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Gong X, Liu Y, Liang K, Chen Z, Ding K, Qiu L, Wei J, Du H. Cucurbitacin I exerts its anticancer effects by inducing cell cycle arrest via the KAT2a-ube2C/E2F1 pathway and inhibiting HepG2-induced macrophage M2 polarization. Biochem Biophys Res Commun 2024; 738:150508. [PMID: 39151295 DOI: 10.1016/j.bbrc.2024.150508] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 07/26/2024] [Accepted: 08/05/2024] [Indexed: 08/19/2024]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignancies globally, particularly prevalent in China, where it accounts for nearly half of the world's new cases and deaths each year, but has limited therapeutic options. This study systematically investigated the impact of cucurbitacin I on HCC cell lines including SK-Hep-1, Huh-7, and HepG2. The results revealed that cucurbitacin I not only inhibited cell proliferation, cell migration and colony formation, but also induced apoptosis in HCC cells. The apoptotic induction was accompanied by a decrease in the expression of the anti-apoptotic factor B-cell lymphoma 2 (Bcl2), and an elevation in the expression levels of pro-apoptotic factors, including tumor protein p53 (P53), bcl2 associated X-apoptosis regulator (Bax), and caspase3 (Cas3). Additionally, cucurbitacin I caused cell cycle arrest by modulating the lysine acetyltransferase 2A (KAT2A)-E2F transcription factor 1 (E2F1)/Ubiquitin-conjugating enzyme E2 C (UBE2C) signaling axis. In terms of regulation on tumor microenvironment, cucurbitacin I was demonstrated the ability to inhibit HCC cell-induced M2 polarization of macrophages. This comprehensive study unveils the multifaceted anti-cancer mechanisms of cucurbitacin I, providing robust support for its potential application in the treatment of HCC, offering new avenues for the future development of HCC treatment strategies.
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Affiliation(s)
- Xiaocheng Gong
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou, PR China
| | - Yunfei Liu
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou, PR China
| | - Keying Liang
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou, PR China
| | - Zixi Chen
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou, PR China
| | - Ke Ding
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou, PR China
| | - Li Qiu
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou, PR China
| | - Jinfen Wei
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou, PR China
| | - Hongli Du
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou, PR China.
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Pang NQ, Chan ACY, Kow AWC. Trends of liver transplantation in Asia. Updates Surg 2024:10.1007/s13304-024-01924-1. [PMID: 39046632 DOI: 10.1007/s13304-024-01924-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Accepted: 06/18/2024] [Indexed: 07/25/2024]
Abstract
Liver transplantation (LT) in Asia started comparatively early in 1964, just 1 year after Starzl's trail-blazing first attempt. Despite the quick start, LT was slow to develop in this region. Limited access to universal healthcare, lack of public understanding and support as well as the absence of strong legislation, on a backdrop of a wide range of diverse social, religious, economic and cultural background are all contributory factors. Through strong administrative efforts, the number of DDLTs in selected Asian countries has been slowly rising in recent years. However, Asians are generally still less likely to donate organs than Caucasians after death. The strong demand for LT with limited access to deceased organs has, therefore, led to constant need for innovation in LT this region, with the pioneering of various LDLT techniques and safe expansion of donor pool being driven primarily by Asian centers. Familiarity and the development of technical expertise in donor surgery have also resulted in Asian centers repeatedly pushing the boundaries on minimally invasive donor and recipient surgery. In this article, we focus on the past and present states of LT in Asia and explore the future trends of LT in this region.
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Affiliation(s)
- Ning Qi Pang
- Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, National University Hospital, National University Health System, NUHS Tower Block, 1E, Kent Ridge Road, Level 8, Singapore, 119228, Singapore
- National University Centre for Organ Transplantation (NUCOT), National University Hospital, National University Health System, Singapore, Singapore
| | - Albert C Y Chan
- Division of Liver Transplantation, Department of Surgery, The University of Hong Kong, Hong Kong SAR, China
| | - Alfred Wei Chieh Kow
- Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, National University Hospital, National University Health System, NUHS Tower Block, 1E, Kent Ridge Road, Level 8, Singapore, 119228, Singapore.
- National University Centre for Organ Transplantation (NUCOT), National University Hospital, National University Health System, Singapore, Singapore.
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
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Endo Y, Sasaki K, Munir MM, Woldesenbet S, Tsilimigras DI, Katayama E, Yang J, Limkemann A, Schenk A, Washburn K, Pawlik TM. Effect of the opioid crisis on the liver transplantation donor pool: A national analysis. Clin Transplant 2024; 38:e15290. [PMID: 38545890 DOI: 10.1111/ctr.15290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 01/22/2024] [Accepted: 03/03/2024] [Indexed: 04/20/2024]
Abstract
BACKGROUND Over the last decade there has been a surge in overdose deaths due to the opioid crisis. We sought to characterize the temporal change in overdose donor (OD) use in liver transplantation (LT), as well as associated post-LT outcomes, relative to the COVID-19 era. METHODS LT candidates and donors listed between January 2016 and September 2022 were identified from the Scientific Registry of Transplant Recipients database. Trends in LT donors and changes related to OD were assessed pre- versus post-COVID-19 (February 2020). RESULTS Between 2016 and 2022, most counties in the United States experienced an increase in overdose-related deaths (n = 1284, 92.3%) with many counties (n = 458, 32.9%) having more than a doubling in drug overdose deaths. Concurrently, there was an 11.2% increase in overall donors, including a 41.7% increase in the number of donors who died from drug overdose. In pre-COVID-19 overdose was the 4th top mechanism of donor death, while in the post-COVID-19 era, overdose was the 2nd most common cause of donor death. OD was younger (OD: 35 yrs, IQR 29-43 vs. non-OD: 43 yrs, IQR 31-56), had lower body mass index (≥35 kg/cm2, OD: 31.2% vs. non-OD: 33.5%), and was more likely to be HCV+ (OD: 28.9% vs. non-OD: 5.4%) with lower total bilirubin (≥1.1 mg/dL, OD: 12.9% vs. non-OD: 20.1%) (all p < .001). Receipt of an OD was not associated with worse graft survival (HR .94, 95% CI .88-1.01, p = .09). CONCLUSIONS Opioid deaths markedly increased following the COVID-19 pandemic, substantially altering the LT donor pool in the United States.
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Affiliation(s)
- Yutaka Endo
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Kazunari Sasaki
- Department of Surgery, Stanford University, Stanford, California, USA
| | - Muhammad Musaab Munir
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Selamawit Woldesenbet
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Diamantis I Tsilimigras
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Erryk Katayama
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Jason Yang
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Ashley Limkemann
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Austin Schenk
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Kenneth Washburn
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
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4
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Endo Y, Sasaki K, Moazzam Z, Woldesenbet S, Lima HA, Alaimo L, Munir MM, Shaikh CF, Yang J, Azap L, Katayama E, Kitago M, Schenk A, Washburn K, Pawlik TM. Liver transplantation access and outcomes: Impact of variations in liver-specific specialty care. Surgery 2024; 175:868-876. [PMID: 37743104 DOI: 10.1016/j.surg.2023.06.043] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 05/08/2023] [Accepted: 06/28/2023] [Indexed: 09/26/2023]
Abstract
BACKGROUND We sought to characterize the impact access to gastroenterologists/hepatologists has on liver transplantation listing, as well as time on the liver transplantation waitlist and post-transplant outcomes. METHODS Liver transplantation registrants aged >18 years between January 1, 2004 and December 31, 2019 were identified from the Scientific Registry of Transplant Recipients Standard Analytic Files. The liver transplantation registration ratio was defined as the ratio of liver transplant waitlist registrations in a given county per 1,000 liver-related deaths. RESULTS A total of 150,679 liver transplantation registrants were included. Access to liver transplantation centers and liver-specific specialty physicians varied markedly throughout the United States. Of note, the liver transplantation registration ratio was lower in counties with poor access to liver-specific care versus counties with adequate access (poor access 137.2, interquartile range 117.8-163.2 vs adequate access 157.6, interquartile range 127.3-192.2, P < .001). Among patients referred for liver transplantation, the cumulative incidence of waitlist mortality and post-transplant graft survival was comparable among patients with poor versus adequate access to liver-specific care (both P > .05). Among liver transplantation recipients living in areas with poor access, after controlling for recipient and donor characteristics, cold ischemic time, and model for end-stage liver disease score, the area deprivation index predicted graft survival (referent, low area deprivation index; medium area deprivation index, hazard ratio 1.52, 95% confidence interval 1.03-12.23; high area deprivation index, 1.45, 95% confidence interval 1.01-12.09, both P < .05). CONCLUSION Poor access to liver-specific care was associated with a reduction in liver transplantation registration, and individuals residing in counties with high social deprivation had worse graft survival among patients living in counties with poor access to liver-specific care.
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Affiliation(s)
- Yutaka Endo
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
| | | | - Zorays Moazzam
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
| | - Selamawit Woldesenbet
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
| | - Henrique A Lima
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
| | - Laura Alaimo
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
| | - Muhammad Musaab Munir
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
| | - Chanza F Shaikh
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
| | - Jason Yang
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
| | - Lovette Azap
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
| | - Erryk Katayama
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
| | - Minoru Kitago
- Department of Surgery, Keio University, Tokyo, Japan
| | - Austin Schenk
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
| | - Kenneth Washburn
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH.
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5
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Munir MM, Endo Y, Mehdi Khan MM, Woldesenbet S, Yang J, Washburn K, Limkemann A, Schenk A, Pawlik TM. Association of Neighborhood Deprivation and Transplant Center Quality with Liver Transplantation Outcomes. J Am Coll Surg 2024; 238:291-302. [PMID: 38050968 DOI: 10.1097/xcs.0000000000000905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2023]
Abstract
BACKGROUND Social determinants of health can impact the quality of liver transplantation (LT) care. We sought to assess whether the association between neighborhood deprivation and transplant outcomes can be mitigated by receiving care at high-quality transplant centers. STUDY DESIGN In this population-based cohort study, patients who underwent LT between 2004 and 2019 were identified in the Scientific Registry of Transplant Recipients. LT-recipient neighborhoods were identified at the county level and stratified into quintiles relative to Area Deprivation Index (ADI). Transplant center quality was based on the Scientific Registry of Transplant Recipients 5-tier ranking using standardized transplant rate ratios. Multivariable Cox regression was used to assess the relationship between ADI, hospital quality, and posttransplant survival. RESULTS A total of 41,333 recipients (median age, 57.0 [50.0 to 63.0] years; 27,112 [65.4%] male) met inclusion criteria. Patients residing in the most deprived areas were more likely to have nonalcoholic steatohepatitis, be Black, and travel further distances to reach a transplant center. On multivariable analysis, post-LT long-term mortality was associated with low- vs high-quality transplant centers (hazard ratio [HR] 1.19, 95% CI 1.07 to 1.32), as well as among patients residing in high- vs low-ADI neighborhoods (HR 1.25, 95% CI 1.16 to 1.34; both p ≤ 0.001). Of note, individuals residing in high- vs low-ADI neighborhoods had a higher risk of long-term mortality after treatment at a low-quality (HR 1.31, 95% CI 1.06 to 1.62, p = 0.011) vs high-quality (HR 1.12, 95% CI 0.83 to 1.52, p = 0.471) LT center. CONCLUSIONS LT at high-quality centers may be able to mitigate the association between posttransplant survival and neighborhood deprivation. Investments and initiatives that increase access to referrals to high-quality centers for patients residing in higher deprivation may lead to better outcomes and help mitigate disparities in LT.
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Affiliation(s)
- Muhammad Musaab Munir
- From the Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
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Cha DI, Kang TW, Jeong WK, Kim JM, Choi GS, Joh JW, Yi NJ, Ahn SH. Preoperative assessment of microvascular invasion risk using gadoxetate-enhanced MRI for predicting outcomes after liver transplantation for single hepatocellular carcinoma within the Milan criteria. Eur Radiol 2024; 34:498-508. [PMID: 37505248 DOI: 10.1007/s00330-023-09936-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 05/10/2023] [Accepted: 05/15/2023] [Indexed: 07/29/2023]
Abstract
OBJECTIVE To compare therapeutic outcomes after liver transplantation (LT) between hepatocellular carcinomas (HCC) with low and high risk for microvascular invasion (MVI) within the Milan criteria evaluated preoperatively. METHODS Eighty patients with a single HCC who underwent LT as the initial therapy between 2008 and 2017 were included from two tertiary referral medical centers in a HBV-predominant population. A preoperative MVI-risk model was used to identify low- and high-risk patients. Recurrence-free survival (RFS) after LT between the two risk groups was compared using Kaplan-Meier curves with the log-rank test. Prognostic factors for RFS were identified using a multivariable Cox hazard regression analysis. RESULTS Eighty patients were included (mean age, 51.8 years +/- 7.5 [standard deviation], 65 men). Patients were divided into low-risk (n = 64) and high-risk (n = 16) groups for MVI. The RFS rates after LT were significantly lower in the MVI high-risk group compared to the low-risk group at 1 year (75.0% [95% CI: 56.5-99.5%] vs. 96.9% [92.7-100%], p = 0.048), 3 years (62.5% [42.8-91.4%] vs. 95.3% [90.3-100%], p = 0.008), and 5 years (62.5% [42.8-91.4%] vs. and 95.3% [90.3-100%], p = 0.008). In addition, multivariable analysis showed that MVI high risk was the only significant factor for poor RFS (p = 0.016). CONCLUSION HCC patients with a high risk of MVI showed significantly lower RFS after LT than those without. This model could aid in selecting optimal candidates in addition to the Milan criteria when considering upfront LT for patients with HCC if alternative treatment options are available. CLINICAL RELEVANCE STATEMENT High risk for microvascular invasion (MVI) in hepatocellular carcinoma patients lowered recurrence-free survival after liver transplantation, despite meeting the Milan criteria. Identifying MVI risk could aid candidate selection for upfront liver transplantation, particularly if alternative treatments are available. KEY POINTS • A predictive model-derived microvascular invasion (MVI) high- and low-risk groups had a significant difference in the incidence of MVI on pathology. • Recurrence-free survival after liver transplantation (LT) for single hepatocellular carcinoma (HCC) within the Milan criteria was significantly different between the MVI high- and low-risk groups. • The peak incidence of tumor recurrence was 20 months after liver transplantation, probably indicating that HCC with high risk for MVI had a high risk of early (≤ 2 years) tumor recurrence.
