Liver Transplantation for Locally Advanced Hepatocellular Carcinoma

2020 ◽  
Vol 04 (01) ◽  
pp. 003-012
Author(s):  
Norio Kawamura ◽  
Akinobu Taketomi
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Liver Transplant ◽  
Early Stage ◽  
Locally Advanced ◽  
Tumor Biology ◽  
Locoregional Therapy ◽  
Milan Criteria ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc

AbstractSince the Milan criteria were accepted as the gold standard, liver transplantation has been widely performed as a curative treatment for early-stage hepatocellular carcinoma (HCC). The outcome of liver transplantation in early-stage HCC is excellent; however, the Milan criteria are strict, and therefore, only limited numbers of patients can benefit from liver transplantation. Many HCC patients are diagnosed at an advanced stage, which falls outside the Milan criteria, so it has been proposed over the last two decades that liver transplant surgeons should perform liver transplantation in locally advanced HCC, when presenting without recurrence. Several trials exploring the upper limits of liver transplantation have been performed, and extensive research on tumor biology has enabled the expansion of liver transplant indication for HCC. Simultaneously, locoregional therapy for advanced HCC was found to be an effective procedure when used to distinguish potentially transplantable patients. This treatment approach, known as a downstaging strategy, has been developed over the last two decades and became an essential treatment option for locally advanced HCC. In this article, the current strategies of liver transplantation for the treatment of locally advanced HCC are reviewed.

scholarly journals Liver Transplantation for Hepatocellular Carcinoma beyond Milan Criteria: Multidisciplinary Approach to Improve Outcome

2014 ◽  
Vol 2014 ◽  
pp. 1-25 ◽  
Author(s):  
A. Kornberg
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Multidisciplinary Approach ◽  
Early Stage ◽  
Selection Process ◽  
Imaging Techniques ◽  
Tumor Biology ◽  
Critical Discussion ◽  
Milan Criteria ◽  
Immunosuppressive Medications

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.

scholarly journals The Treatment Effect of Liver Transplantation versus Liver Resection for HCC: A Review and Future Perspectives

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3730
Author(s):  
Berend R. Beumer ◽  
Roeland F. de Wilde ◽  
Herold J. Metselaar ◽  
Robert A. de Man ◽  
Wojciech G. Polak ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Liver Resection ◽  
Early Stage ◽  
Disease Free Survival ◽  
Milan Criteria ◽  
Term Survival ◽  
Equal Distribution ◽  
Intention To Treat ◽  
Treat Analysis

For patients presenting with hepatocellular carcinoma within the Milan criteria, either liver resection or liver transplantation can be performed. However, to what extent either of these treatment options is superior in terms of long-term survival is unknown. Obviously, the comparison of these treatments is complicated by several selection processes. In this article, we comprehensively review the current literature with a focus on factors accounting for selection bias. Thus far, studies that did not perform an intention-to-treat analysis conclude that liver transplantation is superior to liver resection for early-stage hepatocellular carcinoma. In contrast, studies performing an intention-to-treat analysis state that survival is comparable between both modalities. Furthermore, all studies demonstrate that disease-free survival is longer after liver transplantation compared to liver resection. With respect to the latter, implications of recurrences for survival are rarely discussed. Heterogeneous treatment effects and logical inconsistencies indicate that studies with a higher level of evidence are needed to determine if liver transplantation offers a survival benefit over liver resection. However, randomised controlled trials, as the golden standard, are believed to be infeasible. Therefore, we suggest an alternative research design from the causal inference literature. The rationale for a regression discontinuity design that exploits the natural experiment created by the widely adopted Milan criteria will be discussed. In this type of study, the analysis is focused on liver transplantation patients just within the Milan criteria and liver resection patients just outside, hereby ensuring equal distribution of confounders.

Evaluation of the neutrophil-lymphocyte ratio as a predictor of survival after liver transplantation for hepatocellular carcinoma.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 170-170 ◽  
Author(s):  
A. R. Limaye ◽  
R. Cabrera
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Overall Survival ◽  
Independent Predictor ◽  
Tumor Biology ◽  
Milan Criteria ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Cumulative Survival ◽  
Neutrophil Lymphocyte Ratio

170 Background: The Milan criteria are utilized to predict outcomes in patients with hepatocellular carcinoma (HCC) who undergo liver transplantation (LT). Though the survival of these patients has significantly improved since the adoption of these criteria, the risk of recurrence after LT is as high as 20 percent. One limitation of the Milan criteria is the lack of any estimation of tumor biology. The neutrophil-lymphocyte ratio (NLR) has been proposed as a peripheral surrogate for tumor biology. The predictive power of the NLR has been demonstrated for several solid tumors, and early evidence points to a role in HCC. We hypothesize that the NLR is predictive of overall survival and recurrence-free survival in patients with HCC who undergo LT. Methods: This is a retrospective analysis of adult patients undergoing LT for HCC between 2000 and 2008 at our institution. We defined an elevated NLR as a ratio of five or greater. Results: We identified 160 patients who underwent LT for HCC, 28 of whom had an elevated NLR. Seventeen subjects experienced recurrent HCC during the study period. The cumulative survival for subjects with an elevated NLR (1-year cumulative survival 70% ± 0.08, 3-year cumulative survival 48% ± 0.09, 5-year cumulative survival 38% ± 0.11) was significantly lower than for subjects with a normal NLR (1-year survival 80% ± 0.04, 3-year survival 75% ± 0.04, 5-year survival 68% ± 0.06). On univariate analysis, seven factors (including an elevated NLR) predicted decreased overall and recurrence-free survival. However, after multivariate analysis, only three factors (including elevated NLR) remained significant as predictors of overall survival. Additionally, multivariate analysis revealed that an elevated NLR was the only significant independent predictor of recurrence-free survival. Conclusions: Preoperative NLR is a powerful independent predictor of overall survival and recurrence-free survival in patients undergoing LT for HCC. Measurement of NLR could serve as a useful and easily obtained adjunct to the MELD score and Milan criteria when evaluating this patient population and determining which patients will gain the most survival benefit from transplant. No significant financial relationships to disclose.

