678 results on '"René Adam"'
Search Results
2. Tumors located in the central column of the liver are associated with increased surgical difficulty and postoperative complications following open liver resection for colorectal metastases
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Daniel Azoulay, Christophe Desterke, Prashant Bhangui, Chady Salloum, Maria Conticchio, Eric Vibert, Daniel Cherqui, René Adam, Philippe Ichai, Faouzi Saliba, Annie Elmaleh, Salima Naili, Chetana Lim, and Cyrille Feray
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Postoperative Complications ,Hepatology ,Liver Neoplasms ,Gastroenterology ,Hepatectomy ,Humans ,Vena Cava, Inferior ,Colorectal Neoplasms ,Retrospective Studies - Abstract
To assess the impact of difficult location (based on preoperative computed tomography) of liver metastases from colorectal cancer (LMCRC) on surgical difficulty, and occurrence of severe postoperative complications (POCs).A retrospective single-centre study of 911 consecutive patients with LMCRC who underwent hepatectomy by the open approach between 1998 and 2011, before implementation of laparoscopic surgery to obviate approach selection bias. LMCRC with at least one of the following four features on preoperative imaging: tumor invading the hepatocaval confluence or retro-hepatic inferior vena cava, centrally located (Segments 4,5,8) and10 cm in diameter, abutting the supra-hilar area, or involving the paracaval portion or caudate process of Segment 1; were considered as topographically difficult (top-diff). Independent predictors of surgical difficulty assessed by number of blood units transfused, duration of ischemia, and number of sessions of pedicle clamping during surgery and of severe POCs were identified by multivariate analysis before, and after propensity score matching.Top-diff tumor location independently predicted surgical difficulty. Severe POCs were associated with the tumor location [top-diff vs. topographically non difficult (non top-diff)], preoperative portal vein embolization, and variables related to surgical difficulty.LMCRC in difficult location independently predicts surgical difficulty and severe POCs.
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- 2022
3. The impact of advanced patient age in liver transplantation: a European Liver Transplant Registry propensity-score matching study
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Gabriel C Oniscu, Concepcion Gomez Gavara, Eylon Lahat, Constantino Fondevila, Daniel Esono, Daniel Azoulay, Daniel Cherqui, Krzysztof Zieniewicz, Jacques Pirenne, Chady Salloum, Stefan Schneeberger, Chris J Watson, Darius F. Mirza, Johann Pratschke, Karim Boudjema, Francesco Esposito, Chetana Lim, René Adam, Cyrille Feray, Vincent Karam, and Michael A. Heneghan
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medicine.medical_specialty ,Carcinoma, Hepatocellular ,Hepatology ,business.industry ,medicine.medical_treatment ,Graft Survival ,Liver Neoplasms ,Gastroenterology ,Liver transplantation ,Liver Transplantation ,Liver Cirrhosis, Alcoholic ,Risk Factors ,Patient age ,Internal medicine ,Propensity score matching ,Humans ,Medicine ,Registries ,Propensity Score ,business ,Aged ,Retrospective Studies - Abstract
The futility of liver transplantation in elderly recipients remains under debate in the HCV eradication era.The aim was to assess the effect of older age on outcome after liver transplantation. We used the ELTR to study the relationship between recipient age and post-transplant outcome. Young and elderly recipients were compared using a PSM method.A total of 10,172 cases were analysed. Recipient age65 years was identified as an independent risk factor associated with reduced patient survival (HR:1.42 95%CI:1.23-1.65,p 0.001). After PSM, 2124 patients were matched, and the same association was found between elderly recipients and patient survival and graft survival (p 0.001). As hepatocellular carcinoma and alcoholic cirrhosis were independent prognostic factors for patient and graft survival a propensity score-matching was performed for each. Patient and graft survival were significantly worse (p 0.05) in the alcoholic cirrhosis elderly group. However, patient and graft survival in the hepatocellular carcinoma cohort were similar (p 0.05) between groups.Liver transplantation is an acceptable and safe curative option for elderly transplant candidates, with worse long-term outcomes compare to young candidates. The underlying liver disease for liver transplantation has a significant impact on the selection of elderly patients.
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- 2022
4. End-ischemic Hypothermic Oxygenated Perfusion for Extended Criteria Donors in Liver Transplantation – A multicenter, randomized controlled trial - HOPExt
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Pierre Pradat, Solène Pantel, Marianne Maynard, Laure Lalande, Sylvie Thevenon, René Adam, Marc-Antoine < Allard, Fabien Robin, Michel Rayar, Emmanuel BOLESLAWSKI, Olivier Scatton, Mircea Chirica, François Faitot, Philippe Bachellier, Olivier Soubrane, Kayvan Mohkam, Jean-Yves Mabrut, and Mickaël Lesurtel
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Background: Given the scarce donor supply, an increasing number of so-called marginal or extended criteria donor (ECD) organs are used for liver transplantation. These ECD liver grafts are however known to be associated with a higher rate of early allograft dysfunction and primary non-function because of a greater vulnerability to ischemia-reperfusion injury. The end-ischemic Hypothermic Oxygenated Machine Perfusion (HOPE) technique may improve outcomes of liver transplantation with ECD grafts by decreasing reperfusion injury. Methods: HOPExt trial is a comparative open-label, multicenter, national, prospective, randomized, controlled study, in two parallel groups, using static cold storage, the gold standard procedure, as control. The trial will enroll adult patients on the transplant waiting list for liver failure or liver cirrhosis and/or liver malignancy requiring liver transplantation and receiving an ECD liver graft from a brain-dead donor. In the experimental group, ECD liver grafts will first undergo a classical static cold (4°C) storage followed by a hypothermic oxygenated perfusion (HOPE) for a period of 1 to 4 hours. The control group will consist of the classic static cold storage which is the gold standard procedure in liver transplantation. The primary objective of this trial is to study the efficacy of HOPE used before transplantation of ECD liver grafts from brain-dead donors in reducing postoperative early allograft dysfunction within the first 7 postoperative days compared to simple cold static storage. Discussion: We present in this protocol all study procedures in regard to the achievement of the HOPExt trial, to prevent biased analysis of trial outcomes and improve the transparency of the trial results. Enrollment of patients in the HOPExt trial has started on June 31, 2021, and is ongoing Trial registration: ClinicalTrials.gov NCT03929523. Registered on April 29, 2019, before the start of inclusion.
