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Barteselli C, Mazza S, Ravetta V, Viera FT, Veronese L, Frigerio C, Gori G, Bergamaschi G, Sgarlata C, Facciorusso A, Maestri M, Di Sabatino A, Anderloni A. Ultrasound Patterns of Hepatocellular Carcinoma and Their Prognostic Impact: A Retrospective Study. Cancers (Basel) 2023; 15:5396. [PMID: 38001656 PMCID: PMC10670191 DOI: 10.3390/cancers15225396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Revised: 11/07/2023] [Accepted: 11/10/2023] [Indexed: 11/26/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death. Abdominal ultrasound (US) is by far the most widely used first-level exam for the diagnosis of HCC. We aimed to assess whether different ultrasound patterns were related to tumor prognosis. METHODS We retrospectively reviewed all patients with a new diagnosis of HCC (single nodule) and undergoing radiofrequency thermal ablation (RFTA) at our clinic between January 2009 and December 2021. Patients were classified according to four HCC ultrasound patterns: 1A, single capsulated nodule; 1B, well capsulated intra-node nodule; 1C, cluster consisting of capsulated nodules; and 2, non-capsulated nodule. RESULTS 149 patients were analysed; median follow-up time was 43 months. US patterns 1A (32.9%) and 1B (61.1%) were the most commonly seen. Median overall survival (OS) and recurrence-free survival (RFS) from RFTA were 54 months (95% CI, 42-66) and 22 months (95% CI, 12-32), respectively. Pattern 1A showed the best OS. Compared to pattern 1A, 1B was independently associated with worse OS (51 months (95% CI, 34-68) vs. 46 months (95% CI, 18-62)) and RFS (34 months (95% CI, 27-41) vs. 18 months (95% CI, 12-24)). Patterns 1C and 2 were associated with worse RFS compared to 1A, while no difference was seen for OS. Among baseline clinical variables, pattern 1B exhibited higher histological grade (p = 0.048) and tumor dimension (p = 0.034) compared to pattern 1A. CONCLUSIONS Our findings demonstrate that different US patterns correlate with different survival outcomes and tumor behavior in patients with HCC. Prospective studies are needed to confirm these results.
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Affiliation(s)
- Chiara Barteselli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Stefano Mazza
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Valentina Ravetta
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Francesca Torello Viera
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Letizia Veronese
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Chiara Frigerio
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Giulia Gori
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, 27100 Pavia, Italy
| | - Gaetano Bergamaschi
- First Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Carmelo Sgarlata
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Antonio Facciorusso
- Gastroenterology Unit, Department of Medical and Surgical Sciences, University of Foggia, Viale Luigi Pinto 1, 71122 Foggia, Italy
| | - Marcello Maestri
- General Surgery I, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy;
| | - Antonio Di Sabatino
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, 27100 Pavia, Italy
- First Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Andrea Anderloni
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
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Allaire M, Bruix J, Korenjak M, Manes S, Maravic Z, Reeves H, Salem R, Sangro B, Sherman M. What to do about hepatocellular carcinoma: Recommendations for health authorities from the International Liver Cancer Association. JHEP Rep 2022; 4:100578. [PMID: 36352896 PMCID: PMC9638834 DOI: 10.1016/j.jhepr.2022.100578] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2022] [Revised: 08/26/2022] [Accepted: 08/29/2022] [Indexed: 12/02/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a major public health problem worldwide for which the incidence and mortality are similar, pointing to the lack of effective treatment options. Knowing the different issues involved in the management of HCC, from risk factors to screening and management, is essential to improve the prognosis and quality of life of affected individuals. This document summarises the current state of knowledge and the unmet needs for all the different stakeholders in the care of liver cancer, meaning patients, relatives, physicians, regulatory agencies and health authorities so that optimal care can be delivered to patients. The document was commissioned by the International Liver Cancer Association and was reviewed by senior members, including two ex-presidents of the Association. This document lays out the recommended approaches to the societal management of HCC based on the economic status of a given region.
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Key Words
- AASLD, American Association for the Study of Liver Disease
- AFP, alpha-fetoprotein
- ALT, alanine aminotransferase
- APRI, aspartate aminotransferase-to-platelet ratio index
- Alcohol consumption
- BCLC, Barcelona clinic liver cancer
- DCP, des-gammacarboxy prothrombin
- DEB-TACE, TACE with drug-eluting beads
- EASL, European Association for the study of the Liver
- EBRT, external beam radiation therapy
- ELF, enhanced liver fibrosis
- GGT, gamma-glutamyltransferase
- HCC, hepatocellular carcinoma
- Hepatocellular carcinoma
- Hepatocellular carcinoma surveillance
- Hepatocellular carcinoma treatment
- Li-RADS, Liver Imaging Reporting and Data System
- NAFLD, non-alcoholic fatty liver disease
- Obesity
- RFA, radiofrequency ablation
- TACE, transarterial chemoembolisation
- TARE, transarterial radioembolisation
- TKI, tyrosine kinase inhibitor
- Viral hepatitis
- cTACE, conventional TACE
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Affiliation(s)
- Manon Allaire
- AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service d’Hépato-gastroentérologie, Paris, France
| | - Jordi Bruix
- University Hospital Clinic IDIBAPS, Barcelona, Spain
| | - Marko Korenjak
- European Liver Patients' Association (ELPA), Brussels, Belgium
| | - Sarah Manes
- Global Liver Institute Washington District of Columbia, USA
| | | | - Helen Reeves
- The Newcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK
| | - Riad Salem
- Department of Radiology, Section of Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Chicago, IL 60611, USA
| | - Bruno Sangro
- Liver Unit and HPB Oncology Area, Clinica Universidad de Navarra and CIBEREHD, Pamplona, Spain
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Ah Hwang J, Wook Kang T, Hye Min J, Kon Kim Y, Hyun Kim S, Hyun Sinn D, Kim K. Association between intensity of imaging surveillance and clinical outcomes in patients with hepatocellular carcinoma. Eur J Radiol 2022; 151:110328. [DOI: 10.1016/j.ejrad.2022.110328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 04/10/2022] [Accepted: 04/16/2022] [Indexed: 11/15/2022]
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Adeniji N, Dhanasekaran R. Current and Emerging Tools for Hepatocellular Carcinoma Surveillance. Hepatol Commun 2021; 5:1972-1986. [PMID: 34533885 PMCID: PMC8631096 DOI: 10.1002/hep4.1823] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Revised: 08/04/2021] [Accepted: 08/30/2021] [Indexed: 12/13/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer‐related mortality worldwide. Early detection of HCC enables patients to avail curative therapies that can improve patient survival. Current international guidelines advocate for the enrollment of patients at high risk for HCC, like those with cirrhosis, in surveillance programs that perform ultrasound every 6 months. In recent years, many studies have further characterized the utility of established screening strategies and have introduced new promising tools for HCC surveillance. In this review, we provide an overview of the most promising new imaging modalities and biomarkers for the detection of HCC. We discuss the role of imaging tools like ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) in the early detection of HCC, and describe recent innovations which can potentially enhance their applicability, including contrast enhanced ultrasound, low‐dose CT scans, and abbreviated MRI. Next, we outline the data supporting the use of three circulating biomarkers (i.e., alpha‐fetoprotein [AFP], AFP lens culinaris agglutinin‐reactive fraction, and des‐gamma‐carboxy prothrombin) in HCC surveillance, and expand on multiple emerging liquid biopsy biomarkers, including methylated cell‐free DNA (cfDNA), cfDNA mutations, extracellular vesicles, and circulating tumor cells. These promising new imaging modalities and biomarkers have the potential to improve early detection, and thus improve survival, in patients with HCC.
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Affiliation(s)
- Nia Adeniji
- Stanford School of Medicine, Stanford, CA, USA
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Kuzuu K, Misawa N, Ashikari K, Kessoku T, Kato S, Hosono K, Yoneda M, Nonaka T, Matsushima S, Komatsu T, Nakajima A, Higurashi T. Gastrointestinal Cancer Stage at Diagnosis Before and During the COVID-19 Pandemic in Japan. JAMA Netw Open 2021; 4:e2126334. [PMID: 34546368 PMCID: PMC8456386 DOI: 10.1001/jamanetworkopen.2021.26334] [Citation(s) in RCA: 85] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
IMPORTANCE The COVID-19 pandemic has delayed medical consultations, possibly leading to the diagnosis of gastrointestinal cancer at advanced stages. OBJECTIVE To evaluate stage at diagnosis among patients with gastrointestinal cancer in Japan before and during the COVID-19 pandemic. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study included patients in a hospital-based cancer registry who were diagnosed with gastrointestinal cancer (ie, esophageal, gastric, colorectal, pancreatic, liver, and biliary tract cancers) between January 2016 and December 2020 at 2 tertiary Japanese hospitals. EXPOSURES The pre-COVID-19 period was defined as January 2017 to February 2020, and the COVID-19 period was defined as March 2020 to December 2020. MAIN OUTCOME AND MEASURE Monthly numbers of patients with newly diagnosed cancer were aggregated, classified by stage, and compared. RESULTS The study evaluated 5167 patients, including 4218 patients (2825 [67.0%] men; mean [SD] age, 71.3 [10.9] years) in the pre-COVID-19 period and 949 patients (607 [64.0%] men; mean [SD] age, 71.8 [10.7] years) in the COVID-19 period. Comparing the pre-COVID-19 period with the COVID-19 period, significant decreases were observed in the mean (SD) number of patients with newly diagnosed gastric cancer (30.63 [6.62] patients/month vs 22.40 [5.85] patients/month; -26.87% change; P < .001) and colorectal cancer (41.61 [6.81] patients/month vs 36.00 [6.72] patients/month; -13.47% change; P = .03). Significant decreases were also observed in the mean (SD) number of cases of stage I gastric cancer (21.55 [5.66] cases/month vs 13.90 [5.99] cases/month; -35.51% change; P < .001), stage 0 colorectal cancer (10.58 [3.36] cases/month vs 7.10 [4.10] cases/month; -32.89% change; P = .008), and stage I colorectal cancer (10.16 [3.14] cases/month vs 6.70 [2.91] cases/month; -34.04% change; P = .003). No significant increases were observed for esophageal, gastric, pancreatic, liver, or biliary tract cancers. A significant decrease was observed in the mean (SD) number of cases per month of stage II colorectal cancer (7.42 [3.06] cases/month vs 4.80 [1.75] cases/month; -35.32% change; P = .01); a significant increase was observed for the mean (SD) number of cases per month of stage III colorectal cancer (7.18 [2.85] cases/month vs 12.10 [2.42] cases/month; 68.42% change; P < .001). CONCLUSIONS AND RELEVANCE In this cohort study of patients in a hospital-based cancer registry form Japan, significantly fewer patients were diagnosed with stage I gastric and colorectal cancers during the COVID-19 pandemic. Thus, the number of screening-detected cancers might have decreased, and colorectal cancer may have been diagnosed at more advanced stages.
