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Prosperi E, Cescon M, Lai Q, Bonatti C, Prosperi E, Rizzo F, Maroni L, Laurenzi A, Serenari M, Morelli MC, Ravaioli M. The Italian Score for Organ Allocation: A Ten-Year Monocentric Retrospective Analysis in Liver Transplantation for Hepatocellular Carcinoma. Cancers (Basel) 2025; 17:1720. [PMID: 40427217 PMCID: PMC12110210 DOI: 10.3390/cancers17101720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2025] [Revised: 05/10/2025] [Accepted: 05/14/2025] [Indexed: 05/29/2025] Open
Abstract
BACKGROUND The Italian Score for Organ Allocation (ISO), a transplant benefit oriented allocation system, was introduced in Italy in 2016. The main objective of this study is to identify risk factors for Drop-Out in hepatocellular (HCC) patients enlisted for LT before (Pre-ISO Era) and after ISO (ISO Era) introduction, while the secondary objective is to evaluate the survival results. METHODS CIFs for liver transplantation and Drop-Out were estimated and compared between eras. Factors associated with Drop-Out were identified through multivariable competing risks regression. Survival results were compared using the log-rank test. RESULTS Between 2011 and 2020, 410 patients with HCC were listed for LT. We observed 103 vs. 217 LT and 49 vs. 41 Drop-Outs (p < 0.001) during the Pre-ISO and ISO Era, respectively. In the multivariable analysis, ISO ([sHR] 0.43; 95%CI 0.28-0.66, p < 0.001) and Alcoholic Cirrhosis ([sHR] 0.27, 95%CI 0.11-0.70; p = 0.007) were revealed to be protective factors for Drop-Out. One year after listing, the CI for Drop-Out decreased from 13.2% to 6.2% (p = 0.02). Despite no differences observed in post-LT survival, a significant difference in the intention-to-treat survival from enlisting was found (p = 0.0019). CONCLUSIONS Among other factors, ISO results were protective for the Drop-Out risk in HCC patients awaiting LT, with a benefit in ITT-OS survival.
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Affiliation(s)
- Enrico Prosperi
- Hepatobiliary and Transplant Surgery Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (M.C.); (C.B.); (E.P.); (F.R.); (L.M.); (A.L.); (M.S.)
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy
| | - Matteo Cescon
- Hepatobiliary and Transplant Surgery Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (M.C.); (C.B.); (E.P.); (F.R.); (L.M.); (A.L.); (M.S.)
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy
| | - Quirino Lai
- General Surgery and Organ Transplantation Unit, AOU Policlinico Umberto I, Sapienza University of Rome, 00185 Rome, Italy;
| | - Chiara Bonatti
- Hepatobiliary and Transplant Surgery Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (M.C.); (C.B.); (E.P.); (F.R.); (L.M.); (A.L.); (M.S.)
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy
| | - Edoardo Prosperi
- Hepatobiliary and Transplant Surgery Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (M.C.); (C.B.); (E.P.); (F.R.); (L.M.); (A.L.); (M.S.)
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy
| | - Francesca Rizzo
- Hepatobiliary and Transplant Surgery Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (M.C.); (C.B.); (E.P.); (F.R.); (L.M.); (A.L.); (M.S.)
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy
| | - Lorenzo Maroni
- Hepatobiliary and Transplant Surgery Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (M.C.); (C.B.); (E.P.); (F.R.); (L.M.); (A.L.); (M.S.)
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy
| | - Andrea Laurenzi
- Hepatobiliary and Transplant Surgery Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (M.C.); (C.B.); (E.P.); (F.R.); (L.M.); (A.L.); (M.S.)
| | - Matteo Serenari
- Hepatobiliary and Transplant Surgery Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (M.C.); (C.B.); (E.P.); (F.R.); (L.M.); (A.L.); (M.S.)
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy
| | - Maria Cristina Morelli
- Internal Medicine Unit for the Treatment of Severe Organ Failure, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy;
| | - Matteo Ravaioli
- Hepatobiliary and Transplant Surgery Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (M.C.); (C.B.); (E.P.); (F.R.); (L.M.); (A.L.); (M.S.)
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy
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Arar A, Heglin A, Veluri S, Alnablsi MW, Benjamin JL, Choudhary M, Pillai A. Radioembolization of HCC and secondary hepatic tumors: a comprehensive review. THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING : OFFICIAL PUBLICATION OF THE ITALIAN ASSOCIATION OF NUCLEAR MEDICINE (AIMN) [AND] THE INTERNATIONAL ASSOCIATION OF RADIOPHARMACOLOGY (IAR), [AND] SECTION OF THE SOCIETY OF... 2024; 68:270-287. [PMID: 39088238 DOI: 10.23736/s1824-4785.24.03572-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/02/2024]
Abstract
Transarterial radioembolization (TARE), also called Selective Internal Radiation Therapy (SIRT), has emerged as an effective locoregional therapy for primary and secondary hepatic tumors, utilizing yttrium-90 (Y90) microspheres and other agents such as holmium-166 and rhenium-188. TARE has various applications in the management of HCC across different BCLC stages. Radiation segmentectomy, which involves administering high doses of Y90 (>190 Gy), can be both curative and ablative, achieving complete necrosis of the tumor. In contrast, radiation lobectomy involves administering a lower dose of Y90 (80-120 Gy) as a neoadjuvant treatment modality to improve local control and induce future liver remnant (FLR) hypertrophy in patients who are planned to undergo surgery but have insufficient FLR. Modified radiation lobectomy combines both techniques and offers several advantages over portal vein embolization (PVE). Y90 is also used in downstaging HCC patients outside liver transplantation criteria, as well as bridging those awaiting liver transplantation (LT). Multiple studies and combined analyses were described to highlight the outcomes of TARE and compare it with other treatment modalities, including TACE and sorafenib. Additionally, the review delves into the efficacy and safety of radioembolization in managing metastatic colorectal cancer and other metastatic tumors to the liver. Recent studies have emphasized the role of personalized dosimetry for improved outcomes, and thus we described the different methods used for this purpose. Pretherapy imaging, estimating lung shunt, selection of therapeutic radionuclides, adverse effects, and cost-effectiveness were all discussed as well.
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Affiliation(s)
- Ahmad Arar
- Division of Interventional Radiology, Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA -
| | - Alex Heglin
- Division of Nuclear Medicine, Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Shriya Veluri
- The University of Texas Health Science Center, San Antonio, TX, USA
| | - Mhd Wisam Alnablsi
- Division of Interventional Radiology, Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Jamaal L Benjamin
- Division of Interventional Radiology, Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Moaz Choudhary
- Division of Interventional Radiology, Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Anil Pillai
- Division of Interventional Radiology, Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
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Moctezuma-Velázquez C. Liver transplantation or resection for early hepatocellular carcinoma: More questions than answers. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2024; 89:319-322. [PMID: 38472061 DOI: 10.1016/j.rgmxen.2023.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Accepted: 11/09/2023] [Indexed: 03/14/2024]
Affiliation(s)
- C Moctezuma-Velázquez
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Alberta, Canada.
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Liu F, Tan L, Luo L, Pan JJ. Comparison of laparoscopic hepatectomy and percutaneous radiofrequency ablation for the treatment of small hepatocellular carcinoma: a meta-analysis. BMC Surg 2024; 24:83. [PMID: 38443897 PMCID: PMC10913421 DOI: 10.1186/s12893-024-02376-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Accepted: 02/28/2024] [Indexed: 03/07/2024] Open
Abstract
AIM The purpose of this study was to compare the long-term outcomes of laparoscopic hepatectomy (LH) and percutaneous radiofrequency ablation (PRFA) for the treatment of small hepatocellular carcinoma. METHODS We systematically searched PubMed, Embase, Web of Science, and Medline from January 2000 to May 2022 for literature comparing the efficacy of LH and PRFA in the treatment of small hepatocellular carcinoma (largest tumour diameter ≤ 3 cm, number of intrahepatic tumours ≤3, or diameter of a single intrahepatic lesion ≤5 cm. ). We assessed overall survival (OS), recurrence-free survival (RFS), local recurrence and complication rates. RESULTS A total of 1886 patients with small HCC were included in the 8 studies included in this study, of which 839 underwent LH and 1047 underwent PRAF. The results of the meta-analysis showed that the two groups had the same 3-year (HR: 0.99, 95% CI: 0.67 to 1.47) and 5-year (HR: 1.30, 95% CI: 0.90 to 1.87) OS rates, and the LH group had better 3-year (HR: 0.58, 95% CI: 0.49 to 0.68) and 5-year (HR: 0.56, 95% CI: 0.37 to 0.85) RFS rates. The LH group had a lower local recurrence rate (OR: 0.19, 95% CI: 0.12 to 0.32), but the PRFA group had a lower complication rate (OR: 2.49, 95% CI: 1.76 to 3.54). CONCLUSION There was no difference in OS between LH and PRFA in the treatment of small HCC. LH had a higher RFS rate and a lower local recurrence rate, but PRFA had a lower complication rate. In general, the long-term efficacy of LH in the treatment of small HCC is better than that of PRFA. Considering the advantages of less trauma and a low complication rate of PRFA, a large number of RCT studies are needed for further verification in the future.
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Affiliation(s)
- Fei Liu
- Department of General Surgery, Second People's Hospital of Yibin City, Yibin, 644000, Sichuan, China
| | - Ling Tan
- Department of Urology, People's Hospital Affiliated to Chongqing Three Gorges Medical College, Chongqing, 404041, China
| | - Lan Luo
- Department of General Surgery, Second People's Hospital of Yibin City, Yibin, 644000, Sichuan, China
| | - Jun-Jiang Pan
- Department of General Surgery, Second People's Hospital of Yibin City, Yibin, 644000, Sichuan, China.
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Mohamed IB, Ismail MS, El Sabagh A, Afifi Abdelwahab AM, Polychronopoulou E, Kuo Y, Hassan M, Goss JA, Kanwal F, Jalal PK. Radiological-histopathological discordance in patients transplanted for HCC and its impact on post-transplant outcomes. Cancer Med 2023; 12:15011-15025. [PMID: 37326440 PMCID: PMC10417193 DOI: 10.1002/cam4.6161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 04/19/2023] [Accepted: 05/15/2023] [Indexed: 06/17/2023] Open
Abstract
BACKGROUND AND AIMS Contrast-enhanced cross-sectional imaging is the cornerstone in the diagnosis, staging, and management of HCC, including eligibility for liver transplantation (LT). Radiological-histopathological discordance may lead to improper staging and may impact patient outcomes. We aimed to assess the radiological-histopathological discordance at the time of LT in HCC patients and its impact on the post-LT outcomes. METHODS We analyzed further the effect of 6-month waiting policy on the discordance. Using United Network for Organ Sharing-Organ Procurement and Transplantation Network (UNOS-OPTN) database, we examined the discordance between pre-LT imaging and explant histopathology for all adult HCC patients who received liver transplants from deceased donors between April 2012 and December 2017. Kaplan-Meier methods and Cox regression analyses were used to evaluate the impact of discordance on 3-year HCC recurrence and mortality. RESULTS Of 6842 patients included in the study, 66.7% were within Milan criteria on both imaging and explant histopathology, and 33.3% were within the Milan based on imaging but extended beyond Milan on explant histopathology. Male gender, increasing numbers of tumors, bilobar distribution, larger tumor size, and increasing AFP are associated with increased discordance. Post-LT HCC recurrence and death were significantly higher in patients who were discordant, with histopathology beyond Milan (adj HR 1.86, 95% CI 1.32-2.63 for mortality and 1.32, 95% CI 1.03-1.70 for recurrence). Graft allocation policy with 6-month waiting time led to increased discordance (OR 1.19, CI 1.01-1.41), although it did not impact post-LT outcome. CONCLUSION Current practice for staging of HCC based on radiological imaging features alone results in underestimation of HCC burden in one out of three patients with HCC. This discordance is associated with a higher risk of post-LT HCC recurrence and mortality. These patients will need enhanced surveillance to optimize patient selection and aggressive LRT to reduce post-LT recurrence and increase survival.
