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He M, Xie W, Yuan Z, Chen J, Wang J, Fu Y, Hu Z, Meng Q, Gao W, Hu D, Zhang Y, Pan Y, Zhou Z. Comparing PD-L1 and PD-1 inhibitors plus bevacizumab combined with hepatic arterial interventional therapies in unresetable hepatocellular carcinoma: A single-center, real-world study. Int J Cancer 2025; 156:1972-1985. [PMID: 39834172 DOI: 10.1002/ijc.35341] [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: 09/21/2024] [Revised: 12/18/2024] [Accepted: 01/02/2025] [Indexed: 01/22/2025]
Abstract
With the rise of anti-vascular endothelial growth factor antibody and programmed cell death-ligand 1 (PD-L1) regimens, particularly bevacizumab and atezolizumab, as first-line treatments for advanced hepatocellular carcinoma (HCC), there is a need to explore PD-L1 and programmed cell death 1 inhibitors in combination therapies for unresectable HCC (uHCC). Integrating systemic therapies with locoregional approaches is also emerging as a potent strategy. This study compares the outcomes of atezolizumab (PD-L1 inhibitor) and sintilimab (programmed cell death 1 inhibitor) with bevacizumab or its biosimilar, combined with hepatic arterial interventional therapies (HAIT) in uHCC patients. From January 2020 to September 2023, a retrospective analysis was conducted on 138 uHCC patients at Sun Yat-sen University Cancer Center. The cohort included 69 patients treated with atezolizumab with bevacizumab (Bev/Ate) and 69 with bevacizumab biosimilar with sintilimab (Bio/Sin), combined with HAIT. The propensity score matching was also employed to further explore the efficacy and safety. The median progression-free survival (mPFS) was 13.8 months for the Bev/Ate group and 10.0 months for the Bio/Sin group (p = 0.188). The Bev/Ate group showed significantly longer intrahepatic mPFS (HR 0.381; 95% confidence interval 0.176-0.824; p = .018) and higher overall response rates compared with the Bio/Sin group (60.87% vs. 31.88%, p = .001; 69.57% vs. 49.28%, p = .024) based on Response Evaluation Criteria in Solid Tumors v1.1 and modified Response Evaluation Criteria in Solid Tumors criteria. Treatment-related adverse events were similar between groups (p > .050). Combining atezolizumab or sintilimab with bevacizumab or its biosimilar alongside HAIT provided similar overall PFS in uHCC patients. However, the atezolizumab-bevacizumab combination with HAIT showed superior intrahepatic PFS and control rates, warranting further validation.
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Affiliation(s)
- Minrui He
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University, Guangzhou, PR China
- Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, PR China
| | - Wa Xie
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University, Guangzhou, PR China
- Imaging Diagnostic and Interventional Center, Sun Yat-Sen University Cancer Center, Guangzhou, PR China
| | - Ze Yuan
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University, Guangzhou, PR China
- Department of Neurosurgery/NeuroOncology, Sun Yat-Sen University Cancer Center, Guangzhou, PR China
| | - Jinbin Chen
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University, Guangzhou, PR China
- Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, PR China
| | - Juncheng Wang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University, Guangzhou, PR China
- Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, PR China
| | - Yizhen Fu
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University, Guangzhou, PR China
- Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, PR China
| | - Zili Hu
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University, Guangzhou, PR China
- Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, PR China
| | - Qi Meng
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University, Guangzhou, PR China
- Department of Clinical Research, Sun Yat-Sen University Cancer Center, Guangzhou, PR China
| | - Wenqing Gao
- Department of Oncology, Tengchong People's Hospital, Baoshan, PR China
| | - Dandan Hu
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University, Guangzhou, PR China
- Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, PR China
| | - Yaojun Zhang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University, Guangzhou, PR China
- Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, PR China
| | - Yangxun Pan
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University, Guangzhou, PR China
- Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, PR China
| | - Zhongguo Zhou
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University, Guangzhou, PR China
- Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, PR China
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Cai L, Du Y, Xiong H, Zheng H. Application of nanotechnology in the treatment of hepatocellular carcinoma. Front Pharmacol 2024; 15:1438819. [PMID: 39679376 PMCID: PMC11637861 DOI: 10.3389/fphar.2024.1438819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2024] [Accepted: 11/19/2024] [Indexed: 12/17/2024] Open
Abstract
Hepatocellular carcinoma is the predominant histologic variant of hepatic malignancy and has become a major challenge to global health. The increasing incidence and mortality of hepatocellular carcinoma has created an urgent need for effective prevention, diagnosis, and treatment strategies. This is despite the impressive results of multiple treatments in the clinic. However, the unique tumor immunosuppressive microenvironment of hepatocellular carcinoma increases the difficulty of treatment and immune tolerance. In recent years, the application of nanoparticles in the treatment of hepatocellular carcinoma has brought new hope for tumor patients. Nano agents target tumor-associated fibroblasts, regulatory T cells, myeloid suppressor cells, tumor-associated macrophages, tumor-associated neutrophils, and immature dendritic cells, reversed the immunosuppressive microenvironment of hepatocellular carcinoma. In addition, he purpose of this review is to summarize the advantages of nanotechnology in guiding surgical excision, local ablation, TACE, standard chemotherapy, and immunotherapy, application of nano-vaccines has also continuously enriched the treatment of liver cancer. This study aims to investigate the potential applications of nanotechnology in the management of hepatocellular carcinoma, with the ultimate goal of enhancing therapeutic outcomes and improving the prognosis for patients affected by this malignancy.
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Affiliation(s)
| | | | | | - Honggang Zheng
- Department of Oncology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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Sachar Y, Congly SE, Burak KW, Manko A, Ko HH, Ramji A, Rahman HS, Talia J, Jeyaparan J, Wong DW, Fung S, Cooper C, Kelly EM, Ma MM, Bailey R, Minuk G, Wong A, Doucette K, Elkashab M, Sebastiani G, Wong P, Coffin CS, Brahmania M. Epidemiology, Treatment Patterns and Survival in Canadian Patients With Chronic Hepatitis B-Related Hepatocellular Carcinoma. J Viral Hepat 2024; 31:739-745. [PMID: 39148449 DOI: 10.1111/jvh.13989] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Accepted: 07/17/2024] [Indexed: 08/17/2024]
Abstract
Chronic hepatitis B (CHB) is the leading cause of hepatocellular carcinoma (HCC) globally. We described and evaluated the outcomes of patients with CHB-HCC in Canada. In this retrospective cross-sectional cohort study, data were analysed from CHB mono-infected subjects seen between 1 January 2012 and 31 December 2022, and entered the Canadian Hepatitis B Network Registry. Descriptive analysis and chi-squared modelling were used to compare cohorts, followed by multivariable survival analysis regarding survival post-diagnosis. Statistical analyses were completed in R version 2.2. Of the 6711 patients with CHB who met inclusion criteria, 232 (3.5%) developed HCC. Compared with the CHB cohort, the majority of CHB-HCC cohort were male, SEA and HBeAg negative and born in endemic area (80% vs. 56%, 73% vs. 55%, 84% vs. 54%, 64% vs. 40% and all p < 0001). Overall, median HBV DNA level was log 2.54 (IQR: 0-4.04). Advanced liver disease, defined as minimum Fibrosis stage F3, was seen in 9.4% of overall cohort, but 92% of HCC cohort. At diagnosis, median tumour size was 2.5 cm (IQR: 1.7-4.0) and mean tumour number was 1.33 (SD: 1.33), with 81% of patients BCLC 0-A. Fifty-three per cent of patients were diagnosed with HCC as part of surveillance protocols. The survival rate after HCC diagnosis was 78.7%, during the median follow-up of 52.9 months (IQR: 17-90). In multivariable analysis, survival was significantly correlated with diagnosis through the screening programme. In this large cohort of patients with CHB-HCC, the majority of patients were detected with early-stage HCC and received treatment with curative intent, resulting in strong survival rates.
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Affiliation(s)
- Y Sachar
- Department of Medicine, Division of Gastroenterology and Multi-Organ Transplant Unit, London Health Sciences Center, Western University, London, Ontario, Canada
| | - S E Congly
- Cumming School of Medicine, Department of Medicine, Division of Gastroenterology and Hepatology, University of Calgary Liver Unit, Calgary, Alberta, Canada
| | - K W Burak
- Cumming School of Medicine, Department of Medicine, Division of Gastroenterology and Hepatology, University of Calgary Liver Unit, Calgary, Alberta, Canada
| | - A Manko
- Cumming School of Medicine, Department of Medicine, Division of Gastroenterology and Hepatology, University of Calgary Liver Unit, Calgary, Alberta, Canada
| | - H H Ko
- Department of Medicine, Division of Gastroenterology, University of British Columbia, Vancouver, British Columbia, Canada
| | - A Ramji
- Department of Medicine, Division of Gastroenterology, University of British Columbia, Vancouver, British Columbia, Canada
| | - H S Rahman
- Department of Medicine, Division of Gastroenterology and Multi-Organ Transplant Unit, London Health Sciences Center, Western University, London, Ontario, Canada
| | - J Talia
- Department of Medicine, Division of Gastroenterology and Multi-Organ Transplant Unit, London Health Sciences Center, Western University, London, Ontario, Canada
| | - J Jeyaparan
- Department of Medicine, Division of Gastroenterology and Multi-Organ Transplant Unit, London Health Sciences Center, Western University, London, Ontario, Canada
| | - D W Wong
- Toronto Center of Liver Medicine, Department of Medicine, Division of Gastroenterology, University of Toronto, Toronto, Ontario, Canada
| | - S Fung
- Toronto Center of Liver Medicine, Department of Medicine, Division of Gastroenterology, University of Toronto, Toronto, Ontario, Canada
| | - C Cooper
- Division of Infectious Diseases, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada
| | - E M Kelly
- Department of Medicine, Division of Gastroenterology, University of Ottawa, Ontario, Canada
| | - M M Ma
- Department of Medicine, Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada
| | - R Bailey
- Department of Medicine, Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada
| | - G Minuk
- Department of Pharmacology and Therapeutics, Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
| | - A Wong
- Department of Medicine, Division of Infectious Diseases, University of Saskatchewan, Regina, Saskatchewan, Canada
| | - K Doucette
- Department of Medicine, Division of Infectious Diseases, University of Alberta, Edmonton, Alberta, Canada
| | - M Elkashab
- Toronto Center of Liver Medicine, Department of Medicine, Division of Gastroenterology, University of Toronto, Toronto, Ontario, Canada
| | - G Sebastiani
- Department of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
| | - P Wong
- Department of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
| | - C S Coffin
- Cumming School of Medicine, Department of Medicine, Division of Gastroenterology and Hepatology, University of Calgary Liver Unit, Calgary, Alberta, Canada
| | - M Brahmania
- Cumming School of Medicine, Department of Medicine, Division of Gastroenterology and Hepatology, University of Calgary Liver Unit, Calgary, Alberta, Canada
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Callan L, Razeghi H, Grindrod N, Gaede S, Wong E, Tan D, Vickress J, Patrick J, Lock M. Prognostic Index for Liver Radiation (PILiR). Curr Oncol 2024; 31:5862-5872. [PMID: 39451740 PMCID: PMC11506490 DOI: 10.3390/curroncol31100436] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 09/25/2024] [Accepted: 09/27/2024] [Indexed: 10/26/2024] Open
Abstract
A Prognostic Index for Liver Radiation (PILiR) for improved patient selection for stereotactic liver-directed radiotherapy (SBRT) was developed. Using a large single-center database, 195 patients treated with SBRT for local control, including 66 with hepatocellular carcinoma (HCC) and 129 with metastatic liver disease, were analyzed. Only patients ineligible for alternative treatments were included. Overall survival was 11.9 months and 9.4 months in the HCC group and metastatic groups, respectively. In the combined dataset, Child-Pugh Score (CPS) (p = 0.002), serum albumin (p = 0.039), and presence of extrahepatic disease (p = 0.012) were significant predictors of early death on multivariable analysis and were included in the PILiR (total score 0 to 5). Median survival was 23.8, 9.1, 4.5, and 2.6 months for patients with 0, 1-2, 3, and 4-5 points, respectively. In the HCC dataset, CPS (p < 0.001) and gross tumor volume (p = 0.013) were predictive of early death. In the metastatic dataset, serum albumin (p < 0.001) and primary disease site (p = 0.003) were predictive of early death. The AUC for the combined, HCC, and metastatic datasets are 0.78, 0.84, and 0.80, respectively. Poor liver function (defined by CPS and serum albumin) and extrahepatic disease were most predictive of early death, providing clinically important expected survival information for patients and caregivers.
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Affiliation(s)
| | - Haddis Razeghi
- Radiation Oncology, London Health Sciences Centre, London, ON N6A 5W9, Canada; (H.R.); (N.G.); (S.G.); (E.W.); (J.V.); (J.P.)
- Faculty of Nursing, Western University, London, ON N6A 3K7, Canada
| | - Natalie Grindrod
- Radiation Oncology, London Health Sciences Centre, London, ON N6A 5W9, Canada; (H.R.); (N.G.); (S.G.); (E.W.); (J.V.); (J.P.)
- Pathology & Labaratory Medicine, Western University, London, ON N6A 3K7, Canada
| | - Stewart Gaede
- Radiation Oncology, London Health Sciences Centre, London, ON N6A 5W9, Canada; (H.R.); (N.G.); (S.G.); (E.W.); (J.V.); (J.P.)
- Department of Physics and Astronomy, Western University, London, ON N6A 3K7, Canada
| | - Eugene Wong
- Radiation Oncology, London Health Sciences Centre, London, ON N6A 5W9, Canada; (H.R.); (N.G.); (S.G.); (E.W.); (J.V.); (J.P.)
- Department of Physics and Astronomy, Western University, London, ON N6A 3K7, Canada
| | - David Tan
- Asian Alliance Radiation & Oncology, Centre for Stereotactic Radiosurgery, Singapore 289891, Singapore;
| | - Jason Vickress
- Radiation Oncology, London Health Sciences Centre, London, ON N6A 5W9, Canada; (H.R.); (N.G.); (S.G.); (E.W.); (J.V.); (J.P.)
- Department of Physics and Astronomy, Western University, London, ON N6A 3K7, Canada
| | - John Patrick
- Radiation Oncology, London Health Sciences Centre, London, ON N6A 5W9, Canada; (H.R.); (N.G.); (S.G.); (E.W.); (J.V.); (J.P.)
| | - Michael Lock
- Radiation Oncology, London Health Sciences Centre, London, ON N6A 5W9, Canada; (H.R.); (N.G.); (S.G.); (E.W.); (J.V.); (J.P.)
- Schulich School of Medicine, Western University, London, ON N6A 3K7, Canada
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Cordón Avila A, Abayazid M. Liver respiratory-induced motion estimation using abdominal surface displacement as a surrogate: robotic phantom and clinical validation with varied correspondence models. Int J Comput Assist Radiol Surg 2024; 19:1477-1487. [PMID: 38809319 PMCID: PMC11329552 DOI: 10.1007/s11548-024-03176-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Accepted: 05/03/2024] [Indexed: 05/30/2024]
Abstract
PURPOSE This work presents the implementation of an RGB-D camera as a surrogate signal for liver respiratory-induced motion estimation. This study aims to validate the feasibility of RGB-D cameras as a surrogate in a human subject experiment and to compare the performance of different correspondence models. METHODS The proposed approach uses an RGB-D camera to compute an abdominal surface reconstruction and estimate the liver respiratory-induced motion. Two sets of validation experiments were conducted, first, using a robotic liver phantom and, secondly, performing a clinical study with human subjects. In the clinical study, three correspondence models were created changing the conditions of the learning-based model. RESULTS The motion model for the robotic liver phantom displayed an error below 3 mm with a coefficient of determination above 90% for the different directions of motion. The clinical study presented errors of 4.5, 2.5, and 2.9 mm for the three different motion models with a coefficient of determination above 80% for all three cases. CONCLUSION RGB-D cameras are a promising method to accurately estimate the liver respiratory-induced motion. The internal motion can be estimated in a non-contact, noninvasive and flexible approach. Additionally, three training conditions for the correspondence model are studied to potentially mitigate intra- and inter-fraction motion.
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Affiliation(s)
- Ana Cordón Avila
- Robotics and Mechatronics, Faculty of Electrical Engineering, Mathematics and Computer Science, University of Twente, 7500 AE, Enschede, Netherlands.
| | - Momen Abayazid
- Robotics and Mechatronics, Faculty of Electrical Engineering, Mathematics and Computer Science, University of Twente, 7500 AE, Enschede, Netherlands
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Zhuang RZ, Zhuo JY, Dong SY, Ling Q, Zhu HK, Xu X. Prognostic value of innate immune cell densities in patients with hepatocellular carcinoma after liver transplantation. Hepatobiliary Pancreat Dis Int 2024:S1499-3872(24)00104-8. [PMID: 39089944 DOI: 10.1016/j.hbpd.2024.07.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Accepted: 07/15/2024] [Indexed: 08/04/2024]
Affiliation(s)
- Run-Zhou Zhuang
- Department of Thoracic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China
| | - Jian-Yong Zhuo
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China
| | - Si-Yi Dong
- National Center for Healthcare Quality Management of Liver Transplant, Hangzhou 310003, China
| | - Qi Ling
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Heng-Kai Zhu
- Department of Hepatobiliary and Pancreatic Surgery, Department of Liver Transplantation, Shulan (Hangzhou) Hospital, Zhejiang Shuren University School of Medicine, Hangzhou 310022, China
| | - Xiao Xu
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China; Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310014, China; Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou 310000, China.
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Haak F, Karli T, Takes M, Zech CJ, Kollmar O, Soysal SD. A Retrospective Cohort Analysis of Transarterial Chemoembolization for Hepatocellular Cancer at a Tertiary Center in Switzerland. J Clin Med 2024; 13:3279. [PMID: 38892990 PMCID: PMC11172573 DOI: 10.3390/jcm13113279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Revised: 05/24/2024] [Accepted: 05/29/2024] [Indexed: 06/21/2024] Open
Abstract
Background/Objectives: International guidelines recommend transarterial chemoembolization (TACE) for intermediate-stage hepatocellular carcinoma (HCC). However, it is used outside these recommendations and has proven beneficial in prolonging survival. Since the role of TACE outside BCLC stage B is unclear, the present study analyzed the results of TACE performed at a tertiary center in Switzerland for different treatment groups, and aims to highlight the treatment outcomes for these groups. Methods: This retrospective cohort study includes 101 HCC patients undergoing TACE at our center. Patients were further subdivided into groups according to therapy combinations (therapies applied before and after index TACE). Kaplan-Meier survival curves were calculated for the Barcelona Center for Liver Cancer (BCLC) subgroups. Results: After TACE, the median survival was 28.1 months for BCLC 0, 31.5 months for BCLC A, 20.5 months for BCLC B, 10.8 for BCLC C, and 7.5 months for BCLC D. A lesion size larger than 55 mm was negatively associated with survival (HR 2.8, 95% CI 1.15-6.78). Complications occurred after TACE procedures: Clavien-Dindo I + II = 30, Clavien-Dindo > 3 = 2. Conclusions: TACE was performed in a substantial part of our cohort outside of routinely used treatment guidelines. The combination of the survival data and complication rate in these patients suggests it was a safe and beneficial strategy. Furthermore, our data show that in our cohort, the survival benefit associated with TACE was restricted to patients with a lesion size smaller than 55 mm.