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Affiliation(s)
- Kento Kuzuu
- Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Kanazawa-ku, Yokohama, Japan
| | - Noboru Misawa
- Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Kanazawa-ku, Yokohama, Japan
| | - Keiichi Ashikari
- Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Kanazawa-ku, Yokohama, Japan
| | - Takaomi Kessoku
- Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Kanazawa-ku, Yokohama, Japan
| | - Shingo Kato
- Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Kanazawa-ku, Yokohama, Japan
| | - Kunihiro Hosono
- Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Kanazawa-ku, Yokohama, Japan
| | - Masato Yoneda
- Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Kanazawa-ku, Yokohama, Japan
| | - Takashi Nonaka
- National Hospital Organization Yokohama Medical Center, Totuka-ku, Yokohama, Japan
| | - Shozo Matsushima
- National Hospital Organization Yokohama Medical Center, Totuka-ku, Yokohama, Japan
| | - Tatsuji Komatsu
- National Hospital Organization Yokohama Medical Center, Totuka-ku, Yokohama, Japan
| | - Atsushi Nakajima
- Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Kanazawa-ku, Yokohama, Japan
| | - Takuma Higurashi
- Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Kanazawa-ku, Yokohama, Japan
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Kim DY, Lee HW, Kang W, Kim GM, Won JY, Yun M. Metabolic activity assessment by 18 F-fluorodeoxyglucose positron emission tomography in patients with hepatocellular carcinoma undergoing Yttrium-90 transarterial radioembolization. J Gastroenterol Hepatol 2021; 36:1679-1684. [PMID: 33226706 DOI: 10.1111/jgh.15357] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Revised: 11/16/2020] [Accepted: 11/20/2020] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIM 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) is a functional image technique that can inform clinical decisions related to prognosis. We investigated the predictive role of 18 F-fluorodeoxyglucose PET/CT in patients with hepatocellular carcinoma (HCC) undergoing Yttrium-90 (Y-90) transarterial radioembolization (TARE). METHODS Patients with HCC treated with TARE and pre-TARE PET/CT scan were recruited between 2009 and 2013. Maximum standardized uptake value and tumor-to-non-tumorous liver uptake ratio (TLR) were measured. Tumor response was evaluated in accordance with modified RECIST criteria at 3-month intervals after Y-90 TARE. RESULTS Forty patients were included in the final analysis. The median age was 56.5 years and male predominant. Disease control in treated lesion was achieved in 82.5% (n = 33) of patients. During median 18.3-month follow-up, 27.5% (n = 11) of patients achieved progression-free survival. The cutoff of TLR, which was related to the median value, did not affect disease control rate, progression-free survival, and overall survival in patients with Y-90 TARE. CONCLUSIONS The TLR-based stratification may be a simple method, but our study did not show the usefulness in predicting prognosis in HCC patients with Y-90 TARE. Further studies with large number of patients are needed.
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Affiliation(s)
- Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Wonseok Kang
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Gyoung Min Kim
- Department of Radiology, Yonsei University College of Medicine, Seoul, South Korea
| | - Jong Yun Won
- Department of Radiology, Yonsei University College of Medicine, Seoul, South Korea
| | - Mijin Yun
- Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, South Korea
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de Freitas LBR, Longo L, Santos D, Grivicich I, Álvares-da-Silva MR. Hepatocellular carcinoma staging systems: Hong Kong liver cancer vs Barcelona clinic liver cancer in a Western population. World J Hepatol 2019; 11:678-688. [PMID: 31602288 PMCID: PMC6783400 DOI: 10.4254/wjh.v11.i9.678] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Revised: 07/08/2019] [Accepted: 08/20/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Despite being the world's most widely used system for staging and therapeutic guidance in hepatocellular carcinoma (HCC) treatment, the Barcelona clinic liver cancer (BCLC) system has limitations, especially regarding intermediate-grade (BCLC-B) tumors. The recently proposed Hong Kong liver cancer (HKLC) staging system appears useful but requires validation in Western populations. AIM To evaluate the agreement between BCLC and HKLC staging on the management of HCC in a Western population, estimating the overall patient survival. METHODS This was a retrospective study of HCC patients treated at a university hospital in southern Brazil between 2011 and 2016. Demographic, clinical, and laboratory data were collected. HCC staging was carried out according to the HKLC and BCLC systems to assess treatment agreement. Overall survival was estimated based on the treatment proposed in each system. RESULTS A total of 519 HCC patients were assessed. Of these, 178 (34.3%) were HKLC-I; 95 (18.3%) HKLC-IIA; 47 (9.1%) HKLC-IIB; 29 (5.6%) HKLC-IIIA; 30 (5.8%) HKLC-IIIB; 75 (14.4%) HKLC-IV; and 65 (12.5%) HKLC-V. According to the BCLC, 25 (4.9%) were BCLC-0; 246 (47.4%) BCLC-A; 107 (20.6%) BCLC-B; 76 (14.6%) BCLC-C; and 65 (12.5%) BCLC-D. The general agreement between the two systems was 80.0% - BCLC-0 and HKLC-I (100%); BCLC-A and HKLC-I/HKLC-II (96.7%); BCLC-B and HKLC-III (46.7%); BCLC-C and HKLC-IV (98.7%); BCLC-D and HKLC-V (41.5%). When sub-classifying BCLC-A, HKLC-IIB, HKLC-IIIA and HKLC-IIIB stages according to the up-to-7 in/out criterion, 13.4, 66.0, 100 and 36.7%, respectively, of the cases were classified as up-to-7 out. CONCLUSION In a Western population, the general agreement between the two systems was 80.0%, although in BCLC-B cases the agreement was low, suggesting that some individuals could be candidates for the curative treatment recommended by the HKLC. The authors suggest that the BCLC system should be routinely employed, although for BCLC-B cases it should be associated with the HKLC system.
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Affiliation(s)
- Laura Bainy Rodrigues de Freitas
- Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil
- Experimental Hepatology and Gastroenterology Laboratory, Center for Experimental Research, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS 90035-003, Brazil.
| | - Larisse Longo
- Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil
- Experimental Hepatology and Gastroenterology Laboratory, Center for Experimental Research, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS 90035-003, Brazil
| | - Deivid Santos
- School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil
| | - Ivana Grivicich
- Graduate Program in Health-Applied Cellular and Molecular Biology, ULBRA. Canoas, RS 92425-900, Brazil
| | - Mário Reis Álvares-da-Silva
- Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil
- Experimental Hepatology and Gastroenterology Laboratory, Center for Experimental Research, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS 90035-003, Brazil
- School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil
- Department of Gastroenterology, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS 90035-003, Brazil
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Huang X, Lee F, Teng Y, Lingam CB, Chen Z, Sun M, Song Z, Balachander GM, Leo HL, Guo Q, Shah I, Yu H. Sequential drug delivery for liver diseases. Adv Drug Deliv Rev 2019; 149-150:72-84. [PMID: 31734169 DOI: 10.1016/j.addr.2019.11.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2019] [Revised: 11/03/2019] [Accepted: 11/04/2019] [Indexed: 12/12/2022]
Abstract
The liver performs critical physiological functions such as metabolism/detoxification and blood homeostasis/biliary excretion. A high degree of blood access means that a drug's resident time in any cell is relatively short. This short drug exposure to cells requires local sequential delivery of multiple drugs for optimal efficacy, potency, and safety. The high metabolism and excretion of drugs also impose both technical challenges and opportunities to sequential drug delivery. This review provides an overview of the sequential events in liver regeneration and the related liver diseases. Using selected examples of liver cancer, hepatitis B viral infection, fatty liver diseases, and drug-induced liver injury, we highlight efforts made for the sequential delivery of small and macromolecular drugs through different biomaterials, cells, and microdevice-based delivery platforms that allow fast delivery kinetics and rapid drug switching. As this is a nascent area of development, we extrapolate and compare the results with other sequential drug delivery studies to suggest possible application in liver diseases, wherever appropriate.
