL), lower aspartate aminotransferase level (median 30.0 vs. 43.0 IU/L), lower alkaline phosphatase level (median 79.0 vs. 103.0 IU/L), lower alpha-fetoprotein level (median 12.7 vs. 39.9 ng/mL), lower des-gamma-carboxyprothrombin level (median 575.5 vs. 2772.0 mAU/mL), lower model for end-stage liver disease (MELD) score (median 6.0 vs. 7.0), and smaller maximal tumor diameter (median 6.3 vs. 9.0 cm) compared to those who did not achieve CR (all p < 0.005). Multivariate Cox regression analysis showed that lower MELD score (hazard ratio (HR) = 0.436, p = 0.015) and maximal tumor size < 9 cm (HR = 11.180, p = 0.020) were independent predictors of an increased probability of radiological CR after TARE. Conclusions: Low MELD score and small maximal tumor size were independently associated with an increased probability of CR after TARE in patients with intrahepatic HCC.
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Wu H, Chen Y, Li B, Li C, Guo J, You J, Hu X, Kuang D, Qi S, Liu P, Li L, Xu C. Targeting ROCK1/2 blocks cell division and induces mitotic catastrophe in hepatocellular carcinoma. Biochem Pharmacol 2021; 184:114353. [PMID: 33278350 DOI: 10.1016/j.bcp.2020.114353] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 11/28/2020] [Accepted: 11/30/2020] [Indexed: 01/10/2023]
Abstract
BACKGROUND Rho-Associated kinases ROCK1 and ROCK2 have been extensively investigated in the pathogenesis of cardiovascular disease. However, their roles are not fully understood in carcinogenesis. In this study, we investigated whether ROCK1 or ROCK2 is required for the survival and growth of hepatocellular carcinoma (HCC) cells and underlying mechanism. METHODS ROCKs expression was determined in human HCC tissue and cell lines using qRT-PCR, western blotting, and immunohistochemistry (IHC). Cell growth and proliferation were assayed using cell counting kit-8 (CCK-8) and EdU incorporation assay. Cell cycle and apoptosis analysis were performed using flow cytometry. HCC cell division or mitosis was observed using a confocal microscope and a time relapse fluorescence microscope. Inhibitory role of targeting ROCK1/2 on HCC was assayed in both xenograft and primary HCC mouse models. RESULTS Both ROCK1 and ROCK2 are over-expressed in human HCC tissues and cell lines. Knockdown of ROCK1 or ROCK2 inhibited HCC cell growth. Pharmacological inactivation of ROCK1/2 with Fasudil further blocked the growth and survival of HCC both in vitro and in vivo. Mechanically, Fasudil induces cell cycle arrest in HCC cells, but not apoptosis. Instead, Fasudil treatment led to mitotic catastrophe in HCC cells, characterized with the multipolar and asymmetric mitosis, and disassociated stress fibers. Knockdown of cofilin restored the cell morphology and division, and reduced the mitotic catastrophe induced by Fasudil. CONCLUSIONS Both ROCK1 and ROCK2 are required for HCC cell division and growth. Targeting ROCK1 or ROCK2 rather than both can serve as a potential approach for HCC treatment and may reduce the side effects.