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Affiliation(s)
- Fabian Haak
- Clarunis, Department of Visceral Surgery, University Digestive Health Care Center, St. Clara Hospital and University Hospital Basel, 4058 Basel, Switzerland
- Department of Visceral, Transplant, Thoracic and Vascular Surgery, Division of Hepatobiliary Surgery and Visceral Transplant Surgery, University Hospital Leipzig, 04103 Leipzig, Germany
| | - Tobias Karli
- Clarunis, Department of Visceral Surgery, University Digestive Health Care Center, St. Clara Hospital and University Hospital Basel, 4058 Basel, Switzerland
| | - Martin Takes
- Interventional Radiology, Radiology and Nuclear Medicine, University Hospital Basel, University of Basel, 4001 Basel, Switzerland
| | - Christoph J. Zech
- Interventional Radiology, Radiology and Nuclear Medicine, University Hospital Basel, University of Basel, 4001 Basel, Switzerland
| | - Otto Kollmar
- Clarunis, Department of Visceral Surgery, University Digestive Health Care Center, St. Clara Hospital and University Hospital Basel, 4058 Basel, Switzerland
| | - Savas D. Soysal
- Medical Faculty, University of Basel, 4001 Basel, Switzerland
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Thirumurugan S, Dash P, Sakthivel R, Lin YC, Sun YS, Lin CP, Wang AN, Liu X, Dhawan U, Chung RJ. Gold nanoparticles decorated on MOF derived Cu 5Zn 8 hollow porous carbon nanocubes for magnetic resonance imaging guided tumor microenvironment-mediated synergistic chemodynamic and photothermal therapy. BIOMATERIALS ADVANCES 2024; 158:213778. [PMID: 38325029 DOI: 10.1016/j.bioadv.2024.213778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Revised: 01/06/2024] [Accepted: 01/15/2024] [Indexed: 02/09/2024]
Abstract
Combining chemodynamic therapy (CDT) with photothermal therapy (PTT) has developed as a promising approach for cancer treatment, as it enhances therapeutic efficiency through redox reactions and external laser induction. In this study, we designed metal organic framework (MOF) -derived Cu5Zn8/HPCNC through a carbonization process and decorated them with gold nanoparticles (Au@Cu5Zn8/HPCNC). The resulting nanoparticles were employed as a photothermal agent and Fenton catalyst. The Fenton reaction facilitated the conversation of Cu2+ to Cu+ through reaction with local H2O2, generating reactive hydroxyl radicals (·OH) with potent cytotoxic effects. To enhance the Fenton-like reaction and achieve combined therapy, laser irradiation of the Au@Cu5Zn8/HPCNC induced efficient photothermal therapy by generating localized heat. With a significantly increased absorption of Au@Cu5Zn8/HPCNC at 808 nm, the photothermal efficiency was determined to be 57.45 %. Additionally, Au@Cu5Zn8/HPCNC demonstrated potential as a contrast agent for magnetic resonance imaging (MRI) of cancers. Furthermore, the synergistic combination of PTT and CDT significantly inhibited tumor growth. This integrated approach of PTT and CDT holds great promise for cancer therapy, offering enhanced CDT and modulation of the tumor microenvironment (TME), and opening new avenues in the fight against cancer.
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Affiliation(s)
- Senthilkumar Thirumurugan
- Department of Chemical Engineering and Biotechnology, National Taipei University of Technology (Taipei Tech), Taipei 10608, Taiwan
| | - Pranjyan Dash
- Department of Chemical Engineering and Biotechnology, National Taipei University of Technology (Taipei Tech), Taipei 10608, Taiwan
| | - Rajalakshmi Sakthivel
- Department of Chemical Engineering and Biotechnology, National Taipei University of Technology (Taipei Tech), Taipei 10608, Taiwan
| | - Yu-Chien Lin
- Department of Chemical Engineering and Biotechnology, National Taipei University of Technology (Taipei Tech), Taipei 10608, Taiwan
| | - Ying-Sui Sun
- School of Dental Technology, College of Oral Medicine, Taipei Medical University, Taipei 11031, Taiwan
| | - Ching-Po Lin
- Institute of Neuroscience, National Yang-Ming University, Taipei 11221, Taiwan
| | | | - Xinke Liu
- College of Materials Science and Engineering, Chinese Engineering and Research Institute of Microelectronics, Shenzhen University, Shenzhen 518060, China; Department of Electrical and Computer Engineering, National University of Singapore, Singapore 117583, Singapore
| | - Udesh Dhawan
- Centre for the Cellular Microenvironment, Division of Biomedical Engineering, James Watt School of Engineering, Mazumdar-Shaw Advanced Research Centre, University of Glasgow, Glasgow G116EW, UK
| | - Ren-Jei Chung
- Department of Chemical Engineering and Biotechnology, National Taipei University of Technology (Taipei Tech), Taipei 10608, Taiwan; High-value Biomaterials Research and Commercialization Center, National Taipei University of Technology (Taipei Tech), Taipei 10608, Taiwan.
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Agarwal A, Biswas S, Swaroop S, Aggarwal A, Agarwal A, Jain G, Elhence A, Vaidya A, Gupte A, Mohanka R, Kumar R, Mishra AK, Gamanagatti S, Paul SB, Acharya SK, Shukla A, Shalimar. Clinical profile and outcomes of hepatocellular carcinoma in primary Budd-Chiari syndrome. World J Gastrointest Oncol 2024; 16:699-715. [PMID: 38577460 PMCID: PMC10989380 DOI: 10.4251/wjgo.v16.i3.699] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Revised: 12/22/2023] [Accepted: 01/16/2024] [Indexed: 03/12/2024] Open
Abstract
BACKGROUND There is scant literature on hepatocellular carcinoma (HCC) in patients with Budd-Chiari syndrome (BCS). AIM To assess the magnitude, clinical characteristics, feasibility, and outcomes of treatment in BCS-HCC. METHODS A total of 904 BCS patients from New Delhi, India and 1140 from Mumbai, India were included. The prevalence and incidence of HCC were determined, and among patients with BCS-HCC, the viability and outcomes of interventional therapy were evaluated. RESULTS In the New Delhi cohort of 35 BCS-HCC patients, 18 had HCC at index presentation (prevalence 1.99%), and 17 developed HCC over a follow-up of 4601 person-years, [incidence 0.36 (0.22-0.57) per 100 person-years]. BCS-HCC patients were older when compared to patients with BCS alone (P = 0.001) and had a higher proportion of inferior vena cava block, cirrhosis, and long-segment vascular obstruction. The median alpha-fetoprotein level was higher in patients with BCS-HCC at first presentation than those who developed HCC at follow-up (13029 ng/mL vs 500 ng/mL, P = 0.01). Of the 35 BCS-HCC, 26 (74.3%) underwent radiological interventions for BCS, and 22 (62.8%) patients underwent treatment for HCC [transarterial chemoembolization in 18 (81.8%), oral tyrosine kinase inhibitor in 3 (13.6%), and transarterial radioembolization in 1 (4.5%)]. The median survival among patients who underwent interventions for HCC compared with those who did not was 3.5 years vs 3.1 mo (P = 0.0001). In contrast to the New Delhi cohort, the Mumbai cohort of BCS-HCC patients were predominantly males, presented with a more advanced HCC [Barcelona Clinic Liver Cancer C and D], and 2 patients underwent liver transplantation. CONCLUSION HCC is not uncommon in patients with BCS. Radiological interventions and liver transplantation are feasible in select primary BCS-HCC patients and may improve outcomes.
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Affiliation(s)
- Ankit Agarwal
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110029, Delhi, India
| | - Sagnik Biswas
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110029, Delhi, India
| | - Shekhar Swaroop
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110029, Delhi, India
| | - Arnav Aggarwal
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110029, Delhi, India
| | - Ayush Agarwal
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110029, Delhi, India
| | - Gautam Jain
- Department of Gastroenterology, Seth Gordhandas Sunderdas Medical College and KEM Hospital, Mumbai 400012, Maharashtra, India
| | - Anshuman Elhence
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110029, Delhi, India
| | - Arun Vaidya
- Department of Gastroenterology, Seth Gordhandas Sunderdas Medical College and KEM Hospital, Mumbai 400012, Maharashtra, India
| | - Amit Gupte
- Department of Gastroenterology, Sir HN Reliance Foundation Hospital, Mumbai 400004, India
| | - Ravi Mohanka
- Department of Liver Transplant and HPB, Sir HN Reliance Foundation Hospital, Mumbai 400004, India
| | - Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, India
| | - Ashwani Kumar Mishra
- Professor of Biostatistics, National Drug Dependence Treatment Centre (NDDTC), All India Institute of Medical Sciences, New Delhi 110029, India
| | - Shivanand Gamanagatti
- Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi 110029, Delhi, India
| | - Shashi Bala Paul
- Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi 110029, Delhi, India
| | - Subrat Kumar Acharya
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110029, Delhi, India
| | - Akash Shukla
- Department of Gastroenterology, Seth Gordhandas Sunderdas Medical College and KEM Hospital, Mumbai 400012, Maharashtra, India
| | - Shalimar
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110029, Delhi, India
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10
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van de Braak C, Willemssen FEJA, de Man RA, van der Lugt A, Uyl-de Groot CA, Bos D, Dwarkasing RS. Non-contrast short MRI surveillance for HCC screening: the study protocol of the SMS-HCC prospective multicenter study. Eur Radiol Exp 2024; 8:29. [PMID: 38467990 PMCID: PMC10928023 DOI: 10.1186/s41747-024-00432-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Accepted: 01/11/2024] [Indexed: 03/13/2024] Open
Abstract
Hepatocellular carcinoma (HCC) comprises 75 to 85% of all primary liver cancers. Current guidelines recommend a biannual HCC surveillance using ultrasound (US) for high-risk patients. However, due to its low sensitivity for detection of early-stage HCC lesions, there is an urgency for more sensitive surveillance tools. Here, we describe the potential of a short MRI surveillance (SMS) protocol for HCC, including axial T1-weighted in-out phase, fat-saturated T2-weighted, and diffusion-weighted sequences. In this prospective, multicenter, patient cohort study, patients will be recruited from existing HCC surveillance cohorts of six medical centers in The Netherlands. Surveillance patients who undergo biannual US, will be invited for SMS on the same day for 3 years. In case of a suspicious finding on either US or SMS, patients will be invited for a full MRI liver protocol including gadolinium-based contrast agent intravenous injection within 2 weeks. To our knowledge, this will be the first study to perform a head-to-head comparison with a paired US-MRI design. We hypothesize that the sensitivity of SMS for detection of early-stage HCC will be higher than that of US leading to improved survival of surveillance patients through timely HCC diagnosis. Furthermore, we hypothesize that the SMS-HCC protocol will prove cost-effective.Relevance statement The US sensitivity for detecting early-stage HCC has been reported to be less than 50%. We expect that the proposed SMS will detect at least twice as many early-stage HCC lesions and therefore prove to be cost-effective. Key points • The low sensitivity of US necessitates better imaging tools for HCC screening.• This is the first study with a paired US-MRI design.• This design will allow a head-to-head comparison in both diagnostics and patient-acceptance.• We expect that SMS can contribute to a higher survival rate.
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Affiliation(s)
- Céline van de Braak
- Department of Radiology & Nuclear Medicine, Erasmus Medical Center, Dr. Molewaterplein 40, Rotterdam, 3015GD, The Netherlands.
| | - François E J A Willemssen
- Department of Radiology & Nuclear Medicine, Erasmus Medical Center, Dr. Molewaterplein 40, Rotterdam, 3015GD, The Netherlands
| | - Rob A de Man
- Department of Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Aad van der Lugt
- Department of Radiology & Nuclear Medicine, Erasmus Medical Center, Dr. Molewaterplein 40, Rotterdam, 3015GD, The Netherlands
| | - Carin A Uyl-de Groot
- Erasmus School of Health Policy & Management and Institute for Medical Technology Assessment, Erasmus University Rotterdam, Rotterdam, The Netherlands
| | - Daniel Bos
- Department of Radiology & Nuclear Medicine, Erasmus Medical Center, Dr. Molewaterplein 40, Rotterdam, 3015GD, The Netherlands
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Roy S Dwarkasing
- Department of Radiology & Nuclear Medicine, Erasmus Medical Center, Dr. Molewaterplein 40, Rotterdam, 3015GD, The Netherlands.
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11
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Rodríguez-Espinosa D, Morantes L, García J, Broseta JJ, Cuadrado-Payán E, Colmenero J, Torregrosa JV, Diekmann F, Esforzado N. Long-Term Outcomes of Incidental Liver Malignancies in Simultaneous Liver-Kidney Transplant Recipients. Transplant Proc 2024; 56:330-334. [PMID: 38350821 DOI: 10.1016/j.transproceed.2024.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2023] [Accepted: 01/16/2024] [Indexed: 02/15/2024]
Abstract
BACKGROUND The pretransplant diagnosis of liver malignancies in nodular cirrhotic livers remains a diagnostic challenge despite current advances. Although the prognostic impact of incidental hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (iCC) in liver transplant recipients is well documented, there are no data on the impact in simultaneous liver kidney transplant (LKT) recipients. METHODS This is a single-center observational, retrospective study of all LKT performed from May 1993 to April 2022. Among these patients, demographic data, immunosuppressive therapy, rejection episodes, and prevalence of incidental HCC or iCC were evaluated. RESULTS One hundred eight LKTs were performed and 6 were excluded. There were 13 patients with incidental carcinomas in the explanted liver: one of them with both an HCC and iCC, one with an iCC, and the remaining with an HCC. One case of iCC died. No other recurrences occurred. There were no cases of incidental HCC nor iCC in patients with a hereditary or metabolic LKT indication. We found no differences in the 5-year patient survival, and death-censored kidney and liver graft survival rates for those LKT with an incidental HCC and those without it (76.9% vs 84.2%, P = .5; 100% vs 91.6%, P = .28; and 100% vs 94.7%, P = 0.39, respectively). Finally, there were no significant associations between explant carcinoma and rejections of the liver (7.7% vs 17.9%, P = .34) or kidney graft (0% vs 16.8%, P = 0.11). CONCLUSION Despite a high prevalence of incidental HCC or iCC, patient, kidney, and liver graft 5-year survival were unaffected by incidental HCC.
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Affiliation(s)
- Diana Rodríguez-Espinosa
- Department of Nephrology and Renal Transplantation, Hospital Clínic of Barcelona, Barcelona, Spain.
| | - Laura Morantes
- Department of Nephrology and Renal Transplantation, Hospital Clínic of Barcelona, Barcelona, Spain
| | - Jenmy García
- Department of Nephrology and Renal Transplantation, Hospital Clínic of Barcelona, Barcelona, Spain
| | - José Jesús Broseta
- Department of Nephrology and Renal Transplantation, Hospital Clínic of Barcelona, Barcelona, Spain
| | - Elena Cuadrado-Payán
- Department of Nephrology and Renal Transplantation, Hospital Clínic of Barcelona, Barcelona, Spain
| | | | - Josep Vicens Torregrosa
- Department of Nephrology and Renal Transplantation, Hospital Clínic of Barcelona, Barcelona, Spain
| | - Fritz Diekmann
- Department of Nephrology and Renal Transplantation, Hospital Clínic of Barcelona, Barcelona, Spain
| | - Nuria Esforzado
- Department of Nephrology and Renal Transplantation, Hospital Clínic of Barcelona, Barcelona, Spain
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12
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Matevish L, Patel MS, Vagefi PA. Downstaging Techniques for Hepatocellular Carcinoma in Candidates Awaiting Liver Transplantation. Surg Clin North Am 2024; 104:145-162. [PMID: 37953033 DOI: 10.1016/j.suc.2023.07.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2023]
Abstract
During the last decade, downstaging for hepatocellular carcinoma has expanded the pool of patients eligible for liver transplantation. The literature is rife with attempts to elucidate best treatment strategies with novel locoregional and systemic therapies continuing to emerge. Several trials have confirmed the large-scale success of downstaging protocols, with equitable long-term survival and recurrence rates after liver transplant. We review the currently available techniques used for downstaging, including their indications, complications, and efficacies. New frontiers have focused on the potential role of immunotherapy in the neoadjuvant setting, although more research is needed to delineate its role in current treatment paradigms.
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Affiliation(s)
- Lauren Matevish
- Division of Surgical Transplantation, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Madhukar S Patel
- Division of Surgical Transplantation, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Parsia A Vagefi
- Division of Surgical Transplantation, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
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13
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Argentiero A, Delvecchio A, Fasano R, Andriano A, Caradonna IC, Memeo R, Desantis V. The Complexity of the Tumor Microenvironment in Hepatocellular Carcinoma and Emerging Therapeutic Developments. J Clin Med 2023; 12:7469. [PMID: 38068521 PMCID: PMC10706931 DOI: 10.3390/jcm12237469] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/10/2024] Open
Abstract
This review explores various aspects of the HCC TME, including both cellular and non-cellular components, to elucidate their roles in tumor development and progression. Specifically, it highlights the significance of cancer-associated fibroblasts (CAFs) and their contributions to tumor progression, angiogenesis, immune suppression, and therapeutic resistance. Moreover, this review emphasizes the role of immune cells, such as tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), and regulatory T-cells (Tregs), in shaping the immunosuppressive microenvironment that promotes tumor growth and immune evasion. Furthermore, we also focused only on the non-cellular components of the HCC TME, including the extracellular matrix (ECM) and the role of hypoxia-induced angiogenesis. Alterations in the composition of ECM and stiffness have been implicated in tumor invasion and metastasis, while hypoxia-driven angiogenesis promotes tumor growth and metastatic spread. The molecular mechanisms underlying these processes, including the activation of hypoxia-inducible factors (HIFs) and vascular endothelial growth factor (VEGF) signaling, are also discussed. In addition to elucidating the complex TME of HCC, this review focuses on emerging therapeutic strategies that target the TME. It highlights the potential of second-line treatments, such as regorafenib, cabozantinib, and ramucirumab, in improving overall survival for advanced HCC patients who have progressed on or were intolerant to first-line therapy. Furthermore, this review explores the implications of the Barcelona Clinic Liver Cancer (BCLC) staging and classification system in guiding HCC management decisions. The BCLC system, which incorporates tumor stage, liver function, and performance status, provides a framework for treatment stratification and prognosis prediction in HCC patients. The insights gained from this review contribute to the development of novel therapeutic interventions and personalized treatment approaches for HCC patients, ultimately improving clinical outcomes in this challenging disease.
