52 results on '"Dumortier, J"'
Search Results
2. Evaluation of a delayed liver transplantation strategy for patients with HCC receiving bridging therapy: the DELTA-HCC study.
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Lamarque C, Segaux L, Bachellier P, Buchard B, Chermak F, Conti F, Decaens T, Dharancy S, Di Martino V, Dumortier J, Francoz-Caudron C, Gugenheim J, Hardwigsen J, Muscari F, Radenne S, Salamé E, Uguen T, Ursic-Bedoya J, Antoine C, Deshayes A, Jacquelinet C, Natella PA, Leroy V, Cherqui D, Oubaya N, and Duvoux C
- Subjects
- Humans, Male, Female, Middle Aged, France epidemiology, Aged, Neoplasm Recurrence, Local epidemiology, Survival Rate, Time-to-Treatment statistics & numerical data, Time Factors, Retrospective Studies, Liver Transplantation methods, Liver Transplantation statistics & numerical data, Carcinoma, Hepatocellular surgery, Carcinoma, Hepatocellular mortality, Liver Neoplasms surgery, Liver Neoplasms mortality, Waiting Lists mortality
- Abstract
Background & Aims: To maximize utility and prevent premature liver transplantation (LT), a delayed LT strategy (DS) was adopted in France in 2015 in patients listed for any single HCC treated with resection or thermal ablation during the waiting phase. The DS involves postponing LT until recurrence. The purpose of this study was to evaluate the DS to make sure that it did not hamper pre- and post-LT outcomes., Methods: Patients listed for HCC in France between 2015 and 2018 were studied. After data extraction from the national LT database, 2,025 patients were identified and classified according to six groups: single tumor entering DS, single tumor not entering DS, multiple tumors, no curative treatment, untreatable HCC or T1 tumors. Kaplan-Meier estimates of the 18-month risk of dropout for death, too sick to be transplanted or tumor progression before LT, 5-year post-LT HCC recurrence and post-LT survival rates were compared., Results: Median waiting-time in the DS group was 910 days. Pre-LT dropout probability was significantly lower in the DS group compared to other groups (13% vs. 19%, p = 0.0043) and significantly higher in the T1 group (25.4%, p = 0.05). Post-LT HCC recurrence rate in the multiple nodules group was significantly higher (19.6%, p = 0.019), while 5-year post-LT survival did not differ among groups and was 74% in the DS group (p = 0.22)., Conclusion: The DELTA-HCC study shows that DS does not negatively impact either pre- nor post-LT patient outcomes, and has the potential to allow for redistribution of organs to patients in more urgent need of LT. It can reasonably be proposed and pursued. The unexpectedly high risk of dropout in T1 patients seems related to the MELD-based offering rules underserving this subgroup., Impacts and Implications: To maximize utility and prevent premature liver transplantation (LT), a delayed LT strategy was adopted in France in 2015. It involves postponing LT until recurrence in patients listed for any single HCC curatively treated by surgical resection or thermal ablation. The DELTA-HCC study was conducted to evaluate this nationwide strategy. It shows in a European LT program that delayed strategy does not negatively impact pre- nor post-LT patient outcomes and is relevant to up to 20% of LT candidates; thus, it could potentially enable the redistribution of organs to patients in more urgent need of LT. Such a delayed strategy can reasonably be pursued and extended to other LT programs. Of note, an unexpectedly high risk of dropout in T1 patients, seemingly related to MELD-based offering rules which underserve these patients, calls for further scrutinization and revision of allocation rules in this subgroup., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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3. Hepatocellular Cancer Surveillance in Patients with Advanced Chronic Liver Disease.
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Gu W, de Lédinghen V, Aubé C, Krag A, Strassburg C, Castéra L, Dumortier J, Friedrich-Rust M, Pol S, Grgurevic I, Zeleke Y, Praktiknjo M, Schierwagen R, Klein S, Francque S, Gottfriedová H, Sporea I, Schindler P, Rennebaum F, Brol MJ, Schulz M, Uschner FE, Fischer J, Margini C, Wang W, Delamarre A, Best J, Canbay A, Bauer DJM, Simbrunner B, Semmler G, Reiberger T, Boursier J, Rasmussen DN, Vilgrain V, Guibal A, Zeuzem S, Vassord C, Vonghia L, Šenkeříková R, Popescu A, Berzigotti A, Laleman W, Thiele M, Jansen C, and Trebicka J
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- Humans, Male, Female, Middle Aged, Aged, Algorithms, Risk Factors, Liver Diseases epidemiology, Liver Diseases diagnostic imaging, Liver Diseases diagnosis, Adult, Chronic Disease, Liver Neoplasms epidemiology, Liver Neoplasms diagnostic imaging, Liver Neoplasms diagnosis, Carcinoma, Hepatocellular epidemiology, Carcinoma, Hepatocellular diagnostic imaging, Carcinoma, Hepatocellular diagnosis, Elasticity Imaging Techniques
- Abstract
Background: Patients with advanced chronic liver disease (ACLD) are at high risk of developing hepatocellular carcinoma (HCC). Therefore, biannual surveillance is recommended. This large-scale multicenter study aimed to stratify the risk of HCC development in ACLD., Methods: From 3016 patients with ACLD screened in 17 European and Chinese centers, 2340 patients with liver stiffness measurement (LSM) determined using different techniques (two-dimensional shear-wave elastography [2D-SWE], transient elastography, and point shear-wave elastography) and with different disease severities were included. Cox regression was used to explore risk factors for HCC. We used these data to create an algorithm, named PLEASE, but referred to in this manuscript as "the algorithm"; the algorithm was validated in internal and two external cohorts across elastography techniques., Results: HCC developed in 127 (5.4%) patients during follow-up. LSM by 2D-SWE (hazard ratio: 2.28) was found to be associated with developing HCC, alongside age, sex, etiology, and platelet count (C-index: 0.8428). We thus established the algorithm with applicable cutoffs, assigning a maximum of six points: platelet count less than 150×10
9 /l, LSM greater than or equal to 15 kPa, age greater than or equal to 50 years, male sex, controlled/uncontrolled viral hepatitis, or presence of steatotic liver diseases. Within 2 years, with a median follow-up of 13.7 months, patients in the high-risk group (≥4 points) had an HCC incidence of 15.6% (95% confidence interval [CI], 12.1% to 18.7%) compared with the low-risk group, at 1.7% (95% CI, 0.9% to 2.5%)., Conclusions: Our algorithm stratified patients into two groups: those at higher risk of developing HCC and those at lower risk. Our data provide equipoise to test the prospective utility of the algorithm with respect to clinical decisions about screening patients with ACLD for incident HCC. (Funded by the German Research Foundation and others; ClinicalTrials.gov number, NCT03389152.).- Published
- 2024
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4. Combination of heterozygous APOB gene mutation with PNPLA3 and TM6SF2 variants promotes steatotic liver disease, cirrhosis and HCC development.
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Chouik Y, Di Filippo M, Radenne S, Dumortier J, Moulin P, and Levrero M
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- Humans, Fatty Liver genetics, Male, Female, Apolipoprotein B-100 genetics, Middle Aged, Acyltransferases, Phospholipases A2, Calcium-Independent, Membrane Proteins genetics, Carcinoma, Hepatocellular genetics, Lipase genetics, Liver Cirrhosis genetics, Liver Neoplasms genetics, Mutation, Heterozygote
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- 2024
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5. Massive peritoneal tumoral dissemination after hepatocellular carcinoma percutaneous microwave ablation with intraperitoneal CO 2 insufflation.
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L'Huillier R, Michoud C, Dumortier J, and Milot L
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- Humans, Radiofrequency Ablation adverse effects, Carbon Dioxide administration & dosage, Carcinoma, Hepatocellular surgery, Carcinoma, Hepatocellular pathology, Insufflation adverse effects, Liver Neoplasms surgery, Liver Neoplasms pathology, Microwaves therapeutic use, Peritoneal Neoplasms
- Abstract
Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest.
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- 2024
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6. Good outcome of liver transplantation in patients with pre-existing renal cell carcinoma.
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Lassailly G, Ningarhari M, Dumortier J, Lafforgue C, Bouye S, Amrani ME, Lebuffe G, Villers A, Truant S, Mathurin P, Louvet A, Boillot O, Boleslawski E, and Dharancy S
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- Humans, Treatment Outcome, Carcinoma, Renal Cell surgery, Liver Transplantation, Liver Neoplasms surgery, Kidney Neoplasms surgery
- Abstract
The presence of a pre-existing or recent extra-hepatic solid tumor was considered for a long time as an absolute contraindication to liver transplantation, by fear of futility with an unacceptable increase in non-liver-related mortality. However, cancer-related mortality in solid malignancies is heterogeneous, and experts suggest that case-by-case multidisciplinary decisions should be made. Here, we report the cases of 3 patients with favorable oncological and liver outcome in patients with renal cell carcinoma detected during pre-transplant evaluation that nonetheless underwent liver transplantation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Masson SAS.)
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- 2024
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7. Robotic-assisted percutaneous irreversible electroporation for the treatment of hepatocellular carcinoma.
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L'Huillier R, Dumortier J, Mastier C, Cayot B, Chambon C, Benech N, Stacoffe N, Valette PJ, and Milot L
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- Humans, Treatment Outcome, Electroporation, Carcinoma, Hepatocellular diagnostic imaging, Carcinoma, Hepatocellular therapy, Carcinoma, Hepatocellular pathology, Liver Neoplasms diagnostic imaging, Liver Neoplasms therapy, Liver Neoplasms pathology, Robotic Surgical Procedures, Ablation Techniques
- Abstract
Competing Interests: Declaration of Competing Interest Laurent Milot and Charles Mastier are consultant for Quantum Surgical. All other authors have no competing interest.
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- 2023
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8. Impact of the COVID-19 pandemic on liver transplant waitlist outcome in France.
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Legeai C, Antoine C, Jasseron C, Kerbaul F, and Dumortier J
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- Humans, Pandemics, Severity of Illness Index, Carcinoma, Hepatocellular epidemiology, Carcinoma, Hepatocellular surgery, Carcinoma, Hepatocellular etiology, Liver Transplantation adverse effects, Liver Neoplasms epidemiology, Liver Neoplasms surgery, Liver Neoplasms etiology, COVID-19 epidemiology, COVID-19 etiology, End Stage Liver Disease
- Abstract
The objective of this study was to investigate the impact of the COVID-19 pandemic on the outcome of patients on the liver transplantation (LT) waitlist in 2020 in France, in particular, the incidence of deaths and delisting for worsening condition, depending on the allocation score component. The 2020 cohort of patients on the waiting list was compared with the 2018/2019 cohorts. 2020 saw fewer LTs than in either 2019 or 2018 (1128, 1356, and 1325, respectively), together with fewer actual brain dead donors (1355, 1729, and 1743). In 2020, deaths or delisting for worsening condition increased significantly versus 2018/2019 (subdistribution hazard ratio 1.4, 95% confidence interval [CI] 1.2-1.7), after adjustment for age, place of care, diabetes, blood type, and score component, although COVID-19-related mortality was low. This increased risk mainly concerned patients with hepatocellular carcinoma (1.52, 95% CI 1.22-1.90), with 650 MELD exception points (2.19, 95% CI 1.08-4.43), and especially those without HCC and MELD scores from 25 to 30 (3.36 [95% CI 1.82-6.18]). In conclusion, by significantly decreasing LT activity in 2020, the COVID-19 pandemic increased the number of waitlist deaths and delisting for worsening condition, and significantly more for particular components of the score, including intermediate severity cirrhosis., (© 2023. The Author(s).)