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Affiliation(s)
- Islam B. Mohamed
- Section of Gastroenterology and HepatologyBaylor College of MedicineHoustonTexasUSA
| | - Mohamed Saleh Ismail
- Section of Gastroenterology and HepatologyBaylor College of MedicineHoustonTexasUSA
| | - Ahmed El Sabagh
- Section of Gastroenterology and HepatologyBaylor College of MedicineHoustonTexasUSA
| | | | | | - Yong‐Fang Kuo
- Department of EpidemiologyThe University of Texas MD Anderson Cancer CenterHoustonTexasUSA
| | - Manal Hassan
- Department of BiostatisticsThe University of Texas Medical BranchGalvestonTexasUSA
| | - John A. Goss
- Division of Abdominal TransplantationBaylor College of Medicine Michael E. DeBakey Department of SurgeryHoustonTexasUSA
| | - Fasiha Kanwal
- Section of Gastroenterology and HepatologyBaylor College of MedicineHoustonTexasUSA
| | - Prasun K. Jalal
- Section of Gastroenterology and HepatologyBaylor College of MedicineHoustonTexasUSA
- Division of Abdominal TransplantationBaylor College of Medicine Michael E. DeBakey Department of SurgeryHoustonTexasUSA
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Yin C, Armstrong S, Shin R, Geng X, Wang H, Satoskar RS, Fishbein T, Smith C, Banovac F, Kim AY, He AR. Bridging and downstaging with TACE in early and intermediate stage hepatocellular carcinoma: Predictors of receiving a liver transplant. Ann Gastroenterol Surg 2023; 7:295-305. [PMID: 36998293 PMCID: PMC10043769 DOI: 10.1002/ags3.12622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2022] [Accepted: 09/05/2022] [Indexed: 11/27/2022] Open
Abstract
Background and Aims In patients with surgically unresectable early and intermediate stage hepatocellular carcinoma (HCC), only liver transplant (LT) offers a cure. Locoregional therapies, such as transarterial chemoembolization (TACE), are widely used to bridge patients waiting for an LT or downstage tumors beyond Milan Criteria (MC). However, there are no formal guidelines on the number of TACE procedures patients should receive. Our study explores the extent to which repeated TACE might offer diminishing gains toward LT. Approach We retrospectively analyzed 324 patients with BCLC stage A and B HCC who had received TACE with the intention of disease downstaging or bridging to LT. In addition to baseline demographics, we collected data on LT status, survival, and the number of TACE procedures. Overall survival (OS) rates were estimated using the Kaplan-Meier method, and correlative studies were calculated using chi-square or Fisher's exact test. Results Out of 324 patients, 126 (39%) received an LT, 32 (25%) of whom had responded favorably to TACE. LT significantly improved OS: HR 0.174 (0.094-0.322, P < .001). However, the LT rate significantly decreased if patients received ≥3 vs < 3 TACE procedures (21.6% vs 48.6%, P < .001). If their cancer was beyond MC after the third TACE, the LT rate was 3.7%. Conclusions An increased number of TACE procedures may have diminishing returns in preparing patients for LT. Our study suggests that alternatives to LT, such as novel systemic therapies, should be considered for patients whose cancers are beyond MC after three TACE procedures.
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Affiliation(s)
- Chao Yin
- Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer CenterGeorgetown UniversityWashingtonDistrict of ColumbiaUSA
| | - Samantha Armstrong
- Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer CenterGeorgetown UniversityWashingtonDistrict of ColumbiaUSA
| | - Richard Shin
- Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer CenterGeorgetown UniversityWashingtonDistrict of ColumbiaUSA
| | - Xue Geng
- Department of BiostatisticsGeorgetown UniversityWashingtonDistrict of ColumbiaUSA
| | - Hongkun Wang
- Department of BiostatisticsGeorgetown UniversityWashingtonDistrict of ColumbiaUSA
| | - Rohit S. Satoskar
- MedStar Georgetown Transplant InstituteWashingtonDistrict of ColumbiaUSA
| | - Thomas Fishbein
- MedStar Georgetown Transplant InstituteWashingtonDistrict of ColumbiaUSA
| | - Coleman Smith
- MedStar Georgetown Transplant InstituteWashingtonDistrict of ColumbiaUSA
| | - Filip Banovac
- Department of RadiologyGeorgetown University Medical CenterWashingtonDistrict of ColumbiaUSA
| | - Alexander Y. Kim
- Department of RadiologyGeorgetown University Medical CenterWashingtonDistrict of ColumbiaUSA
| | - Aiwu Ruth He
- Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer CenterGeorgetown UniversityWashingtonDistrict of ColumbiaUSA
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Korean Liver Cancer Association (KLCA) and National Cancer Center (NCC) Korea. 2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. JOURNAL OF LIVER CANCER 2023; 23:1-120. [PMID: 37384024 PMCID: PMC10202234 DOI: 10.17998/jlc.2022.11.07] [Citation(s) in RCA: 80] [Impact Index Per Article: 40.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Accepted: 11/07/2022] [Indexed: 06/30/2023]
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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Affiliation(s)
- Korean Liver Cancer Association (KLCA) and National Cancer Center (NCC) Korea
- Corresponding author: KLCA-NCC Korea Practice Guideline Revision Committee (KPGRC) (Committee Chair: Joong-Won Park) Center for Liver and Pancreatobiliary Cancer, Division of Gastroenterology, Department of Internal Medicine, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 10408, Korea Tel. +82-31-920-1605, Fax: +82-31-920-1520, E-mail:
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Elkomos BE, Abdo M, Mamdouh R, Abdelaal A. Can living donor liver transplantation provide similar outcomes to deceased-donor liver transplantation for hepatocellular carcinoma? A systematic review and meta-analysis. Hepatol Int 2023; 17:18-37. [PMID: 36564609 PMCID: PMC9894961 DOI: 10.1007/s12072-022-10435-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Accepted: 10/03/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND AND AIM A potential solution to the deceased organ shortage is to include live organ donations and to identify patients with lower rates of HCC recurrence to fairly allocate liver grafts. Our aims were to detect the long-term outcomes of LDLT versus DDLT for HCC and predictors of recurrence after transplantation. METHODS PubMed, Scopus, Web of Science, Cochrane library were searched for eligible studies from inception to July 2021 and a systematic review and meta-analysis were done. RESULTS 35 studies with a total of 7822 patients were included. The 1-, 3-, 4 year-OS showed trivial improvement for LDLT recipients. However, the two modalities had similar 5-, 6- and 10-year OS. A significant improvement in the ITT-OS was observed for LDLT recipients. Regarding the DFS and recurrence after transplantation, no significant difference was observed between LDLT and DDLT. In addition to that, the pooled hazard ratio of the included studies showed that Milan criteria, level of AFP, presence of vascular invasion, tumor differentiation were significant predictors of recurrence. CONCLUSION The cancer biology (not the graft type) is the most important determinant of recurrence and survival after LT. However, LDLT provided much better survival benefits to HCC patients especially in regions that suffer from low deceased organ availability.
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Affiliation(s)
| | - Mostafa Abdo
- General Surgery Department, Ain Shams University Hospital, Cairo, Egypt
| | - Remon Mamdouh
- General Surgery Department, Ain Shams University Hospital, Cairo, Egypt
| | - Amr Abdelaal
- General Surgery Department, Ain Shams University Hospital, Cairo, Egypt
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Yttrium-90 Radioembolization: Current Indications and Outcomes. J Gastrointest Surg 2022; 27:604-614. [PMID: 36547759 DOI: 10.1007/s11605-022-05559-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Accepted: 12/06/2022] [Indexed: 01/20/2023]
Abstract
BACKGROUND Radioembolization (RE) with 90Yttrium (Y90) has generally been used to treat patients with advanced disease. Recent data suggest, however, that RE is also safe and feasible to treat patients with early or intermediate stage disease. We herein review the current evidence regarding the use of RE with Y90 for patients with HCC. METHODS A comprehensive review of the literature was performed using MEDLINE/PubMed and Web of Science databases with a search end date of August 1, 2022. RESULTS Patients with HCC are often treated according to the BCLC staging system. Among patients with early-stage HCC (BCLC A), intermediate-stage HCC (BCLC B), and advanced-stage HCC (BCLC C), RE with Y90 has demonstrated promising results with comparable overall survival, time to disease progression, and radiological response compared with other standard of care treatment modalities. Moreover, Y90 RE can be used as a downstaging treatment modality for patients with advanced HCC who have a disease burden that is initially outside LT criteria. Radiation lobectomy (RL) has been described as a treatment modality with the intent of treating the ipsilateral liver that harbors the HCC, while also causing compensatory hypertrophy of the future liver remnant (FLR). CONCLUSION While initially considered as a palliative option for HCC patients, Y90 RE has emerged as an important part of the multi-modality care of patients with HCC across a wide spectrum of clinical indications.
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2022 KLCA-NCC Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Korean J Radiol 2022; 23:1126-1240. [PMID: 36447411 PMCID: PMC9747269 DOI: 10.3348/kjr.2022.0822] [Citation(s) in RCA: 82] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 10/28/2022] [Indexed: 11/18/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. Clin Mol Hepatol 2022; 28:583-705. [PMID: 36263666 PMCID: PMC9597235 DOI: 10.3350/cmh.2022.0294] [Citation(s) in RCA: 174] [Impact Index Per Article: 58.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 09/23/2022] [Indexed: 01/27/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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Huang AC, Dodge JL, Yao FY, Mehta N. National Experience on Waitlist Outcomes for Down-Staging of Hepatocellular Carcinoma: High Dropout Rate in All-Comers. Clin Gastroenterol Hepatol 2022; 21:1581-1589. [PMID: 36038129 DOI: 10.1016/j.cgh.2022.08.023] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 07/26/2022] [Accepted: 08/16/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The United Network for Organ Sharing (UNOS) grants priority listing for liver transplant for patients with hepatocellular carcinoma after successful down-staging to Milan criteria. We evaluated the national experience on down-staging by comparing 2 down-staging groups: tumor burden meeting UNOS down-staging (UNOS-DS) inclusion criteria, and all-comers (AC)-DS with initial tumor burden beyond UNOS-DS criteria vs patients always within Milan criteria. METHODS We performed a retrospective analysis of the UNOS database of 23,398 patients listed for liver transplant who had submitted a hepatocellular carcinoma Model for End-Stage Liver Disease exception application from 2010 to 2019, classified as always within Milan (n = 20,579), UNOS-DS (n = 2151), and AC-DS (n = 668). RESULTS The 2-year cumulative probabilities of dropout were 19% for Milan, 25% for UNOS-DS (P < .001), and 30% for AC-DS (P < .001). In multivariate analysis of the down-staging groups, factors predicting dropout included Model for End-Stage Liver Disease at listing (hazard ratio [HR], 1.06; P < .001) and initial total tumor diameter (HR, 1.04; P = .002). Compared with α-fetoprotein (AFP) level ≤20 ng/mL, AFP levels of 21 to 100, 101 to 1000, and greater than 1000 ng/mL were associated with a higher risk of dropout (HRs, 1.63, 2.06, and 4.58, respectively; P < .001). A subset of all-comers with AFP levels greater than 100 ng/mL had a 2-year probability of dropout of 52% vs 26% for all others beyond Milan criteria (P < .001). CONCLUSIONS All-comers had a significantly higher risk for waitlist dropout compared with the UNOS-DS and Milan groups after initial successful down-staging to Milan criteria. In particular, the subgroup of AC-DS with an AFP level greater than 100 ng/mL had a greater than 50% probability of dropout in the next 2 years. These observations suggest a high likelihood of failure when expanding the indications for down-staging.
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Affiliation(s)
- Annsa C Huang
- Division of Gastroenterology/Hepatology, Department of Medicine, University of California San Francisco, San Francisco, California
| | - Jennifer L Dodge
- Division of Gastroenterology, Department of Medicine, University of Southern California, Los Angeles, California; Department of Preventive Medicine, University of Southern California, Los Angeles, California
| | - Francis Y Yao
- Division of Gastroenterology/Hepatology, Department of Medicine, University of California San Francisco, San Francisco, California; Department of Surgery, University of California San Francisco, San Francisco, California
| | - Neil Mehta
- Division of Gastroenterology/Hepatology, Department of Medicine, University of California San Francisco, San Francisco, California.
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13
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Bhardwaj H, Fritze D, Mais D, Kadaba V, Arora SP. Neoadjuvant Therapy With Cabozantinib as a Bridge to Liver Transplantation in Patients With Hepatocellular Carcinoma (HCC): A Case Report. FRONTIERS IN TRANSPLANTATION 2022; 1:863086. [PMID: 38994388 PMCID: PMC11235223 DOI: 10.3389/frtra.2022.863086] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Accepted: 03/17/2022] [Indexed: 07/13/2024]
Abstract
Liver transplant (LT) is the treatment of choice for unresectable, localized hepatocellular carcinoma (HCC). However, transplant is not recommended for patients who have extensive tumor growth and do not meet specific criteria. For these cases, "bridging" therapies are often used to either downstage or prevent tumor progression while patients are on the transplant list. Various pre-transplant therapies have been used, including transarterial chemoembolization, radiofrequency ablation, and systemic therapies. Sorafenib is a well-known systemic agent used for HCC, but research is limited on its use as well as the use of newer agents as bridging therapy. Prospective studies are also lacking. We discuss cases of two patients diagnosed with HCC and treated systemically with cabozantinib prior to transplant without treatment-related complications. This suggests that cabozantinib could be safely used after sorafenib therapy to control disease related to HCC while awaiting liver transplantation.