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Affiliation(s)
| | - Antonella Delvecchio
- Unit of Hepato-Biliary and Pancreatic Surgery, “F. Miulli” General Hospital, 70021 Bari, Italy
| | | | - Alessandro Andriano
- Department of Precision and Regenerative Medicine and Ionian Area, Pharmacology Section, University of Bari Aldo Moro Medical School, 70124 Bari, Italy
| | - Ingrid Catalina Caradonna
- Department of Precision and Regenerative Medicine and Ionian Area, Pharmacology Section, University of Bari Aldo Moro Medical School, 70124 Bari, Italy
| | - Riccardo Memeo
- Unit of Hepato-Biliary and Pancreatic Surgery, “F. Miulli” General Hospital, 70021 Bari, Italy
| | - Vanessa Desantis
- Department of Precision and Regenerative Medicine and Ionian Area, Pharmacology Section, University of Bari Aldo Moro Medical School, 70124 Bari, Italy
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14
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Brown N. Reimbursement of interventional oncology in Australia: How it works and how it does not. J Med Imaging Radiat Oncol 2023; 67:915-925. [PMID: 38105584 DOI: 10.1111/1754-9485.13608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Accepted: 11/09/2023] [Indexed: 12/19/2023]
Abstract
The practice of interventional oncology (IO) embodies all the qualities that one would expect to find in a modern, value-based healthcare system. A dynamic, cutting-edge specialty like IO uses highly-targeted, minimally-invasive, image-guided techniques to deliver cost-effective, personalised medicine for cancer patients. Unfortunately, the technical and clinical sophistication of IO is not matched by the reimbursement models and funding arrangements in Australia to fully support this critical component of patient care. Differences between state and federal funding lead to inequity of access to 'standard of care' interventions for patients across public and private hospitals. IO procedures are poorly represented in the Medicare Benefits Schedule and often inadequately funded to cover the true costs of providing care. Complex private health fund reimbursements and inconsistent rebates for prostheses and essential equipment result in inconsistent access to important services and widely variable out-of-pocket costs for patients. IO techniques must be supported by fair, consistent and equitable funding arrangements at all levels to allow for integrated contemporary patient care; only then will the full clinical and economic benefits of IO be realised.
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Affiliation(s)
- Nicholas Brown
- The Wesley Hospital, Brisbane, Queensland, Australia
- The University of Queensland, School of Medicine, Brisbane, Queensland, Australia
- The Prince Charles' Hospital, Brisbane, Queensland, Australia
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15
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Choi JY, Choi SH, Byun JH, Lee SJ, Kim SY, Won HJ, Shin YM. Liver Imaging Reporting and Data System version 2018 for diagnosing hepatocellular carcinoma in alcoholic liver cirrhosis and virus-related cirrhosis. Eur J Radiol 2023; 168:111139. [PMID: 37856941 DOI: 10.1016/j.ejrad.2023.111139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Revised: 09/01/2023] [Accepted: 10/05/2023] [Indexed: 10/21/2023]
Abstract
PURPOSE We aimed to evaluate and compare the diagnostic performance of Liver Imaging Reporting and Data System (LI-RADS) v2018 for hepatocellular carcinoma (HCC) ≤ 3.0 cm on gadoxetic acid-enhanced MRI according to the etiology of cirrhosis. METHODS Thirty-eight patients with alcoholic liver cirrhosis (ALC) and 37 with hepatitis C virus-related cirrhosis (HCV) who underwent preoperative MRI and subsequent surgical resection or transplantation were included. For comparison groups, patients with hepatitis B virus-related cirrhosis (HBV) were included by 1:1 matching with HCV and ALC groups according to age, lesion size, and Child-Pugh classification. The imaging characteristics of background liver and focal lesions were analyzed. The diagnostic performance of LI-RADS was compared between HCV and HBV groups, and between ALC and HBV groups. RESULTS ALC group showed significantly higher frequency of hepatic steatosis (25.8 % vs. 6.1 %, p =.04) and lower frequency of nonperipheral washout on portal venous-phase in HCC (63.2 % vs. 97.1 %, p <.001) compared with HBV group. ALC group showed significantly lower sensitivity than HBV group (52.6 % vs. 88.6 %, p<.001). No significant differences in diagnostic performance were found between HCV and HBV groups. In ALC group, hepatobiliary-phase hypointensity provided significantly higher sensitivity (76.3 % vs. 52.6 %, p =.008). CONCLUSION The sensitivity of LI-RADS for diagnosing HCC ≤ 3.0 cm was significantly lower in the ALC group than in the HBV group.
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Affiliation(s)
- Ji Young Choi
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; Department of Radiology, Kangbuk Samsung Hospital, Sungkyunkwan University College of Medicine, Seoul, Republic of Korea
| | - Sang Hyun Choi
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jae Ho Byun
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - So Jung Lee
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - So Yeon Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Hyung Jin Won
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Yong Moon Shin
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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16
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Kohansal-Nodehi M, Swiatek-de Lange M, Kroeniger K, Rolny V, Tabarés G, Piratvisuth T, Tanwandee T, Thongsawat S, Sukeepaisarnjaroen W, Esteban JI, Bes M, Köhler B, Chan HLY, Busskamp H. Discovery of a haptoglobin glycopeptides biomarker panel for early diagnosis of hepatocellular carcinoma. Front Oncol 2023; 13:1213898. [PMID: 37920152 PMCID: PMC10619681 DOI: 10.3389/fonc.2023.1213898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Accepted: 09/20/2023] [Indexed: 11/04/2023] Open
Abstract
Background There is a need for new serum biomarkers for early detection of hepatocellular carcinoma (HCC). Haptoglobin (Hp) N-glycosylation is altered in HCC, but the diagnostic value of site-specific Hp glycobiomarkers is rarely reported. We aimed to determine the site-specific glycosylation profile of Hp for early-stage HCC diagnosis. Method Hp glycosylation was analyzed in the plasma of patients with liver diseases (n=57; controls), early-stage HCC (n=50) and late-stage HCC (n=32). Hp phenotype was determined by immunoblotting. Hp was immunoisolated and digested into peptides. N-glycopeptides were identified and quantified using liquid chromatography-mass spectrometry. Cohort samples were compared using Wilcoxon rank-sum (Mann-Whitney U) tests. Diagnostic performance was assessed using receiver operating characteristic (ROC) curves and area under curve (AUC). Results Significantly higher fucosylation, branching and sialylation of Hp glycans, and expression of high-mannose glycans, was observed as disease progressed from cirrhosis to early- and late-stage HCC. Several glycopeptides demonstrated high values for early diagnosis of HCC, with an AUC of 93% (n=1), >80% (n=3), >75% (n=13) and >70% (n=11), compared with alpha-fetoprotein (AFP; AUC of 79%). The diagnostic performance of the identified biomarkers was only slightly affected by Hp phenotype. Conclusion We identified a panel of Hp glycopeptides that are significantly differentially regulated in early- and late-stage HCC. Some glycobiomarkers exceeded the diagnostic value of AFP (the most commonly used biomarker for HCC diagnosis). Our findings provide evidence that glycobiomarkers can be effective in the diagnosis of early HCC - individually, as a panel of glycopeptides or combined with conventional serological biomarkers.
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Affiliation(s)
| | | | | | - Vinzent Rolny
- Roche Diagnostics GmbH, Research and Development Core Lab, Penzberg, Germany
| | - Glòria Tabarés
- Roche Diagnostics GmbH, Research and Development Core Lab, Penzberg, Germany
| | - Teerha Piratvisuth
- NKC Institute of Gastroenterology and Hepatology, Songklanagarind Hospital, Prince of Songkla University, Hat Yai, Thailand
| | - Tawesak Tanwandee
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Satawat Thongsawat
- Department of Internal Medicine, Maharaj Nakorn Chiang Mai Hospital, Chiang Mai University, Chiang Mai, Thailand
| | | | | | - Marta Bes
- Transfusion Safety Laboratory, Banc de Sang i Teixits (BST), Barcelona, Spain
| | - Bruno Köhler
- Department of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany
- Liver Cancer Center Heidelberg, Heidelberg, Germany
| | - Henry Lik-Yuen Chan
- Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Holger Busskamp
- Roche Diagnostics GmbH, Research and Development Core Lab, Penzberg, Germany
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17
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Leslie J, Hunter JE, Collins A, Rushton A, Russell LG, Ramon‐Gil E, Laszczewska M, McCain M, Zaki MYW, Knox A, Seow Y, Sabater L, Geh D, Perkins ND, Reeves HL, Tiniakos D, Mann DA, Oakley F. c-Rel-dependent Chk2 signaling regulates the DNA damage response limiting hepatocarcinogenesis. Hepatology 2023; 78:1050-1063. [PMID: 36089330 PMCID: PMC10521790 DOI: 10.1002/hep.32781] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Revised: 09/08/2022] [Accepted: 09/08/2022] [Indexed: 12/30/2022]
Abstract
BACKGROUND AND AIMS Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death. The NF-κB transcription factor family subunit c-Rel is typically protumorigenic; however, it has recently been reported as a tumor suppressor. Here, we investigated the role of c-Rel in HCC. APPROACH AND RESULTS Histological and transcriptional studies confirmed expression of c-Rel in human patients with HCC, but low c-Rel expression correlated with increased tumor cell proliferation and mutational burden and was associated with advanced disease. In vivo , global ( Rel-/- ) and epithelial specific ( RelAlb ) c-Rel knockout mice develop more tumors, with a higher proliferative rate and increased DNA damage, than wild-type (WT) controls 30 weeks after N-diethylnitrosamine injury. However, tumor burden was comparable when c-Rel was deleted in hepatocytes once tumors were established, suggesting c-Rel signaling is important for preventing HCC initiation after genotoxic injury, rather than for HCC progression. In vitro , Rel-/- hepatocytes were more susceptible to genotoxic injury than WT controls. ATM-CHK2 DNA damage response pathway proteins were suppressed in Rel-/- hepatocytes following genotoxic injury, suggesting that c-Rel is required for effective DNA repair. To determine if c-Rel inhibition sensitizes cancer cells to chemotherapy, by preventing repair of chemotherapy-induced DNA damage, thus increasing tumor cell death, we administered single or combination doxorubicin and IT-603 (c-Rel inhibitor) therapy in an orthotopic HCC model. Indeed, combination therapy was more efficacious than doxorubicin alone. CONCLUSION Hepatocyte c-Rel signaling limits genotoxic injury and subsequent HCC burden. Inhibiting c-Rel as an adjuvant therapy increased the effectiveness of DNA damaging agents and reduced HCC growth.
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Affiliation(s)
- Jack Leslie
- Newcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle‐upon‐Tyne, UK
| | - Jill E. Hunter
- Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle‐upon‐Tyne, UK
| | - Amy Collins
- Newcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle‐upon‐Tyne, UK
| | - Amelia Rushton
- Newcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle‐upon‐Tyne, UK
| | - Lauren G. Russell
- Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle‐upon‐Tyne, UK
| | - Erik Ramon‐Gil
- Newcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle‐upon‐Tyne, UK
| | - Maja Laszczewska
- Newcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle‐upon‐Tyne, UK
| | - Misti McCain
- Newcastle University Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle‐upon‐Tyne, UK
| | - Marco Y. W. Zaki
- Newcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle‐upon‐Tyne, UK
- Biochemistry Department, Faculty of Pharmacy, Minia University, Minia, Egypt
| | - Amber Knox
- Newcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle‐upon‐Tyne, UK
| | - Yixin Seow
- Newcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle‐upon‐Tyne, UK
| | - Laura Sabater
- Newcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle‐upon‐Tyne, UK
| | - Daniel Geh
- Newcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle‐upon‐Tyne, UK
- Department of Medicine, Freeman Hospital, Newcastle‐upon‐Tyne Hospitals NHS Foundation Trust, Newcastle‐upon‐Tyne, UK
| | - Neil D. Perkins
- Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle‐upon‐Tyne, UK
| | - Helen L. Reeves
- Newcastle University Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle‐upon‐Tyne, UK
- Department of Medicine, Freeman Hospital, Newcastle‐upon‐Tyne Hospitals NHS Foundation Trust, Newcastle‐upon‐Tyne, UK
| | - Dina Tiniakos
- Newcastle University Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle‐upon‐Tyne, UK
- Department of Pathology, Aretaieion Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Derek A. Mann
- Newcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle‐upon‐Tyne, UK
| | - Fiona Oakley
- Newcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle‐upon‐Tyne, UK
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Turco C, Hobeika C, Allard MA, Tabchouri N, Brustia R, Nguyen T, Cauchy F, Barbier L, Salamé E, Cherqui D, Vibert E, Soubrane O, Scatton O, Goumard C. Open Versus Laparoscopic Right Hepatectomy for Hepatocellular Carcinoma Following Sequential TACE-PVE: A Multicentric Comparative Study. Ann Surg Oncol 2023; 30:6615-6625. [PMID: 37394670 DOI: 10.1245/s10434-023-13752-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Accepted: 06/01/2023] [Indexed: 07/04/2023]
Abstract
BACKGROUND Right hepatectomy (RH) for hepatocellular carcinoma (HCC) is ideally preceded by transcatheter arterial chemoembolization (TACE) and portal vein embolization (PVE). Laparoscopic approach improves short-term outcome and textbook outcome (TO), which reflects the "ideal" surgical outcome, after RH. However, laparoscopic RH on an underlying diseased liver and after TACE/PVE remains a challenging procedure. The aim of this study was to compare the outcomes in patients who underwent laparoscopic liver resection (LLR) or open liver resection (OLR) following TACE/PVE. PATIENTS AND METHODS All patients with HCC who underwent RH after TACE/PVE in five French centers were retrospectively included. Outcomes were compared between the LLR group and the OLR group using propensity score matching (PSM). Quality of surgical care was defined by TO. RESULTS Between 2005 and 2019, 117 patients were included (41 in LLR group, 76 in OLR group). Overall morbidity was comparable (51% versus 53%, p = 0.24). In LLR group, TO was completed in 66% versus 37% in OLR group (p = 0.02). LLR and absence of clamping were the only factors associated with TO completion [hazard ratio (HR) 4.27, [1.77-10.28], p = 0.001]. After PSM, 5-year overall survival (OS) and progression-free survival (PFS) were 55% in matched LLR versus 77% in matched OLR, p = 0.35, and 13% in matched LLR versus 17% in matched OLR, p = 0.97. TO completion was independently associated with a better 5-year OS (65.2% versus 42.5%, p = 0.007). CONCLUSION Major LLR after TACE/PVE should be considered as a valuable option in expert centers to increase the chance of TO, the latter being associated with a better 5-year OS.
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Affiliation(s)
- Célia Turco
- Department of Digestive, Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP Pitié-Salpêtrière Hospital, Paris, France
- Sorbonne Université, Centre de Recherche Saint Antoine, INSERM UMRS-938, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Christian Hobeika
- Department of Hepato-Biliary, Liver Transplantation, and Pancreatic Surgery, Hospital Beaujon, Clichy, France
| | - Marc-Antoine Allard
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Université Paris Saclay, Inserm U 935, Villejuif, France
| | - Nicolas Tabchouri
- Service de Chirurgie Digestive, Oncologique, Endocrinienne et Transplantation Hépatique, CHRU Hôpital Trousseau, Chambray, Tours, France
| | - Raffaele Brustia
- Department of Digestive and Hepato-Pancreatico-Biliary Surgery, Henri Mondor University Hospital, APHP, Créteil, France
| | - Tu Nguyen
- Department of Digestive, Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP Pitié-Salpêtrière Hospital, Paris, France
| | - François Cauchy
- Department of Hepato-Biliary, Liver Transplantation, and Pancreatic Surgery, Hospital Beaujon, Clichy, France
| | - Louise Barbier
- Service de Chirurgie Digestive, Oncologique, Endocrinienne et Transplantation Hépatique, CHRU Hôpital Trousseau, Chambray, Tours, France
| | - Ephrem Salamé
- Service de Chirurgie Digestive, Oncologique, Endocrinienne et Transplantation Hépatique, CHRU Hôpital Trousseau, Chambray, Tours, France
| | - Daniel Cherqui
- Department of Digestive and Hepato-Pancreatico-Biliary Surgery, Henri Mondor University Hospital, APHP, Créteil, France
| | - Eric Vibert
- Department of Digestive and Hepato-Pancreatico-Biliary Surgery, Henri Mondor University Hospital, APHP, Créteil, France
| | - Olivier Soubrane
- Department of Hepato-Biliary, Liver Transplantation, and Pancreatic Surgery, Hospital Beaujon, Clichy, France
| | - Olivier Scatton
- Department of Digestive, Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP Pitié-Salpêtrière Hospital, Paris, France
- Sorbonne Université, Centre de Recherche Saint Antoine, INSERM UMRS-938, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Claire Goumard
- Department of Digestive, Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP Pitié-Salpêtrière Hospital, Paris, France.
- Sorbonne Université, Centre de Recherche Saint Antoine, INSERM UMRS-938, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.
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Torzilli G. Sorafenib and surgery for hepatocellular carcinoma - a controversial relation: Lesson learned? Glob Health Med 2023; 5:246-248. [PMID: 37655183 PMCID: PMC10461332 DOI: 10.35772/ghm.2023.01020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Accepted: 05/14/2023] [Indexed: 09/02/2023]
Abstract
Sorafenib is a breakthrough in the medical treatment aiming to control hepatocellular carcinoma (HCC) progression, but there is some controversy in patients' selection. The introduction of Sorafenib has led to several positive effects. New more than promising antiangiogenic molecules have followed. Immunotherapy combined with antiangiogenic therapy has also strongly entered into the treatment of HCC. All of that has induced a significant guideline revision profiling Sorafenib as a second line systemic therapy in the event of advanced HCC. However, for those patients with advanced but resectable HCC, the selection of surgery or systemic therapy should be reviewed and reconsidered.
