Hepatocellular Carcinoma and Liver Transplantation: A 12-Year Experience

Varona, M.A.; Pino, José M. del; Barrera, Manuel; Arranz, José Ángel; Hernandez, Brenda; Pérez, Hermes; Padilla, Javier; Fuentes, Javier Segovia; Aguirre, Aaron D.; Méndez, S. Morales; Sanz, Pablo; Moorjani, Rajesh Gianchandani; Perera, A.; Soriano, Arturo

doi:10.1016/j.transproceed.2009.02.029

Cited by 16 publications

(13 citation statements)

References 13 publications

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“…In total, 980 articles were initially identified from the literature search, but only 53 studies fulfilled the inclusion criteria (Fig. ) . There were four studies from one single Italian center, which included patients from overlapping study periods, and it was decided to include only the first two studies , in which the impact of CNIs and/or mTORi on HCC recurrence was evaluated.…”

Section: Resultsmentioning

confidence: 99%

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Mammalian target of rapamycin inhibitors are associated with lower rates of hepatocellular carcinoma recurrence after liver transplantation: a systematic review

et al. 2014

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SummaryCalcineurin inhibitors (CNIs) have been associated in a dose-dependent fashion with an increased risk of post-transplant hepatocellular carcinoma (HCC) recurrence. The mammalian target of rapamycin inhibitors (mTORi) (sirolimus/everolimus) might represent an alternative immunosuppressive regimen with antineoplastic effect. In the present systematic review, the association between mTORi and HCC recurrence after liver transplantation (LT) was evaluated and compared against that of CNIs-treated patients. In total, 3666 HCC liver transplant recipients from 42 studies met the inclusion criteria. Patients under CNIs developed HCC recurrence significantly more frequently, compared with patients under mTORi (448/3227 or 13.8% vs. 35/439 or 8%, P < 0.001), although patients treated with CNIs had a higher proportion of HCC within Milan criteria (74% vs. 69%) and lower rates of microvascular invasion, compared with mTORi-treated patients (22% vs. 44%) (P < 0.05). Patients on everolimus had significantly lower recurrence rates of HCC, compared with those on sirolimus or CNIs (4.1% vs. 10.5% vs. 13.8%, respectively, P < 0.05), but everolimus-treated recipients had shorter follow-up period (13 vs. 30 vs. 43.2 months, respectively) and more frequently been transplanted for HCC within Milan criteria (84% vs. 60.5% vs. 74%, respectively, P < 0.05). Our findings favor the use of mTORi instead of CNIs to control HCC recurrence after LT, but comparative studies with longer follow-up are needed for final conclusions.

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Section: Resultsmentioning

confidence: 99%

“…Finally, two studies from the same center in Japan , both published in 2013, had overlapping study periods; in this case, we included the study with the longer study period (1999–2012 vs. 1999–2011). Thus, 42 studies providing data regarding immunosuppression regimen (CNIs or mTORi) and HCC recurrence were included in our analysis .…”

Section: Resultsmentioning

confidence: 99%

Mammalian target of rapamycin inhibitors are associated with lower rates of hepatocellular carcinoma recurrence after liver transplantation: a systematic review

et al. 2014

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“…Liver transplantation (LT) is the only therapeutic option capable of simultaneously treating HCC and any associated liver diseases such as hepatic cirrhosis [4][5][6]. However, the results of transplantation alone for advanced HCC are disappointing, with a 1-year recurrence rate of 30-60% and a 5-year survival rate of <30% [7,8].…”

Section: Introductionmentioning

confidence: 99%

Combination adjuvant chemotherapy with oxaliplatin, 5-fluorouracil and leucovorin after liver transplantation for hepatocellular carcinoma: a preliminary open-label study

