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Goudsmit BF, Ilaria Prosepe, Tushuizen ME, Mazzaferro V, Alwayn IP, van Hoek B, Braat AE, Putter H. Survival benefit from liver transplantation for patients with and without hepatocellular carcinoma. JHEP Rep 2023; 5:100907. [PMID: 38034881 PMCID: PMC10685016 DOI: 10.1016/j.jhepr.2023.100907] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 08/11/2023] [Accepted: 08/31/2023] [Indexed: 12/02/2023] Open
Abstract
Background & Aims In the USA, inequal liver transplantation (LT) access exists between patients with and without hepatocellular carcinoma (HCC). Survival benefit considers survival without and with LT and could equalise LT access. We calculated bias-corrected LT survival benefit for patients with(out) HCC who underwent a transplant, based on longitudinal data in a recent United States cohort. Methods Adult LT candidates with(out) HCC between 2010 and 2019 were included. Waitlist survival over time was contrasted to post-transplant survival, to estimate 5-year survival benefit from the moment of LT. Waitlist survival was modelled with a bias-corrected Cox regression, and post-transplant survival was estimated through Cox proportional hazards regression. Results Mean HCC survival without LT was always lower than non-HCC waitlist survival. Below model for end-stage liver disease (sodium) (MELD(-Na)) 30, patients with HCC gained more life-years from LT than patients without HCC at the same MELD(-Na) score. Only patients without HCC below MELD(-Na) 9 had negative benefit. Most patients with HCC underwent a transplant below MELD(-Na) 14, and most patients without HCC underwent a transplant above MELD(-Na) 26. Liver function [MELD(-Na), albumin] was the main predictor of 5-year benefit. Therefore, during 5 years, most patients with HCC gained 0.12 to 1.96 years from LT, whereas most patients without HCC gained 2.48 to 3.45 years. Conclusions On an individual level, performing a transplant in patients with HCC resulted in survival benefit. However, on a population level, benefit was indirectly decreased, as patients without HCC were likely to gain more survival owing to decreased liver function. For patients who underwent a transplant, a constructed online calculator estimates 5-year survival benefit given specific patient characteristics. Survival benefit scores could serve to equalise LT access. Impact and implications Benefit is a comparison of the survival with and without liver transplantation, and it is important when deciding who should undergo a transplant. Liver function is most important when predicting possible benefit from transplantation. Patients with liver cancer die sooner on the waiting list than similar patients without liver cancer. However, patients with liver cancer more often have better liver function. Most patients without liver cancer derive more benefit from transplantation than patients with liver cancer.
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Affiliation(s)
- Ben F.J. Goudsmit
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Ilaria Prosepe
- Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
| | - Maarten E. Tushuizen
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
- Transplant Center, Leiden University Medical Center, Leiden, The Netherlands
| | - Vincenzo Mazzaferro
- Department of Oncology, University of Milan, Milan, Italy
- Hepatology and Liver Transplantation Unit, Department of Surgery, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale Tumori, Milan, Italy
| | - Ian P.J. Alwayn
- Transplant Center, Leiden University Medical Center, Leiden, The Netherlands
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Bart van Hoek
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
- Transplant Center, Leiden University Medical Center, Leiden, The Netherlands
| | - Andries E. Braat
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Hein Putter
- Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
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Mehta N, Dodge JL, Roberts JP, Yao FY. A novel waitlist dropout score for hepatocellular carcinoma - identifying a threshold that predicts worse post-transplant survival. J Hepatol 2021; 74:829-837. [PMID: 33188904 PMCID: PMC7979440 DOI: 10.1016/j.jhep.2020.10.033] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 10/08/2020] [Accepted: 10/29/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS It has been suggested that patients with hepatocellular carcinoma (HCC) at high risk of wait-list dropout would have done poorly after liver transplantation (LT) because of tumour aggressiveness. To test this hypothesis, we analysed risk of wait-list dropout among patients with HCC in long-wait regions (LWRs) to create a dropout risk score, and applied this score in short (SWRs) and mid-wait regions (MWRs) to evaluate post-LT outcomes. We sought to identify a threshold in dropout risk that predicts worse post-LT outcome. METHODS Using the United Network for Organ Sharing database, including all patients with T2 HCC receiving priority listing from 2010 to 2014, a dropout risk score was created from a developmental cohort of 2,092 patients in LWRs, and tested in a validation cohort of 1,735 patients in SWRs and 2,894 patients in MWRs. RESULTS On multivariable analysis, 1 tumour (3.1-5 cm) or 2-3 tumours, alpha-fetoprotein (AFP) >20 ng/ml, and increasing Child-Pugh and model for end-stage liver disease-sodium scores significantly predicted wait-list dropout. A dropout risk score using these 4 variables (C-statistic 0.74) was able to stratify 1-year cumulative incidence of dropout from 7.1% with a score ≤7 to 39.5% with a score >23. Patients with a dropout risk score >30 had 5-year post-LT survival of 60.1% vs. 71.8% for those with a score ≤30 (p = 0.004). There were no significant differences in post-LT survival below this threshold. CONCLUSIONS This study provided evidence that patients with HCC with the highest dropout risk have aggressive tumour biology that would also result in poor post-LT outcomes when transplanted quickly. Below this threshold risk score of ≤30, priority status for organ allocation could be stratified based on the predicted risks of wait-list dropout without significant differences in post-LT survival. LAY SUMMARY Prioritising patients with hepatocellular carcinoma for liver transplant based on risk of wait-list dropout has been considered but may lead to inferior post-transplant survival. In this study of nearly 7,000 patients, we created a threshold dropout risk score based on tumour and liver-related factors beyond which patients with hepatocellular carcinoma will likely have poor post-liver transplant outcomes (60% at 5 years). For patients below this risk score threshold, priority status could be stratified based on the predicted risk of wait-list dropout without compromising post-transplant survival.
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Affiliation(s)
- Neil Mehta
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
| | - Jennifer L Dodge
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, USA
| | - John P Roberts
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, USA
| | - Francis Y Yao
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA; Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, USA
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3
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Kumar S, Lin S, Schold JD. Impact of donation after circulatory death donor allografts on outcomes following liver transplantation for fulminant hepatic failure in the United States. Am J Transplant 2021; 21:382-390. [PMID: 32865321 DOI: 10.1111/ajt.16286] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2020] [Revised: 08/18/2020] [Accepted: 08/19/2020] [Indexed: 01/25/2023]
Abstract
Limited data exist regarding the impact of donation after circulatory death (DCD) allografts on outcomes following liver transplantation in fulminant hepatic failure (FHF). Utilizing the Scientific Registry of Transplant Recipients (SRTR), we compared outcomes after DCD in FHF to donation after brain death (DBD) in FHF and DCD in non-FHF over a 15-year period. Primary outcome measures were graft and patient survival. A total of 117, 3437, and 4379 recipients underwent DCD-FHF, DBD-FHF and DCD-non-FHF, respectively. One-year graft survival in DCD-FHF was inferior to DBD-FHF (72.9% vs. 83.8%, p = .002), but comparable to DCD-non-FHF (72.9% vs. 82.7%, p = .23). However, 3- and 5-year graft survival in DCD-FHF were comparable to DBD-FHF (67.9 vs. 77.6%, p = .63; 57.8% vs. 73.2%, p = .27) and DCD-non-FHF (67.9% vs. 72.9%, p = .44; 57.8% vs. 66.6%, p = .06). One-, 3-, and 5-year patient survival were also comparable among the three groups. Graft and patient survival in DCD-FHF improved over the study period. Multivariable analysis identified recipient age, male gender, African American ethnicity, donor age, and cold ischemia time as predictors of graft and patient survival in FHF, while DCD status was only predictive of graft survival. Long-term graft survival and patient survival in DCD-FHF are comparable to DBD-FHF and DCD-non-FHF. Consideration of DCD in FHF could help expand the donor pool in this subset of critically ill patients.