scholarly journals Locoregional Combined With Systemic Therapies for Advanced Hepatocellular Carcinoma: An Inevitable Trend of Rapid Development

2021 ◽  
Vol 8 ◽  
Author(s):  
Xin Li ◽  
Yaxi Wang ◽  
Xin Ye ◽  
Ping Liang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Rapid Development ◽  
Locoregional Therapy ◽  
Current Status ◽  
Advanced Hepatocellular Carcinoma ◽  
Antitumor Effects ◽  
Primary Tumors ◽  
Advanced Hcc ◽  
Number Of Patients ◽  
Locoregional Therapies

Despite the application of antiviral drugs and improved surveillance tools, the number of patients diagnosed with hepatocellular carcinoma (HCC) at an advanced stage and with a dismal prognosis is still on the rise. Systemic treatment with multiple multitargeted tyrosine kinase inhibitors (TKIs), such as sorafenib, has been a widely utilized approach for a decade. In addition, the use of a combination of TKIs with other types of compounds, including immune checkpoint inhibitors (ICIs) and antiangiogenic inhibitors, has shown efficacy in treating advanced HCC. However, the presence of intolerable adverse events, low disease response and control rates, and relative short overall survival of such combinatory therapies makes novel or optimized therapies for advance HCC urgently needed. Locoregional therapy (transarterial chemoembolization, and thermal ablation) can destroy primary tumors and decrease tumor burden and is widely used for HCC management. This type of treatment modality can result in local hypoxia and increased vascular permeability, inducing immunogenic effects by releasing tumor antigens from dying cancer cells and producing damage-associated molecular patterns that facilitate antiangiogenic therapy and antitumor immunity. The combination of systemic and locoregional therapies may further produce synergistic effects without overlapping toxicity that can improve prognoses for advanced HCC. In preliminary studies, several combinations of therapeutic modes exhibited promising levels of safety, feasibility, and antitumor effects in a clinical setting and have, thus, garnered much attention. This review aims to provide a comprehensive, up-to-date overview of the underlying mechanisms of combined systemic and locoregional therapies in the treatment of advanced HCC, commenting on both their current status and future direction.

Impact of Pretransplant Bridging Locoregional Therapy for Patients With Hepatocellular Carcinoma Within Milan Criteria Undergoing Liver Transplantation

2017 ◽  
Vol 266 (3) ◽  
pp. 525-535 ◽  
Author(s):  
Vatche G. Agopian ◽  
Michael P. Harlander-Locke ◽  
Richard M. Ruiz ◽  
Goran B. Klintmalm ◽  
Srinath Senguttuvan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Locoregional Therapy ◽  
Milan Criteria

Impact of HCV treatment in patients with advanced hepatocellular carcinoma on sorafenib.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15645-e15645
Author(s):  
Michael Herman ◽  
Yuhua Zhang ◽  
Lisa Wang ◽  
Hao-Wen Sim ◽  
Jennifer J. Knox
Keyword(s):  
Hepatocellular Carcinoma ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Early Stage ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Advanced Hepatocellular Carcinoma ◽  
Sorafenib Treatment ◽  
Advanced Hcc ◽  
Significant Difference

e15645 Background: Hepatocellular carcinoma (HCC) is the 4th leading cause of global cancer deaths. In North America, HCC is most commonly caused by Hepatitis C virus (HCV). Direct acting antivirals (DAAs) have dramatically increased sustained virologic response (SVR) rates for HCV. Studies of DAAs in early stage HCC have had conflicting results on HCC outcomes. A small Asian study of 58 advanced HCC patients treated with sorafenib demonstrated SVR improved survival, but whether the same effect occurs in North American patients is unknown. Methods: Inclusion criteria for this retrospective study were: biopsy or clinically proven advanced incurable HCC, sorafenib treatment at Princess Margaret Cancer Centre between January 1 2008-June 30 2018 and a history of HCV. Survival was analyzed using the Kaplan Meier method and a cox proportional hazards model was fit to determine the effect of SVR on OS. Results: 93 patients were included with a median duration of sorafenib therapy of 3 months. 89% were ECOG 0-1 and 96% were BCLC-C (See table 1). Of those receiving antivirals, 95% were given before sorafenib. Overall, SVR was achieved in 23 (50%) patients. Median OS of patients achieving SVR vs not in SVR was 10.3 vs 8.9 months respectively (HR 0.67, 95% CI 0.36-1.24, p = 0.20). Median PFS was 6.4 vs 5.0 months in patients with or without SVR (HR 0.66, 95% CI 0.39-1.13, p = 0.13). There was no significant difference between mean dose of sorafenib or discontinuation due to toxicity in patients by SVR status. Conclusions: Antiviral therapy with SVR lead to a non-statistically significant improvement in OS in patients with Child-Pugh A-B liver disease, advanced HCC treated with sorafenib and HCV. These results should be validated in larger data-sets. [Table: see text]

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