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Affiliation(s)
- Dong Ik Cha
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea
| | - Tae Wook Kang
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
| | - Woo Kyoung Jeong
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea
| | - Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Gyu-Seong Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jae-Won Joh
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Soo Hyun Ahn
- Department of Mathematics, Ajou University, Suwon, Republic of Korea
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Zhang J, Shi M, Ding W, Duan M, Dai Z, Chen Y. Effect of minimally invasive versus open surgery in hepatectomy on postoperative wound complications in patients with hepatocellular carcinoma: A meta-analysis. Int Wound J 2023; 20:4159-4165. [PMID: 37442783 PMCID: PMC10681463 DOI: 10.1111/iwj.14313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 06/29/2023] [Accepted: 07/01/2023] [Indexed: 07/15/2023] Open
Abstract
In a meta-analysis, we assessed the impact of different surgical approaches on the outcome of hepatectomy with hepatocellular carcinoma. Four databases, including PubMed, Embase, Cochrane Library, and the Web of Science, have been critically reviewed through the full literature through June 2023. Eleven related trials were examined once they had met the trial's classification and exclusion criteria, as well as the assessment of the quality. A random effects approach was applied to analysis of operative organ infections, and a fixed-effect model was applied to determine the 95% CI and OR. Analysis of the data was done with RevMan 5.3. Our findings indicated that patients undergoing minimally invasive liver cancer surgery had significantly lower risks of surgical organ infection (OR, 0.35; 95% CI, 0.16-0.77; p = 0.009) and wound infection (OR, 0.19; 95% CI, 0.13-0.28; p < 0.001) compared to those undergoing open surgery. There was no heterogeneity observed between the two groups (I2 = 0) in wound infection. Nevertheless, because of the limited number of randomised controlled trials in this meta-analysis, care should be taken and carefully considered in the treatment of these values. Further high-quality studies involving a large number of samples are needed to validate and reinforce the results.
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Affiliation(s)
- Junli Zhang
- Department of AnesthesiologyThe Sixth Medical Center of PLA General HospitalBeijingChina
| | - Meiping Shi
- Department of AnesthesiologyThe Sixth Medical Center of PLA General HospitalBeijingChina
| | - Wan Ding
- Department of AnesthesiologyThe Sixth Medical Center of PLA General HospitalBeijingChina
| | - Mingda Duan
- Department of AnesthesiologyHainan Branch of General Hospital of People's Liberation ArmySanyaChina
| | - Ziqing Dai
- Department of Medical RecordsThe Sixth Medical Center of PLA General HospitalBeijingChina
| | - Yu Chen
- Department of AnesthesiologyThe Sixth Medical Center of PLA General HospitalBeijingChina
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Khalil A, Quaglia A, Gélat P, Saffari N, Rashidi H, Davidson B. New Developments and Challenges in Liver Transplantation. J Clin Med 2023; 12:5586. [PMID: 37685652 PMCID: PMC10488676 DOI: 10.3390/jcm12175586] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 08/15/2023] [Accepted: 08/26/2023] [Indexed: 09/10/2023] Open
Abstract
Liver disease is increasing in incidence and is the third most common cause of premature death in the United Kingdom and fourth in the United States. Liver disease accounts for 2 million deaths globally each year. Three-quarters of patients with liver disease are diagnosed at a late stage, with liver transplantation as the only definitive treatment. Thomas E. Starzl performed the first human liver transplant 60 years ago. It has since become an established treatment for end-stage liver disease, both acute and chronic, including metabolic diseases and primary and, at present piloting, secondary liver cancer. Advances in surgical and anaesthetic techniques, refined indications and contra-indications to transplantation, improved donor selection, immunosuppression and prognostic scoring have allowed the outcomes of liver transplantation to improve year on year. However, there are many limitations to liver transplantation. This review describes the milestones that have occurred in the development of liver transplantation, the current limitations and the ongoing research aimed at overcoming these challenges.
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Affiliation(s)
- Amjad Khalil
- Liver Unit, Wellington Hospital, London NW8 9TA, UK
- Centre for Surgical Innovation, Organ Regeneration and Transplantation, University College London, London NW3 2PS, UK
- Clinical Service of HPB Surgery and Liver Transplantation, Royal Free Hospital, London NW3 2QG, UK
| | - Alberto Quaglia
- Cancer Institute, University College London, London WC1E 6DD, UK
| | - Pierre Gélat
- Division of Surgery and Interventional Science, University College London, London NW3 2PS, UK
| | - Nader Saffari
- Department of Mechanical Engineering, University College London, London WC1E 7JE, UK
| | - Hassan Rashidi
- Institute of Child Health, University College London, London WC1N 1EH, UK;
| | - Brian Davidson
- Liver Unit, Wellington Hospital, London NW8 9TA, UK
- Centre for Surgical Innovation, Organ Regeneration and Transplantation, University College London, London NW3 2PS, UK
- Clinical Service of HPB Surgery and Liver Transplantation, Royal Free Hospital, London NW3 2QG, UK
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9
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Morise Z, Aldrighetti L, Belli G, Ratti F, Cheung TT, Lo CM, Tanaka S, Kubo S, Okamura Y, Uesaka K, Monden K, Sadamori H, Hashida K, Kawamoto K, Gotohda N, Chen K, Kanazawa A, Takeda Y, Ohmura Y, Ueno M, Ogura T, Suh KS, Kato Y, Sugioka A, Belli A, Nitta H, Yasunaga M, Cherqui D, Abdul Halim N, Laurent A, Kaneko H, Otsuka Y, Kim KH, Cho HD, Lin CCW, Ome Y, Seyama Y, Troisi RI, Berardi G, Rotellar F, Wilson GC, Geller DA, Soubrane O, Yoh T, Kaizu T, Kumamoto Y, Han HS, Ekmekcigil E, Dagher I, Fuks D, Gayet B, Buell JF, Ciria R, Briceno J, O’Rourke N, Lewin J, Edwin B, Shinoda M, Abe Y, Hilal MA, Alzoubi M, Tanabe M, Wakabayashi G. An International Retrospective Observational Study of Liver Functional Deterioration after Repeat Liver Resection for Patients with Hepatocellular Carcinoma. Cancers (Basel) 2022; 14:2598. [PMID: 35681578 PMCID: PMC9179920 DOI: 10.3390/cancers14112598] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Revised: 05/08/2022] [Accepted: 05/11/2022] [Indexed: 02/06/2023] Open
Abstract
Whether albumin and bilirubin levels, platelet counts, ALBI, and ALPlat scores could be useful for the assessment of permanent liver functional deterioration after repeat liver resection was examined, and the deterioration after laparoscopic procedure was evaluated. For 657 patients with liver resection of segment or less in whom results of plasma albumin and bilirubin levels and platelet counts before and 3 months after surgery could be retrieved, liver functional indicators were compared before and after surgery. There were 268 patients who underwent open repeat after previous open liver resection, and 224 patients who underwent laparoscopic repeat after laparoscopic liver resection. The background factors, liver functional indicators before and after surgery and their changes were compared between both groups. Plasma levels of albumin (p = 0.006) and total bilirubin (p = 0.01) were decreased, and ALBI score (p = 0.001) indicated worse liver function after surgery. Laparoscopic group had poorer preoperative performance status and liver function. Changes of liver functional values before and after surgery and overall survivals were similar between laparoscopic and open groups. Plasma levels of albumin and bilirubin and ALBI score could be the indicators for permanent liver functional deterioration after liver resection. Laparoscopic group with poorer conditions showed the similar deterioration of liver function and overall survivals to open group.
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Affiliation(s)
- Zenichi Morise
- Department of General Surgery, Fujita Health University School of Medicine Okazaki Medical Center, Okazaki 444-0827, Japan
| | - Luca Aldrighetti
- Hepatobiliary Division in Department of Surgery, San Raffaele Hospital, 20132 Milano, Italy; (L.A.); (F.R.)
| | - Giulio Belli
- Department of General and HPB Surgery, Loreto Nuovo Hospital, 80127 Naples, Italy;
| | - Francesca Ratti
- Hepatobiliary Division in Department of Surgery, San Raffaele Hospital, 20132 Milano, Italy; (L.A.); (F.R.)
| | - Tan To Cheung
- Division of HBP and Liver Transplant, University of Hong Kong Queen Mary Hospital, Hong Kong, China; (T.T.C.); (C.M.L.)
| | - Chung Mau Lo
- Division of HBP and Liver Transplant, University of Hong Kong Queen Mary Hospital, Hong Kong, China; (T.T.C.); (C.M.L.)
| | - Shogo Tanaka
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka 545-8586, Japan; (S.T.); (S.K.)
| | - Shoji Kubo
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka 545-8586, Japan; (S.T.); (S.K.)
| | - Yukiyasu Okamura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, Sunto, Shizuoka 411-8777, Japan; (Y.O.); (K.U.)
| | - Katsuhiko Uesaka
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, Sunto, Shizuoka 411-8777, Japan; (Y.O.); (K.U.)
| | - Kazuteru Monden
- Departments of Surgery, Fukuyama City Hospital, Fukuyama 721-8511, Japan; (K.M.); (H.S.)
| | - Hiroshi Sadamori
- Departments of Surgery, Fukuyama City Hospital, Fukuyama 721-8511, Japan; (K.M.); (H.S.)
| | - Kazuki Hashida
- Department of Surgery, Kurashiki Central Hospital, Kurashiki 710-8602, Japan; (K.H.); (K.K.)
| | - Kazuyuki Kawamoto
- Department of Surgery, Kurashiki Central Hospital, Kurashiki 710-8602, Japan; (K.H.); (K.K.)
| | - Naoto Gotohda
- Division of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Kashiwa 277-8577, Japan;
| | - KuoHsin Chen
- Division of General Surgery, Department of Surgery, Far-Eastern Memorial Hospital, New Taipei City 220, Taiwan;
- Department of Electrical Engineering, Yuan Ze University, Taoyuan City 320, Taiwan
| | - Akishige Kanazawa
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City General Hospital, Osaka 534-0021, Japan;
| | - Yutaka Takeda
- Department of Surgery, Kansai Rosai Hospital, Amagasaki 660-8511, Japan; (Y.T.); (Y.O.)
| | - Yoshiaki Ohmura
- Department of Surgery, Kansai Rosai Hospital, Amagasaki 660-8511, Japan; (Y.T.); (Y.O.)
| | - Masaki Ueno
- Second Department of Surgery, Wakayama Medical University, Wakayama 641-8509, Japan;
| | - Toshiro Ogura
- Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo 113-8510, Japan; (T.O.); (M.T.)
| | - Kyung Suk Suh
- Department of Hepatobiliary and Pancreatic Surgery, Seoul National University Hospital, Seoul 03080, Korea;
| | - Yutaro Kato
- Department of Gastrointestinal Surgery, Fujita Health University School of Medicine, Toyoake 470-1192, Japan; (Y.K.); (A.S.)
| | - Atsushi Sugioka
- Department of Gastrointestinal Surgery, Fujita Health University School of Medicine, Toyoake 470-1192, Japan; (Y.K.); (A.S.)
| | - Andrea Belli
- Department of Abdominal Surgical Oncology, Fondazione G.Pascale-IRCCS, National Cancer Institute of Naples, 80131 Napoli, Italy;
| | - Hiroyuki Nitta
- Department of Surgery, Iwate Medical University, Morioka 028-3695, Japan;
| | - Masafumi Yasunaga
- Department of Surgery, Kurume University School of Medicine, Kurume 830-0011, Japan;
| | - Daniel Cherqui
- Paul Brousse Hospital, 94800 Villejuif, France; (D.C.); (N.A.H.)