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- 2023
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9. Robotic-assisted percutaneous microwave ablation of hepatocellular carcinoma.
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Milot L, L'Huillier R, Dumortier J, Gérard L, and Valette PJ
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- Humans, Microwaves therapeutic use, Treatment Outcome, Carcinoma, Hepatocellular diagnostic imaging, Carcinoma, Hepatocellular surgery, Carcinoma, Hepatocellular pathology, Liver Neoplasms diagnostic imaging, Liver Neoplasms surgery, Liver Neoplasms pathology, Robotic Surgical Procedures, Radiofrequency Ablation, Catheter Ablation
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- 2023
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10. Antineoplastic chemotherapy and immunosuppression in liver transplant recipients: Squaring the circle?
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Coupier A, Gallien Y, Boillot O, Walter T, Guillaud O, Vallin M, Thimonier E, Erard D, and Dumortier J
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- Male, Humans, Retrospective Studies, Immunosuppressive Agents, Immunosuppression Therapy adverse effects, Calcineurin Inhibitors therapeutic use, Transplant Recipients, Graft Rejection drug therapy, Graft Rejection etiology, Carcinoma, Hepatocellular drug therapy, Carcinoma, Hepatocellular surgery, Liver Transplantation adverse effects, Liver Neoplasms drug therapy, Liver Neoplasms surgery, Liver Neoplasms etiology, Antineoplastic Agents
- Abstract
Background: Malignancies are a major cause of late death after liver transplantation (LT). In LT recipients presenting a malignancy, antineoplastic chemotherapy is central part of the therapeutic arsenal, but management of both immunosuppressive and antineoplastic chemotherapy can be very challenging. The aim of the present retrospective study was to describe a recent single center cohort of LT recipients treated with antineoplastic cytotoxic chemotherapy., Methods: All LT recipients who received antineoplastic chemotherapy in our center between 2005 and 2021 were included., Results: The study population included 72 antineoplastic chemotherapy courses in 69 patients. There was a majority of men (81.9%); median age at LT was 54.9 (range 1-68) and was 63.0 (18-79) at the diagnosis of malignancy. Lung carcinomas (23.6%), head and neck carcinomas (20.8%), lymphomas (16.7%), and recurrent hepatocellular carcinoma (HCC) (8.3%) were the most frequent malignancies. Neoadjuvant (30.6%), adjuvant (12.5%) or palliative (54.2%) chemotherapy was performed. Immunosuppressive regimen was modified from a calcineurin inhibitor (CNI)-based to an everolimus-based regimen (63.5% of CNI discontinuation). Median survival after diagnosis of malignancy was 22.5 months and 5-year survival was 30.1%. Chemotherapy regimen was considered optimal in 81.9% of the cases. Multivariate analysis disclosed that non-PTLD N+ stage malignancy (HR = 5.52 95%CI [1.40;21.69], p = .014), non-PTLD M+ stage malignancy (HR = 10.55 95%CI [3.20;34.73], p = .0001), and suboptimal chemotherapy (HR = 2.73 95%CI [1.34;5.56], p = .005) were significantly associated with poorer prognosis. No rejection episode occurred during chemotherapy., Conclusions: The present study is the first one focused on antineoplastic chemotherapy in LT recipients. Our results suggest that immunosuppressive drugs and antineoplastic chemotherapy can be managed satisfactorily in most cases but this needs confirmation from larger cohorts., (© 2022 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)
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- 2023
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11. Patients Treated for HCV Infection and Listed for Liver Transplantation in a French Multicenter Study: What Happens at Five Years?
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Meunier L, Belkacemi M, Pageaux GP, Radenne S, Vallet-Pichard A, Houssel-Debry P, Duvoux C, Botta-Fridlund D, de Ledinghen V, Conti F, Anty R, Di Martino V, Debette-Gratien M, Leroy V, Gerster T, Lebray P, Alric L, Abergel A, Dumortier J, Besch C, Montialoux H, Samuel D, Duclos-Vallée JC, and Coilly A
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- Humans, Antiviral Agents therapeutic use, Hepacivirus, Retrospective Studies, Ascites, Waiting Lists, Liver Cirrhosis drug therapy, Liver Transplantation adverse effects, Carcinoma, Hepatocellular pathology, Liver Neoplasms etiology, Hepatitis C, Chronic complications, Hepatitis C, Chronic drug therapy, Hepatitis C complications, Hepatitis C drug therapy
- Abstract
Background: Direct-acting antiviral (DAA) agents for the treatment of hepatitis C virus (HCV) infection have been proven safe and effective in cirrhotic patients awaiting liver transplantation (LT). However, in the long term, data remain minimal regarding the clinical impact of viral eradication on patients listed for decompensated cirrhosis or hepatocellular carcinoma (HCC). We aimed to elucidate the clinical outcomes of patients regarding delisting and the evolution of HCC during the long-term follow-up., Methods: An observational, multicenter, retrospective analysis was carried out on prospectively collected data from HCV-positive patients treated with an interferon-free regimen while awaiting LT in 18 French hospitals., Results: A total of 179 patients were included in the study. The indication for LT was HCC in 104 (58.1%) patients and cirrhosis in 75 (41.9%) patients. The sustained virological response was 84.4% and the treatment was well tolerated. At five years, among 75 patients with cirrhosis treated for HCV, 19 (25.3%) were delisted following improvement after treatment. Predictive factors for delisting highlighted an absence of ascites, MELD score ≤ 15, and Child-Pugh score ≤ 7. No patients with refractory ascites were delisted. Among patients with HCC, 82 (78.9%) were transplanted. The drop-out rate was low (6.7%) and few recurrences of HCC after LT were observed., Conclusions: DAAs are safe and effective in patients awaiting LT for cirrhosis or HCC. A quarter of patients with cirrhosis can be delisted because of clinical improvement. Predictive factors for delisting, as a result of improvement, may assist prescribers, before initiating HCV infection therapy in the long-term perspective.
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- 2022
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12. Five-year outcomes in liver transplant patients receiving everolimus with or without a calcineurin inhibitor: Results from the CERTITUDE study.
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Saliba F, Duvoux C, Dharancy S, Dumortier J, Calmus Y, Gugenheim J, Kamar N, Salamé E, Neau-Cransac M, Vanlemmens C, Durand F, Pageaux GP, Hardwigsen J, Benkhatar Y, Derquenne F, and Conti F
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- Calcineurin Inhibitors adverse effects, Everolimus adverse effects, Graft Rejection prevention & control, Graft Survival, Humans, Immunosuppressive Agents adverse effects, Tacrolimus adverse effects, Carcinoma, Hepatocellular etiology, Liver Neoplasms etiology, Liver Transplantation adverse effects
- Abstract
Background and Aims: To report 5-year outcomes of the CERTITUDE study., Methods: An observational study in patients with liver transplantation (LTx) compared the long-term impact of immunosuppression (with/without a calcineurin inhibitor) on renal function, cancers, major cardiovascular events (MACEs) and other safety parameters. All patients completing the 6-month SIMCER study were recruited and analysed according to treatment received at randomization and actual treatment received during the follow-up., Results: Of the 143 enrolled patients, 119 completed the 5-year follow-up (everolimus [EVR], n = 55; tacrolimus [TAC], n = 64). The mean absolute change in estimated glomerular filtration rate was not statistically different between both groups (TAC, -15.53 ml/min/1.73 m
2 and EVR, -14.56 ml/min/1.73 m2 ). In the treatment subgroups based on actual treatment received, renal function was preserved better in the EVR subgroup compared with other subgroups (p = .051). Treated biopsy-proven acute rejection was higher in the EVR group (15.4% vs. 6.4%); however, the majority of events were mild in severity. MACE occurred in 9.2% vs. 14.1% of patients in the EVR and TAC groups respectively (p = .370). De novo cancer was reported in 14 and 5 patients in EVR and TAC groups respectively. Hepatocellular carcinoma (HCC) recurrence was observed in the TAC group alone (n = 4). Adverse events and treatment discontinuation owing to an adverse event were higher in the EVR group., Conclusions: The CERTITUDE study demonstrated that EVR- and TAC-based regimens have comparable efficacy, safety and tolerability up to 5 years post-LTx., (© 2022 The Authors. Liver International published by John Wiley & Sons Ltd.)- Published
- 2022
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13. Liver transplantation for NAFLD cirrhosis: Age and recent coronary angioplasty are major determinants of survival.
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Villeret F, Dharancy S, Erard D, Abergel A, Barbier L, Besch C, Boillot O, Boudjema K, Coilly A, Conti F, Corpechot C, Duvoux C, Faitot F, Faure S, Francoz C, Giostra E, Gugenheim J, Hardwigsen J, Hilleret MN, Hiriart JB, Houssel-Debry P, Kamar N, Lassailly G, Latournerie M, Pageaux GP, Samuel D, Vanlemmens C, Saliba F, and Dumortier J
- Subjects
- Adult, Aged, 80 and over, Angioplasty, Humans, Liver Cirrhosis etiology, Male, Retrospective Studies, Treatment Outcome, Carcinoma, Hepatocellular etiology, Carcinoma, Hepatocellular surgery, End Stage Liver Disease complications, Liver Neoplasms complications, Liver Neoplasms surgery, Liver Transplantation adverse effects, Non-alcoholic Fatty Liver Disease etiology
- Abstract
Background and Aims: Liver transplantation (LT) is the treatment of end-stage non-alcoholic liver disease (NAFLD), that is decompensated cirrhosis and/or complicated by hepatocellular carcinoma (HCC). Few data on long-term outcome are available. The aim of this study was to evaluate overall patient and graft survivals and associated predictive factors., Method: This retrospective multicentre study included adult transplant patients for NAFLD cirrhosis between 2000 and 2019 in participating French-speaking centres., Results: A total of 361 patients (69.8% of male) were included in 20 centres. The median age at LT was 62.3 years [57.4-65.9] and the median MELD score was 13.9 [9.1-21.3]; 51.8% of patients had HCC on liver explant. Between 2004 and 2018, the number of LT for NAFLD cirrhosis increased by 720%. A quarter of the patients had cardiovascular history before LT. Median follow-up after LT was 39.1 months [15.8-72.3]. Patient survival at 1, 5 and 10 years after LT was 89.3%, 79.8% and 68.1% respectively. The main causes of death were sepsis (37.5%), malignancies (29.2%) and cardiovascular events (22.2%). In multivariate analysis, three risk factors for overall mortality after LT were recipient pre-LT BMI < 32 kg/m
2 at LT time (OR: 2.272; p = .012), pre-LT angioplasty during CV check-up (OR: 2.916; p = .016), a combined donor and recipient age over 135 years (OR: 2.020; 95%CI: p = .035)., Conclusion: Survival after LT for NAFLD cirrhosis is good at 5 years. Donor and recipient age, and cardiovascular history, are major prognostic factors to consider., (© 2022 The Authors. Liver International published by John Wiley & Sons Ltd.)- Published
- 2022
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14. Fatal myositis and myasthenia induced by atezolizumab for the treatment of hepatocellular carcinoma.