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- 2023
5. Supplementary Figure 2 from A Validated Prognostic Multigene Expression Assay for Overall Survival in Resected Colorectal Cancer Liver Metastases
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Michael I. D'Angelica, William R. Jarnagin, Ronald P. DeMatteo, Peter J. Allen, T. Peter Kingham, René Adam, Inne H.M. Borel Rinkes, Sander R. van Hooff, Nikol Snoeren, Agnes Viale, Jinru Shia, Simon Turcotte, Hiromichi Ito, Mithat Gönen, Arshi Arora, and Vinod P. Balachandran
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A. Overall survival in derivation (MSKCC) and validation (European) cohorts. B. Recurrence free survival in derivation (MSKCC) and validation (European) cohorts.
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- 2023
6. Supplementary Figure 3 from A Validated Prognostic Multigene Expression Assay for Overall Survival in Resected Colorectal Cancer Liver Metastases
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Michael I. D'Angelica, William R. Jarnagin, Ronald P. DeMatteo, Peter J. Allen, T. Peter Kingham, René Adam, Inne H.M. Borel Rinkes, Sander R. van Hooff, Nikol Snoeren, Agnes Viale, Jinru Shia, Simon Turcotte, Hiromichi Ito, Mithat Gönen, Arshi Arora, and Vinod P. Balachandran
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mRNA expression and hierarchical clustering of molecular risk score (MRS) genes in colorectal liver metastases in derivation cohort. Genes are indicated on the x-axis, patients on the y-axis.
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- 2023
7. Data from A Validated Prognostic Multigene Expression Assay for Overall Survival in Resected Colorectal Cancer Liver Metastases
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Michael I. D'Angelica, William R. Jarnagin, Ronald P. DeMatteo, Peter J. Allen, T. Peter Kingham, René Adam, Inne H.M. Borel Rinkes, Sander R. van Hooff, Nikol Snoeren, Agnes Viale, Jinru Shia, Simon Turcotte, Hiromichi Ito, Mithat Gönen, Arshi Arora, and Vinod P. Balachandran
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Purpose: Risk stratification after surgery for colorectal cancer liver metastases (CRLM) is achieved using clinicopathologic variables, however, is of limited accuracy. We sought to derive and externally validate a multigene expression assay prognostic of overall survival (OS) that is superior to clinicopathologic variables in patients with surgically resected CRLM.Experimental Design: We measured mRNA expression in prospectively collected frozen tumor from 96 patients with surgically resected CRLM at Memorial Sloan Kettering Cancer Center (MSKCC, New York, NY). We retrospectively generated a 20-gene molecular risk score (MRS) and compared its prognostic utility for OS and recurrence-free survival (RFS) with three common clinical risk scores (CRS). We then tested the prognostic ability of the MRS in an external validation cohort (European) of 119 patients with surgically resected CRLM at the University Medical Center Utrecht (Utrecht, the Netherlands) and Paul Brousse Hospital (Villejuif, France).Results: For OS in the MSKCC cohort, MRS was the strongest independent prognosticator (HR, 3.7–4.9; P < 0.001) followed by adjuvant chemotherapy (HR, 0.3; P ≤ 0.001). For OS in the European cohort, MRS was the only independent prognosticator (HR, 3.5; P = 0.007). For RFS, MRS was also independently prognostic in the MSKCC cohort (HR, 2.4–2.6; P ≤ 0.001) and the European cohort (HR, 1.6–2.5; P ≤ 0.05).Conclusions: Compared with CRSs, the MRS is more accurate, broadly applicable, and an independent prognostic biomarker of OS in resected CRLM. This MRS is the first externally validated prognostic multigene expression assay after metastasectomy for CRLM and warrants prospective validation. Clin Cancer Res; 22(10); 2575–82. ©2016 AACR.
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- 2023
8. Supplementary Tables from A Validated Prognostic Multigene Expression Assay for Overall Survival in Resected Colorectal Cancer Liver Metastases
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Michael I. D'Angelica, William R. Jarnagin, Ronald P. DeMatteo, Peter J. Allen, T. Peter Kingham, René Adam, Inne H.M. Borel Rinkes, Sander R. van Hooff, Nikol Snoeren, Agnes Viale, Jinru Shia, Simon Turcotte, Hiromichi Ito, Mithat Gönen, Arshi Arora, and Vinod P. Balachandran
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Univariate and multivariate analyses of recurrence free survival in derivation (Table 1) and validation (Table 2) cohorts.
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- 2023
9. Supplementary Figure 1 from A Validated Prognostic Multigene Expression Assay for Overall Survival in Resected Colorectal Cancer Liver Metastases
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Michael I. D'Angelica, William R. Jarnagin, Ronald P. DeMatteo, Peter J. Allen, T. Peter Kingham, René Adam, Inne H.M. Borel Rinkes, Sander R. van Hooff, Nikol Snoeren, Agnes Viale, Jinru Shia, Simon Turcotte, Hiromichi Ito, Mithat Gönen, Arshi Arora, and Vinod P. Balachandran
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Genes selected for molecular risk score (MRS).