- Paris-Sud University, 91190 Gif-sur-Yvette, France;
| | | | | | - Hironori Kaneko
- Division of General and Gastroenterological Surgery, Department of Surgery, Toho University Faculty of Medicine, Tokyo 143-8540, Japan; (H.K.); (Y.O.)
| | - Yuichiro Otsuka
- Division of General and Gastroenterological Surgery, Department of Surgery, Toho University Faculty of Medicine, Tokyo 143-8540, Japan; (H.K.); (Y.O.)
| | - Ki Hun Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Ulsan University and Asan Medical Center, Seoul 05505, Korea; (K.H.K.); (H.-D.C.)
| | - Hwui-Dong Cho
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Ulsan University and Asan Medical Center, Seoul 05505, Korea; (K.H.K.); (H.-D.C.)
| | - Charles Chung-Wei Lin
- Department of Surgery and Surgical Oncology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei 112, Taiwan;
- IRCAD-AITS, Changhua 505, Taiwan
| | - Yusuke Ome
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo 113-8677, Japan; (Y.O.); (Y.S.)
| | - Yasuji Seyama
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo 113-8677, Japan; (Y.O.); (Y.S.)
| | - Roberto I. Troisi
- Department of Clinical Medicine and Surgery, University of Naples Federico II, 80138 Napoli, Italy;
| | - Giammauro Berardi
- General Hepato-Biliary and Liver Transplantation Surgery, Ghent University Hospital Medical School, 9000 Gent, Belgium;
| | - Fernando Rotellar
- Hepato-Bilio-Pancreatic Unit of Clinica Universitaria de Navarra, 31008 Pamplona, Spain;
| | - Gregory C. Wilson
- Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA; (G.C.W.); (D.A.G.)
| | - David A. Geller
- Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA; (G.C.W.); (D.A.G.)
| | - Olivier Soubrane
- Department of HPB Surgery and Liver Transplant, Beaujon Hospital, Clichy 92110, France; (O.S.); (T.Y.)
| | - Tomoaki Yoh
- Department of HPB Surgery and Liver Transplant, Beaujon Hospital, Clichy 92110, France; (O.S.); (T.Y.)
| | - Takashi Kaizu
- Department of Surgery, Kitasato University School of Medicine, Sagamihara 252-0374, Japan; (T.K.); (Y.K.)
| | - Yusuke Kumamoto
- Department of Surgery, Kitasato University School of Medicine, Sagamihara 252-0374, Japan; (T.K.); (Y.K.)
| | - Ho-Seong Han
- Seoul National University College of Medicine, Bundang Hospital, Seongnam-si 13620, Korea; (H.-S.H.); (E.E.)
| | - Ela Ekmekcigil
- Seoul National University College of Medicine, Bundang Hospital, Seongnam-si 13620, Korea; (H.-S.H.); (E.E.)
| | | | - David Fuks
- Department of Digestive Diseases, Institute Mutualiste Montsouris, University of Paris Descartes, 75014 Paris, France; (D.F.); (B.G.)
| | - Brice Gayet
- Department of Digestive Diseases, Institute Mutualiste Montsouris, University of Paris Descartes, 75014 Paris, France; (D.F.); (B.G.)
| | - Joseph F. Buell
- Tulane Transplant Abdominal Institute, Tulane University, New Orleans, LA 70112, USA;
| | - Ruben Ciria
- Unit of Hepatobiliary Surgery and Liver Transplantation, University Hospital Reina Sofia, 30003 Murcia, Spain; (R.C.); (J.B.)
| | - Javier Briceno
- Unit of Hepatobiliary Surgery and Liver Transplantation, University Hospital Reina Sofia, 30003 Murcia, Spain; (R.C.); (J.B.)
| | - Nicholas O’Rourke
- Department of General Surgery and HPB Surgery, Royal Brisbane Hospital, The University of Queensland, St Lucia, QLD 4072, Australia; (N.O.); (J.L.)
| | - Joel Lewin
- Department of General Surgery and HPB Surgery, Royal Brisbane Hospital, The University of Queensland, St Lucia, QLD 4072, Australia; (N.O.); (J.L.)
| | - Bjorn Edwin
- Department of Hepatopancreatobiliary Surgery, Oslo University Hospital-Rikshospitalet, 0372 Oslo, Norway;
| | - Masahiro Shinoda
- Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan; (M.S.); (Y.A.)
| | - Yuta Abe
- Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan; (M.S.); (Y.A.)
| | - Mohammed Abu Hilal
- Istituto Ospedaliero—Fondazione Poliambulanza, 25124 Brescia, BS, Italy;
- University Hospital Southampton, Hampshire SO16 6YD, UK;
| | - Mohammad Alzoubi
- University Hospital Southampton, Hampshire SO16 6YD, UK;
- General Surgery Department, The University of Jordan, Amman 11972, Jordan
| | - Minoru Tanabe
- Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo 113-8510, Japan; (T.O.); (M.T.)
| | - Go Wakabayashi
- Department of Surgery, Ageo Central General Hospital, Ageo 362-8588, Japan;
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10
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Yoon YI, Song GW, Lee S, Moon D, Hwang S, Kang WH, Cho HD, Ha SM, Kim MJ, Kim SH, Na BG, Yang G, Min Kim S, Hyun Shim J, Park JI. Salvage living donor liver transplantation versus repeat liver resection for patients with recurrent hepatocellular carcinoma and Child-Pugh class A liver cirrhosis: A propensity score-matched comparison. Am J Transplant 2022; 22:165-176. [PMID: 34383368 DOI: 10.1111/ajt.16790] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 07/29/2021] [Accepted: 07/31/2021] [Indexed: 01/27/2023]
Abstract
Following curative liver resection (LR), resectable tumor recurrence in patients with preserved liver function leads to deciding between a repeat LR and a salvage liver transplantation (LT), if a donor's liver is available. This retrospective study compared survival outcomes and recurrence pattern following salvage living donor LT (LDLT) and repeat LR in patients with recurrent hepatocellular carcinoma (HCC). We reviewed the medical records of patients who underwent repeat LR (n = 163) or LDLT (n = 84) for recurrent HCC following curative resections, between January 2005 and December 2017 at a single institution. A 1:1 propensity score matching led to 42 patients per group. Disease-specific and recurrence-free survival were significantly better in the salvage LDLT group than in the repeat LR group (p = .042; HR = 2.40; 95% CI, 0.69-6.00 and p < .001; HR = 4.23; 95% CI, 2.05-8.71, respectively). Despite significant differences in recurrence patterns between the two groups (p = .019), the patient death rates, after recurrence, were similar for both groups (p = .760). This study indicates that salvage LDLT is superior to repeat LR for treating patients with transplantable, intrahepatic HCC recurrence, even in patients with Child-Pugh class A liver cirrhosis.
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Affiliation(s)
- Young-In Yoon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gi-Won Song
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - SungGyu Lee
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - DeokBog Moon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Shin Hwang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Woo-Hyoung Kang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hwui-Dong Cho
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Su-Min Ha
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Min-Jae Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sang-Hoon Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Byeong-Gon Na
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Geunhyeok Yang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung Min Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ju Hyun Shim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jeong-Ik Park
- Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
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11
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Hwang SH, Park MS, Park S, Lim JS, Kim SU, Park YN. Comparison of the current guidelines for diagnosing hepatocellular carcinoma using gadoxetic acid-enhanced magnetic resonance imaging. Eur Radiol 2021; 31:4492-4503. [PMID: 33409787 DOI: 10.1007/s00330-020-07468-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 10/12/2020] [Accepted: 11/04/2020] [Indexed: 12/12/2022]
Abstract
OBJECTIVES To compare the performance of current guidelines applicable to the diagnosis of hepatocellular carcinomas (HCCs) using gadoxetic acid-enhanced magnetic resonance imaging (MRI). METHODS Two hundred and forty-one hepatic lesions (149 HCCs, six other malignancies, 86 benign lesions) in 177 patients at risk of HCC without a history of previous treatment for hepatic malignancy in a tertiary center were retrospectively reviewed. Either histopathology results or long-term (> 24 months) follow-up images were used as a standard of reference. All lesions were categorized according to the Liver Imaging Reporting and Data System (LI-RADS), European Association for the Study of the Liver (EASL), Asian Pacific Association for the Study of the Liver (APASL), and Korean Liver Cancer Study Group-National Cancer Center (KLCSG-NCC) guidelines. The sensitivity and specificity thereof were assessed using a generalized estimation equation. RESULTS For gadoxetic acid-enhanced MRI, LI-RADS (95%, 95% confidence interval [CI] 88-98) and EASL (94%, 95% CI 86-97) yielded the highest specificity, while EASL yielded the lowest sensitivity (54% [95% CI 46-62]). APASL yielded the highest sensitivity (91% [95% CI 86-95]) with the lowest specificity (78% [95% CI 69-86]). KLCSG-NCC showed balanced sensitivity (85% [79-90]) and specificity (88% [95% CI 80-93]). Differences were more prominent in small nodules between 1 and 2 cm. CONCLUSION The diagnostic performance of current guidelines for HCC on gadoxetic acid-enhanced MRI was significantly different, and a potential inverse association between sensitivity and specificity was observed. KEY POINTS • EASL and LI-RADS yielded the highest specificity with the lowest sensitivity, whereas APASL yielded the highest sensitivity with the lowest specificity. • Differences in the diagnostic performances of guidelines were prominent in small nodules between 1 and 2 cm. • Additional evaluation of CT findings improved the diagnostic sensitivity and accuracy of EASL and LI-RADS. Although doing so decreased specificity, it remained above 89-90%.
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Affiliation(s)
- Shin Hye Hwang
- Department of Radiology, National Health Insurance Service Ilsan Hospital, Goyang, South Korea
- Department of Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Mi-Suk Park
- Department of Medicine, Yonsei University College of Medicine, Seoul, South Korea.
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
| | - Sumi Park
- Department of Radiology, National Health Insurance Service Ilsan Hospital, Goyang, South Korea
| | - Joon Seok Lim
- Department of Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Seung Up Kim
- Department of Internal Medicine, Severance Hospital, Seoul, South Korea
| | - Young Nyun Park
- Department of Pathology, Severance Hospital, Seoul, South Korea
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12
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Wang R, Zhu Y, Chen J, Wang Y, Song X, Wu Y, Jin F, Wang Y. The quinazoline derivative, 04NB-03, induces cell cycle arrest and apoptosis in hepatocellular carcinoma cells in a reactive oxygen species-dependent manner. Chem Biol Interact 2021; 338:109371. [PMID: 33582112 DOI: 10.1016/j.cbi.2021.109371] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2020] [Revised: 12/14/2020] [Accepted: 01/04/2021] [Indexed: 10/22/2022]
Abstract
Hepatocellular carcinoma (HCC) is one of the most deadly malignancies worldwide. However, current therapeutic drugs for HCC are far from satisfactory. Thus, the development of new drugs is urgently needed. In this study, we identified a novel quinazoline derivative, 04NB-03, with potent anti-HCC activities both in vitro and in vivo. 04NB-03 effectively suppressed the viability and proliferation of HCC cells. It induced both cell cycle arrest at the G2/M phase and apoptosis in concentration- and time-dependent manners. Moreover, 04NB-03 treatment significantly reduced xenograft tumor growth without notable toxic effects. Mechanistically, 04NB-03 induced endogenous reactive oxygen species (ROS) accumulation in concentration- and time-dependent manners. Scavenging the ROS reversed 04NB-03-induced cell cycle arrest and apoptosis. Taken together, these results indicate that the quinazoline derivative, 04NB-03, inhibits the growth of HCC cells through the induction of cell cycle arrest and apoptosis in an ROS-dependent manner. 04NB-03 is, therefore, a potential small molecule candidate for the development of antitumor drugs targeting HCC.
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Affiliation(s)
- Rongze Wang
- Guangzhou Jinan Biomedicine Research and Development Center, Key Laboratory of Bioengineering Medicine of Guangdong Province, Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China
| | - Yexuan Zhu
- Guangzhou Jinan Biomedicine Research and Development Center, Key Laboratory of Bioengineering Medicine of Guangdong Province, Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China
| | - Jingyi Chen
- Guangzhou Jinan Biomedicine Research and Development Center, Key Laboratory of Bioengineering Medicine of Guangdong Province, Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China
| | - Yiliang Wang
- Guangzhou Jinan Biomedicine Research and Development Center, Key Laboratory of Bioengineering Medicine of Guangdong Province, Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China
| | - Xiaowei Song
- Guangzhou Jinan Biomedicine Research and Development Center, Key Laboratory of Bioengineering Medicine of Guangdong Province, Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China
| | - Yanting Wu
- Guangzhou Jinan Biomedicine Research and Development Center, Key Laboratory of Bioengineering Medicine of Guangdong Province, Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China
| | - Fujun Jin
- Guangzhou Jinan Biomedicine Research and Development Center, Key Laboratory of Bioengineering Medicine of Guangdong Province, Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China; Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, 510632, China.
| | - Yifei Wang
- Guangzhou Jinan Biomedicine Research and Development Center, Key Laboratory of Bioengineering Medicine of Guangdong Province, Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China; Key Laboratory of Virology of Guangzhou, Jinan University, Guangzhou, 510632, China.
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13
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Xu G, Jin B, Xian X, Yang H, Zhao H, Du S, Makuuchi M, Pawlik TM, Mao Y. Evolutions in the Management of Hepatocellular Carcinoma over Last 4 Decades: An Analysis from the 100 Most Influential Articles in the Field. Liver Cancer 2021; 10:137-150. [PMID: 33977090 PMCID: PMC8077437 DOI: 10.1159/000513412] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Accepted: 11/26/2020] [Indexed: 02/04/2023] Open
Abstract
INTRODUCTION Over the past 4 decades, the management of hepatocellular carcinoma (HCC) has changed dramatically. The publications that have had the most significant impact on HCC management have not been quantitatively analyzed. In this article, we analyzed the 100 most influential articles over the past 4 decades using bibliometric citation analysis to characterize the evolution in HCC treatment. METHODS The top-cited publications were identified and analyzed from the Clarivate Analytics Web of Science Core Collection database. RESULTS The 100 most cited articles were identified with an average of 738 citations (range: 349-6,799). There was an increase in the number of influential articles in the late 1990s, which was paralleled by an increase in reports focused on locoregional treatment of HCC. Most top 100 articles came from the USA (n = 35), followed by Italy (n = 28), mainland China (n = 26), and Japan (n = 24). The surgical management was the most studied topic (n = 33). The Annals of Surgery published the highest number of papers (n = 26) with 13,978 citations. While other 3 topics (surgical management, locoregional treatment, and outcome prediction) declined among publications beginning in the 2000s, there was an emergence of highly cited papers on targeted drugs and immune checkpoint inhibitors with a concomitant increase in the number of publications on systemic therapy. CONCLUSIONS Based on bibliometric analysis of the literature over the last 40 years, a comprehensive analysis of the most historically significant HCC management articles highlighted the key contributions made to the evolution and advancement of this specialist field. The data should provide clinicians and researchers insight into future directions relative to the advancement of HCC management.