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Affiliation(s)
- Hua Wu
- School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Yuyuan Chen
- School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Bin Li
- School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Chun Li
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Jun Guo
- School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Jia You
- School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Xian Hu
- Department of Biosciences, University of Oslo, Oslo, Norway
| | - Dong Kuang
- Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Department of Pathology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Shibo Qi
- Department of Pharmacy, General Hospital of Benxi Iron and Steel Company, Benxi 117000, China
| | - Pin Liu
- Department of Pediatrics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Lei Li
- School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
| | - Chuanrui Xu
- School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
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Increased infiltration of regulatory T cells in hepatocellular carcinoma of patients with hepatitis B virus pre-S2 mutant. Sci Rep 2021; 11:1136. [PMID: 33441885 PMCID: PMC7807072 DOI: 10.1038/s41598-020-80935-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Accepted: 12/28/2020] [Indexed: 12/13/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a frequent and deadly human cancer worldwide that is intimately associated with chronic hepatitis B virus (HBV) infection. Pre-S2 mutant is a HBV oncoprotein that plays important roles in HCC development and is linked to poor prognosis in HCC patients. However, the profiles of tumor-infiltrating lymphocytes in HCC tissues of pre-S2 mutant-positive patients remain unknown. In this study, we performed fluorescent immunohistochemistry staining to detect the infiltration of 'anti-tumor' cytotoxic T lymphocytes (CTLs) and 'pro-tumor' regulatory T cells (Tregs) in pre-S2 mutant-positive and -negative HCC patients. We showed that pre-S2 mutant-positive patients had a significantly higher infiltration of CD4+CD25+ cells and forkhead box P3 (Foxp3)-expressing cells but similar CTLs and lower granzyme B-expressing cells in HCC tissues compared with pre-S2 mutant-negative patients. Moreover, the percentage of pre-S2 plus pre-S1 + pre-S2 deletion (pre-S2 mutant) was positively correlated with the density of CD4+CD25+ cells and Foxp3-expressing cells but negatively with granzyme B-expressing cells in HCC tissues. Considering that increased intratumoral Tregs have been shown to promote tumor immune evasion, our data may provide new insights into the pathogenesis of HBV pre-S2 mutant-induced HCC and suggest that therapeutics targeting Tregs may be a promising strategy for treating pre-S2 mutant-positive high-risk patient population.
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Teng CF, Li TC, Wang T, Wu TH, Wang J, Wu HC, Shyu WC, Su IJ, Jeng LB. Increased Expression of Programmed Death Ligand 1 in Hepatocellular Carcinoma of Patients with Hepatitis B Virus Pre-S2 Mutant. J Hepatocell Carcinoma 2020; 7:385-401. [PMID: 33365286 PMCID: PMC7751729 DOI: 10.2147/jhc.s282818] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Accepted: 11/27/2020] [Indexed: 12/14/2022] Open
Abstract
Purpose Chronic hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC), a leading cause of cancer-related death worldwide. The HCC patients who harbor HBV pre-S2 mutant, an oncoprotein that plays key roles in HCC development, have been closely associated with a worse prognosis after curative surgical resection, suggesting an urgent need for alternative therapeutic options to improve their survival. In this study, we aimed to evaluate the expression profiles of programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1), two of the most well-studied immune checkpoint molecules that promote tumor immune evasion, in tumor of the pre-S2 mutant-positive/high HCC patients. Methods We classified 40 HBV-related HCC patients into the pre-S2-positive/high and -negative/low groups by a next-generation sequencing-based approach. The fluorescent immunohistochemistry staining was performed to detect the expression of PD-1 and PD-L1 in HCC tissues of patients. Results We showed that patients with either deletion spanning pre-S2 gene segment or high percentage of pre-S2 plus pre-S1+pre-S2 deletion (the pre-S2 mutant-positive/high group) exhibited a significantly higher density of PD-L1-positive cells in HCC tissues than those without. Moreover, the percentage of pre-S2 plus pre-S1+pre-S2 deletion displayed a high positive correlation with the density of PD-L1-positive cells in HCC tissues. Conclusion The increased expression of PD-L1 in tumor tissues of the pre-S2 mutant-positive HCC patients suggest that pre-S2 mutant may play a potential role in dysregulation of tumor immune microenvironment in the progression of HBV-related HCC, implicating for the development of future therapeutic strategies.
