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Sommier L, Lim C, Jeune F, Goumard C, Turco C, Salloum C, Llado L, Savier E, Perdigao F, Rousseau G, Ramos E, Lopez-Dominguez J, Cachero A, Toubert C, Roucaute S, Al Taweel B, Georges P, Poppen T, Lioret P, Herrero A, Navarro F, Heyd B, Soubrane O, Azoulay D, Scatton O. European validation of the classification for the anticipated difficulty of liver transplantation. HPB (Oxford) 2024; 26:1033-1039. [PMID: 38806366 DOI: 10.1016/j.hpb.2024.05.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 05/03/2024] [Accepted: 05/11/2024] [Indexed: 05/30/2024]
Abstract
BACKGROUND Appropriate risk stratification for the difficulty of liver transplantation (LT) is essential to guide the selection and acceptance of grafts and avoid morbidity and mortality. METHODS Based on 987 LTs collected from 5 centers, perioperative outcomes were analyzed across the 3 difficulty levels. Each LT was retrospectively scored from 0 to 10. Scores of 0-2, 3-5 and 6-10 were then translated into respective difficulty levels: low, moderate and high. Complications were reported according to the comprehensive complication index (CCI). RESULTS The difficulty level of LT in 524 (53%), 323 (32%), and 140 (14%) patients was classified as low, moderate and high, respectively. The values of major intraoperative outcomes, such as cold ischemia time (p = 0.04) and operative time (p < 0.0001) increased gradually with statistically significant values among difficulty levels. There was a corresponding increase in CCI (p = 0.04), severe complication rates (p = 0.05) and length of ICU (p = 0.01) and hospital (p = 0.004) stays across the different difficulty levels. CONCLUSION The LT difficulty classification has been validated.
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Affiliation(s)
- Lazare Sommier
- Department of Digestive, Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP Pitié-Salpêtrière Hospital, Paris, France; Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, Montpellier University Hospital, Montpellier, France
| | - Chetana Lim
- Department of Digestive, Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP Pitié-Salpêtrière Hospital, Paris, France; Research Unit, Université de Picardie-Jules Verne, UR UPJV 7518 SSPC, Amiens, France; Sorbonne Université, Paris, France
| | - Florence Jeune
- Department of Digestive, Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP Pitié-Salpêtrière Hospital, Paris, France
| | - Claire Goumard
- Department of Digestive, Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP Pitié-Salpêtrière Hospital, Paris, France; Sorbonne Université, Paris, France; Centre de Recherche de Saint-Antoine (CRSA), INSERM, UMRS-938, Paris, France
| | - Célia Turco
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, Besançon University Hospital, Besancon, France
| | - Chady Salloum
- Centre Hépato-Biliaire, Hôpital Universitaire Paul Brousse, Université Paris-Saclay, Villejuif, France
| | - Laura Llado
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, Hospital Universitari de Bellvitge, IDIBELL, Barcelona, Spain
| | - Eric Savier
- Department of Digestive, Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP Pitié-Salpêtrière Hospital, Paris, France; Sorbonne Université, Paris, France
| | - Fabiano Perdigao
- Department of Digestive, Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP Pitié-Salpêtrière Hospital, Paris, France
| | - Géraldine Rousseau
- Department of Digestive, Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP Pitié-Salpêtrière Hospital, Paris, France
| | - Emilio Ramos
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, Hospital Universitari de Bellvitge, IDIBELL, Barcelona, Spain
| | - Josefina Lopez-Dominguez
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, Hospital Universitari de Bellvitge, IDIBELL, Barcelona, Spain
| | - Alba Cachero
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, Hospital Universitari de Bellvitge, IDIBELL, Barcelona, Spain
| | - Cyprien Toubert
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, Montpellier University Hospital, Montpellier, France
| | - Simon Roucaute
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, Montpellier University Hospital, Montpellier, France
| | - Bader Al Taweel
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, Montpellier University Hospital, Montpellier, France
| | - Pauline Georges
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, Besançon University Hospital, Besancon, France
| | - Théo Poppen
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, Besançon University Hospital, Besancon, France
| | - Perrine Lioret
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, Besançon University Hospital, Besancon, France
| | - Astrid Herrero
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, Montpellier University Hospital, Montpellier, France
| | - Francis Navarro
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, Montpellier University Hospital, Montpellier, France
| | - Bruno Heyd
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, Besançon University Hospital, Besancon, France
| | - Olivier Soubrane
- Department of Digestive, Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP Pitié-Salpêtrière Hospital, Paris, France; Department of Digestive Surgery, Institut Mutualiste Montsouris, Paris, France
| | - Daniel Azoulay
- Centre Hépato-Biliaire, Hôpital Universitaire Paul Brousse, Université Paris-Saclay, Villejuif, France
| | - Olivier Scatton
- Department of Digestive, Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP Pitié-Salpêtrière Hospital, Paris, France; Sorbonne Université, Paris, France; Centre de Recherche de Saint-Antoine (CRSA), INSERM, UMRS-938, Paris, France.