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Dumortier J, Simon M, and Bouhour F
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- Antibodies, Monoclonal, Humanized adverse effects, Humans, Muscle Weakness, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy, Myositis chemically induced, Myositis therapy
- Published
- 2022
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15. Non-invasive diagnosis and follow-up in liver transplantation.
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Dumortier J, Besch C, Moga L, Coilly A, Conti F, Corpechot C, Del Bello A, Faitot F, Francoz C, Hilleret MN, Houssel-Debry P, Jezequel C, Lavayssière L, Neau-Cransac M, Erard-Poinsot D, de Lédinghen V, Bourlière M, Bureau C, and Ganne-Carrié N
- Subjects
- Follow-Up Studies, Graft Rejection diagnosis, Humans, Liver pathology, Neoplasm Recurrence, Local pathology, Recurrence, Severity of Illness Index, Carcinoma, Hepatocellular diagnosis, Carcinoma, Hepatocellular pathology, Carcinoma, Hepatocellular surgery, End Stage Liver Disease, Liver Neoplasms diagnosis, Liver Neoplasms pathology, Liver Neoplasms surgery, Liver Transplantation adverse effects
- Abstract
The field of liver transplantation directly or indirectly embodies all liver diseases, in addition to specific ones related to organ rejection (cellular and humoral). The recommended non-invasive methods for determining the indication for liver transplantation are the Model for End-stage Liver Disease score, and the alpha-foetoprotein score in case of hepatocellular carcinoma. Radiological methods are the cornerstones for the diagnosis of vascular and biliary complications after liver transplantation. The possible diseases of the liver graft after transplantation are multiple and often intertwined. Non-invasive diagnostic methods have been poorly evaluated in this context, apart from the recurrence of hepatitis C. Liver biopsy remains the gold standard for evaluating graft lesions in the majority of cases, especially graft rejection., (Copyright © 2021. Published by Elsevier Masson SAS.)
- Published
- 2022
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16. How will NAFLD change the liver transplant landscape in the 2020s?
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Villeret F, Dumortier J, and Erard-Poinsot D
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- Humans, Liver Cirrhosis complications, Liver Cirrhosis surgery, Risk Factors, United States, Carcinoma, Hepatocellular etiology, Liver Neoplasms etiology, Liver Transplantation adverse effects, Non-alcoholic Fatty Liver Disease complications, Non-alcoholic Fatty Liver Disease surgery
- Abstract
Liver steatosis is the hepatic manifestation of the metabolic syndrome, and is now the leading cause of chronic liver disease worldwide. The treatment of metabolic cirrhosis with liver failure and/or hepatocellular carcinoma is liver transplantation (LT). During the past decade, metabolic cirrhosis represented an increasing cause for LT, especially in the United States. At listing, patients with metabolic cirrhosis are older, with numerous cardiovascular (CV) and renal comorbidities, and this requires multidisciplinary pre-transplant assessment. After LT, 5-year survival is similar to other indications. The leading causes of death are infectious, cancers and CV. The recurrence of the initial disease is very frequent, and a significant part of the patients progress towards graft cirrhosis. No specific immunosuppressive regimen is recommended, but the toxicity profiles must probably be taken into account. In these patients, the only etiological treatment is that of obesity, in the absence of specific therapy for non-alcoholic steatohepatitis. The place of bariatric surgery has to be defined, probably sleeve gastrectomy, in a stable patient, 6-12 months after LT., (Copyright © 2021. Published by Elsevier Masson SAS.)
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- 2022
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17. Intrathoracic Rupture of Hepatocellular Carcinoma.
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Guillaud O, Proust C, Henry L, and Dumortier J
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- Humans, Rupture, Spontaneous, Carcinoma, Hepatocellular diagnostic imaging, Carcinoma, Hepatocellular pathology, Liver Neoplasms diagnostic imaging, Liver Neoplasms pathology
- Published
- 2021
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18. Risk factors of de novo malignancies after liver transplantation: a French national study on 11004 adult patients.
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Altieri M, Sérée O, Lobbedez T, Segol P, Abergel A, Blaizot X, Boillot O, Boudjema K, Coilly A, Conti F, Chazouillères O, Debette-Gratien M, Dharancy S, Durand F, Duvoux C, Francoz C, Gugenheim J, Hardwigsen J, Houssel-Debry P, Kamar N, Latournerie M, Lebray P, Leroy V, Neau-Cransac M, Pageaux GP, Radenne S, Salamé E, Saliba F, Samuel D, Vanlemmens C, Besch C, Launoy G, and Dumortier J
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- Adult, Humans, Incidence, Male, Retrospective Studies, Risk Factors, Liver Neoplasms epidemiology, Liver Neoplasms etiology, Liver Transplantation
- Abstract
Background: After liver transplantation (LT),de novo malignancies are one of the leading causes of late mortality. The aim of the present retrospective study was to identify the risk factors of de novo malignancies in a large cohort of LT recipients in France, using Fine and Gray competing risks regression analysis., Methods: The study population consisted in 11004 adults transplanted between 2000 and 2013, who had no history of pre-transplant malignancy, except primary liver tumor. A Cox model adapted to the identification of prognostic factors (competitive risks) was used., Results: From the entire cohort, one (or more)de novo malignancy was reported in 1480 L T recipients (13.45%). The probability to develop a de novo malignancy after LT was 2.07% at 1 year, 13.30% at 5 years, and 28.01% at 10 years. Of the known reported malignancies, the most common malignancies were hematological malignancy (22.36%), non-melanoma skin cancer (19.53%) and lung cancer (12.36%). According to Fine and Gray competing risks regression multivariate analysis, were significant risk factors for post-LT de novo malignancy: recipient age (Subdistribution Hazard Ratio (SHR) = 1.03 95%CI 1.03-1.04), male gender (SHR = 1.45 95%CI 1.27-1.67), non-living donor (SHR = 1.67 95%CI 1.14-2.38), a first LT (SHR = 1.35 95%CI 1.09-1.69) and the type of initial liver disease (alcohol-related liver disease (SHR = 1.63 95%CI 1.22-2.17), primary sclerosing cholangitis (SHR = 1.98 95%CI 1.34-2.91), and primary liver tumor (SHR = 1.88 95%CI 1.41-2.54)). Initial immunosuppressive regimen had no significant impact., Conclusion: The present study confirms that LT recipient characteristics are associated with the risk ofde novo malignancy and this underlines the need for personalized screening in order to improve survival., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)
- Published
- 2021
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19. Hemorrhagic and necrotic adenoma associated with a congenital portosystemic shunt.
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Dumortier J, Lachaux A, Collardeau-Frachon S, and Valette PJ
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- Adenoma diagnostic imaging, Adenoma etiology, Child, Female, Humans, Hyperammonemia etiology, Liver Neoplasms diagnostic imaging, Liver Neoplasms etiology, Magnetic Resonance Imaging, Tomography, X-Ray Computed, Adenoma pathology, Liver Neoplasms pathology, Portal Vein abnormalities
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- 2020
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20. Idarubicin-loaded Beads for Chemoembolization of Hepatocellular Carcinoma: The IDASPHERE II Single-Arm Phase II Trial.
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Guiu B, Chevallier P, Assenat E, Barbier E, Merle P, Bouvier A, Dumortier J, Nguyen-Khac E, Gugenheim J, Rode A, Oberti F, Valette PJ, Yzet T, Chevallier O, Barbare JC, Latournerie M, and Boulin M
- Subjects
- Aged, Aged, 80 and over, Antibiotics, Antineoplastic administration & dosage, Antibiotics, Antineoplastic adverse effects, Female, Humans, Idarubicin administration & dosage, Idarubicin adverse effects, Male, Middle Aged, Antibiotics, Antineoplastic therapeutic use, Carcinoma, Hepatocellular therapy, Chemoembolization, Therapeutic methods, Idarubicin therapeutic use, Liver Neoplasms therapy
- Abstract
Background A prior in vitro study showed that idarubicin was the most cytotoxic agent for hepatocellular carcinoma (HCC) cell lines. Idarubicin-loaded beads for transarterial chemoembolization (TACE) were previously evaluated for the appropriate dose in a phase I dose-escalation study. Purpose To evaluate objective response rate (ORR), safety, and survival after TACE by using idarubicin-loaded beads for unresectable HCC. Materials and Methods This prospective single-arm phase II study was conducted between January 2015 and January 2017. Participants with unresectable HCC were included in the trial and underwent TACE with idarubicin-eluting beads. The primary end point was 6-month ORR assessed with independent central review by using modified Response Evaluation Criteria in Solid Tumors. Secondary end points were best ORR during the first 6 months, overall survival, progression-free survival, time to progression, and safety. A two-stage Fleming statistical design was used. Results Forty-six study participants (mean age, 71.2 years ± 10.2; six women and 40 men) were included; 44 participants underwent at least one TACE session. The 6-month ORR was 52% (23 of 44). The best ORR achieved was 68% (30 of 44). Fourteen of 44 (32%) participants underwent a curative treatment after TACE. Median progression-free survival, time to progression, and overall survival were 6.6 months, 9.5 months, and 18.6 months, respectively. TACE was discontinued for toxicity in four of 44 (9%) participants. The most frequent grade 3-4 adverse events were elevated aspartate aminotransferase (14 of 44, 32%), elevated γ-glutamyl transpeptidase (eight of 44, 18%), hyperbilirubinemia (seven of 44, 16%), elevated alanine aminotransferase (seven of 44, 16%), and pain (seven of 44, 16%). Conclusion Idarubicin-eluting beads showed a good safety profile and promising objective response rate and time to progression when used as part of a transarterial chemoembolization regimen for unresectable hepatocellular carcinoma. © RSNA, 2019 See also the editorial by Padia in this issue.
- Published
- 2019
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21. De Novo Primary Liver Cancer After Liver Transplantation: A French National Study on 15803 Patients.
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Allaire M, Sérée O, Coilly A, Houssel-Debry P, Neau-Cransac M, Pageaux GP, Dumortier J, and Altieri M
- Subjects
- Adult, Aged, Carcinoma, Hepatocellular diagnosis, Carcinoma, Hepatocellular mortality, Carcinoma, Hepatocellular therapy, Databases, Factual, Female, France epidemiology, Humans, Immunocompromised Host, Immunosuppressive Agents adverse effects, Liver Neoplasms diagnosis, Liver Neoplasms mortality, Liver Neoplasms therapy, Male, Middle Aged, Risk Factors, Time Factors, Treatment Outcome, Young Adult, Carcinoma, Hepatocellular epidemiology, Liver Neoplasms epidemiology, Liver Transplantation adverse effects
- Published
- 2018
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22. Gastrointestinal stromal tumors (GIST) presenting in the liver: Diagnostic, prognostic and therapeutic issues.