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- 2023
10. The rex shunt for left portal vein reconstruction during hepatectomy for malignancy using of rex-shunt in adults for oncoliver surgery
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Maria Conticchio, Chady Salloum, Marc Antoine Allard, Nicolas Golse, Gabriella Pittau, Oriana Ciacio, Eric Vibert, Antonio Sa Cunha, Daniel Cherqui, René Adam, and Daniel Azoulay
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Adult ,Male ,Treatment Outcome ,Portal Vein ,Neoplasms ,Humans ,Hepatectomy ,Female ,Surgery ,Middle Aged ,Retrospective Studies - Abstract
Immediate portal reperfusion is mandatory following hepatectomy combined with portal vein (PV) resection. This retrospective study analyzes the feasibility and the outcomes of the Rex shunt (RS) for reconstruction of the left portal vein (LPV) and reperfusion of the remnant left liver or lobe following hepatectomy for cancer combined with resection of the PV in adult patients.From 2018 to 2021, an RS was used in the above setting to achieve R0 resection or when the standard LPV reconstruction failed or was deemed technically impossible.There were 6 male and 5 female patients (median age, 58 years) with perihilar cancer (5 cases) or miscellaneous cancers invading the PV (6 cases). A major hepatectomy was performed in 10/11 patients. The RS was indicated to achieve R0 resection or for technical reasons in 8 and 3 cases, respectively, and was feasible in all consecutive attempts with (10 cases) or without an interposed synthetic graft (1 case). Two fatal complications (PV thrombosis and pulmonary embolism) and three non-severe complications occurred in four patients within 90 days of surgery. Two patients died of tumor recurrence with a patent RS at 13 and 29 months, and 7 were recurrence free with a patent shunt with a follow-up of 1 to 37 months (median, 15 months).In case of remnant left liver or lobe following hepatectomy combined with resection of the PV, the RS may help to achieve R0 resection and is a valuable option to perform technically satisfying portal reperfusion of the remnant left liver or lobe.
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- 2022
11. Chemotherapy (doublet or triplet) plus targeted therapy by RAS status as conversion therapy in colorectal cancer patients with initially unresectable liver-only metastases. The UNICANCER PRODIGE-14 randomised clinical trial
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Marc Ychou, Michel Rivoire, Simon Thezenas, Rosine Guimbaud, Francois Ghiringhelli, Anne Mercier-Blas, Laurent Mineur, Eric Francois, Faiza Khemissa, Marion Chauvenet, Reza Kianmanesh, Marianne Fonck, Philippe Houyau, Thomas Aparicio, Marie-Pierre Galais, Franck Audemar, Eric Assenat, Evelyne Lopez-Crapez, Claire Jouffroy, Antoine Adenis, René Adam, and Olivier Bouché
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Male ,Cancer Research ,Liver Neoplasms ,Leucovorin ,Cetuximab ,Middle Aged ,Article ,Bevacizumab ,Pancreatic Neoplasms ,Oncology ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Camptothecin ,Fluorouracil ,Colorectal Neoplasms - Abstract
BACKGROUND: Colorectal cancer (CRC) patients have a better prognosis if metastases are resectable. Initially, unresectable liver-only metastases can be converted to resectable with chemotherapy plus a targeted therapy. We assessed which of chemotherapy doublet (2-CTx) or triplet (3-CTx), combined with targeted therapy by RAS status, would be better in this setting. METHODS: PRODIGE 14 was an open-label, multicenter, randomised Phase 2 trial. CRC patients with initially defined unresectable liver-only metastases received either, 2-CTx (FOLFOX or FOLFIRI) or 3-CTx (FOLFIRINOX), plus bevacizumab/cetuximab by RAS status. The primary endpoint was to increase the R0/R1 liver-resection rate from 50 to 70% with the 3-CTx. RESULTS: Patients (n = 256) were mainly men with an ECOG PS of 0, and a median age of 60 years. In total, 109 patients (42.6%) had RAS-mutated tumours. After a median follow-up of 45.6 months, the R0/R1 liver-resection rate was 56.9% (95% CI: 48–66) with the 3-CTx versus 48.4% (95% CI: 39–57) with the 2-CTx (P = 0.17). Median overall survival was 43.4 months with 3-CTx versus 40 months with 2-CTx. CONCLUSION: We failed to increase from 50 to 70% the R0/R1 liver-resection rate with the use of 3-CTx combined with bevacizumab or cetuximab by RAS status in CRC patients with initially unresectable liver metastases.
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- 2022
12. Liver transplantation for iatrogenic bile duct injury during cholecystectomy: a French retrospective multicenter study
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Bertrand Suc, Laurence Chiche, Bruno Heyd, Philippe Bachellier, Stéphanie Truant, Jean-Philippe Adam, Olivier Soubrane, Christophe Laurent, Ephrem Salamé, René Adam, Maxime Guieu, Karim Boudjema, Jean-Christophe Vaillant, Francis Navarro, CHU Bordeaux [Bordeaux], CHU Strasbourg, CHU Toulouse [Toulouse], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hépato-Biliaire [Hôpital Paul Brousse] (CHB), Hôpital Paul Brousse-Assistance Publique - Hôpitaux de Paris, CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), We declare we received no funding for this manuscript., Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Rennes (UR), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
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medicine.medical_specialty ,Cirrhosis ,[SDV]Life Sciences [q-bio] ,medicine.medical_treatment ,Biliary cirrhosis ,Iatrogenic Disease ,030230 surgery ,Liver transplantation ,03 medical and health sciences ,0302 clinical medicine ,Humans ,Medicine ,Cholecystectomy ,Retrospective Studies ,Hepatology ,business.industry ,Bile duct ,Mortality rate ,Gastroenterology ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Retrospective cohort study ,medicine.disease ,Liver Transplantation ,3. Good health ,Surgery ,Transplantation ,medicine.anatomical_structure ,Cholecystectomy, Laparoscopic ,030220 oncology & carcinogenesis ,Bile Ducts ,business - Abstract
The results of this study were presented during the 13th Congress of the E-AHPBA on June 3th 2019, in Amsterdam.; International audience; BACKGROUND: Major bile duct injuries (BDI) following cholecystectomy require complex reconstructive surgery. The aim was to collect the liver transplantations (LT) performed in France for major BDI following cholecystectomy, to analyze the risk factors and to report the results. METHODS: National multicenter observational retrospective study. All the patients who underwent a LT in France between 1994 and 2017, for BDI following cholecystectomy, were included. RESULTS: 30 patients were included. 25 BDI occurred in non hepato-biliary expert centers, 20 were initially treated in these centers. Median time between injury and LT was 3 years in case of an associated vascular injury (11 injuries), versus 11.7 years without vascular injury (p = 0.006). Post-transplant morbidity rate was 86.7%, mortality 23.5% at 5 years. CONCLUSION: Iatrogenic BDI remains a real concern with severe cases, associated with vascular damages or leading to cirrhosis, with no solution but LT. It is associated with high morbidity and not optimal results. This enlights the necessity of early referral of all major BDI in expert centers to prevent dramatic outcome. Decision to perform transplantation should be taken before dismal infectious situations or biliary cirrhosis and access to graft should be facilitated by Organ Sharing Organizations.