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Arvind A, Seif El Dahan K, Malhotra R, Daher D, Rich NE, Patel MS, VanWagner LB, Lieber SR, Cotter TG, Louissaint J, Mufti AR, Kulik L, Pillai A, Parikh ND, Singal AG. Association between bridging therapy and posttransplant outcomes in patients with HCC within Milan criteria: A systematic review and meta-analysis. Liver Transpl 2024; 30:595-606. [PMID: 38466889 DOI: 10.1097/lvt.0000000000000357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Accepted: 01/15/2024] [Indexed: 03/13/2024]
Abstract
Liver transplantation is the curative therapy of choice for patients with early-stage HCC. Locoregional therapies are often employed as a bridge to reduce the risk of waitlist dropout; however, their association with posttransplant outcomes is unclear. We conducted a systematic review using Ovid MEDLINE and EMBASE to identify studies published between database inception and August 2, 2023, which reported posttransplant recurrence-free survival and overall survival among patients transplanted for HCC within Milan criteria, stratified by receipt of bridging therapy. Pooled HRs were calculated for each outcome using the DerSimonian and Laird method for a random-effects model. We identified 38 studies, including 19,671 patients who received and 20,148 patients who did not receive bridging therapy. Bridging therapy was not associated with significant differences in recurrence-free survival (pooled HR: 0.91, 95% CI: 0.77-1.08; I2 =39%) or overall survival (pooled HR: 1.09, 95% CI: 0.95-1.24; I2 =47%). Results were relatively consistent across subgroups, including geographic location and study period. Studies were discordant regarding the differential strength of association by pretreatment tumor burden and pathologic response, but potential benefits of locoregional therapy were mitigated in those who received 3 or more treatments. Adverse events were reported in a minority of studies, but when reported occurred in 6%-15% of the patients. Few studies reported loss to follow-up and most had a risk of residual confounding. Bridging therapy is not associated with improvements in posttransplant recurrence-free or overall survival among patients with HCC within Milan criteria. The risk-benefit ratio of bridging therapy likely differs based on the risk of waitlist dropout.
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Affiliation(s)
- Ashwini Arvind
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Karim Seif El Dahan
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Riya Malhotra
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Darine Daher
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Nicole E Rich
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Madhukar S Patel
- Department of Surgery, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Lisa B VanWagner
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Sarah R Lieber
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Thomas G Cotter
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Jeremy Louissaint
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Arjmand R Mufti
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Laura Kulik
- Department of Internal Medicine, Northwestern Medicine, Chicago, Illinois, USA
| | - Anjana Pillai
- Department of Internal Medicine, University of Chicago, Chicago, Illinois, USA
| | - Neehar D Parikh
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Amit G Singal
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA
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Cesario S, Genovesi V, Salani F, Vasile E, Fornaro L, Vivaldi C, Masi G. Evolving Landscape in Liver Transplantation for Hepatocellular Carcinoma: From Stage Migration to Immunotherapy Revolution. Life (Basel) 2023; 13:1562. [PMID: 37511937 PMCID: PMC10382048 DOI: 10.3390/life13071562] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 06/30/2023] [Accepted: 07/10/2023] [Indexed: 07/30/2023] Open
Abstract
Liver transplantation (LT) represents the primary curative option for HCC. Despite the extension of transplantation criteria and conversion with down-staging loco-regional treatments, transplantation is not always possible. The introduction of new standards of care in advanced HCC including a combination of immune checkpoint inhibitor-based therapies led to an improvement in response rates and could represent a promising strategy for down-staging the tumor burden. In this review, we identify reports and series, comprising a total of 43 patients who received immune checkpoint inhibitors as bridging or down-staging therapies prior to LT. Overall, treated patients registered an objective response rate of 21%, and 14 patients were reduced within the Milan criteria. Graft rejection was reported in seven patients, resulting in the death of four patients; in the remaining cases, LT was performed safely after immunotherapy. Further investigations are required to define the duration of immune checkpoint inhibitors, their minimum washout period and the LT long-term safety of this strategy. Some randomized clinical trials including immunotherapy combinations, loco-regional treatment and/or tyrosine kinase inhibitors are ongoing and will likely determine the appropriateness of immune checkpoint inhibitors' administration before LT.