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Affiliation(s)
- Shiva Kumar
- Department of Gastroenterology & Hepatology, Digestive Disease Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - Songhua Lin
- Department of Quantitative Health Sciences, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Jesse D Schold
- Department of Quantitative Health Sciences, Cleveland Clinic Foundation, Cleveland, Ohio, USA.,Center for Populations Health Research, Cleveland Clinic Foundation, Cleveland, Ohio, USA
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Brondfield MN, Dodge JL, Hirose R, Heimbach J, Yao FY, Mehta N. Unfair Advantages for Hepatocellular Carcinoma Patients Listed for Liver Transplant in Short-Wait Regions Following 2015 Hepatocellular Carcinoma Policy Change. Liver Transpl 2020; 26:662-672. [PMID: 31833634 PMCID: PMC8751234 DOI: 10.1002/lt.25701] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Accepted: 12/05/2019] [Indexed: 02/07/2023]
Abstract
For patients with hepatocellular carcinoma (HCC) listed for liver transplantation (LT), United Network for Organ Sharing (UNOS) enacted policy changes in 2015 to improve equity between HCC and non-HCC patients. We evaluated the impact of these changes on regional disparities in wait-list dropout and LT. We included patients in the UNOS database listed with Model for End-Stage Liver Disease HCC exceptions in long-wait regions (LWRs), mid-wait regions (MWRs), and short-wait regions (SWRs) before these policy changes (era 1, January 1 to December 31, 2013) and after (era 2, October 7, 2015, to October 7, 2016). Cumulative incidence of wait-list dropout and LT were evaluated using competing risk regression. Median time to LT increased by 3.6 months (3.1 to 6.7 months) in SWRs and 1.3 months (6.9 to 8.2 months) in MWRs (P < 0.001), with a slight decrease in LWRs (13.4 to 12.9 months; P = 0.02). The 2-year cumulative incidence of dropout increased from 9.7% to 14.8% in SWRs (P = 0.03) and from 18.9% to 22.6% in MWRs (P = 0.18) but decreased in LWRs from 26.7% to 24.8% (P = 0.31). Factors predicting wait-list dropout included listing in era 2 (hazard ratio [HR], 1.17), in LWRs (HR, 2.56), and in MWRs (HR, 1.91). Regional differences in wait-list outcomes decreased with policy changes, but HCC patients in SWRs remain advantaged. Recent policy change may narrow these disparities.
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Affiliation(s)
| | - Jennifer L. Dodge
- Division of Transplant Surgery, Department of Surgery University of California, San Francisco, CA
| | - Ryutaro Hirose
- Division of Transplant Surgery, Department of Surgery University of California, San Francisco, CA
| | - Julie Heimbach
- Division of Transplantation, Department of Surgery, Mayo Clinic, Rochester, MN
| | - Francis Y. Yao
- Division of Transplant Surgery, Department of Surgery University of California, San Francisco, CA;,Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA
| | - Neil Mehta
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA
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Spaggiari M, Okoye O, Tulla K, Di Cocco P, Almario J, Benedetti E, Tzvetanov I. Geographic Disparities in Liver Allocation and Distribution in the United States: Where Are We Now? Transplant Proc 2019; 51:3205-3212. [PMID: 31732201 DOI: 10.1016/j.transproceed.2019.07.018] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Revised: 05/24/2019] [Accepted: 07/09/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND Equitable deceased donor liver allocation and distribution has remained a heated topic in transplant medicine. Despite the establishment of numerous policies, mixed reports regarding organ allocation persist. METHODS Patient data was obtained from the United Network for Organ Sharing liver transplant database between January 2016 and September 2017. A total of 20,190 patients were included in the analysis. Of this number, 8790 transplanted patients had a median Model for End-Stage Liver Disease (MELD) score of 25 (17-33), after a wait time of 129 (32-273) days. Patients were grouped into low MELD and high MELD regions using a score 25 as the cutoff. RESULTS Significant differences were noted between low and high MELD regions in ethnicity (white 77.4% vs 60.4%, Hispanic 8.1% vs 24.5%; P < .001) and highest level of education (grade school 4.8% vs 8.5%, Associate/Bachelor's degree 19% vs 15.7%, P < .001), respectively. Patients in high MELD regions were more likely to be multiply listed if they had a diagnosis of hepatocellular carcinoma (12.1% vs 15%, P = .046). Wait-list mortality (4.8% vs 6%, P < .001) and wait-list time (110 [27-238] vs 156 [42-309] days, P < .001) were greater in the high MELD regions. CONCLUSIONS These results highlight some of the existing disparities in the recently updated allocation and distribution policy of deceased donor livers. Our findings are consistent with previous work and support the liver distribution policy revision.
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Affiliation(s)
- Mario Spaggiari
- Division of Transplantation, Department of General Surgery, University of Illinois at Chicago, Chicago, Illinois.
| | - Obi Okoye
- Division of Transplantation, Department of General Surgery, University of Illinois at Chicago, Chicago, Illinois
| | - Kiara Tulla
- Division of Transplantation, Department of General Surgery, University of Illinois at Chicago, Chicago, Illinois
| | - Pierpaolo Di Cocco
- Division of Transplantation, Department of General Surgery, University of Illinois at Chicago, Chicago, Illinois
| | - Jorge Almario
- Division of Transplantation, Department of General Surgery, University of Illinois at Chicago, Chicago, Illinois
| | - E Benedetti
- Division of Transplantation, Department of General Surgery, University of Illinois at Chicago, Chicago, Illinois
| | - Ivo Tzvetanov
- Division of Transplantation, Department of General Surgery, University of Illinois at Chicago, Chicago, Illinois
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6
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Mehta N, Dodge JL, Hirose R, Roberts JP, Yao FY. Predictors of low risk for dropout from the liver transplant waiting list for hepatocellular carcinoma in long wait time regions: Implications for organ allocation. Am J Transplant 2019; 19:2210-2218. [PMID: 30861298 PMCID: PMC7072024 DOI: 10.1111/ajt.15353] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Revised: 02/24/2019] [Accepted: 02/28/2019] [Indexed: 01/25/2023]
Abstract
All patients with hepatocellular carcinoma meeting United Network for Organ Sharing T2 criteria currently receive the same listing priority for liver transplant (LT). A previous study from our center identified a subgroup with a very low risk of waitlist dropout who may not derive immediate LT benefit. To evaluate this issue at a national level, we analyzed within the United Network for Organ Sharing database 2052 patients with T2 hepatocellular carcinoma receiving priority listing from 2011 to 2014 in long wait time regions 1, 5, and 9. Probabilities of waitlist dropout were 18.3% at 1 year and 27% at 2 years. In multivariate analysis, factors associated with a lower risk of waitlist dropout included Model for End-Stage Liver Disease-Na < 15, Child's class A, single 2- to 3-cm lesion, and α-fetoprotein ≤20 ng/mL. The subgroup of 245 (11.9%) patients meeting these 4 criteria at LT listing had a 1-year probability of dropout of 5.5% vs 20% for all others (P < .001). On explant, the low dropout risk group was more likely to have complete tumor necrosis (35.5% vs 24.9%, P = .01) and less likely to exceed Milan criteria (9.9% vs 17.7%, P = .03). We identified a subgroup with a low risk of waitlist dropout who should not receive the same LT listing priority.