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Affiliation(s)
- Xiaozhong Huang
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, MD9-04-11, 2 Medical Drive, Singapore 117593, Singapore; Institute of Bioengineering and Nanotechnology, A*STAR, The Nanos, #06-01, 31 Biopolis Way, Singapore 138669, Singapore
| | - Fan Lee
- Institute of Bioengineering and Nanotechnology, A*STAR, The Nanos, #06-01, 31 Biopolis Way, Singapore 138669, Singapore
| | - Yao Teng
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, MD9-04-11, 2 Medical Drive, Singapore 117593, Singapore; Institute of Bioengineering and Nanotechnology, A*STAR, The Nanos, #06-01, 31 Biopolis Way, Singapore 138669, Singapore
| | - Corey Bryen Lingam
- Department of Biomedical Engineering, National University of Singapore, Engineering Drive 3, Engineering Block 4, #04-08, Singapore 117583, Singapore
| | - Zijian Chen
- Department of Biomedical Engineering, National University of Singapore, Engineering Drive 3, Engineering Block 4, #04-08, Singapore 117583, Singapore; Department of Biomedical Engineering, Southern University of Science and Technology, 1088 Xueyuan Avenue, Shenzhen 518055, China
| | - Min Sun
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, MD9-04-11, 2 Medical Drive, Singapore 117593, Singapore
| | - Ziwei Song
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, MD9-04-11, 2 Medical Drive, Singapore 117593, Singapore; Institute of Bioengineering and Nanotechnology, A*STAR, The Nanos, #06-01, 31 Biopolis Way, Singapore 138669, Singapore
| | - Gowri M Balachander
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, MD9-04-11, 2 Medical Drive, Singapore 117593, Singapore
| | - Hwa Liang Leo
- Department of Biomedical Engineering, National University of Singapore, Engineering Drive 3, Engineering Block 4, #04-08, Singapore 117583, Singapore
| | - Qiongyu Guo
- Department of Biomedical Engineering, Southern University of Science and Technology, 1088 Xueyuan Avenue, Shenzhen 518055, China
| | - Imran Shah
- National Center for Computational Toxicology, United States Environmental Protection Agency, 4930 Old Page Rd., Durham, NC 27703, USA
| | - Hanry Yu
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, MD9-04-11, 2 Medical Drive, Singapore 117593, Singapore; Institute of Bioengineering and Nanotechnology, A*STAR, The Nanos, #06-01, 31 Biopolis Way, Singapore 138669, Singapore; Mechanobiology Institute, National University of Singapore, T-Lab, #05-01, 5A Engineering Drive 1, Singapore 117411, Singapore; CAMP, Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, Level 4 Enterprise Wing, Singapore 138602, Singapore; Gastroenterology Department, Southern Medical University, Guangzhou 510515, China.
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KASL clinical practice guidelines for management of chronic hepatitis B. Clin Mol Hepatol 2019; 25:93-159. [PMID: 31185710 PMCID: PMC6589848 DOI: 10.3350/cmh.2019.1002] [Citation(s) in RCA: 161] [Impact Index Per Article: 26.8] [Reference Citation Analysis] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Accepted: 03/25/2019] [Indexed: 02/06/2023] Open
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Ultrasound Screening and Surveillance in Hepatocellular Carcinoma. CURRENT RADIOLOGY REPORTS 2019. [DOI: 10.1007/s40134-019-0317-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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Toyoda H, Kumada T, Tada T, Mizuno K, Hiraoka A, Tsuji K, Ishikawa T, Akita T, Tanaka J. Impact of hepatocellular carcinoma aetiology and liver function on the benefit of surveillance: A novel approach for the adjustment of lead-time bias. Liver Int 2018; 38:2260-2268. [PMID: 29981527 DOI: 10.1111/liv.13927] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2018] [Revised: 05/26/2018] [Accepted: 07/02/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Surveillance reportedly has benefit on survival in patients with hepatocellular carcinoma (HCC), even after adjustment for lead-time bias. However, previous adjustment for lead-time bias using tumour volume doubling time (TVDT) had inherent problem in accuracy. We evaluated survival benefit of HCC surveillance with newly developed approach for adjusting lead-time bias. In addition, survival benefit was evaluated according to HCC aetiology and liver function. METHODS A total of 3899 patients were studied. TVDT was calculated in 255 study patients with ≥2 tumour size measurements before the diagnosis of HCC. Adjusted survival time was calculated based on TVDT, as the time from when HCC was assumed to be 5 mm to death or last follow-up. Survival rates based on this adjusted survival time were compared between the surveillance and nonsurveillance groups and categorized by HCC aetiology and liver function. RESULTS Calculated TVDT varied widely by study patients (median 141.9, IQR, 73.1-261.7 days). Survival rates based on adjusted survival time were higher in the surveillance group overall and by patients HCC aetiology. Whereas adjusted survival rates were higher in the surveillance group in Child-Pugh class A patients, the survival benefit was smaller in Child-Pugh class B patients and not statistically significant in Child-Pugh class C patients. CONCLUSIONS The survival benefit of surveillance for patients with HCC was demonstrated after adjustment for lead-time bias with novel, more accurate methodology. However, the benefits differed based on liver function and may vary largely by patients because of wide variation in TVDT.
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Affiliation(s)
- Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Takashi Kumada
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Toshifumi Tada
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Kazuyuki Mizuno
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Atsushi Hiraoka
- Department of Gastroenterology, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Kunihiko Tsuji
- Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan
| | - Toru Ishikawa
- Department of Hepatology, Saiseikai Niigata Daini Hospital, Niigata, Japan
| | - Tomoyuki Akita
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
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12
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Kim HY, Nam JY, Lee JH, Lee HA, Chang Y, Lee HY, Cho H, Lee DH, Cho YY, Cho EJ, Yu SJ, Lee JM, Kim YJ, Yoon JH. Intensity of surveillance for hepatocellular carcinoma determines survival in patients at risk in a hepatitis B-endemic area. Aliment Pharmacol Ther 2018; 47:1490-1501. [PMID: 29611209 DOI: 10.1111/apt.14623] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2018] [Revised: 02/01/2018] [Accepted: 03/01/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND Data are insufficient regarding the survival benefit of surveillance for hepatocellular carcinoma (HCC). AIM To investigate the effectiveness of HCC surveillance in a hepatitis B-endemic population. METHODS This retrospective cohort study included 1402 consecutive patients who were newly diagnosed with HCC between 2005 and 2012 at a single tertiary hospital in Korea. The primary endpoint was overall survival. Lead-time and length-time biases were adjusted (sojourn time = 140 days) and sensitivity analyses were performed. RESULTS The most common aetiology was hepatitis B (80.4%). Cirrhosis was present in 78.2%. HCC was diagnosed during regular surveillance (defined as mean interval of ultrasonography <8 months, n = 834), irregular surveillance (n = 104) or nonsurveillance (n = 464). Patients in the regular surveillance group were diagnosed at earlier stages ([very] early stage, 64.4%) than the irregular surveillance (40.4%) or nonsurveillance (26.9%) groups and had more chance for curative treatments (52.4%) than the irregular surveillance (39.4%) or nonsurveillance (23.3%) groups (all P < 0.001). Mortality risk was significantly lower in the regular surveillance group (adjusted hazard ratio [aHR], 0.69; 95% [CI], 0.57-0.83) but not in the irregular surveillance group (aHR, 0.94; 95% CI, 0.69-1.28) compared with the nonsurveillance group after adjusting for confounding factors and lead-time. When the subjects were restricted to cirrhotic patients or Child-Pugh class A/B patients, similar results were obtained for mortality risk reduction between groups. CONCLUSIONS HCC surveillance was associated with longer survival owing to earlier diagnosis and curative treatment. Survival advantage was significant with regular surveillance but not with irregular surveillance.
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Affiliation(s)
- H Y Kim
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea
| | - J Y Nam
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - J-H Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - H A Lee
- Clinical Trial Center, Ewha Womans University Mokdong Hospital, Seoul, Korea
| | - Y Chang
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - H Y Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - H Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - D H Lee
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Y Y Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - E J Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - S J Yu
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - J M Lee
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Y J Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - J-H Yoon
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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13
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Sheppard-Law S, Zablotska-Manos I, Kermeen M, Holdaway S, Lee A, George J, Zekry A, Maher L. Utilisation of hepatocellular carcinoma screening in Australians at risk of hepatitis B virus-related carcinoma and prescribed anti-viral therapy. J Clin Nurs 2018; 27:2673-2683. [PMID: 29603817 DOI: 10.1111/jocn.14367] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/18/2018] [Indexed: 12/17/2022]
Abstract
AIMS AND OBJECTIVES To investigate hepatocellular carcinoma screening utilisation and factors associated with utilisation among patients prescribed hepatitis B virus anti-viral therapy and at risk of hepatocellular carcinoma. BACKGROUND The incidence of hepatocellular carcinoma has increased in Australia over the past three decades with chronic hepatitis B virus infection a major contributor. hepatocellular carcinoma surveillance programs aim to detect cancers early enabling curative treatment options, longer survival and longer times to recurrence. DESIGN Multi-site cross-sectional survey. METHODS An online study questionnaire was administered to eligible participants attending three Sydney tertiary hospitals. Data were grouped into six mutually exclusive hepatocellular carcinoma risk factor categories as per American Association for the Study of Liver Diseases guidelines. All analyses were undertaken in STATA. Logistic regression was used to assess the associations between covariates and screening utilisation. Multivariate models described were assessed using the Hosmer-Lemeshow goodness of fit. RESULTS Of the 177 participants, 137 (77.4%) self-reported that US had been performed in the last six months. Awareness that screening should be performed and knowing the correct frequency of US screening were independently associated with screening utilisation. Participants who knew that screening should be undertaken were three times more likely to have had pretreatment education or were prescribed hepatitis B virus anti-viral treatment for >4 years. Participants reporting a family history of hepatocellular carcinoma were less likely to know that screening should be undertaken every 6 months. CONCLUSION While utilisation of hepatocellular carcinoma surveillance programs was higher in this study than in previous reports, strategies to further improve surveillance remain necessary. RELEVANCE TO CLINICAL PRACTICE Findings from this research form the basis for proposing strategies to improve utilisation of hepatocellular carcinoma screening, inform hepatitis B virus-related clinical practice and for the delivery of care and nursing education to people receiving hepatitis B virus anti-viral therapy and at risk of developing hepatocellular carcinoma.