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Affiliation(s)
- Gang Xu
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC and Chinese Academy of Medical Sciences, Beijing, China
| | - Bao Jin
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC and Chinese Academy of Medical Sciences, Beijing, China
| | - Xiaomeng Xian
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC and Chinese Academy of Medical Sciences, Beijing, China
| | - Huayu Yang
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC and Chinese Academy of Medical Sciences, Beijing, China
| | - Haitao Zhao
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC and Chinese Academy of Medical Sciences, Beijing, China
| | - Shunda Du
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC and Chinese Academy of Medical Sciences, Beijing, China
| | - Masatoshi Makuuchi
- President of the Koto Hospital, Tokyo, Japan,***Prof. Masatoshi Makuuchi, MD, President of the Koto Hospital, Tokyo (Japan),
| | - Timothy M. Pawlik
- Department of Surgery, Wexner Medical Center, The Ohio State University, Columbus, Ohio, USA,**Timothy Pawlik, Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH (USA),
| | - Yilei Mao
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC and Chinese Academy of Medical Sciences, Beijing, China,*Yilei Mao, Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC and Chinese Academy of Medical Sciences, Beijing 100730 (China),
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14
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Ito K, Takemura N, Inagaki F, Mihara F, Kokudo N. Difference in treatment algorithms for hepatocellular carcinoma between world's principal guidelines. Glob Health Med 2020; 2:282-291. [PMID: 33330822 PMCID: PMC7731415 DOI: 10.35772/ghm.2020.01066] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Revised: 09/24/2020] [Accepted: 09/28/2020] [Indexed: 12/15/2022]
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer-related death globally. Clinical guidelines for HCC have been established and revised by many countries and regions. We summarized and compared the treatment algorithms in the updated HCC guidelines established by Japan, China, Hong Kong, the Asian-Pacific Association for the Study of the Liver, the American Association for the Study of Liver Diseases, and the European Association for the Study of the Liver and European Organization for Research and Treatment of Cancer. Variations in treatment algorithms between the guidelines is inevitable, considering the differences in the prevalence and etiology of HCC, local clinical practice, and medical and insurance systems between countries or regions, and this might be confusing for practitioners worldwide. A comprehensive understanding of the guidelines that are globally available might be useful for future improvement of each guideline.
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Affiliation(s)
- Kyoji Ito
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Nobuyuki Takemura
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Fuyuki Inagaki
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Fuminori Mihara
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Norihiro Kokudo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan
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15
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Myocardial Adaptation in Pseudohypoxia: Signaling and Regulation of mPTP via Mitochondrial Connexin 43 and Cardiolipin. Cells 2019; 8:cells8111449. [PMID: 31744200 PMCID: PMC6912244 DOI: 10.3390/cells8111449] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Accepted: 11/15/2019] [Indexed: 12/26/2022] Open
Abstract
Therapies intended to mitigate cardiovascular complications cannot be applied in practice without detailed knowledge of molecular mechanisms. Mitochondria, as the end-effector of cardioprotection, represent one of the possible therapeutic approaches. The present review provides an overview of factors affecting the regulation processes of mitochondria at the level of mitochondrial permeability transition pores (mPTP) resulting in comprehensive myocardial protection. The regulation of mPTP seems to be an important part of the mechanisms for maintaining the energy equilibrium of the heart under pathological conditions. Mitochondrial connexin 43 is involved in the regulation process by inhibition of mPTP opening. These individual cardioprotective mechanisms can be interconnected in the process of mitochondrial oxidative phosphorylation resulting in the maintenance of adenosine triphosphate (ATP) production. In this context, the degree of mitochondrial membrane fluidity appears to be a key factor in the preservation of ATP synthase rotation required for ATP formation. Moreover, changes in the composition of the cardiolipin’s structure in the mitochondrial membrane can significantly affect the energy system under unfavorable conditions. This review aims to elucidate functional and structural changes of cardiac mitochondria subjected to preconditioning, with an emphasis on signaling pathways leading to mitochondrial energy maintenance during partial oxygen deprivation.
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16
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Morise Z. Developments and perspectives of laparoscopic liver resection in the treatment of hepatocellular carcinoma. Surg Today 2019; 49:649-655. [PMID: 30649611 DOI: 10.1007/s00595-019-1765-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Accepted: 12/24/2018] [Indexed: 02/06/2023]
Abstract
Laparoscopic liver resection (LLR) was introduced in the early 1990s, initially for partial resection of the anterolateral segments, from where it has expanded in a stepwise fashion. Movement restriction makes bleeding control demanding. Managing pneumoperitoneum pressure with inflow control can inhibit venous bleeding and create a dry surgical field for easier hemostasis. Since the lack of overview leads to disorientation, simulation and navigation with imaging studies have become important. Improved direct access to the liver inside the rib cage can be obtained in LLR, reducing destruction of the associated structures and decreasing the risk of refractory ascites and liver failure, especially in patients with a cirrhotic liver. Although LLR can be performed as bridging therapy to transplantation for severe cirrhosis, its impact on expanding the indications of liver resection (LR) and the consequent survival benefits must be evaluated. For repeat LR, LLR is advantageous by producing fewer adhesions and reducing the need for adhesiolysis. The laparoscopic approach facilitates better access in a small operative field between adhesions. Further evaluations are needed for repeat anatomical resection, since alterations of the anatomy and surrounding scars and adhesions of major vessels have a larger impact.
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Affiliation(s)
- Zenichi Morise
- Department of Surgery, Fujita Health University School of Medicine, 1-98 Dengakugakubo Kutsukakecho, Toyoake, Aichi, Japan.
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17
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Su XY, Zhao JQ, Li N, Kumar M, yang AMO. Chemoprotective Effects of Resveratrol Against Diethylnitrosamine Induced Hepatocellular Carcinoma in Wistar Rats. INT J PHARMACOL 2019. [DOI: 10.3923/ijp.2019.549.559] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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18
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Schmitz S, Lurje G, Ulmer F, Andert A, Bruners P, Schulze-Hagen M, Neumann U, Schoening W. Loco-regional hepatocellular carcinoma treatment services as a bridge to liver transplantation. Hepatobiliary Pancreat Dis Int 2019; 18:228-236. [PMID: 30718181 DOI: 10.1016/j.hbpd.2019.01.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Accepted: 01/15/2019] [Indexed: 02/05/2023]
Abstract
BACKGROUND Liver transplantation remains the main curative treatment option for hepatocellular carcinoma (HCC) patients. In the Eurotransplant area Milan criteria are used to assign priority extra points (exceptional MELD, exMELD) for patients on the waiting list. To prevent patients from tumor progression, loco-regional (neoadjuvant) treatment (LRT) is used. For patients unlikely to timely receive an organ via primary allocation, "extended critera donor (ECD) organs" are used. The present study aimed to investigate the survival after LT with a strategy of minimizing waiting list dropouts by using LRT for bridging and transplanting ECD organs if possible and necessary. METHODS Between October 2010 and May 2015, 50 liver transplants for HCC were included in this retrospective study. Of those, 42 (84%) met the Milan criteria according to the preoperative radiological examination. Forty-one patients (82%) received LRT. The waiting time was analyzed according to LRT. Kaplan-Meier curves with log-rank statistics were used for survival analyses. RESULTS One- and five-year overall survival within Milan criteria was 94.3% and 83.7% compared with 91.7% and 67.9% beyond Milan criteria, though statistical significance was not reached (P = 0.487). LRT had no impact on overall survival (P = 0.629). Median waiting time was shorter if no LRT was performed (4.6 months vs. 1.5 months, P = 0.006) and there were no cases of waiting list dropouts. Using ECD organs had no impact on overall survival (P = 0.663). CONCLUSIONS Patients with an expected waiting time to transplantation of >6 months could be successfully treated with LRT as a bridge to transplant. Overall and disease-free survival for patients within and beyond Milan criteria was comparable and the use of ECD organs in this cohort of HCC patients proved to be a safe option.
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Affiliation(s)
- Sophia Schmitz
- Department of General-, Visceral- and Transplantation Surgery, University Hospital of RWTH Aachen, Aachen, Germany
| | - Georg Lurje
- Department of General-, Visceral- and Transplantation Surgery, University Hospital of RWTH Aachen, Aachen, Germany
| | - Florian Ulmer
- Department of General-, Visceral- and Transplantation Surgery, University Hospital of RWTH Aachen, Aachen, Germany
| | - Anne Andert
- Department of General-, Visceral- and Transplantation Surgery, University Hospital of RWTH Aachen, Aachen, Germany
| | - Philipp Bruners
- Department of Diagnostic and Interventional Radiology, University Hospital of RWTH Aachen, Aachen, Germany
| | - Maximilian Schulze-Hagen
- Department of Diagnostic and Interventional Radiology, University Hospital of RWTH Aachen, Aachen, Germany
| | - Ulf Neumann
- Department of General-, Visceral- and Transplantation Surgery, University Hospital of RWTH Aachen, Aachen, Germany; Department of Surgery, Maastricht University Medical Center (MUMC), Maastricht, Netherlands
| | - Wenzel Schoening
- Department of General-, Visceral- and Transplantation Surgery, University Hospital of RWTH Aachen, Aachen, Germany; Department of Surgery, Charité - University Medicine at Berlin, Germany.
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Abstract
Despite advancements in early diagnosis and medico-surgical treatment, hepatocellular carcinoma (HCC) is still a major cancer that causes substantial mortality in Asian countries. Liver transplantation (LT) has been accepted worldwide as the most effective treatment modality for patients with HCC; however, with the high incidence of HCC and low organ donation rate, Asia has developed distinctive features of indications and strategies for the application of LT. Unlike Western countries, living donor liver transplantation (LDLT) accounts for most LT cases for HCC in Asian countries, and most major transplantation centers perform LDLT for HCC patients with extended criteria. This article reviewed the current practice and outcome of LDLT for HCC from an Asian perspective and summarized the strategies that the high-volume LT centers in Asia use to obtain satisfactory oncologic results.
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20
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Cho CW, Choi GS, Kim JM, Kwon CHD, Kim DJ, Joh JW. Clinical usefulness of transarterial chemoembolization response prior to liver transplantation as predictor of optimal timing for living donor liver transplantation. Ann Surg Treat Res 2018; 95:111-120. [PMID: 30079328 PMCID: PMC6073044 DOI: 10.4174/astr.2018.95.2.111] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2017] [Revised: 11/22/2017] [Accepted: 12/05/2017] [Indexed: 12/13/2022] Open
Abstract
Purpose Response to preoperative transarterial chemoembolization (TACE) has been recommended as a biological selection criterion for liver transplantation (LT). The aim of our study was to identify optimal timing of living donor liver transplantation (LDLT) after TACE based on the TACE response. Methods We performed a retrospective study to assess recurrence in 128 hepatocellular carcinoma (HCC) patients who underwent LDLT following sequential TACE from January 2002 to March 2015 at a single institute. Cox proportional hazard models and Kaplan-Meier analysis were utilized to estimate HCC recurrence and find optimal timing for LDLT. Results Seventy-three and 61 patients were divided as the responder and nonresponder, respectively. Multivariate analysis showed independent pre-liver transplantation (pre-LT) predictors of recurrence were larger sized tumor (>3 cm, P = 0.024), nonresponse to TACE (P = 0.031), vascular invasion (P = 0.002), and extrahepatic nodal involvement (P = 0.001). In the 3-month time difference between last pre-LT TACE and LDLT subgroup, TACE responders showed significantly higher adjusted hazard ratio (aHR) of recurrence free survival (aHR, 6.284; P = 0.007), cancer specific survival (aHR, 7.033; P = 0.016), and overall survival (aHR, 7.055; P = 0.005). Moreover, for overall patients and responder groups, the significant time difference between last pre-LT TACE and LDLT was 2 months in the minimum P-value approach. Conclusion In selected patients who showed good response to pre-LT TACE, a shorter time interval between TACE and LDLT may be associated with higher recurrence free survival, cancer specific survival, and overall survival.
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Affiliation(s)
- Chan Woo Cho
- Department of Surgery, Yeungnam University College of Medicine, Daegu, Korea
| | - Gyu-Seong Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Choon Hyuck David Kwon
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Doo Jin Kim
- Department of Surgery, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea
| | - Jae-Won Joh
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Morise Z. Laparoscopic liver resection for the patients with hepatocellular carcinoma and chronic liver disease. Transl Gastroenterol Hepatol 2018; 3:41. [PMID: 30148226 PMCID: PMC6088100 DOI: 10.21037/tgh.2018.07.01] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2018] [Accepted: 06/29/2018] [Indexed: 12/12/2022] Open
Abstract
Liver resection (LR), liver transplantation (LT), transarterial chemoembolization, and local ablation therapy are the treatment options for hepatocellular carcinoma (HCC). Although LR, LT and local ablation therapy (only for small tumor) provide the best hope for cure, most patients with HCC have also chronic liver disease (CLD) backgrounds, including HCV-liver cirrhosis. Therefore, they are at high risk for development of postoperative complications-sometimes fatal-and metachronous multicentric recurrent tumors occurring from the preneoplastic CLD background. Appropriate treatment is selected for HCC patients, on the combined evaluations of tumor condition and liver function. However, not small number of patients cannot undergo any treatment option due to poor liver function and/or complicated tumor condition. After repeated treatments, it can happen more often. It is thought that the features of laparoscopic LR could lead to the expansion of the LR indication to those patients, in the settings of severe CLD, repeat LR and bridging to LT. In our experience, Child-Pugh (CP) score is one of the promising candidates as a selection indicator which correlates well to our indication criteria of surface small laparoscopic LR to severe CLD patients, patient's performance status, and prognosis. Portal hypertension should be also counted in the selection criteria.