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Affiliation(s)
- Neil Mehta
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, California
| | - Jennifer L. Dodge
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, California
| | - Ryutaro Hirose
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, California
| | - John P. Roberts
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, California
| | - Francis Y. Yao
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, California
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, California
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7
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Mehta N, Dodge JL, Hirose R, Roberts JP, Yao FY. Increasing Liver Transplantation Wait-List Dropout for Hepatocellular Carcinoma With Widening Geographical Disparities: Implications for Organ Allocation. Liver Transpl 2018; 24:1346-1356. [PMID: 30067889 PMCID: PMC6445639 DOI: 10.1002/lt.25317] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Revised: 06/25/2018] [Accepted: 07/24/2018] [Indexed: 12/22/2022]
Abstract
Given the increasing incidence of hepatocellular carcinoma (HCC) and regional variation in liver transplantation (LT) rates for HCC, we investigated temporal and geographic disparities in LT and wait-list dropout. LT candidates receiving Model for End-Stage Liver Disease (MELD) exception from 2005 to 2014 were identified from the United Network for Organ Sharing database (n = 14,320). Temporal differences were compared across 2 eras (2005-2009 and 2010-2014). Regional groups were defined based on median wait time as long-wait region (LWR; regions 1, 5, and 9), mid-wait region (MWR; regions 2, 4, 6, 7, and 8), and short-wait region (SWR; regions 3, 10, and 11). Fine and Gray competing risk regression estimated risk of wait-list dropout as hazard ratios (HRs). The cumulative probability of LT within 3 years was 70% in the LWR versus 81% in the MWR and 91% in the SWR (P < 0.001). From 2005-2009 to 2010-2014, median time to LT increased by 6.0 months (5.6 to 11.6 months) in the LWR compared with 3.8 months (2.6 to 6.4 months) in the MWR and 1.3 months (1.0 to 2.3 months) in the SWR. The cumulative probability of dropout within 3 years was 24% in the LWR versus 16% in the MWR and 8% in the SWR (P < 0.001). From 2005-2009 to 2010-2014, the LWR also had the greatest increase in probability of dropout. Risk of dropout was increased in the LWR (HR, 3.5; P < 0.001) and the MWR (HR, 2.2; P < 0.001) compared with the SWR, and year of MELD exception 2010-2014 (HR, 1.9; P < 0.001) compared with 2005-2009. From 2005-2009 to 2010-2014, intention-to-treat 3-year survival decreased from 69% to 63% in the LWR (P < 0.001), 72% to 69% in the MWR (P = 0.008), and remained at 74% in the SWR (P = 0.48). In conclusion, we observed a significant increase in wait-list dropout in HCC patients in recent years that disproportionately impacted LWR patients. Widening geographical disparities call for changes in allocation policy as well as enhanced efforts at increasing organ donation and utilization.
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Affiliation(s)
- Neil Mehta
- Divisions of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA
| | - Jennifer L. Dodge
- Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA
| | - Ryutaro Hirose
- Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA
| | - John P. Roberts
- Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA
| | - Francis Y. Yao
- Divisions of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA,Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA
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Abstract
Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. In select patients, surgical treatment in the form of either resection or transplantation offers a curative option. The aims of this review are to (1) review the current American Association for the Study of Liver Diseases/European Association for the Study of the Liver guidelines on the surgical management of HCC and (2) review the proposed changes to these guidelines and analyze the strength of evidence underlying these proposals. Three authors identified the most relevant publications in the literature on liver resection and transplantation for HCC and analyzed the strength of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification. In the United States, the liver allocation system provides priority for liver transplantation to patients with HCC within the Milan criteria. Current evidence suggests that liver transplantation may also be indicated in certain patient groups beyond Milan criteria, such as pediatric patients with large tumor burden or adult patients who are successfully downstaged. Patients with no underlying liver disease may also benefit from liver transplantation if the HCC is unresectable. In patients with no or minimal (compensated) liver disease and solitary HCC ≥2 cm, liver resection is warranted. If liver transplantation is not available or contraindicated, liver resection can be offered to patients with multinodular HCC, provided that the underlying liver disease is not decompensated. Many patients may benefit from surgical strategies adapted to local resources and policies (hepatitis B prevalence, organ availability, etc). Although current low-quality evidence shows better overall survival with aggressive surgical strategies, this approach is limited to select patients. Larger and well-designed prospective studies are needed to better define the benefits and limits of such approach.
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Affiliation(s)
- Daniel Zamora-Valdes
- 1 Divisions of Transplantation Surgery, William J. von Liebig Transplant Center, Mayo Clinic, Rochester, MN, USA
| | - Timucin Taner
- 1 Divisions of Transplantation Surgery, William J. von Liebig Transplant Center, Mayo Clinic, Rochester, MN, USA
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9
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Rudnick SR, Russo MW. Liver transplantation beyond or downstaging within the Milan criteria for hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol 2018; 12:265-275. [PMID: 29231769 DOI: 10.1080/17474124.2018.1417035] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Unresectable hepatocellular carcinoma (HCC) is a common indication for liver transplantation (LT). The Milan criteria became standard criteria but expansion beyond the Milan criteria (tumor size and number) have resulted in similar post-transplant outcomes, thus suggesting LT is a viable treatment option for HCC presenting beyond the Milan criteria Areas covered: Expanded criteria and the use of downstaging therapies to meet Milan criteria are reviewed. Surrogates of tumor biology (including biomarkers and response to therapy) are described in detail. The controversy regarding treatment of HCV infection prior to transplant for HCC is addressed. Predictors of post-transplant recurrence and therapeutic options are explored. English-language manuscripts pertaining to LT criteria for HCC, downstaging, and tumor prognosis were reviewed. Effort was made to include manuscripts from throughout the world to ensure the reader a broad international perspective. Expert commentary: Patients can be successfully transplanted with HCC beyond Milan criteria, or patients beyond Milan criteria can be downstaged to within Milan criteria and achieve successful post-liver transplant outcomes. The current reliance on tumor burden (size and number) alone ignores the mounting data supporting the prognostic use of additional surrogates of tumor biology in identifying appropriate candidates.
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Affiliation(s)
- Sean R Rudnick
- a Division of Gastroenterology , Wake Forest University School of Medicine , Winston-Salem , NC , USA
| | - Mark W Russo
- b Division of Hepatology , Carolinas HealthCare System , Charlotte , NC , USA
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10
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Abstract
Over the last several years, liver transplantation has evolved to become a widely used treatment for hepatocellular carcinoma (HCC). The criteria used were developed in order to have acceptable outcomes for transplant with survival similar to other indications for transplant. These criteria are discussed in detail along with alternate options, including surgical resection and downstaging of HCC in cirrhotics. Technical considerations of liver transplantation must be considered, and living donor liver transplant is a possibility for treatment.
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Affiliation(s)
- Jennifer Berumen
- Department of Surgery, University of California, San Diego, 9300 Campus Point Dr, MC 7745, La Jolla, CA, 92037, USA.
| | - Alan Hemming
- Department of Surgery, University of California, San Diego, 9300 Campus Point Dr, MC 7745, La Jolla, CA, 92037, USA
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11
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Bridging locoregional therapy: Longitudinal trends and outcomes in patients with hepatocellular carcinoma. Transplant Rev (Orlando) 2017; 31:136-143. [PMID: 28214240 DOI: 10.1016/j.trre.2017.01.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2016] [Accepted: 01/28/2017] [Indexed: 12/19/2022]
Abstract
The purpose of this article is to analyze longitudinal trends in locoregional therapy (LRT) use and review locoregional therapy's role in the management of hepatocellular carcinoma prior to orthotropic liver transplantation Porrett et al. (2006) . LRT has a role in both bridge to transplantation and downstaging of patients not initially meeting Milan or UCSF Criteria. Due to the lack of randomized controlled trials, no specific bridging LRT modality is recommended over another for treating patients on the waiting list, however each modality has unique and patient-specific advantages. Pre-transplant LRT use in the United States has increased dramatically over the last two decades with more than 50% of the currently listed patients receiving LRT Freeman et al. (2008) . Despite these national trends, significant differences in LRT utilization, referral patterns, recurrence rates and survival have been observed among UNOS regions, socioeconomic levels and races. The use of LRT as a biologic selection tool based on response to treatment has shown promising results in its ability to predict successful post-transplant outcomes.
