scholarly journals Upper Limits of Downstaging for Hepatocellular Carcinoma in Liver Transplantation

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6337
Author(s):  
Marco Biolato ◽  
Tiziano Galasso ◽  
Giuseppe Marrone ◽  
Luca Miele ◽  
Antonio Grieco
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
San Francisco ◽  
The United States ◽  
Milan Criteria ◽  
Eligibility Criteria ◽  
Proper Patient Selection ◽  
Systemic Treatments ◽  
Upper Limits ◽  
Liver Transplantations

In Europe and the United States, approximately 1100 and 1800 liver transplantations, respectively, are performed every year for hepatocellular carcinoma (HCC), compared with an annual incidence of 65,000 and 39,000 new cases, respectively. Because of organ shortages, proper patient selection is crucial, especially for those exceeding the Milan criteria. Downstaging is the reduction of the HCC burden to meet the eligibility criteria for liver transplantation. Many techniques can be used in downstaging, including ablation, chemoembolisation, radioembolisation and systemic treatments, with a reported success rate of 60–70%. In recent years, an increasing number of patient responders to downstaging procedures has been included in the waitlist, generally with a comparable five-year post-transplant survival but with a higher probability of dropout than HCC patients within the Milan criteria. While the Milan criteria are generally accepted as the endpoint of downstaging, the upper limits of tumour burden for downstaging HCC for liver transplantation are controversial. Very challenging situations involve HCC patients with large nodules, macrovascular invasion or even extrahepatic metastasis at baseline who respond to increasingly more effective downstaging procedures and who aspire to be placed on the waitlist for transplantation. This narrative review analyses the most important evidence available on cohorts subjected to “extended” downstaging, including HCC patients over the up-to-seven criteria and over the University of California San Francisco downstaging criteria. We also address surrogate markers of biological aggressiveness, such as alpha-fetoprotein and the response stability to locoregional treatments, which are very useful in selecting responders to downstaging procedures for waitlisting inclusion.

scholarly journals Comparison of Models for Tumor Recurrence after Liver Transplantation for the Patients with Hepatocellular Carcinoma: A Multicenter Long-Term Follow-Up Study

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1295 ◽  
Author(s):  
Young Chang ◽  
Yuri Cho ◽  
Jeong-Hoon Lee ◽  
Yun Bin Lee ◽  
Eun Ju Cho ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Overall Survival ◽  
San Francisco ◽  
Tumor Recurrence ◽  
Milan Criteria ◽  
Group Model ◽  
Donor Liver Transplantation ◽  
Cumulative Risks

Background and Aims: Several models have been developed to predict tumor the recurrence of hepatocellular carcinoma (HCC) after liver transplantation besides the conventional Milan criteria (MC), including the MoRAL score. This study aimed to compare the prognostication power of the MoRAL score to most models designed so far in the Eastern and Western countries. Methods: This study included 564 patients who underwent living donor liver transplantation (LDLT) in three large-volume hospitals in Korea. The primary and secondary endpoints were time-to-recurrence, and overall survival (OS), respectively. The performance of the MoRAL score was compared with those of other various Liver transplantation (LT) criteria, including the Milan criteria, University of California San Francisco (UCSF) criteria, up-to-seven criteria, Kyoto criteria, AFP model, total tumor volume/AFP criteria, Metroticket 2.0 model, and Weill Cornell Medical College group model. Results: The median follow-up duration was 78.1 months. Among all models assessed, the MoRAL score showed the best discrimination function for predicting the risk of tumor recurrence after LT, with c-index of 0.78, compared to other models (all p < 0.001). The MoRAL score also represented the best calibration function by Hosmer-Lemeshow test (p = 0.15). Especially in the beyond-MC sub-cohort, the MoRAL score predicted tumor recurrence (c-index, 0.80) and overall survival (OS) (c-index, 0.70) significantly better than any other models (all p < 0.001). When the MoRAL score was low (<314.8), the five-year cumulative risks of tumor recurrence and death were excellent in beyond-MC (27.8%, and 20.5%, respectively) and within-MC (16.3%, and 21.1%, respectively) sub-cohorts. Conclusions: The MoRAL score provides the most refined prognostication for predicting HCC recurrence after LDLT.

scholarly journals Oncological feasibility of liver transplantation for hepatocellular carcinoma