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Affiliation(s)
- Suzanne Sheppard-Law
- Faculty of Health, University of Technology, Sydney, Ultimo, NSW, Australia.,Sydney Children's Hospital Network-Sydney Children's Hospital, Randwick, NSW, Australia.,The Kirby Institute, UNSW Australia, Sydney, NSW, Australia
| | | | - Melissa Kermeen
- Department of Gastroenterology and Liver Services, Concord Repatriation General Hospital, Concord, NSW, Australia
| | - Susan Holdaway
- Storr Liver Unit, Westmead Hospital, Westmead, NSW, Australia
| | - Alice Lee
- Department of Gastroenterology and Liver Services, Concord Repatriation General Hospital, Concord, NSW, Australia
| | - Jacob George
- Storr Liver Unit, Westmead Hospital, Westmead, NSW, Australia.,Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital, University of Sydney, Westmead, NSW, Australia
| | - Amany Zekry
- Department of Gastroenterology & Hepatology, St George Hospital, Kogarah, NSW, Australia.,St George Hospital Clinical Group School of Medicine, UNSW Australia, Sydney, NSW, Australia
| | - Lisa Maher
- The Kirby Institute, UNSW Australia, Sydney, NSW, Australia
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14
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Ringelhan M, McKeating JA, Protzer U. Viral hepatitis and liver cancer. Philos Trans R Soc Lond B Biol Sci 2018; 372:rstb.2016.0274. [PMID: 28893941 PMCID: PMC5597741 DOI: 10.1098/rstb.2016.0274] [Citation(s) in RCA: 227] [Impact Index Per Article: 32.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/09/2017] [Indexed: 02/07/2023] Open
Abstract
Hepatitis B and C viruses are a global health problem causing acute and chronic infections that can lead to liver cirrhosis and hepatocellular carcinoma (HCC). These infections are the leading cause for HCC worldwide and are associated with significant mortality, accounting for more than 1.3 million deaths per year. Owing to its high incidence and resistance to treatment, liver cancer is the second leading cause of cancer-related death worldwide, with HCC representing approximately 90% of all primary liver cancer cases. The majority of viral-associated HCC cases develop in subjects with liver cirrhosis; however, hepatitis B virus infection can promote HCC development without prior end-stage liver disease. Thus, understanding the role of hepatitis B and C viral infections in HCC development is essential for the future design of treatments and therapies for this cancer. In this review, we summarize the current knowledge on hepatitis B and C virus hepatocarcinogenesis and highlight direct and indirect risk factors. This article is part of the themed issue ‘Human oncogenic viruses’.
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Affiliation(s)
- Marc Ringelhan
- Institute of Virology, Technical University of Munich/Helmholtz Zentrum München, Trogerstrasse 30, 81675 Muenchen, Germany.,Department of Internal Medicine II, University Hopsital rechts der Isar, Technical University of Munich, Ismaninger Strasse 22, 81675 Muenchen, Germany.,German Center for Infection Research (DZIF), partner site Munich
| | - Jane A McKeating
- Institute for Advanced Science, Technical University of Munich, Muenchen, Germany .,Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Ulrike Protzer
- Institute of Virology, Technical University of Munich/Helmholtz Zentrum München, Trogerstrasse 30, 81675 Muenchen, Germany .,German Center for Infection Research (DZIF), partner site Munich.,Institute for Advanced Science, Technical University of Munich, Muenchen, Germany
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15
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Abstract
This article provides a glimpse into the future of the Liver Imaging Reporting and Data System (LI-RADS), discussing the immediate and long-term plans for its continuing improvement and expansion. To complement the Core and Essentials components of the latest version of LI-RADS, a comprehensive manual will be released soon, and it will include technical recommendations, management guidance, as well as reporting instructions and templates. In this article, we briefly review the process by which LI-RADS has been developed until now, a process guided by a variable combination of data, expert opinion, and desire for congruency with other diagnostic systems in North America. We then look forward, envisioning that forthcoming updates to LI-RADS will occur regularly every 3 to 5 years, driven by emerging high-quality scientific evidence. We highlight some of the key knowledge and technology gaps that will need to be addressed to enable the needed refinements. We also anticipate future expansions in scope to meet currently unaddressed clinical needs. Finally, we articulate a vision for eventual unification of imaging system for HCC screening and surveillance, diagnosis and staging, and treatment response assessment.
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16
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Affiliation(s)
- Necati Örmeci
- Department of Gastroenterology, Ankara University Medical School, Ankara, Turkey.
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17
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Lemoine M, Thursz MR. Battlefield against hepatitis B infection and HCC in Africa. J Hepatol 2017; 66:645-654. [PMID: 27771453 DOI: 10.1016/j.jhep.2016.10.013] [Citation(s) in RCA: 70] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2016] [Revised: 09/12/2016] [Accepted: 10/13/2016] [Indexed: 12/14/2022]
Abstract
Despite effective and safe hepatitis B virus (HBV) vaccine and antiviral therapies, HBV-related hepatocellular carcinoma (HCC) remains a major cause of deaths in young adults in Africa. There are multiple barriers to control the burden of HBV infection and HCC. In comparison to other major infectious diseases, HBV infection and liver diseases have received remarkably little attention from the global health community. There is an urgent need to improve birth dose vaccine coverage and implementing screening and treatment interventions. This requires a dramatic simplification of the management of chronic hepatitis B in Africa, with access to reliable, robust and inexpensive diagnostic tools and strong support from the local governments and the international health community. This review analyses 1) the characteristics of HBV hepatitis and HCC epidemics in Africa and 2) the barriers and potential solutions to control it.
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18
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Maida M, Malizia G, Affronti A, Virdone R, Maida C, Margherita V, D’amico G. Screening and surveillance for hepatocellular carcinoma: perspective of a new era? Expert Rev Anticancer Ther 2016; 16:1291-1302. [PMID: 27730841 DOI: 10.1080/14737140.2016.1246965] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Marcello Maida
- Section of Gastroenterology, Villa Sofia, V. Cervello Hospital, Palermo, Italy
| | - Giuseppe Malizia
- Section of Gastroenterology, Villa Sofia, V. Cervello Hospital, Palermo, Italy
| | - Andrea Affronti
- Section of Internal Medicine, Villa Sofia, V. Cervello Hospital, Palermo, Italy
| | - Roberto Virdone
- Section of Internal Medicine, Villa Sofia, V. Cervello Hospital, Palermo, Italy
| | - Carlo Maida
- Section of Internal Medicine, DIBIMIS, University of Palermo, Palermo, Italy
| | - Vito Margherita
- Department of Medical Sciences, Surgical and Advanced Technologies, University of Catania, Catania, Italy
| | - Gennaro D’amico
- Section of Gastroenterology, Villa Sofia, V. Cervello Hospital, Palermo, Italy
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19
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Llovet JM, Zucman-Rossi J, Pikarsky E, Sangro B, Schwartz M, Sherman M, Gores G. Hepatocellular carcinoma. Nat Rev Dis Primers 2016; 2:16018. [PMID: 27158749 DOI: 10.1038/nrdp.2016.18] [Citation(s) in RCA: 1813] [Impact Index Per Article: 201.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Liver cancer is the second leading cause of cancer-related deaths globally and has an incidence of approximately 850,000 new cases per year. Hepatocellular carcinoma (HCC) represents approximately 90% of all cases of primary liver cancer. The main risk factors for developing HCC are well known and include hepatitis B and C virus infection, alcohol intake and ingestion of the fungal metabolite aflatoxin B1. Additional risk factors such as non-alcoholic steatohepatitis are also emerging. Advances in the understanding of the molecular pathogenesis of HCC have led to identification of critical driver mutations; however, the most prevalent of these are not yet druggable targets. The molecular classification of HCC is not established, and the Barcelona Clinic Liver Cancer staging classification is the main clinical algorithm for the stratification of patients according to prognosis and treatment allocation. Surveillance programmes enable the detection of early-stage tumours that are amenable to curative therapies - resection, liver transplantation or local ablation. At more developed stages, only chemoembolization (for intermediate HCC) and sorafenib (for advanced HCC) have shown survival benefits. There are major unmet needs in HCC management that might be addressed through the discovery of new therapies and their combinations for use in the adjuvant setting and for intermediate- and advanced-stage disease. Moreover, biomarkers for therapy stratification, patient-tailored strategies targeting driver mutations and/or activating signalling cascades, and validated measurements of quality of life are needed. Recent failures in the testing of systemic drugs for intermediate and advanced stages have indicated a need to refine trial designs and to define novel approaches.