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Affiliation(s)
- Zenichi Morise
- Department of Surgery, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
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22
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Kositamongkol P, Sanphasitvong V, Sirivatanauksorn Y, Pongpaibul A, Limsrichamrern S, Mahawithitwong P, Asavakarn S, Tovikkai C, Dumronggittigule W. Outcome of Liver Transplantation in Hepatocellular Carcinoma Patients at Siriraj Hospital. Transplant Proc 2018; 49:1114-1117. [PMID: 28583538 DOI: 10.1016/j.transproceed.2017.03.047] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
BACKGROUND Liver transplantation (LT) is one of the standard treatments for hepatocellular carcinoma (HCC), and the outcomes have become better after introduction of strict patient selection, such as the Milan criteria. However, several expanded criteria, such as the University of California San Francisco (UCSF) criteria, have demonstrated similar survival outcomes. The aim of this study was to verify survival outcomes of LT for HCC at Siriraj Hospital. METHODS Sixty-three patients diagnosed with HCC who underwent cadaveric LT at Siriraj Hospital from 2002 to 2011 were included. All patients' characteristics, blood chemistries, size and number of tumors, bridging therapy, and survival and recurrence data were retrospectively reviewed and analyzed. RESULTS Nearly all (62 patients, 98.4%) fulfilled the Milan criteria based on preoperative imaging. Explant pathology revealed that 40 patients (63.5%) were within Milan criteria and 50 patients (83%) within UCSF criteria. Demographic data, clinical laboratory, and bridging therapy were similar in patients within and outside both Milan and UCSF criteria. The 1-, 3-, and 5-year survival rates of patients within Milan were 85%, 75%, and 67.5%, and of those outside Milan were 69.6%, 52.2%, 52.2%, respectively (P = .25). Interestingly, with the use of the UCSF criteria, the 1-, 3-, and 5-year survival rates of patients within UCSF were significantly better than of those outside UCSF (84%, 76%, and 70% vs 61.5%, 30.8%, and 30.8%, respectively; P = .01). CONCLUSIONS Outcome of LT in HCC patients within Milan criteria demonstrated good long-term survival. However, providing the opportunity for HCC patients by expanding from Milan to UCSF criteria revealed similar outcomes.
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Affiliation(s)
- P Kositamongkol
- Hepatopancreatobiliary and Transplant Surgery Unit, Division of General Surgery, Department of Surgery, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - V Sanphasitvong
- Hepatopancreatobiliary and Transplant Surgery Unit, Division of General Surgery, Department of Surgery, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Y Sirivatanauksorn
- Hepatopancreatobiliary and Transplant Surgery Unit, Division of General Surgery, Department of Surgery, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
| | - A Pongpaibul
- Department of Pathology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - S Limsrichamrern
- Hepatopancreatobiliary and Transplant Surgery Unit, Division of General Surgery, Department of Surgery, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - P Mahawithitwong
- Hepatopancreatobiliary and Transplant Surgery Unit, Division of General Surgery, Department of Surgery, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - S Asavakarn
- Hepatopancreatobiliary and Transplant Surgery Unit, Division of General Surgery, Department of Surgery, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - C Tovikkai
- Hepatopancreatobiliary and Transplant Surgery Unit, Division of General Surgery, Department of Surgery, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - W Dumronggittigule
- Hepatopancreatobiliary and Transplant Surgery Unit, Division of General Surgery, Department of Surgery, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
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Immunosuppressive Medication Adherence in Liver Transplant Recipients. Transplant Proc 2017; 48:1198-201. [PMID: 27320586 DOI: 10.1016/j.transproceed.2015.12.097] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2015] [Accepted: 12/30/2015] [Indexed: 11/21/2022]
Abstract
BACKGROUND Immunosuppressive medication is one of the pivotal factors in the outcome of liver transplant patients. Nonadherence to immunosuppressive therapy is a common problem after transplantation and affects graft and patient survival. This study aimed to assess immunosuppressive medication adherence in liver transplant recipients. METHODS Liver transplant recipients who underwent the Siriraj-Support Medication Adherence in Organ Transplantation (S-SMAOT) program were included in this cross-sectional study. Immunosuppressive medication adherence was assessed with the use of the Immunosuppressive Therapy Adherence Scale (ITAS, which is scored from 0 to 12; very poor to excellence adherence). The correlations between ITAS scores and the clinical profiles of the patients, duration after transplantation, and transplant educational scores post-test were also analyzed. RESULTS From October 2012 to September 2014, a total of 50 liver transplant recipients (86 visits) were enrolled in this study. The ratio of male to female patients was 48:52. The proportions of patients with ITAS scores of 12, 10-11, and 0-9 were 82.6%, 16.3% and 1.2%, respectively. ITAS score was significantly correlated with the duration after transplantation (P < .001) and the educational scores (P = .009). CONCLUSIONS Consistent assessment of patients' immunosuppressive medication adherence is essential to avoid problems of noncompliance and to improve the outcome after liver transplantation. The S-SMAOT program was an effective approach to significantly improve the medication adherence in liver transplant recipients.
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Kim JH, Sinn DH, Gwak GY, Choi GS, Kim JM, Kwon CHD, Joh JW, Kim KY, Kim K, Paik YH, Choi MS, Lee JH, Koh KC, Paik SW. Factors determining long-term outcomes of hepatocellular carcinoma within the Milan criteria: liver transplantation versus locoregional therapy: A retrospective cohort study. Medicine (Baltimore) 2016; 95:e4735. [PMID: 27583916 PMCID: PMC5008600 DOI: 10.1097/md.0000000000004735] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Patients with hepatocellular carcinoma (HCC) satisfying the Milan criteria are candidates for liver transplantation (LT), but locoregional therapies could be another options for them.A total of 1859 treatment-naïve HCC patients fulfilling the Milan criteria were analyzed. Survival tree analysis was performed to generate survival nodes with similar survival risks in 1729 non-LT group, and compared with the survival of 130 patients who received LT.Among patients who did not receive LT, survival tree analysis classified patients into 6 nodes according to Child-Pugh (CP) score, serum alphafetoprotein (AFP) levels, tumor size, and age, with different mortality risks (5-year survival rate of 87.3%, 77.5%, 65.8%, 64.7%, 44.0%, and 28.7% for nodes 1-6, respectively; P < 0.001). The overall survival of patients in nodes 1 (CP score 5 with AFP levels <5 ng/mL) and 2 (CP score 5 with maximal tumor size <2.5 cm) were comparable with that of patients who received LT (both P > 0.05), but the survival rates of patients in nodes 3 to 6 were worse than that of LT (P < 0.05 for all). In each survival node, survival differed slightly according to initial treatment modality for patients who did not receive LT. For patients who received LT, tumor stage at the time of LT was associated with long-term outcome.Certain groups of non-LT patients showed survival rates that were similar to the survival rates of LT patients. CP score, AFP levels, tumor size, and age were baseline factors that can help estimate the long-term outcomes of non-LT treatment. In addition, tumor stage at the time of LT and specific initial treatment modality in non-LT patients affected the long-term outcomes. These factors can help estimate the long-term outcomes of HCC patients diagnosed within the Milan criteria.
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Affiliation(s)
| | | | | | | | | | | | | | - Ki Yeon Kim
- Department of Biostatistics and Clinical Epidemiology Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Korea
| | - Kyunga Kim
- Department of Biostatistics and Clinical Epidemiology Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Korea
| | | | | | | | | | - Seung Woon Paik
- Department of Medicine
- Correspondence: Seung Woon Paik, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Korea (e-mail: )
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25
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O’Connor DB, Burke JP, Hegarty J, McCormick AP, Nolan N, Hoti E, Maguire D, Geoghegan J, Traynor O. Liver transplantation for hepatocellular carcinoma in Ireland: Pre-operative alpha-fetoprotein predicts tumour recurrence in a 14-year single-centre national experience. World J Transplant 2016; 6:396-402. [PMID: 27358785 PMCID: PMC4919744 DOI: 10.5500/wjt.v6.i2.396] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2015] [Revised: 04/07/2016] [Accepted: 05/09/2016] [Indexed: 02/05/2023] Open
Abstract
AIM: To examine the results of orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) in Ireland over a 14-year period.
METHODS: Cases of HCC receiving OLT between January 1995 and September 2009 in the Irish Liver Transplant Unit were reviewed from a prospectively maintained database. Outcome measures included overall and recurrence free survival, alpha-fetoprotein (AFP) and tumour pathological features.
RESULTS: On explant pathology, 57 patients had HCC. The median follow-up time was 42.7 mo. The overall 1, 3 and 5 years survival was 87.7%, 72.1% and 72.4%. There was no difference in survival when compared to patients undergoing OLT without malignancy. The tumour recurrence rate was 14%. The Milan criteria were exceeded in 32% of cases but this did not predict overall survival or recurrence. On multivariate analysis pre-operative AFP > 100 ng/mL was an independent risk factor for recurrence (RR = 5.2, CI: 1.1-24.3, P = 0.036).
CONCLUSION: Patients undergoing OLT for HCC had excellent survival even when conventional listing criteria were exceeded. Pre-operative AFP predicts recurrence independent of tumour size and its role in selection criteria should be investigated in larger studies.
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Takahara T, Wakabayashi G, Nitta H, Hasegawa Y, Katagiri H, Takeda D, Makabe K, Sasaki A. Laparoscopic liver resection for hepatocellular carcinoma with cirrhosis in a single institution. Hepatobiliary Surg Nutr 2016; 4:398-405. [PMID: 26734624 DOI: 10.3978/j.issn.2304-3881.2015.12.04] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND In a statement by the second International Consensus Conference for Laparoscopic Liver Resection (LLR), minor LLR was confirmed to be a standard surgical practice, as it has become adopted by an increasing proportion of surgeons. However, it is unclear whether this applies to the more complex group of patients suffering from cirrhosis. Therefore, the aim of this retrospective study was to compare the feasibility and safety of LLR for hepatocellular carcinoma (HCC) between non-liver cirrhosis (NLC) patients and liver cirrhosis (LC) patients at a single high-volume laparoscopy center. METHODS From the beginning of 2000 to the end of 2013, open liver resection (OLR) was performed in 99 HCC patients, and LLR was in 118. The HCC patients who underwent LLR were divided into NLC-LLR (n=60) and LC-LLR (n=58) groups, and we compare the short-term outcomes between them. RESULTS There was no significant difference in the incidence of blood loss and transfusion requirements between the NLC-LLR group and the LC-LLR group, although wedge resection was mainly performed in the LC-LLR group. There was no significant difference in the complication rate between the two groups, and the remarkable finding was that there was a significantly lower incidence of postoperative ascites in the LC-LLR group than in the NLC-LLR group. CONCLUSIONS According to our experience, it appears that LLR for selected HCC patients with cirrhosis is a feasible and promising procedure that is associated with less blood loss and fewer postoperative complications, especially the incidence of postoperative ascites. Further investigations are clearly warranted.
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Affiliation(s)
- Takeshi Takahara
- 1 Department of Surgery, School of Medicine, Iwate Medical University, Iwate, Japan ; 2 Department of Surgery, Ageo Central General Hospital, Saitama, Japan
| | - Go Wakabayashi
- 1 Department of Surgery, School of Medicine, Iwate Medical University, Iwate, Japan ; 2 Department of Surgery, Ageo Central General Hospital, Saitama, Japan
| | - Hiroyuki Nitta
- 1 Department of Surgery, School of Medicine, Iwate Medical University, Iwate, Japan ; 2 Department of Surgery, Ageo Central General Hospital, Saitama, Japan
| | - Yasushi Hasegawa
- 1 Department of Surgery, School of Medicine, Iwate Medical University, Iwate, Japan ; 2 Department of Surgery, Ageo Central General Hospital, Saitama, Japan
| | - Hirokatsu Katagiri
- 1 Department of Surgery, School of Medicine, Iwate Medical University, Iwate, Japan ; 2 Department of Surgery, Ageo Central General Hospital, Saitama, Japan
| | - Daiki Takeda
- 1 Department of Surgery, School of Medicine, Iwate Medical University, Iwate, Japan ; 2 Department of Surgery, Ageo Central General Hospital, Saitama, Japan
| | - Kenji Makabe
- 1 Department of Surgery, School of Medicine, Iwate Medical University, Iwate, Japan ; 2 Department of Surgery, Ageo Central General Hospital, Saitama, Japan
| | - Akira Sasaki
- 1 Department of Surgery, School of Medicine, Iwate Medical University, Iwate, Japan ; 2 Department of Surgery, Ageo Central General Hospital, Saitama, Japan
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Ahn SY, Lee JM, Joo I, Lee ES, Lee SJ, Cheon GJ, Han JK, Choi BI. Prediction of microvascular invasion of hepatocellular carcinoma using gadoxetic acid-enhanced MR and (18)F-FDG PET/CT. ACTA ACUST UNITED AC 2015; 40:843-51. [PMID: 25253426 DOI: 10.1007/s00261-014-0256-0] [Citation(s) in RCA: 95] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
PURPOSE To identify the gadoxetic acid-enhanced MR and the (18)F-fludeoxyglucose (FDG) PET/CT findings associated with microvascular invasion (MVI) of hepatocellular carcinoma (HCC) in patients who are undergoing liver transplantation (LT). METHODS Fifty-one patients with 78 HCCs underwent LT. Preoperative MRI and (18)F-FDG PET/CT findings were retrospectively analyzed and the association of the imaging findings with MVI was assessed. RESULTS Univariate analysis revealed that hypointensity seen on T1WI (OR = 4.329, p = 0.011), peritumoral enhancement (OR = 7.000, p = 0.008), inhomogeneity on arterial phase (OR = 4.321, p = 0.011), delayed phase (OR = 4.519, p = 0.009) or hepatobiliary phase (OR = 3.564, p = 0.032), and the large tumor size (>5 cm) (OR = 12.091, p = 0.001) showed statistically significant associations with MVI. The ratio of tumor maximum standardized uptake value (SUV) to normal liver mean SUV (TSUVmax/LSUVmean) (2.05 ± 1.43 vs. 1.08 ± 0.37) revealed significantly higher value in the MVI-positive group. Multivariate analysis revealed that peritumoral enhancement and a TSUVmax/LSUVmean of 1.2 or greater had a statistically significant association with MVI, with odds ratios of 10.648 (p = 0.016) and 14.218 (p = 0.001), respectively. CONCLUSIONS Preoperative imaging findings such as peritumoral enhancement seen on gadoxetic acid-enhanced MR and a TSUVmax/LSUVmean of 1.2 or more on (18)F-FDG PET/CT, may suggest the presence of MVI in HCC patients.