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Joyon N, Dumortier J, Aline-Fardin A, Caramella C, Valette PJ, Blay JY, Scoazec JY, and Dartigues P
- Subjects
- Fatal Outcome, Female, Humans, Male, Middle Aged, Prognosis, Gastrointestinal Stromal Tumors diagnosis, Gastrointestinal Stromal Tumors drug therapy, Liver Neoplasms diagnosis, Liver Neoplasms drug therapy
- Abstract
Context: Extra-gastrointestinal stromal tumors (E-GIST) presenting in the liver are exceedingly rare and raise difficult diagnostic and therapeutic challenges., Methods: We report on two cases of liver E-GIST with different clinical presentations. We describe their clinical and imaging features, their histopathological and molecular characteristics, their treatment and their course., Results: The first case was that of a 56-year-old male presenting with a 10-cm liver mass; the initial diagnosis, made in 1986 from a biopsy sample, was leiomyosarcoma; liver transplantation was performed in 1987; no extra-hepatic tumor was found; the course was uneventful until 1999, when tumor recurrence was diagnosed along the initial biopsy route; after reevaluation of available material, the definitive pathological diagnosis was GIST; imatinib treatment resulted in major response; the patient died of end-stage kidney disease 22 years after the initial diagnosis and 9 years after tumor recurrence. The second case is that of a 59-year-old female presenting with a 23-cm abdominal mass connected to the liver; on biopsy, the tumor was diagnosed as epithelioid GIST with exon 11 KIT mutation; imatinib treatment resulted in stable disease., Conclusions: The diagnosis of E-GIST must be for any sarcoma presenting in the liver and confirmed by immunohistochemical and molecular techniques. Treatment might require aggressive strategies, which can be successful despite apparently adverse histoprognostic factors., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)
- Published
- 2018
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23. Survival and prognostic factors after adjuvant 131 iodine-labeled lipiodol for hepatocellular carcinoma: a retrospective analysis of 106 patients over 20 years.
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Olesinski J, Mithieux F, Guillaud O, Hilleret MN, Lombard-Bohas C, Henry L, Boillot O, Walter T, Partensky C, Paliard P, Valette PJ, Vuillez JP, Borson-Chazot F, Scoazec JY, and Dumortier J
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma, Hepatocellular diagnosis, Cohort Studies, Ethiodized Oil adverse effects, Female, Humans, Liver Neoplasms diagnosis, Male, Middle Aged, Prognosis, Radiotherapy, Adjuvant, Recurrence, Retrospective Studies, Safety, Treatment Outcome, Young Adult, Carcinoma, Hepatocellular radiotherapy, Ethiodized Oil therapeutic use, Iodine Radioisotopes therapeutic use, Liver Neoplasms radiotherapy
- Abstract
Objective: Hepatocellular carcinoma (HCC) has high recurrence rate after curative treatment. The aim of the present study was to report our experience with adjuvant use of
131 I-lipiodol after curative treatment of HCC in terms of recurrence and survival in a large cohort of patients with a long follow-up., Methods: All patients treated with131 I-lipiodol after curative treatment of HCC in two French centers from 1991 to 2009 were included in a retrospective cohort study., Results: One hundred and six patients were included. The median (range) follow-up was 6 years (0.3-22). Forty-three patients (41%) had cirrhosis. Recurrence-free survival rates at 1, 2, 5, 10, and 20 years were 73, 57, 40, 30, and 14%, respectively. Cirrhosis was an independent predictive factor of recurrence [RR = 1.18, 95% CI (1.11-3.02), p = 0.019]. Overall, survival rates at 1, 2, 5, 10, and 20 years were 90, 83, 59, 37, and 23%, respectively. Prognostic factors were recurrence [RR = 2.73, 95% CI (1.35-5.54); p = 0.005], age over 60 years (RR = 1.91, 95% CI [1.02-3.61]; p = 0.044), and tumor number over 3 [RR = 3.31, 95% CI (1.25-8.77); p = 0.016]., Conclusion: Our results suggest that the effect of131 I-lipiodol after curative treatment of HCC could be related to a beneficial impact on risk factors of early tumor recurrence. This could be evaluated in further studies using modern radioembolization methods.- Published
- 2017
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24. Prediction of hepatocellular carcinoma recurrence after liver transplantation: Comparison of four explant-based prognostic models.
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Costentin CE, Amaddeo G, Decaens T, Boudjema K, Bachellier P, Muscari F, Salamé E, Bernard PH, Francoz C, Dharancy S, Vanlemmens C, Radenne S, Dumortier J, Hilleret MN, Chazouillères O, Pageaux GP, Calderaro J, Laurent A, Roudot-Thoraval F, and Duvoux C
- Subjects
- Adult, Area Under Curve, Carcinoma, Hepatocellular pathology, Disease-Free Survival, Female, France epidemiology, Humans, Kaplan-Meier Estimate, Liver Neoplasms pathology, Male, Middle Aged, Neoplasm Recurrence, Local pathology, Neoplasm Staging, Prognosis, Retrospective Studies, Risk Factors, Tumor Burden, Carcinoma, Hepatocellular surgery, Liver Neoplasms surgery, Liver Transplantation, Models, Theoretical, Neoplasm Recurrence, Local epidemiology
- Abstract
Aim: Discordance between pre-LT imaging and explanted liver findings have been reported after liver transplantation (LT) for hepatocellular carcinoma (HCC), suggesting the need of reassessing the risk of HCC recurrence post-LT. Our aims were to compare pre-LT imaging and explants features and to test the performances of four explant-based predictive models of recurrence in an external cohort., Methods: Staging according to pre-LT imaging and explant features were compared. Four explants-based models were retrospectively tested in a cohort of 372 patients transplanted for HCC in 19 French centres between 2003 and 2005. Accuracies of the scores were compared., Results: Pre-LT imaging underestimated tumour burden in 83 (22.7%) patients according to Milan criteria. The highest AUCs for prediction of 5-years recurrence were observed in the "Up to seven" (0.7915 [95% CI: 0.7339-0.849]) and Decaens models (0.747 [95% CI: 0.6877-0.806]), with two levels of risk: low (10%) and high (>50%). Chan and Iwatsuki models identified 3 and 4 levels of risk, but had lower AUCs (0.68 and 0.70) respectively. Accuracy of the "Up to seven" model was superior to the Decaens model (P=.034), which was superior to the Chan model (P=.0041) but not to the Iwatsuki model (P=.17)., Conclusion: Pre-LT imaging underestimates tumour burden, and prediction of recurrence should be reassessed after LT. The explant-based "Up to seven" and Decaens models provided the best accuracy for prediction of 5-year recurrence, identifying only two levels of risk. New models are needed to further refine the prediction of recurrence after LT., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2017
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25. Use of everolimus in liver transplantation: The French experience.
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Dumortier J, Dharancy S, Calmus Y, Duvoux C, Durand F, Salamé E, and Saliba F
- Subjects
- France, Graft Rejection, Humans, Immunosuppressive Agents, Neoplasm Recurrence, Local, Sirolimus, Carcinoma, Hepatocellular surgery, Everolimus therapeutic use, Liver Neoplasms surgery, Liver Transplantation
- Abstract
The mammalian target of rapamycin (mTOR) inhibitor everolimus is approved for rejection prophylaxis after liver transplantation. The current article pools the experience of French liver transplant surgeons and physicians in use of everolimus and, particularly, practical guidance on dosing, appropriate concomitant immunosuppression and management of adverse events. In terms of indication, introduction of everolimus from week 4 after liver transplantation, with or without concomitant calcineurin inhibitor (CNI) therapy, offers a significant renal benefit without loss of immunosuppressive efficacy. De novo treatment with everolimus, either selectively or systematically, may play a role in the prevention and treatment of recurrence of hepatocellular cancer and de novo malignancies. For maintenance patients, the most frequent indications for introducing everolimus are in response to renal dysfunction, recurrent hepatocellular cancer, diabetes, hypertension, or neurotoxicity, or as a preventative approach to avoid malignancies. Of these, the strongest evidence exists for a renoprotective effect. However, the low rate of acute rejection following switch of maintenance patients from CNI-based to everolimus-based therapy means that this can be considered even where robust data are not yet available. Most adverse events associated with mTOR inhibitors can usually be managed successfully, often with concentration-controlled dose reductions. Dosing algorithms are provided, with suggestions for target ranges in specific settings, and treatment strategies for the most common side effects are proposed. Although further research is required, everolimus has become an established part of the immunosuppressive arsenal for liver transplant recipients over the last decade. Sharing experience from units which have embraced its use may help other centers develop their own protocols., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
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26. Liver transplantation for adenomatosis: European experience.
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Chiche L, David A, Adam R, Oliverius MM, Klempnauer J, Vibert E, Colledan M, Lerut J, Mazzafero VV, Di-Sandro S, Laurent C, Scuderi V, Suc B, Troisi R, Bachelier P, Dumortier J, Gugenheim J, Mabrut JY, Gonzalez-Pinto I, Pruvot FR, Le-Treut YP, Navarro F, Ortiz-de-Urbina J, Salamé E, Spada M, and Bioulac-Sage P
- Subjects
- Adenoma, Liver Cell pathology, Adult, Carcinoma, Hepatocellular pathology, Clinical Decision-Making methods, Cohort Studies, Europe epidemiology, Female, Glycogen Storage Disease Type I surgery, Humans, Liver Neoplasms pathology, Male, Registries statistics & numerical data, Retrospective Studies, Treatment Outcome, Adenoma, Liver Cell surgery, Carcinoma, Hepatocellular surgery, Liver Neoplasms surgery, Liver Transplantation statistics & numerical data, Rare Diseases surgery
- Abstract
The aim of this study was to collect data from patients who underwent liver transplantation (LT) for adenomatosis; to analyze the symptoms, the characteristics of the disease, and the recipient outcomes; and to better define the role of LT in this rare indication. This retrospective multicenter study, based on data from the European Liver Transplant Registry, encompassed patients who underwent LT for adenomatosis between January 1, 1986, and July 15, 2013, in Europe. Patients with glycogen storage disease (GSD) type IA were not excluded. This study included 49 patients. Sixteen patients had GSD, and 7 had liver vascular abnormalities. The main indications for transplantation were either a suspicion of hepatocellular carcinoma (HCC; 15 patients) or a histologically proven HCC (16 patients), but only 17 had actual malignant transformation (MT) of adenomas. GSD status was similar for the 2 groups, except for age and the presence of HCC on explants (P = 0.030). Three patients with HCC on explant developed recurrence after transplantation. We obtained and studied the pathomolecular characteristics for 23 patients. In conclusion, LT should remain an extremely rare treatment for adenomatosis. Indications for transplantation primarily concern the MT of adenomas. The decision should rely on morphological data and histological evidence of MT. Additional indications should be discussed on a case-by-case basis. In this report, we propose a simplified approach to this decision-making process., (© 2016 American Association for the Study of Liver Diseases.)
- Published
- 2016
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27. Natural history, treatment and prevention of hepatitis C recurrence after liver transplantation: past, present and future.