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Affiliation(s)
- Chiao-Fang Teng
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.,Organ Transplantation Center, China Medical University Hospital, Taichung, Taiwan.,Research Center for Cancer Biology, China Medical University, Taichung, Taiwan
| | - Tsai-Chung Li
- Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan.,Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan
| | - Ting Wang
- Organ Transplantation Center, China Medical University Hospital, Taichung, Taiwan
| | - Tzu-Hua Wu
- Organ Transplantation Center, China Medical University Hospital, Taichung, Taiwan
| | - John Wang
- Department of Pathology, China Medical University Hospital, Taichung, Taiwan
| | - Han-Chieh Wu
- National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan
| | - Woei-Cherng Shyu
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.,Department of Occupational Therapy, Asia University, Taichung, Taiwan.,Department of Neurology, China Medical University Hospital, Taichung, Taiwan.,Translational Medicine Research Center, China Medical University Hospital, Taichung, Taiwan
| | - Ih-Jen Su
- Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan
| | - Long-Bin Jeng
- Organ Transplantation Center, China Medical University Hospital, Taichung, Taiwan
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Teng CF, Li TC, Huang HY, Chan WL, Wu HC, Shyu WC, Su IJ, Jeng LB. Hepatitis B virus pre-S2 deletion (nucleotide 1 to 54) in plasma predicts recurrence of hepatocellular carcinoma after curative surgical resection. PLoS One 2020; 15:e0242748. [PMID: 33237972 PMCID: PMC7688176 DOI: 10.1371/journal.pone.0242748] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Accepted: 11/06/2020] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Despite curative surgical resection, high recurrence of HCC after surgery results in poor patient survival. To develop prognostic markers is therefore important for better prevention and therapy of recurrent HCC to improve patient outcomes. Deletion mutations over the pre-S1 and pre-S2 gene segments of hepatitis B virus (HBV) have been closely associated with recurrence of HCC after curative surgical resection. In this study, we applied a next-generation sequencing-based approach to further evaluate the association of pre-S deletion regions with HCC recurrence. We demonstrated that the pre-S2 deletion (nucleotide 1 to 54) was the most predominant deletion regions of pre-S gene in plasma of HBV-related HCC patients. Moreover, patients with the pre-S2 deletion (nucleotide 1 to 54) exhibited a significantly higher risk of HCC recurrence after curative surgical resection than those without. The pre-S2 deletion (nucleotide 1 to 54) in plasma represented a prognostic factor that independently predicted HCC recurrence with greater performance than other clinicopathological and viral factors. Our data suggest that detection of the pre-S2 deletion (nucleotide 1 to 54) in plasma may be a promising noninvasive strategy for identifying patients at high risk for HCC recurrence after curative surgical resection.
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Affiliation(s)
- Chiao-Fang Teng
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
- Organ Transplantation Center, China Medical University Hospital, Taichung, Taiwan
- Research Center for Cancer Biology, China Medical University, Taichung, Taiwan
- * E-mail: (CFT); (IJS); (LBJ)
| | - Tsai-Chung Li
- Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan
- Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan
| | - Hsi-Yuan Huang
- Department of Laboratory Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Wen-Ling Chan
- Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan
- Epigenome Research Center, China Medical University Hospital, Taichung, Taiwan
| | - Han-Chieh Wu
- National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan
| | - Woei-Cherng Shyu
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
- Department of Occupational Therapy, Asia University, Taichung, Taiwan
- Department of Neurology, China Medical University Hospital, Taichung, Taiwan
- Translational Medicine Research Center, China Medical University Hospital, Taichung, Taiwan
| | - Ih-Jen Su
- Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan
- * E-mail: (CFT); (IJS); (LBJ)
| | - Long-Bin Jeng
- Organ Transplantation Center, China Medical University Hospital, Taichung, Taiwan
- * E-mail: (CFT); (IJS); (LBJ)
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Size measurements of hepatocellular carcinoma: comparisons between contrast and two-dimensional ultrasound. BMC Gastroenterol 2020; 20:390. [PMID: 33213375 PMCID: PMC7678053 DOI: 10.1186/s12876-020-01535-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 11/10/2020] [Indexed: 02/06/2023] Open
Abstract
Background Ultrasound (US) imaging is known to underestimate tumor size in clinical. This study is aimed to compare the size measurements of hepatocellular carcinoma (HCC) in three US imaging modalities, i.e. two-dimensional (2D) imaging, the arterial phase (AP) and the late phase (LP) imaging of contrast-enhanced US (CEUS). Methods Fifty-eight clinically proved HCC patients were included. The 2D and CEUS imaging were performed with Siemens S2000, Philips iu22 and BioSound Twice. 2.5 mL of SonoVue® was injected for every CEUS performance. Two physicians measured the maximal longitudinal and the transverse diameters of the tumors in 2D, the AP and the LP of CEUS from one image section. The three measurements were compared by paired t test. Results The mean longitudinal diameter of HCC appeared to be maximal in the AP (4.73 ± 2.04 cm) of CEUS and minimal in the LP (3.98 ± 1.99 cm) of CEUS. The 2D diameter (4.26 ± 2.07 cm) was in the middle between two CEUS measurements. There were significant differences between any two measurements. Conclusion There is size difference between the three kinds of HCC measurement. It appeared to be maximal in the AP of CEUS and minimal in the LP. The 2D diameter was in the middle.