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Affiliation(s)
- Josep M Llovet
- Liver Cancer Program, Division of Liver Diseases and RM Transplant Institute, Tisch Cancer Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, Madison Avenue 1425, 11F-70, Box 1123, New York, New York 10029, USA.,Liver Cancer Translational Research Laboratory, Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, IDIBAPS - Hospital Clinic, CIBERehd, University of Barcelona, Catalonia, Spain.,Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain
| | - Jessica Zucman-Rossi
- INSERM, UMR-1162, Génomique Fonctionnelle des Tumeurs Solides, Equipe Labellisée Ligue Contre le Cancer, Institut Universitaire d'Haematologie, Paris, France.,Université Paris Descartes, Labex Immuno-Oncology, Sorbonne Paris Cité, Faculté de Médecine, Paris, France.,Université Paris 13, Sorbonne Paris Cité, Unité de Formation et de Recherche Santé, Médecine, Biologie Humaine, Bobigny, France.,Université Paris Diderot, Paris, France
| | - Eli Pikarsky
- Lautenberg Center for Immunology and Cancer Research and Department of Pathology, Hebrew University Hadassah-Medical School, Jerusalem, Israel
| | - Bruno Sangro
- Liver Unit, Clínica Universidad de Navarra, Pamplona, Spain.,Instituto de Investigación Sanitaria de Navarra (IDISNA) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Pamplona, Spain
| | - Myron Schwartz
- Liver Cancer Program, Division of Liver Diseases and RM Transplant Institute, Tisch Cancer Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, Madison Avenue 1425, 11F-70, Box 1123, New York, New York 10029, USA
| | - Morris Sherman
- Department of Gastroenterology, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Gregory Gores
- Mayo Clinic, Mayo College of Medicine, Rochester, Minnesota, USA
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20
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Bruix J, Reig M, Sherman M. Evidence-Based Diagnosis, Staging, and Treatment of Patients With Hepatocellular Carcinoma. Gastroenterology 2016; 150:835-53. [PMID: 26795574 DOI: 10.1053/j.gastro.2015.12.041] [Citation(s) in RCA: 1258] [Impact Index Per Article: 139.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2015] [Revised: 12/09/2015] [Accepted: 12/16/2015] [Indexed: 02/07/2023]
Abstract
Evidence-based management of patients with hepatocellular carcinoma (HCC) is key to their optimal care. For individuals at risk for HCC, surveillance usually involves ultrasonography (there is controversy over use of biomarkers). A diagnosis of HCC is made based on findings from biopsy or imaging analyses. Molecular markers are not used in diagnosis or determination of prognosis and treatment for patients. The Barcelona Clinic Liver Cancer algorithm is the most widely used staging system. Patients with single liver tumors or as many as 3 nodules ≤3 cm are classified as having very early or early-stage cancer and benefit from resection, transplantation, or ablation. Those with a greater tumor burden, confined to the liver, and who are free of symptoms are considered to have intermediate-stage cancer and can benefit from chemoembolization if they still have preserved liver function. Those with symptoms of HCC and/or vascular invasion and/or extrahepatic cancer are considered to have advanced-stage cancer and could benefit from treatment with the kinase inhibitor sorafenib. Patients with end-stage HCC have advanced liver disease that is not suitable for transplantation and/or have intense symptoms. Studies now aim to identify molecular markers and imaging techniques that can detect patients with HCC at earlier stages and better predict their survival time and response to treatment.
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Affiliation(s)
- Jordi Bruix
- Barcelona Clinic Liver Cancer Group, Liver Unit, Hospital Clinic, IDIBAPS, University of Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain.
| | - Maria Reig
- Barcelona Clinic Liver Cancer Group, Liver Unit, Hospital Clinic, IDIBAPS, University of Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
| | - Morris Sherman
- Division of Gastroenterology, Department of Medicine, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
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21
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Kim DY, Kim HJ, Han KH, Han SY, Heo J, Woo HY, Um SH, Kim YH, Kweon YO, Lim HY, Yoon JH, Lee WS, Lee BS, Lee HC, Ryoo BY, Yoon SK. Real-Life Experience of Sorafenib Treatment for Hepatocellular Carcinoma in Korea: From GIDEON Data. Cancer Res Treat 2016; 48:1243-1252. [PMID: 26910470 PMCID: PMC5080829 DOI: 10.4143/crt.2015.278] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2015] [Accepted: 02/15/2016] [Indexed: 12/22/2022] Open
Abstract
Purpose The purpose of this study is to report real life experiences of sorafenib therapy for hepatocellular carcinoma (HCC) in Korea, using a subset of data from GIDEON (Global Investigation of Therapeutic Decisions in HCC and of Its Treatment with Sorafenib; a large, prospective, observational study). Materials and Methods Between January 2009 and April 2012, a total of 497 patients were enrolled from 11 sites in Korea. Of these, 482 patients were evaluable for safety analyses. Case report forms of paper or electronic version were used to record safety and efficacy data from all patients. Results More patients of Child-Pugh A received sorafenib for > 8 weeks than did patients of Child-Pugh B (55.5% vs. 34.3%). Child-Pugh score did not appear to influence the starting dose of sorafenib, and approximately 70% of patients both in Child-Pugh A and B groups received the recommended initial daily dose of 800 mg (69.0% and 69.5%, respectively). The median overall survival (OS) and time to progression (TTP) were 8.5 months and 2.5 months. In Child-Pugh A patients, the median OS and TTP were 10.2 months and 2.5 months. The most frequent treatment-emergent drug-related adverse event was hand-foot skin reaction (31.7%), followed by diarrhea (18.0%). The incidence of treatment-emergent adverse events was similar in both Child-Pugh A (85.4%) and Child-Pugh B (84.8%) patients. Conclusion Sorafenib was well tolerated by Korean HCC patients in clinical settings, and the safety profile did not appear to differ by Child-Pugh status. Survival benefit in Korean patients was in line with that of a previous pivotal phase III trial (SHARP).
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Affiliation(s)
- Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Hye Jin Kim
- Medical Affairs, Bayer Healthcare Pharmaceuticals, Seoul, Korea
| | - Kwang-Hyub Han
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Sang Young Han
- Department of Internal Medicine, Donga University College of Medicine, Busan, Korea
| | - Jeong Heo
- Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea
| | - Hyun Young Woo
- Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea
| | - Soon Ho Um
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Yeul Hong Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Young Oh Kweon
- Department of Internal Medicine, Kyungpook National University College of Medicine, Daegu, Korea
| | - Ho Yeong Lim
- Department of Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jung Hwan Yoon
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Wan Sik Lee
- Department of Internal Medicine, Chonnam National University College of Medicine, Gwangju, Korea
| | - Byung Seok Lee
- Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Korea
| | - Han Chu Lee
- Department of Gastroenterology, University of Ulsan College of Medicine, Seoul, Korea
| | - Baek-Yeol Ryoo
- Department of Oncology, University of Ulsan College of Medicine, Seoul, Korea
| | - Seung Kew Yoon
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
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22
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Wells SA, Hinshaw JL, Lubner MG, Ziemlewicz TJ, Brace CL, Lee FT. Liver Ablation: Best Practice. Radiol Clin North Am 2015; 53:933-71. [PMID: 26321447 DOI: 10.1016/j.rcl.2015.05.012] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Tumor ablation in the liver has evolved to become a well-accepted tool in the management of increasing complex oncologic patients. At present, percutaneous ablation is considered first-line therapy for very early and early hepatocellular carcinoma and second-line therapy for colorectal carcinoma liver metastasis. Because thermal ablation is a treatment option for other primary and secondary liver tumors, an understanding of the underlying tumor biology is important when weighing the potential benefits of ablation. This article reviews ablation modalities, indications, patient selection, and imaging surveillance, and emphasizes technique-specific considerations for the performance of percutaneous ablation.
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Affiliation(s)
- Shane A Wells
- Department of Radiology, University of Wisconsin, 600 Highland Avenue, CSC, Madison, WI 53792, USA.
| | - J Louis Hinshaw
- Department of Radiology, University of Wisconsin, 600 Highland Avenue, CSC, Madison, WI 53792, USA
| | - Meghan G Lubner
- Department of Radiology, University of Wisconsin, 600 Highland Avenue, CSC, Madison, WI 53792, USA
| | - Timothy J Ziemlewicz
- Department of Radiology, University of Wisconsin, 600 Highland Avenue, CSC, Madison, WI 53792, USA
| | - Christopher L Brace
- Department of Radiology, University of Wisconsin, 600 Highland Avenue, CSC, Madison, WI 53792, USA; Department of Biomedical Engineering, University of Wisconsin, 600 Highland Avenue, CSC, Madison, WI 53792, USA
| | - Fred T Lee
- Department of Radiology, University of Wisconsin, 600 Highland Avenue, CSC, Madison, WI 53792, USA; Department of Biomedical Engineering, University of Wisconsin, 600 Highland Avenue, CSC, Madison, WI 53792, USA
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23
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van Meer S, de Man RA, Coenraad MJ, Sprengers D, van Nieuwkerk KMJ, Klümpen HJ, Jansen PLM, IJzermans JNM, van Oijen MGH, Siersema PD, van Erpecum KJ. Surveillance for hepatocellular carcinoma is associated with increased survival: Results from a large cohort in the Netherlands. J Hepatol 2015; 63:1156-63. [PMID: 26100498 DOI: 10.1016/j.jhep.2015.06.012] [Citation(s) in RCA: 102] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2014] [Revised: 06/07/2015] [Accepted: 06/10/2015] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Effectiveness of surveillance for hepatocellular carcinoma is controversial. We here explore its effects in "real life" clinical practice. METHODS Patients with hepatocellular carcinoma diagnosed in the period 2005-2012 in five Dutch academic centers were evaluated. Surveillance was defined as ⩾2 screening tests during three preceding years and at least one radiologic imaging test within 18 months before diagnosis. RESULTS 295 (27%) of 1074 cases underwent surveillance. Median time interval between last negative radiologic imaging and hepatocellular carcinoma diagnosis was 7.5 months. In the surveillance group, cirrhosis (97% vs. 60%, p<0.001) and viral hepatitis were more frequent, and non-alcoholic fatty liver disease or absence of risk factors less frequent. In case of surveillance, tumor size was significantly smaller (2.7 vs. 6.0 cm), with lower alpha-fetoprotein levels (16 vs. 44 μg/L), earlier tumor stage (BCLC 0 and A combined: 61% vs. 21%) and resection/transplantation (34% vs. 25%) or radiofrequency ablation (23% vs. 7%) more often applied, with significantly higher 1-, 3-, and 5-year survival rates. Survival benefit by surveillance remained significant after adjustment for lead-time bias based on assumed tumor doubling time of 90 days, but not with doubling time of ⩾120 days. In multivariate analysis, surveillance was an independent predictor for mortality (for interval ⩽9 respectively >9 months: adjusted HRs 0.51 and 0.50, 95% confidence intervals: 0.39-0.67 and 0.37-0.69). CONCLUSIONS Surveillance for hepatocellular carcinoma was associated with smaller tumor size, earlier tumor stage, with an impact on therapeutic strategy and was an independent predictor of survival.