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Affiliation(s)
- Silvia Cesario
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, 56126 Pisa, Italy
| | - Virginia Genovesi
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, 56126 Pisa, Italy
| | - Francesca Salani
- Institute of Interdisciplinary Research "Health Science", Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, 56124 Pisa, Italy
| | - Enrico Vasile
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, 56126 Pisa, Italy
| | - Lorenzo Fornaro
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, 56126 Pisa, Italy
| | - Caterina Vivaldi
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, 56126 Pisa, Italy
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy
| | - Gianluca Masi
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, 56126 Pisa, Italy
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy
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Number of Local Regional Therapies for Hepatocellular Carcinoma and Peri-Operative Outcomes after Liver Transplantation. Cancers (Basel) 2023; 15:cancers15030620. [PMID: 36765576 PMCID: PMC9913666 DOI: 10.3390/cancers15030620] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Revised: 01/12/2023] [Accepted: 01/17/2023] [Indexed: 01/20/2023] Open
Abstract
The wait times for patients with hepatocellular carcinoma (HCC) listed for liver transplant are longer than ever, which has led to an increased reliance on the use of pre-operative LRTs. The impact that multiple rounds of LRTs have on peri-operative outcomes following transplant is unknown. This was a retrospective single center analysis of 298 consecutive patients with HCC who underwent liver transplant (January 2017 to May 2021). The data was obtained from two institution-specific databases and the TransQIP database. Of the 298 patients, 27 (9.1%) underwent no LRTs, 156 (52.4%) underwent 1-2 LRTs, and 115 (38.6%) underwent ≥3 LRTs prior to LT. The patients with ≥3 LRTs had a significantly higher rate of bile leak compared to patients who received 1-2 LRTs (7.0 vs. 1.3%, p = 0.014). Unadjusted and adjusted regression analyses demonstrated a significant association between the total number of LRTs administered and bile leak, but not rates of overall biliary complications. The total number of LRTs was not significantly associated with any other peri-operative or post-operative outcome measure. These findings support the aggressive use of LRTs to control HCC in patients awaiting liver transplant, with further evaluation needed to confirm the biliary leak findings.
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Role of Pretransplant Treatments for Patients with Hepatocellular Carcinoma Waiting for Liver Transplantation. Cancers (Basel) 2022; 14:cancers14020396. [PMID: 35053558 PMCID: PMC8773674 DOI: 10.3390/cancers14020396] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 01/09/2022] [Accepted: 01/12/2022] [Indexed: 02/01/2023] Open
Abstract
Simple Summary Hepatocellular carcinoma (HCC) is the fifth most common cancer in men worldwide and the second leading cause of cancer death. Liver transplantation (LT) is one of the treatment options for patients with HCC. Recently, there have been many reports of the usefulness of locoregional therapy, such as transarterial chemoembolization and radiofrequency ablation, for HCC as pretreatment before LT. In Western countries, locoregional therapy is used to bridge until transplantation to prevent drop-outs from the waiting list or for downstaging to treat patients with advanced HCC who initially exceed the criteria for LT. With the progress of locoregional therapy, new reports on the effects of bridging and downstaging locoregional therapy as pretransplant treatment are increasing in number. Abstract Recently, there have been many reports of the usefulness of locoregional therapy such as transarterial chemoembolization and radiofrequency ablation for hepatocellular carcinoma (HCC) as pretreatment before liver transplantation (LT). Locoregional therapy is performed with curative intent in Japan, where living donor LT constitutes the majority of LT due to the critical shortage of deceased donors. However, in Western countries, where deceased donor LT is the main procedure, LT is indicated for early-stage HCC regardless of liver functional reserve, and locoregional therapy is used for bridging until transplantation to prevent drop-outs from the waiting list or for downstaging to treat patients with advanced HCC who initially exceed the criteria for LT. There are many reports of the effect of bridging and downstaging locoregional therapy before LT, and its indications and efficacy are becoming clear. Responses to locoregional therapy, such as changes in tumor markers, the avidity of FDG-PET, etc., are considered useful for successful bridging and downstaging. In this review, the effects of bridging and downstaging locoregional therapy as a pretransplant treatment on the results of transplantation are clarified, focusing on recent reports.
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Xu L, Chen L, Zhang W. Neoadjuvant treatment strategies for hepatocellular carcinoma. World J Gastrointest Surg 2021; 13:1550-1566. [PMID: 35070063 PMCID: PMC8727178 DOI: 10.4240/wjgs.v13.i12.1550] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 06/27/2021] [Accepted: 11/30/2021] [Indexed: 02/06/2023] Open
Abstract
The incidence of hepatocellular carcinoma (HCC) remains high globally. Surgical treatment is the best treatment for improving the prognosis of patients with HCC. Neoadjuvant therapy plays a key role in preventing tumor progression and even downstaging HCC. The liver transplantation rate and resectability rate have increased for neoadjuvant therapy. Neoadjuvant therapy is effective in different stages of HCC. In this review, we summarized the definition, methods, effects, indications and contraindications of neoadjuvant therapy in HCC, which have significance for guiding treatment.
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Affiliation(s)
- Lei Xu
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Lin Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Wei Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
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