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Affiliation(s)
- Guido Torzilli
- Department of Biomedical Sciences, Humanitas University, Milan, Italy:
- Division of Hepatobiliary & General Surgery, Department of Surgery - IRCCS, Humanitas Research Hospital, Milan, Italy
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20
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Wang G, Li J, Zhu L, Zhou Z, Ma Z, Zhang H, Yang Y, Niu Q, Wang X. Identification of hepatocellular carcinoma-related subtypes and development of a prognostic model: a study based on ferritinophagy-related genes. Discov Oncol 2023; 14:147. [PMID: 37555866 PMCID: PMC10412519 DOI: 10.1007/s12672-023-00756-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2023] [Accepted: 07/14/2023] [Indexed: 08/10/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma still has a high incidence and mortality rate worldwide, and further research is needed to investigate its occurrence and development mechanisms in depth in order to identify new therapeutic targets. Ferritinophagy is a type of autophagy and a key factor in ferroptosis that could influence tumor onset and progression. Although, the potential role of ferritinophagy-related genes (FRGs) in liver hepatocellular carcinoma (LIHC) is unknown. METHODS Single-cell RNA sequencing (scRNA-seq) data of LIHC were obtained from the Gene Expression Omnibus (GEO) dataset. In addition, transcriptome and clinical follow-up outcome data of individuals with LIHC were extracted from the The Cancer Genome Atlas (TCGA) dataset. FRGs were collected through the GeneCards database. Differential cell subpopulations were distinguished, and differentially expressed FRGs (DEFRGs) were obtained. Differential expression of FRGs and prognosis were observed according to the TCGA database. An FRG-related risk model was constructed to predict patient prognosis by absolute shrinkage and selection operator (LASSO) and COX regression analyses, and its prognosis predictive power was validated. Ultimately, the association between risk score and tumor microenvironment (TME), immune cell infiltration, immune checkpoints, drug sensitivity, and tumor mutation burden (TMB) was analyzed. We also used quantitative reverse transcription polymerase chain reaction (qRT-PCR) to validate the expression of key genes in normal liver cells and liver cancer cells. RESULTS We ultimately identified 8 cell types, and 7 differentially expressed FRGs genes (ZFP36, NCOA4, FTH1, FTL, TNF, PCBP1, CYB561A3) were found among immune cells, and we found that Monocytes and Macrophages were closely related to FRGs genes. Subsequently, COX regression analysis showed that patients with high expression of FTH1, FTL, and PCBP1 had significantly worse prognosis than those with low expression, and our survival prediction model, constructed based on age, stage, and risk score, showed better prognostic prediction ability. Our risk model based on 3 FRGs genes ultimately revealed significant differences between high-risk and low-risk groups in terms of immune infiltration and immune checkpoint correlation, drug sensitivity, and somatic mutation risk. Finally, we validated the key prognostic genes FTH1, FTL, using qRT-PCR, and found that the expression of FTH1 and FTL was significantly higher in various liver cancer cells than in normal liver cells. At the same time, immunohistochemistry showed that the expression of FTH1, FTL in tumor tissues was significantly higher than that in para-tumor tissues. CONCLUSION This study identifies a considerable impact of FRGs on immunity and prognosis in individuals with LIHC. The collective findings of this research provide new ideas for personalized treatment of LIHC and a more targeted therapy approach for individuals with LIHC to improve their prognosis.
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Affiliation(s)
- Ganggang Wang
- Department of Hepatobiliary Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, China
| | - Jian Li
- Endoscopy Center, Minhang Hospital, Fudan University, Shanghai, 201199, China
| | - Lingkang Zhu
- Jing'an District Central Hospital, Fudan University, Shanghai, 200040, China
| | - Zhijie Zhou
- Department of Hepatobiliary Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, China
| | - Zenghui Ma
- Department of Hepatobiliary Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, China
| | - Hao Zhang
- Department of Hepatobiliary Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, China
| | - Yulong Yang
- Institute of Gallstone Disease, Center of Gallbladder Disease, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
| | - Qiang Niu
- Department of General Surgery, Shidong Hospital, Shidong Hospital Affiliated to University of Shanghai for Science and Technology, Yangpu District, Shanghai, 200438, China.
| | - Xiaoliang Wang
- Department of Hepatobiliary Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, China.
- Department of General Surgery, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai, China.
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Jang HJ, Choi SH, Choi SJ, Choi WM, Byun JH, Won HJ, Shin YM. LI-RADS version 2018 for hepatocellular carcinoma < 1.0 cm on gadoxetate disodium-enhanced magnetic resonance imaging. Eur Radiol 2023; 33:5792-5800. [PMID: 37017700 DOI: 10.1007/s00330-023-09554-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Revised: 02/04/2023] [Accepted: 02/22/2023] [Indexed: 04/06/2023]
Abstract
OBJECTIVES We aimed to develop and evaluate a modified Liver Imaging Reporting and Data System (LI-RADS) version 2018 using significant ancillary features for diagnosing hepatocellular carcinoma (HCC) < 1.0 cm on gadoxetate disodium-enhanced magnetic resonance imaging (MRI). METHODS Patients who underwent preoperative gadoxetate disodium-enhanced MRI for focal solid nodules < 2.0 cm within 1 month of MRI between January 2016 and December 2020 were retrospectively analyzed. Major and ancillary features were compared between HCCs of < 1.0 cm and 1.0-1.9 cm using the chi-square test. Significant ancillary features associated with HCC < 1.0 cm were determined by univariable and multivariable logistic regression analysis. The sensitivity and specificity of LR-5 were compared between LI-RADS v2018 and our modified LI-RADS (applying the significant ancillary feature) using generalized estimating equations. RESULTS Of 796 included nodules, 248 were < 1.0 cm and 548 were 1.0-1.9 cm. HCC < 1.0 cm less frequently showed an enhancing capsule (7.1% vs. 31.1%, p < .001) and threshold growth (0% vs. 8.3%, p = .007) than HCC of 1.0-1.9 cm. Restricted diffusion was the only ancillary feature significant for diagnosing HCC < 1.0 cm (adjusted odds ratio = 11.50, p < .001). In the diagnosis of HCC, our modified LI-RADS using restricted diffusion had significantly higher sensitivity than LI-RADS v2018 (61.8% vs. 53.5%, p < .001), with similar specificity (97.3% vs. 97.8%, p = .157). CONCLUSION Restricted diffusion was the only significant independent ancillary feature for diagnosing HCC < 1.0 cm. Our modified LI-RADS using restricted diffusion can improve the sensitivity for HCC < 1.0 cm. KEY POINTS • The imaging features of hepatocellular carcinoma (HCC) < 1.0 cm differed from those of HCC of 1.0-1.9 cm. • Restricted diffusion was the only significant independent ancillary feature for HCC < 1.0 cm. • Modified Liver Imaging Reporting and Data System (LI-RADS) with the addition of restricted diffusion can improve the sensitivity for HCC < 1.0 cm.
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Affiliation(s)
- Hyeon Ji Jang
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea
| | - Sang Hyun Choi
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea.
| | - Se Jin Choi
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea
| | - Won-Mook Choi
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea
| | - Jae Ho Byun
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea
| | - Hyung Jin Won
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea
| | - Yong Moon Shin
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea
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22
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Costa F, Wiedenmann B, Roderburg C, Mohr R, Abou‐Alfa GK. Systemic treatment in patients with Child-Pugh B liver dysfunction and advanced hepatocellular carcinoma. Cancer Med 2023; 12:13978-13990. [PMID: 37162288 PMCID: PMC10358256 DOI: 10.1002/cam4.6033] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 02/27/2023] [Accepted: 04/23/2023] [Indexed: 05/11/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a major cause of death among patients with liver cirrhosis. The rise of immuno-oncology has revolutionized treatment for advanced HCC. However, most pivotal randomized controlled trials have excluded patients with moderate liver dysfunction (Child-Pugh-Turcotte B), despite the high incidence of liver disease in patients with HCC at the time of diagnosis. Overall survival in patients with HCC and moderate liver dysfunction treated with sorafenib has been found to be only approximately 3-5 months, underlining the need for improved treatment algorithms for this increasingly important subgroup of patients. In this review, we summarize available data on the treatment of patients with HCC and moderate liver dysfunction. Opportunities, as well as clinical challenges, are discussed in detail, highlighting potential changes to the therapeutic landscape.
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Affiliation(s)
| | - Bertram Wiedenmann
- Department of Hepatology and GastroenterologyCharité University HospitalBerlinGermany
| | - Christoph Roderburg
- Clinic for Gastroenterology, Hepatology and Infectious DiseasesUniversity Hospital DüsseldorfDüsseldorfGermany
| | - Raphael Mohr
- Department of Hepatology and GastroenterologyCharité University HospitalBerlinGermany
| | - Ghassan K. Abou‐Alfa
- Memorial Sloan Kettering Cancer CenterNew YorkNew YorkUSA
- Weill Medical School at Cornell UniversityNew YorkNew YorkUSA
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23
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Shaik MR, Sagar PR, Shaik NA, Randhawa N. Liquid Biopsy in Hepatocellular Carcinoma: The Significance of Circulating Tumor Cells in Diagnosis, Prognosis, and Treatment Monitoring. Int J Mol Sci 2023; 24:10644. [PMID: 37445822 DOI: 10.3390/ijms241310644] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 06/17/2023] [Accepted: 06/19/2023] [Indexed: 07/15/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is an aggressive malignancy with poor outcomes when diagnosed at an advanced stage. Current curative treatments are most effective in early-stage HCC, highlighting the importance of early diagnosis and intervention. However, existing diagnostic methods, such as radiological imaging, alpha-fetoprotein (AFP) testing, and biopsy, have limitations that hinder early diagnosis. AFP elevation is absent in a significant portion of tumors, and imaging may have low sensitivity for smaller tumors or in the presence of cirrhosis. Additionally, as our understanding of the molecular pathogenesis of HCC grows, there is an increasing need for molecular information about the tumors. Biopsy, although informative, is invasive and may not always be feasible depending on tumor location. In this context, liquid biopsy technology has emerged as a promising approach for early diagnosis, enabling molecular characterization and genetic profiling of tumors. This technique involves analyzing circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), or tumor-derived exosomes. CTCs are cancer cells shed from the primary tumor or metastatic sites and circulate in the bloodstream. Their presence not only allows for early detection but also provides insights into tumor metastasis and recurrence. By detecting CTCs in peripheral blood, real-time tumor-related information at the DNA, RNA, and protein levels can be obtained. This article provides an overview of CTCs and explores their clinical significance for early detection, prognosis, treatment selection, and monitoring treatment response in HCC, citing relevant literature.
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Affiliation(s)
- Mohammed Rifat Shaik
- Department of Medicine, University of Maryland Medical Center Midtown Campus, Baltimore, MD 21201, USA
| | - Prem Raj Sagar
- Department of Medicine, University of Maryland Medical Center Midtown Campus, Baltimore, MD 21201, USA
| | - Nishat Anjum Shaik
- Department of Medicine, University of Maryland Medical Center Midtown Campus, Baltimore, MD 21201, USA
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Le DC, Nguyen TM, Nguyen DH, Nguyen DT, Nguyen LTM. Survival Outcome and Prognostic Factors Among Patients With Hepatocellular Carcinoma: A Hospital-Based Study. Clin Med Insights Oncol 2023; 17:11795549231178171. [PMID: 37359273 PMCID: PMC10286205 DOI: 10.1177/11795549231178171] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Accepted: 05/08/2023] [Indexed: 06/28/2023] Open
Abstract
Background Hepatocellular carcinoma (HCC) is a leading cancer with very high incidence and mortality and low survival rate in Vietnam and worldwide. This study aimed to investigate the survival outcome and its prognostic factors among HCC patients. Methods This is a retrospective descriptive study on patients newly diagnosed with HCC at Hanoi Oncology Hospital, Vietnam from January 2018 to December 2020. Overall survival (OS) was calculated by the Kaplan-Meier method. Log-rank test and Cox regression were used to investigate the association among patients' OS and their diagnosis and treatment factors. Results A total of 674 patients were included. The median OS was 10.0 months. The survival rates at 6, 12, 24, and 36 months were 57.3%, 46.6%, 34.8%, and 29.7%, respectively. The initial performance status (PS), Child-Pugh score, and Barcelona Clinic Liver Cancer (BCLC) stage at the time of diagnosis are prognostic factors of HCC OS. A total of 451 (66.8%) patients have died, most of them (375 equally 83.1%) died at home, and only 76 (16.9%) died at hospital. Hepatocellular carcinoma patients living in the rural area more likely died at home than those living in the urban area (85.9% vs 74.8%, P = .007). Conclusions Hepatocellular carcinoma has a poor prognosis with low OS. Performance status, Child-Pugh score, and BCLC stage were the independent prognostic factors for the survival outcome of HCC patients. The fact that most HCC patients died at home suggested that home-based hospice care needs to be paid special attention.
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Affiliation(s)
- Dinh Cong Le
- Palliative Care Department, Hanoi Oncology Hospital, Hanoi, Vietnam
| | - Thang Minh Nguyen
- On-Demand Day Care Department, Hanoi Oncology Hospital, Hanoi, Vietnam
| | - Duong Hoang Nguyen
- On-Demand Gastrointestinal Medical Oncology Department, Hanoi Oncology Hospital, Hanoi, Vietnam
| | - Dung Thi Nguyen
- On-Demand Gastrointestinal Medical Oncology Department, Hanoi Oncology Hospital, Hanoi, Vietnam
| | - Lan Thi Mai Nguyen
- Medical Oncology II Department, Board of Directors, Hanoi Oncology Hospital, Hanoi, Vietnam
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25
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Mustafa G, Younas S, Mahrosh HS, Albeshr MF, Bhat EA. Molecular Docking and Simulation-Binding Analysis of Plant Phytochemicals with the Hepatocellular Carcinoma Targets Epidermal Growth Factor Receptor and Caspase-9. Molecules 2023; 28:molecules28083583. [PMID: 37110817 PMCID: PMC10143645 DOI: 10.3390/molecules28083583] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 04/14/2023] [Accepted: 04/18/2023] [Indexed: 04/29/2023] Open
Abstract
Among primary liver cancers, hepatocellular carcinoma (HCC) is one of the most common forms and it has been categorized as the joint-fourth largest reason of cancer-related deaths globally. Different factors such as alcohol abuse, hepatitis B and C, viral infections, and fatty liver diseases are mainly related to the pathogenesis of HCC. In the current study, 1000 total various plant phytochemicals were docked to proteins involved in HCC. The compounds were docked to the active site amino acids of epidermal growth factor receptor and caspase-9 as receptor proteins in order to explore their inhibiting potential. The top five compounds against each receptor protein were explored as potential drug candidates on the basis of their binding affinity and root-mean square deviation values. The top two compounds against each protein were found to be liquoric acid (S-score -9.8 kcal/mol) and madecassic acid (S-score -9.3 kcal/mol) against EGFR, and limonin (S-score -10.5 kcal/mol) and obamegine (S-score -9.3 kcal/mol) against the caspase-9 protein. The selected phytochemicals were further assessed through drug scanning using Lipinski's rule of five to explore their molecular properties and druggability. According to the ADMET analysis, the selected phytochemicals were found to be non-toxic and non-carcinogenic. Finally, the molecular dynamics simulation study revealed that liquoric acid and limonin were stabilized within the binding pockets of EGFR and capase-9, respectively, and stayed firmly bound throughout the simulation. In light of the current findings, the phytochemicals reported in this study, especially liquoric acid and limonin, could be used as potential drugs for the treatment of HCC in the future.
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Affiliation(s)
- Ghulam Mustafa
- Department of Biochemistry, Government College University Faisalabad, Faisalabad 38000, Pakistan
| | - Shumaila Younas
- Department of Biochemistry, Government College University Faisalabad, Faisalabad 38000, Pakistan
| | - Hafiza Salaha Mahrosh
- Department of Biochemistry, University of Agriculture Faisalabad, Faisalabad 38000, Pakistan
| | - Mohammed Fahad Albeshr
- Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
| | - Eijaz Ahmed Bhat
- Centre de Biologie Structurale (CBS), INSERM, CNRS, Université de Montpellier, 34090 Montpellier, France
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Polydopamine-Coated Cu-BTC Nanowires for Effective Magnetic Resonance Imaging and Photothermal Therapy. Pharmaceutics 2023; 15:pharmaceutics15030822. [PMID: 36986682 PMCID: PMC10058397 DOI: 10.3390/pharmaceutics15030822] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 01/20/2023] [Accepted: 02/20/2023] [Indexed: 03/06/2023] Open
Abstract
Herein, we present a one-pot hydrothermal approach for synthesizing metal–organic framework-derived copper (II) benzene-1,3,5-tricarboxylate (Cu-BTC) nanowires (NWs) using dopamine as the reducing agent and precursor for a polydopamine (PDA) surface coating formation. In addition, PDA can act as a PTT agent and enhance NIR absorption, producing photothermal effects on cancer cells. These NWs displayed a photothermal conversion efficiency of 13.32% after PDA coating and exhibited good photothermal stability. Moreover, NWs with a suitable T1 relaxivity coefficient (r1 = 3.01 mg−1 s−1) can be effectively used as magnetic resonance imaging (MRI) contrast agents. By increasing concentrations, cellular uptake studies showed a greater uptake of Cu-BTC@PDA NWs into cancer cells. Further, in vitro studies showed PDA-coated Cu-BTC NWs possess exceptional therapeutic performance by 808 nm laser irradiation, destroying 58% of cancer cells compared with the absence of laser irradiation. This promising performance is anticipated to advance the research and implementation of copper-based NWs as theranostic agents for cancer treatment.