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12
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Makay Ö, Özçınar B, Şimşek T, Arıcı C, Güngör B, Özbaş S, Akça T, Emre AU, Karadeniz Çakmak G, Akçay M, Ünal B, Girgin M, Girgin S, Görgülü S, Sezer A, Karataş A, Özemir İA, Aksakal N, Erel S, Uğurlu MÜ, Filiz Aİ, Atalay C, Uzunköy A, Deveci U, Kotan Ç, İçöz G, Kurt Y, Kebudi A, Cantürk NZ, Erbil Y, Pandev R, Güllüoğlu BM. Regional Clinical and Biochemical Differences among Patients with Primary Hyperparathyroidism. Balkan Med J 2017; 34:28-34. [PMID: 28251020 PMCID: PMC5322512 DOI: 10.4274/balkanmedj.2015.0865] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2015] [Accepted: 01/27/2016] [Indexed: 01/03/2023] Open
Abstract
Background: Environmental habitat may play a role in clinical disparities of primary hyperparathyroidism (pHPT) patients. Aims: To compare preoperative clinical symptoms and associated conditions and surgical findings in patients with pHPT, living in different geographical regions from the Black Sea, Mediterranean and Anatolia regions. Study Design: Retrospective, clinical-based multi-centric study of 694 patients with pHPT. Methods: Patients from 23 centers and 8 different geographical regions were included. Data related to baseline demographics, clinical, pathologic and treatment characteristics of 8 regions were collected and included age, gender, residential data, symptoms, history of fracture, existence of brown tumor, serum total Ca and p levels, serum parathormone (PTH) levels, serum 25-OH vitamin D levels, bone mineral density, size of the resected abnormal parathyroid gland(s), histology, as well as the presence of ectopia, presence of dual adenoma, and multiple endocrine neoplasia (MEN)- or familial-related disease. Results: The median age was 54. Asymptomatic patient rate was 25%. The median PTH level was 232 pg/mL and serum total Ca was 11.4 mg/dL. Eighty-seven percent of patients had an adenoma and 90% of these had a single adenoma. Hyperplasia was detected in 79 patients and cancer in 9 patients. The median adenoma size was 16 mm. Significant parameters differing between regions were preoperative symptoms, serum Ca and p levels, and adenoma size. All patients from South-East Anatolia were symptomatic, while the lowest p values were reported from East Anatolia and the largest adenoma size, as well as highest Ca levels, were from Bulgaria. Conclusion: Habitat conditions vary between geographical regions. This affects the clinicopathological features of patients with pHPT.
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Affiliation(s)
- Özer Makay
- Department of General Surgery, Division of Endocrine Surgery, Ege University School of Medicine, İzmir, Turkey
| | - Beyza Özçınar
- Department of General Surgery, Division of Endocrine Surgery, İstanbul University İstanbul School of Medicine, İstanbul, Turkey
| | - Turgay Şimşek
- Department of General Surgery, Kocaeli University School of Medicine, Kocaeli, Turkey
| | - Cumhur Arıcı
- Department of General Surgery, Division of Endocrine Surgery, Akdeniz University School of Medicine, Antalya, Turkey
| | - Bülent Güngör
- Department of General Surgery, Ondokuz Mayıs University School of Medicine, Samsun, Turkey
| | - Serdar Özbaş
- Department of General Surgery, Güven Hospital, Ankara, Turkey
| | - Tamer Akça
- Department of General Surgery, Division of Endocrine Surgery, Mersin University School of Medicine, Mersin, Turkey
| | - Ali Uğur Emre
- Department of General Surgery, Bülent Ecevit University School of Medicine, Zonguldak, Turkey
| | | | - Müfide Akçay
- Department of General Surgery, Atatürk University School of Medicine, Erzurum, Turkey
| | - Bülent Ünal
- Department of General Surgery, İnönü University School of Medicine, Malatya, Turkey
| | - Mustafa Girgin
- Department of General Surgery, Fırat University School of Medicine, Elazığ, Turkey
| | - Sadullah Girgin
- Department of General Surgery, Dicle University School of Medicine, Diyarbakır, Turkey
| | - Semih Görgülü
- Department of General Surgery, Gülhane Training and Research Hospital, Ankara, Turkey
| | - Atakan Sezer
- Department of General Surgery, Trakya University School of Medicine, Edirne, Turkey
| | - Adem Karataş
- Department of General Surgery, İstanbul University Cerrahpaşa School of Medicine, İstanbul, Turkey
| | - İbrahim Ali Özemir
- Department of General Surgery, İstanbul Medeniyet University School of Medicine, İstanbul, Turkey
| | - Nihat Aksakal
- Department of General Surgery, Division of Endocrine Surgery, İstanbul University İstanbul School of Medicine, İstanbul, Turkey
| | - Serap Erel
- Department of General Surgery, Ankara Training and Research Hospital, Ankara, Turkey
| | - M Ümit Uğurlu
- Department of General Surgery, Marmara University School of Medicine, İstanbul, Turkey
| | - Ali İlker Filiz
- Department of General Surgery, Okan University School of Medicine, Istanbul, Turkey
| | - Can Atalay
- Department of General Surgery, Ankara Oncology Training Hospital, Ankara, Turkey
| | - Ali Uzunköy
- Department of General Surgery, Harran University School of Medicine, Şanlıurfa, Turkey
| | - Uğur Deveci
- Department of Gernral Surgery, Sultan Abdülhamid Training and Research Hospital, İstanbul, Turkey
| | - Çetin Kotan
- Department of General Surgery, Yüzüncü Yıl University School of Medicine, Van, Turkey
| | - Gökhan İçöz
- Department of General Surgery, Division of Endocrine Surgery, Ege University School of Medicine, İzmir, Turkey
| | - Yavuz Kurt
- Department of Gernral Surgery, Sultan Abdülhamid Training and Research Hospital, İstanbul, Turkey
| | - Abut Kebudi
- Department of General Surgery, Okan University School of Medicine, Istanbul, Turkey
| | - N Zafer Cantürk
- Department of General Surgery, Kocaeli University School of Medicine, Kocaeli, Turkey
| | - Yeşim Erbil
- Department of General Surgery, Division of Endocrine Surgery, İstanbul University İstanbul School of Medicine, İstanbul, Turkey
| | - Rumen Pandev
- Department of General Surgery, Division of Endocrine Surgery, Tsaritsa Yoanna University School of Medicine, Sofia, Bulgaria
| | - Bahadır M Güllüoğlu
- Department of General Surgery, Marmara University School of Medicine, İstanbul, Turkey
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13
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Magnetta MJ, Xing M, Zhang D, Kim HS. The Effect of Bridging Locoregional Therapy and Sociodemographics on Survival in Hepatocellular Carcinoma Patients Undergoing Orthotopic Liver Transplantation: A United Network for Organ Sharing Population Study. J Vasc Interv Radiol 2016; 27:1822-1828. [PMID: 27692856 DOI: 10.1016/j.jvir.2016.07.023] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2016] [Revised: 07/10/2016] [Accepted: 07/24/2016] [Indexed: 01/31/2023] Open
Abstract
PURPOSE To investigate socioeconomic and demographic factors associated with transplantation outcomes in patients with hepatocellular carcinoma (HCC) treated with bridging locoregional therapy (LRT) before orthotopic liver transplantation (OLT). MATERIALS AND METHODS The United Network for Organ Sharing (UNOS) database was used to identify all patients in the United States with HCC who were listed for OLT between 2002 and 2013. Mean overall survival (OS) after OLT was stratified based on age, sex, ethnicity, transplant year, region, and insurance status. Kaplan-Meier estimation was used for survival analysis with log-rank test and Cox proportional hazards model to assess independent prognostic factors for OS. RESULTS Of the 17,291 listed patients with HCC, 14,511 underwent OLT. Mean age was 57.4 years (76.8% male). Favorable sociodemographic factors were associated with increased rates of bridging LRT before OLT and longer wait time on the transplant list and were shown to be independent prognostic factors for prolonged OS after OLT using multivariate analysis. Favorable demographic factors included patient age < 60 years, donor age < 45 years, year of diagnosis between 2008 and 2013, UNOS regions 4 and 5, Asian ethnicity, high functional status, postgraduate education, private payer insurance, and employment at the time of OLT. CONCLUSIONS Patients with favorable sociodemographics had higher rates of LRT before OLT performed for HCC cure. These patients had longer transplant wait times and longer OS after OLT.