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- 2022
13. Influence of the ABO Blood Group System on Hepatocellular Carcinoma Recurrence After Liver Transplantation
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Kayvan, Mohkam, Raëf, Abdallah, Gisèle, N'kontchou, Nathalie, Ganne, Louise, Barbier, Ephrem, Salamé, Petru, Bucur, Michel, Rayar, Fabien, Robin, Karim, Boudjema, Daniel, Pietrasz, Daniel, Cherqui, René, Adam, Chetana, Lim, Eric, Savier, Olivier, Scatton, Charlotte, Maulat, Bertrand, Suc, Fabrice, Muscari, Alexis, Laurent, Christophe, Duvoux, Bruno, Heyd, Célia, Turco, Alexandre, Doussot, Philippe, Merle, Teresa, Antonini, Mickaël, Lesurtel, Cyril, Cossé, François, Durand, Olivier, Soubrane, François, Cauchy, and Jean-Yves, Mabrut
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Transplantation ,Carcinoma, Hepatocellular ,Risk Factors ,Liver Neoplasms ,Humans ,Neoplasm Recurrence, Local ,ABO Blood-Group System ,Liver Transplantation ,Retrospective Studies - Abstract
The ABO blood group system may influence tumorigenesis, but its prognostic value in liver transplantation (LT) for hepatocellular carcinoma (HCC) has never been assessed.All consecutive patients who underwent LT for HCC between 2013 and 2017 at 9 centers were analyzed. Predictors of tumor recurrence were identified using multivariable analysis, while comparison between group A and non-A recipients was performed after propensity score matching.Among 925 LT recipients, 406 were blood group A, 94 group B, 380 group O, and 45 group AB. On multivariable analysis, group A was associated with tumor recurrence (hazard ratio [HR] = 1.574 [95% confidence interval; 95% CI = 1.034-2.394] P = 0.034). After propensity score matching, 1- and 5-y recurrence rates were 7.4% and 20.1% in group A recipients versus 3.3% and 13.2% in non-A recipients (HR = 1.66 [95% CI = 1.12-2.45], P = 0.011). One and 5-y recurrence-free survivals were 85.2% and 66.8% in group A recipients versus 88.5% and 71.3% in non-A recipients (HR = 1.38 [95% CI = 1.01-1.90], P = 0.045). Among recipients within Milan criteria (n = 604), 1- and 5-y recurrence rates were 5.8% and 12.7% in group A recipients versus 3.1% and 12.2% in non-A recipients (HR = 1.197 [95% CI = 0.721-1.987], P = 0.485). Among recipients outside Milan criteria (n = 182), 1- and 5-y recurrence rates were 12.1% and 43.8% in group A recipients versus 3.9% and 15.6% in non-A recipients (HR = 3.175 [95% CI = 1.526-6.608], P = 0.002).ABO blood system influences the oncological outcome of recipients undergoing LT for HCC. Its incorporation in the prognostication model of LT for HCC may allow improving the management of LT candidates.