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Affiliation(s)
- Su Yeon Ahn
- Department of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea
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Choi TW, Kim HC, Lee JH, Yu SJ, Kang B, Hur S, Lee M, Jae HJ, Chung JW. The Safety and Clinical Outcomes of Chemoembolization in Child-Pugh Class C Patients with Hepatocellular Carcinomas. Korean J Radiol 2015; 16:1283-93. [PMID: 26576118 PMCID: PMC4644750 DOI: 10.3348/kjr.2015.16.6.1283] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2015] [Accepted: 07/11/2015] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVE To evaluate the safety and clinical outcomes of chemoembolization in Child-Pugh class C patients with hepatocellular carcinomas (HCC). MATERIALS AND METHODS The study comprised 55 patients with HCC who were classified as Child-Pugh class C and who underwent initial chemoembolization between January 2003 and December 2012. Selective chemoembolization was performed in all technically feasible cases to minimize procedure-related complications. All adverse events within 30 days were recorded using the Common Terminology Criteria for Adverse Events (CTCAE). The tumor response to chemoembolization was evaluated using the modified Response Evaluation Criteria In Solid Tumors. RESULTS Thirty (54.5%) patients were within the Milan criteria, and 25 (45.5%) were beyond. The mortality of study subjects at 30 days was 5.5%. Major complications were observed in five (9.1%) patients who were all beyond the Milan criteria: two hepatic failures, one hepatic encephalopathy, and two CTCAE grade 3 increases in aspartate aminotransferase/alanine aminotransferase abnormality. The mean length of hospitalization was 6.3 ± 8.3 days (standard deviation), and 18 (32.7%) patients were discharged on the next day after chemoembolization. The tumor responses of the patients who met the Milan criteria were significantly higher (p = 0.014) than those of the patients who did not. The overall median survival was 7.1 months (95% confidence interval: 4.4-9.8 months). CONCLUSION Even in patients with Child-Pugh class C, chemoembolization can be performed safely with a selective technique in selected cases with a small tumor burden.
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Affiliation(s)
- Tae Won Choi
- Department of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul 03080, Korea
| | - Hyo-Cheol Kim
- Department of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul 03080, Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul 03080, Korea
| | - Su Jong Yu
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul 03080, Korea
| | - Beomsik Kang
- Department of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul 03080, Korea
| | - Saebeom Hur
- Department of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul 03080, Korea
| | - Myungsu Lee
- Department of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul 03080, Korea
| | - Hwan Jun Jae
- Department of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul 03080, Korea
| | - Jin Wook Chung
- Department of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul 03080, Korea
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Morise Z. Perspective of laparoscopic liver resection for hepatocellular carcinoma. World J Gastrointest Surg 2015; 7:102-106. [PMID: 26225191 PMCID: PMC4513431 DOI: 10.4240/wjgs.v7.i7.102] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2015] [Revised: 03/30/2015] [Accepted: 06/02/2015] [Indexed: 02/06/2023] Open
Abstract
Liver resection (LR) for hepatocellular carcinoma (HCC) in patients with chronic liver disease (CLD) is associated with high risks of developing significant postoperative complications and multicentric metachronous lesions, which can result in the need for repeated treatments. Studies comparing laparoscopic procedures to open LR consistently report reduced blood loss and transfusions requirements, lower postoperative morbidity, and shorter hospital stays, with no differences in oncologic outcomes. In addition, laparoscopic LR is associated with reduced postoperative ascites and a lower incidence of liver failure for HCC patients with CLD, due to the reduced surgery-induced parenchymal injury to the residual liver and limited destruction of the collateral blood/lymphatic flow around the liver. Finally, this procedure facilitates subsequent repeat LR due to minimal adhesion formation and improved vision/manipulation between adhesions. These characteristics of laparoscopic LR may lead to an expansion of the indications for LR. This editorial is based on the review and meta-analysis presented at the 2nd International Consensus Conference on Laparoscopic Liver Resection in Iwate, Japan, in October 2014 (Chairperson of the congress is Professor Go Wakabayashi from the Department of Surgery, Iwate Medical University School of Medicine), which is published in the Journal of Hepato-Biliary-Pancreatic Sciences.
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2014 KLCSG-NCC Korea Practice Guideline for the Management of Hepatocellular Carcinoma. Gut Liver 2015; 9:267-317. [PMID: 25918260 PMCID: PMC4413964 DOI: 10.5009/gnl14460] [Citation(s) in RCA: 101] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2014] [Accepted: 03/09/2015] [Indexed: 12/23/2022] Open
Abstract
The guideline for the management of hepatocellular carcinoma (HCC) was first developed in 2003 and revised in 2009 by the Korean Liver Cancer Study Group and the National Cancer Center, Korea. Since then, many studies on HCC have been carried out in Korea and other countries. In particular, a substantial body of knowledge has been accumulated on diagnosis, staging, and treatment specific to Asian characteristics, especially Koreans, prompting the proposal of new strategies. Accordingly, the new guideline presented herein was developed on the basis of recent evidence and expert opinions. The primary targets of this guideline are patients with suspicious or newly diagnosed HCC. This guideline provides recommendations for the initial treatment of patients with newly diagnosed HCC.
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2014 Korean Liver Cancer Study Group-National Cancer Center Korea practice guideline for the management of hepatocellular carcinoma. Korean J Radiol 2015; 16:465-522. [PMID: 25995680 PMCID: PMC4435981 DOI: 10.3348/kjr.2015.16.3.465] [Citation(s) in RCA: 143] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2015] [Accepted: 04/02/2015] [Indexed: 02/07/2023] Open
Abstract
The guideline for the management of hepatocellular carcinoma (HCC) was first developed in 2003 and revised in 2009 by the Korean Liver Cancer Study Group and the National Cancer Center, Korea. Since then, many studies on HCC have been carried out in Korea and other countries. In particular, a substantial body of knowledge has been accumulated on diagnosis, staging, and treatment specific to Asian characteristics, especially Koreans, prompting the proposal of new strategies. Accordingly, the new guideline presented herein was developed on the basis of recent evidence and expert opinions. The primary targets of this guideline are patients with suspicious or newly diagnosed HCC. This guideline provides recommendations for the initial treatment of patients with newly diagnosed HCC.
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Yim HJ, Suh SJ, Um SH. Current management of hepatocellular carcinoma: an Eastern perspective. World J Gastroenterol 2015; 21:3826-42. [PMID: 25852267 PMCID: PMC4385529 DOI: 10.3748/wjg.v21.i13.3826] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2014] [Revised: 12/11/2014] [Accepted: 02/12/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death, especially in Eastern areas. With advancements in diagnosis and treatment modalities for HCC, the survival and prognosis of HCC patients are improving. However, treatment patterns are not uniform between areas despite efforts to promote a common protocol. Although many hepatologists in Asian countries may adopt the principles of the Barcelona Clinic Liver Cancer staging system, they are also independently making an effort to expand the indications of each treatment and to combine therapies for better outcomes. Several expanded criteria for liver transplantation in HCC have been developed in Asian countries. Living donor liver transplantation is much more commonly performed in these countries than deceased donor liver transplantation, and it may be preceded by other treatments such as the down-staging of tumors. Local ablation therapies are often combined with transarterial chemoembolization (TACE) and the outcome is comparable to that of surgical resection. The indications of TACE are expanding, and there are new types of transarterial therapies. Although data on drug-eluting beads, TACE, and radioembolization in Asian countries are still relatively sparse compared with Western countries, these methods are gradually gaining popularity because of better tolerability and the possibility of improved response rates. Hepatic arterial infusion chemotherapy and radiotherapy are not included in Western guidelines, but are currently being used actively in several Asian countries. For more advanced HCCs, appropriate combinations of TACE, radiotherapy, and sorafenib can be considered, and emerging data indicate improved outcomes of combination therapies compared with single therapies. To include these paradigm shifts into newer treatment guidelines, more studies may be needed, but they are certainly in progress.
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Morise Z, Ciria R, Cherqui D, Chen KH, Belli G, Wakabayashi G. Can we expand the indications for laparoscopic liver resection? A systematic review and meta-analysis of laparoscopic liver resection for patients with hepatocellular carcinoma and chronic liver disease. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2015; 22:342-52. [PMID: 25663288 DOI: 10.1002/jhbp.215] [Citation(s) in RCA: 117] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/10/2014] [Accepted: 12/18/2014] [Indexed: 02/06/2023]
Abstract
Liver resection (LR) for patients with hepatocellular carcinoma (HCC) and chronic liver disease (CLD) poses a high risk of serious postoperative complications and multicentric metachronous lesions requiring repeated treatment. The efficacy of laparoscopic LR (LLR) for such patients has yet to be established. The objective of this study is to test the outcomes of LLR for HCC with the aim of considering potential expansion of the indications for LLR. We performed a systematic review of the pertinent English-language literature. Our search yielded four meta-analyses and 23 comparative studies of LLR for HCC. On the basis of the findings from these studies and our newly conducted meta-analysis, the possibility for expanding the indications for LLR to HCC was examined. The studies show that LLR (vs open) for HCC generally yields better short-term outcomes without compromising long-term outcomes, and that incidences of postoperative ascites and liver failure are decreased with LLR. Several studies show the benefits of LLR for patients with severe CLD and for repeat surgery. Reductions of postoperative ascites and liver failure are among the advantages of LLR. These characteristics of LLR may allow us to expand the indications of LLR to HCC with CLD.
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Affiliation(s)
- Zenichi Morise
- Department of Surgery, Fujita Health University School of Medicine, Banbuntane Houtokukai Hospital, 3-6-10 Otobashi, Nakagawa-ku, Nagoya, Aichi, 454-8509, Japan.
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Abstract
Hepatocellular carcinoma (HCC) is an epithelial tumor derived from hepatocytes; it accounts for 80% of all primary liver cancers and ranks globally as the fourth leading cause of cancer-related deaths. HCC treatment is a multidisciplinary and a multimodal task, with surgery in the form of liver resection and liver transplantation (LT) representing the only potentially curative modality. However, there are variable opinions and discussions about applying these surgical options and using other supporting treatments. This article is a narrative review that includes articles published from 1984 to 2013 located by searching scientific databases such as PubMed, SCOPUS, and Elsevier, with the main keyword of hepatocellular carcinoma in addition to other keywords such as liver transplantation, liver resection, transarterial chemoembolization, portal vein embolization, bridging therapy, and downstaging. In this review, we focus mainly on the surgical treatment options offered for HCC, in order to illustrate the current relevant data available in the literature to help in applying these surgical options and to use other supporting treatment modalities when appropriate.
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Affiliation(s)
- Ahmad A. Madkhali
- Department of Surgery, College of Medicine, King Saud University, Riyadh, Saudi Arabia,Section of Hepatopancreatobilairy and Transplant, Transplant, McGill University, Montreal, Canada
| | - Zahir T. Fadel
- Section of Hepatopancreatobilairy and Transplant, Transplant, McGill University, Montreal, Canada,Department of Surgery, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Murad M. Aljiffry
- Department of Surgery, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Mazen M. Hassanain
- Department of Surgery, College of Medicine, King Saud University, Riyadh, Saudi Arabia,Department of Oncology, McGill University, Montreal, Canada,Address for correspondence: Dr. Mazen Hassanain, Assistant Professor of Surgery and Consultant HPB and Transplant Surgery, Department of Surgery, College of Medicine, Scientific Director Liver Disease Research Centre, King Saud University, P.O.Box 25179, Riyadh, 11466, Saudi Arabia. E-mail:
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Lim KC, Wang VW, Siddiqui FJ, Shi L, Chan ESY, Oh HC, Tan SB, Chow PKH. Cost-effectiveness analysis of liver resection versus transplantation for early hepatocellular carcinoma within the Milan criteria. Hepatology 2015; 61:227-37. [PMID: 24638991 DOI: 10.1002/hep.27135] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2013] [Accepted: 03/13/2014] [Indexed: 12/13/2022]
Abstract
UNLABELLED Both liver resection (LR) and cadaveric liver transplantation (CLT) are potentially curative treatments for patients with hepatocellular carcinoma (HCC) within the Milan criteria and with adequate liver function. Adopting either as a first-line therapy carries major cost and resource implications. The objective of this study was to estimate the relative cost-effectiveness of LR against CLT for patients with HCC within the Milan criteria using a decision analytic model. A Markov cohort model was developed to simulate a cohort of patients aged 55 years with HCC within the Milan criteria and Child-Pugh A/B cirrhosis, undergoing LR or CLT, and followed up over their remaining life expectancy. Analysis was performed in different geographical cost settings: the USA, Switzerland and Singapore. Transition probabilities were obtained from systematic literature reviews, supplemented by databases from Singapore and the Organ Procurement and Transplantation Network (USA). Utility and cost data were obtained from open sources. LR produced 3.9 quality-adjusted life years (QALYs) while CLT had an additional 1.4 QALYs. The incremental cost-effectiveness ratio (ICER) of CLT versus LR ranged from $111,821/QALY in Singapore to $156,300/QALY in Switzerland, and was above thresholds for cost-effectiveness in all three countries. Sensitivity analysis revealed that CLT-related 5-year cumulative survival, one-time cost of CLT, and post-LR 5-year cumulative recurrence rates were the most sensitive parameters in all cost scenarios. ICERs were reduced below threshold when CLT-related 5-year cumulative survival exceeded 84.9% and 87.6% in Singapore and the USA, respectively. For Switzerland, the ICER remained above the cost-effectiveness threshold regardless of the variations. CONCLUSION In patients with HCC within the Milan criteria and Child-Pugh A/B cirrhosis, LR is more cost-effective than CLT across three different costing scenarios: the USA, Switzerland, Singapore.
