scholarly journals Liver Transplantation for Hepatocellular Carcinoma: How Should We Improve the Thresholds?

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 419
Author(s):  
Tsuyoshi Shimamura ◽  
Ryoichi Goto ◽  
Masaaki Watanabe ◽  
Norio Kawamura ◽  
Yasutsugu Takada
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Patient Selection ◽  
Tumor Burden ◽  
Biological Behavior ◽  
Locoregional Therapy ◽  
Milan Criteria ◽  
Surrogate Markers ◽  
Patient Selection Criteria ◽  
Fdg Pet Ct

Hepatocellular carcinoma (HCC) is the third highest cause of cancer-related mortality, and liver transplantation is the ideal treatment for this disease. The Milan criteria provided the opportunity for HCC patients to undergo LT with favorable outcomes and have been the international gold standard and benchmark. With the accumulation of data, however, the Milan criteria are not regarded as too restrictive. After the implementation of the Milan criteria, many extended criteria have been proposed, which increases the limitations regarding the morphological tumor burden, and incorporates the tumor’s biological behavior using surrogate markers. The paradigm for the patient selection for LT appears to be shifting from morphologic criteria to a combination of biologic, histologic, and morphologic criteria, and to the establishment of a model for predicting post-transplant recurrence and outcomes. This review article aims to characterize the various patient selection criteria for LT, with reference to several surrogate markers for the biological behavior of HCC (e.g., AFP, PIVKA-II, NLR, 18F-FDG PET/CT, liquid biopsy), and the response to locoregional therapy. Furthermore, the allocation rules in each country and the present evidence on the role of down-staging large tumors are addressed.

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 in Patients with Hepatocellular Carcinoma beyond the Milan Criteria: A Comprehensive Review

2021 ◽  
Vol 10 (17) ◽  
pp. 3932
Author(s):  
Pierluigi Toniutto ◽  
Elisa Fumolo ◽  
Ezio Fornasiere ◽  
Davide Bitetto
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Selection Criterion ◽  
Surrogate Marker ◽  
Tumor Burden ◽  
Current Data ◽  
Milan Criteria ◽  
Biological Variables ◽  
Expanded Criteria ◽  
Histological Characteristics

The Milan criteria (MC) were developed more than 20 years ago and are still considered the benchmark for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). However, the strict application of MC might exclude some patients who may receive a clinical benefit of LT. Several expanded criteria have been proposed. Some of these consider pretransplant morphological and biological variables of the tumor, others consider post-LT variables such as the histology of the tumor, and others combine pre- and post-LT variables. More recently, the HCC response to locoregional treatments before transplantation emerged as a surrogate marker of the biological aggressiveness of the tumor to be used as a better selection criterion for LT in patients beyond the MC at presentation. This essential review aims to present the current data on the pretransplant selection criteria for LT in patients with HCC exceeding the MC at presentation based on morphological and histological characteristics of the tumor and to critically discuss those that have been validated in clinical practice. Moreover, the role of HCC biological markers and the tumor response to downstaging procedures as new tools for selecting patients with a tumor burden outside of the MC for LT is evaluated.

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

scholarly journals Using Hepatocellular Carcinoma Tumor Burden Score to Stratify Prognosis after Liver Transplantation

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3372
Author(s):  
Dimitrios Moris ◽  
Brian I. Shaw ◽  
Lisa McElroy ◽  
Andrew S. Barbas
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Continuous Variable ◽  
Tumor Burden ◽  
Milan Criteria ◽  
Transplant Recipients ◽  
Liver Transplants ◽  
Free Survival ◽  
Promising Tool ◽  
Tumor Number

Liver transplantation (LT) remains a mainstay of treatment for hepatocellular carcinoma (HCC). Tumor factors such as size and number of tumors define eligibility for LT using the Milan criteria. The tumor burden score (TBS) incorporates both tumor number and size into a single continuous variable and has been used to differentiate prognosis among patients undergoing resection for HCC. The objective of the present study was to evaluate the ability of the TBS to predict overall and recurrence-free survival in patients undergoing LT for HCC. The Scientific Registry of Transplant Recipients (SRTR) was used to analyze all liver transplants for HCC, with initial tumor size data from 2004 to 2018. There were 12,486 patients in the study period. In the unadjusted analyses, patients with a high TBS had worse overall (p < 0.0001) and recurrence-free (p < 0.0001) survival. In the adjusted analyses, a high TBS was associated with a greater hazard ratio (HR) of death (HR = 1.21; 95%CI, [1.13–1.30]; p < 0.001) and recurrence (HR = 1.49; 95%CI [1.3–1.7]; p < 0.001). When we superimposed the TBS on the Milan criteria, we saw that a higher TBS was associated with a higher hazard of recurrence at values that were either all within (HR = 1.20; 95%CI, [1.04–1.37]; p = 0.011) or variably within (HR = 1.53; 95%CI, [1.16–2.01]; p = 0.002) the Milan criteria. In conclusion, the TBS is a promising tool in predicting outcomes in patients with HCC after LT.

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