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27
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Heo S, Choi SH, Hong S, Kim DW. Visualization Score of Gadoxetic Acid-Enhanced Magnetic Resonance Imaging: The Effect on the Diagnostic Accuracy for Hepatocellular Carcinoma. J Magn Reson Imaging 2023; 57:941-949. [PMID: 35849038 DOI: 10.1002/jmri.28357] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2022] [Revised: 06/30/2022] [Accepted: 07/01/2022] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The visualization score of hepatobiliary-phase (HBP) images has been introduced as an image quality index for gadoxetic acid-enhanced MRI. It may be associated with hepatic function and could have an implication on the diagnostic accuracy for hepatocellular carcinoma (HCC). PURPOSE To investigate the association between the visualization score of gadoxetic acid-enhanced MRI and clinical factors and to evaluate its effect on the diagnostic accuracy for HCC ≤ 3.0 cm. STUDY TYPE Retrospective. POPULATION A total of 493 focal lesions from 397 patients. FIELD STRENGTH/SEQUENCE A 5-T or 3.0 -T with pre/postcontrast T1-weighted 3D gradient echo sequence, and T2-weighted fast spin-echo sequence ASSESSMENT: Child-Pugh classification and albumin-bilirubin (ALBI) score were assessed. Three readers evaluated the visualization score of each MRI examination (A, no or minimal; B, moderate; and C, severe limitations), and major features (arterial-phase hyperenhancement, washout, enhancing capsule, threshold growth) and ancillary features of each focal lesion. STATISTICAL TESTS Univariable and multivariable logistic regression analyses were performed to determine significant clinical factors associated with a suboptimal visualization score (B or C). Generalized estimating equations were used to compare the sensitivity and specificity for diagnosing HCC between the two group (visualization score A vs. B or C). A P value < 0.05 was considered statistically significant. RESULTS Of the 397 MRI examinations, the incidence of suboptimal visualization score was 13%. A suboptimal visualization score was significantly associated with Child-Pugh classification B or C (adjusted odds ratio [OR] = 15.2) and ALBI grade 2 or 3 (OR = 4.7). Compared with the visualization score A group, the suboptimal visualization score group showed significantly lower sensitivity (56.8% vs. 75.2%) and less frequent washout in HCC (62.2% vs. 84.0%). DATA CONCLUSION The visualization score on gadoxetic acid-enhanced MRI can be an important image quality index and the diagnostic accuracy for HCC ≤ 3.0 cm may not be sufficient in the suboptimal visualization score group. LEVEL OF EVIDENCE 3 TECHNICAL EFFICACY STAGE: 3.
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Affiliation(s)
- Subin Heo
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.,Department of Radiology, Ajou University School of Medicine, Suwon, Korea
| | - Sang Hyun Choi
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Sun Hong
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Dong Wook Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
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Preoperative Predictors of Early Recurrence After Liver Resection for Multifocal Hepatocellular Carcinoma. J Gastrointest Surg 2023:10.1007/s11605-023-05592-1. [PMID: 36857014 DOI: 10.1007/s11605-023-05592-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Accepted: 01/07/2023] [Indexed: 03/02/2023]
Abstract
BACKGROUND Liver transplantation remains the optimal treatment for multifocal hepatocellular carcinoma (HCC). However, due to resource constrains, other therapeutic modalities such as liver resection (LR), are frequently utilized. LR, however, has to be balanced against potential morbidity and mortality along with the risks of early recurrence leading to futile surgery. In this study, we evaluated preoperative factors, including inflammatory indices, in predicting early (< 1 year) recurrence in patients who underwent LR for multifocal HCC. METHODS This was a post hoc analysis of 250 consecutive patients with multifocal HCC who underwent LR. RESULTS After exclusion of 10 patients with 30-day/in-hospital mortality, 240 were included of which 134 (55.8%) developed early recurrence. Hepatitis B/C aetiology, 3/ > more hepatic nodules and elevated alpha-fetoprotein (AFP) ≥ 200 ng/ml were significant independent preoperative predictors of early recurrence. The early recurrence rate was 72.1% when 2 out of 3 significant predictive factors were present. The conglomerate of all 3 factors predicted early recurrence of 100% with a statistically significant association between number of predictive factors and early recurrence (p < 0.001). CONCLUSION Better patient selection via the use of preoperative predictive factors of early recurrence such as hepatitis B/C aetiology, ≥ 3 nodules and elevated AFP ≥ 200 ng/ml may assist in identifying patients in whom LR is deemed futile and improve resource allocation.
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Choi SJ, Choi SH, Kim DW, Kwag M, Byun JH, Won HJ, Shin YM. Value of threshold growth as a major diagnostic feature of hepatocellular carcinoma in LI-RADS. J Hepatol 2023; 78:596-603. [PMID: 36402451 DOI: 10.1016/j.jhep.2022.11.006] [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: 03/22/2022] [Revised: 10/17/2022] [Accepted: 11/01/2022] [Indexed: 11/18/2022]
Abstract
BACKGROUND & AIMS The Liver Reporting and Data System (LI-RADS) version 2018 simplified the definition of threshold growth to '≥50% size increase in a mass in ≤6 months'. However, the diagnostic value of threshold growth for hepatocellular carcinoma (HCC) remained unclear. We evaluated the value of threshold growth, as defined by LI-RADS v2018, in diagnosing HCCs. METHODS Patients who underwent preoperative gadoxetate disodium-enhanced MRI because of the presence of LI-RADS category 2, 3, or 4 rather than category 5 on prior CT/MRI between January 2017 and December 2020 were retrospectively evaluated. Pathologic or clinical diagnoses were used as reference standards. Imaging features were evaluated by three readers according to LI-RADS v2018. The frequency and diagnostic odds ratio of threshold growth were calculated. The diagnostic performance of LI-RADS category 5 was separately evaluated when threshold growth was and was not considered a major feature, and results were compared using generalized estimation equations. Subgroups of patients who underwent CT/MRI during the previous 3-6 months were analyzed. RESULTS Analysis of 340 observations in 243 patients found that the frequency of threshold growth was 18.8% and it gradually increased over time. Threshold growth was significantly associated with HCC (diagnostic odds ratio 5.2; 95% CI 2.1-12.7; p <0.001). Use of threshold growth as a major feature significantly increased sensitivity in both the overall (66.4% vs. 57.3%, p <0.001) and subgroup (73.4% vs. 58.2%, p <0.001) cohorts, but had no effect on specificity in either the overall (97.5% vs. 98.3%, p = 0.319) or subgroup (95.9% vs. 98.0%, p = 0.323) cohorts. CONCLUSION The revised threshold growth of LI-RADS v2018 was significantly associated with HCC. Use of threshold growth as a major diagnostic feature of HCC can improve the sensitivity of LI-RADS v2018. IMPACT AND IMPLICATIONS We found that the revised threshold growth in the Liver Imaging Reporting and Data System version 2018 (LI-RADS v2018) was a significant predictor of hepatocellular carcinoma (HCC). The use of threshold growth as a major imaging feature of HCC significantly increased the sensitivity of LI-RADS v2018, especially small HCCs (≤3.0 cm), compared with its non-use. Because these small HCCs are eligible for curative treatments, the additional detection of small HCCs is clinically meaningful.
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Affiliation(s)
- Se Jin Choi
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of Korea
| | - Sang Hyun Choi
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of Korea.
| | - Dong Wook Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of Korea
| | - Minha Kwag
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of Korea
| | - Jae Ho Byun
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of Korea
| | - Hyung Jin Won
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of Korea
| | - Yong Moon Shin
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of Korea
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The Additive Value of Radiomics Features Extracted from Baseline MR Images to the Barcelona Clinic Liver Cancer (BCLC) Staging System in Predicting Transplant-Free Survival in Patients with Hepatocellular Carcinoma: A Single-Center Retrospective Analysis. Diagnostics (Basel) 2023; 13:diagnostics13030552. [PMID: 36766656 PMCID: PMC9914401 DOI: 10.3390/diagnostics13030552] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 01/30/2023] [Accepted: 01/31/2023] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND To study the additive value of radiomics features to the BCLC staging system in clustering HCC patients. METHODS A total of 266 patients with HCC were included in this retrospective study. All patients had undergone baseline MR imaging, and 95 radiomics features were extracted from 3D segmentations representative of lesions on the venous phase and apparent diffusion coefficient maps. A random forest algorithm was utilized to extract the most relevant features to transplant-free survival. The selected features were used alongside BCLC staging to construct Kaplan-Meier curves. RESULTS Out of 95 extracted features, the three most relevant features were incorporated into random forest classifiers. The Integrated Brier score of the prediction error curve was 0.135, 0.072, and 0.048 for the BCLC, radiomics, and combined models, respectively. The mean area under the receiver operating curve (ROC curve) over time for the three models was 81.1%, 77.3%, and 56.2% for the combined radiomics and BCLC models, respectively. CONCLUSIONS Radiomics features outperformed the BCLC staging system in determining prognosis in HCC patients. The addition of a radiomics classifier increased the classification capability of the BCLC model. Texture analysis features could be considered as possible biomarkers in predicting transplant-free survival in HCC patients.
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Hong SB, Hong S, Choi SH, Park SY, Shim JH, Kim SY, Lee SS, Kim S. Multiple arterial-phase MRI with gadoxetic acid improves diagnosis of hepatocellular carcinoma ≤3.0 cm. Liver Int 2023; 43:462-470. [PMID: 36317670 DOI: 10.1111/liv.15470] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 10/18/2022] [Accepted: 10/30/2022] [Indexed: 11/06/2022]
Abstract
BACKGROUND AND AIMS Multiple arterial-phase magnetic resonance imaging (MA-MRI) was introduced to overcome the limitations of gadoxetic acid-enhanced MRI, but its clinical impacts on hepatocellular carcinoma (HCC) diagnosis have not been well assessed. We investigated whether MA-MRI with gadoxetic acid could improve the diagnosis of HCC ≤3.0 cm in comparison with single arterial-phase MRI (SA-MRI). METHODS This retrospective study included 397 patients from two tertiary institutions who underwent gadoxetic acid-enhanced MRI (243 patients with 271 lesions in cohort-1 underwent SA-MRI, and 154 patients with 166 lesions in cohort-2 underwent MA-MRI). The patients had 437 hepatic lesions ≤3.0 cm with pathologic confirmation. The arterial-phase image quality and diagnostic performance of SA-MRI and MA-MRI were analysed and compared. To minimize the effects of selection bias because of potential confounding between the two groups, propensity score-matching was additionally performed. RESULTS MA-MRI showed a significantly higher percentage of optimal arterial-phase timing (94.2% vs. 74.5%, p < .001) and lower incidence of inadequate examinations (1.3% vs. 5.8%, p = .034) than SA-MRI. MA-MRI had a significantly higher non-rim arterial-phase hyperenhancement (APHE) detection rate (94.9% vs. 85.5%, p = .005) and sensitivity for diagnosing HCC (87.4% vs. 70.0%, p < .001) than SA-MRI, but no significant difference in specificity (92.9% vs. 93.1%, p = .966). In 123 pairs of propensity score-matched patients, MA-MRI had significantly higher sensitivity (89.1% vs. 74.5%, p = .006) than SA-MRI with equal specificity (92.3% vs. 92.3%, p > .999). CONCLUSIONS Compared with SA-MRI, MA-MRI with gadoxetic acid can detect more non-rim APHE and significantly improve sensitivity for diagnosing HCC ≤3.0 cm, without a significant decrease in specificity.
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Affiliation(s)
- Seung Baek Hong
- Department of Radiology, Biomedical Research Institute, Pusan National University Hospital, and Pusan National University School of Medicine, Busan, Republic of Korea
| | - Sun Hong
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Sang Hyun Choi
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Seo Young Park
- Department of Statistics and Data Science, Korea National Open University, Seoul, Republic of Korea
| | - Ju Hyun Shim
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - So Yeon Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Seung Soo Lee
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Suk Kim
- Department of Radiology, Biomedical Research Institute, Pusan National University Hospital, and Pusan National University School of Medicine, Busan, Republic of Korea
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Youssef E, El-Khouly N, Elzahrani YA, Tash RME, Khalifa EA, Bayoumy ESM, Khalil M, Edreis AE, Mohamed FS, Abdou AE, Seliem N, Sofy M, Fakhrelden S, Marmoush SMH, Elmohaseb GF, Elhosary AA. TGF-1 mRNA, AFP-L3, and Annexin II in the Early and Late Detection of Hepatocellular Carcinoma: The Diagnostic Value. Open Access Maced J Med Sci 2022. [DOI: 10.3889/oamjms.2022.10814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/11/2023] Open
Abstract
BACKGROUND: Alpha-fetoprotein (AFP) is the recommended screening biomarker for hepatocellular carcinoma (HCC), despite its drawbacks: AFP-negative HCC, poor specificity, and sensitivity. As a result, new HCC-sensitive and specific biomarkers are urgently needed.
AIM: This study aimed to determine the diagnostic value of transforming growth factor (TGF)-β1 mRNA and Annexin II in the early detection and follow-up of HCC.
PATIENT AND METHODS: This research involved 75 HCC patients (30 early and 45 late) and 75 liver cirrhosis (LC) patients (all patients have HCV), and 75 healthy individuals as controls. Reverse transcription polymerase chain reaction measured TGF-β1 mRNA. Enzyme-linked immunosorbent assay ELISA measured Annexin II, AFP-L3, and AFP.
RESULTS: Annexin II was a biomarker with a significant difference between the LC and early HCC groups. TGF-β1 mRNA showed a significant difference when the LC group was compared to the control group and the late HCC group.
CONCLUSION: Annexin II has better sensitivity and specificity for early HCC detection than AFP, and TGF-β1 mRNA can be used for the assessment of the degree of HCC, and TGF-1 signaling inhibitors may be a possible new treatment choice for HCC.
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Li M, Zhang X, Wang M, Wang Y, Qian J, Xing X, Wang Z, You Y, Guo K, Chen J, Gao D, Zhao Y, Zhang L, Chen R, Cui J, Ren Z. Activation of Piezo1 contributes to matrix stiffness-induced angiogenesis in hepatocellular carcinoma. Cancer Commun (Lond) 2022; 42:1162-1184. [PMID: 36181398 PMCID: PMC9648387 DOI: 10.1002/cac2.12364] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Revised: 06/23/2022] [Accepted: 09/15/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Despite integrin being highlighted as a stiffness-sensor molecule in matrix stiffness-driven angiogenesis, other stiffness-sensor molecules and their mechanosensory pathways related to angiogenesis in hepatocellular carcinoma (HCC) remain obscure. Here, we explored the interplay between Piezo1 and integrin β1 in the mechanosensory pathway and their effects on HCC angiogenesis to better understand matrix stiffness-induced angiogenesis. METHODS The role of Piezo1 in matrix stiffness-induced angiogenesis was investigated using orthotopic liver cancer SD rat models with high liver stiffness background, and its clinical significance was evaluated in human HCC tissues. Matrix stiffness-mediated Piezo1 upregulation and activation were assayed using an in vitro fibronectin (FN)-coated cell culture system with different stiffness, Western blotting and Ca2+ probe. The effects of shPiezo1-conditioned medium (CM) on angiogenesis were examined by tube formation assay, wound healing assay and angiogenesis array. The underlying mechanism by which Piezo1 participated in matrix stiffness-induced angiogenesis was analyzed by microRNA quantitative real-time polymerase chain reaction (qRT-PCR), matrix stiffness measurement, dual-luciferase reporter assay, ubiquitination assay and co-immunoprecipitation. RESULTS Increased matrix stiffness significantly upregulated Piezo1 expression at both cellular and tissue levels, and high expression of Piezo1 indicated an unfavorable prognosis. High matrix stiffness also noticeably enhanced the activation level of Piezo1, similar to its expression level. Piezo1 knockdown significantly suppressed tumor growth, angiogenesis, and lung metastasis of HCC rat models with high liver stiffness background. shPiezo1-CM from HCC cells attenuated tube formation and migration abilities of vascular endothelial cells remarkably, and analysis of differentially expressed pro-angiogenic factors revealed that Piezo1 promoted the expression and secretion of vascular endothelial growth factor (VEGF), CXC chemokine ligand 16 (CXCL16) and insulin-like growth factor binding protein 2 (IGFBP2). Matrix stiffness-caused Piezo1 upregulation/activation restrained hypoxia inducible factor-1α (HIF-1α) ubiquitination, subsequently enhanced the expression of downstream pro-angiogenic factors to accelerate HCC angiogenesis. Besides, collagen 1 (COL1)-reinforced tissue stiffening resulted in more expression of Piezo1 via miR-625-5p. CONCLUSIONS This study unravels a new mechanism by which the integrin β1/Piezo1 activation/Ca2+ influx/HIF-1α ubiquitination/VEGF, CXCL16 and IGFBP2 pathway participates in matrix stiffness-driven HCC angiogenesis. Simultaneously, a positive feedback regulation loop as stiff matrix/integrin β1/miR-625-5p/Piezo1 and COL1/stiffer matrix mediates matrix stiffness-caused Piezo1 upregulation.