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Affiliation(s)
- Hiral Bhardwaj
- Mays Cancer Center, University of Texas Health San Antonio, San Antonio, TX, United States
| | - Danielle Fritze
- Mays Cancer Center, University of Texas Health San Antonio, San Antonio, TX, United States
| | - Daniel Mais
- Mays Cancer Center, University of Texas Health San Antonio, San Antonio, TX, United States
| | - Venkatesh Kadaba
- Mays Cancer Center, University of Texas Health San Antonio, San Antonio, TX, United States
| | - Sukeshi Patel Arora
- Mays Cancer Center, University of Texas Health San Antonio, San Antonio, TX, United States
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14
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Ivanics T, Nelson W, Patel MS, Claasen MPAW, Lau L, Gorgen A, Abreu P, Goldenberg A, Erdman L, Sapisochin G. The Toronto Postliver Transplantation Hepatocellular Carcinoma Recurrence Calculator: A Machine Learning Approach. Liver Transpl 2022; 28:593-602. [PMID: 34626159 DOI: 10.1002/lt.26332] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 09/13/2021] [Accepted: 09/23/2021] [Indexed: 01/02/2023]
Abstract
Liver transplantation (LT) listing criteria for hepatocellular carcinoma (HCC) remain controversial. To optimize the utility of limited donor organs, this study aims to leverage machine learning to develop an accurate posttransplantation HCC recurrence prediction calculator. Patients with HCC listed for LT from 2000 to 2016 were identified, with 739 patients who underwent LT used for modeling. Data included serial imaging, alpha-fetoprotein (AFP), locoregional therapies, treatment response, and posttransplantation outcomes. We compared the CoxNet (regularized Cox regression), survival random forest, survival support vector machine, and DeepSurv machine learning algorithms via the mean cross-validated concordance index. We validated the selected CoxNet model by comparing it with other currently available recurrence risk algorithms on a held-out test set (AFP, Model of Recurrence After Liver Transplant [MORAL], and Hazard Associated with liver Transplantation for Hepatocellular Carcinoma [HALT-HCC score]). The developed CoxNet-based recurrence prediction model showed a satisfying overall concordance score of 0.75 (95% confidence interval [CI], 0.64-0.84). In comparison, the recalibrated risk algorithms' concordance scores were as follows: AFP score 0.64 (outperformed by the CoxNet model, 1-sided 95% CI, >0.01; P = 0.04) and MORAL score 0.64 (outperformed by the CoxNet model 1-sided 95% CI, >0.02; P = 0.03). The recalibrated HALT-HCC score performed well with a concordance of 0.72 (95% CI, 0.63-0.81) and was not significantly outperformed (1-sided 95% CI, ≥0.05; P = 0.29). Developing a comprehensive posttransplantation HCC recurrence risk calculator using machine learning is feasible and can yield higher accuracy than other available risk scores. Further research is needed to confirm the utility of machine learning in this setting.
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Affiliation(s)
- Tommy Ivanics
- Multi-Organ Transplant Program, Division of General Surgery, Toronto General Hospital, University Health Network, University of Toronto, Toronto, ON, Canada.,Department of Surgery, Henry Ford Hospital, Detroit, MI.,Department of Surgical Sciences, Uppsala University, Akademiska Sjukhuset, Uppsala, Sweden
| | - Walter Nelson
- Centre for Data Science and Digital Health, Hamilton Health Sciences, Hamilton, ON, Canada.,Department of Statistical Sciences, University of Toronto, Toronto, ON, Canada
| | - Madhukar S Patel
- Division of Surgical Transplantation, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX
| | - Marco P A W Claasen
- Multi-Organ Transplant Program, Division of General Surgery, Toronto General Hospital, University Health Network, University of Toronto, Toronto, ON, Canada.,Department of Surgery, Erasmus MC, University Medical Center Rotterdam, the Netherlands
| | - Lawrence Lau
- Multi-Organ Transplant Program, Division of General Surgery, Toronto General Hospital, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Andre Gorgen
- Multi-Organ Transplant Program, Division of General Surgery, Toronto General Hospital, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Phillipe Abreu
- Multi-Organ Transplant Program, Division of General Surgery, Toronto General Hospital, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Anna Goldenberg
- Centre for Computational Medicine, SickKids Research Institute, University of Toronto, Toronto, ON, Canada
| | - Lauren Erdman
- Centre for Computational Medicine, SickKids Research Institute, University of Toronto, Toronto, ON, Canada.,Center for Computational Medicine, SickKids Research Institute, Toronto, ON, Canada
| | - Gonzalo Sapisochin
- Multi-Organ Transplant Program, Division of General Surgery, Toronto General Hospital, University Health Network, University of Toronto, Toronto, ON, Canada.,Abdominal Transplant & HPB Surgical Oncology, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
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15
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Papaconstantinou D, Hewitt DB, Brown ZJ, Schizas D, Tsilimigras DI, Pawlik TM. Patient stratification in hepatocellular carcinoma: impact on choice of therapy. Expert Rev Anticancer Ther 2022; 22:297-306. [PMID: 35157530 DOI: 10.1080/14737140.2022.2041415] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
INTRODUCTION HCC comprises around 60 to 80% of all primary liver cancers and exhibits wide geographical variability. Appropriate treatment allocation needs to include both patient and tumor characteristics. AREAS COVERED Current HCC classification systems to guide therapy are either liver function-centric and evaluate physiologic liver function to guide therapy or prognostic stratification classification systems broadly based on tumor morphologic parameters, patient performance status, and liver reserve assessment. This review focuses on different classification systems for HCC, their strengths, and weaknesses as well as the use of artificial intelligence in improving prognostication in HCC. EXPERT OPINION Future HCC classification systems will need to incorporate clinic-pathologic data from a multitude of sources and emerging therapies to develop patient-specific treatment plans targeting a patient's unique tumor profile.
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Affiliation(s)
- Dimitrios Papaconstantinou
- Third Department of Surgery, Attikon University Hospital, National and Kapodistrian University of Athens, Medical School, Greece
| | - D Brock Hewitt
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio
| | - Zachary J Brown
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio
| | - Dimitrios Schizas
- First Department of Surgery, Laikon General Hospital, National and Kapodistrian University of Athens, Medical School, Greece
| | - Diamantis I Tsilimigras
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio
| | - Timothy M Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio
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16
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Hendriquez R, Keihanian T, Goyal J, Abraham RR, Mishra R, Girotra M. Radiofrequency ablation in the management of primary hepatic and biliary tumors. World J Gastrointest Oncol 2022; 14:203-215. [PMID: 35116111 PMCID: PMC8790419 DOI: 10.4251/wjgo.v14.i1.203] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 06/15/2021] [Accepted: 12/07/2021] [Indexed: 02/06/2023] Open
Abstract
In the United States, 80%-90% of primary hepatic tumors are hepatocellular carcinomas and 10%-15% are cholangiocarcinomas (CCA), both with high mortality rate, particularly CCA, which portends a worse prognosis. Traditional management with surgery has good outcomes in appropriately selected patients; however, novel ablative treatment options have emerged, such as radiofrequency ablation (RFA), which can improve the prognosis of both hepatic and biliary tumors. RFA is aimed to generate an area of necrosis within the targeted tissue by applying thermal therapy via an electrode, with a goal to completely eradicate the tumor while preserving surrounding healthy tissue. Role of RFA in management of hepatic and biliary tumors forms the focus of our current mini-review article.
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Affiliation(s)
- Richard Hendriquez
- Department of Internal Medicine, University of Central Florida, Orlando, FL 32816, United States
| | - Tara Keihanian
- Department of Gastroenterology and Hepatology, University of Miami, Miami, FL 33136, United States
| | - Jatinder Goyal
- Department of Gastroenterology and Hepatology, Wellspan Digestive Health - York Hospital, York, PA 17403, United States
| | - Rtika R Abraham
- Department of Endocrinology, Swedish Medical Center, Seattle, WA 98104, United States
| | - Rajnish Mishra
- Digestive Health Institute, Section of Gastroenterology and Interventional Endoscopy, Swedish Medical Center, Seattle, WA 98104, United States
| | - Mohit Girotra
- Digestive Health Institute, Section of Gastroenterology and Interventional Endoscopy, Swedish Medical Center, Seattle, WA 98104, United States
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17
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Kwong A, Hameed B, Syed S, Ho R, Mard H, Arshad S, Ho I, Suleman T, Yao F, Mehta N. Machine learning to predict waitlist dropout among liver transplant candidates with hepatocellular carcinoma. Cancer Med 2022; 11:1535-1541. [PMID: 35029055 PMCID: PMC8921896 DOI: 10.1002/cam4.4538] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Revised: 10/30/2021] [Accepted: 12/04/2021] [Indexed: 12/18/2022] Open
Abstract
Background Accurate prediction of outcome among liver transplant candidates with hepatocellular carcinoma (HCC) remains challenging. We developed a prediction model for waitlist dropout among liver transplant candidates with HCC. Methods The study included 18,920 adult liver transplant candidates in the United States listed with a diagnosis of HCC, with data provided by the Organ Procurement and Transplantation Network. The primary outcomes were 3‐, 6‐, and 12‐month waitlist dropout, defined as removal from the liver transplant waitlist due to death or clinical deterioration. Results Using 1,181 unique variables, the random forest model and Spearman's correlation analyses converged on 12 predictive features involving 5 variables, including AFP (maximum and average), largest tumor size (minimum, average, and most recent), bilirubin (minimum and average), INR (minimum and average), and ascites (maximum, average, and most recent). The final Cox proportional hazards model had a concordance statistic of 0.74 in the validation set. An online calculator was created for clinical use and can be found at: http://hcclivercalc.cloudmedxhealth.com/. Conclusion In summary, a simple, interpretable 5‐variable model predicted 3‐, 6‐, and 12‐month waitlist dropout among patients with HCC. This prediction can be used to appropriately prioritize patients with HCC and their imminent need for transplant.
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Affiliation(s)
- Allison Kwong
- Division of Gastroenterology and Hepatology Stanford University Stanford USA
| | - Bilal Hameed
- Division of Gastroenterology University of California San Francisco California USA
| | - Shareef Syed
- Division of Transplant Surgery University of California San Francisco California USA
| | - Ryan Ho
- CloudMedx, Inc Palo Alto California USA
| | | | | | - Isaac Ho
- CloudMedx, Inc Palo Alto California USA
| | | | - Francis Yao
- Division of Gastroenterology University of California San Francisco California USA
| | - Neil Mehta
- Division of Gastroenterology University of California San Francisco California USA
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18
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Bredt LC, Peres LAB. Artificial neural network for prediction of acute kidney injury after liver transplantation for cirrhosis and hepatocellular carcinoma. Artif Intell Cancer 2021; 2:51-59. [DOI: 10.35713/aic.v2.i5.51] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 10/22/2021] [Accepted: 10/27/2021] [Indexed: 02/06/2023] Open
Abstract
Acute kidney injury (AKI) has serious consequences on the prognosis of patients undergoing liver transplantation (LT) for liver cancer and cirrhosis. Artificial neural network (ANN) has recently been proposed as a useful tool in many fields in the setting of solid organ transplantation and surgical oncology, where patient prognosis depends on a multidimensional and nonlinear relationship between variables pertaining to the surgical procedure, the donor (graft characteristics), and the recipient comorbidities. In the specific case of LT, ANN models have been developed mainly to predict survival in patients with cirrhosis, to assess the best donor-to-recipient match during allocation processes, and to foresee postoperative complications and outcomes. This is a specific opinion review on the role of ANN in the prediction of AKI after LT for liver cancer and cirrhosis, highlighting potential strengths of the method to forecast this serious postoperative complication.
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Affiliation(s)
- Luis Cesar Bredt
- Department of Surgical Oncology and General Surgery, University Hospital of Western Paraná, State University of Western Paraná, Cascavel 85819-110, Paraná, Brazil
| | - Luis Alberto Batista Peres
- Department of Nephrology, University Hospital of Western Paraná, State University of Western Paraná, Cascavel 85819-110, Paraná, Brazil
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19
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Tonon F, Farra R, Zennaro C, Pozzato G, Truong N, Parisi S, Rizzolio F, Grassi M, Scaggiante B, Zanconati F, Bonazza D, Grassi G, Dapas B. Xenograft Zebrafish Models for the Development of Novel Anti-Hepatocellular Carcinoma Molecules. Pharmaceuticals (Basel) 2021; 14:803. [PMID: 34451900 PMCID: PMC8400454 DOI: 10.3390/ph14080803] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 08/02/2021] [Accepted: 08/03/2021] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the sixth most common type of tumor and the second leading cause of tumor-related death worldwide. Liver cirrhosis is the most important predisposing factor for HCC. Available therapeutic approaches are not very effective, especially for advanced HCC, which is the most common form of the disease at diagnosis. New therapeutic strategies are therefore urgently needed. The use of animal models represents a relevant tool for preclinical screening of new molecules/strategies against HCC. However, several issues, including animal husbandry, limit the use of current models (rodent/pig). One animal model that has attracted the attention of the scientific community in the last 15 years is the zebrafish. This freshwater fish has several attractive features, such as short reproductive time, limited space and cost requirements for husbandry, body transparency and the fact that embryos do not show immune response to transplanted cells. To date, two different types of zebrafish models for HCC have been developed: the transgenic zebrafish and the zebrafish xenograft models. Since transgenic zebrafish models for HCC have been described elsewhere, in this review, we focus on the description of zebrafish xenograft models that have been used in the last five years to test new molecules/strategies against HCC.