2020 ◽  
Vol 25 (2) ◽  
pp. 77-85
Author(s):  
D. Ju. Efimov ◽  
A. E. Shcherba ◽  
S. V. Korotkov ◽  
O. O. Rummo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
San Francisco ◽  
Intermediate Stage ◽  
Waiting List ◽  
University Of California ◽  
Locoregional Therapy ◽  
Milan Criteria ◽  
Serological Response ◽  
One Year

Aim. To evaluate the effectiveness of the liver transplantation in patients with hepatocellular carcinoma and cirrhosis according to morphological (Milan criteria) and oncological criteria.Materials and methods. A retrospective cohort study of 105 recipients with hepatocellular carcinoma who underwent liver transplantation from 2008 to 2019 was performed. The patients were divided into 3 groups. In the 1st group, transplantation was performed according to the Milan criteria (“Milan”), in the 2nd group – to recipients that did not meet the Milan and University of California San Francisco (UCSF) criteria (“extra-UCSF”), in the 3rd group – to the recipients meeting the Barcelona Clinic Liver Cancer criteria B (Intermediate stage), subjected to locoregional therapy and assessment of radiological and serological response (“Lerut”). The frequency of progression in the waiting list, the frequency of tumor recurrence after transplantation, hospital mortality, the frequency of arterial and biliary complications, and cancer-associated mortality were studied.Results. The highest rate of hepatocellular carcinoma progression on the waiting list was observed in the “extra University of California San Francisco” group of patients (36% versus 11% (p = 0.03) and 15% (p = 0.1) in the “Milan” and “Lerut” groups, respectively). The worst cancer-associated mortality rates were found in the extraUniversity of California San Francisco group. The one-year, three-year and five-year overall survival rate in the groups were 87.5%; 80.1% and 70.3% for the Milan group; 78.6%; 62.9% and 62.9% for the extra-University of California San Francisco group and 96.4%; 86.4% and 78.7% for the Lerut group, respectively.Conclusion. The oncological prognosis for patients with hepatocellular carcinoma is formed increasingly on the basis of the biological characteristics of the tumor. The use of locoregional therapy for hepatocellular carcinoma combines a therapeutic component that allows for better survival and stratification, which allows patients with an unfavorable prognosis to be selected and to allow patients beyond the accepted criteria to expect transplantation.

scholarly journals Liver transplantation and expanded Milan criteria: does it really work?

2012 ◽  
Vol 49 (3) ◽  
pp. 189-194 ◽  
Author(s):  
Marina Vilela Chagas Ferreira ◽  
Eleazar Chaib ◽  
Maurício Ursoline do Nascimento ◽  
Rafael Souza Fava Nersessian ◽  
Daniel Takeshi Setuguti ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
San Francisco ◽  
Orthotopic Liver Transplantation ◽  
Tumor Recurrence ◽  
Patient Survival ◽  
Milan Criteria ◽  
English Only ◽  
Significant Difference ◽  
Free Rate

CONTEXT: Orthotopic liver transplantation is an excellent treatment approach for hepatocellular carcinoma in well-selected candidates. Nowadays some institutions tend to Expand the Milan Criteria including tumor with more than 5 cm and also associate with multiple tumors none larger than 3 cm in order to benefit more patients with the orthotopic liver transplantation. METHODS: The data collected were based on the online database PubMED. The key words applied on the search were "expanded Milan criteria" limited to the period from 2000 to 2009. We excluded 19 papers due to: irrelevance of the subject, lack of information and incompatibility of the language (English only). We compiled patient survival and tumor recurrence free rate from 1 to 5-years in patients with hepatocellular carcinoma submitted to orthotopic liver transplantation according to expanded the Milan criteria from different centers. RESULTS: Review compiled data from 23 articles. Fourteen different criteria were found and they are also described in detail, however the University of California - San Francisco was the most studied one among them. CONCLUSION: Expanded the Milan criteria is a useful attempt for widening the preexistent protocol for patients with hepatocellular carcinoma in waiting-list for orthotopic liver transplantation. However there is no significant difference in patient survival rate and tumor recurrence free rate from those patients that followed the Milan criteria.

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.

scholarly journals Patient and tumour biology predict survival beyond the Milan criteria in liver transplantation for hepatocellular carcinoma

HPB ◽  
2015 ◽  
Vol 17 (2) ◽  
pp. 168-175 ◽  
Author(s):  
Andreas Andreou ◽  
Safak Gül ◽  
Andreas Pascher ◽  
Wenzel Schöning ◽  
Hussein Al‐Abadi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Milan Criteria ◽  
Tumour Biology
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