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Intention to treat survival following liver transplantation for hepatocellular carcinoma within a donor service area.

ABSTRACT: BACKGROUND: This study aimed to assess the impact of wait times on patient survival following liver transplantation for hepatocellular carcinoma (HCC) in a single donor service area. PATIENTS AND METHODS: Patients listed in the New England Organ Bank (NEOB) from 1996 to 2005 for liver transplantation with a diagnosis of HCC were identified from the United Network for Organ Sharing database. The following data were extracted: date of listing, date removed from the wait list, indication for wait list removal, patient death and date of last known follow-up. Kaplan-Meier survival estimates were calculated from the time of listing for transplant (intention to treat liver transplant survival, ITT OLT) and compared to those calculated from the date of transplant (liver transplant, OLT). RESULTS: There were 63 new registrations to the transplant list during the study period. Sixty-one patients were removed from the waiting list: transplanted 41 (65%), death seven (11%), candidate condition deteriorated/too sick to transplant eight (13%), medically unsuitable one (2%), other one (2%), transferred to another center two (3%), and transplanted at another center one (2%). Three-year survival following liver transplantation for primary liver cancer was 85%. When the results were analyzed using an intention to treat analysis there was a 10-20% decrease in survival rate at every time point due to wait list drop-out. CONCLUSION: Wait list drop-out adversely affects liver transplant survival in transplant centers served by the NEOB. These data should be considered when recommending transplant versus resection as first line therapy for stage I or II HCC in our region.

SUBMITTER: Charpentier KP

PROVIDER: S-EPMC2597314 | biostudies-other | 2008

REPOSITORIES: biostudies-other

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Project description:BackgroundThe reoperation rate remains high after liver transplantation and the impact of reoperation on graft and recipient outcome is unclear. The aim of our study is to evaluate the impact of early reoperation following living-donor liver transplantation (LDLT) on graft and recipient survival.MethodsRecipients that underwent LDLT (n = 111) at the University of Tokyo Hospital between January 2007 and December 2012 were divided into two groups, a reoperation group (n = 27) and a non-reoperation group (n = 84), and case-control study was conducted.ResultsEarly reoperation was performed in 27 recipients (24.3%). Mean time [standard deviation] from LDLT to reoperation was 10 [9.4] days. Female sex, Child-Pugh class C, Non-HCV etiology, fulminant hepatitis, and the amount of intraoperative fresh frozen plasma administered were identified as possibly predictive variables, among which females and the amount of FFP were identified as independent risk factors for early reoperation by multivariable analysis. The 3-, and 6- month graft survival rates were 88.9% (95%confidential intervals [CI], 70.7-96.4), and 85.2% (95%CI, 66.5-94.3), respectively, in the reoperation group (n = 27), and 95.2% (95%CI, 88.0-98.2), and 92.9% (95%CI, 85.0-96.8), respectively, in the non-reoperation group (n = 84) (the log-rank test, p = 0.31). The 12- and 36- month overall survival rates were 96.3% (95%CI, 77.9-99.5), and 88.3% (95%CI, 69.3-96.2), respectively, in the reoperation group, and 89.3% (95%CI, 80.7-94.3) and 88.0% (95%CI, 79.2-93.4), respectively, in the non-reoperation group (the log-rank test, p = 0.59).ConclusionsObserved graft survival for the recipients who underwent reoperation was lower compared to those who did not undergo reoperation, though the result was not significantly different. Recipient overall survival with reoperation was comparable to that without reoperation. The present findings enhance the importance of vigilant surveillance for postoperative complication and surgical rescue at an early postoperative stage in the LDLT setting.

Project description:BackgroundLiver cancer, of which hepatocellular carcinoma (HCC) is by far the most common type, is the second most deadly cancer (746,000 deaths in 2012). Currently, the only curative treatment for HCC is surgery to remove the malignancy (resection) or to remove the entire diseased liver followed by transplantation of healthy liver tissue. Given the shortage of healthy livers, it is crucial to provide transplants to patients that have the best chance of long-term survival. Currently, transplantation is determined via the Milan criteria-patients within Milan (single tumor < 5 cm or 2-3 tumors < 3 cm with no extrahepatic spread nor intrahepatic vascular invasion) are typically eligible for transplantation. However, combining microRNA expression profiling with the Milan criteria can improve prediction of recurrence. HCC often presents with multiple distinct tumor foci arising from local spread of a primary tumor or from the oncogenic predisposition of the diseased liver. Substantial genomic heterogeneity between tumor foci within a single patient has been reported; therefore, biomarker development must account for the possibility of highly heterogeneous genomic profiles from the same individual.MethodsMicroRNA profiling was performed on 180 HCC tumor samples from 89 patients who underwent liver transplantation at the University of Rochester Medical Center. The primary outcome was recurrence-free survival time, and patients were observed for 3 years post-transplantation.ResultsMicroRNA expression profiles were used to develop a biomarker that distinguishes HCC patients at greater risk of recurrence post-transplantation. Unsupervised clustering uncovered two distinct subgroups with vast differences in standard transplantation selection criteria and recurrence-free survival times. These subgroups were subsequently used to identify microRNAs strongly associated with HCC recurrence. Our results show that reduced expression of five specific microRNAs is significantly associated with HCC recurrence post-transplantation.ConclusionsMicroRNA profiling of distinct tumor foci, coupled with methods that address within-subject tumor heterogeneity, has the potential to significantly improve prediction of HCC recurrence post-transplantation. The development of a clinically applicable HCC biomarker would inform treatment options for patients and contribute to liver transplant selection criteria for practitioners.

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Intention to treat survival following liver transplantation for hepatocellular carcinoma within a donor service area.

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