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Affiliation(s)
- Federica Tonon
- Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Hospital, Strada di Fiume, 447, I 34149 Trieste, Italy; (F.T.); (R.F.); (C.Z.); (G.P.); (F.Z.); (D.B.)
| | - Rossella Farra
- Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Hospital, Strada di Fiume, 447, I 34149 Trieste, Italy; (F.T.); (R.F.); (C.Z.); (G.P.); (F.Z.); (D.B.)
| | - Cristina Zennaro
- Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Hospital, Strada di Fiume, 447, I 34149 Trieste, Italy; (F.T.); (R.F.); (C.Z.); (G.P.); (F.Z.); (D.B.)
| | - Gabriele Pozzato
- Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Hospital, Strada di Fiume, 447, I 34149 Trieste, Italy; (F.T.); (R.F.); (C.Z.); (G.P.); (F.Z.); (D.B.)
| | - Nhung Truong
- Stem Cell Research and Application Laboratory, VNUHCM, University of Science, Ho Chi Minh City 72711, Vietnam;
| | - Salvatore Parisi
- Pathology Unit, CRO Aviano, National Cancer Institute, IRCCS, I 33081 Aviano, Italy; (S.P.); (F.R.)
- Doctoral School in Molecular Biomedicine, University of Trieste, I 34127 Trieste, Italy
| | - Flavio Rizzolio
- Pathology Unit, CRO Aviano, National Cancer Institute, IRCCS, I 33081 Aviano, Italy; (S.P.); (F.R.)
- Department of Molecular Sciences and Nanosystems, Ca’ Foscari University of Venice, I 30170 Mestre, Italy
| | - Mario Grassi
- Department of Engineering and Architecture, University of Trieste, Via Valerio 6/A, I 34127 Trieste, Italy;
| | - Bruna Scaggiante
- Department of Life Sciences, Cattinara University Hospital, Trieste University, Strada di Fiume 447, I 34149 Trieste, Italy; (B.S.); (B.D.)
| | - Fabrizio Zanconati
- Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Hospital, Strada di Fiume, 447, I 34149 Trieste, Italy; (F.T.); (R.F.); (C.Z.); (G.P.); (F.Z.); (D.B.)
| | - Deborah Bonazza
- Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Hospital, Strada di Fiume, 447, I 34149 Trieste, Italy; (F.T.); (R.F.); (C.Z.); (G.P.); (F.Z.); (D.B.)
| | - Gabriele Grassi
- Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Hospital, Strada di Fiume, 447, I 34149 Trieste, Italy; (F.T.); (R.F.); (C.Z.); (G.P.); (F.Z.); (D.B.)
- Department of Life Sciences, Cattinara University Hospital, Trieste University, Strada di Fiume 447, I 34149 Trieste, Italy; (B.S.); (B.D.)
| | - Barbara Dapas
- Department of Life Sciences, Cattinara University Hospital, Trieste University, Strada di Fiume 447, I 34149 Trieste, Italy; (B.S.); (B.D.)
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20
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Eng NAM, Arjunan V, Prabhakar V, Mannalithara A, Ghaziani T, Ahmed A, Kwo P, Nguyen M, Melcher ML, Busuttil RW, Florman SS, Haydel B, Ruiz RM, Klintmalm GB, Lee DD, Taner CB, Hoteit MA, Verna EC, Halazun KJ, Tevar AD, Humar A, Chapman WC, Vachharajani N, Aucejo F, Nydam TL, Markmann JF, Mobley C, Ghobrial M, Langnas AN, Carney CA, Berumen J, Schnickel GT, Sudan DL, Hong JC, Rana A, Jones CM, Fishbein TM, Agopian V, Dhanasekaran R. Posttransplant Outcomes in Older Patients With Hepatocellular Carcinoma Are Driven by Non-Hepatocellular Carcinoma Factors. Liver Transpl 2021; 27:684-698. [PMID: 33306254 PMCID: PMC8140549 DOI: 10.1002/lt.25974] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Revised: 10/13/2020] [Accepted: 11/05/2020] [Indexed: 01/10/2023]
Abstract
The incidence of hepatocellular carcinoma (HCC) is growing in the United States, especially among the elderly. Older patients are increasingly receiving transplants as a result of HCC, but the impact of advancing age on long-term posttransplant outcomes is not clear. To study this, we used data from the US Multicenter HCC Transplant Consortium of 4980 patients. We divided the patients into 4 groups by age at transplantation: 18 to 64 years (n = 4001), 65 to 69 years (n = 683), 70 to 74 years (n = 252), and ≥75 years (n = 44). There were no differences in HCC tumor stage, type of bridging locoregional therapy, or explant residual tumor between the groups. Older age was confirmed to be an independent and significant predictor of overall survival even after adjusting for demographic, etiologic, and cancer-related factors on multivariable analysis. A dose-response effect of age on survival was observed, with every 5-year increase in age older than 50 years resulting in an absolute increase of 8.3% in the mortality rate. Competing risk analysis revealed that older patients experienced higher rates of non-HCC-related mortality (P = 0.004), and not HCC-related death (P = 0.24). To delineate the precise cause of death, we further analyzed a single-center cohort of patients who received a transplant as a result of HCC (n = 302). Patients older than 65 years had a higher incidence of de novo cancer (18.1% versus 7.6%; P = 0.006) after transplantation and higher overall cancer-related mortality (14.3% versus 6.6%; P = 0.03). Even carefully selected elderly patients with HCC have significantly worse posttransplant survival rates, which are mostly driven by non-HCC-related causes. Minimizing immunosuppression and closer surveillance for de novo cancers can potentially improve the outcomes in elderly patients who received a transplant as a result of HCC.
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Affiliation(s)
| | - Vinodhini Arjunan
- Division of Gastroenterology and Hepatology, Stanford University, Stanford, CA
| | | | - Ajitha Mannalithara
- Division of Gastroenterology and Hepatology, Stanford University, Stanford, CA
| | - Tara Ghaziani
- Division of Gastroenterology and Hepatology, Stanford University, Stanford, CA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University, Stanford, CA
| | - Paul Kwo
- Division of Gastroenterology and Hepatology, Stanford University, Stanford, CA
| | - Mindie Nguyen
- Division of Gastroenterology and Hepatology, Stanford University, Stanford, CA
| | - Marc L. Melcher
- Department: Surgery - Multi-Organ Transplantation, Stanford University, Stanford, CA
| | - Ronald W. Busuttil
- Dumont-UCLA (University of California, Los Angeles) Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Sander S. Florman
- Recanati/Miller Transplantation Institute, Mount Sinai Medical Center, New York, NY
| | - Brandy Haydel
- Recanati/Miller Transplantation Institute, Mount Sinai Medical Center, New York, NY
| | - Richard M. Ruiz
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX
| | - Goran B. Klintmalm
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX
| | - David D. Lee
- Department of Transplantation, Mayo Clinic, Jacksonville, FL
| | - C. Burcin Taner
- Department of Transplantation, Mayo Clinic, Jacksonville, FL
| | - Maarouf A. Hoteit
- Division of Gastroenterology and Hepatology, Penn Transplant Institute, University of Pennsylvania
| | | | | | - Amit D. Tevar
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Abhinav Humar
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - William C. Chapman
- Section of Transplantation, Department of Surgery, Washington University in St. Louis, St. Louis, MO
| | - Neeta Vachharajani
- Section of Transplantation, Department of Surgery, Washington University in St. Louis, St. Louis, MO
| | | | - Trevor L. Nydam
- Division of Transplant Surgery, Department of Surgery, University of Colorado School of Medicine, Denver, CO
| | - James F. Markmann
- Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Constance Mobley
- Sherrie & Alan Conover Center for Liver Disease & Transplantation, Houston Methodist Hospital, Houston, TX
| | - Mark Ghobrial
- Sherrie & Alan Conover Center for Liver Disease & Transplantation, Houston Methodist Hospital, Houston, TX
| | - Alan N. Langnas
- Department of Surgery, University of Nebraska Medical Center, Omaha, NE
| | - Carol A. Carney
- Department of Surgery, University of Nebraska Medical Center, Omaha, NE
| | - Jennifer Berumen
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of California, San Diego, San Diego, CA
| | - Gabriel T. Schnickel
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of California, San Diego, San Diego, CA
| | - Debra L. Sudan
- Department of Surgery, Duke University Medical Center; Durham, NC
| | - Johnny C. Hong
- Division of Transplant Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI
| | - Abbas Rana
- Department of Surgery, Baylor College of Medicine, Houston, TX
| | | | - Thomas M. Fishbein
- Section of Hepatobiliary and Transplant Surgery, University of Louisville School of Medicine, Louisville, KY,Medstar Georgetown Transplant Institute, Georgetown University, Washington, District of Columbia
| | - Vatche Agopian
- Dumont-UCLA (University of California, Los Angeles) Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA
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21
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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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22
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Cheung TT, Ma KW, She WH. A review on radiofrequency, microwave and high-intensity focused ultrasound ablations for hepatocellular carcinoma with cirrhosis. Hepatobiliary Surg Nutr 2021; 10:193-209. [PMID: 33898560 DOI: 10.21037/hbsn.2020.03.11] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Importance Hepatocellular carcinoma (HCC) is usually accompanied by liver cirrhosis, which makes treatment of this disease challenging. Liver transplantation theoretically provides an ultimate solution to the disease, but the maximal surgical stress and the scarcity of liver graft make this treatment option impossible for some patients. In an ideal situation, a treatment that is safe and effective should provide a better outcome for patients with the dilemma. Objective This article aims to give a comprehensive review of various types of loco-ablative treatment for HCC. Evidence Review Loco-ablative treatment bridges the gap between surgical resection and transarterial chemotherapy. Various types of ablative therapy have their unique ability, and evidence-based outcome analysis is the most important key to assisting clinicians to choose the most suitable treatment modality for their patients. Findings Radiofrequency ablation (RFA) has a relatively longer history and more evidence to support its effectiveness. Microwave ablation (MWA) is gaining momentum because of its shorter ablation time and consistent ablation zone. High-intensity focused ultrasound (HIFU) ablation is a relatively new technology that provides non-invasive treatment for patients with HCC. It has been carried out at centers of excellence and it is a safe and effective treatment option for selected patients with HCC and liver cirrhosis. Conclusion and Relevance Selective use of different loco-ablative therapies will enhance clinicians' treatment options for treatment of HCC.
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Affiliation(s)
- Tan To Cheung
- Department of Surgery, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China
| | - Ka Wing Ma
- Department of Surgery, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China
| | - Wong Hoi She
- Department of Surgery, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China
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23
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Wang YF, Dai YH, Lin CS, Chang HC, Shen PC, Yang JF, Hsiang CW, Lo CH, Huang WY. Clinical outcome and pathologic correlation of stereotactic body radiation therapy as a bridge to transplantation for advanced hepatocellular carcinoma: a case series. Radiat Oncol 2021; 16:15. [PMID: 33446231 PMCID: PMC7807861 DOI: 10.1186/s13014-020-01739-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2020] [Accepted: 12/26/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Stereotactic body radiotherapy (SBRT) is an emerging modality for hepatocellular carcinoma (HCC). However, there is scant information about its safety and effectiveness in the neoadjuvant setting prior to liver transplantation (LT). We present the clinical outcome and pathologic assessment of SBRT followed by LT for patients with advanced HCC. METHODS This retrospective study included HCC patients treated with neoadjuvant SBRT prior to LT between 2009 and 2018. Radiographic response and adverse effects, including radiation-induced liver disease (RILD), were evaluated. Pathologic response was assessed by the percentage of tumor necrosis relative to the total tumor volume. Overall survival (OS) and recurrence-free survival (RFS) were calculated using the Kaplan-Meier method. RESULTS Fourteen patients underwent SBRT for a total of 25 HCC lesions, followed by LT. The median tumor size was 4.45 cm in diameter, and the median prescribed dose was 45 Gy in 5 fractions. SBRT provided significant AFP reduction, 100% infield control, and a 62.5% response rate. The maximum detected toxicity included grade 3 thrombocytopenia and two grade 3-4 hyperbilirubinemia. One patient developed non-classic RILD. Patients were bridged to LT with a median time of 8.4 months after SBRT, and 23.1% of them achieved a complete pathologic response. The median OS and RFS were 37.8 and 18.3 months from the time of LT, respectively. CONCLUSIONS SBRT provides favorable tumor control and acceptable adverse effects for patients awaiting LT. Further prospective studies to test SBRT as a bridging therapy for LT are feasible.