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Abstract
Patients with hepatocellular carcinoma (HCC) have many treatment options. For patients with surgical indication, consideration of future liver remnant and the surgical complexity of the procedure is essential. A new 3-level complexity classification categorizing 11 liver resection procedures predicts surgical complexity and postoperative morbidity better than reported classifications. Preoperative portal vein embolization can mitigate the risk of hepatic insufficiency. For small HCCs, both liver resection and ablation are effective. New medical treatment options are promising and perioperative use of these drugs may further improve outcomes for patients undergoing liver resection and lead to changes in current treatment guidelines.
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Affiliation(s)
- Yoshikuni Kawaguchi
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX 77030, USA; Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Heather A Lillemoe
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX 77030, USA
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX 77030, USA.
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Komatsu S, Yano Y, Sofue K, Kido M, Tanaka M, Kuramitsu K, Awazu M, Gon H, Yamamoto A, Yanagimoto H, Toyama H, Kodama Y, Murakami T, Fukumoto T. Assessment of lenvatinib treatment for unresectable hepatocellular carcinoma with liver cirrhosis. HPB (Oxford) 2020; 22:1450-1456. [PMID: 32238302 DOI: 10.1016/j.hpb.2020.03.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 01/16/2020] [Accepted: 03/02/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND The present study aimed to assess the clinical features of patients who received lenvatinib treatment for unresectable hepatocellular carcinoma (HCC). METHODS The clinical characteristics, adverse events, and radiological responses were evaluated for 51 consecutive patients. RESULTS Of the study subjects, 37 patients had Child-Pugh class A (CPA) liver function, and 14 patients had Child-Pugh class B (CPB) liver function. The overall response rates in the CPA and CPB groups were 42.9% and 25.0%, respectively, and disease control rates were 82.9% and 83.3%, respectively, without significant difference (p = 0.2621 and 0.9697). There was no significant difference between CPA and CPB groups regarding the incidence of adverse events, except for hepatic coma. No significant difference was observed in the relative dose intensity between the CPA and CPB groups, for the first month, 1-2 months, or 2-3 months (p = 0.2368, 0.9368, and 0.9293). CONCLUSION The comparable outcomes between the CPA and CPB groups suggest the acceptability of lenvatinib treatment in patients with impaired liver function, at least in the acute phase. With careful follow-up, the dose can be relatively intensified, even in patients with impaired liver function and this may contribute to offering comparable treatment.