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Affiliation(s)
- Kheng Choon Lim
- Centre for Quantitative Medicine, Duke-NUS Graduate Medical School, Singapore; Office of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore
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Kawabe N, Morise Z, Tomishige H, Nagata H, Kawase J, Arakawa S, Isetani M. Laparoscopic liver resection for the treatment of hepatocellular carcinoma. World J Surg Proced 2015; 5:137. [DOI: 10.5412/wjsp.v5.i1.137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2014] [Revised: 12/21/2014] [Accepted: 01/19/2015] [Indexed: 02/06/2023] Open
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Hur BY, Lee JY, Chu AJ, Kim SH, Han JK, Choi BI. UltraFast Doppler ultrasonography for hepatic vessels of liver recipients: preliminary experiences. Ultrasonography 2014; 34:58-65. [PMID: 25409662 PMCID: PMC4282230 DOI: 10.14366/usg.14038] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2014] [Revised: 09/19/2014] [Accepted: 10/04/2014] [Indexed: 12/15/2022] Open
Abstract
Purpose: The purpose of this study was to investigate the value of UltraFast Doppler ultrasonography (US) for evaluating hepatic vessels in liver recipients. Methods: Thirty-nine liver Doppler US sessions were conducted in 20 liver recipients. Each session consisted of UltraFast and conventional liver Doppler US in a random order. We compared the velocities and phasicities of the hepatic vessels, duration of each Doppler study, occurrence of technical failures, and differences in clinical decisions. Results: The velocities and resistive index values of hepatic vessels showed a strong positive correlation between the two Doppler studies (mean R=0.806; range, 0.710 to 0.924). The phasicities of the hepatic vessels were the same in both Doppler US exams. With respect to the duration of the Doppler US exam, there was no significant difference between the UltraFast (251±99 seconds) and conventional (231±117 seconds) Doppler studies (P=0.306). In five poor breath-holders, in whom the duration of conventional Doppler US was longer, UltraFast Doppler US (272±157 seconds) required a shorter time than conventional Doppler US (381±133 seconds; P=0.005). There was no difference between the two techniques with respect to technical failures and clinical decisions. Conclusion: UltraFast Doppler US is clinically equivalent to conventional Doppler US with advantages for poor breath-holders during the post-liver transplantation work-up.
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Affiliation(s)
- Bo Yun Hur
- Department of Radiology, SMG-SNU Boramae Medical Center, Seoul National University Hospital, Seoul, Korea
| | - Jae Young Lee
- Department of Radiology, Seoul National University Hospital, Seoul, Korea ; Department of Institute of Radiation Medicine, Seoul National University Hospital, Seoul, Korea
| | - A Jung Chu
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
| | - Se Hyung Kim
- Department of Radiology, Seoul National University Hospital, Seoul, Korea ; Department of Institute of Radiation Medicine, Seoul National University Hospital, Seoul, Korea
| | - Joon Koo Han
- Department of Radiology, Seoul National University Hospital, Seoul, Korea ; Department of Institute of Radiation Medicine, Seoul National University Hospital, Seoul, Korea
| | - Byung Ihn Choi
- Department of Radiology, Seoul National University Hospital, Seoul, Korea ; Department of Institute of Radiation Medicine, Seoul National University Hospital, Seoul, Korea
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Akamatsu N, Sugawara Y, Kokudo N. Living-donor vs deceased-donor liver transplantation for patients with hepatocellular carcinoma. World J Hepatol 2014; 6:626-631. [PMID: 25276278 PMCID: PMC4179141 DOI: 10.4254/wjh.v6.i9.626] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2014] [Revised: 07/29/2014] [Accepted: 08/27/2014] [Indexed: 02/06/2023] Open
Abstract
With the increasing prevalence of living-donor liver transplantation (LDLT) for patients with hepatocellular carcinoma (HCC), some authors have reported a potential increase in the HCC recurrence rates among LDLT recipients compared to deceased-donor liver transplantation (DDLT) recipients. The aim of this review is to encompass current opinions and clinical reports regarding differences in the outcome, especially the recurrence of HCC, between LDLT and DDLT. While some studies report impaired recurrence - free survival and increased recurrence rates among LDLT recipients, others, including large database studies, report comparable recurrence - free survival and recurrence rates between LDLT and DDLT. Studies supporting the increased recurrence in LDLT have linked graft regeneration to tumor progression, but we found no association between graft regeneration/initial graft volume and tumor recurrence among our 125 consecutive LDLTs for HCC cases. In the absence of a prospective study regarding the use of LDLT vs DDLT for HCC patients, there is no evidence to support the higher HCC recurrence after LDLT than DDLT, and LDLT remains a reasonable treatment option for HCC patients with cirrhosis.
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Affiliation(s)
- Nobuhisa Akamatsu
- Nobuhisa Akamatsu, Yasuhiko Sugawara, Norihiro Kokudo, Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan
| | - Yasuhiko Sugawara
- Nobuhisa Akamatsu, Yasuhiko Sugawara, Norihiro Kokudo, Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan
| | - Norihiro Kokudo
- Nobuhisa Akamatsu, Yasuhiko Sugawara, Norihiro Kokudo, Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan
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Akamatsu N, Sugawara Y, Kokudo N. Living donor liver transplantation for patients with hepatocellular carcinoma. Liver Cancer 2014; 3:108-118. [PMID: 24945001 PMCID: PMC4057790 DOI: 10.1159/000343866] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Liver transplantation has become an established treatment for cirrhotic patients with hepatocellular carcinoma (HCC), and the Milan criteria are now widely accepted and applied as an indication for deceased donor liver transplantation (DDLT) in Western countries. In contrast, however, due to the severe organ shortage, living donor liver transplantation (LDLT) is mainstream in Japan and in other Asian countries. SUMMARY Unlike DDLT, LDLT is not limited by the restrictions imposed by the nationwide allocation system, and the indication for LDLT in patients with HCC often depends on institutional or case-by-case considerations, balancing the burden on the donor, the operative risk, and the overall survival benefit for the recipient. Accumulating data from a nationwide survey as well as individual center experience indicate that extending the Milan criteria is warranted. KEY MESSAGES While the promotion of DDLT should be intensified in Japan and other Asian countries, LDLT will continue to be a mainstay for the treatment of HCC in cirrhotic patients.
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Affiliation(s)
| | - Yasuhiko Sugawara
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
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Kornberg A. Liver Transplantation for Hepatocellular Carcinoma beyond Milan Criteria: Multidisciplinary Approach to Improve Outcome. ISRN HEPATOLOGY 2014; 2014:706945. [PMID: 27335840 PMCID: PMC4890913 DOI: 10.1155/2014/706945] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/15/2013] [Accepted: 01/03/2014] [Indexed: 12/12/2022]
Abstract
The implementation of the Milan criteria (MC) in 1996 has dramatically improved prognosis after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). Liver transplantation has, thereby, become the standard therapy for patients with "early-stage" HCC on liver cirrhosis. The MC were consequently adopted by United Network of Organ Sharing (UNOS) and Eurotransplant for prioritization of patients with HCC. Recent advancements in the knowledge about tumor biology, radiographic imaging techniques, locoregional interventional treatments, and immunosuppressive medications have raised a critical discussion, if the MC might be too restrictive and unjustified keeping away many patients from potentially curative LT. Numerous transplant groups have, therefore, increasingly focussed on a stepwise expansion of selection criteria, mainly based on tumor macromorphology, such as size and number of HCC nodules. Against the background of a dramatic shortage of donor organs, however, simple expansion of tumor macromorphology may not be appropriate to create a safe extended criteria system. In contrast, rather the implementation of reliable prognostic parameters of tumor biology into selection process prior to LT is mandatory. Furthermore, a multidisciplinary approach of pre-, peri-, and posttransplant modulating of the tumor and/or the patient has to be established for improving prognosis in this special subset of patients.
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Affiliation(s)
- A. Kornberg
- Department of Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaningerstraße 22, D-81675 Munich, Germany
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Liver Computed Tomography With Low Tube Voltage and Model-Based Iterative Reconstruction Algorithm for Hepatic Vessel Evaluation in Living Liver Donor Candidates. J Comput Assist Tomogr 2014; 38:367-75. [DOI: 10.1097/rct.0b013e3182ab6cc0] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
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Tang C, Yang JT, Chen HX, Liang XC, Liu HM, Chen P. A novel technique for central hepatectomy: Maintain the blood supply and biliary drainage on one side and the blood supply from the portal vein on the other. Exp Ther Med 2013; 7:51-54. [PMID: 24348763 PMCID: PMC3861111 DOI: 10.3892/etm.2013.1367] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2013] [Accepted: 10/14/2013] [Indexed: 01/01/2023] Open
Abstract
Central hepatectomy is amongst the most difficult surgeries of liver tumors. For the routine local excision of a tumor, if the tumor has invaded the blood vessels or bile duct of the liver, then half of the liver or three lobes of the liver are resected. This results in two major drawbacks, one of which is that the residual hepatic lobe may not compensate for the damage, so it is not possible to perform conventional partial resection. The other is that the volume of normal liver tissue removed may be much more than the volume of tumor removed, causing substantial waste. In the present study, surgery was performed to resect a central liver tumor. In that surgery, the V segment and parts of the IV, VI and VIII segments were resected, and the blood supply and biliary drainage of the left hepatic lobe were kept intact. However, for the remaining VI, VII and VIII segments of the right hepatic lobe, only the blood supply from the portal vein was maintained and no arterial blood supply or biliary drainage was kept so that the patient had the opportunity to undergo radical resection and successful rehabilitation. The reason these opportunities may be possible is that the residual right liver is a temporary replacement therapy in the perioperative period. Therefore, for central hepatic tumors, particularly tumors that have invaded the neighboring bile ducts or blood vessels, if the blood supply and biliary drainage on one side is maintained and the blood supply to the other side from the portal vein is kept intact, then it is possible to perform radical resection. This provides a novel approach to the clinical resection of central liver tumors.
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Affiliation(s)
- Chun Tang
- Department of Hepatobiliary Surgery, Daping Hospital, Third Military Medical University, Institute of Surgery, Chongqing 400042, P.R. China
| | - Jun-Tao Yang
- Department of Hepatobiliary Surgery, Daping Hospital, Third Military Medical University, Institute of Surgery, Chongqing 400042, P.R. China
| | - Hong-Xu Chen
- Department of Hepatobiliary Surgery, Daping Hospital, Third Military Medical University, Institute of Surgery, Chongqing 400042, P.R. China
| | - Xian-Chun Liang
- Department of Hepatobiliary Surgery, Daping Hospital, Third Military Medical University, Institute of Surgery, Chongqing 400042, P.R. China
| | - Hong-Ming Liu
- Department of Hepatobiliary Surgery, Daping Hospital, Third Military Medical University, Institute of Surgery, Chongqing 400042, P.R. China
| | - Ping Chen
- Department of Hepatobiliary Surgery, Daping Hospital, Third Military Medical University, Institute of Surgery, Chongqing 400042, P.R. China
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Gao T, Xia Q, Qiu DK, Feng YY, Chi JC, Wang SY, Xi ZF, Zhang JJ, Xu N, Chen SY, Qiu YL, Shen LW, Zhou TT, Dong XJ, Li QG, Li H. Comparison of survival and tumor recurrence rates in patients undergoing liver transplantation for hepatitis B-related hepatocellular carcinoma using Milan, Shanghai Fudan and Hangzhou criteria. J Dig Dis 2013; 14:552-8. [PMID: 23782458 DOI: 10.1111/1751-2980.12083] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES To assess the performance of the Milan, Shanghai Fudan and Hangzhou criteria based on a preoperative evaluation in patients undergoing liver transplantation (LT) for hepatitis B-related hepatocellular carcinoma (HCC). METHODS Using a prospectively collected database, the data of consecutive patients with hepatitis B-related HCC undergoing LT at the Department of Liver Surgery of Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University from January 2005 to December 2009 were reviewed. Overall survival and tumor recurrence rates of patients fulfilling the Milan, Shanghai Fudan and Hangzhou criteria were compared using log-rank test. RESULTS Altogether 148 patients were enrolled in the study, among whom 88 fulfilled the Milan criteria and 24 and 39 were beyond Milan but within the Shanghai Fudan or Hangzhou criteria, respectively. After a median follow-up of 44 months, survival rates did not differ among the three groups (P = 0.8780). Recurrence rates were significantly higher for newly eligible patients by the Shanghai Fudan or Hangzhou criteria compared with those within the Milan criteria. CONCLUSIONS The Milan criteria should be used as the preferred criteria for the selection of hepatitis B-related HCC for LT. Considering the high tumor recurrence rates and donor scarcity, a moderate expansion of the Milan criteria must be performed cautiously until high-quality clinical trials are conducted.