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- 2021
14. Perihilar Cholangiocarcinoma - Novel Benchmark Values for Surgical and Oncological Outcomes From 24 Expert Centers
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Camila Hidalgo-Salinas, Ryota Higuchi, Elissaios Kontis, Eva Breuer, Ho-Seong Han, Andrea Ruzzenente, Jennifer A. Yonkus, Victor Lopez-Lopez, Warsan Ismail, Richard D. Schulick, Matteo Mueller, Masayuki Ohtsuka, Wojciech G. Polak, Kim C Wagner, René Adam, Keun Soo Ahn, Rory L. Smoot, Joon Seong Park, Karim Boudjema, Takashi Mizuno, Ana Gleisner, Masato Nagino, Tsukasa Takayashiki, Gregory J. Gores, Tiffany C.L. Wong, Johann Pratschke, Chaya Shwaartz, Pierre-Alain Clavien, Mizelle D'Silva, Fabian Bartsch, Constantino Fondevila, Hauke Lang, Takehiro Noji, Ulf P. Neumann, Ricardo Robles-Campos, Ganesh Gunasekaran, Masakazu Yamamoto, Olivier Soubrane, Francesca Ratti, Andreas Prachalias, Katsuhiko Uesaka, Joris I. Erdmann, Myron Schwartz, Pål-Dag Line, Christian Benzing, Luca Aldrighetti, Amelia J. Hessheimer, Jan Bednarsch, Karl J. Oldhafer, Koo Jeong Kang, Michelle L. de Oliveira, Charles de Ponthaud, Chung Mau Lo, Gonzalo Sapisochin, Heithem Jeddou, Lynn E Nooijen, Hyung Sun Kim, Noémie Ammar-Khodja, Teiichi Sugiura, Bas Groot Koerkamp, Alfredo Guglielmi, Satoshi Hirano, Giuseppe Fusai, Mueller, M., Breuer, E., Mizuno, T., Bartsch, F., Ratti, F., Benzing, C., Ammar-Khodja, N., Sugiura, T., Takayashiki, T., Hessheimer, A., Kim, H. S., Ruzzenente, A., Ahn, K. S., Wong, T., Bednarsch, J., D'Silva, M., Koerkamp, B. G., Jeddou, H., Lopez-Lopez, V., de Ponthaud, C., Yonkus, J. A., Ismail, W., Nooijen, L. E., Hidalgo-Salinas, C., Kontis, E., Wagner, K. C., Gunasekaran, G., Higuchi, R., Gleisner, A., Shwaartz, C., Sapisochin, G., Schulick, R. D., Yamamoto, M., Noji, T., Hirano, S., Schwartz, M., Oldhafer, K. J., Prachalias, A., Fusai, G. K., Erdmann, J. I., Line, P. -D., Smoot, R. L., Soubrane, O., Robles-Campos, R., Boudjema, K., Polak, W. G., Han, H. -S., Neumann, U. P., Lo, C. -M., Kang, K. J., Guglielmi, A., Park, J. S., Fondevila, C., Ohtsuka, M., Uesaka, K., Adam, R., Pratschke, J., Aldrighetti, L., De Oliveira, M. L., Gores, G. J., Lang, H., Nagino, M., Clavien, P. -A., and Surgery
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Adult ,Male ,medicine.medical_specialty ,Percentile ,Asia ,Time Factors ,MEDLINE ,outcomes ,High morbidity ,Postoperative Complications ,SDG 3 - Good Health and Well-being ,Diabetes mellitus ,Internal medicine ,benchmarks ,80 and over ,Medicine ,Hepatectomy ,Humans ,Perihilar Cholangiocarcinoma ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,CCI ,Mortality rate ,Middle Aged ,medicine.disease ,surgical complications ,major liver surgery ,United States ,Europe ,Benchmarking ,Editorial ,Bile Duct Neoplasms ,Benchmark (computing) ,Surgery ,Female ,business ,Body mass index ,perihilar cholangiocarcinoma ,Follow-Up Studies ,Klatskin Tumor - Abstract
OBJECTIVE: The aim of this study was to define robust benchmark values for the surgical treatment of perihilar cholangiocarcinomas (PHC) to enable unbiased comparisons. BACKGROUND: Despite ongoing efforts, postoperative mortality and morbidity remains high after complex liver surgery for PHC. Benchmark data of best achievable results in surgical PHC treatment are however still lacking. METHODS: This study analyzed consecutive patients undergoing major liver surgery for PHC in 24 high-volume centers in 3 continents over the recent 5-year period (2014-2018) with a minimum follow-up of 1 year in each patient. Benchmark patients were those operated at high-volume centers (≥50 cases during the study period) without the need for vascular reconstruction due to tumor invasion, or the presence of significant co-morbidities such as severe obesity (body mass index ≥35), diabetes, or cardiovascular diseases. Benchmark cutoff values were derived from the 75th or 25th percentile of the median values of all benchmark centers. RESULTS: Seven hundred eight (39%) of a total of 1829 consecutive patients qualified as benchmark cases. Benchmark cut-offs included: R0 resection ≥57%, postoperative liver failure (International Study Group of Liver Surgery): ≤35%; in-hospital and 3-month mortality rates ≤8% and ≤13%, respectively; 3-month grade 3 complications and the CCI: ≤70% and ≤30.5, respectively; bile leak-rate: ≤47% and 5-year overall survival of ≥39.7%. Centers operating mostly on complex cases disclosed better outcome including lower post-operative liver failure rates (4% vs 13%; P = 0.002). Centers from Asia disclosed better outcomes. CONCLUSION: Surgery for PHC remains associated with high morbidity and mortality with now the availability of benchmark values covering 21 outcome parameters, which may serve as key references for comparison in any future analyses of individuals, group of patients or centers.
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- 2021
15. Characteristics, Trends, and Outcomes of Liver Transplantation for Primary Sclerosing Cholangitis in Female Versus Male Patients
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Herold J. Metselaar, Bo-Göran Ericzon, Vincent Karam, Marina Berenguer, Ulrich Baumann, René Adam, Darius F. Mirza, Tommaso Di Maira, Victoria Aguilera, Peter Lodge, Michael A. Heneghan, Krzysztof Zieniewicz, Pål-Dag Line, Christopher J.E. Watson, Jürgen Klempnauer, William Bennet, and Gastroenterology & Hepatology
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Adult ,Male ,medicine.medical_specialty ,Time Factors ,Databases, Factual ,medicine.medical_treatment ,Cholangitis, Sclerosing ,Population ,030230 surgery ,Liver transplantation ,Risk Assessment ,Primary sclerosing cholangitis ,03 medical and health sciences ,Sex Factors ,0302 clinical medicine ,Risk Factors ,Internal medicine ,medicine ,Humans ,Registries ,Healthcare Disparities ,education ,Transplantation ,education.field_of_study ,business.industry ,Incidence ,Incidence (epidemiology) ,Graft Survival ,Immunosuppression ,Health Status Disparities ,Middle Aged ,medicine.disease ,Liver Transplantation ,Europe ,Treatment Outcome ,Male patient ,Cohort ,Female ,030211 gastroenterology & hepatology ,business - Abstract
Background. The influence of sex on primary sclerosing cholangitis (PSC), pre- and postliver transplantation (LT) is unclear. Aims are to assess whether there have been changes in incidence, profile, and outcome in LT-PSC patients in Europe with specific emphasis on sex. Methods. Analysis of the European Liver Transplant Registry database (PSC patients registered before 2018), including baseline demographics, donor, biochemical, and clinical data at LT, immunosuppression, and outcome. Results. European Liver Transplant Registry analysis (n = 6463, 32% female individuals) demonstrated an increasing number by cohort (1980-1989, n = 159; 1990-1999, n = 1282; 2000-2009, n = 2316; 2010-2017, n = 2549) representing on average 4% of all transplant indications. This increase was more pronounced in women (from 1.8% in the first cohort to 4.3% in the last cohort). Graft survival rate at 1, 5, 10, 15, 20, and 30 y was 83.6%, 70.8%, 57.7%, 44.9%, 30.8%, and 11.6%, respectively. Variables independently associated with worse survival were male sex, donor and recipient age, cholangiocarcinoma at LT, nondonation after brain death donor, and reduced size of the graft. These findings were confirmed using a more recent LT population closer to the current standard of care (LT after the y 2000). Conclusions. An increasing number of PSC patients, particularly women, are being transplanted in European countries with better graft outcomes in female recipients. Other variables impacting outcome include donor and recipient age, cholangiocarcinoma, nondonation after brain death donor, and reduced graft size.
