Liver Transplantation for the Treatment of Small Hepatocellular Carcinomas in Patients with Cirrhosis

Mazzaferro, Vincenzo; Regalia, Enrico; Doci, Roberto; Andreola, Salvatore; Pulvirenti, Andrea; Bozzetti, Federico; Montalto, Fabrizio; Ammatuna, Mario; Morabito, Alberto; Gennari, Leandro

doi:10.1056/nejm199603143341104

Cited by 6,486 publications

(5,131 citation statements)

References 26 publications

Supporting

100

Mentioning

4,740

Contrasting

Unclassified

158

Order By: Relevance

“…[1][2][3] The prioritization of LT recipients with HCC by use of the Model for End-Stage Liver Disease (MELD) allocation system [4][5][6] has resulted in LTs for HCCs now accounting for nearly 25% of all transplants in the United States. 7 Despite continuous refinements in the HCC MELD exception policy, LT recipients with HCC continue to be overprioritized compared with patients with liver failure who do not have cancer, with many studies revealing higher transplant rates despite lower risks of waitlist dropout and inferior survival.…”

mentioning

confidence: 99%

Evaluation of Patients With Hepatocellular Carcinomas That Do Not Produce α-Fetoprotein

et al. 2017

View full text Add to dashboard Cite

IMPORTANCE Serum α-fetoprotein (AFP) is a biomarker for hepatocellular carcinomas (HCCs) associated with a more aggressive tumor phenotype and inferior outcomes after a liver transplant (LT). Data on the outcomes for patients with HCCs that do not produce AFP are limited.OBJECTIVE To compare characteristics and outcomes among LT recipients with radiographically apparent HCC lesions with AFP-producing tumors or with tumors that do not produce AFP (hereafter referred to as non-AFP-producing tumors), and to identify factors influencing recurrence in LT recipients with non-AFP-producing tumors. DESIGN, SETTING, AND PARTICIPANTSRetrospective analysis at a university transplant center of 665 adults with HCC who underwent an LT during the period from 1989 to 2013. Of the 665 LT recipients, 457 (68.7%) had AFP-producing tumors, and 208 (31.3%) had non-AFP-producing tumors (the maximum AFP level before an LT was Յ10 ng/mL). Dates of study analysis were from August 2015 to June 2016. INTERVENTION Liver transplant. MAIN OUTCOMES AND MEASURESRecurrence-free survival and recurrence rates. RESULTSPatients with non-AFP-producing tumors had radiographic tumor characteristics similar to those of patients with AFP-producing tumors, but, pathologically, they had fewer lesions (25% vs 35% with >2 lesions; P = .03), smaller cumulative tumor diameters (4.2 vs 5.0 cm; P = .02), fewer microvascular (17% vs 22%) and macrovascular (2% vs 9%) invasions (P < .001), and fewer poorly differentiated tumors (15% vs 28%; P < .001). Patients with non-AFP-producing tumors also had significantly superior recurrence-free survival at 1, 3, and 5 years (88%, 74%, and 67% vs 76%, 59%, and 51%, respectively; P = .002) and lower 5-year recurrence rates (8.8% vs 22%; P < .001) than patients with AFP-producing tumors. When stratified by radiologic Milan criteria, 5-year survival was better, and recurrence lowest, among patients with non-AFP-producing tumors within the Milan criteria (71% survival and 6% recurrence), and survival was worse, and recurrence highest, for patients with AFP-producing tumors outside the Milan criteria (40% survival and 42% recurrence; P < .001). Significant predictors of recurrence among patients with non-AFP-producing tumors include radiologic (>2 tumors [HR, 4.98; 95% CI, 1.72-14.4; P = .003]; cumulative diameter [1.70 per log SD; 1.12-2.59; P < .001]; outside the Milan criteria [10.0; 3.7-33.3; P < .001) and pathologic factors (>2 tumors [4.39; 1.32-14.6; P = .02]; cumulative diameter [2.32 per log SD; 1.43-3.77; P = .001]; microvascular [3.07; 1.02-9.24; P = .05] and macrovascular invasion [8.75; 2.15-35.6; P = .002]).CONCLUSIONS AND RELEVANCE Nearly one-third of patients with radiographically apparent HCC have non-AFP-producing tumors that have more favorable pathologic characteristics, lower posttransplant recurrence, and superior survival compared with patients with AFP-producing tumors. Posttransplant HCC recurrence for patients with non-AFP-producing tumors is predicted by important radiologic and pathologic factors, an...