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Affiliation(s)
- Michael J Magnetta
- Departments of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Minzhi Xing
- Division of Interventional Radiology, Department of Radiology, Yale School of Medicine, 330 Cedar Street, TE 2-224, New Haven, CT 06510
| | - Di Zhang
- Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Hyun S Kim
- Departments of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania; Division of Interventional Radiology, Department of Radiology, Yale School of Medicine, 330 Cedar Street, TE 2-224, New Haven, CT 06510; Yale Cancer Center, New Haven, Connecticut..
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14
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Chiu CC, Wang JJ, Chen YS, Chen JJ, Tsai TC, Lai CC, Sun DP, Shi HY. Trends and predictors of outcomes after surgery for hepatocellular carcinoma: A nationwide population-based study in Taiwan. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2015; 41:1170-1178. [PMID: 26048295 DOI: 10.1016/j.ejso.2015.04.023] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2014] [Revised: 04/19/2015] [Accepted: 04/27/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND Despite the huge and growing global burden of hepatocellular carcinoma (HCC), high-quality population-based studies of HCC prevalence and outcomes are scarce. PURPOSE To analyze trends and predictors of hospital resource utilization and mortality rates in a population of patients who had received HCC surgery. PATIENTS AND MATERIALS This population-based patient cohort study retrospectively analyzed 23,107 patients who had received surgical treatment for HCC from 1998 to 2009. RESULTS The prevalence rate of surgical treatment in HCC patients significantly increased by 167.4% from 4.857 per 100,000 persons in 1998 to 12.989 per 100,000 persons in 2009 (P < 0.001). Age, gender, Deyo-Charlson co-morbidity index score, hospital volume, surgeon volume, digestive system disease, hepatitis type and liver cirrhosis were significantly associated with HCC surgical outcomes (P < 0.05). Over the 12-year period analyzed, the estimated mean hospital treatment cost increased 9.4% whereas mean length of stay (LOS) decreased 25.3%. The estimated mean overall survival time after HCC surgery was 40.9 months (SD 1.2 months), and the overall in-hospital 1-, 3-, and 5-year survival rates were 97.2%, 79.9%, 61.1%, and 54.6%, respectively. CONCLUSIONS These population-based data reveal that the prevalence of HCC has increased, especially in older patients. Additionally, hospital treatment costs for HCC have increased despite decreases in LOS. These analytical results should be applicable to most countries with relatively small populations. Additionally, healthcare providers and patients should recognize that attributes of both the patient and the hospital may affect outcomes.
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Affiliation(s)
- C-C Chiu
- Department of General Surgery, Chi Mei Medical Center, Tainan and Liouying, Taiwan; Department of Electrical Engineering, Southern Taiwan University of Science and Technology, Tainan, Taiwan
| | - J-J Wang
- Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan
| | - Y-S Chen
- Department of Surgery, E-Da Hospital, Kaohsiung, Taiwan
| | - J-J Chen
- Department of Gastroenterology & Hepatology, Chi Mei Medical Center, Tainan and Liouying, Taiwan
| | - T-C Tsai
- Department of General Surgery, Chi Mei Medical Center, Tainan and Liouying, Taiwan
| | - C-C Lai
- Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan and Liouying, Taiwan
| | - D-P Sun
- Department of General Surgery, Chi Mei Medical Center, Tainan and Liouying, Taiwan
| | - H-Y Shi
- Department of Healthcare Administration and Medical Informatics, Kaohsiung Medical University, Kaohsiung, Taiwan.
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15
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Ghaoui R, Garb J, Gordon F, Pomfret E. Impact of geography on organ allocation: Beyond the distance to the transplantation center. World J Hepatol 2015; 7:1782-7. [PMID: 26167251 PMCID: PMC4491907 DOI: 10.4254/wjh.v7.i13.1782] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2015] [Revised: 05/09/2015] [Accepted: 06/15/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To illustrate the application and utility of Geographic Information System (GIS) in exploring patterns of liver transplantation. Specifically, we aim to describe the geographic distribution of transplant registrations and identify disparities in access to liver transplantation across United Network of Organ Sharing (UNOS) region 1. METHODS Based on UNOS data, the number of listed transplant candidates by ZIP code from 2003 to 2012 for Region 1 was obtained. Choropleth (color-coded) maps were used to visualize the geographic distribution of transplant registrations across the region. Spatial interaction analysis was used to analyze the geographic pattern of total transplant registrations by ZIP code. Factors tested included ZIP code log population and log distance from each ZIP code to the nearest transplant center; ZIP code population density; distance from the nearest city over 50000; and dummy variables for state residence and location in the southern portion of the region. RESULTS Visualization of transplant registrations revealed geographic disparities in organ allocation across Region 1. The total number of registrations was highest in the southern portion of the region. Spatial interaction analysis, after adjusting for the size of the underlying population, revealed statistically significant clustering of high and low rates in several geographic areas could not be predicted based solely on distance to the transplant center or density of population. CONCLUSION GIS represents a new method to evaluate the access to liver transplantation within one region and can be used to identify the presence of disparities and reasons for their existence in order to alleviate them.
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Affiliation(s)
- Rony Ghaoui
- Rony Ghaoui, Division of Gastroenterology, Baystate Medical Center, Tufts University School of Medicine, Springfield, MA 01199, United States
| | - Jane Garb
- Rony Ghaoui, Division of Gastroenterology, Baystate Medical Center, Tufts University School of Medicine, Springfield, MA 01199, United States
| | - Fredric Gordon
- Rony Ghaoui, Division of Gastroenterology, Baystate Medical Center, Tufts University School of Medicine, Springfield, MA 01199, United States
| | - Elizabeth Pomfret
- Rony Ghaoui, Division of Gastroenterology, Baystate Medical Center, Tufts University School of Medicine, Springfield, MA 01199, United States
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16
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Toso C, Mazzaferro V, Bruix J, Freeman R, Mentha G, Majno P. Toward a better liver graft allocation that accounts for candidates with and without hepatocellular carcinoma. Am J Transplant 2014; 14:2221-7. [PMID: 25220672 DOI: 10.1111/ajt.12923] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2014] [Revised: 06/13/2014] [Accepted: 07/06/2014] [Indexed: 01/25/2023]
Abstract
In some countries where the Model for End-Stage Liver Disease (MELD) score is used for graft allocation, selected patients with hepatocellular carcinoma (HCC) receive a fixed number of exception points at listing, and increasing priority on the list by accruing additional exception points at regular time intervals. This system originally aimed at balancing the risks of HCC patients of developing contraindications and of non-HCC patients of dying before transplantation, is not ideal because it appears to offer an advantage to HCC patients, regardless of tumor characteristics and response to loco-regional treatment. Scores modulated by HCC characteristics have been proposed. They are based on a more refined estimate of the risk of pretransplant drop-out or of the posttransplant transplant benefit expressed as the life-years gained for each graft. This review describes the newly proposed systems, and discusses their advantages and drawbacks. We believe that the current exception points allocation should be revised and that drop-out-equivalent or transplant benefit-equivalent models should be studied further. As with all policy changes, these should be done under close monitoring that allows subsequent revisions.
