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

Toniutto, Pierluigi; Fumolo, Elisa; Fornasiere, Ezio; Bitetto, Davide

doi:10.3390/jcm10173932

Cited by 15 publications

(24 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In 2001, Yao et al proposed the UCSF criteria (14), which allowed approximately 20% of patients who did not meet the Milan criteria to benefit from LT. However, many studies have reported that patients with these expanded OLT criteria had lower OS and DFS than those who met the Milan criteria (7,9). Given the severe organ shortages, the selection criteria are based on the utility principle assuring the maximal post-transplant survival rather than extended criteria that might lead to short-term survival.…”

Section: Discussionmentioning

confidence: 99%

“…Milan criteria proposed by Professor Mazzaferro are a metric for OLT and defined by a single tumor diameter of ≤ 5 cm, multiple tumor nodules of ≤ 3, each nodule of ≤ 3 cm, no vessel invasion, and no metastases (4). Milan criteria are restrictive: many patients who might obtain good survival after liver transplantation do not have the opportunity to be OLT candidates (5)(6)(7). Therefore, more expanded OLT criteria have been explored to benefit more patients with HCC.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Combination of AFP and “Up-To-Seven” Criteria May Be a Better Strategy for Liver Transplantation in Chinese Cirrhotic HCC Patients

Zhang

Feng²,

He³

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

BackgroundOrthotopic liver transplantation (OLT) is a life-saving option for patients with hepatocellular carcinoma (HCC), but the expanded OLT criteria remain controversial.ObjectiveThe study aimed to explore whether expanded OLT criteria can be applied to Chinese cirrhotic patients with HCC.MethodsThis retrospective study analyzed risk factors for HCC recurrence and death and compared patients’ tumor characteristics and outcomes in groups of Milan, “Up-to-seven,” and Hangzhou criteria, and groups between met and unmet the combinative criteria of “Up-to-seven” and AFP of < 1000 ng/mL.ResultsAmong 153 patients who underwent OLT for HCC from January 2015 to February 2019 in 4 years of follow-up, 20 (13.1%) patients had HCC recurrence, and 11 (7.2%) had HCC-related death. Multivariate Cox regression analysis showed that preoperative alpha-fetoprotein (AFP) of > 1000 ng/mL (hazard ratio [HR]: 10.05, 95% confidence interval [CI]: 2.45–41.13, P = 0.001) was an independent risk factor for HCC recurrence and HCC-related death (HR: 6.63, 95%CI: 1.31–33.52, P = 0.022). Patients who did not meet Milan criteria but satisfied the “Up-to-seven” criteria had no differences in overall survival (OS) (P = 0.69) and disease-free survival (DFS) (P = 0.35) than patients who met the Milan criteria. The combination of “Up-to-seven” criteria and AFP of < 1000 ng/mL differed significantly (HR: 18.9; 95% CI: 4.0–89.2; P < 0.001). Patients with HCC who met the “Up-to-seven” criteria and AFP of < 1000 ng/mL (n = 121) had excellent survival with 4-year OS of 91.6% (P < 0.001) and DFS of 90.8% (P < 0.001), which is significantly better compared to the other group (n = 32) (OS of 67.5% and DFS of 46.5%) and patients who met the Milan criteria (n = 108, OS of 89.8%, DFS of 89.6%), allowing 28.9% (13/45) of patients who did not meet the Milan criteria to benefit from OLT.ConclusionChinese cirrhotic patients with HCC who met the combinative criteria of “Up-to-seven” and AFP of < 1000 ng/mL had better survival than those who met the Milan criteria, and these combinative criteria benefited more patients and may become a better option for OLT.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Combination of AFP and “Up-To-Seven” Criteria May Be a Better Strategy for Liver Transplantation in Chinese Cirrhotic HCC Patients

Zhang

Feng²,

He³

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…The response to locoregional therapies likely serves as a useful surrogate marker for predicting HCC recurrence after liver transplantation [ 90 ]. Indeed, accumulated evidence shows that the radiographic response to locoregional therapy should be included in the selection criteria for optimizing survival post-transplantation.…”

Section: Candidates Of Surrogate Markers For Biological Behavior Of Hccmentioning

confidence: 99%

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

Shimamura

Goto

Watanabe

et al. 2022

Cancers

View full text Add to dashboard Cite

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.

show abstract

“…Three contributions presented in this issue of JCM have been devoted to providing the main updated knowledge regarding the approach to treat patients with hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). One article focused on CCA [ 19 ], and two focused on HCC [ 20 , 21 ]. CCA is anatomically classified in intrahepatic (iCCA), perihilar (pCCA) and distal (dCCA) CCA.…”

mentioning

confidence: 99%

“…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. These issues have been comprehensively updated in this JCM Special Issue [ 21 ] to present new policies that may be applied to better select patients with HCC for LT. The main innovative approach to select patients for LT presenting at baseline beyond the MC is to evaluate the characteristics and the duration of tumor response after locoregional (or systemic) therapies (downstaging treatment) and consider it a surrogate marker of biological HCC aggressiveness and of the risk of recurrence.…”

mentioning

confidence: 99%

Special Issue “New Therapies of Liver Diseases”

Toniutto

2022

JCM

Self Cite

View full text Add to dashboard Cite

show abstract

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

Cited by 15 publications

References 89 publications

The Combination of AFP and “Up-To-Seven” Criteria May Be a Better Strategy for Liver Transplantation in Chinese Cirrhotic HCC Patients

The Combination of AFP and “Up-To-Seven” Criteria May Be a Better Strategy for Liver Transplantation in Chinese Cirrhotic HCC Patients

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

Special Issue “New Therapies of Liver Diseases”

Contact Info

Product

Resources

About