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Dumortier J, Boillot O, and Scoazec JY
- Subjects
- Carcinoma, Hepatocellular diagnosis, Carcinoma, Hepatocellular virology, Hepacivirus pathogenicity, Hepatitis C complications, Hepatitis C diagnosis, Humans, Liver Cirrhosis diagnosis, Liver Cirrhosis virology, Liver Neoplasms diagnosis, Liver Neoplasms virology, Recurrence, Time Factors, Treatment Outcome, Antiviral Agents therapeutic use, Carcinoma, Hepatocellular surgery, Hepacivirus genetics, Hepatitis C drug therapy, Liver Cirrhosis surgery, Liver Neoplasms surgery, Liver Transplantation adverse effects, Virus Activation drug effects
- Abstract
Hepatitis C virus (HCV)-related liver disease, including cirrhosis and hepatocellular carcinoma is the main indication for liver transplantation (LT) worldwide. Post-transplant HCV re-infection is almost universal and results in accelerated progression from acute hepatitis to chronic hepatitis, and liver cirrhosis. Comprehension and treatment of recurrent HCV infection after LT have been major issues for all transplant hepatologists and transplant surgeons for the last decades. The aim of this paper is to review the evolution of our knowledge on the natural history of HCV recurrence after LT, including risk factors for disease progression, and antiviral therapy. We will focus our attention on possible ways (present and future) to improve the final long-term results of LT for HCV-related liver disease.
- Published
- 2014
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28. Adjuvant Intraarterial Lipiodol or ¹³¹I-Lipiodol After Curative Treatment of Hepatocellular Carcinoma: A Prospective Randomized Trial.
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Dumortier J, Decullier E, Hilleret MN, Bin-Dorel S, Valette PJ, Boillot O, Partensky C, Letoublon C, Ducerf C, Leroy V, Vuillez JP, and Borson-Chazot F
- Subjects
- Adult, Aged, Aged, 80 and over, Chemoradiotherapy, Adjuvant adverse effects, Ethiodized Oil administration & dosage, Ethiodized Oil adverse effects, Female, Humans, Injections, Intra-Arterial, Iodine Radioisotopes therapeutic use, Male, Middle Aged, Prospective Studies, Recurrence, Survival Analysis, Treatment Outcome, Young Adult, Carcinoma, Hepatocellular therapy, Chemoradiotherapy, Adjuvant methods, Ethiodized Oil therapeutic use, Liver Neoplasms therapy
- Abstract
Unlabelled: The prevention of tumor recurrence after curative treatment of hepatocellular carcinoma (HCC) is unresolved. Postoperative intraarterial injection of (131)I-labeled lipiodol has been proposed as adjuvant treatment. The aim of this prospective randomized trial was to evaluate if a single dose of postoperative adjuvant intraarterial (131)I-lipiodol (vs. unlabeled lipiodol) could reduce the rate of intrahepatic recurrence at 2 y., Methods: Patients who underwent curative treatment for HCC and recovered within 6 wk were randomly assigned to receive a single 2,200-MBq (131)I-lipiodol dose or a single unlabeled lipiodol dose on a 1:1 basis. Recurrence-free and overall survival rates were analyzed., Results: Between June 2005 and February 2009, we included 58 patients (median age of 63 y [range, 23-85 y]): 29 received intraarterial (131)I-lipiodol and 29 received lipiodol adjuvant treatment. At 2 y after treatment, the rate of patients with intrahepatic recurrence was 28% in the (131)I-lipiodol group and 56% in the lipiodol group (P = 0.0449). The Kaplan-Meier analysis confirmed this result, with a 2-y recurrence-free survival in the (131)I-lipiodol and lipiodol groups of 73% and 45%, respectively (P = 0.0259). The 5-y recurrence-free survival rates in the (131)I-lipiodol and lipiodol groups were 40% and 0%, respectively (P = 0.0184). The overall and specific survivals were not significantly different between groups (P = 0.9378 and P = 0.1339, respectively). (131)I-lipiodol had no severe toxic effects., Conclusion: After curative treatment of patients with HCC, one 2,200-MBq dose of intraarterial (131)I-lipiodol significantly decreased the rate of intrahepatic recurrence but failed to improve overall or specific survival., (© 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)
- Published
- 2014
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29. Unrecognized intrahepatic cholangiocarcinoma: an analysis of 993 adult cirrhotic liver explants.
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Vallin M, Sturm N, Lamblin G, Guillaud O, Hilleret MN, Hervieu V, Joubert J, Abergel A, Leroy V, Boillot O, Dumortier J, and Scoazec JY
- Subjects
- Adult, Bile Duct Neoplasms, Bile Ducts, Intrahepatic, Carcinoma, Hepatocellular etiology, Carcinoma, Hepatocellular mortality, Cholangiocarcinoma etiology, Cholangiocarcinoma mortality, Diagnosis, Differential, Female, Follow-Up Studies, Humans, Liver Cirrhosis mortality, Liver Cirrhosis surgery, Liver Neoplasms etiology, Liver Neoplasms mortality, Liver Transplantation mortality, Male, Middle Aged, Neoplasm Recurrence, Local etiology, Neoplasm Recurrence, Local mortality, Prognosis, Risk Factors, Survival Rate, Carcinoma, Hepatocellular diagnosis, Cholangiocarcinoma diagnosis, Liver Cirrhosis complications, Liver Neoplasms diagnosis, Liver Transplantation adverse effects, Neoplasm Recurrence, Local diagnosis
- Abstract
Liver cirrhosis is a recognized risk factor for intrahepatic cholangiocarcinoma (I-CCa). Small I-CCa nodules might be undiagnosed or misdiagnosed as hepatocellular carcinoma (HCC) in the context of liver cirrhosis. The aim of this study was to determine the prevalence and clinical impact of undetected I-CCa in liver explants of adult cirrhotic patients undergoing liver transplantation (LT). From December 1985 to November 2008, a first LT was performed in 993 adult cirrhotic patients in three French academic Hospitals. All liver explants were analyzed for the presence of nodules. The diagnosis of HCC was made in 331 cases (33.3% of the patients). Similarly, an I-CCa was identified in 10 (1%) patients, with a mean size of 31 ± 17 mm. The mean age at transplantation was 58.8 yr (range 45 - 66), and all the patients were men. The mean follow-up after LT was 33 months (range 4-52). Post-transplant tumor recurrence was observed in five patients (50%), after a mean delay of 10 months. All five patients died. Malignant recurrence was associated with the presence of venous emboli on liver explants. Our results suggest that unrecognized I-CCa complicating liver cirrhosis is a rare entity, associated with high risk of recurrence and poor prognosis., (© 2013 John Wiley & Sons A/S.)
- Published
- 2013
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30. Evaluation of shearwave elastography for the characterisation of focal liver lesions on ultrasound.
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Guibal A, Boularan C, Bruce M, Vallin M, Pilleul F, Walter T, Scoazec JY, Boublay N, Dumortier J, and Lefort T
- Subjects
- Adult, Aged, Aged, 80 and over, Diagnosis, Differential, Female, Humans, Male, Middle Aged, Reproducibility of Results, Sensitivity and Specificity, Adenoma diagnostic imaging, Cholangiocarcinoma diagnostic imaging, Elasticity Imaging Techniques methods, Liver Neoplasms diagnostic imaging
- Abstract
Objectives: To determine the elasticity characteristics of focal liver lesions (FLLs) by shearwave elastography (SWE)., Methods: We used SWE in 108 patients with 161 FLLs and in the adjacent liver for quantitative and qualitative FLLs stiffness assessment. The Mann-Whitney test was used to assess the difference between the groups of lesions where a P value less than 0.05 was considered significant., Results: SWE acquisitions failed in 22 nodules (14 %) in 13 patients. For the 139 lesions successfully evaluated, SWE values were (in kPa), for the 3 focal fatty sparings (FFS) 6.6 ± 0.3, for the 10 adenomas 9.4 ± 4.3, for the 22 haemangiomas 13.8 ± -5.5, for the 16 focal nodular hyperplasias (FNHs) 33 ± -14.7, for the 2 scars 53.7 ± 4.7, for the 26 HCCs 14.86 ± 10, for the 53 metastasis 28.8 ± 16, and for the 7 cholangiocarcinomas 56.9 ± 25.6. FNHs had significant differences in stiffness compared with adenomas (P = 0.0002). Fifty percent of the FNHs had a radial pattern of elevated elasticity. A significant difference was also found between HCCs and cholangiocarcinomas elasticity (P = 0.0004)., Conclusions: SWE could be useful in differentiating FNHs and adenomas, or HCCs and cholangiocarcinomas by ultrasound.
- Published
- 2013
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31. Liver transplantation for hepatocellular carcinoma: a model including α-fetoprotein improves the performance of Milan criteria.
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Duvoux C, Roudot-Thoraval F, Decaens T, Pessione F, Badran H, Piardi T, Francoz C, Compagnon P, Vanlemmens C, Dumortier J, Dharancy S, Gugenheim J, Bernard PH, Adam R, Radenne S, Muscari F, Conti F, Hardwigsen J, Pageaux GP, Chazouillères O, Salame E, Hilleret MN, Lebray P, Abergel A, Debette-Gratien M, Kluger MD, Mallat A, Azoulay D, and Cherqui D
- Subjects
- Adult, Area Under Curve, Carcinoma, Hepatocellular pathology, Carcinoma, Hepatocellular surgery, Female, Humans, Liver Neoplasms pathology, Liver Neoplasms surgery, Male, Middle Aged, Multivariate Analysis, Neoplasm Invasiveness, Practice Guidelines as Topic, Predictive Value of Tests, Proportional Hazards Models, Carcinoma, Hepatocellular blood, Decision Support Techniques, Liver Neoplasms blood, Liver Transplantation, Neoplasm Recurrence, Local blood, Patient Selection, alpha-Fetoproteins metabolism
- Abstract
Background & Aims: The aim of this study was to generate an improved prognostic model for predicting recurrence in liver transplant candidates with hepatocellular carcinoma (HCC)., Methods: Predictors of recurrence were tested by a Cox model analysis in a training cohort of 537 patients transplanted for HCC. A prognostic score was developed and validated in a national cohort of 435 patients followed up prospectively., Results: α-Fetoprotein (AFP) independently predicted tumor recurrence and correlated with vascular invasion and differentiation. At a Cox score threshold of 0.7 (area under the receiver operating characteristic curve, 0.701; 95% confidence interval, 0.63-0.76; accuracy, 75.8%), a model combining log(10) AFP, tumor size, and number was highly predictive of tumor recurrence and death. By using a simplified version of the model, with untransformed AFP values, a cut-off value of 2 was identified. In the validation cohort, a score greater than 2 predicted a marked increase in 5-year risk of recurrence (50.6% ± 10.2% vs 8.8% ± 1.7%; P < .001) and decreased survival (47.5% ± 8.1% vs 67.8% ± 3.4%; P = .002) as compared with others. Among patients exceeding Milan criteria, a score of 2 or lower identified a subgroup of patients with AFP levels less than 100 ng/mL with a low 5-year risk of recurrence (14.4% ± 5.3% vs 47.6% ± 11.1%; P = .006). Among patients within Milan criteria, a score greater than 2 identified a subgroup of patients with AFP levels greater than 1000 ng/mL at high risk of recurrence (37.1% ± 8.9% vs 13.3% ± 2.0%; P < .001). Net reclassification improvement showed that predictability of the AFP model was superior to Milan criteria., Conclusions: Prediction of tumor recurrence is improved significantly by a model that incorporates AFP. We propose the adoption of new selection criteria for HCC transplant candidates, taking into account AFP., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Published
- 2012
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32. Hepar lobatum carcinomatosum revealing an occult metastatic lobular carcinoma of the breast.