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Affiliation(s)
- C Toso
- Division of Transplant and Abdominal Surgery, Department of Surgery, University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland; Hepato-Pancreato-Biliary Centre, University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland
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17
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Goel A, Mehta N, Guy J, Fidelman N, Yao F, Roberts J, Terrault N. Hepatic artery and biliary complications in liver transplant recipients undergoing pretransplant transarterial chemoembolization. Liver Transpl 2014; 20:1221-8. [PMID: 25045002 PMCID: PMC4804463 DOI: 10.1002/lt.23945] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2014] [Revised: 05/31/2014] [Accepted: 06/11/2014] [Indexed: 02/06/2023]
Abstract
Liver transplantation (LT) is the treatment of choice for patients with cirrhosis and hepatocellular carcinoma (HCC) not amenable to resection. Locoregional therapies for HCC are often used to reduce tumor burden, bridge patients to LT, and down-stage HCC so that patients are eligible for LT. We hypothesized that prior endovascular antitumor therapy may increase the risk of hepatic artery (HA) and biliary complications after LT. The aim of this study was to compare HA and biliary complications in LT recipients with HCC who received transarterial chemoembolization (TACE) before LT with complications in LT recipients with HCC who did not receive TACE before LT. This was a retrospective cohort study of HCC patients at two transplant centers. The prevalence of HA complications (HA thrombosis, stenosis, or pseudoaneurysm) and biliary complications (nonanastomotic stricture, bile leak, and diffuse injury) were compared between patients treated with or without TACE. There were 456 HCC patients with a median age of 61 years (77% were male, and 63% had hepatitis C virus), and 328 (72%) received TACE before LT. The overall prevalence of HA complications was 4.7% in the no-TACE group and 7.9% in the TACE group (P = 0.22). All HA stenosis complications (n = 14) occurred in the TACE group (P = 0.018 versus the no-TACE group). An older donor age and a lower albumin level significantly increased the odds of HA complications. There was a nonstatistically significant increased odds of HA complications in the TACE group versus the no-TACE group according to an adjusted analysis (odds ratio = 2.02, 95% confidence interval = 0.79-5.16, P = 0.14). The overall prevalence of biliary complications was 16.4% in the no-TACE group and 19.8% in the TACE group (P = 0.40). In conclusion, a lower pre-LT albumin level and an older donor age were significantly associated with higher odds of HA complications after LT. TACE was not associated with higher odds of overall HA complications but was associated with a higher prevalence of HA stenosis. Further studies are warranted to confirm the HA stenosis findings and elucidate the pathogenesis.
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Affiliation(s)
- Aparna Goel
- Department of Medicine, University of California San Francisco, San Francisco, CA
| | - Neil Mehta
- Department of Medicine, University of California San Francisco, San Francisco, CA
| | - Jennifer Guy
- California Pacific Medical Center, San Francisco, CA
| | - Nicholas Fidelman
- Department of Radiology, University of California San Francisco, San Francisco, CA
| | - Francis Yao
- Department of Medicine, University of California San Francisco, San Francisco, CA
| | - John Roberts
- Department of Surgery, University of California San Francisco, San Francisco, CA
| | - Norah Terrault
- Department of Medicine, University of California San Francisco, San Francisco, CA
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18
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Bittermann T, Hoteit MA, Abt PL, Forde KA, Goldberg D. Waiting time and explant pathology in transplant recipients with hepatocellular carcinoma: a novel study using national data. Am J Transplant 2014; 14:1657-63. [PMID: 24902486 DOI: 10.1111/ajt.12774] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2013] [Revised: 03/03/2014] [Accepted: 03/03/2014] [Indexed: 01/25/2023]
Abstract
Risk factors for hepatocellular carcinoma (HCC) recurrence after liver transplantation have been well described. It has been surmised that longer time on the waitlist may select for tumors with a lower-risk of recurrence posttransplant, as patients with unfavorable tumor characteristics would be delisted due to tumor progression. Utilizing national explant pathology records from transplant recipients waitlisted with T2 HCC exception points, this study explored the correlation between waiting time and the development of pathologic HCC features associated with increased risk of tumor recurrence. Of 1976 explant pathology reports submitted nationally between April 8, 2012 and June 30, 2013, 1453 (73.5%) were from recipients with automatic T2 HCC exception points. There was no association between pretransplant waiting time and the proportion of HCC explants with either: (i) a poorly differentiated tumor; (ii) macrovascular invasion; (iii) HCC beyond Milan or University of California San Francisco criteria; (iv) HCC beyond the "up-to-seven" criteria; or (v) extra-hepatic or lymph node involvement. Though there was a statistically significant increase in microvascular invasion in recipients with pretransplant waiting 6-12 months, this association was not seen when adjusted for United Network for Organ Sharing region. These findings suggest that waiting time alone may not select for tumors with more favorable characteristics.
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Affiliation(s)
- T Bittermann
- Division of Hematology-Oncology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA
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19
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Kluger MD, Halazun KJ, Barroso RT, Fox AN, Olsen SK, Madoff DC, Siegel AB, Weintraub JL, Sussman J, Brown RS, Cherqui D, Emond JC. Bland embolization versus chemoembolization of hepatocellular carcinoma before transplantation. Liver Transpl 2014; 20:536-43. [PMID: 24493271 PMCID: PMC4095977 DOI: 10.1002/lt.23846] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2013] [Accepted: 12/26/2013] [Indexed: 01/26/2023]
Abstract
There is conflicting literature regarding the superiority of transarterial chemoembolization (TACE) versus bland transarterial embolization (TAE), and this has not been well studied before transplantation. Twenty-five TAE patients were matched in a 1:2 ratio with TACE patients by the initial radiographic tumor size and number in a retrospective, case-controlled study. The patients were otherwise treated according to the same protocols. The method of embolization was chosen on the basis of interventionalist practices at 2 sites within the program. Kaplan-Meier survival analyses at 1 and 3 years were the primary endpoints. There were no significant demographic differences between the groups. The mean adjusted Model for End-Stage Liver Disease scores at transplantation and waiting times were not significantly different between the TAE and TACE patients (MELD scores: 26 ± 3 versus 24 ± 3 points, P = 0.12; waiting times: 13 ± 8 versus 11 ± 10 months, P = 0.43). TAE patients (16%) were less likely than TACE patients (40%) to require 2 procedures (P = 0.04). Explant tumors were completely necrotic for 36% of the TAE patients and for 26% of the TACE patients. The 3-year overall survival rates were 78% for the TAE patients and 74% for the TACE patients (P = 0.66), and the 3-year recurrence-free survival rates were 72% for the TAE patients and 68% for the TACE patients (P = 0.67). On an intention-to-treat basis, there was no significant risk of wait-list dropout associated with TAE or TACE (P = 0.83). In conclusion, there were no significant differences in wait-list dropout or in overall or recurrence-free survival between HCC patients undergoing TAE and HCC patients undergoing TACE before transplantation.