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- 2021
16. Impact of body mass index on hepatocellular carcinoma recurrence after liver transplantation through long-term follow-up
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Jihan A Shawky, Wafaa Ibrahim, G. Pittau, Khaled Amer, V. Karam, Didier Samuel, Daniel Cherqui, Rodolphe Sobesky, René Adam, Eric Vibert, Maysaa Abdallah Saeed, Faouzi Saliba, and Nada El-Domiaty
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medicine.medical_specialty ,Long term follow up ,business.industry ,medicine.medical_treatment ,Incidence (epidemiology) ,Retrospective cohort study ,Liver transplantation ,medicine.disease ,Obesity ,Gastroenterology ,Log-rank test ,Internal medicine ,Hepatocellular carcinoma ,medicine ,Original Article ,business ,Body mass index - Abstract
BACKGROUND: Obesity is associated with increased oncological risk and outcomes but the evidence surrounding the effect of body mass index (BMI) on increased risk of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) is still questionable. The purpose of this retrospective study of a large cohort of adult patients transplanted for HCC was to investigate the effect of BMI on the incidence of HCC recurrence and outcome. METHODS: Data from 427 adult recipients transplanted for HCC between 2000 and 2017 were collected. Patients were classified at time of LT according to the World Health Organization BMI classification into 3 groups; group 1: BMI
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- 2021
17. Health-related quality of life in locally advanced hepatocellular carcinoma treated by either radioembolisation or sorafenib (SARAH trial)
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Helena Pereira, Mohamed Bouattour, Marco D. Burgio, Eric Assenat, Jules Grégory, Jean-Pierre Bronowicki, Gilles Chatellier, Valérie Vilgrain, Elisabeth Delhom-Christol, Marjolène Fourcade, Boris Guiu, Alina Diana Ilonca, Julie Lonjon, Georges-Philippe Pageaux, Mohamed Abdel-Rehim, Wassim Allaham, Laurent Castera, Arnaud Dieudonné, Rachida Lebtahi, Maxime Ronot, Annie Sibert, Hélène Chor, Julie Devictor, Hélène Barraud, Christophe Bazin, Laetitia Imbert, Valérie Laurent, Elodie Mathias, Carine Chagneau-Derrode, Christelle Gallais, Rémy Perdrisot, Christine Silvain, Jean Pierre Tasu, Patrick Borentain, Bardia Farman, René Gerolami, Olivier Mundler, Jean-Francois Seitz, Vincent Vidal, Christophe Aubé, Francis Bouchet, Antoine Bouvier, Olivier Couturier, Frédéric Oberti, Laurent Vervueren, Isabelle Brenot-Rossi, Julien Darreon, Jean Luc Raoul, Anthony Sarran, Julia Chalaye, Charlotte Costentin, Emmanuel Itti, Hicham Kobeiter, Alain Luciani, Hélène Masset, René Adam, Maïté Lewin, Didier Samuel, Julien Edeline, Etienne Garin, Sophie Laffont, Yan Rolland, Isabelle Archambeaud, Thomas Carlier, Thomas Eugene, Eric Frampas, Christophe Cassinotto, Martine Guyot, Jean-Baptiste Hiriart, Bruno Lapuyade, Karine Tendero, Julien Vergniol, Philippe Bachellier, Julien Détour, Bernard Duclos, Michel Greget, Francois Habersetzer, Alessio Imperiale, Elise Enderlin, Philippe Merle, Agnès Rode, Julie Morvan, Eric Nguyen-Khac, Antoine Talbot, Thierry Yzet, Guillaume Baudin, Patrick Chevallier, Abakar Mahamat, Fabien Maurel, Thierry Piche, Micheline Razzouk, Patrick Hillon, Romaric Loffroy, Michel Toubeau, Julie Vincent, Jean-Marc Vrigneaud, Gabriele Barabino, Nadia Bouarioua, Muriel Cuilleron, Marie Ecochard, Nathalie Prevot-Bitot, Evelyne Rousset, Vincent Leroy, Ghislaine Reboulet, Julie Roux, Christian Sengel, Valérie Bourcier, Nathalie Ganne-Carrie, Olivier Seror, Sylvie Costo, Thông Dao, Cédric Desmonts, Jean-Pierre Pelage, Didier Defez, Jérôme Dumortier, Francesco Giammarile, Pierre-Jean Valette, Michela Bernardini, Nadia Ghazar, Olivier Pellerin, Julien Taieb, Pierre Weinmann, Alexandra Heurgue-Berlot, Claude Marcus, Daniele Sommacale, Maria-Angéla Castilla-Lièvre, Aurélie Forbes, Sophie Maitre, Lysiane Marthey, CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Equipe IFTIM [ImViA - EA7535], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Imagerie et Vision Artificielle [Dijon] (ImViA), and Université de Bourgogne (UB)-Université de Bourgogne (UB)
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Male ,Sorafenib ,Cancer Research ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Tare weight ,[PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph] ,Locally advanced ,Quality of life ,Internal medicine ,medicine ,Humans ,ComputingMilieux_MISCELLANEOUS ,Aged ,Social functioning ,Health related quality of life ,business.industry ,Liver Neoplasms ,Middle Aged ,medicine.disease ,Embolization, Therapeutic ,digestive system diseases ,Confidence interval ,Oncology ,Hepatocellular carcinoma ,Quality of Life ,Female ,business ,medicine.drug - Abstract