Zhang

Chen

Li³

et al. 2011

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The purpose of this study was to evaluate the efficacy of postoperative adjuvant chemotherapy with FOLFOX regimen on the outcome after LT for HCC patients who did not meet the Milan criteria. Ninety-five consecutive HCC patients with liver cirrhosis undergoing LT were enrolled. Fifty-eight who did not meet the Milan criteria were randomized to open-label treatment with or without adjuvant chemotherapy after LT (n = 29/group). The FOLFOX chemotherapy protocol comprised 3-week cycles of oxaliplatin 100 mg/m(2) on day 1, leucovorin (calcium folinate, CF) 200 mg/m(2) on day 1 followed by 3-day, and 5-fluorouracil (5-FU) 2000 mg/m(2) as a 48-h continuous infusion, for up to six courses in the 1st year after transplantation. Median survival was extended by 4.57 months by combination chemotherapy. The 1- and 3-year survival rates were 89.7% and 79.3% with chemotherapy versus 69.0% and 62.1% without chemotherapy. The cumulative 1-year survival was significantly increased by chemotherapy (log-rank test, P = 0.043). The 6-month tumor-free survival rate was 24.1% higher with chemotherapy than without. The recurrence rate after LT was significantly different between the two groups at 6 months (P = 0.036), but not at 3 years (P = 0.102). The chemotherapy regimen was generally well tolerated. Post-LT adjuvant chemotherapy with oxaliplatin/5-FU/CF could not prevent tumor recurrence post-LT but may contribute to improve the survival of HCC patients who do not meet the Milan criteria. These results should be verified in a larger sample with a longer follow-up period.

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“…We will refer to this as the French model. Our group [64] , based on our previous experience with LT for patients with HCC and cirrhosis, has performed an analysis of the risk factors for HCC relapse and applied the French AFP model to LT for HCC and cirrhosis patients who met the MC [65] . We were able to confirm the predictive value for tumor relapse of the French AFP model both pre-and postoperatively.…”

Section: Distinguishing Between Wellandmentioning

confidence: 99%

Selection of patients with hepatocellular carcinoma for liver transplantation: Past and future

Soriano¹

2016

WJH

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The aim of liver transplantation (LT) for hepatocellular carcinoma (HCC) is to ensure a rate of disease-free survival similar to that of patients transplanted due to benign disease. Therefore, we are forced to adopt strict criteria when selecting candidates for LT and prioritizing patients on the waiting list (WL), to have clarified indications for bridging therapy for groups at risk for progression or recurrence, and to establish certain limits for downstaging therapies. Although the Milan criteria (MC) remain the standard and most employed criteria for indication of HCC patients for LT by far, in the coming years, criteria will be consolidated that take into account not only data regarding the size/ volume and number of tumors but also their biology. This criteria will mainly include the alpha fetoprotein (AFP) values and, in view of their wide variability, any of the published logarithmic models for the selection of candidates for LT. Bridging therapy is necessary for HCC patients on the WL who meet the MC and have the possibility of experiencing a delay for LT greater than 6 mo or any of the known risk factors for recurrence. It is difficult to define single AFP values that would indicate bridging therapy (200, 300 or 400 ng/mL); therefore, it is preferable to rely on the criteria of a French AFP model score > 2. Other single indications for bridging therapy include a tumor diameter greater than 3 cm, more than one tumor, and having an AFP slope greater than 15 ng/mL per month or > 50 ng/mL for three months during strict monitoring while on the WL. When considering the inclusion of patients on the WL who do not meet the MC, it is mandatory to determine their eligibility for downstaging therapy prior to inclusion. The upper limit for this therapy could be one lesion up to 8 cm, 2-3 lesions with a total tumor diameter up to 8 cm, or a total tumor volume of 115 cm 3 . Selection of patients with hepatocellular carcinoma for liver transplantation: Past and future the WL should take into account the recently described HCC model for end-stage liver disease, which considers hepatic function, HCC size and the number and the log of AFP values. This formula has been calibrated with the survival data of non-HCC patients and produces a dynamic and more accurate assessment model.

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Hepatocellular Carcinoma and Liver Transplantation: A 12-Year Experience

Cited by 16 publications

References 13 publications

Mammalian target of rapamycin inhibitors are associated with lower rates of hepatocellular carcinoma recurrence after liver transplantation: a systematic review

Mammalian target of rapamycin inhibitors are associated with lower rates of hepatocellular carcinoma recurrence after liver transplantation: a systematic review

Combination adjuvant chemotherapy with oxaliplatin, 5-fluorouracil and leucovorin after liver transplantation for hepatocellular carcinoma: a preliminary open-label study

Selection of patients with hepatocellular carcinoma for liver transplantation: Past and future

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