- Author
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Graber I, Dumortier J, Poncet G, Queneau PE, Mathevet P, and Scoazec JY
- Subjects
- Biopsy, Breast Neoplasms drug therapy, Budd-Chiari Syndrome diagnosis, Budd-Chiari Syndrome pathology, Carcinoma, Lobular drug therapy, Diagnosis, Differential, Drug Therapy, Fatal Outcome, Female, Humans, Liver blood supply, Liver pathology, Liver Cirrhosis diagnosis, Liver Cirrhosis drug therapy, Liver Cirrhosis pathology, Liver Neoplasms drug therapy, Middle Aged, Breast Neoplasms pathology, Carcinoma, Lobular diagnosis, Carcinoma, Lobular secondary, Liver Neoplasms diagnosis, Liver Neoplasms secondary
- Abstract
Hepar lobatum carcinomatosum is an unusual cause of chronic liver failure, usually maskerading as cirrhosis. The pathogenesis of this syndrome is unclear. We report a case of liver failure revealing an occult lobular carcinoma of the breast, which offers the opportunity to gain further insight into the mechanisms of this rare cause of chronic liver disease. A 57-year-old woman, without history of malignancy, presented with hepatomegaly, ascites and altered liver tests (serum transaminase activity >5 N and hyperbilirubinemia). The transjugular liver biopsy performed at diagnosis showed an extensive fibrosis, containing scattered tumor cells, typical of metastatic lobular carcinoma of the breast. Four months later, after discovery of a rectal adenocarcinoma, a laparoscopy was performed; peritoneal carcinomatosis was discovered. A surgical biopsy of the liver was taken during the procedure: it showed histological features suggestive of chronic Budd-Chiari syndrome, with venocentric fibrosis and reversed lobulation. Intraluminal invasion of small hepatic veins and sinusoidal obstruction by neoplastic cells were observed. A small focus of lobular carcinoma was eventually discovered in the left mammary gland. The present case report expands the spectrum of clinical presentations associated with hepar lobatum carcinomatosum and points out to the importance of vascular injury in the pathogenesis of this rare cause of chronic liver disease., (Copyright © 2010 Elsevier Inc. All rights reserved.)
- Published
- 2010
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33. Polycythemia and elevated serum erythropoietin associated with a liver haemangioma.
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Lanne JS, Dumortier J, Hervieu V, Pilleul F, Scoazec JY, and Adham M
- Subjects
- Adult, Biomarkers blood, Diagnosis, Differential, Hemangioma, Cavernous blood, Hemangioma, Cavernous surgery, Hepatectomy, Humans, Liver Neoplasms blood, Liver Neoplasms surgery, Male, Polycythemia blood, Polycythemia surgery, Treatment Outcome, Erythropoietin blood, Hemangioma, Cavernous complications, Hemangioma, Cavernous diagnosis, Liver Neoplasms complications, Liver Neoplasms diagnosis, Polycythemia diagnosis, Polycythemia etiology
- Abstract
Background: Secondary polycythemia is a rare condition, which is usually associated to neoplasia or chronic pulmonary disorders., Case Report: A 41-year-old man man with no history of liver disease was admitted for erythrocytosis. The paraclinical investigations revealed an increased erythropoietin level in the serum and a voluminous hepatic tumor but its identification was unclear. A liver resection was performed and the histopathological examination concluded that the tumor was a giant cavernous haemangioma with extensive myxoid changes. After surgical resection of the haemangioma, normal haemoglobin and serum erythropoietin were obtained without any further treatment., Conclusion: Liver haemangioma must be included in rare cause of secondary polycythemia, and surgical resection of the haemangioma should be considered as the standard to induce complete remission., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)
- Published
- 2010
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34. Liver transplantation for multiple angiomyolipomas complicating tuberous sclerosis complex.
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Dumortier J, Guillaud O, Walter T, Ber CE, Partensky C, Boillot O, and Scoazec JY
- Subjects
- Adult, Angiomyolipoma complications, Angiomyolipoma pathology, Fatal Outcome, Humans, Liver Neoplasms complications, Liver Neoplasms pathology, Male, Neoplasms, Multiple Primary pathology, Pneumonia, Bacterial, Postoperative Complications, Pseudomonas Infections, Pseudomonas aeruginosa, Angiomyolipoma surgery, Liver Neoplasms surgery, Liver Transplantation, Neoplasms, Multiple Primary surgery, Tuberous Sclerosis complications
- Abstract
Tuberous sclerosis complex is a genetic multisystem disorder characterised by widespread hamartomas in several organs, including the brain, heart, skin, eyes, kidney, lung, and liver. Hepatic multiple, bilateral angiomyolipomas are a rare and usually asymptomatic complication in patients with tuberous sclerosis. We report here the case of a patient who needed liver transplantation because of debilitating manifestations and mechanical complications of massive liver involvement by multiple angiomyolipomas (severe malnutrition, anorexia and abdominal pain). Seventeen tumors, from 2 to 16 cm in diameter, were identified at examination of the liver explant. No feature suggestive of malignant behaviour was identified at histological examination. In conclusion, this unusual indication of liver transplantation underlines the interest of this therapeutic approach for benign tumors for which the multiplicity of the lesions and their huge volume prevent any attempt at surgical resection., (Copyright © 2010. Published by Elsevier Masson SAS.)
- Published
- 2010
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35. Complete response of hepatocellular carcinoma with systemic combination chemotherapy: not to get out the chemotherapy?
- Author
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Boschetti G, Walter T, Hervieu V, Cassier P, Lombard-Bohas C, Adham M, Scoazec JY, and Dumortier J
- Subjects
- Adult, Antineoplastic Agents therapeutic use, Carcinoma, Hepatocellular pathology, Deoxycytidine analogs & derivatives, Deoxycytidine therapeutic use, Humans, Liver Neoplasms pathology, Male, Niacinamide analogs & derivatives, Organoplatinum Compounds therapeutic use, Oxaliplatin, Peritoneal Neoplasms secondary, Peritoneal Neoplasms surgery, Phenylurea Compounds, Remission Induction, Sorafenib, alpha-Fetoproteins analysis, Gemcitabine, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Benzenesulfonates therapeutic use, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy, Pyridines therapeutic use
- Abstract
Since 2007, sorafenib is the new standard for the first-line treatment of advanced hepatocellular carcinoma (HCC), with proved effectiveness on survival, but no complete response. We encountered a case of complete and durable response after gemcitabine plus oxaliplatine (GEMOX) in a patient with metastatic HCC. The use of GEMOX was considered because the patient was young, without other liver disease, with bone and hepatic lesions, a rapidly progressive disease, and a poorly differentiated component on histological aspect. After 12 cycles of GEMOX, complete response occurs with disappearance of metastases and normalization of serum level of alpha-fetoprotein. This is the first case report of complete response of HCC to GEMOX. That is why the association of chemotherapy and molecular targeted therapies is a promising direction of research. Our report shows that another important challenge remains in the identification of predictive factors of response to standard chemotherapy or molecular targeted agents.
- Published
- 2010
- Full Text
- View/download PDF
36. Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study.
- Author
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Lammer J, Malagari K, Vogl T, Pilleul F, Denys A, Watkinson A, Pitton M, Sergent G, Pfammatter T, Terraz S, Benhamou Y, Avajon Y, Gruenberger T, Pomoni M, Langenberger H, Schuchmann M, Dumortier J, Mueller C, Chevallier P, and Lencioni R
- Subjects
- Aged, Drug Carriers, Drug Implants, Female, Humans, Male, Prospective Studies, Single-Blind Method, Treatment Outcome, Antibiotics, Antineoplastic administration & dosage, Carcinoma, Hepatocellular therapy, Chemoembolization, Therapeutic methods, Doxorubicin administration & dosage, Liver Neoplasms therapy
- Abstract
Transcatheter arterial chemoembolization (TACE) offers a survival benefit to patients with intermediate hepatocellular carcinoma (HCC). A widely accepted TACE regimen includes administration of doxorubicin-oil emulsion followed by gelatine sponge-conventional TACE. Recently, a drug-eluting bead (DC Bead) has been developed to enhance tumor drug delivery and reduce systemic availability. This randomized trial compares conventional TACE (cTACE) with TACE with DC Bead for the treatment of cirrhotic patients with HCC. Two hundred twelve patients with Child-Pugh A/B cirrhosis and large and/or multinodular, unresectable, N0, M0 HCCs were randomized to receive TACE with DC Bead loaded with doxorubicin or cTACE with doxorubicin. Randomization was stratified according to Child-Pugh status (A/B), performance status (ECOG 0/1), bilobar disease (yes/no), and prior curative treatment (yes/no). The primary endpoint was tumor response (EASL) at 6 months following independent, blinded review of MRI studies. The drug-eluting bead group showed higher rates of complete response, objective response, and disease control compared with the cTACE group (27% vs. 22%, 52% vs. 44%, and 63% vs. 52%, respectively). The hypothesis of superiority was not met (one-sided P = 0.11). However, patients with Child-Pugh B, ECOG 1, bilobar disease, and recurrent disease showed a significant increase in objective response (P = 0.038) compared to cTACE. DC Bead was associated with improved tolerability, with a significant reduction in serious liver toxicity (P < 0.001) and a significantly lower rate of doxorubicin-related side effects (P = 0.0001). TACE with DC Bead and doxorubicin is safe and effective in the treatment of HCC and offers a benefit to patients with more advanced disease.
- Published
- 2010
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- View/download PDF
37. Primary acinar cell carcinoma of the liver.
- Author
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Hervieu V, Lombard-Bohas C, Dumortier J, Boillot O, and Scoazec JY
- Subjects
- Adult, Carcinoma, Acinar Cell metabolism, Carcinoma, Acinar Cell surgery, Female, Humans, Immunohistochemistry, Liver chemistry, Liver surgery, Liver Neoplasms metabolism, Liver Neoplasms surgery, Treatment Outcome, alpha 1-Antitrypsin analysis, alpha-Fetoproteins analysis, Carcinoma, Acinar Cell pathology, Liver pathology, Liver Neoplasms pathology
- Abstract
We report a case of acinar cell carcinoma primary to the liver. The tumor was diagnosed in a 35-year-old woman complaining of abdominal pain and asthenia; serum alpha-fetoprotein (AFP) levels were increased at 6,000 IU/mL; imaging studies showed a hypervascular mass located in the left lobe of the liver. A left lobectomy was performed. The tumor had a heterogeneous appearance. In well-differentiated areas, tumor cells formed acinar structures, had a pyramidal shape and a highly eosinophilic, granular cytoplasm, PAS diastase resistant. In less-differentiated areas, tumor cells were endocrinelike. The immunohistochemical study showed that tumor cells expressed trypsin. Alpha-fetoprotein and alphal-antritrypsin were detected in about 30% of cells; HepPar1 was present in 15% of cells. Chromogranin A and synaptophysin were detected in rare cells. After surgery, serum AFP levels quickly returned to normal; no evidence of recurrence or metastasis was observed during follow-up. The final diagnosis, based on histological, immunohistochemical, and ultrastructural arguments, was extra-pancreatic acinar cell carcinoma, primary to the liver. This unusual lesion is likely to be the result of an abnormal differentiation pathway involving a transformed multipotential progenitor cell.