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Affiliation(s)
- Miao Li
- Liver Cancer InstituteZhongshan HospitalFudan University & Key Laboratory of Carcinogenesis and Cancer InvasionMinistry of EducationShanghai200032P. R. China
| | - Xi Zhang
- Liver Cancer InstituteZhongshan HospitalFudan University & Key Laboratory of Carcinogenesis and Cancer InvasionMinistry of EducationShanghai200032P. R. China
| | - Mimi Wang
- Liver Cancer InstituteZhongshan HospitalFudan University & Key Laboratory of Carcinogenesis and Cancer InvasionMinistry of EducationShanghai200032P. R. China
| | - Yaohui Wang
- Department of RadiologyShanghai Cancer CenterFudan UniversityShanghai200032P. R. China
| | - Jiali Qian
- Department of EndocrinologyHuashan HospitalFudan UniversityShanghai200032P. R. China
| | - Xiaoxia Xing
- Liver Cancer InstituteZhongshan HospitalFudan University & Key Laboratory of Carcinogenesis and Cancer InvasionMinistry of EducationShanghai200032P. R. China
| | - Zhiming Wang
- Department of OncologyZhongshan HospitalFudan UniversityShanghai200032P. R. China
| | - Yang You
- Department of OncologyZhongshan HospitalFudan UniversityShanghai200032P. R. China
| | - Kun Guo
- Liver Cancer InstituteZhongshan HospitalFudan University & Key Laboratory of Carcinogenesis and Cancer InvasionMinistry of EducationShanghai200032P. R. China
| | - Jie Chen
- Liver Cancer InstituteZhongshan HospitalFudan University & Key Laboratory of Carcinogenesis and Cancer InvasionMinistry of EducationShanghai200032P. R. China
| | - Dongmei Gao
- Liver Cancer InstituteZhongshan HospitalFudan University & Key Laboratory of Carcinogenesis and Cancer InvasionMinistry of EducationShanghai200032P. R. China
| | - Yan Zhao
- Liver Cancer InstituteZhongshan HospitalFudan University & Key Laboratory of Carcinogenesis and Cancer InvasionMinistry of EducationShanghai200032P. R. China
| | - Lan Zhang
- Liver Cancer InstituteZhongshan HospitalFudan University & Key Laboratory of Carcinogenesis and Cancer InvasionMinistry of EducationShanghai200032P. R. China
| | - Rongxin Chen
- Liver Cancer InstituteZhongshan HospitalFudan University & Key Laboratory of Carcinogenesis and Cancer InvasionMinistry of EducationShanghai200032P. R. China
| | - Jiefeng Cui
- Liver Cancer InstituteZhongshan HospitalFudan University & Key Laboratory of Carcinogenesis and Cancer InvasionMinistry of EducationShanghai200032P. R. China
| | - Zhenggang Ren
- Liver Cancer InstituteZhongshan HospitalFudan University & Key Laboratory of Carcinogenesis and Cancer InvasionMinistry of EducationShanghai200032P. R. China
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Utility of PET Scans in the Diagnosis and Management of Gastrointestinal Tumors. Dig Dis Sci 2022; 67:4633-4653. [PMID: 35908126 DOI: 10.1007/s10620-022-07616-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/27/2022] [Indexed: 12/14/2022]
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Si T, Huang Z, Khorsandi SE, Ma Y, Heaton N. Hepatic arterial infusion chemotherapy versus transarterial chemoembolization for unresectable hepatocellular carcinoma: A systematic review with meta-analysis. Front Bioeng Biotechnol 2022; 10:1010824. [PMID: 36237208 PMCID: PMC9551027 DOI: 10.3389/fbioe.2022.1010824] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 09/08/2022] [Indexed: 11/13/2022] Open
Abstract
Background: Interest has revived in the use of hepatic arterial infusion chemotherapy (HAIC) for intermediate-advanced hepatocellular carcinoma (HCC) while transarterial chemoembolization (TACE) has been a longstanding loco-regional therapy. Aim: We conducted a systematic review and meta-analysis of patients with unresectable HCC treated with HAIC or TACE to look for differences in survival, adverse events, mortality and downstaging. Methods: All studies published before 29 July 2022 were identified by searching PubMed, Embase, Web of Science and Cochrane Library databases for patients with unresectable HCC and received HAIC or TACE as initial treatment. Data extracted from studies was statistically analysed using RevMan5.3 software. Results: A total of one randomized controlled trial (RCT) and 7 cohort studies (5 retrospective, 2 prospective) including 1,060 (TACE group: 534, HAIC group: 526) patients were screened. Compared with the TACE group, patients who received HAIC as initial therapy had better overall survival (OS) (HR = 0.53, 95%CI [0.40, 0.69]) and progression-free survival (PFS) (HR = 0.54, 95%CI [0.40, 0.72]). Further subgroup analysis revealed that HAIC showed priority over TACE on prognosis outcome regardless of tumour stage, especially in patients with advanced portal vein tumour thrombus (PVTT). Utilization of port system will not boost the efficacy of HAIC whereas using a replaced-microcatheter for each procedure could better reduce the progressive disease (PD) rate (RR = 0.55, 95%CI [0.40, 0.76]). The pooled RR favoured the HAIC group with regard to partial response (PR) (RR = 2.87, 95%CI [2.18, 3.78]) and this was validated by both GRADE summary and trial sequential analysis. The rate of resection after treatment was higher in the HAIC group (RR = 2.37, 95%CI [1.54, 3.66]), whilst no difference was found with procedure-related mortality (RR = 0.56, 95%CI [0.13, 2.38]) between two groups. Compared with the traditional chemotherapy regimen (fluorouracil/leucovorin/oxaliplatin) FOLFOX-HAIC appears to be better in improving the treatment efficacy. Conclusion: Patients with unresectable HCC could potentially benefit more from HAIC rather than standard TACE treatment. A re-evaluation of HAIC as a treatment option in intermediate and advanced HCC is warranted.
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Affiliation(s)
- Tengfei Si
- Department of Inflammation Biology, Faculty of Life Sciences & Medicine, Institute of Liver Studies, King’s College Hospital, King’s College London, Denmark Hill, London, United Kingdom
| | - Zhenlin Huang
- Department of Inflammation Biology, Faculty of Life Sciences & Medicine, Institute of Liver Studies, King’s College Hospital, King’s College London, Denmark Hill, London, United Kingdom
- The MOE Key Laboratory for Standardization of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Shirin Elizabeth Khorsandi
- Department of Inflammation Biology, Faculty of Life Sciences & Medicine, Institute of Liver Studies, King’s College Hospital, King’s College London, Denmark Hill, London, United Kingdom
- Transplant Services, King’s College Hospital, Denmark Hill, London, United Kingdom
- The Roger Williams Institute of Hepatology, Foundation for Liver Research, London, United Kingdom
| | - Yun Ma
- Department of Inflammation Biology, Faculty of Life Sciences & Medicine, Institute of Liver Studies, King’s College Hospital, King’s College London, Denmark Hill, London, United Kingdom
- *Correspondence: Yun Ma, ; Nigel Heaton,
| | - Nigel Heaton
- Transplant Services, King’s College Hospital, Denmark Hill, London, United Kingdom
- *Correspondence: Yun Ma, ; Nigel Heaton,
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Kwag M, Choi SH, Choi SJ, Byun JH, Won HJ, Shin YM. Simplified LI-RADS for Hepatocellular Carcinoma Diagnosis at Gadoxetic Acid-enhanced MRI. Radiology 2022; 305:614-622. [PMID: 35972362 DOI: 10.1148/radiol.220659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2022]
Abstract
Background Although various modifications to the Liver Imaging Reporting and Data System (LI-RADS) at gadoxetic acid-enhanced MRI have been suggested, LI-RADS shows suboptimal sensitivity for hepatocellular carcinoma (HCC) and is perceived to be too complex. Purpose To evaluate clinical usefulness of a simplified LI-RADS for diagnosing HCCs of 30 mm or smaller at gadoxetic acid-enhanced MRI. Materials and Methods Patients who underwent gadoxetic acid-enhanced MRI examination and subsequent resection, transplantation, or biopsy for focal solid nodules of 30 mm or smaller between January 2019 and December 2020 at a single tertiary referral institution were retrospectively analyzed. Two strategies for simplified LI-RADS using one size criterion (≥10 mm) were evaluated (strategy A, using classifications for nodules of 10-19 mm for nodules both 10-19 mm and ≥20 mm; strategy B, using classifications for nodules ≥20 mm for nodules both 10-19 mm and ≥20 mm). Multivariable analysis was performed to determine significant ancillary features for HCC. Generalized estimating equations were used to compare diagnostic performance for LR-5 (definite HCC) between LI-RADS version 2018 and simplified LI-RADS. The time required for LI-RADS category assignment was compared between the two systems with use of a paired t test. Results A total of 645 nodules from 510 patients (mean age ± SD, 60 years ± 10; 393 men) were evaluated. Compared with strategy A, strategy B had a higher sensitivity of 74% (347 of 470 nodules [95% CI: 70, 78]) vs 73% (342 of 470 nodules [95% CI: 69, 77]) (P = .02) with the same specificity of 96% (168 of 175 nodules [95% CI: 92, 98]) vs 96% (168 of 175 nodules [95% CI: 92, 98]) (P > .99). In strategy B, transitional phase hypointensity was an independent ancillary feature for HCC (P = .04) in LR-4 of at least 10 mm with arterial phase hyperenhancement and no other major features. In all 645 nodules, simplified LI-RADS with use of both strategy B and transitional phase hypointensity had a higher sensitivity of 82% (387 of 470 nodules [95% CI: 79, 86]) vs 73% (343 of 470 nodules [95% CI: 69, 77]) (P < .001) than LI-RADS version 2018, without lower specificity (94%, 165 of 175 nodules [95% CI: 90, 97] vs 96%, 168 of 175 nodules [95% CI: 92, 98], P = .08). Compared with LI-RADS version 2018, simplified LI-RADS reduced the time for LI-RADS category assignment (44 seconds ± 23 vs 74 seconds ± 22, P < .001). Conclusion A simplified Liver Imaging Reporting and Data System was found to be clinically useful for diagnosing hepatocellular carcinomas of 30 mm or smaller at gadoxetic acid-enhanced MRI. © RSNA, 2022 Online supplemental material is available for this article.
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Affiliation(s)
- Minha Kwag
- From the Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43 gil, Songpa-Gu, Seoul 05505, Korea
| | - Sang Hyun Choi
- From the Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43 gil, Songpa-Gu, Seoul 05505, Korea
| | - Se Jin Choi
- From the Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43 gil, Songpa-Gu, Seoul 05505, Korea
| | - Jae Ho Byun
- From the Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43 gil, Songpa-Gu, Seoul 05505, Korea
| | - Hyung Jin Won
- From the Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43 gil, Songpa-Gu, Seoul 05505, Korea
| | - Yong Moon Shin
- From the Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43 gil, Songpa-Gu, Seoul 05505, Korea
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Stereotactic Body Radiation Therapy for the Management of Hepatocellular Carcinoma: Efficacy and Safety. Cancers (Basel) 2022; 14:cancers14163892. [PMID: 36010885 PMCID: PMC9405555 DOI: 10.3390/cancers14163892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Accepted: 08/09/2022] [Indexed: 11/16/2022] Open
Abstract
Simple Summary This study aimed to describe treatment efficacy and safety in patients with hepatocellular carcinoma (HCC) undergoing stereotactic body radiation therapy (SBRT). In one of the largest retrospective studies to date, we analyzed the data of 318 patients. The median follow-up period was 70.2 months. The local control rate at 24 and 60 months was 94% (91–97%) and 94% (91–97%), respectively. Relapse-free survival at 12, 24, and 60 months was 62% (55–67%), 29% (23–36%), and 13% (8–19%), respectively. OS at 12, 24, and 60 months was 72% (95%CI 67–77%), 44% (38–50%), and 11% (7–15%), respectively. The outcome is highly related to the natural evolution of the underlying cirrhosis. Child-Pugh score B-C, high BCLC score, portal thrombosis, GTV volume, and higher PTV volume reported on total hepatic volume ratio were significantly associated with OS. SBRT is efficient for the management of HCC with a favorable toxicity profile. Abstract This study aimed to describe patient characteristics, treatment efficacy, and safety in patients with hepatocellular carcinoma (HCC) undergoing stereotactic body radiation therapy (SBRT). We retrospectively analyzed data of 318 patients with 375 HCC treated between June 2007 and December 2018. Efficacy (overall survival [OS], relapse-free survival, and local control) and acute and late toxicities were described. The median follow-up period was 70.2 months. Most patients were treated with 45 Gy in three fractions. The median (range) PTV volume was 90.7 (2.6–1067.6) cc. The local control rate at 24 and 60 months was 94% (91–97%) and 94% (91–97%), respectively. Relapse-free survival at 12, 24, and 60 months was 62% (55–67%), 29% (23–36%), and 13% (8–19%), respectively. OS at 12, 24, and 60 months was 72% (95%CI 67–77%), 44% (38–50%), and 11% (7–15%), respectively. Approximately 51% and 38% experienced acute and late toxicity, respectively. Child-Pugh score B-C, high BCLC score, portal thrombosis, high GTV volume, and higher PTV volume reported on total hepatic volume ratio were significantly associated with OS. SBRT is efficient for the management of HCC with a favorable toxicity profile. The outcome is highly related to the natural evolution of the underlying cirrhosis.
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Zhang R, Zeng J, Liu W, Meng J, Wang C, Shi L, Yang S, Chang J, Xing D. The role of NPC1L1 in cancer. Front Pharmacol 2022; 13:956619. [PMID: 36034854 PMCID: PMC9399402 DOI: 10.3389/fphar.2022.956619] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Accepted: 07/11/2022] [Indexed: 11/13/2022] Open
Abstract
Lipid metabolism appears to play significant roles in the development of cancer. Numerous studies have shown that the evolution of malignancies, including breast, prostate, and colorectal cancers, involves cholesterol in a profound manner. A crucial part in the intestinal absorption of cholesterol is played by Niemann–Pick C1-like 1 (NPC1L1), a cholesterol transporter protein that is widely expressed in the small intestine and liver. The importance of NPC1L1 in tumor prognosis has been demonstrated in investigations in the interim. NPC1L1 also has the potential to develop into a new therapeutic target and a cancer marker. There is, however, no comprehensive review that summarizes NPC1L1’s function in cancer. To this end, we outlined NPC1L1’s functions in carcinogenesis and treatment, along with resources that can be used to further comprehend the connection between NPC1L1 and tumors.
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Affiliation(s)
- Renshuai Zhang
- Qingdao Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
| | - Jun Zeng
- Qingdao Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
- School of Basic Medicine, Qingdao University, Qingdao, China
| | - Wenjing Liu
- Qingdao Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
- School of Basic Medicine, Qingdao University, Qingdao, China
| | - Jingsen Meng
- Qingdao Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
- School of Basic Medicine, Qingdao University, Qingdao, China
| | - Chao Wang
- Qingdao Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
| | - Lingyu Shi
- Qingdao Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
- School of Basic Medicine, Qingdao University, Qingdao, China
| | - Shanbo Yang
- Qingdao Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
- School of Basic Medicine, Qingdao University, Qingdao, China
| | - Jing Chang
- Qingdao Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
- School of Basic Medicine, Qingdao University, Qingdao, China
| | - Dongming Xing
- Qingdao Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
- School of Life Sciences, Tsinghua University, Beijing, China
- *Correspondence: Dongming Xing,
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Wan H, Lu S, Xu L, Yuan K, Xiao Y, Xie K, Wu H. Immune-Related Biomarkers Improve Performance of Risk Prediction Models for Survival in Patients With Hepatocellular Carcinoma. Front Oncol 2022; 12:925362. [PMID: 35936682 PMCID: PMC9353009 DOI: 10.3389/fonc.2022.925362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Accepted: 06/20/2022] [Indexed: 01/27/2023] Open
Abstract
ObjectThe prediction of hepatocellular carcinoma (HCC) prognosis faced great challenge due to tumor heterogeneity. The purpose of this study was to explore the correlation between the immune infiltrate and prognosis. Moreover, we aimed to establish a risk prediction model for survival in HCC patients based on clinicopathological and immune indicators.MethodsIn this study, 316 patients with HCC who underwent radical resection in West China Hospital from 2009 to 2014 were included. Clinicopathological data and pathological specimens were collected. H&E staining and immunohistochemical staining were performed on the pathological tissue sections. The evaluation of tumor-infiltrating lymphocyte (TIL) density was based on H&E slices, and the assessment of the expressions of CD8, CD68, Lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin domain and mucin domain-3 (TIM-3), Programmed Cell Death Protein 1 (PD-1), Programmed Cell Death Ligand 1 (PD-L1), OX40, CD66b, and Tryptase. was performed on the immunohistochemical slices. A risk prediction model for survival in HCC patients was established by integrating immune-related biomarkers and clinicopathological indicators.ResultsThe Barcelona Clinic Liver Cancer (BCLC) stage; the microvascular invasion status; the density of TILs; the expressing levels of CD66b, OX40, and PD-L1 in the immune cell; CD68; and CD8 were the predictors of patients’ overall survival (OS). The BCLC stage; the density of TILs; and the expressions of OX40, CD68, and CD8 were associated with disease-free survival (DFS). The expressions of CD66b, CD68, OX40, and CD8 had a cumulative effect on prognosis. The area under the curve of the prediction model for OS based on clinicopathological features was improved from 0.62 to 0.74 by adding to CD8, OX40, CD68, CD66b, and TILs, whereas it was improved from 0.59 to 0.73 for the DFS prediction model.ConclusionOur results, if confirmed, indicated that immune-related biomarkers should be taken into account or stratified in survival analysis for HCC.
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Affiliation(s)
- Haifeng Wan
- Department of Liver Surgery and Liver Transplantation, West China Hospital, Sichuan University, Chengdu, China
| | - Shan Lu
- Department of Breast Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Lin Xu
- Laboratory of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Kefei Yuan
- Laboratory of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Yang Xiao
- Department of Plastic and Burn Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Kunlin Xie
- Department of Liver Surgery and Liver Transplantation, West China Hospital, Sichuan University, Chengdu, China
- *Correspondence: Hong Wu, ; Kunlin Xie,
| | - Hong Wu
- Department of Liver Surgery and Liver Transplantation, West China Hospital, Sichuan University, Chengdu, China
- *Correspondence: Hong Wu, ; Kunlin Xie,
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Peptide vaccine-treated, long-term surviving cancer patients harbor self-renewing tumor-specific CD8 + T cells. Nat Commun 2022; 13:3123. [PMID: 35660746 PMCID: PMC9166698 DOI: 10.1038/s41467-022-30861-z] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 05/23/2022] [Indexed: 11/09/2022] Open
Abstract
The behaviors and fates of immune cells in cancer patients, such as dysfunction and stem-like states leading to memory formation in T cells, are in intense focus of investigation. Here we show, by post hoc analysis of peripheral blood lymphocytes of hepatocellular carcinoma patients previously undergoing vaccination with tumour-associated antigen-derived peptides in our clinical trials (registration numbers UMIN000003511, UMIN000004540, UMIN000005677, UMIN000003514 and UMIN000005678), that induced peptide-specific T cell responses may persist beyond 10 years following vaccination. Tracking TCR clonotypes at the single cell level reveals in two patients that peptide-specific long-lasting CD8+ T cells acquire an effector memory phenotype that associates with cell cycle-related genes (CCNA2 and CDK1), and are characterized by high expression of IL7R, SELL, and NOSIP along with a later stage promotion of the AP-1 transcription factor network (5 years or more past vaccination). We conclude that effective anti-tumor immunity is governed by potentially proliferative memory T cells, specific to cancer antigens.
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Morise Z, Aldrighetti L, Belli G, Ratti F, Cheung TT, Lo CM, Tanaka S, Kubo S, Okamura Y, Uesaka K, Monden K, Sadamori H, Hashida K, Kawamoto K, Gotohda N, Chen K, Kanazawa A, Takeda Y, Ohmura Y, Ueno M, Ogura T, Suh KS, Kato Y, Sugioka A, Belli A, Nitta H, Yasunaga M, Cherqui D, Abdul Halim N, Laurent A, Kaneko H, Otsuka Y, Kim KH, Cho HD, Lin CCW, Ome Y, Seyama Y, Troisi RI, Berardi G, Rotellar F, Wilson GC, Geller DA, Soubrane O, Yoh T, Kaizu T, Kumamoto Y, Han HS, Ekmekcigil E, Dagher I, Fuks D, Gayet B, Buell JF, Ciria R, Briceno J, O’Rourke N, Lewin J, Edwin B, Shinoda M, Abe Y, Hilal MA, Alzoubi M, Tanabe M, Wakabayashi G. An International Retrospective Observational Study of Liver Functional Deterioration after Repeat Liver Resection for Patients with Hepatocellular Carcinoma. Cancers (Basel) 2022; 14:2598. [PMID: 35681578 PMCID: PMC9179920 DOI: 10.3390/cancers14112598] [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: 04/24/2022] [Revised: 05/08/2022] [Accepted: 05/11/2022] [Indexed: 02/06/2023] Open
Abstract
Whether albumin and bilirubin levels, platelet counts, ALBI, and ALPlat scores could be useful for the assessment of permanent liver functional deterioration after repeat liver resection was examined, and the deterioration after laparoscopic procedure was evaluated. For 657 patients with liver resection of segment or less in whom results of plasma albumin and bilirubin levels and platelet counts before and 3 months after surgery could be retrieved, liver functional indicators were compared before and after surgery. There were 268 patients who underwent open repeat after previous open liver resection, and 224 patients who underwent laparoscopic repeat after laparoscopic liver resection. The background factors, liver functional indicators before and after surgery and their changes were compared between both groups. Plasma levels of albumin (p = 0.006) and total bilirubin (p = 0.01) were decreased, and ALBI score (p = 0.001) indicated worse liver function after surgery. Laparoscopic group had poorer preoperative performance status and liver function. Changes of liver functional values before and after surgery and overall survivals were similar between laparoscopic and open groups. Plasma levels of albumin and bilirubin and ALBI score could be the indicators for permanent liver functional deterioration after liver resection. Laparoscopic group with poorer conditions showed the similar deterioration of liver function and overall survivals to open group.