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Affiliation(s)
- Suzanne van Meer
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Robert A de Man
- Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Minneke J Coenraad
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Dave Sprengers
- Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Karin M J van Nieuwkerk
- Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands
| | - Heinz-Josef Klümpen
- Department of Medical Oncology, Academic Medical Center Amsterdam, Amsterdam, The Netherlands
| | - Peter L M Jansen
- Department of Gastroenterology and Hepatology, Academic Medical Center Amsterdam, Amsterdam, The Netherlands
| | - Jan N M IJzermans
- Department of Surgery, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Martijn G H van Oijen
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Peter D Siersema
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Karel J van Erpecum
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands.
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24
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An C, Choi YA, Choi D, Paik YH, Ahn SH, Kim MJ, Paik SW, Han KH, Park MS. Growth rate of early-stage hepatocellular carcinoma in patients with chronic liver disease. Clin Mol Hepatol 2015; 21:279-86. [PMID: 26523271 PMCID: PMC4612289 DOI: 10.3350/cmh.2015.21.3.279] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2015] [Revised: 08/02/2015] [Accepted: 08/13/2015] [Indexed: 12/17/2022] Open
Abstract
Background/Aims The goal of this study was to estimate the growth rate of hepatocellular carcinoma (HCC) and identify the host factors that significantly affect this rate. Methods Patients with early-stage HCC (n=175) who underwent two or more serial dynamic imaging studies without any anticancer treatment at two tertiary care hospitals in Korea were identified. For each patient, the tumor volume doubling time (TVDT) of HCC was calculated by comparing tumor volumes between serial imaging studies. Clinical and laboratory data were obtained from the medical records of the patients. Results The median TVDT was 85.7 days, with a range of 11 to 851.2 days. Multiple linear regression revealed that the initial tumor diameter (a tumor factor) and the etiology of chronic liver disease (a host factor) were significantly associated with the TVDT. The TVDT was shorter when the initial tumor diameter was smaller, and was shorter in HCC related to hepatitis B virus (HBV) infection than in HCC related to hepatitis C virus (HCV) infection (median, 76.8 days vs. 137.2 days; P=0.0234). Conclusions The etiology of chronic liver disease is a host factor that may significantly affect the growth rate of early-stage HCC, since HBV-associated HCC grows faster than HCV-associated HCC.
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Affiliation(s)
- Chansik An
- Department of Radiology, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Korea
| | - Youn Ah Choi
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dongil Choi
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yong Han Paik
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sang Hoon Ahn
- Department of Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Myeong-Jin Kim
- Department of Radiology, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Korea
| | - Seung Woon Paik
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kwang-Hyub Han
- Department of Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Mi-Suk Park
- Department of Radiology, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Korea
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25
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Kim DY, Kim HJ, Jeong SE, Kim SG, Kim HJ, Sinn DH, Lee YJ, Jeong WK, Choi KS, Heo NY, Kim DJ, Kim YS, Kim YB, Kim YJ, Kim HR, Park M, Lee CW, Tak WY, Chung JH, Kim SY, Kim Y, Lee WC, Kim HS. The Korean guideline for hepatocellular carcinoma surveillance. JOURNAL OF THE KOREAN MEDICAL ASSOCIATION 2015; 58:385. [DOI: 10.5124/jkma.2015.58.5.385] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2025] Open
Affiliation(s)
- Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Hyun Jung Kim
- Institute for Preventive Medicine, Korea University College of Medicine, Seoul, Korea
| | - Seung Eun Jeong
- Department of Radiology, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Sang Gyune Kim
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea
| | - Hyung Joon Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yong Joo Lee
- Department of Family Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Woo Kyoung Jeong
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kui Son Choi
- Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea
| | - Nae-Yun Heo
- Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Dong Joon Kim
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - Young Seok Kim
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea
| | | | - Yoon Jun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Hyoung-Ryoul Kim
- Department of Occupational and Environmental Medicine, The Catholic University of Korea School of Medicine, Seoul, Korea
| | - Minseon Park
- Department of Family Medicine, Seoul National University Hospital, Seoul, Korea
| | - Chan Wha Lee
- Department of Radiology, National Cancer Center, Goyang, Korea
| | - Won Young Tak
- Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea
| | - Ji Hye Chung
- National Cancer Control Institute, National Cancer Center, Goyang, Korea
| | - Soo Young Kim
- Department of Family Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Yeol Kim
- National Cancer Control Institute, National Cancer Center, Goyang, Korea
| | - Won-Chul Lee
- Department of Preventive Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Hong Soo Kim
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea
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Abstract
Chronic hepatitis B (CHB) infection is the major cause of hepatocellular carcinoma (HCC), accounting for approximately 50% of the underlying etiologies. We reviewed the primary, secondary, and tertiary measures for the prevention of hepatitis B virus (HBV)-related HCC. The most effective method for preventing HBV-related HCC is vaccination. Universal hepatitis B vaccination has been shown to reduce the rates of HBV infection and HCC significantly. Once chronic HBV infection is established, antiviral treatment using interferon or nucleos(t)ide analogs is used to prevent disease progression to cirrhosis, HCC, or both. Studies have found viral replication indicated by HBV DNA level to be a strong risk factor for development of HCC. Additionally, periodic surveillance using ultrasonography and serum α-fetoprotein for earlier detection of HCC is also important so that curative treatments with survival benefit can be possible. Finally, adjuvant antiviral treatment using interferon or nucleos(t)ide analogs is used to prevent tumor recurrence after curative resection. Adjuvant interferon treatment prevented early recurrence, not late recurrence, probably due to its antiangiogenetic and antiproliferative effects. Adjuvant nucleos(t)ide analogs demonstrated promising results for preventing late recurrence, probably due to effective suppression of viral replication. Further investigations are required to establish the optimal preventive plans for HBV-related HCC.
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Affiliation(s)
- Mi Na Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea; Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.
| | - Kwang-Hyub Han
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea; Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea; Brain Korea 21 Project for Medical Science, Seoul, Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea; Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea; Brain Korea 21 Project for Medical Science, Seoul, Korea
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27
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Hung HH, Chao Y, Chiou YY, Li CP, Lee RC, Huo TI, Huang YH, Chau GY, Su CW, Yeh YC, Lin HC, Lee SD, Wu JC. A comparison of clinical manifestations and prognoses between patients with hepatocellular carcinoma and Child-Pugh scores of 5 or 6. Medicine (Baltimore) 2014; 93:e348. [PMID: 25546689 PMCID: PMC4602592 DOI: 10.1097/md.0000000000000348] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
The objective of this work is to compare the outcomes between the Child-Pugh score 5 (A5 group) and Child-Pugh score 6 (A6 group) in patients with hepatocellular carcinoma (HCC). Whether HCC patients with A5 and A6 groups have different prognoses is still obscure. We enrolled 2462 consecutive treatment-naive HCC patients from 2007 to 2012. Among them, 1486 patients had Child-Pugh grade A, including 1016 in the A5 group and 470 in the A6 group. Factors in the prognoses were analyzed by multivariate analysis. Compared with those in the A6 group, patients in the A5 group were younger, had higher proportions of tumors within the Milan criteria, and more of them underwent curative therapies. The cumulative survival rates at 5 years were 51.3% and 37.1% for patients in the A5 and A6 groups, respectively (P < 0.001). Multivariate analysis showed that the independent risk factors associated with poor overall survival were nonhepatitis C virus carrier, serum albumin ≤ 4 g/dL, aspartate aminotransferase > 45 U/L, α-fetoprotein > 20 ng/mL, multinodularity, tumor size > 3 cm, vascular invasion, and noncurative therapies, but not the Child-Pugh numeric score. The Child-Pugh numeric score had a significant prognostic effect only in patients who had tumors beyond the Milan criteria and received noncurative therapies. HCC patients with A5 group had a better overall survival rate than those with A6 group due to the early tumor stage and higher rate of receiving curative treatments. Tumor factors and treatment modalities were more important than the Child-Pugh numeric score.