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Affiliation(s)
- Ying-Fu Wang
- Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Cheng-Gong Rd, Neihu, Taipei, 114, Taiwan
| | - Yang-Hong Dai
- Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Cheng-Gong Rd, Neihu, Taipei, 114, Taiwan
| | - Chun-Shu Lin
- Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Cheng-Gong Rd, Neihu, Taipei, 114, Taiwan
| | - Hao-Chih Chang
- Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Cheng-Gong Rd, Neihu, Taipei, 114, Taiwan
| | - Po-Chien Shen
- Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Cheng-Gong Rd, Neihu, Taipei, 114, Taiwan
| | - Jen-Fu Yang
- Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Cheng-Gong Rd, Neihu, Taipei, 114, Taiwan
| | - Chih-Weim Hsiang
- Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Cheng-Gong Rd, Neihu, Taipei, 114, Taiwan
| | - Cheng-Hsiang Lo
- Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Cheng-Gong Rd, Neihu, Taipei, 114, Taiwan.
| | - Wen-Yen Huang
- Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Cheng-Gong Rd, Neihu, Taipei, 114, Taiwan.
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24
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Evaluation of Apelin/APJ system expression in hepatocellular carcinoma as a function of clinical severity. Clin Exp Med 2020; 21:269-275. [DOI: 10.1007/s10238-020-00672-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Accepted: 11/04/2020] [Indexed: 12/14/2022]
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25
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Heimbach JK. Evolution of Liver Transplant Selection Criteria and U.S. Allocation Policy for Patients with Hepatocellular Carcinoma. Semin Liver Dis 2020; 40:358-364. [PMID: 32942324 DOI: 10.1055/s-0040-1709492] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Liver transplantation (LT) is an optimal treatment option for early-stage unresectable hepatocellular carcinoma (HCC) in patients with cirrhosis as it provides a treatment for underlying liver disease as well as a decreased incidence of recurrent cancer compared with alternative treatment strategies. A primary barrier to LT for HCC is the critical shortage of available liver allografts. The system of prioritization and access to deceased donor transplantation for patient with HCC in the United States has continued to evolve, while variable approaches including no additional priority, are in use around the world. While the Milan criteria remain the most well-established pretransplantation selection criteria, multiple other algorithms which expand beyond Milan have been proposed. The current review focuses on liver allocation for HCC as well as the principles and varied models available for pretransplant patient selection.
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Affiliation(s)
- Julie K Heimbach
- Department of Transplant Surgery, William J. von Liebig Transplant Center, Mayo Clinic College of Medicine, Rochester, Minnesota
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26
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Finotti M, Vitale A, Volk M, Cillo U. A 2020 update on liver transplant for hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol 2020; 14:885-900. [PMID: 32662680 DOI: 10.1080/17474124.2020.1791704] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2020] [Accepted: 07/01/2020] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Hepatocellular carcinoma is the most frequent liver tumor and is associated with chronic liver disease in 90% of cases. In selected cases, liver transplantation represents an effective therapy with excellent overall survival. AREA COVERED Since the introduction of Milan criteria in 1996, numerous alternative selection systems to LT for HCC patients have been proposed. Debate remains about how best to select HCC patients for transplant and how to prioritize them on the waiting list. EXPERT OPINION The selection of the best scoring system to propose in the context of LT for HCC is far to be identified. In this review, we analyze and categorize the various selection systems, assessing their roles in the different decisional phases.
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Affiliation(s)
- Michele Finotti
- Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplantation Unit, Padova University Hospital , Padova, Italy
| | - Alessandro Vitale
- Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplantation Unit, Padova University Hospital , Padova, Italy
| | - Michael Volk
- Division of Gastroenterology and Hepatology, Loma Linda University Health , Loma Linda, California, USA
| | - Umberto Cillo
- Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplantation Unit, Padova University Hospital , Padova, Italy
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27
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Silverstein J, Roll G, Dodge JL, Grab JD, Yao FY, Mehta N. Donation After Circulatory Death Is Associated With Similar Posttransplant Survival in All but the Highest-Risk Hepatocellular Carcinoma Patients. Liver Transpl 2020; 26:1100-1111. [PMID: 32531867 PMCID: PMC8722407 DOI: 10.1002/lt.25819] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Revised: 04/28/2020] [Accepted: 05/13/2020] [Indexed: 12/15/2022]
Abstract
Liver transplantation (LT) recipients with hepatocellular carcinoma (HCC) receive a higher proportion of livers from donation after circulatory death (DCD) donors compared with non-HCC etiologies. Nevertheless, data on outcomes in patients with HCC receiving DCD grafts are limited. We evaluated the influence of DCD livers on post-LT outcome among HCC patients. We identified 7563 patients in the United Network for Organ Sharing (UNOS) database who underwent LT with Model for End-Stage Liver Disease score exceptions from 2012 to 2016, including 567 (7.5%) who received a DCD donor organ and 6996 (92.5%) who received a donation after brain death (DBD) donor organ. Kaplan-Meier probabilities of post-LT HCC recurrence at 3 years were 7.6% for DCD and 6.4% for DBD recipients (P = 0.67) and post-LT survival at 3 years was 81.1% versus 85.5%, respectively (P = 0.008). On multivariate analysis, DCD donor (hazard ratio, 1.38; P = 0.005) was an independent predictor of post-LT mortality. However, a survival difference after LT was only observed in subgroups at higher risk for HCC recurrence including Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score ≥4 (DCD 57.0% versus DBD 72.6%; P = 0.02), alpha-fetoprotein (AFP) ≥100 (60.1% versus 76.9%; P = 0.049), and multiple viable tumors on last imaging before LT (69.9% versus 83.1%; P = 0.002). In this analysis of HCC patients receiving DCD versus DBD livers in the UNOS database, we found that patients with a low-to-moderate risk of HCC recurrence (80%-90% of the DCD cohort) had equivalent survival regardless of donor type. It appears that DCD donation can best be used to increase the donor pool for HCC patients with decompensated cirrhosis or partial response/stable disease after locoregional therapy with AFP at LT <100 ng/mL.
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Affiliation(s)
- Jordyn Silverstein
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA
| | - Garrett Roll
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA
| | - Jennifer L. Dodge
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA
| | - Joshua D. Grab
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA
| | - Francis Y. Yao
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA,Division of Transplant Surgery, Department of Surgery, 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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28
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Satiya J, Schwartz I, Tabibian JH, Kumar V, Girotra M. Ablative therapies for hepatic and biliary tumors: endohepatology coming of age. Transl Gastroenterol Hepatol 2020; 5:15. [PMID: 32258519 PMCID: PMC7063520 DOI: 10.21037/tgh.2019.10.17] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Accepted: 10/23/2019] [Indexed: 12/12/2022] Open
Abstract
Ablative therapies refer to minimally invasive procedures performed to destroy abnormal tissue that may arise with many conditions, and can be achieved clinically using chemical, thermal, and other techniques. In this review article, we explore the different ablative therapies used in the management of hepatic and biliary malignancies, namely hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), with a particular focus on radiofrequency ablation (RFA) and photodynamic therapy (PDT) techniques.
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Affiliation(s)
- Jinendra Satiya
- Internal Medicine, University of Miami/JFK Medical Center Palm Beach Regional GME Consortium, West Palm Beach, FL, USA
| | - Ingrid Schwartz
- Internal Medicine, University of Miami Miller School of Medicine/Jackson Memorial Hospital, Miami, FL, USA
| | - James H. Tabibian
- Geffen School of Medicine, University of California, Los Angeles, CA, USA
- Division of Gastroenterology, Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA, USA
| | - Vivek Kumar
- Gastroenterology and Hepatology, UPMC Susquehanna, Williamsport, PA, USA
| | - Mohit Girotra
- Division of Gastroenterology and Hepatology, University of Miami Miller School of Medicine, Miami, FL, USA
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29
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30
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Rodríguez S, Fleck ADM, Mucenic M, Marroni C, Brandão A. HEPATOCELLULAR CARCINOMA PATIENTS ARE ADVANTAGED IN THE CURRENT BRAZILIAN LIVER TRANSPLANT ALLOCATION SYSTEM. A COMPETING RISK ANALYSIS. ARQUIVOS DE GASTROENTEROLOGIA 2020; 57:19-23. [PMID: 32294731 DOI: 10.1590/s0004-2803.202000000-05] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/23/2019] [Accepted: 10/27/2019] [Indexed: 01/26/2023]
Abstract
BACKGROUND In Brazil, the Model for End-Stage Liver Disease (MELD) score is used to prioritize patients for deceased donor liver transplantation (DDLT). Patients with hepatocellular carcinoma (HCC) receive standardized MELD exception points to account for their cancer risk of mortality, which is not reflected by their MELD score. OBJECTIVE To compare DDLT rates between patients with and without HCC in Rio Grande do Sul, the Southernmost state of Brazil. METHODS - We retrospectively studied 825 patients on the liver-transplant waiting list from January 1, 2007, to December 31, 2016, in a transplant center located in Porto Alegre, the capital of Rio Grande do Sul, to compare DDLT rates between those with and without HCC. The time-varying hazard of waiting list/DDLT was estimated, reporting the subhazard ratio (SHR) of waiting list/DDLT/dropout with 95% confidence intervals (CI). The final competing risk model was adjusted for age, MELD score, exception points, and ABO group. RESULTS Patients with HCC underwent a transplant almost three times faster than patients with a calculated MELD score (SHR 2.64; 95% CI 2.10-3.31; P<0.001). The DDLT rate per 100 person-months was 11.86 for HCC patients vs 3.38 for non-HCC patients. The median time on the waiting list was 5.6 months for patients with HCC and 25 months for patients without HCC. CONCLUSION Our results demonstrated that, in our center, patients on the waiting list with HCC have a clear advantage over candidates listed with a calculated MELD score.
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Affiliation(s)
- Santiago Rodríguez
- Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Faculdade de Medicina, Programa de Pós-Graduação em Medicina, Hepatologia, Porto Alegre, RS, Brasil
| | - Alfeu de Medeiros Fleck
- Santa Casa de Misericórdia de Porto Alegre, Grupo de Transplante de Fígado, Porto Alegre, RS, Brasil
| | - Marcos Mucenic
- Santa Casa de Misericórdia de Porto Alegre, Grupo de Transplante de Fígado, Porto Alegre, RS, Brasil
| | - Cláudio Marroni
- Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Faculdade de Medicina, Programa de Pós-Graduação em Medicina, Hepatologia, Porto Alegre, RS, Brasil
- Santa Casa de Misericórdia de Porto Alegre, Grupo de Transplante de Fígado, Porto Alegre, RS, Brasil
| | - Ajacio Brandão
- Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Faculdade de Medicina, Programa de Pós-Graduação em Medicina, Hepatologia, Porto Alegre, RS, Brasil
- Santa Casa de Misericórdia de Porto Alegre, Grupo de Transplante de Fígado, Porto Alegre, RS, Brasil
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31
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Patterns and Predictors of Mortality After Waitlist Dropout of Patients With Hepatocellular Carcinoma Awaiting Liver Transplantation. Transplantation 2019; 103:2136-2143. [DOI: 10.1097/tp.0000000000002616] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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32
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Giard JM, Dodge JL, Terrault N. Superior Wait-List Outcomes in Patients with Alcohol-Associated Liver Disease Compared With Other Indications for Liver Transplantation. Liver Transpl 2019; 25:1310-1320. [PMID: 31063642 PMCID: PMC8544021 DOI: 10.1002/lt.25485] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Accepted: 04/17/2019] [Indexed: 01/18/2023]
Abstract
Alcohol-associated liver disease (ALD) is the most common indication for liver transplantation (LT) in the United States and Europe. A 6-month alcohol abstinence period has been required by many transplant programs prior to listing, which may influence wait-list (WL) outcomes. Therefore, we examined WL events in patients with ALD versus non-ALD with a special interest in whether these outcomes differed by sex. All US adults listed for LT from January 2002 to December 2016 were eligible except status 1 patients, Model for End-Stage Liver Disease exceptions, retransplants and those with acute alcoholic hepatitis. The outcomes of interest were cumulative WL death or being too sick and WL removal for improvement within 2 years of listing. Competing risk regression models were used to evaluate recipient factors associated with the outcomes. Among the 83,348 eligible WL patients, 23% had ALD. Unadjusted cumulative WL removal within 2 years was 19.0% for ALD versus 21.1% for non-ALD (P < 0.001). In fully adjusted models, ALD was associated with a significantly lower risk of WL removal for death or being too sick (subhazard ratio [SHR], 0.84; 95% confidence interval [CI], 0.81-0.87; P < 0.001) and a higher risk of removal for improvement (SHR, 2.91; 95% CI, 2.35-3.61; P < 0.001) versus non-ALD patients. After adjusting for potential confounders, women with ALD had a higher risk of removal for death or being too sick (SHR, 1.09; 95% CI, 1.00-1.08; P < 0.001) and a higher chance for improvement (SHR, 2.91; 95% CI, 2.35-3.61; P < 0.001) than men with ALD. In conclusion, WL candidates with ALD have more favorable WL outcomes than non-ALD patients with a 16% lower risk of removal for deterioration and 191% higher risk of removal for improvement. This result likely reflects the benefits of alcohol abstinence, but it suggests that listing criteria for ALD may be too restrictive, with patients who might derive benefit from LT not being listed.