show abstract

mentioning

confidence: 99%

Evaluation of Patients With Hepatocellular Carcinomas That Do Not Produce α-Fetoprotein

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Surgery, liver transplantation, or resection is hindered by a high frequency of relapse and cannot be proposed to most patients due to size or local extension of the tumor at the time of diagnosis. [5][6][7][8][9][10][11] For these patients, intraarterial chemoembolization or percutaneous ethanol injection have been proposed but have failed to show any survival benefit. 9,12,13 Therefore, it is of importance to develop new therapeutic approaches such as gene transfer strategies.…”

mentioning

confidence: 99%

Gene transfer to hepatocellular carcinoma: Transduction efficacy and transgene expression kinetics by using retroviral and lentiviral vectors

et al. 2000

View full text Add to dashboard Cite

Gene therapy is an attractive therapy for hepatocarcinoma, and several approaches have been studied using murine leukemia virus-derived retroviruses. We compared gene transfer efficacy and transgene expression kinetics after transduction of hepatocarcinoma cell lines using enhanced green fluorescent protein (EGFP)-expressing murine leukemia virus-derived retroviral vectors and HIV-derived lentiviral vectors. First, we showed that both retroviral and lentiviral vectors efficiently transduce cycling hepatocarcinoma cell lines in vitro. However, after cell cycle arrest, transduction efficacy remained the same for lentiviral vectors but it decreased by 80% for retroviral vectors. Second, we studied EGFP expression kinetics using lentiviral vectors expressing EGFP under the control of cytomegalovirus (CMV) or phosphoglycerolkinase (PGK) promoter. We show that the CMV promoter allows a stronger EGFP expression than the PGK promoter. However, in contrast to PGK-driven EGFP expression, which persists up to 2 months after transduction, CMV-driven EGFP expression rapidly decreased with time. This phenomenon is due to promoter silencing, and EGFP expression can be restored in transduced cells by using transcription activators such as interleukin-6 or phorbol myristate acetate/ionomycin and, to a lesser extent, the demethylating agent 5Ј-azacytidine. Altogether, our results suggest that lentiviral vectors, which allow efficient transduction of hepatocarcinoma cell lines with a strong and a sustained expression according to the promoter used, are promising tools for gene therapy of hepatocarcinomas.

show abstract

“…21 In 1993, Bismuth et al 22 reported that patients with fewer than 3 tumor nodules (each < 3 cm in diameter) were suitable candidates for liver transplantation because their disease-free survival rate after the procedure was superior to the rate after liver resection. Consequently, the performance of liver transplantation for patients with small HCCs became established after the 1996 publication of a study by Mazzaferro et al 23 They reported excellent outcomes after liver transplantation for patients with a solitary HCC nodule less than 5 cm in diameter or with up to 3 HCC nodules that were each less than 3 cm in diameter; these features were designated the Milan criteria. The 5-year survival rate of patients with HCC selected according to the Milan criteria currently exceeds 70%.…”

Section: History Of Liver Transplantation For Hccmentioning

confidence: 99%

Toward optimizing the indications for orthotopic liver transplantation in hepatocellular carcinoma

Samuel

Colombo²,

El-Serag

et al. 2011

Liver Transpl

View full text Add to dashboard Cite

Liver Transplantation for the Treatment of Small Hepatocellular Carcinomas in Patients with Cirrhosis

Abstract: Liver transplantation is an effective treatment for small, unresectable hepatocellular carcinomas in patients with cirrhosis.

Cited by 6,486 publications

References 26 publications

Evaluation of Patients With Hepatocellular Carcinomas That Do Not Produce α-Fetoprotein

Evaluation of Patients With Hepatocellular Carcinomas That Do Not Produce α-Fetoprotein

Gene transfer to hepatocellular carcinoma: Transduction efficacy and transgene expression kinetics by using retroviral and lentiviral vectors

Toward optimizing the indications for orthotopic liver transplantation in hepatocellular carcinoma

Contact Info

Product

Resources

About