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Affiliation(s)
- Hung-Hsu Hung
- From the Division of Gastroenterology (H-HH, S-DL), Department of Medicine, Cheng Hsin General Hospital; Faculty of Medicine, School of Medicine (H-HH, YC, Y-YC, C-PL, R-CL, G-YC, C-WS, Y-CY, H-CL, S-DL); Institute of Clinical Medicine and Genomic Research Center (H-HH, Y-HH, J-CW), National Yang-Ming University; Division of Chemoradiotherapy (YC), Department of Oncology Medicine; Division of Gastrointestinal Radiology (Y-YC), Department of Radiology; Division of Gastroenterology (C-PL, T-IH, Y-HH, C-WS, H-CL), Department of Medicine; Division of Pediatric Radiology (R-CL), Department of Radiology, Taipei Veterans General Hospital; Institute of Pharmacology (T-IH), School of Medicine, National Yang-Ming University; Division of General Surgery (G-YC), Department of Surgery; Department of Pathology and Laboratory Medicine (Y-CY); and Division of Translational Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan (J-CW)
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28
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Sherman M. Surveillance for hepatocellular carcinoma. Best Pract Res Clin Gastroenterol 2014; 28:783-93. [PMID: 25260308 DOI: 10.1016/j.bpg.2014.08.008] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2014] [Accepted: 08/15/2014] [Indexed: 01/31/2023]
Abstract
When hepatocellular carcinoma presents with symptoms cure is seldom possible and death usually follows within months. However, it is possible to detect HCC early, at which stage it is curable. This requires a surveillance program. The components of such a program include: identification of the at risk population, provision of appropriate surveillance tests, and an appropriate method of determining whether the abnormalities found on screening are cancer or not. Surveillance for liver cancer meets all these criteria. Unfortunately high quality evidence showing benefit of liver cancer surveillance is lacking, but lesser quality evidence is plentiful, including several cost efficacy analyses that all show that surveillance does decrease mortality. Therefore all the continental liver disease societies and all national liver disease societies have recommended that surveillance should be undertaken.
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Affiliation(s)
- Morris Sherman
- University of Toronto, University Health Network, Toronto General Hospital, 200 Elizabeth Street, Toronto, ON M5G 2C4, Canada.
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29
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Ramachandran J. Surveillance for hepatocellular carcinoma. J Clin Exp Hepatol 2014; 4:S50-6. [PMID: 25755611 PMCID: PMC4284216 DOI: 10.1016/j.jceh.2014.03.050] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2013] [Accepted: 03/03/2014] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a dreaded complication of cirrhosis as it is the commonest cause of mortality in these patients. The last few years have seen a dramatic improvement in the management of this tumor as nearly 50-70% of selected patients with early HCC survive for a median period of up to 5 years after liver transplantation, resection or local ablation. Surveillance has been found to be an effective tool to detect early tumors and expand the applicability of these curative treatment options. Semiannual ultrasonogram is recommended for surveillance by the American, European and Asia Pacific liver societies and is the standard of care in many countries. There is increasing evidence that this practice improves survival too. Since the only way to improve the outlook of HCC is its diagnosis prior to commencement of symptoms, providing surveillance becomes a major responsibility of physicians caring for patients with chronic liver disease. This review attempts to discuss the population at risk of HCC, modalities and frequency of surveillance tests, cost effectiveness and also the logistics of its delivery in the Indian context.
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Affiliation(s)
- Jeyamani Ramachandran
- Address for correspondence: Jeyamani Ramachandran, Professor, Department of Hepatology, Christian Medical College, Vellore, Tamil Nadu, India.
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30
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Kumar A, Acharya SK, Singh SP, Saraswat VA, Arora A, Duseja A, Goenka MK, Jain D, Kar P, Kumar M, Kumaran V, Mohandas KM, Panda D, Paul SB, Ramachandran J, Ramesh H, Rao PN, Shah SR, Sharma H, Thandassery RB. The Indian National Association for Study of the Liver (INASL) Consensus on Prevention, Diagnosis and Management of Hepatocellular Carcinoma in India: The Puri Recommendations. J Clin Exp Hepatol 2014; 4:S3-S26. [PMID: 25755608 PMCID: PMC4284289 DOI: 10.1016/j.jceh.2014.04.003] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2013] [Accepted: 04/08/2014] [Indexed: 02/08/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the major causes of morbidity, mortality and healthcare expenditure in patients with chronic liver disease. There are no consensus guidelines on diagnosis and management of HCC in India. The Indian National Association for Study of the Liver (INASL) set up a Task-Force on HCC in 2011, with a mandate to develop consensus guidelines for diagnosis and management of HCC, relevant to disease patterns and clinical practices in India. The Task-Force first identified various contentious issues on various aspects of HCC and these issues were allotted to individual members of the Task-Force who reviewed them in detail. The Task-Force used the Oxford Center for Evidence Based Medicine-Levels of Evidence of 2009 for developing an evidence-based approach. A 2-day round table discussion was held on 9th and 10th February, 2013 at Puri, Odisha, to discuss, debate, and finalize the consensus statements. The members of the Task-Force reviewed and discussed the existing literature at this meeting and formulated the INASL consensus statements for each of the issues. We present here the INASL consensus guidelines (The Puri Recommendations) on prevention, diagnosis and management of HCC in India.
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Key Words
- AFP, alpha-fetoprotein
- AIIMS, All India Institute of Medical Sciences
- ASMR, age standardized mortality rate
- BCLC, Barcelona-Clinic Liver Cancer
- CEUS, contrast enhanced ultrasound
- CT, computed tomography
- DCP, des-gamma-carboxy prothrombin
- DDLT, deceased donor liver transplantation
- DE, drug eluting
- FNAC, fine needle aspiration cytology
- GPC-3, glypican-3
- GS, glutamine synthase
- Gd-EOB-DTPA, gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid
- HBV, Hepatitis B virus
- HCC, hepatocellular carcinoma
- HCV, Hepatitis C virus
- HSP-70, heat shock protein-70
- HVPG, hepatic venous pressure gradient
- ICG, indocyanine green
- ICMR, Indian Council of Medical Research
- INASL, Indian National Association for Study of the Liver
- LDLT, living donor liver transplantation
- MRI, magnetic resonance imaging
- Mabs, monoclonal antibodies
- NAFLD, non-alcoholic fatty liver disease
- OLT, orthotopic liver transplantation
- PAI, percutaneous acetic acid injection
- PEI, percutaneous ethanol injection
- PET, positron emission tomography
- PVT, portal vein thrombosis
- RECIST, Response Evaluation Criteria in Solid Tumors
- RFA
- RFA, radio frequency ablation
- SVR, sustained viral response
- TACE
- TACE, transarterial chemoembolization
- TART, trans-arterial radioisotope therapy
- UCSF, University of California San Francisco
- liver cancer
- targeted therapy
- transplant
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Affiliation(s)
- Ashish Kumar
- Department of Gastroenterology & Hepatology, Sir Ganga Ram Hospital, New Delhi, India
| | - Subrat K. Acharya
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Road, New Delhi 110 029, India
| | - Shivaram P. Singh
- Department of Gastroenterology, SCB Medical College, Cuttack, Odisha, India
| | - Vivek A. Saraswat
- Department of Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Anil Arora
- Department of Gastroenterology & Hepatology, Sir Ganga Ram Hospital, New Delhi, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Mahesh K. Goenka
- Department of Gastroenterology, Apollo Gleneagles Hospital, 58, Canal Circular Road, Kolkata, West Bengal 700 054, India
| | - Deepali Jain
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Premashish Kar
- Department of Medicine, Maulana Azad Medical College, University of Delhi, New Delhi, India
| | - Manoj Kumar
- Department of Hepatology, Institute of Liver & Biliary Sciences, New Delhi, India
| | - Vinay Kumaran
- Department of Surgical Gastroenterology and Liver Transplantation, Sir Ganga Ram Hospital, New Delhi, India
| | - Kunisshery M. Mohandas
- Department of Digestive Diseases, Tata Medical Center, Kolkata, West Bengal 700156, India
| | - Dipanjan Panda
- Department of Oncology, Institute of Liver & Biliary Sciences, New Delhi, India
| | - Shashi B. Paul
- Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India
| | - Jeyamani Ramachandran
- Department of Hepatology, Christian Medical College, Vellore, Tamil Nadu 632 004, India
| | - Hariharan Ramesh
- Department of Surgical Gastroenterology, Lakeshore Hospital and Research Center, Cochin, Kerala, India
| | - Padaki N. Rao
- Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Somajiguda, Hyderabad, India
| | - Samir R. Shah
- Department of Gastroenterology, Jaslok Hospital and Research Centre, Peddar Road, Mumbai, Maharashtra 400 026, India
| | - Hanish Sharma
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Road, New Delhi 110 029, India
| | - Ragesh B. Thandassery
- Department of Gastroenterology, Apollo Gleneagles Hospital, 58, Canal Circular Road, Kolkata, West Bengal 700 054, India
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31
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Cucchetti A, Trevisani F, Pecorelli A, Erroi V, Farinati F, Ciccarese F, Rapaccini GL, Di Marco M, Caturelli E, Giannini EG, Zoli M, Borzio F, Cabibbo G, Felder M, Gasbarrini A, Sacco R, Foschi FG, Missale G, Morisco F, Baroni GS, Virdone R, Bernardi M, Pinna AD. Estimation of lead-time bias and its impact on the outcome of surveillance for the early diagnosis of hepatocellular carcinoma. J Hepatol 2014; 61:333-41. [PMID: 24717522 DOI: 10.1016/j.jhep.2014.03.037] [Citation(s) in RCA: 87] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2013] [Revised: 03/11/2014] [Accepted: 03/24/2014] [Indexed: 12/31/2022]
Abstract
BACKGROUND & AIMS Lead-time is the time by which diagnosis is anticipated by screening/surveillance with respect to the symptomatic detection of a disease. Any screening program, including surveillance for hepatocellular carcinoma (HCC), is subject to lead-time bias. Data regarding lead-time for HCC are lacking. Aims of the present study were to calculate lead-time and to assess its impact on the benefit obtainable from the surveillance of cirrhotic patients. METHODS One-thousand three-hundred and eighty Child-Pugh class A/B patients from the ITA.LI.CA database, in whom HCC was detected during semiannual surveillance (n = 850), annual surveillance (n = 234) or when patients came when symptomatic (n = 296), were selected. Lead-time was estimated by means of appropriate formulas and Monte Carlo simulation, including 1000 patients for each arm. RESULTS The 5-year overall survival after HCC diagnosis was 32.7% in semiannually surveilled patients, 25.2% in annually surveilled patients, and 12.2% in symptomatic patients (p<0.001). In a 10-year follow-up perspective, the median lead-time calculated for all surveilled patients was 6.5 months (7.2 for semiannual and 4.1 for annual surveillance). Lead-time bias accounted for most of the surveillance benefit until the third year of follow-up after HCC diagnosis. However, even after lead-time adjustment, semiannual surveillance maintained a survival benefit over symptomatic diagnosis (number of patients needed to screen = 13), as did annual surveillance (18 patients). CONCLUSIONS Lead-time bias is the main determinant of the short-term benefit provided by surveillance for HCC, but this benefit becomes factual in a long-term perspective, confirming the clinical utility of an anticipated diagnosis of HCC.