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Affiliation(s)
- Michael D. Kluger
- Department of Surgery, NewYork–Presbyterian Hospital/Columbia Presbyterian Medical Center, New York, NY
| | - Karim J. Halazun
- Department of Surgery, NewYork–Presbyterian Hospital/Columbia Presbyterian Medical Center, New York, NY
| | - Ryan T. Barroso
- Department of Surgery, NewYork–Presbyterian Hospital/Columbia Presbyterian Medical Center, New York, NY
| | - Alyson N. Fox
- Section of Digestive and Liver Diseases, Department of Medicine, NewYork–Presbyterian Hospital/Weill-Cornell Medical Center, New York, NY
| | - Sonja K. Olsen
- Section of Digestive and Liver Diseases, Department of Medicine, NewYork–Presbyterian Hospital/Weill-Cornell Medical Center, New York, NY
| | - David C. Madoff
- Division of Interventional Radiology, Department of Radiology, NewYork–Presbyterian Hospital/Weill-Cornell Medical Center, New York, NY
| | - Abby B. Siegel
- Division of Hematology and Oncology, Department of Medicine, NewYork–Presbyterian Hospital/Columbia Presbyterian Medical Center, New York, NY
| | - Joshua L. Weintraub
- Division of Interventional Radiology, Department of Radiology, NewYork–Presbyterian Hospital/Columbia Presbyterian Medical Center, New York, NY
| | - Jonathan Sussman
- Division of Interventional Radiology, Department of Radiology, NewYork–Presbyterian Hospital/Columbia Presbyterian Medical Center, New York, NY
| | - Robert S. Brown
- Section of Digestive and Liver Diseases, Department of Medicine, NewYork–Presbyterian Hospital/Columbia Presbyterian Medical Center, New York, NY
| | - Daniel Cherqui
- Department of Surgery, NewYork–Presbyterian Hospital/Columbia Presbyterian Medical Center, New York, NY
| | - Jean C. Emond
- Department of Surgery, NewYork–Presbyterian Hospital/Columbia Presbyterian Medical Center, New York, NY
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20
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Mehta N, Dodge JL, Goel A, Roberts JP, Hirose R, Yao FY. Identification of liver transplant candidates with hepatocellular carcinoma and a very low dropout risk: implications for the current organ allocation policy. Liver Transpl 2013; 19:1343-53. [PMID: 24285611 PMCID: PMC3883622 DOI: 10.1002/lt.23753] [Citation(s) in RCA: 124] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2013] [Revised: 08/05/2013] [Accepted: 08/25/2013] [Indexed: 12/16/2022]
Abstract
It has been shown that patients with hepatocellular carcinoma (HCC) meeting the United Network for Organ Sharing T2 (Milan) criteria have an advantage in comparison with patients without HCC under the current organ allocation system for liver transplantation (LT). We hypothesized that within the T2 HCC group, there is a subgroup with a low risk of wait-list dropout that should not receive the same listing priority. This study evaluated 398 consecutive patients with T2 HCC listed for LT with a Model for End-Stage Liver Disease exception from March 2005 to January 2011 at our center. Competing risk (CR) regression was used to determine predictors of dropout. The probabilities of dropout due to tumor progression or death without LT according to the CR analysis were 9.4% at 6 months and 19.6% at 12 months. The median time from listing to LT was 8.8 months, and the median time from listing to dropout or death without LT was 7.2 months. Significant predictors of dropout or death without LT according to a multivariate CR regression included 1 tumor of 3.1 to 5 cm (versus 1 tumor of 3 cm or less), 2 or 3 tumors, a lack of a complete response to the first locoregional therapy (LRT), and a high alpha-fetoprotein (AFP) level after the first LRT. A subgroup (19.9%) that met certain criteria (1 tumor of 2 to 3 cm, a complete response after the first LRT, and an AFP level ≤ 20 ng/mL after the first LRT) had 1- and 2-year probabilities of dropout of 1.3% and 1.6%, respectively, whereas the probabilities were 21.6% and 26.5% for all other patients (P = 0.004). In conclusion, a combination of tumor characteristics and a complete response to the first LRT define a subgroup of patients with a very low risk of wait-list dropout who do not require the same listing priority. Our results may have important implications for the organ allocation policy for HCC.
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Affiliation(s)
- Neil Mehta
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco
| | - Jennifer L. Dodge
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco
| | - Aparna Goel
- Department of Internal Medicine, University of California, San Francisco
| | - John P. Roberts
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco
| | - Ryutaro Hirose
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco
| | - Francis Y. Yao
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco,Division of Transplant Surgery, Department of Surgery, University of California, San Francisco
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21
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Pompili M, Francica G, Ponziani FR, Iezzi R, Avolio AW. Bridging and downstaging treatments for hepatocellular carcinoma in patients on the waiting list for liver transplantation. World J Gastroenterol 2013; 19:7515-7530. [PMID: 24282343 PMCID: PMC3837250 DOI: 10.3748/wjg.v19.i43.7515] [Citation(s) in RCA: 87] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2013] [Revised: 09/30/2013] [Accepted: 10/18/2013] [Indexed: 02/06/2023] Open
Abstract
Several therapeutic procedures have been proposed as bridging treatments for patients with hepatocellular carcinoma (HCC) awaiting liver transplantation (LT). The most used treatments include transarterial chemoembolization and radiofrequency ablation. Surgical resection has also been successfully used as a bridging procedure, and LT should be considered a rescue treatment in patients with previous HCC resection who experience tumor recurrence or post-treatment severe decompensation of liver function. The aims of bridging treatments include decreasing the waiting list dropout rate before transplantation, reducing HCC recurrence after transplantation, and improving post-transplant overall survival. To date, no data from prospective randomized studies are available; however, for HCC patients listed for LT within the Milan criteria, prolonging the waiting time over 6-12 mo is a risk factor for tumor spread. Bridging treatments are useful in containing tumor progression and decreasing dropout. Furthermore, the response to pre-LT treatments may represent a surrogate marker of tumor biological aggressiveness and could therefore be evaluated to prioritize HCC candidates for LT. Lastly, although a definitive conclusion can not be reached, the experiences reported to date suggest a positive impact of these treatments on both tumor recurrence and post-transplant patient survival. Advanced HCC may be downstaged to achieve and maintain the current conventional criteria for inclusion in the waiting list for LT. Recent studies have demonstrated that successfully downstaged patients can achieve a 5-year survival rate comparable to that of patients meeting the conventional criteria without requiring downstaging.
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22
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Davies RR, Haldeman S, Pizarro C. Regional variation in survival before and after pediatric heart transplantation--an analysis of the UNOS database. Am J Transplant 2013; 13:1817-29. [PMID: 23714390 DOI: 10.1111/ajt.12259] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2012] [Revised: 02/21/2013] [Accepted: 03/14/2013] [Indexed: 01/25/2023]
Abstract
Geographic variation occurs in a variety of health outcomes. Regional influences on outcomes before and after listing for pediatric heart transplantation have not been assessed. Review of the UNOS dataset identified 5398 pediatric (≤ 18 years) patients listed for heart transplantation 2000-2011. Patients were stratified based on the region of listing. Regional-level variables were correlated with individual risk-adjusted outcomes. Mean time spent on the waitlist varied from 91.0 ± 163 days (Region 6 [R6]) to 248.1 ± 493 days (R4, p < 0.0001). Regions with more transplant centers (p < 0.0001) and fewer transplants (p = 0.0015) had higher waitlist mortality. Risk-adjusted individual waitlist mortality varied from 6.9% (R1, CI 6.2-7.8) to 19.2% (R5, CI 18.0-20.6). Waitlist mortality was higher for individuals awaiting transplant in regions with more listings per center (OR 1.04, CI 1.01-1.08) and lower in regions with more donors per center (OR 0.95, CI 0.90-0.99 per donor). Posttransplant risk-adjusted survival varied across regions (R4: 5.4%, CI 4.2-7.4; R7: 18.0%, CI 12.4-32.5), but regional variables were not correlated with outcomes. Outcomes among children undergoing heart transplantation vary by region. Factors leading to increased competition for donor allografts are associated with poorer waitlist survival. Equitable allocation of cardiac allografts requires further investigation of these findings.