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Affiliation(s)
- Shohei Komatsu
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
| | - Yoshihiko Yano
- Department of Internal Medicine, Division of Gastroenterology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Keitaro Sofue
- Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Masahiro Kido
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Motofumi Tanaka
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Kaori Kuramitsu
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Masahide Awazu
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Hidetoshi Gon
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Atsushi Yamamoto
- Department of Internal Medicine, Division of Gastroenterology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Hiroaki Yanagimoto
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Hirochika Toyama
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Yuzo Kodama
- Department of Internal Medicine, Division of Gastroenterology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Takamichi Murakami
- Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Takumi Fukumoto
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
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Transarterial chemoembolization for hepatocellular carcinoma: quality of life, tumour response, safety and survival comparing two types of drug-eluting beads. Abdom Radiol (NY) 2020; 45:3326-3336. [PMID: 31781900 DOI: 10.1007/s00261-019-02349-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
PURPOSE To compare two different types of drug-eluting microspheres with regard to impact on HRQoL after first TACE, tumour response, peri-procedural complications, adverse events and 1-year survival in patients suffering from unresectable hepatocellular carcinoma (HCC). METHODS HRQoL was prospectively assessed with validated questionnaires (EORTC QLQ-C30 and -HCC18) before and 2 weeks after treatment with their first drug-eluting beads (DEB-)TACE with either acrylamido-polyvinylalcohol-AMPS hydrogel microspheres (groupDCB; 20 patients) or polyvinyl alcohol-co-acrylic acid microspheres (groupHS; 16 patients). Baseline characteristics, peri-procedural complications, treatment-related adverse events and 1-year survival were compared between both types of microspheres. Treatment response and objective response rates (ORR) were analysed using established tumour response criteria. Subgroup analysis for pooled groups with small (groupSMALL; 21 patients) versus large particles (groupLARGE; 15 patients) was performed. RESULTS At baseline, there were no significant differences between the treated microsphere groups. No significant differences were found in absolute HRQoL changes after first DEB-TACE between the different types of microspheres. Response rates and survival were comparable between the investigated microsphere groups. For groupSMALL, we found a significant difference in post-interventional deterioration of physical function (- 19.4%) compared to groupLARGE (- 8%; p = 0.025). Tumour response and ORR according to mRECIST were significantly higher in groupSMALL (p = 0.008; p = 0.009). CONCLUSION DEB-TACE is generally well tolerated and effective, with comparable changes in HRQoL for both types of drug-eluting microspheres. Tumour response is better with small microspheres. A relevant deterioration of physical function underlines that an aggressive TACE using small beads should be well deliberated.
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Lu X, Li Z, Liu Y, Wang Z, Peng F, Yu Q, Fu X, Ji B. The Long-Term Efficacy of Radiofrequency Ablation Versus Laparoscopic Hepatectomy for Small Hepatocellular Carcinoma in East Asia: A Systematic Review and Meta-Analysis. IRANIAN RED CRESCENT MEDICAL JOURNAL 2020; 22. [DOI: 10.5812/ircmj.102876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 06/21/2020] [Accepted: 07/19/2020] [Indexed: 07/28/2023]
Abstract
Context: Hepatocellular carcinoma (HCC) is a common malignant cancer and the second leading cause of cancer-related deaths around the world. Radiofrequency ablation (RFA) and laparoscopic hepatectomy (LH) have been adopted for the treatment of HCC. The aim of the meta-analysis was to explore the long-term efficacy of RFA compared with LH for small HCC (sHCC) patients in the East Asian population. Evidence Acquisition: We performed a systematic review and meta-analysis by the literature search on PubMed, Cochrane Library, EMBASE, Chinese Biological Medical Literature (CBM), Chinese National Knowledge Infrastructure (CNKI), and Wanfang from their inception until October 10, 2019, for comparing the long-term efficacy outcomes of RFA with LH. Results: Fourteen retrospective studies with 1,390 subjects were included in the meta-analysis. Compared with the LH-treated group, RFA could raise the local recurrence rate under median follow-up duration and reduce disease-free survival (DFS) rates at 1 - 3 years. However, it failed to affect 5-year overall survival (OS) and DFS rates. In the subgroup analyses, different RFA approaches had significantly higher local recurrence rates than the LH group. A similar effect on OS and DFS rates within five years for single early (≤ 3 cm) HCCs and on the 1- and 5-year DFS rates for nodules ≤ 5 cm were observed between the two groups, but RFA approaches could reduce the 3-y OS and DFS rates for single nodules ≤ 5 cm. The percutaneous radiofrequency ablation (PRFA) group had significantly lower 3- and 5-year OS and the 1- and 3-year DFS rates than the LH group, while no significant difference in OS and DFS rates in the laparoscopic radiofrequency ablation (LRFA) approach. The RFA approach improved the 3-year OS compared with the LH group in Japan, but reduced the 3-year OS and DFS rates within 3 years in China. Conclusions: Our results support that LH treating sHCC had a better long-term efficacy and a lower local recurrence rate than RFA in the East Asian population. Further high-quality prospective studies are required to confirm the long-term efficacy.
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