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Affiliation(s)
- Ting Gao
- Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, China
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Morise Z, Kawabe N, Kawase J, Tomishige H, Nagata H, Ohshima H, Arakawa S, Yoshida R, Isetani M. Pure laparoscopic hepatectomy for hepatocellular carcinoma with chronic liver disease. World J Hepatol 2013; 5:487-495. [PMID: 24073300 PMCID: PMC3782686 DOI: 10.4254/wjh.v5.i9.487] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2013] [Revised: 07/06/2013] [Accepted: 08/20/2013] [Indexed: 02/06/2023] Open
Abstract
Pure laparoscopic hepatectomy is a less invasive procedure than conventional open hepatectomy for the resection of hepatic lesions. Increases in experiences with the technique, in combination with advances in technology, have promoted the popularity of pure laparoscopic hepatectomy. However, indications for usage and potential contraindications of the procedure remain unresolved. The characteristics and specific advantages of the procedure, especially for hepatocellular carcinoma (HCC) patients with chronic liver diseases, are reviewed and discussed in this paper. For cirrhotic patients with liver tumors, pure laparoscopic hepatectomy minimizes destruction of the collateral blood and lymphatic flow from laparotomy and mobilization, and mesenchymal injury from compression. Therefore, pure laparoscopic hepatectomy has the specific advantage of minimal postoperative ascites production that leads to lowering the risk of disturbance in water or electrolyte balance and hypoproteinemia. It minimizes complications that routinely trigger postoperative serious liver failure. Under adequate patient positioning and port arrangement, the partial resection of the liver in the area of subphrenic space, peri-inferior vena cava area or next to the attachment of retro-peritoneum is facilitated in pure laparoscopic surgery by providing good vision and manipulation in the small operative field. Furthermore, the features of reduced post-operative adhesion, good vision, and manipulation within the small area between the adhesions make this procedure safer in the context of repeat hepatectomy procedures. These improved features are especially advantageous for patients with liver cirrhosis and multicentric and/or metachronous HCCs.
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Abstract
The first human liver transplant operation was performed by Thomas Starzl in 1963. The next two decades were marked by difficulties with donor organ quality, recipient selection, operative and perioperative management, immunosuppression and infectious complications. Advances in each of these areas transformed liver transplantation from an experimental procedure to a standard treatment for end-stage liver disease and certain cancers. From the handful of pioneering programmes, liver transplantation has expanded to hundreds of programmes in >80 countries. 1-year patient survival rates have exceeded 80% and outcomes continue to improve. This success has created obstacles. Ongoing challenges of liver transplantation include those concerning donor organ shortages, recipients with more advanced disease at transplant, growing need for retransplantation, toxicities and adverse effects associated with long-term immunosuppression, obesity and NASH epidemics, HCV recurrence and the still inscrutable biology of hepatocellular carcinoma. This Perspectives summarizes this transformation over time and details some of the challenges ahead.
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Affiliation(s)
- Ali Zarrinpar
- Ronald Reagan UCLA Medical Center, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, 757 Westwood Plaza, Los Angeles, CA 90095-7054, USA
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Shim JH, Lee HC, Han S, Kang HJ, Yu E, Lee SG. Hepatocyte nuclear factor 1β is a novel prognostic marker independent of the Milan criteria in transplantable hepatocellular carcinoma: a retrospective analysis based on tissue microarrays. Liver Transpl 2013. [PMID: 23203386 DOI: 10.1002/lt.23584] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
We retrospectively investigated the prognostic value of hepatocyte nuclear factor 1 (HNF1) proteins in 159 liver transplant patients with hepatocellular carcinoma (HCC), including 36 (22.6%) exceeding the Milan criteria. The expression of alpha-fetoprotein (AFP), HNF1α, and HNF1β was examined with immunohistochemistry on duplicate tissue microarray slides containing HCC tumor explants. The times to recurrence and cancer death were analyzed with a Cox regression model and were compared according to the expression of markers of interest. We compared risk predictions with area under the receiver operator curves (AUROCs) and C statistics. AFP, HNF1α, and HNF1β were positive in 22.6%, 46.5%, and 61.0% of the tumor immunoprofiles, respectively. Although several variables were associated with the times to recurrence and cancer death in univariate Cox analyses, only AFP expression for the time to recurrence and the Milan criteria and HNF1β expression for the times to recurrence and cancer death remained significant after multivariate adjustments. The expression of HNF1β (but not HNF1α) was related to a serum AFP level ≥ 200 ng/mL, microvascular invasion, and AFP expression (P < 0.05 for all). A subgroup analysis showed that in the group meeting the Milan criteria, recurrence and cancer death rates at 10 years in the HNF1β-negative patients were approximately one-tenth of those in the HNF1β-positive patients, but the difference was not significant in the group exceeding the Milan criteria. The addition of HNF1β expression to the Milan criteria increased the C statistics and AUROCs for both recurrence and mortality (P < 0.05 for all). In conclusion, the immunohistological detection of HNF1β predicts recurrence and HCC-specific death after transplantation and provides an additive benefit in comparison with the Milan selection criteria on their own.
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Affiliation(s)
- Ju Hyun Shim
- Department of Gastroenterology (Asan Liver Center), University of Ulsan College of Medicine, Seoul, Korea
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Hwang S. Recent advances in hepatic resection and liver transplantation for hepatocellular carcinoma. JOURNAL OF THE KOREAN MEDICAL ASSOCIATION 2013. [DOI: 10.5124/jkma.2013.56.11.956] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Affiliation(s)
- Shin Hwang
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Abstract
Liver transplantation (LT) may be the best curative treatment that offers a chance of cure for the tumor and the underlying cirrhosis by complete extirpation of both. In Asia, where the supply of cadaveric grafts remains scarce and the incidence of HCC combined with chronic hepatitis B virus (HBV)- and hepatitis C virus (HCV)-related liver disease is high, adult living donor liver transplantation (LDLT) has been settled upon as a practical alternative to deceased-donor liver transplantation (DDLT). Even in Western countries, where adequate access to DDLT is feasible for HCC patients satisfying the Milan criteria, the necessity for LDLT is well established in particular for more advanced HCC patients who are disadvantaged by current allocation algorithms for grafts from deceased donors due to organ shortage, increasing waiting lists, and the expectation that many patients listed for LT will die while awaiting a suitable organ. In the field of LDLT in Asia, numerous technical innovations were achieved to secure donor safety, as well as to ensure patient survival. The experience with LDLT for HCC has been progressively increasing in many Asian countries to date. Although there are questions regarding the higher recurrence of HCC after LDLT than after DDLT, the application of the Milan and UCSF criteria to LDLT in high-volume multicenter cohorts from Japan and Korea has resulted in patient survival outcomes very similar to those following DDLT. Recently, inclusion of biologic tumor markers such as alpha fetoprotein (AFP), protein induced by vitamin K antagonist II (PIVKA II), and positive positron emission tomography (PET) in addition to parameters of tumor morphology might be the key to establishing the best criteria for LDLT for HCC. As pretransplant treatments, most LDLT centers in Asia cannot adopt the strategy of bridging therapy under scarcity of cadaveric organ donation but have to use those multi-modality treatments as a salvage intending for primary curative treatment or a downstaging therapy before LDLT. After LDLT, basically there is no difference in the management strategy for HCC recurrence between DDLD and LDLT.
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Xiong JJ, Altaf K, Javed MA, Huang W, Mukherjee R, Mai G, Sutton R, Liu XB, Hu WM. Meta-analysis of laparoscopic vs open liver resection for hepatocellular carcinoma. World J Gastroenterol 2012; 18:6657-68. [PMID: 23236242 PMCID: PMC3516221 DOI: 10.3748/wjg.v18.i45.6657] [Citation(s) in RCA: 129] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2012] [Revised: 09/17/2012] [Accepted: 09/22/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To conduct a meta-analysis to determine the safety and efficacy of laparoscopic liver resection (LLR) and open liver resection (OLR) for hepatocellular carcinoma (HCC).
METHODS: PubMed (Medline), EMBASE and Science Citation Index Expanded and Cochrane Central Register of Controlled Trials in the Cochrane Library were searched systematically to identify relevant comparative studies reporting outcomes for both LLR and OLR for HCC between January 1992 and February 2012. Two authors independently assessed the trials for inclusion and extracted the data. Meta-analysis was performed using Review Manager Version 5.0 software (The Cochrane Collaboration, Oxford, United Kingdom). Pooled odds ratios (OR) or weighted mean differences (WMD) with 95%CI were calculated using either fixed effects (Mantel-Haenszel method) or random effects models (DerSimonian and Laird method). Evaluated endpoints were operative outcomes (operation time, intraoperative blood loss, blood transfusion requirement), postoperative outcomes (liver failure, cirrhotic decompensation/ascites, bile leakage, postoperative bleeding, pulmonary complications, intraabdominal abscess, mortality, hospital stay and oncologic outcomes (positive resection margins and tumor recurrence).
RESULTS: Fifteen eligible non-randomized studies were identified, out of which, 9 high-quality studies involving 550 patients were included, with 234 patients in the LLR group and 316 patients in the OLR group. LLR was associated with significantly lower intraoperative blood loss, based on six studies with 333 patients [WMD: -129.48 mL; 95%CI: -224.76-(-34.21) mL; P = 0.008]. Seven studies involving 416 patients were included to assess blood transfusion requirement between the two groups. The LLR group had lower blood transfusion requirement (OR: 0.49; 95%CI: 0.26-0.91; P = 0.02). While analyzing hospital stay, six studies with 333 patients were included. Patients in the LLR group were found to have shorter hospital stay [WMD: -3.19 d; 95%CI: -4.09-(-2.28) d; P < 0.00001] than their OLR counterpart. Seven studies including 416 patients were pooled together to estimate the odds of developing postoperative ascites in the patient groups. The LLR group appeared to have a lower incidence of postoperative ascites (OR: 0.32; 95%CI: 0.16-0.61; P = 0.0006) as compared with OLR patients. Similarly, fewer patients had liver failure in the LLR group than in the OLR group (OR: 0.15; 95%CI: 0.02-0.95; P = 0.04). However, no significant differences were found between the two approaches with regards to operation time [WMD: 4.69 min; 95%CI: -22.62-32 min; P = 0.74], bile leakage (OR: 0.55; 95%CI: 0.10-3.12; P = 0.50), postoperative bleeding (OR: 0.54; 95%CI: 0.20-1.45; P = 0.22), pulmonary complications (OR: 0.43; 95%CI: 0.18-1.04; P = 0.06), intra-abdominal abscesses (OR: 0.21; 95%CI: 0.01-4.53; P = 0.32), mortality (OR: 0.46; 95%CI: 0.14-1.51; P = 0.20), presence of positive resection margins (OR: 0.59; 95%CI: 0.21-1.62; P = 0.31) and tumor recurrence (OR: 0.95; 95%CI: 0.62-1.46; P = 0.81).
CONCLUSION: LLR appears to be a safe and feasible option for resection of HCC in selected patients based on current evidence. However, further appropriately designed randomized controlled trials should be undertaken to ascertain these findings.
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Lai Q, Avolio AW, Lerut J, Singh G, Chan SC, Berloco PB, Tisone G, Agnes S, Chok KS, Sharr W, Rossi M, Manzia TM, Lo CM. Recurrence of hepatocellular cancer after liver transplantation: the role of primary resection and salvage transplantation in East and West. J Hepatol 2012; 57:974-979. [PMID: 22771712 DOI: 10.1016/j.jhep.2012.06.033] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2012] [Revised: 06/04/2012] [Accepted: 06/27/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Greater tumor aggressiveness and different management modalities of hepatocellular cancer (HCC) before liver transplantation (LT) may explain the higher recurrence rates reported in Asia. This study investigates the prognostic factors for HCC recurrence in a Western and an Eastern HCC patient cohort in order to analyze the respective roles of tumor- and management-related factors on the incidence of post-LT HCC recurrence. METHODS Data of 273 HCC patients, transplanted during the period January 1999-March 2009, were obtained from the Rome Inter-University Liver Transplant Consortium (n=157) and Hong Kong University (n=116) databases. Median follow-up was 4.3 years (range: 0.2-12). Recurrence rate and multivariate logistic regression analysis was performed on the entire population and on Milan criteria-in (MC-in) patients. RESULTS Multivariate analysis on the entire population identified four independent risk factors for post-LT HCC recurrence: microvascular invasion (odds ratio, OR=4.88; p=0.001), poor tumor grading (OR=6.86; p=0.002), diameter of the largest tumor (OR=4.72; p=0.05), and previous liver resection (LR) (OR=3.34; p=0.04). After removal of LR, only tumor-related variables were independent risk factors for recurrence. When only MC-in patients were analyzed, no difference was observed between the two cohorts in terms of recurrence rate after LR patient removal. CONCLUSIONS LR followed by salvage "for HCC recurrence" LT represents the main reason for a higher HCC recurrence rate in the Hong Kong patients, but not LR followed by salvage "for liver failure" LT in the Roman group. This approach towards HCC before LT may not be universally applicable. The precise patient background must be taken into account in order to identify the best pre-LT strategy.
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Affiliation(s)
- Quirino Lai
- Department of General Surgery and Organ Transplantation, Sapienza University, Umberto I Hospital, Rome, Italy.
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