Background The aim of this ancillary study of the SARAH trial is to compare health-related quality of life (HRQoL) in patients with locally advanced or inoperable hepatocellular carcinoma (HCC) treated with transarterial radioembolisation (TARE) or sorafenib. Methods This study included randomised patients who received either TARE or at least one dose of sorafenib with no major deviation in the protocol and who had at least one QoL follow-up assessment in addition to the baseline evaluation. QoL was assessed from the date of randomisation using the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire, until disease progression or other reasons for stopping study participation. Data were analysed using linear mixed and time-dependent models. Results A total of 285 patients were included (122 and 163, in the TARE and sorafenib groups, respectively). Questionnaire completion rates were similar (77.5% versus 80.4%, in the TARE and sorafenib groups, respectively, p = 0.25). Longitudinal HRQoL analysis showed a significant treatment and time effects for fatigue and global health status, and significant treatment, time and treatment by time interaction effects for appetite loss, diarrhoea and social functioning. The median time to deterioration for the global health status was 3.9 months (95% confidence interval [CI] 3.7–4.3) versus 2.6 months (95% CI 2.0–3.0) in the TARE and sorafenib groups, respectively. Conclusions HRQoL was preserved longer with TARE than with sorafenib in locally advanced HCC. These data could be used to optimise management of patients with advanced or inoperable HCC.
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- 2021
18. Towards refining the utility of dual (18F-FDG / 18F-Choline) PET/CT for the management of hepatocellular carcinoma: a tertiary center study
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Recep E. SÖNMEZ, Florent L. BESSON, Jerome GHİDAGLİA, Maïté LEWİN, Lea GOMEZ, Chady SALLOUM, Gabriella PİTTAU, Oriana CIACIO, Marc A. ALLARD, Daniel CHERQUİ, René ADAM, Antonio SA CUNHA, Daniel AZOULAY, Eric VİBERT, and Nicolas GOLSE
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Radiology, Nuclear Medicine and imaging - Abstract
The role of positron emission tomography / computed tomography (PET/CT) in hepatocellular carcinoma (HCC) management is not clearly defined. Our objective was to analyze the utility of dual-PET/CT (18F-FDG + 18F-Choline) imaging findings on the BCLC staging and treatment decision for HCC patients.Between January 2011 and April 2019, 168 consecutive HCC patients with available baseline dual-PET/CT imaging data were retrospectively analyzed. To identify potential refinement criteria for surgically-treated patients, survival Kaplan-Meier curves of various standard-of-care and dual-PET/CT baseline parameters were estimated. Finally, multivariate cox proportional hazard ratios of the most relevant clinico-biological and/or PET parameters were estimated.Dual-PET/CT findings increased the score of BCLC staging in 21 (12.5%) cases. In 24.4% (n=41) of patients, the treatment strategy was modified by the PET findings. Combining AFP levels at a threshold of 10 ng/ml with 18F-FDG or 18F-Choline N status significantly impacted DFS (p0.05). In particular, the combined criteria of the N+ status assessed by 18F-Choline with AFP threshold of 10 ng/ml provided a highly predictive composite parameter for estimation of DFS according to multivariate analysis (HR=10.6, p0.05).The 18F-Choline / AFP composite parameter appears promising, and further prospective studies are mandatory to validate its oncological impact.
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- 2022
19. Cytoreductive surgery for colorectal liver metastases: is it worthwhile?
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René, Adam, Caterina, Accardo, and Marc-Antoine, Allard
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Antineoplastic Combined Chemotherapy Protocols ,Liver Neoplasms ,Humans ,Hepatectomy ,Surgery ,Cytoreduction Surgical Procedures ,Colorectal Neoplasms - Abstract
To date, surgery of colorectal liver metastases is the only chance of long-term survival with the principle of resecting all the metastases to be potentially curative (R0-R1 resection). However, 10-20% of patients are initially resectable. Along with the increasing efficacy of chemotherapy, around 20% of initially unresectable patients could be switched to secondary resectability after tumor downsizing with real hope of long-term survival. However, still a majority of patients remain "curatively" unresectable while responding to chemotherapy, owing to the impossibility to resect all the initial tumoral disease. For such extensive cases, cytoreductive surgery might provide a survival benefit, provided an objective tumor response with chemotherapy and optimal cytoreduction with almost no macroscopic residual disease.