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Affiliation(s)
- Jeanne-Marie Giard
- University of California San Francisco, San Francisco, CA, United States.,Université de Montréal, Montréal, Québec, Canada
| | - Jennifer L. Dodge
- University of California San Francisco, San Francisco, CA, United States
| | - Norah Terrault
- University of California San Francisco, San Francisco, CA, United States
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33
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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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2018 Korean Liver Cancer Association-National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Korean J Radiol 2019; 20:1042-1113. [PMID: 31270974 PMCID: PMC6609431 DOI: 10.3348/kjr.2019.0140] [Citation(s) in RCA: 191] [Impact Index Per Article: 31.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Accepted: 02/24/2019] [Indexed: 01/10/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer globally and the fourth most common cancer in men in Korea, where the prevalence of chronic hepatitis B infection is high in middle-aged and elderly patients. These practice guidelines will provide useful and constructive advice for the clinical management of patients with HCC. A total of 44 experts in hepatology, oncology, surgery, radiology, and radiation oncology in the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2014 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions.
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Local Ablation Does Not Worsen Perioperative Outcomes After Liver Transplant for Hepatocellular Carcinoma. AJR Am J Roentgenol 2019; 213:702-709. [PMID: 31120785 DOI: 10.2214/ajr.18.20993] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE. Local ablation of hepatocellular carcinoma (HCC) before liver transplant has important advantages, such as preventing disease progression, tumor downstaging, and offering a test of time. However, it might render liver transplant more technically demanding. Thus far, its potential effect on liver transplant outcomes is still unknown, and, therefore, the current study was performed. MATERIALS AND METHODS. Patients who underwent liver transplant for HCC at a single tertiary referral center between 2008 and 2016 were included and retrospectively analyzed. Patients who underwent liver resection and local ablation before liver transplant were excluded. Patients treated with local ablation before liver transplant were compared with those not treated with local ablation, both before and after propensity score matching. In addition, the local ablation group was compared with patients who underwent primary resection before liver transplant. Posttreatment mortality and morbidity were determined, and overall and disease-free survival rates were calculated. RESULTS. In total, 182 patients were included. Twenty-six patients underwent resection but not local ablation before liver transplant. Of the remaining 156 patients, 66 (42%) underwent local ablation before liver transplant and 90 (58%) did not. Perioperative mortality and morbidity were similar in both groups before and after propensity score matching (8% and 74% in the local ablation group vs 10% and 83% in the non-local ablation group, p = 0.60 and 0.17, respectively). In addition, no significant differences in long-term outcomes were observed between the groups before and after propensity score matching. Also, no differences were observed in outcomes in the local ablation group versus the liver resection group. CONCLUSION. Local ablation before liver transplant does not have a negative effect on outcomes after liver transplant for HCC.
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2018 Korean Liver Cancer Association-National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Gut Liver 2019; 13:227-299. [PMID: 31060120 PMCID: PMC6529163 DOI: 10.5009/gnl19024] [Citation(s) in RCA: 241] [Impact Index Per Article: 40.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Accepted: 01/24/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer globally and the fourth most common cancer in men in Korea, where the prevalence of chronic hepatitis B infection is high in middle-aged and elderly patients. These practice guidelines will provide useful and constructive advice for the clinical management of patients with HCC. A total of 44 experts in hepatology, oncology, surgery, radiology and radiation oncology in the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2014 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions.
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Abstract
Identifying the optimal allocation policy with regard to hepatocellular carcinoma has been a persistent and evolving challenge. The current criteria for LT for HCC endorsed by the United Network of Organ Sharing (UNOS) are based on the Milan Criteria: a solitary tumor < 5 cm, or maximum of three tumors ≤ 3 cm each, without vascular invasion or evidence of extrahepatic spread. Contraindications to HCC exception points include: stage 1 HCC, ruptured HCC, extrahepatic HCC, and main portal or hepatic vein HCC invasion. Based upon projected waitlist dropout rates due to tumor growth, patients with HCC are assigned MELD standardized exception points. In addition to tumor size and number, AFP levels are an important predictor of recurrence of HCC following liver transplantation. Standardized exception points for HCC patients are not awarded to patients with AFP levels > 1000 ng/mL that do not decrease to < 500 ng/mL with treatment. Appeals for MELD exception points for patients with HCC vary widely between UNOS regions, with success of nonstandardized exception point appeals varying from 3.1 to 21% between regions. In an effort to make prioritization for HCC more consistent, a national liver review board (NLRB)is being convened that will focus on developing a national guidance for assessing common requests and addressing exception points, including for HCC.
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Abstract
The average age of liver transplant donors and recipients has increased over the years. Independent of the cause of liver disease, older candidates have more comorbidities, higher waitlist mortality and higher post-transplant mortality than younger patients. However, transplant benefit may be similar in older and younger recipients, provided older recipients are carefully selected. The cohort of elderly patients transplanted decades ago is also increasingly raising issues concerning long-term exposure to immunosuppression and aging of the transplanted liver. Excellent results can be achieved with elderly donors and there is virtually no upper age limit for donors after brain death liver transplantation. The issue is how to optimise selection, procurement and matching to ensure good results with elderly donors. The impact of old donor age is more pronounced in younger recipients and patients with a high model for end-stage liver disease score. Age matching between the donor and the recipient should be incorporated into allocation policies with a multistep approach. However, age matching may vary depending on the objectives of different allocation policies. In addition, age matching must be revisited in the era of direct-acting antivirals. More restrictive limits have been adopted in donation after circulatory death. Perfusion machines which are currently under investigation may help expand these limits. In living donor liver transplantation, donor age limit is essentially guided by morbidity related to procurement. In this review we summarise changing trends in recipient and donor age. We discuss the implications of older age donors and recipients. We also consider different options for age matching in liver transplantation that could improve outcomes.
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Ogawa K, Kaido T, Okajima H, Fujimoto Y, Yoshizawa A, Yagi S, Hori T, Iida T, Takada Y, Uemoto S. Impact of pretreatments on outcomes after living donor liver transplantation for hepatocellular carcinoma. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2019; 26:73-81. [PMID: 30561147 DOI: 10.1002/jhbp.602] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND The purpose of this study was to examine the impact of pretreatments on outcomes after living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC). METHODS From February 1999 to March 2015, 223 patients underwent LDLT for HCC. Until December 2006, there was no restriction in patient selection criteria regarding the number and size of tumors, following which we implemented the Kyoto criteria (tumor number ≤10, maximal diameter ≤5 cm, and des-gamma-carboxy prothrombin ≤400 mAU/ml) since January 2007. RESULTS Of 223 patients, 156 had a history of pretreatments. Among 101 patients meeting the Milan criteria at the initial diagnosis, 38 progressed to beyond the criteria at liver transplantation (LT). Twenty-two out of 38 met the Kyoto criteria, and their survival and recurrence rates were significantly better than those of patients exceeding the Kyoto criteria (P = 0.004 and 0.035, respectively). Regarding the number of pretreatments (0 vs. 1-4 vs. ≥5), recurrence rate was significantly higher in the ≥5 pretreatments group than the 0 group. However, for patients meeting the Kyoto criteria, there were no significant differences in recurrence rates between these three groups. CONCLUSION Better outcomes will be achieved by performing LT for HCCs meeting the Kyoto criteria even after repeated pretreatments.
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Affiliation(s)
- Kohei Ogawa
- Department of Hepatobiliary Pancreatic Surgery and Transplantation, Kyoto University, Kyoto, Japan
| | - Toshimi Kaido
- Department of Hepatobiliary Pancreatic Surgery and Transplantation, Kyoto University, Kyoto, Japan
| | - Hideaki Okajima
- Department of Hepatobiliary Pancreatic Surgery and Transplantation, Kyoto University, Kyoto, Japan
| | - Yasuhiro Fujimoto
- Department of Hepatobiliary Pancreatic Surgery and Transplantation, Kyoto University, Kyoto, Japan
| | - Atsushi Yoshizawa
- Department of Hepatobiliary Pancreatic Surgery and Transplantation, Kyoto University, Kyoto, Japan
| | - Shintaro Yagi
- Department of Hepatobiliary Pancreatic Surgery and Transplantation, Kyoto University, Kyoto, Japan
| | - Tomohide Hori
- Department of Hepatobiliary Pancreatic Surgery and Transplantation, Kyoto University, Kyoto, Japan
| | - Taku Iida
- Department of Hepatobiliary Pancreatic Surgery and Transplantation, Kyoto University, Kyoto, Japan
| | - Yasutsugu Takada
- Department of Hepatobiliary Pancreatic and Breast Surgery, Ehime University, Toon, Ehime, Japan
| | - Shinji Uemoto
- Department of Hepatobiliary Pancreatic Surgery and Transplantation, Kyoto University, Kyoto, Japan
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Patterns of Discordance Between Pretransplant Imaging Stage of Hepatocellular Carcinoma and Posttransplant Pathologic Stage: A Contemporary Appraisal of the Milan Criteria. Transplantation 2018; 102:648-655. [PMID: 29319629 DOI: 10.1097/tp.0000000000002056] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Patients with hepatocellular carcinoma (HCC) exceeding Milan criteria on explant pathology are at increased risk of recurrence and death. Discordance between contemporary magnetic resonance imaging (MRI) and explant pathology, and preoperative characteristics predictive of discordance are not well understood. METHODS Patients who underwent orthotopic liver transplantation for HCC after preoperative MRI were identified in a prospectively collected institutional database (January 2003 to December 2013). Patients were dichotomized to "within" or "outside" Milan criteria by both imaging and explant pathologic evaluation. Binary logistic regression and Kaplan-Meier methodology were used to identify independent predictors of imaging/pathologic discordance and its impact on posttransplant survival. RESULTS Of 318 patients with HCC meeting Milan criteria by MRI at the time of orthotopic liver transplantation, 248 (78.0%) remained within a pathological correlate of Milan criteria on explant examination. Understaging was associated with worse median recurrence-free survival (64.0 months vs 140.0 months, P = 0.002) and overall survival (96.0 months vs 143.0 months, P = 0.005), and did not vary between patients exceeding criteria due to tumor explant greater than 5 cm, more than 3 tumor foci, or a tumor greater than 3 cm in the setting of multifocality. Discordance was independently associated with an increasing serum alpha fetal protein level (odds ratio, 2.82; 95% confidence interval, 1.37-5.79; P = 0.005). CONCLUSIONS Underestimating HCC burden before liver transplant remains frequent despite contemporary imaging technologies. Patients with an increasing alpha fetal protein before transplantation may benefit from more frequent testing or novel neoadjuvant therapies.
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Ferre-Aracil C, Lledó JL, Aguilera L, Garcia-Paredes A, Rodríguez-Santiago E, Graus J, García-González M, Nuño J, López-Buenadicha A, López-Hervás P, Rodríguez-Gandía M, Gea F, Albillos A. Current allocation policy is favorable for patients with hepatocellular carcinoma waiting for liver transplantation. Dig Liver Dis 2018; 50:1345-1350. [PMID: 29807872 DOI: 10.1016/j.dld.2018.04.024] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2017] [Revised: 03/04/2018] [Accepted: 04/23/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Patients with hepatocellular carcinoma (HCC) are a growing population of the transplantation waiting list (WL) for orthotopic liver transplantation (OLT). There is no consensus to prioritize these patients while on the WL. AIMS To assess whether patients with HCC were more prioritized than non-HCC patients based on their WL survival as primary outcome. METHODS Restrospective cohort study including patients listed for elective OLT from January 2013 to January 2016. RESULTS 165 patients with cirrhosis were listed for OLT: 64 in the HCC group (38.78%) and 101 in the non-HCC group (61.22%). Outcomes (HCC vs. non-HCC) were: OLT in 75.51% vs. 64.37%; death or dropout due to worsening in 20.41% vs. 27.59%, and delisting because of improvement in 4.08% vs. 8.05%. HCC patients had a significantly higher WL survival rate (HR = 0.45; 95% CI: 0.21-0.96); lower MELD score at transplantation (21 [20-24] vs. 24 [20-30]; p = 0.021); higher delta-MELD - the difference between MELD at transplantation and MELD at listing time - (3 [2-6] vs. 0 [0-5]; p = 0.024) and longer waiting time until OLT (143 [70-233] vs. 67 [21-164] days; p = 0.008). CONCLUSION Despite having to wait longer, patients with HCC showed higher WL survival than non-HCC patients.