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Affiliation(s)
- Zenichi Morise
- Department of General Surgery, Fujita Health University School of Medicine Okazaki Medical Center, Okazaki 444-0827, Japan
| | - Luca Aldrighetti
- Hepatobiliary Division in Department of Surgery, San Raffaele Hospital, 20132 Milano, Italy; (L.A.); (F.R.)
| | - Giulio Belli
- Department of General and HPB Surgery, Loreto Nuovo Hospital, 80127 Naples, Italy;
| | - Francesca Ratti
- Hepatobiliary Division in Department of Surgery, San Raffaele Hospital, 20132 Milano, Italy; (L.A.); (F.R.)
| | - Tan To Cheung
- Division of HBP and Liver Transplant, University of Hong Kong Queen Mary Hospital, Hong Kong, China; (T.T.C.); (C.M.L.)
| | - Chung Mau Lo
- Division of HBP and Liver Transplant, University of Hong Kong Queen Mary Hospital, Hong Kong, China; (T.T.C.); (C.M.L.)
| | - Shogo Tanaka
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka 545-8586, Japan; (S.T.); (S.K.)
| | - Shoji Kubo
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka 545-8586, Japan; (S.T.); (S.K.)
| | - Yukiyasu Okamura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, Sunto, Shizuoka 411-8777, Japan; (Y.O.); (K.U.)
| | - Katsuhiko Uesaka
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, Sunto, Shizuoka 411-8777, Japan; (Y.O.); (K.U.)
| | - Kazuteru Monden
- Departments of Surgery, Fukuyama City Hospital, Fukuyama 721-8511, Japan; (K.M.); (H.S.)
| | - Hiroshi Sadamori
- Departments of Surgery, Fukuyama City Hospital, Fukuyama 721-8511, Japan; (K.M.); (H.S.)
| | - Kazuki Hashida
- Department of Surgery, Kurashiki Central Hospital, Kurashiki 710-8602, Japan; (K.H.); (K.K.)
| | - Kazuyuki Kawamoto
- Department of Surgery, Kurashiki Central Hospital, Kurashiki 710-8602, Japan; (K.H.); (K.K.)
| | - Naoto Gotohda
- Division of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Kashiwa 277-8577, Japan;
| | - KuoHsin Chen
- Division of General Surgery, Department of Surgery, Far-Eastern Memorial Hospital, New Taipei City 220, Taiwan;
- Department of Electrical Engineering, Yuan Ze University, Taoyuan City 320, Taiwan
| | - Akishige Kanazawa
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City General Hospital, Osaka 534-0021, Japan;
| | - Yutaka Takeda
- Department of Surgery, Kansai Rosai Hospital, Amagasaki 660-8511, Japan; (Y.T.); (Y.O.)
| | - Yoshiaki Ohmura
- Department of Surgery, Kansai Rosai Hospital, Amagasaki 660-8511, Japan; (Y.T.); (Y.O.)
| | - Masaki Ueno
- Second Department of Surgery, Wakayama Medical University, Wakayama 641-8509, Japan;
| | - Toshiro Ogura
- Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo 113-8510, Japan; (T.O.); (M.T.)
| | - Kyung Suk Suh
- Department of Hepatobiliary and Pancreatic Surgery, Seoul National University Hospital, Seoul 03080, Korea;
| | - Yutaro Kato
- Department of Gastrointestinal Surgery, Fujita Health University School of Medicine, Toyoake 470-1192, Japan; (Y.K.); (A.S.)
| | - Atsushi Sugioka
- Department of Gastrointestinal Surgery, Fujita Health University School of Medicine, Toyoake 470-1192, Japan; (Y.K.); (A.S.)
| | - Andrea Belli
- Department of Abdominal Surgical Oncology, Fondazione G.Pascale-IRCCS, National Cancer Institute of Naples, 80131 Napoli, Italy;
| | - Hiroyuki Nitta
- Department of Surgery, Iwate Medical University, Morioka 028-3695, Japan;
| | - Masafumi Yasunaga
- Department of Surgery, Kurume University School of Medicine, Kurume 830-0011, Japan;
| | - Daniel Cherqui
- Paul Brousse Hospital, 94800 Villejuif, France; (D.C.); (N.A.H.)
- Paris-Sud University, 91190 Gif-sur-Yvette, France;
| | | | | | - Hironori Kaneko
- Division of General and Gastroenterological Surgery, Department of Surgery, Toho University Faculty of Medicine, Tokyo 143-8540, Japan; (H.K.); (Y.O.)
| | - Yuichiro Otsuka
- Division of General and Gastroenterological Surgery, Department of Surgery, Toho University Faculty of Medicine, Tokyo 143-8540, Japan; (H.K.); (Y.O.)
| | - Ki Hun Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Ulsan University and Asan Medical Center, Seoul 05505, Korea; (K.H.K.); (H.-D.C.)
| | - Hwui-Dong Cho
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Ulsan University and Asan Medical Center, Seoul 05505, Korea; (K.H.K.); (H.-D.C.)
| | - Charles Chung-Wei Lin
- Department of Surgery and Surgical Oncology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei 112, Taiwan;
- IRCAD-AITS, Changhua 505, Taiwan
| | - Yusuke Ome
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo 113-8677, Japan; (Y.O.); (Y.S.)
| | - Yasuji Seyama
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo 113-8677, Japan; (Y.O.); (Y.S.)
| | - Roberto I. Troisi
- Department of Clinical Medicine and Surgery, University of Naples Federico II, 80138 Napoli, Italy;
| | - Giammauro Berardi
- General Hepato-Biliary and Liver Transplantation Surgery, Ghent University Hospital Medical School, 9000 Gent, Belgium;
| | - Fernando Rotellar
- Hepato-Bilio-Pancreatic Unit of Clinica Universitaria de Navarra, 31008 Pamplona, Spain;
| | - Gregory C. Wilson
- Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA; (G.C.W.); (D.A.G.)
| | - David A. Geller
- Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA; (G.C.W.); (D.A.G.)
| | - Olivier Soubrane
- Department of HPB Surgery and Liver Transplant, Beaujon Hospital, Clichy 92110, France; (O.S.); (T.Y.)
| | - Tomoaki Yoh
- Department of HPB Surgery and Liver Transplant, Beaujon Hospital, Clichy 92110, France; (O.S.); (T.Y.)
| | - Takashi Kaizu
- Department of Surgery, Kitasato University School of Medicine, Sagamihara 252-0374, Japan; (T.K.); (Y.K.)
| | - Yusuke Kumamoto
- Department of Surgery, Kitasato University School of Medicine, Sagamihara 252-0374, Japan; (T.K.); (Y.K.)
| | - Ho-Seong Han
- Seoul National University College of Medicine, Bundang Hospital, Seongnam-si 13620, Korea; (H.-S.H.); (E.E.)
| | - Ela Ekmekcigil
- Seoul National University College of Medicine, Bundang Hospital, Seongnam-si 13620, Korea; (H.-S.H.); (E.E.)
| | | | - David Fuks
- Department of Digestive Diseases, Institute Mutualiste Montsouris, University of Paris Descartes, 75014 Paris, France; (D.F.); (B.G.)
| | - Brice Gayet
- Department of Digestive Diseases, Institute Mutualiste Montsouris, University of Paris Descartes, 75014 Paris, France; (D.F.); (B.G.)
| | - Joseph F. Buell
- Tulane Transplant Abdominal Institute, Tulane University, New Orleans, LA 70112, USA;
| | - Ruben Ciria
- Unit of Hepatobiliary Surgery and Liver Transplantation, University Hospital Reina Sofia, 30003 Murcia, Spain; (R.C.); (J.B.)
| | - Javier Briceno
- Unit of Hepatobiliary Surgery and Liver Transplantation, University Hospital Reina Sofia, 30003 Murcia, Spain; (R.C.); (J.B.)
| | - Nicholas O’Rourke
- Department of General Surgery and HPB Surgery, Royal Brisbane Hospital, The University of Queensland, St Lucia, QLD 4072, Australia; (N.O.); (J.L.)
| | - Joel Lewin
- Department of General Surgery and HPB Surgery, Royal Brisbane Hospital, The University of Queensland, St Lucia, QLD 4072, Australia; (N.O.); (J.L.)
| | - Bjorn Edwin
- Department of Hepatopancreatobiliary Surgery, Oslo University Hospital-Rikshospitalet, 0372 Oslo, Norway;
| | - Masahiro Shinoda
- Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan; (M.S.); (Y.A.)
| | - Yuta Abe
- Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan; (M.S.); (Y.A.)
| | - Mohammed Abu Hilal
- Istituto Ospedaliero—Fondazione Poliambulanza, 25124 Brescia, BS, Italy;
- University Hospital Southampton, Hampshire SO16 6YD, UK;
| | - Mohammad Alzoubi
- University Hospital Southampton, Hampshire SO16 6YD, UK;
- General Surgery Department, The University of Jordan, Amman 11972, Jordan
| | - Minoru Tanabe
- Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo 113-8510, Japan; (T.O.); (M.T.)
| | - Go Wakabayashi
- Department of Surgery, Ageo Central General Hospital, Ageo 362-8588, Japan;
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New strategy for Liver Imaging Reporting and Data System category M to improve diagnostic performance of MRI for hepatocellular carcinoma ≤ 3.0 cm. Abdom Radiol (NY) 2022; 47:2289-2298. [PMID: 35523888 DOI: 10.1007/s00261-022-03538-w] [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: 11/18/2021] [Revised: 02/27/2022] [Accepted: 02/28/2022] [Indexed: 11/01/2022]
Abstract
PURPOSE We aimed to determine a new strategy for Liver Imaging Reporting and Data System category M (LR-M) criteria to improve the diagnosis of HCC ≤ 3.0 cm on magnetic resonance imaging (MRI). METHODS A total of 463 pathologically confirmed hepatic observations ≤ 3.0 cm (375 HCCs, 32 other malignancies, 56 benignities) in 384 patients at risk of HCC who underwent gadoxetate-enhanced MRI were retrospectively analyzed. Two radiologists evaluated the presence of major, ancillary, and LR-M features according to LI-RADS v2018. Of the ten LR-M features, those significantly associated with non-HCC malignancy were identified using multivariable logistic regression analysis, and new LR-M criteria for improving the diagnosis of HCC were investigated. Generalized estimating equations were used to compare sensitivity and specificity of LR-5 for diagnosing HCC using the new LR-M criteria with values calculated using the original LR-M criteria. p < 0.05 was considered to indicate a significant difference. RESULTS Of ten LR-M features, rim arterial-phase hyperenhancement, delayed central enhancement, targetoid restriction, and targetoid transitional-phase/hepatobiliary-phase appearance were independently significantly associated with non-HCC malignancy (adjusted odds ratio ≥ 6.2; p ≤ 0.02). Using the new LR-M criteria (two or more of these significant features), the sensitivity of LR-5 for diagnosing HCC was higher than that with the original LR-M criteria (69% [95% confidence interval 64-73%] vs. 65% [61-70%], p = 0.002), whereas the specificity was similar (90% [82-95%] vs. 92% [83-96%], p = 0.28). CONCLUSION The new LR-M criteria (two or more significant features) can improve the sensitivity of LR-5 for diagnosing HCC ≤ 3.0 cm, without compromising specificity.
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Asrani SK, Ghabril MS, Kuo A, Merriman RB, Morgan T, Parikh ND, Ovchinsky N, Kanwal F, Volk ML, Ho C, Serper M, Mehta S, Agopian V, Cabrera R, Chernyak V, El-Serag HB, Heimbach J, Ioannou GN, Kaplan D, Marrero J, Mehta N, Singal A, Salem R, Taddei T, Walling AM, Tapper EB. Quality measures in HCC care by the Practice Metrics Committee of the American Association for the Study of Liver Diseases. Hepatology 2022; 75:1289-1299. [PMID: 34778999 DOI: 10.1002/hep.32240] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Accepted: 09/29/2021] [Indexed: 12/14/2022]
Abstract
The burden of HCC is substantial. To address gaps in HCC care, the American Association for the Study of Liver Diseases (AASLD) Practice Metrics Committee (PMC) aimed to develop a standard set of process-based measures and patient-reported outcomes (PROs) along the HCC care continuum. We identified candidate process and outcomes measures for HCC care based on structured literature review. A 13-member panel with content expertise across the HCC care continuum evaluated candidate measures on importance and performance gap using a modified Delphi approach (two rounds of rating) to define the final set of measures. Candidate PROs based on a structured scoping review were ranked by 74 patients with HCC across 7 diverse institutions. Out of 135 measures, 29 measures made the final set. These covered surveillance (6 measures), diagnosis (6 measures), staging (2 measures), treatment (10 measures), and outcomes (5 measures). Examples included the use of ultrasound (± alpha-fetoprotein [AFP]) every 6 months, need for surveillance in high-risk populations, diagnostic testing for patients with a new AFP elevation, multidisciplinary liver tumor board (MLTB) review of Liver Imaging-Reporting and Data System 4 lesions, standard evaluation at diagnosis, treatment recommendations based on Barcelona Clinic Liver Cancer staging, MLTB discussion of treatment options, appropriate referral for evaluation of liver transplantation candidacy, and role of palliative therapy. PROs include those related to pain, anxiety, fear of treatment, and uncertainty about the best individual treatment and the future. The AASLD PMC has developed a set of explicit quality measures in HCC care to help bridge the gap between guideline recommendations and measurable processes and outcomes. Measurement and subsequent implementation of these metrics could be a central step in the improvement of patient care and outcomes in this high-risk population.
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Affiliation(s)
| | - Marwan S Ghabril
- 12250Division of GastroenterologyDepartment of MedicineIndiana University School of MedicineIndianapolisIndianaUSA
| | - Alexander Kuo
- Division of GastroenterologyCedars-Sinai Medical CenterUniversity of California Los AngelesLos AngelesCaliforniaUSA
| | - Raphael B Merriman
- Division of General and Transplant HepatologyCalifornia Pacific Medical Center and Research InstituteSan FranciscoCaliforniaUSA
| | - Timothy Morgan
- Medicine and Research ServicesVA Long Beach Healthcare SystemLong BeachCaliforniaUSA
| | - Neehar D Parikh
- Division of Gastroenterology and HepatologyUniversity of MichiganAnn ArborMichiganUSA
| | - Nadia Ovchinsky
- Division of Pediatric GastroenterologyChildren's Hospital at MontefioreBronxNew YorkUSA
| | - Fasiha Kanwal
- Section of Gastroenterology and HepatologyDepartment of MedicineBaylor College of MedicineHoustonTexasUSA
- Center for Innovations in Quality, Effectiveness and SafetyMichael E. DeBakey Veterans Affairs Medical CenterHoustonTexasUSA
- Section of Health Services ResearchDepartment of MedicineBaylor College of MedicineHoustonTexasUSA
| | - Michael L Volk
- 4608Division of Gastroenterology and Transplantation InstituteLoma Linda UniversityLoma LindaCaliforniaUSA
| | - Chanda Ho
- Department of TransplantationCalifornia Pacific Medical CenterSan FranciscoCaliforniaUSA
| | - Marina Serper
- Division of Gastroenterology and HepatologyUniversity of Pennsylvania Perelman School of MedicinePhiladelphiaPennsylvaniaUSA
- Leonard Davis Institute of Health EconomicsPhiladelphiaPennsylvaniaUSA
| | | | - Vatche Agopian
- Division of Liver and Pancreas TransplantationDepartment of SurgeryDavid Geffen School of Medicine at University of CaliforniaLos AngelesCaliforniaUSA
| | - Roniel Cabrera
- Department of MedicineDivision of Gastroenterology, Hepatology and NutritionUniversity of FloridaGainesvilleFloridaUSA
| | | | | | - Julie Heimbach
- Division of Transplant SurgeryWilliam J. von Liebig Transplant CenterMayo ClinicRochesterMinnesotaUSA
| | - George N Ioannou
- Division of GastroenterologyDepartment of MedicineVeterans Affairs Puget Sound Health Care System and University of WashingtonSeattleWashingtonUSA
| | - David Kaplan
- Division of Gastroenterology and HepatologyPerelman University of Pennsylvania School of MedicinePhiladelphiaPennsylvaniaUSA
| | - Jorge Marrero
- Digestive and Liver Diseases DivisionDepartment of Internal MedicineUT Southwestern Medical CenterDallasTexasUSA
| | - Neil Mehta
- Division of GastroenterologyUniversity of California San FranciscoSan FranciscoCaliforniaUSA
| | - Amit Singal
- Division of Digestive and Liver DiseasesUT Southwestern Medical CenterDallasTexasUSA
| | - Riad Salem
- Division of Interventional RadiologyDepartment of RadiologyNorthwestern UniversityChicagoIllinoisUSA
| | - Tamar Taddei
- Section of Digestive DiseasesYale School of MedicineNew HavenConnecticutUSA
- VA Connecticut Healthcare SystemWest HavenConnecticutUSA
| | - Anne M Walling
- VA Greater Los Angeles Healthcare SystemLos AngelesCaliforniaUSA
- Division of General Internal Medicine and Health Services ResearchUniversity of CaliforniaLos AngelesCaliforniaUSA
| | - Elliot B Tapper
- Division of Gastroenterology and HepatologyDepartment of Internal MedicineUniversity of MichiganAnn ArborMichiganUSA
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Wang L, Wang L, Xu P, Liu C, Wang S, Luo X, Li M, Liu J, Zhao Z, Lai W, Luo F, Yan J. pH-Responsive Liposomes Loaded with Targeting Procoagulant Proteins as Potential Embolic Agents for Solid Tumor-Targeted Therapy. Mol Pharm 2022; 19:1356-1367. [PMID: 35420039 DOI: 10.1021/acs.molpharmaceut.1c00912] [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] [Indexed: 11/29/2022]
Abstract
Selectively inducing tumor thrombosis and subsequent necrosis is a novel and promising antitumor strategy. We have previously designed a targeting procoagulant protein, called tTF-EG3287, which is a fusion of a truncated tissue factor (tTF) with EG3287, a short peptide against the neuropilin-1 (NRP1) binding site of vascular endothelial growth factor-A 165 (VEGF-A 165). However, off-target effects and high-dose requirements limit the further use of tTF-EG3287 in antitumor therapy. Therefore, we encapsulated tTF-EG3287 into poly(2-ethyl-2-oxazoline)-distearoyl phosphatidyl ethanolamine (PEOz-DSPE)-modified liposomes to construct pH-responsive liposomes as a novel vascular embolization agent, called tTF-EG3287@Liposomes. The liposomes had an average particle size of about 100 nm and showed considerable drug-loading capacity, encapsulation efficiency, and biocompatibility. Under the stimulation of acidic microenvironments (pH 6.5), the lipid membrane of tTF-EG3287@Liposomes collapsed, and the cumulative drug release rate within 72 h was 83 ± 1.26%. When administered to a mouse model of hepatocellular carcinoma (HCC), tTF-EG3287@Liposomes showed prolonged retention and enhanced accumulation in the tumor as well as a superior antitumor effec, compared with tTF-EG3287. This study demonstrates the potential of tTF-EG3287@Liposomes as a novel embolic agent for solid tumors and provides a new strategy for tumor-targeted infarction therapy.