- Published
- 2008
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38. Unresectable hepatocellular carcinoma: survival and prognostic factors after lipiodol chemoembolisation in 89 patients.
- Author
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Dumortier J, Chapuis F, Borson O, Davril B, Scoazec JY, Poncet G, Henry L, Boillot O, Mion F, Berger F, Partensky C, Paliard P, and Valette PJ
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Injections, Intra-Arterial, Male, Middle Aged, Multivariate Analysis, Prognosis, Survival Analysis, Antibiotics, Antineoplastic administration & dosage, Carcinoma, Hepatocellular mortality, Chemoembolization, Therapeutic, Contrast Media administration & dosage, Doxorubicin administration & dosage, Iodized Oil administration & dosage, Liver Neoplasms mortality, Liver Neoplasms therapy
- Abstract
Background: The majority of patients with hepatocellular carcinoma are not eligible for surgical radical treatment (resection or liver transplantation) and lipiodol chemoembolisation is an efficient alternative procedure in this indication., Aims: To identify prognostic factors in patients treated with lipiodol chemoembolisation., Patients and Methods: During 10 years, 89 consecutive patients with unresectable hepatocellular carcinoma underwent lipiodol chemoembolisation as a single treatment. There were 80 males and 9 females, with a median age of 65 years. Treatment consisted of one to six courses of hepatic intra-arterial lipiodol with doxorubicine and gelatin sponge., Results: The median survival was 13 months with a 13.6% survival rate at 4 years. Univariate analysis showed that serum levels of albumin, bilirubin, alkaline phosphatase and alpha-fetoprotein, Child's class, tumour type, tumour size and intensity of lipiodol capture after the first course of lipiodol chemoembolisation were significant prognostic factors of survival. In the multivariate analysis, four parameters remained associated with a significantly better outcome: Child's class A, largest lesion<5 cm, uninodular tumour and intense lipiodol capture., Conclusions: While lipiodol chemoembolisation is associated with good results only in some patients, in the absence of lipiodol capture, it should be ruled out.
- Published
- 2006
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- View/download PDF
39. [Use of the FISH technique to identify the origin of an endocrine carcinoma in a liver graft].
- Author
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de la Fouchardière A, Hervieu V, Dumortier J, Crombe-Ternamian A, Boillot O, and Scoazec JY
- Subjects
- Female, Humans, Middle Aged, Tissue Donors, Carcinoma genetics, Carcinoma pathology, Endocrine Gland Neoplasms genetics, Endocrine Gland Neoplasms pathology, In Situ Hybridization, Fluorescence, Liver Neoplasms genetics, Liver Neoplasms pathology, Liver Transplantation
- Published
- 2005
- Full Text
- View/download PDF
40. Endothelial cell differentiation in hepatocellular adenomas: implications for histopathological diagnosis.
- Author
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Gouysse G, Frachon S, Hervieu V, Fiorentino M, d'Errico A, Dumortier J, Boillot O, Partensky C, Grigioni WF, and Scoazec JY
- Subjects
- Adenoma, Liver Cell diagnosis, Adenoma, Liver Cell metabolism, Adult, Aged, Biomarkers metabolism, Carcinoma, Hepatocellular diagnosis, Carcinoma, Hepatocellular metabolism, Carcinoma, Hepatocellular pathology, Cell Differentiation, Diagnosis, Differential, Endothelial Cells immunology, Endothelial Cells metabolism, Extracellular Matrix Proteins metabolism, Female, Focal Nodular Hyperplasia metabolism, Focal Nodular Hyperplasia pathology, Humans, Immunoenzyme Techniques, Immunophenotyping, Liver Neoplasms diagnosis, Liver Neoplasms metabolism, Male, Middle Aged, Telangiectasis metabolism, Telangiectasis pathology, Adenoma, Liver Cell pathology, Endothelial Cells pathology, Liver Neoplasms pathology
- Abstract
Background/aims: Little information is available about the patterns of endothelial cell differentiation observed in hepatocellular adenomas. We therefore aimed to analyze the endothelial cell immunophenotype in a large series of these tumors and evaluate its possible diagnostic relevance., Methods: The expression of continuous and sinusoidal endothelial cell markers and of extracellular matrix proteins was analyzed by immunoperoxidase in 56 adenomas, as compared with 30 cases of focal nodular hyperplasia (FNH), 2 cases of telangiectatic FNH and 40 cases of hepatocellular carcinoma (HCC)., Results: Twenty-eight adenomas (50%) presented a sinusoidal pattern of endothelial cell differentiation, characterized by the expression of specific sinusoidal endothelial cell markers and the presence of a subendothelial matrix resembling the normal perisinusoidal matrix. Eleven tumors (19.5%) presented a continuous pattern of endothelial cell differentiation. Seventeen tumors (30.5%) showed a mixed pattern. Twenty-eight FNH presented a sinusoidal pattern of endothelial cell differentiation; all HCC presented a continuous pattern of endothelial cell differentiation., Conclusions: In hepatocellular adenomas, intra-tumoral vessels usually present a sinusoidal pattern of endothelial cell differentiation. However, the vascular phenotypic heterogeneity observed in our study questions the potential relevance of endothelial cell immunophenotyping for the differential diagnosis between hepatocellular adenomas and well differentiated HCC.
- Published
- 2004
- Full Text
- View/download PDF
41. [Paraneoplastic hypereosinophilia associated with hepatocellular carcinoma].
- Author
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Bonaventure C, Etienne-Mastroianni B, Alessio A, Scoazec JY, Boillot O, and Dumortier J
- Subjects
- Humans, Male, Middle Aged, Carcinoma, Hepatocellular complications, Hypereosinophilic Syndrome etiology, Hypereosinophilic Syndrome pathology, Liver Neoplasms complications, Paraneoplastic Syndromes etiology, Paraneoplastic Syndromes pathology
- Published
- 2003
42. Expression, regulation, and function of alpha V integrins in hepatocellular carcinoma: an in vivo and in vitro study.
- Author
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Nejjari M, Hafdi Z, Gouysse G, Fiorentino M, Béatrix O, Dumortier J, Pourreyron C, Barozzi C, D'errico A, Grigioni WF, and Scoazec JY
- Subjects
- Adult, Aged, Antigens, CD analysis, Antigens, CD biosynthesis, Carcinoma, Hepatocellular pathology, Cell Adhesion, Cell Movement, Female, Fibronectins analysis, Fibronectins biosynthesis, Fibronectins metabolism, Focal Nodular Hyperplasia metabolism, Focal Nodular Hyperplasia pathology, Hepatocytes chemistry, Hepatocytes cytology, Humans, In Vitro Techniques, Integrin alphaV, Liver Neoplasms pathology, Male, Middle Aged, Prognosis, Tumor Cells, Cultured, Vitronectin analysis, Vitronectin biosynthesis, Vitronectin metabolism, Antigens, CD metabolism, Carcinoma, Hepatocellular metabolism, Hepatocytes metabolism, Liver Neoplasms metabolism
- Abstract
The expression of alpha V integrins by neoplastic cells contributes to the promotion of local invasion and metastasis. The most characteristic extracellular ligands of alpha V integrins are vitronectin and fibronectin. Hepatocytes are the main source of vitronectin, and the capacity to synthesize and secrete vitronectin is usually retained in hepatocellular carcinoma. The aim of this study was to explore the expression, regulation, and functional role of alpha V integrins in hepatocellular carcinoma. We first analyzed the expression of alpha V integrins and their ligands fibronectin and vitronectin in 80 cases of hepatocellular carcinoma. alpha V integrin chain was detected in 44 cases and vitronectin in 50. Twenty-four of the 44 alpha V-positive tumors contained large amounts of vitronectin. These cases presented more frequently with adverse histoprognostic factors, including infiltrative growth pattern (62.5%), lack of capsule (71%), presence of capsular invasion (57%), and satellite nodules (50%). We then used HepG2 and Hep3B cell lines as in vitro models to study alpha V integrin regulation and function. HepG2 and Hep3B cells expressed alpha V integrin chain and used alpha V beta 1 and alpha V beta 5 for adhesion and migration on vitronectin. Tumor necrosis factor (TNF) alpha and transforming growth factor (TGF) beta significantly increased the expression levels of alpha V integrins and stimulated the adhesion and migration of both HepG2 and Hep3B cell lines on vitronectin. The effects of growth factors on cell adhesion and migration were reproduced by incubation with conditioned medium from rat liver myofibroblasts. In conclusion, our results support the existence of an alpha V integrin/vitronectin connection in hepatocellular carcinoma and suggest that this connection may be an adverse prognostic factor.
- Published
- 2002
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- View/download PDF
43. [Chronic ascites caused by peritoneal carcinosis secondary to hepatocellular carcinoma. Symptomatic treatment with bleomycin intraperitoneal injections].
- Author
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Roman S, Lombard-Bohas C, Henry L, Berger F, Scoazec JY, and Dumortier J
- Subjects
- Aged, Ascitic Fluid etiology, Chronic Disease, Humans, Injections, Intraperitoneal, Male, Peritoneal Neoplasms complications, Peritoneal Neoplasms secondary, Antibiotics, Antineoplastic administration & dosage, Ascitic Fluid drug therapy, Bleomycin administration & dosage, Carcinoma, Hepatocellular secondary, Liver Neoplasms pathology, Peritoneal Neoplasms drug therapy
- Published
- 2001
44. Endothelial cell marker expression in dysplastic lesions of the liver: an immunohistochemical study.
- Author
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Frachon S, Gouysse G, Dumortier J, Couvelard A, Nejjari M, Mion F, Berger F, Paliard P, Boillot O, and Scoazec JY
- Subjects
- Adult, Antigens, CD34 metabolism, Biomarkers, Capillaries metabolism, Capillaries pathology, Carcinoma, Hepatocellular blood supply, Carcinoma, Hepatocellular complications, Diagnosis, Differential, Female, Humans, Immunohistochemistry, Liver blood supply, Liver metabolism, Liver pathology, Liver Cirrhosis complications, Liver Cirrhosis metabolism, Liver Cirrhosis pathology, Liver Neoplasms blood supply, Liver Neoplasms complications, Male, Middle Aged, Platelet Endothelial Cell Adhesion Molecule-1 metabolism, Precancerous Conditions blood supply, Precancerous Conditions complications, Retrospective Studies, Carcinoma, Hepatocellular metabolism, Carcinoma, Hepatocellular pathology, Endothelium, Vascular metabolism, Endothelium, Vascular pathology, Liver Neoplasms metabolism, Liver Neoplasms pathology, Precancerous Conditions metabolism, Precancerous Conditions pathology
- Abstract
Backgrounds/aims: Hepatocellular carcinoma usually contains continuous capillary vessels lacking the differentiation markers specific for normal sinusoidal endothelial cells. We therefore aimed to search for alterations in endothelial cell marker expression in precancerous liver lesions., Methods: Expression of the endothelial cell markers CD31, CD34 and BNH9 was analyzed in 138 dysplastic lesions from 40 cirrhotic patients (20 with and 20 without hepatocellular carcinoma)., Results: No expression of the three endothelial cell markers was detected in cirrhotic nodules and in non dysplastic regenerative macronodules. The three markers were detected in 29.8% of dysplastic lesions and 47% of hepatocellular carcinomas. At least one marker was detected in 75% of dysplastic lesions and 100% of hepatocellular carcinomas. The three markers were more frequently expressed in areas of small cell than of large cell change (34 vs 10%). No correlation was found with the grade of dysplasia, the occurrence of arterialization and the association with hepatocellular carcinoma., Conclusions: Alterations in the hepatic microcirculation comparable to those observed in hepatocellular carcinoma are present in a significant proportion of dysplastic lesions of the liver and may be indirect markers of the process of liver carcinogenesis.