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Affiliation(s)
- Carlos Ferre-Aracil
- Departments of Gastroenterology and General Surgery, Liver Transplantation Unit, Hospital Universitario Ramón y Cajal, IRYCIS, CIBERHD-Instituto de Salud Carlos III, Universidad de Alcalá, Madrid, Spain
| | - José-Luis Lledó
- Departments of Gastroenterology and General Surgery, Liver Transplantation Unit, Hospital Universitario Ramón y Cajal, IRYCIS, CIBERHD-Instituto de Salud Carlos III, Universidad de Alcalá, Madrid, Spain
| | - Lara Aguilera
- Departments of Gastroenterology and General Surgery, Liver Transplantation Unit, Hospital Universitario Ramón y Cajal, IRYCIS, CIBERHD-Instituto de Salud Carlos III, Universidad de Alcalá, Madrid, Spain
| | - Ana Garcia-Paredes
- Departments of Gastroenterology and General Surgery, Liver Transplantation Unit, Hospital Universitario Ramón y Cajal, IRYCIS, CIBERHD-Instituto de Salud Carlos III, Universidad de Alcalá, Madrid, Spain
| | - Enrique Rodríguez-Santiago
- Departments of Gastroenterology and General Surgery, Liver Transplantation Unit, Hospital Universitario Ramón y Cajal, IRYCIS, CIBERHD-Instituto de Salud Carlos III, Universidad de Alcalá, Madrid, Spain
| | - Javier Graus
- Departments of Gastroenterology and General Surgery, Liver Transplantation Unit, Hospital Universitario Ramón y Cajal, IRYCIS, CIBERHD-Instituto de Salud Carlos III, Universidad de Alcalá, Madrid, Spain
| | - Miguel García-González
- Departments of Gastroenterology and General Surgery, Liver Transplantation Unit, Hospital Universitario Ramón y Cajal, IRYCIS, CIBERHD-Instituto de Salud Carlos III, Universidad de Alcalá, Madrid, Spain
| | - Javier Nuño
- Departments of Gastroenterology and General Surgery, Liver Transplantation Unit, Hospital Universitario Ramón y Cajal, IRYCIS, CIBERHD-Instituto de Salud Carlos III, Universidad de Alcalá, Madrid, Spain
| | - Adolfo López-Buenadicha
- Departments of Gastroenterology and General Surgery, Liver Transplantation Unit, Hospital Universitario Ramón y Cajal, IRYCIS, CIBERHD-Instituto de Salud Carlos III, Universidad de Alcalá, Madrid, Spain
| | - Pedro López-Hervás
- Departments of Gastroenterology and General Surgery, Liver Transplantation Unit, Hospital Universitario Ramón y Cajal, IRYCIS, CIBERHD-Instituto de Salud Carlos III, Universidad de Alcalá, Madrid, Spain
| | - Miguel Rodríguez-Gandía
- Departments of Gastroenterology and General Surgery, Liver Transplantation Unit, Hospital Universitario Ramón y Cajal, IRYCIS, CIBERHD-Instituto de Salud Carlos III, Universidad de Alcalá, Madrid, Spain
| | - Francisco Gea
- Departments of Gastroenterology and General Surgery, Liver Transplantation Unit, Hospital Universitario Ramón y Cajal, IRYCIS, CIBERHD-Instituto de Salud Carlos III, Universidad de Alcalá, Madrid, Spain
| | - Agustín Albillos
- Departments of Gastroenterology and General Surgery, Liver Transplantation Unit, Hospital Universitario Ramón y Cajal, IRYCIS, CIBERHD-Instituto de Salud Carlos III, Universidad de Alcalá, Madrid, Spain.
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Lai Q, Vitale A. Transplantation for hepatocellular cancer: pushing to the limits? Transl Gastroenterol Hepatol 2018; 3:61. [PMID: 30363754 PMCID: PMC6182031 DOI: 10.21037/tgh.2018.09.07] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2018] [Accepted: 09/04/2018] [Indexed: 12/12/2022] Open
Abstract
Milan criteria (MC) represents the cornerstone in the selection of patients with hepatocellular cancer (HCC) waiting for liver transplantation (LT). MC represent the precursor of the scores based on the idea of "utility": in other terms, the scoring systems typically used in the field of LT oncology present the exclusive aim of selecting the cases with the best post-LT outcomes. However, some other scores have been proposed specifically investigating the risk of death or tumour progression during the waiting list. In this case, the selection process is connected with the idea of "priority": patients at higher risk for drop-out (DO) should be selected, prioritising them or, conversely, deciding to de-list them due to the high risk of post-LT futile transplant. Lastly, models based on the concept of "benefit", namely the balancing between priority and utility, have been recently created. The present review aims to examine these three different types of scoring systems, trying to underline their pro and cons in the allocation process of HCC patients.
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Affiliation(s)
- Quirino Lai
- General Surgery and Organ Transplantation Unit, Department of Surgery, Sapienza University of Rome, Rome, Italy
| | - Alessandro Vitale
- Department of Surgery, Oncology and Gastroenterology, Padua University, Padua, Italy
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Lee HA, Cho EY, Kim TH, Lee Y, Suh SJ, Jung YK, Kim JH, An H, Seo YS, Kim DS, Yim HJ, Yeon JE, Byun KS, Um SH. Risk Factors for Dropout From the Liver Transplant Waiting List of Hepatocellular Carcinoma Patients Under Locoregional Treatment. Transplant Proc 2018; 50:3521-3526. [PMID: 30577230 DOI: 10.1016/j.transproceed.2018.08.021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2018] [Accepted: 08/29/2018] [Indexed: 12/23/2022]
Abstract
BACKGROUND In new organ allocation policy, patients with hepatocellular carcinoma (HCC) experience a 6-month delay in being granted Model for End-Stage Liver Disease exception points. However, it may not be fair for patients at risk of early progression of HCC. METHODS All patients who were diagnosed as United Network for Organ Sharing (UNOS) stage 1 or 2 of HCC between January 2004 and December 2012 were included. Patients who received surgical resection or liver transplant (LT) as a primary treatment and who did not receive any treatment for HCC were excluded. Patients with baseline Model for End-Stage Liver Disease score ≥22 were also excluded because they have a higher chance of receiving LT. Patients who developed extrahepatic progression within 1 year were considered as high-risk for early recurrence after LT. RESULTS A total of 586 patients were included. Mean (SD) age was 59.9 (10.3) years and 409 patients (69.8%) were men. The cumulative incidence of estimated dropout was 8.9% at 6 months; size of the maximum nodule (≥3 cm) and nonachievement of complete response were independent factors. Extrahepatic progression developed in 16 patients (2.7%) within 1 year; size of the maximum nodule (4 cm) and alpha-fetoprotein level (>100 ng/mL) were independent predictors. CONCLUSIONS The estimated dropout rate from the waiting list within 6 months was 8.9%. Advantage points might be needed for patients with maximum nodule size ≥3 cm or those with noncomplete response. However, in patients with maximum nodule size ≥4 cm or alpha-fetoprotein level >100 ng/mL, caution is needed.
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Affiliation(s)
- H A Lee
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - E Y Cho
- Department of Biostatistics, Korea University College of Medicine, Seoul, Korea
| | - T H Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Y Lee
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - S J Suh
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Y K Jung
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - J H Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - H An
- Department of Biostatistics, Korea University College of Medicine, Seoul, Korea
| | - Y S Seo
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
| | - D-S Kim
- Department of Surgery, Korea University College of Medicine, Seoul, Korea
| | - H J Yim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
| | - J E Yeon
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - K S Byun
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - S H Um
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
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Peng L, Yuan XQ, Zhang CY, Peng JY, Zhang YQ, Pan X, Li GC. The emergence of long non-coding RNAs in hepatocellular carcinoma: an update. J Cancer 2018; 9:2549-2558. [PMID: 30026854 PMCID: PMC6036883 DOI: 10.7150/jca.24560] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2017] [Accepted: 03/31/2018] [Indexed: 12/11/2022] Open
Abstract
Hepatocellular carcinoma (HCC) accounting for roughly 90% of all primary liver neoplasms is the sixth most frequent neoplasm and the second prominent reason of tumor fatality worldwide. As regulators of diverse biological processes, long non-coding RNAs (lncRNAs) are involved in onset and development of neoplasms. With the continuous booming of well-featured lncRNAs in HCC from 2016 to now, we reviewed the newly-presented comprehension about the relationship between lncRNAs and HCC in this study. To be specific, we summarized the overview function and study tools of lncRNAs, elaborated the roles of lncRNAs in HCC, and sketched the molecule mechanisms of lncRNAs in HCC. In addition, the application of lncRNAs serving as biomarkers in early diagnosis and outcome prediction of HCC patients was highlighted.
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Affiliation(s)
- Li Peng
- Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha 410078, P.R. China; Cancer Research Institute, Central South University, Changsha 410078, P.R. China
- Guangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Research Center of Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, P.R. China
| | - Xiao-Qing Yuan
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
- Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China
| | - Chao-Yang Zhang
- Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha 410078, P.R. China; Cancer Research Institute, Central South University, Changsha 410078, P.R. China
| | - Jiang-Yun Peng
- Guangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Research Center of Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, P.R. China
| | - Ya-Qin Zhang
- Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha 410078, P.R. China; Cancer Research Institute, Central South University, Changsha 410078, P.R. China
| | - Xi Pan
- Department of Oncology, the third Xiangya Hospital, Central South University, Changsha 410013, P.R. China
| | - Guan-Cheng Li
- Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha 410078, P.R. China; Cancer Research Institute, Central South University, Changsha 410078, P.R. China
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Alferink LJM, Oey RC, Hansen BE, Polak WG, van Buuren HR, de Man RA, Schurink CAM, Metselaar HJ. The impact of infections on delisting patients from the liver transplantation waiting list. Transpl Int 2018; 30:807-816. [PMID: 28403563 DOI: 10.1111/tri.12965] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2017] [Revised: 03/15/2017] [Accepted: 04/06/2017] [Indexed: 12/14/2022]
Abstract
Approximately 20% of the patients listed for liver transplantation die before transplantation can be accomplished. Understanding risk factors for waiting list mortality may help to improve survival and organ allocation. Infections are very common in patients with cirrhosis and are associated with significant morbidity and mortality. This study analysed the frequency and characteristics of infections in patients awaiting liver transplantation, identified risk factors for withdrawal from the waiting list and evaluated the impact of infections on the clinical outcome. A retrospective analysis of consecutive patients listed for liver transplantation in Rotterdam, the Netherlands from 2007 to 2014 was conducted. Infections occurred in 144 of 327 studied patients (44%). In this cohort, 23.4% of the patients on the liver transplantation waiting list were delisted or died before transplantation. Patients with an infection were 5.2 times more likely to become delisted than noninfected patients. In the 30 days after the first infection, patients were 33.8 times more likely to become delisted compared to noninfected patients. High age, high MELD score, refractory ascites and inappropriate antibiotic therapy were independent predictors for delisting due to infection. Infections occur frequently in patients on the liver transplantation waiting list. Emphasis on appropriate and timely antimicrobial therapy is required.
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Affiliation(s)
- Louise J M Alferink
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Rosalie C Oey
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Bettina E Hansen
- Liver Centre, Toronto Western & General Hospital, University Health Network, Toronto, Canada
| | - Wojciech G Polak
- Division Transplant Surgery, Department of Surgery, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Henk R van Buuren
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Robert A de Man
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Carolina A M Schurink
- Department of Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.,Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Herold J Metselaar
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
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Croome KP, Lee DD, Pungpapong S, Keaveny AP, Taner CB. What are the outcomes of declining a public health service increased risk liver donor for patients on the liver transplant waiting list? Liver Transpl 2018; 24:497-504. [PMID: 29341398 DOI: 10.1002/lt.25009] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2017] [Accepted: 12/27/2017] [Indexed: 02/07/2023]
Abstract
The tragedy of the national opioid epidemic has resulted in a significant increase in the number of opioid-related deaths and accordingly an increase in the number of potential donors designated Public Health Service (PHS) increased risk. Previous studies have demonstrated reluctance to use these PHS organs, and as a result, higher discard rates for these organs have been observed. All patients listed for liver transplantation in the United States from January 2005 to December 2016 were investigated. Patients on the waiting list were divided into 2 groups: those in which a PHS liver was used for transplantation (accepted PHS group) and those in which a PHS liver was declined and transplanted into a recipient lower on the match run (declined PHS group). Intention-to-treat patient survival from the time of PHS offer was significantly higher in the accepted PHS compared with the declined PHS group (P < 0.001). On Cox multivariate regression, declining a PHS donor liver was associated with a hazard ratio of 2.36 (95% confidence interval, 2.23-2.49; P < 0.001). For patients in which a PHS organ offer was declined, 11.6% died or were delisted for being too sick within the subsequent year. Donor liver allografts implanted in the accepted PHS group were of a lower donor risk index (1.28 versus 1.44) compared with the non-PHS organs that patients in the declined PHS group ultimately received if they underwent transplantation. In conclusion, there is a significantly higher survival for patients in which a PHS liver is accepted and used compared with those patients in which a PHS organ is declined. These data will help inform decisions about whether or not to accept a PHS donor liver for both patients and transplant professionals. Liver Transplantation 24 497-504 2018 AASLD.