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Affiliation(s)
- R R Davies
- Nemours Cardiac Center, Nemours/A.I. duPont Hospital for Children, Wilmington, DE, USA.
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Quality of life, risk assessment, and safety research in liver transplantation: new frontiers in health services and outcomes research. Curr Opin Organ Transplant 2013; 17:241-7. [PMID: 22476225 DOI: 10.1097/mot.0b013e32835365c6] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
PURPOSE OF REVIEW In this review, we briefly summarize three fruitful, emerging areas in liver transplantation research, quality of life; risk assessment; and patient safety. Our goal is to highlight recent findings in these areas, with a call for increased integration of social scientists and transplant clinicians to address how best to shape policy and improve outcomes. RECENT FINDINGS After liver transplantation, recipients generally experience clinically significant, sustained improvement in their physical, social and emotional well being. However, a sizeable minority of patients do experience excess morbidity that may benefit from ongoing surveillance and/or intervention. There is growing body of research that describes risks associated with liver transplantation, which can be useful aids to better inform decision making by patients, clinicians, payers, and policy makers. In contrast, there has been a relative lack of empirical data on transplant patient safety vulnerabilities, placing the field of surgery in stark contrast to other high-risk industries, wherein such assessments inform continuous process improvement. SUMMARY Health services and outcomes research has grown in importance in the liver transplantation literature, but several important questions remain unanswered that merit programmatic, interdisciplinary research.
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Voigt MD, Hunsicker LG, Snyder JJ, Israni AK, Kasiske BL. Regional variability in liver waiting list removals causes false ascertainment of waiting list deaths. Am J Transplant 2013; 13:369-75. [PMID: 23279706 DOI: 10.1111/ajt.12000] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2012] [Revised: 09/26/2012] [Accepted: 10/18/2012] [Indexed: 01/25/2023]
Abstract
Inconsistent identification of reasons for removal from the liver transplant waiting list by Organ Procurement and Transplantation Network (OPTN) regions may contribute to regional variability in wait-list death rates. We analyzed OPTN and Social Security Administration (SSA) reported deaths of 103 364 liver transplant candidates listed May 8, 2003-April 17, 2011, and determined regional variability in risk of death attributable to differences in use of OPTN removal codes. Only 26% of candidates removed as "too sick" died within 90 days of delisting; 6335 deaths after delisting were not reported to OPTN. The ratio of number of candidates removed as "too sick" to number who died on the waiting list varied by region from 0.23 to 0.94, indicating substantial variability in use of removal codes. Including SSA-reported deaths within 90 days of delisting reduced regional variability in risk of death by 48% compared with deaths on the list alone, and by 35% compared with deaths plus the "too sick" designation. Codes for delisting liver transplant candidates are inconsistently applied among OPTN regions, spuriously elevating estimated regional variability in risk of wait-list death. This variability is ameliorated by including SSA- reported deaths within 90 days of delisting.
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Affiliation(s)
- M D Voigt
- Organ Transplant Center, University of Iowa, Iowa City, IA, USA.
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25
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Socioeconomic factors affect disparities in access to liver transplant for hepatocellular cancer. J Transplant 2012; 2012:870659. [PMID: 23304446 PMCID: PMC3529502 DOI: 10.1155/2012/870659] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2012] [Revised: 10/21/2012] [Accepted: 10/22/2012] [Indexed: 01/02/2023] Open
Abstract
Objective. The incidence/death rate of hepatocellular cancer (HCC) is increasing in America, and it is unclear if access to care contributes to this increase. Design/Patients. 575 HCC cases were reviewed for demographics, education, and tumor size. Main Outcome Measures. Endpoints to determine access to HCC care included whether an eligible patient underwent liver transplantation. Results. Transplant patients versus those not transplanted were younger (55.7 versus 61.8 yrs, P < 0.001), males (89.3% versus 74.4%, P = 0.013), and having completed high school (10.1% versus 1.2%, P = 0.016). There were differences in transplant by ethnicity, insurance, and occupation. Transplant patients with HCC had higher median income via census classification ($54,383 versus $49,383, P = 0.046) and self-reported income ($48,948 versus $38,800, P = 0.002). Differences in access may be related to exclusion criteria for liver transplant, as Pacific Islanders were more likely to have tumor size larger than 5 cm compared to Whites and have BMI > 35 (20.7%) compared to Whites (6.4%) and Asians (4.7%). Conclusions. Ethnic differences in access to transplant are associated with socioeconomic status and factors that can disqualify patients (advanced disease/morbid obesity). Efforts to overcome educational barriers and screening for HCC could improve access to transplant.
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Sourianarayanane A, El-Gazzaz G, Sanabria JR, Menon KVN, Quintini C, Hashimoto K, Kelly D, Eghtesad B, Miller C, Fung J, Aucejo F. Loco-regional therapy in patients with Milan Criteria-compliant hepatocellular carcinoma and short waitlist time to transplant: an outcome analysis. HPB (Oxford) 2012; 14:325-32. [PMID: 22487070 PMCID: PMC3384852 DOI: 10.1111/j.1477-2574.2012.00453.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES Liver transplantation (LT) in Milan Criteria (MC) hepatocellular carcinoma (HCC) has excellent outcomes. Pre-transplant loco-regional therapy (LRT) has been used to downstage HCC to meet the MC. However, its benefit in patients with a brief waiting time to transplant remains unclear. This study evaluated outcomes in patients with short waitlist times to LT for MC-compliant HCC. METHODS Patients undergoing LT for MC HCC at either of two transplant centres between 2002 and 2009 were retrospectively evaluated for outcome. Patients for whom post-transplant follow-up amounted to <12 months were excluded. RESULTS A total of 225 patients were included, 93 (41.3%) of whom received neoadjuvant LRT. The median waiting time to transplant was 48 days. Mean post-transplant follow-up was 32.2 months. Overall and disease-free survival at 1 year, 3 years and 5 years were 93.1%, 82.4% and 72.6%, and 91.3%, 79.3% and 70.6%, respectively. There was no difference in overall (P= 0.94) and disease-free survival (P= 0.94) between groups who received and did not receive pre-LT LRT. There were also no disparities in survival or tumour recurrence among categories of patients (with single tumours measuring <3 cm, with single tumours measuring 3-5 cm, with multiple tumours). CONCLUSIONS Loco-regional therapy followed by rapid transplantation in MC HCC appears not to have an impact on post-transplant outcome.
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Affiliation(s)
| | - Galal El-Gazzaz
- Department of Transplant Surgery, Cleveland ClinicCleveland, OH, USA
| | - Juan R Sanabria
- Division of Transplant and Hepatobiliary Surgery, Department of Surgery, Case Western Reserve University School of Medicine and University Hospitals, Case Medical CenterCleveland, OH, USA
| | - K V Narayanan Menon
- Department of Gastroenterology and Hepatology, Cleveland ClinicCleveland, OH, USA
| | | | - Koji Hashimoto
- Department of Transplant Surgery, Cleveland ClinicCleveland, OH, USA
| | - Dympna Kelly
- Department of Transplant Surgery, Cleveland ClinicCleveland, OH, USA
| | - Bijan Eghtesad
- Department of Transplant Surgery, Cleveland ClinicCleveland, OH, USA
| | - Charles Miller
- Department of Transplant Surgery, Cleveland ClinicCleveland, OH, USA
| | - John Fung
- Department of Transplant Surgery, Cleveland ClinicCleveland, OH, USA
| | - Federico Aucejo
- Department of Transplant Surgery, Cleveland ClinicCleveland, OH, USA
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