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Affiliation(s)
- Li Wang
- Cancer Research Center, Medical College, Xiamen University, Xiamen 361102, China
| | - Lanlan Wang
- Cancer Research Center, Medical College, Xiamen University, Xiamen 361102, China
| | - Peilan Xu
- Cancer Research Center, Medical College, Xiamen University, Xiamen 361102, China
| | - Cong Liu
- Cancer Research Center, Medical College, Xiamen University, Xiamen 361102, China
| | - Shengyu Wang
- Cancer Research Center, Medical College, Xiamen University, Xiamen 361102, China
| | - Xian Luo
- Cancer Research Center, Medical College, Xiamen University, Xiamen 361102, China
| | - Mengqi Li
- Cancer Research Center, Medical College, Xiamen University, Xiamen 361102, China
| | - Jiajing Liu
- Cancer Research Center, Medical College, Xiamen University, Xiamen 361102, China
| | - Zhiyu Zhao
- Cancer Research Center, Medical College, Xiamen University, Xiamen 361102, China
| | - Weisong Lai
- Cancer Research Center, Medical College, Xiamen University, Xiamen 361102, China
| | - Fanghong Luo
- Cancer Research Center, Medical College, Xiamen University, Xiamen 361102, China
| | - Jianghua Yan
- Cancer Research Center, Medical College, Xiamen University, Xiamen 361102, China
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45
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Löffler MW, Gori S, Izzo F, Mayer-Mokler A, Ascierto P, Königsrainer A, Ma YT, Sangro B, Francque S, Vonghia L, Inno A, Avallone A, Ludwig J, Alcoba DD, Flohr C, Aslan K, Mendrzyk R, Schuster H, Borrelli M, Valmori D, Chaumette T, Heidenreich R, Gouttefangeas C, Forlani G, Tagliamonte M, Fusco C, Penta R, Iñarrairaegui M, Gnad-Vogt U, Reinhardt C, Weinschenk T, Accolla RS, Singh H, Rammensee HG, Buonaguro L. Phase I/II multicenter trial of a novel therapeutic cancer vaccine, HepaVac-101, for hepatocellular carcinoma. Clin Cancer Res 2022; 28:2555-2566. [PMID: 35421231 DOI: 10.1158/1078-0432.ccr-21-4424] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 02/25/2022] [Accepted: 04/12/2022] [Indexed: 11/16/2022]
Abstract
PURPOSE Immunotherapy for hepatocellular carcinoma (HCC) shows considerable promise in improving clinical outcomes. HepaVac-101 represents a single-arm, first-in-man Phase I/II multicenter cancer vaccine trial for HCC (NCT03203005). It combines multi-peptide antigens (IMA970A) with the TLR7/8/RIG I agonist CV8102. IMA970A includes 5 HLA-A*24 and 7 HLA-A*02 as well as 4 HLA-DR restricted peptides selected after mass spectrometric identification in human HCC tissues or cell lines. CV8102 is an RNA-based immunostimulator inducing a balanced Th1/Th2 immune response. EXPERIMENTAL DESIGN 82 patients with very early to intermediate stage HCCs were enrolled and screened for suitable HLA haplotypes and 22 put on study treatment. This consisted in a single infusion of low-dose cyclophosphamide followed by 9 intradermal coadministrations of IMA970A and CV8102. Only patients with no disease relapse after standard of care treatments were vaccinated. Primary endpoints of HepaVac-101 clinical trial were safety, tolerability and antigen-specific T-cell responses. Secondary or exploratory endpoints included additional immunological parameters and survival endpoints. RESULTS The vaccination showed a good safety profile. Transient mild-to-moderate injection-site reactions were the most frequent IMA970A/CV8102-related side effects. Immune responses against {greater than or equal to}1 vaccinated HLA class I tumor-associated peptide (TAA) and {greater than or equal to}1 vaccinated HLA class II TAA were respectively induced in 37% and 53% of the vaccinees. CONCLUSION Immunotherapy may provide a great improvement in treatment options for HCC. HepaVac-101 is a first-in-man clinical vaccine trial with multiple novel HLA class I- and class II-restricted TAAs against HCC. The results are initial evidence for safety and immunogenicity of the vaccine. Further clinical evaluations are warranted.
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Affiliation(s)
| | - Stefania Gori
- IRCCS Sacro Cuore Don Calabria, Negrar di Valpolicella, Italy
| | - Francesco Izzo
- Istituto Nazionale per lo Studio e la Cura dei Tumori, Napoli, Italy
| | | | - Paolo Ascierto
- Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Napoli, Italy
| | | | - Yuk Ting Ma
- University of Birmingham, Birmingham, United Kingdom
| | - Bruno Sangro
- Clínica Universidad de Navarra and CIBEREHD, Pamplona, Navarra, Spain
| | | | | | - Alessandro Inno
- IRCCS Ospedale Sacro Cuore Don Calabria, Negrar di Valpolicella, Verona, Italy
| | | | - Jörg Ludwig
- Immatics Biotechnologies (Germany), Tuebingen, Germany
| | | | | | | | | | | | - Marco Borrelli
- ISTITUTO NAZIONALE TUMORI IRCCS - Fondazione Pascale, napoli, napoli, Italy
| | - Danila Valmori
- Institut National de la Sante et de la Recherche Medicale, Nantes-Saint Herblain, France
| | | | | | | | | | | | | | - Roberta Penta
- AORN Santobono-Pausilipon Children's Hospital, Naples, Italy
| | | | | | | | | | | | | | | | - Luigi Buonaguro
- ISTITUTO NAZIONALE TUMORI IRCCS - Fondazione Pascale, NAPLES, Italy
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46
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Ramani NS, Green LK. Metastatic hepatocellular carcinoma to the bone diagnosed by fine needle aspiration in a veteran population. Diagn Cytopathol 2022; 50:335-340. [PMID: 35403368 DOI: 10.1002/dc.24961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 03/31/2022] [Accepted: 04/01/2022] [Indexed: 11/06/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and it may present initially with extrahepatic spread in 5%-15% cases. It most commonly metastasizes to lungs, lymph nodes and adrenal glands. Skeletal metastases from HCC are uncommon and carry a very poor prognosis. METHODS We retrospectively reviewed all fine needle aspiration (FNA) specimens of metastatic HCC at our institution from January 1994 to March 2021 using the SNOMED search computer option. Relevant clinical information was obtained from the review of patient's electronic medical records. RESULTS There were 36 FNAs of metastatic HCC over a period of 27 years. Six patients (16.7%) were found to have skeletal metastases. All six patients were males with a median age of 59 years (54-71 years) and their lesions were osteolytic. The most common site of metastases was vertebra (3/50%). Most patients (67%) had bone metastases as an initial presentation, without prior history of HCC. The mean survival after the diagnosis of skeletal metastases was only 8 months. CONCLUSION Detection of extrahepatic HCC to bone is important to avoid any unwanted surgical intervention. In our patient population, the most common site of skeletal metastases from HCC was vertebra, therefore in FNAs of vertebral lytic masses, metastatic HCC should be considered. On FNA, extrahepatic metastases of HCC can mimic other poorly differentiated tumors. They behave in an aggressive fashion, resulting in a grim prognosis. Cytological substrates can be used for future molecular testing, if needed.
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Affiliation(s)
- Nisha S Ramani
- Department of Pathology, Michael E. DeBakey VA Medical Center, Houston, Texas, USA.,Department of Pathology, Baylor College of Medicine, Houston, Texas, USA
| | - Linda K Green
- Department of Pathology, Michael E. DeBakey VA Medical Center, Houston, Texas, USA.,Department of Pathology, Baylor College of Medicine, Houston, Texas, USA
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47
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Selective internal radiation therapy in older patients with hepatocellular carcinoma: a retrospective analysis. Eur J Gastroenterol Hepatol 2022; 34:417-421. [PMID: 34284416 DOI: 10.1097/meg.0000000000002255] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
BACKGROUND Selective internal radiation therapy (SIRT) is applied to hepatocellular carcinoma (HCC), a disease with increased incidence in the elderly. However, SIRT has rarely been specifically studied in elderly population. The aim of this study was to investigate efficacy and safety of SIRT in elderly HCC patients. METHODS We studied retrospectively data from patients treated with SIRT for HCC. Clinical and laboratory data were retrieved. We used 70-years old as threshold between younger and elderly populations, to compare outcomes. RESULTS A total of 222 patients treated with SIRT for HCC were studied, of which 134 patients were younger and 88 older. Median overall survival (OS) was not significantly different between younger and elderly group: 15.6 months (95% CI, 11.7-19.5) and 14.8 months (95% CI, 9.4-20.3) (P = 0.86). Age was not associated with OS in multivariable analysis, with a Hazard ratio of 1.09 (95% CI, 0.82-1.45, P = 0.55). Results of progression-free survival and responses were also similar in both groups. Toxicities were similar between the two groups, including the occurrence of radioembolization-induced liver disease (11.5 vs. 11.4%, P = 0.97). CONCLUSION SIRT appears to be a well-tolerated treatment with the same efficacy in elderly compared to younger patients in HCC. Our study is the first to study its impact with glass microspheres. This warrants confirmation in large prospective studies.
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Ong DY, Lee ZY, Pua U. Impact of waiting time on hepatocellular carcinoma progression in patients undergoing curative tumour ablation. Quant Imaging Med Surg 2022; 12:1499-1504. [PMID: 35111642 DOI: 10.21037/qims-20-1411] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Accepted: 09/30/2021] [Indexed: 11/06/2022]
Abstract
BACKGROUND A feared consequence to delay in oncological treatment includes disease progression. This study aims to evaluate the relationship between waiting time for ablative therapy in patients with hepatocellular carcinoma (HCC), and the outcomes of local tumour progression, or new HCC foci. METHODS Between January 2011 to July 2017, 215 patients with HCC underwent ablative (microwave and radiofrequency) procedures. Demographic information, and duration between diagnosis on imaging and ablative procedure were recorded. Follow-up imaging data were analysed to assess for development of either new HCC, or local tumour progression. The median waiting time to ablative therapy was 42 days, hence, patients were separated into two groups: wait time <42 days versus wait time ≥42 days. Simple cox regression was conducted to explore the association between wait time and the clinical outcomes of new HCC or local tumour progression. Survival analyses for outcomes of new HCC or local tumour progression were also compared between the two groups using log-rank test. All the statistical analyses were two sided and P value of less than 0.05 was considered as statistically significant. RESULTS Hazard ratio for local tumour progression was 1.002 (0.996, 1.007) P=0.579, while hazard ratio for new HCC foci was 1.002 (0.998, 1.005) P=0.373. There was no statistically significant difference when comparing the two groups (wait time <42 versus ≥42 days) for survival estimates for local tumour progression P=0.346, and for new HCC P=0.680. CONCLUSIONS This study demonstrates that delay in HCC ablative therapy is not associated with significant risk of local tumour progression, or new HCC foci.
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Affiliation(s)
- Daniel Yuxuan Ong
- Department of Diagnostic Radiology, Tan Tock Seng Hospital, Singapore, Singapore
| | - Zhong Yun Lee
- Department of Diagnostic Radiology, Tan Tock Seng Hospital, Singapore, Singapore
| | - Uei Pua
- Department of Diagnostic Radiology, Tan Tock Seng Hospital, Singapore, Singapore
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Duc VT, Chien PC, Huyen LDM, Chau TLM, Chanh NDT, Soan DTM, Huyen HC, Thanh HM, Hy LNG, Nam NH, Uyen MTT, Nhi LHH, Minh LHN. Deep Learning Model With Convolutional Neural Network for Detecting and Segmenting Hepatocellular Carcinoma in CT: A Preliminary Study. Cureus 2022; 14:e21347. [PMID: 35186603 PMCID: PMC8849436 DOI: 10.7759/cureus.21347] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/16/2022] [Indexed: 12/27/2022] Open
Abstract
Introduction Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. Early detection and accurate diagnosis of HCC play an important role in patient management. This study aimed to develop a convolutional neural network-based model to identify and segment HCC lesions utilizing dynamic contrast agent-enhanced computed tomography (CT). Methods This retrospective study used CT image sets of histopathology-confirmed hepatocellular carcinoma over three phases (arterial, venous, and delayed). The proposed convolutional neural network (CNN) segmentation method was based on the U-Net architecture and trained using the domain adaptation technique. The proposed method was evaluated using 115 liver masses of 110 patients (87 men and 23 women; mean age, 56.9 years ± 11.9 (SD); mean mass size, 6.0 cm ± 3.6). The sensitivity for identifying HCC of the model and Dice score for segmentation of liver masses between radiologists and the CNN model were calculated for the test set. Results The sensitivity for HCC identification of the model was 100%. The median Dice score for HCC segmenting between radiologists and the CNN model was 0.81 for the test set. Conclusion Deep learning with CNN had high performance in the identification and segmentation of HCC on dynamic CT.
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50
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Yim SY, Chun HS, Lee JS, Lim JH, Kim TH, Kim BK, Kim SU, Park JY, Ahn SH, Kim GM, Won JY, Seo YS, Kim YH, Um SH, Kim DY. Transarterial Radioembolization for Unresectable Hepatocellular Carcinoma: Real-Life Efficacy and Safety Analysis of Korean Patients. Cancers (Basel) 2022; 14:385. [PMID: 35053546 PMCID: PMC8774028 DOI: 10.3390/cancers14020385] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 01/05/2022] [Accepted: 01/10/2022] [Indexed: 12/29/2022] Open
Abstract
Transarterial radioembolization (TARE) has become widely used in the treatment of HCC, one of the most common causes of cancer mortality worldwide. Here we investigated the long-term clinical outcomes of patients with hepatocellular carcinoma (HCC) treated with TARE in a multi-medical center in Korea. A total of 149 patients treated with TARE from 2008-2014 were recruited. The pre-treatment HCC stage was classified according to the BCLC stage, of which C and D were defined as advanced HCC. Advanced HCC stage and Child-Turcotte-Pugh (CTP) score A were identified in 62 (42%) and 134 (90%) patients, respectively. Portal vein thrombosis (PVT) was identified in 58 patients (38.9%). The median time to progression (TTP) was 14 months, and the median overall survival (OS) and progression-free survival (PFS) were 18.6 and 8.9 months, respectively. The overall tumor response was 47%, and the disease control rate was 78%. OS and PFS differed significantly according to the presence of liver cirrhosis, extrahepatic metastasis, tumor response and curative treatment after TARE (all, p < 0.05). Multiple tumors and major PVT were other independent factors related to OS, while the des-gamma carboxy protein level predicted PFS (all, p < 0.05). Tumor size was an independent predictor of tumor response. TTP, OS and PFS all differed among BCLC stages. The serious adverse effect after TARE was clinically not significant. Therefore, TARE is safe and effective in treating early to advanced HCCs.
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Affiliation(s)
- Sun Young Yim
- Department of Internal Medicine, Korea University College of Medicine, Korea University Anam Hospital, Seoul 02841, Korea; (S.Y.Y.); (J.-H.L.); (T.H.K.); (Y.S.S.); (S.H.U.)
| | - Ho Soo Chun
- Ewha Womans Medical Center, Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul 03760, Korea;
| | - Jae Seung Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea; (J.S.L.); (B.K.K.); (S.U.K.); (J.Y.P.); (S.H.A.)
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul 03722, Korea
| | - Ji-Hwan Lim
- Department of Internal Medicine, Korea University College of Medicine, Korea University Anam Hospital, Seoul 02841, Korea; (S.Y.Y.); (J.-H.L.); (T.H.K.); (Y.S.S.); (S.H.U.)
| | - Tae Hyung Kim
- Department of Internal Medicine, Korea University College of Medicine, Korea University Anam Hospital, Seoul 02841, Korea; (S.Y.Y.); (J.-H.L.); (T.H.K.); (Y.S.S.); (S.H.U.)
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea; (J.S.L.); (B.K.K.); (S.U.K.); (J.Y.P.); (S.H.A.)
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul 03722, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea; (J.S.L.); (B.K.K.); (S.U.K.); (J.Y.P.); (S.H.A.)
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul 03722, Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea; (J.S.L.); (B.K.K.); (S.U.K.); (J.Y.P.); (S.H.A.)
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul 03722, Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea; (J.S.L.); (B.K.K.); (S.U.K.); (J.Y.P.); (S.H.A.)
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul 03722, Korea
| | - Gyoung Min Kim
- Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University School of Medicine, Seoul 03722, Korea; (G.M.K.); (J.Y.W.)
| | - Jong Yun Won
- Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University School of Medicine, Seoul 03722, Korea; (G.M.K.); (J.Y.W.)
| | - Yeon Seok Seo
- Department of Internal Medicine, Korea University College of Medicine, Korea University Anam Hospital, Seoul 02841, Korea; (S.Y.Y.); (J.-H.L.); (T.H.K.); (Y.S.S.); (S.H.U.)
| | - Yun Hwan Kim
- Department of Radiology, Korea University Anam Hospital, Seoul 02841, Korea;
| | - Soon Ho Um
- Department of Internal Medicine, Korea University College of Medicine, Korea University Anam Hospital, Seoul 02841, Korea; (S.Y.Y.); (J.-H.L.); (T.H.K.); (Y.S.S.); (S.H.U.)
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea; (J.S.L.); (B.K.K.); (S.U.K.); (J.Y.P.); (S.H.A.)
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul 03722, Korea
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