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Affiliation(s)
| | - David D Lee
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
| | | | | | - C Burcin Taner
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
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de Haas RJ, Lim C, Bhangui P, Salloum C, Compagnon P, Feray C, Calderaro J, Luciani A, Azoulay D. Curative salvage liver transplantation in patients with cirrhosis and hepatocellular carcinoma: An intention-to-treat analysis. Hepatology 2018; 67:204-215. [PMID: 28806477 DOI: 10.1002/hep.29468] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2017] [Revised: 07/24/2017] [Accepted: 08/06/2017] [Indexed: 12/07/2022]
Abstract
UNLABELLED The salvage liver transplantation (SLT) strategy was conceived for initially resectable and transplantable (R&T) hepatocellular carcinoma (HCC) patients, to try to obviate upfront liver transplantation, with the "safety net" of SLT in case of postresection recurrence. The SLT strategy is successful or curative when patients are recurrence free following primary resection alone, or after SLT for recurrence. The aim of the current study was to determine the SLT strategy's potential for cure in R&T HCC patients, and to identify predictors for its success. From 1994 to 2012, all R&T HCC patients with cirrhosis were enrolled in the SLT strategy. An intention-to-treat (ITT) analysis was used to determine this strategy's outcomes and predictors of success according to the above definition. In total, 110 patients were enrolled in the SLT strategy. Sixty-three patients (57%) had tumor recurrence after initial resection, and in 30 patients SLT could be performed (recurrence transplantability rate = 48%). From the time of initial resection, ITT 5-year overall and disease-free survival rates were 69% and 60%, respectively. The SLT strategy was successful in 60 patients (56%), either by resection alone (36%), or by SLT for recurrence (19%). Preresection predictors of successful SLT strategy at multivariate analysis included Model for End-Stage Liver Disease (MELD) score >10, and absence of neoadjuvant transarterial chemoembolization (TACE). Additional postresection predictive factors were absence of postresection morbidity, and T-stage 1-2 at the resection specimen. CONCLUSION The SLT strategy is curative in only 56% of cases. Higher MELD score at inception of the strategy and no pre-resection TACE are predictors of successful SLT strategy. (Hepatology 2018;67:204-215).
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Affiliation(s)
- Robbert J de Haas
- Medical Imaging Department, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris-Université Paris-Est, Créteil, France.,Department of Radiology, Medical Imaging Center Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Chetana Lim
- Department of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris-Université Paris-Est, Créteil, France
| | - Prashant Bhangui
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, New Delhi, India
| | - Chady Salloum
- Department of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris-Université Paris-Est, Créteil, France
| | - Philippe Compagnon
- Department of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris-Université Paris-Est, Créteil, France.,Unit 955 INSERM, Créteil, France
| | - Cyrille Feray
- Unit 955 INSERM, Créteil, France.,Department of Hepatology, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris-Université Paris-Est, Créteil, France
| | - Julien Calderaro
- Department of Pathology, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris-Université Paris-Est, Créteil, France
| | - Alain Luciani
- Medical Imaging Department, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris-Université Paris-Est, Créteil, France.,Unit 955 INSERM, Créteil, France
| | - Daniel Azoulay
- Department of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris-Université Paris-Est, Créteil, France.,Unit 955 INSERM, Créteil, France
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48
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Guerrini GP, Pinelli D, Marini E, Corno V, Guizzetti M, Zambelli M, Aluffi A, Lincini L, Fagiuoli S, Lucianetti A, Colledan M. Value of HCC-MELD Score in Patients With Hepatocellular Carcinoma Undergoing Liver Transplantation. Prog Transplant 2017; 28:63-69. [PMID: 29251164 DOI: 10.1177/1526924817746686] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
CONTEXT Liver transplantation (LT) is considered the ideal therapy for patients with hepatocellular carcinoma (HCC) having cirrhosis but the shortage of liver donors and the risk of dropout from the wait list due to tumor progression severely limit transplantation. A new prognostic score, the HCC-model for end-stage liver disease (HCC-MELD), was developed by combining α-fetoprotein (AFP), MELD, and tumor size, to improve risk stratification of dropout in patients with HCC. OBJECTIVES In this study, we investigated the ability of the HCC-MELD score in predicting the posttransplant for patients fulfilling Milan criteria (MC). DESIGN Two hundred patients with stage II tumor were retrospectively reviewed from a total of 1290 transplants performed at our institution from October 1997 through April 2015. Cox regression analysis was performed to identify the prognostic factors impacting the posttransplant survival. RESULTS Overall survival at 1, 5, and 10 years was 89.3%, 71.1%, and 67.2%, whereas disease-free survival was 86.4%, 66.5%, and 52.4%, respectively. Multivariate analysis showed HCC-MELD score (hazard ratio [HR] 39.6, P < .001) and microvascular invasion (HR 2.41, P = .002) to be independent risk factors for recurrence, whereas HCC diameter (HR 1.15, P = .041), HCC-MELD (HR 15.611, P = .006), and grading (HR 2.17, P = .03) proved to be predictive factors of poor overall survival. CONCLUSION Our study showed the validity of the HCC-MELD equation in the evaluation of patients undergoing LT for HCC. This score offers a reliable method to assess the risk of waiting list dropout and predict posttransplantation outcomes.
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Affiliation(s)
- Gian Piero Guerrini
- 1 General and oncological surgery Unit, Department of Surgical Oncology, National Cancer institute, Centro di Riferimento Oncologico IRCCS, Aviano, Italy
| | - Domenico Pinelli
- 2 Department of Surgery, General surgery and Abdominal Transplant unit, "Papa Giovanni XXIII" Hospital, Bergamo, Italy
| | - Elena Marini
- 2 Department of Surgery, General surgery and Abdominal Transplant unit, "Papa Giovanni XXIII" Hospital, Bergamo, Italy
| | - Vittorio Corno
- 2 Department of Surgery, General surgery and Abdominal Transplant unit, "Papa Giovanni XXIII" Hospital, Bergamo, Italy
| | - Michela Guizzetti
- 2 Department of Surgery, General surgery and Abdominal Transplant unit, "Papa Giovanni XXIII" Hospital, Bergamo, Italy
| | - Marco Zambelli
- 2 Department of Surgery, General surgery and Abdominal Transplant unit, "Papa Giovanni XXIII" Hospital, Bergamo, Italy
| | - Alessandro Aluffi
- 2 Department of Surgery, General surgery and Abdominal Transplant unit, "Papa Giovanni XXIII" Hospital, Bergamo, Italy
| | - Lisa Lincini
- 3 Pathology Unit, "Papa Giovanni XXIII" Hospital, Bergamo, Italy
| | - Stefano Fagiuoli
- 4 Gastroenterology and Transplant Hepatology, "Papa Giovanni XXIII" Hospital, Bergamo, Italy
| | - Alessandro Lucianetti
- 2 Department of Surgery, General surgery and Abdominal Transplant unit, "Papa Giovanni XXIII" Hospital, Bergamo, Italy
| | - Michele Colledan
- 2 Department of Surgery, General surgery and Abdominal Transplant unit, "Papa Giovanni XXIII" Hospital, Bergamo, Italy
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49
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Henson JB, Patel YA, Wilder JM, Zheng J, Chow SC, King LY, Muir AJ. Differences in Phenotypes and Liver Transplantation Outcomes by Age Group in Patients with Primary Sclerosing Cholangitis. Dig Dis Sci 2017; 62:3200-3209. [PMID: 28391417 PMCID: PMC5861350 DOI: 10.1007/s10620-017-4559-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2017] [Accepted: 03/28/2017] [Indexed: 12/20/2022]
Abstract
BACKGROUND There is increasing evidence for a heterogeneity of phenotypes in primary sclerosing cholangitis (PSC), but differences across the age spectrum in adults with PSC have not been well characterized. AIMS To characterize phenotypic variations and liver transplantation outcomes by age group in adults with PSC. METHODS The United Network for Organ Sharing database was used to identify waitlist registrations for primary liver transplantation in adults with PSC. Patients were split into three age groups: 18-39 (young), 40-59 (middle-aged), and ≥60 (older). Their clinical characteristics and outcomes on the waitlist and post-transplant were compared. RESULTS Overall, 8272 adults with PSC were listed for liver transplantation during the study period, of which 28.9% were young, 52.0% were middle-aged, and 19.1% were older. The young age group had the greatest male predominance (70.0 vs. 66.2 vs. 65.1%, p = 0.001), the highest proportion of black individuals (20.0 vs. 11.0 vs. 5.5%, p < 0.001), and the most patients listed with concomitant autoimmune hepatitis (2.2 vs. 1.0 vs. 0.8%, p < 0.001). Older patients experienced the greatest waitlist and post-transplant mortality. Graft survival was greatest in the middle-aged group. Young patients were most likely to experience acute rejection (31 vs. 22.8 vs. 18.0%, p < 0.001) and have graft failure due to chronic rejection or PSC recurrence (47.8 vs. 42.3 vs. 17.9%, p < 0.001). CONCLUSIONS Age-related differences exist among adults with PSC and are associated with outcomes pre- and post-transplant. Young patients may have a more robust immune-related phenotype that is associated with poorer graft survival. Future studies are needed to further investigate these findings.
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Affiliation(s)
| | - Yuval A Patel
- Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA
| | - Julius M Wilder
- Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA
- Duke Clinical Research Institute, Durham, NC, USA
| | - Jiayin Zheng
- Department of Biostatistics, Duke University School of Medicine, Durham, NC, USA
| | - Shein-Chung Chow
- Department of Biostatistics, Duke University School of Medicine, Durham, NC, USA
- Duke Clinical Research Institute, Durham, NC, USA
| | - Lindsay Y King
- Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA
| | - Andrew J Muir
- Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
- Duke Clinical Research Institute, Durham, NC, USA.
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50
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Croome KP, Lee DD, Nguyen JH, Keaveny AP, Taner CB. Waitlist Outcomes for Patients Relisted Following Failed Donation After Cardiac Death Liver Transplant: Implications for Awarding Model for End-Stage Liver Disease Exception Scores. Am J Transplant 2017; 17:2420-2427. [PMID: 28556380 DOI: 10.1111/ajt.14383] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2017] [Revised: 05/04/2017] [Accepted: 05/11/2017] [Indexed: 01/25/2023]
Abstract
Understanding of outcomes for patients relisted for ischemic cholangiopathy following a donation after cardiac death (DCD) liver transplant (LT) will help standardization of a Model for End-Stage Liver Disease exception scheme for retransplantation. Early relisting (E-RL) for DCD graft failure caused by primary nonfunction (PNF) or hepatic artery thrombosis (HAT) was defined as relisting ≤14 days after DCD LT, and late relisting (L-RL) due to biliary complications was defined as relisting 14 days to 3 years after DCD LT. Of 3908 DCD LTs performed nationally between 2002 and 2016, 540 (13.8%) patients were relisted within 3 years of transplant (168 [4.3%] in the E-RL group, 372 [9.5%] in the L-RL group). The E-RL and L-RL groups had waitlist mortality rates of 15.4% and 10.5%, respectively, at 3 mo and 16.1% and 14.3%, respectively, at 1 year. Waitlist mortality in the L-RL group was higher than mortality and delisted rates for patients with exception points for both hepatocellular carcinoma (HCC) and hepatopulmonary syndrome (HPS) at 3- to 12-mo time points (p < 0.001). Waitlist outcomes differed in patients with early DCD graft failure caused by PNF or HAT compared with those with late DCD graft failure attributed to biliary complications. In L-RL, higher rates of waitlist mortality were noted compared with patients listed with exception points for HCC or HPS.
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Affiliation(s)
- K P Croome
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
| | - D D Lee
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
| | - J H Nguyen
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
| | - A P Keaveny
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
| | - C B Taner
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
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