- Published
- 2001
- Full Text
- View/download PDF
45. [Liver cell dysplasia: a crosstalk between the clinician and the pathologist].
- Author
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Dumortier J and Scoazec JY
- Subjects
- Biopsy, Carcinoma, Hepatocellular diagnosis, Carcinoma, Hepatocellular pathology, Humans, Hyperplasia, Liver Cirrhosis pathology, Liver Neoplasms pathology, Hepatocytes pathology, Liver Neoplasms diagnosis
- Published
- 2001
46. [Palmar fasciitis and paraneoplastic polyarthritis associated with hepatocellular carcinoma].
- Author
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Roman S, Tebib J, Scoazec JY, Menard Y, Paliard P, and Dumortier J
- Subjects
- Anti-Inflammatory Agents therapeutic use, Arthritis diagnosis, Arthritis drug therapy, Biopsy, Carcinoma, Hepatocellular diagnosis, Carcinoma, Hepatocellular therapy, Chemoembolization, Therapeutic, Diagnosis, Differential, Disease Progression, Fasciitis diagnosis, Fasciitis drug therapy, Humans, Liver Neoplasms diagnosis, Liver Neoplasms therapy, Male, Middle Aged, Paraneoplastic Syndromes diagnosis, Paraneoplastic Syndromes drug therapy, Steroids, Tomography, X-Ray Computed, Arthritis etiology, Carcinoma, Hepatocellular complications, Fasciitis etiology, Hand, Liver Neoplasms complications, Paraneoplastic Syndromes etiology
- Published
- 2001
47. [Synopsis. Diagnosis of liver nodules: techniques, approach and main practical problems].
- Author
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Scoazec JY, Labadie M, Dumortier J, and Valette PJ
- Subjects
- Adult, Biopsy, Needle, Cysts diagnosis, Cysts pathology, Diagnosis, Differential, Female, Focal Nodular Hyperplasia diagnosis, Focal Nodular Hyperplasia pathology, Humans, Liver Cirrhosis diagnosis, Liver Cirrhosis pathology, Magnetic Resonance Imaging, Male, Risk Factors, Tomography, X-Ray Computed, Liver pathology, Liver Diseases diagnosis, Liver Diseases pathology, Liver Neoplasms diagnosis, Liver Neoplasms pathology
- Published
- 2000
48. alpha6beta1 integrin expression in hepatocarcinoma cells: regulation and role in cell adhesion and migration.
- Author
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Nejjari M, Hafdi Z, Dumortier J, Bringuier AF, Feldmann G, and Scoazec JY
- Subjects
- Carcinoma, Hepatocellular pathology, Cell Adhesion drug effects, Cell Adhesion physiology, Cell Membrane metabolism, Cell Movement drug effects, Dose-Response Relationship, Drug, Enzyme-Linked Immunosorbent Assay, Fibroblast Growth Factor 2 pharmacology, Flow Cytometry, Humans, Immunoblotting, Immunohistochemistry, Integrin alpha6beta1, Interferon alpha-2, Interferon-alpha pharmacology, Interferon-gamma pharmacology, Interleukin-1 pharmacology, Liver Neoplasms pathology, Recombinant Proteins, Transforming Growth Factor beta pharmacology, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha pharmacology, Carcinoma, Hepatocellular metabolism, Cell Movement physiology, Integrins biosynthesis, Integrins physiology, Liver Neoplasms metabolism
- Abstract
Liver carcinogenesis is associated with striking changes in the integrin repertoire of hepatocytes, including the overexpression of the laminin and collagen receptors alpha1beta1 and the de novo induction of the laminin receptor alpha6beta1. Our aim was to analyze the role of pro-inflammatory cytokines, interferons and fibrogenic cytokines TGF-beta and FGF2 in the regulation of the expression of beta1 integrins by neoplastic hepatocytes. The 2 human hepatocellular cell lines HepG2 and Hep3B were used as models. Integrin expression was assessed by qualitative methods (immunocytochemistry, Western blotting) and semi-quantitative techniques (FACS, cellular ELISA), before and after stimulation by TNFalpha, IL1-beta, TGF-beta, FGF2, interferon gamma and interferon alpha-2b. HepG2 and Hep3B constitutively expressed alpha1, alpha2, alpha6 and beta1 chains. A 24 to 48-hr stimulation with pro-inflammatory cytokines, TGF-beta and FGF2 induced a significant increase in the concentrations of all integrin chains. The maximum induction was registered for beta1 chain, which presented increases amounting up to 3, 4 and 7 times the control values in the presence of, respectively, TNF alpha/IL1-beta, TGF-beta and FGF2. Interferons had no direct effect on integrin expression and partially antagonized the effects of TNF alpha and TGF-beta. The increased concentrations of integrin chains were associated with an increased membrane expression of the corresponding dimers and with an increased adhesion of stimulated hepatocytes to laminin, which was antagonized by neutralizing anti-beta1 and anti-alpha6 antibodies. Finally, anti-alpha6 antibody inhibited the migration of HepG2 and Hep3B cells in reconstituted basement membrane. Our results suggest that the stimulation of alpha6beta1 integrin expression in hepatocarcinoma cells is essential for cell adhesion and migration., (Copyright 1999 Wiley-Liss, Inc.)
- Published
- 1999
- Full Text
- View/download PDF
49. Recurrence of hepatocellular carcinoma as a mixed hepatoblastoma after liver transplantation.
- Author
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Dumortier J, Bizollon T, Chevallier M, Ducerf C, Baulieux J, Scoazec JY, and Trepo C
- Subjects
- Humans, Liver Neoplasms surgery, Male, Middle Aged, Carcinoma, Hepatocellular surgery, Hepatoblastoma pathology, Liver Neoplasms pathology, Liver Transplantation, Neoplasm Recurrence, Local pathology
- Abstract
Background: Hepatoblastoma is an exceptional cause of primary malignant liver tumour in the adult., Patient: The case is reported of an adult patient transplanted for alcoholic cirrhosis complicated by multifocal hepatocellular carcinoma in whom a recurrence in the form of a mixed hepatoblastoma invading the whole transplanted liver developed three months after liver transplantation., Methods: Complete clinical, histopathological, and immunohistochemical data were reviewed., Results: The recurrent tumour invaded the whole liver. The major component was a mixed hepatoblastoma, with an epithelial component expressing cytokeratin and a mesenchymal component expressing vimentin. The tumour also contained a minor hepatocarcinomatous component expressing alpha fetoprotein. The rapid growth of the tumour prevented any attempt at treatment. Although direct evidence is lacking, the most likely hypothesis to explain the observations is a marked phenotypic change in the initial malignant population at recurrence., Conclusion: This case supports a possible filiation between hepatocellular carcinoma and hepatoblastoma in adults.
- Published
- 1999
- Full Text
- View/download PDF
50. Liver transplantation for adenomatosis: European experience
- Author
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Christophe Laurent, Yves Patrice Le-Treut, Jorge Ortiz-de-Urbina, François-René Pruvot, Martin Oliverius, Jean Gugenheim, Phillipe Bachelier, Ephrem Salamé, Anaelle David, Vincenzo Scuderi, Jürgen Klempnauer, René Adam, Stefano Di-Sandro, Paulette Bioulac-Sage, Jan Lerut, Jean Yves Mabrut, Francis Navarro, Jeroˆme Dumortier, Eric Vibert, Marco Spada, Roberto Troisi, Michele Colledan, Ignacio Gonzalez-Pinto, Laurence Chiche, V. Vincenzo Mazzafero, Bertrand Suc, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Centre hépato-biliaire (CHB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Chirurgie Générale et Digestive [Rangueil], CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], CHU Strasbourg, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital de la Croix-Rousse [CHU - HCL], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Chiche, L, David, A, Adam, R, Oliverius, M, Klempnauer, J, Vibert, E, Colledan, M, Lerut, J, Mazzafero, V, Di-Sandro, S, Laurent, C, Scuderi, V, Suc, B, Troisi, R, Bachelier, P, Dumortier, J, Gugenheim, J, Mabrut, J, Gonzalez-Pinto, I, Pruvot, F, Le-Treut, Y, Navarro, F, Ortiz-De-Urbina, J, Salame, E, Spada, M, and Bioulac-Sage, P
- Subjects
Registrie ,Adult ,Male ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,medicine.medical_treatment ,Clinical Decision-Making ,[SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery ,Glycogen Storage Disease Type I ,Liver transplantation ,Gastroenterology ,Adenoma, Liver Cell ,Cohort Studies ,03 medical and health sciences ,Rare Diseases ,0302 clinical medicine ,Rare Disease ,Retrospective Studie ,Internal medicine ,Carcinoma ,Humans ,Medicine ,Registries ,Retrospective Studies ,Transplantation ,Glycogen storage disease type I ,Hepatology ,business.industry ,Liver Neoplasms ,Focal nodular hyperplasia ,Retrospective cohort study ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Hepatocellular adenoma ,medicine.disease ,Liver Transplantation ,3. Good health ,Europe ,Treatment Outcome ,Liver Neoplasm ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Female ,030211 gastroenterology & hepatology ,Surgery ,Cohort Studie ,business ,Human - Abstract
International audience; The aim of this study was to collect data from patients who underwent liver transplantation (LT) for adenomatosis; to analyze the symptoms, the characteristics of the disease, and the recipient outcomes; and to better define the role of LT in this rare indication. This retrospective multicenter study, based on data from the European Liver Transplant Registry, encompassed patients who underwent LT for adenomatosis between January 1, 1986, and July 15, 2013, in Europe. Patients with glycogen storage disease (GSD) type IA were not excluded. This study included 49 patients. Sixteen patients had GSD, and 7 had liver vascular abnormalities. The main indications for transplantation were either a suspicion of hepatocellular carcinoma (HCC; 15 patients) or a histologically proven HCC (16 patients), but only 17 had actual malignant transformation (MT) of adenomas. GSD status was similar for the 2 groups, except for age and the presence of HCC on explants (P = 0.030). Three patients with HCC on explant developed recurrence after transplantation. We obtained and studied the pathomolecular characteristics for 23 patients. In conclusion, LT should remain an extremely rare treatment for adenomatosis. Indications for transplantation primarily concern the MT of adenomas. The decision should rely on morphological data and histological evidence of MT. Additional indications should be discussed on a case-by-case basis. In this report, we propose a simplified approach to this decision-making process.
- Published
- 2016
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