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Affiliation(s)
- Alessandro Cucchetti
- Dipartimento di Scienze Mediche e Chirurgiche, Policlinico S. Orsola-Malpighi, Alma Mater Studiorum - Università of Bologna, Italy.
| | - Franco Trevisani
- Dipartimento di Scienze Mediche e Chirurgiche, Policlinico S. Orsola-Malpighi, Alma Mater Studiorum - Università of Bologna, Italy
| | - Anna Pecorelli
- Dipartimento di Scienze Mediche e Chirurgiche, Policlinico S. Orsola-Malpighi, Alma Mater Studiorum - Università of Bologna, Italy
| | - Virginia Erroi
- Dipartimento di Scienze Mediche e Chirurgiche, Policlinico S. Orsola-Malpighi, Alma Mater Studiorum - Università of Bologna, Italy
| | - Fabio Farinati
- Dipartimento di Scienze Chirurgiche e Gastroenterologiche, Unità di Gastroenterologia, Università di Padova, Padova, Italy
| | | | - Gian Lodovico Rapaccini
- Unità di Medicina Interna e Gastroenterologia, Complesso Integrato Columbus, Università Cattolica di Roma, Roma, Italy
| | - Mariella Di Marco
- Divisione di Medicina, Azienda Ospedaliera Bolognini, Seriate, Italy
| | - Eugenio Caturelli
- Unità Operativa di Gastroenterologia, Ospedale Belcolle, Viterbo, Italy
| | - Edoardo G Giannini
- Dipartimento di Medicina Interna, Unità di Gastroenterologia, Università di Genova, Genova, Italy
| | - Marco Zoli
- Dipartimento di Scienze Mediche e Chirurgiche, Policlinico S. Orsola-Malpighi, Alma Mater Studiorum - Università of Bologna, Italy
| | - Franco Borzio
- Dipartimento di Medicina, Unità di Radiologia, Ospedale Fatebenefratelli, Milano, Italy
| | - Giuseppe Cabibbo
- Dipartimento Biomedico di Medicina Interna e Specialistica, Unità di Gastroenterologia, Università di Palermo, Palermo, Italy
| | - Martina Felder
- Ospedale Regionale di Bolzano, Unità di Gastroenterologia, Bolzano, Italy
| | - Antonio Gasbarrini
- Unità di Medicina Interna e Gastroenterologia, Policlinico Gemelli, Università Cattolica di Roma, Roma, Italy
| | - Rodolfo Sacco
- Unità Operativa Gastroenterologia e Malattie del Ricambio, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | | | - Gabriele Missale
- Unità di Malattie Infettive ed Epatologia, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | - Filomena Morisco
- Dipartimento di Medicina Clinica e Chirurgia, Unità di Gastroenterologia, Università di Napoli "Federico II", Napoli, Italy
| | | | - Roberto Virdone
- Dipartimento Biomedico di Medicina Interna e Specialistica, Unità di Medicina Interna, Palermo, Italy
| | - Mauro Bernardi
- Dipartimento di Scienze Mediche e Chirurgiche, Policlinico S. Orsola-Malpighi, Alma Mater Studiorum - Università of Bologna, Italy
| | - Antonio D Pinna
- Dipartimento di Scienze Mediche e Chirurgiche, Policlinico S. Orsola-Malpighi, Alma Mater Studiorum - Università of Bologna, Italy
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Kim DY, Han KH. Impact of a shortened surveillance interval on hepatocellular carcinoma survival. Hepat Oncol 2014; 1:3-5. [PMID: 30190934 DOI: 10.2217/hep.13.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Affiliation(s)
- Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Kwang-Hyub Han
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
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Abdelmoez AT, Abolmaaty ME, Abbas AA, Abdelfattah M, Mohran Z, Abdelkader NA. Prognostic role of serum interleukin-18 in Egyptian patients with hepatitis c virus-related hepatocellular carcinoma treated by radiofrequency ablation. Indian J Cancer 2014; 51:342-345. [DOI: 10.4103/0019-509x.146739] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
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Giannini EG, Cucchetti A, Erroi V, Garuti F, Odaldi F, Trevisani F. Surveillance for early diagnosis of hepatocellular carcinoma: How best to do it? World J Gastroenterol 2013; 19:8808-8821. [PMID: 24379604 PMCID: PMC3870532 DOI: 10.3748/wjg.v19.i47.8808] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2013] [Revised: 10/31/2013] [Accepted: 11/19/2013] [Indexed: 02/06/2023] Open
Abstract
Surveillance for hepatocellular carcinoma (HCC) is considered a standard of care for patients with chronic liver disease who are at risk of developing this malignancy. Several studies have shown that surveillance can improve the prognosis of patients diagnosed with HCC through an increased likelihood of application of curative or effective treatments. Repetition of liver ultrasonography (US) every 6 mo is the recommended surveillance program to detect early HCCs, and a positive US has to entrain a well-defined recall policy based on contrast-enhanced, dynamic radiological imaging or biopsy for the diagnosis of HCC. Although HCC fulfills the accepted criteria regarding cost-effective cancer screening and surveillance, the implementation of surveillance in clinical practice is defective and this has a negative impact on the cost-effectiveness of the procedure. Education of both physicians and patients is of paramount importance in order to improve the surveillance application and its benefits in patients at risk of HCC. The promotion of specific educational programs for practitioners, clinicians and patients is instrumental in order to expand the correct use of surveillance in clinical practice and eventually improve HCC prognosis.
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Meer SV, Man RAD, Siersema PD, Erpecum KJV. Surveillance for hepatocellular carcinoma in chronic liver disease: Evidence and controversies. World J Gastroenterol 2013; 19:6744-6756. [PMID: 24187450 PMCID: PMC3812474 DOI: 10.3748/wjg.v19.i40.6744] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2013] [Revised: 09/02/2013] [Accepted: 09/17/2013] [Indexed: 02/06/2023] Open
Abstract
Primary liver cancer is the sixth most common cancer in the world and the third cause of cancer-related death. Hepatocellular carcinoma (HCC) represents more than 90% of primary liver cancers and generally occurs in patients with underlying chronic liver disease such as viral hepatitis, hemochromatosis, primary biliary cirrhosis and non-alcoholic steatohepatitis. Especially cirrhotic patients are at risk of HCC and regular surveillance could enable early detection and therapy, with potentially improved outcome. We here summarize existing evidence for surveillance including ultrasound, other radiological modalities and various serum biomarkers, and current international guideline recommendations for surveillance. Ultrasound and α-fetoprotein (alone or in combination) are most frequently used for surveillance, but their sensitivities and specificities are still far from perfect, and evidence for surveillance remains weak and controversial. Various other potential surveillance tools have been tested, including serum markers as des-carboxyprothrombin, lectin-bound α-fetoprotein, and (most recently) circulating TIE2-expressing monocytes, and radiological investigations such as computed tomography-scan or magnetic resonance imaging-scan. Although early results appear promising, these tools have generally been tested in diagnostic rather than surveillance setting, and in most cases, no detailed information is available on their cost-effectiveness. For the near future, it remains important to define those patients with highest risk of HCC and most benefit from surveillance, and to restrict surveillance to these categories.
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Cucchetti A, Piscaglia F, Cescon M, Ercolani G, Pinna AD. Systematic review of surgical resection vs radiofrequency ablation for hepatocellular carcinoma. World J Gastroenterol 2013; 19:4106-4118. [PMID: 23864773 PMCID: PMC3710412 DOI: 10.3748/wjg.v19.i26.4106] [Citation(s) in RCA: 66] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2013] [Revised: 04/26/2013] [Accepted: 06/19/2013] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) represents one of the most common neoplasms worldwide. Surgical resection and local ablative therapies represent the most frequent first lines therapies adopted when liver transplantation can not be offered or is not immediately accessible. Hepatic resection (HR) is currently considered the most curative strategy, but in the last decade local ablative therapies have started to obtain satisfactory results in term of efficacy and, of them, radiofrequency ablation (RFA) is considered the reference standard. An extensive literature review, from the year 2000, was performed, focusing on results coming from studies that directly compared HR and RFA. Qualities of the studies, characteristics of patients included, and patient survival and recurrence rates were analyzed. Except for three randomized controlled trials (RCT), most studies are affected by uncertain methodological approaches since surgical and ablated patients represent different populations as regards clinical and tumor features that are known to affect prognosis. Unfortunately, even the available RCTs report conflicting results. Until further evidences become available, it seems reasonable to offer RFA to very small HCC (< 2 cm) with no technical contraindications, since in this instance complete necrosis is most likely to be achieved. In larger nodules, namely > 2 cm and especially if > 3 cm, and/or in tumor locations in which ablation is not expected to be effective or safe, surgical removal is to be preferred.
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