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- 2022
20. R1 Vascular or Parenchymal Margins: What Is the Impact after Resection of Intrahepatic Cholangiocarcinoma?
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Andrea Mabilia, Alessandro D. Mazzotta, Fabien Robin, Mohammed Ghallab, Eric Vibert, René Adam, Daniel Cherqui, Antonio Sa Cunha, Daniel Azoulay, Chady Salloum, Gabriella Pittau, Oriana Ciacio, Marc Antoine Allard, Karim Boudjema, Laurent Sulpice, and Nicolas Golse
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Cancer Research ,Oncology ,intrahepatic cholangiocarcinoma ,R1 resection ,hepatectomy ,prognosis ,histopathology - Abstract
Background: to date, long-term outcomes of R1 vascular (R1vasc) and R1 parenchymal (R1par) resections in the setting of intrahepatic cholangiocarcinoma (iCCA) have been examined in only one study which did not find significant difference. Patients and Methods: we analyzed consecutive patients who underwent iCCA resection between 2000 and 2019 in two tertiary French medical centers. We report overall survival (OS) and disease-free-survival (DFS). Univariate and multivariate analyses were performed to determine associated factors. Results: 195 patients were analyzed. The number of R0, R1par and R1vasc patients was 128 (65.7%), 57 (29.2%) and 10 (5.1%), respectively. The 1- and 2-year OS rates in the R0, R1par and R1vasc groups were 83%, 87%, 57% and 69%, 75%, 45%, respectively (p = 0.30). The 1- and 2-year DFS rates in the R0, R1par and R1vasc groups were 58%, 50%, 30% and 43%, 28%, 10%, respectively (p = 0.019). Resection classification (HR 1.56; p = 0.003) was one of the independent predictors of DFS in multivariate analysis. Conclusions: the survival outcomes after R1par resection are intermediate to those after R0 or R1vasc resection. R1vasc resection should be avoided in patients with iCCA as it does not provide satisfactory oncological outcomes.
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- 2022
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21. Resectable and transplantable hepatocellular carcinoma: Integration of liver stiffness assessment in the decision-making algorithm
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Pauline Tortajada, Rodrigue Doamba, Luis Cano, Mohammed Ghallab, Marc Antoine Allard, Oriana Ciacio, Gabriella Pittau, Chady Salloum, Daniel Cherqui, René Adam, Antonio Sa Cunha, Daniel Azoulay, Alina Pascale, Eric Vibert, Nicolas Golse, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hépato-Biliaire [Hôpital Paul Brousse] (CHB), Hôpital Paul Brousse-Assistance Publique - Hôpitaux de Paris, Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, and This Research did not receive any specific funding from any agencies in the public, commercial, or not-for-profit areas.
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Carcinoma, Hepatocellular ,[SDV]Life Sciences [q-bio] ,Liver Neoplasms ,Humans ,Surgery ,Neoplasm Recurrence, Local ,Algorithms ,Aged ,Retrospective Studies - Abstract
International audience; BACKGROUND: Liver resection is a curative treatment for hepatocellular carcinoma (HCC) and an alternative to liver transplantation (LT). However, post-liver resection recurrence rates remain high. This study aimed to determine whether liver stiffness measurement (LSM) correlated with recurrence and to propose a method for predicting HCC recurrence exclusively using pre-liver resection criteria. METHODS: This retrospective monocentric study included patients who had undergone LR liver resection for HCC between 2015 and 2018 and who had (1) preoperative alpha-fetoprotein scores indicating initial transplant viability and (2) available preoperative LSM data. We developed a predictive score for recurrence over time using Cox univariate regression and multivariate analysis with a combination plot before selecting the optimal thresholds (receiver operating characteristic curves + Youden test). RESULTS: Sixty-six patients were included. After an average follow-up of 40 months, the recurrence rate was 45% (n = 30). Three-year overall survival was 88%. Four preoperative variables significantly impacted the time to recurrence: age ≥70 years, LSM ≥11 kPa, international normalized ratio (INR) ≥1.2, and maximum HCC diameter ≥3 cm. By assigning 1 point per positive item, patients with a score
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- 2022
22. The Role of IGL-2 Preservation Solution on Rat Livers during SCS and HOPE
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Njikem Asong-Fontem, Arnau Panisello-Rosello, Mylène Sebagh, Mathilde Gonin, Joan Rosello-Catafau, and René Adam
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Machine perfusion ,Caspase 3 ,Ischemia-reperfusion ,Organic Chemistry ,Organ Preservation Solutions ,General Medicine ,Organ Preservation ,ischemia-reperfusion ,glycocalyx ,machine perfusion ,fatty liver ,Glycocalyx ,Catalysis ,Computer Science Applications ,Rats ,Rats, Zucker ,Inorganic Chemistry ,Fatty Liver ,Perfusion ,Liver ,Animals ,Physical and Theoretical Chemistry ,HMGB1 Protein ,Molecular Biology ,Spectroscopy ,Transaminases - Abstract
The scarcity of livers for transplantation is rising, and new strategies to extend the donor pool are being explored. One solution is to use marginal grafts from extended criteria donors, presenting, for example, liver steatosis. As current preservation solutions (UW, HTK, and IGL-1) were mainly designed for static cold storage (SCS) only, IGL-2, a modified version of IGL-1, was developed to be suitable for SCS and dynamic preservation, such as hypothermic oxygenated perfusion (HOPE). In this study, we investigated the combined effect of IGL-2, SCS, and HOPE and compared it to the most used preservation solution (UW and Belzer MPS). Four experimental groups with six rats each were designed using Zucker rats. All groups underwent 24 h of SCS (in IGL-2 or UW) + 2 h of normothermic machine perfusion (NMP) at 37 °C to mimic transplantation. HOPE (IGL-2 or Belzer MPS) was performed before NMP on half of the rats. The IGL-2 group demonstrated lower transaminases and a significantly low level of glycocalyx proteins, CASP3, and HMGB1 in the perfusates. These data suggest the protective role of IGL-2 for fatty livers in preserving the endothelial glycocalyx, apoptosis, and inflammation.
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- 2022
23. Pre-Ischemic Hypothermic Oxygenated Perfusion Alleviates Protective Molecular Markers of Ischemia-Reperfusion Injury in Rat Liver
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Njikem Asong-Fontem, Arnau Panisello-Rosello, Nassiba Beghdadi, Alexandre Lopez, Joan Rosello-Catafau, and René Adam
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Perfusion ,Transplantation ,Liver ,Reperfusion Injury ,Animals ,Surgery ,Organ Preservation ,Warm Ischemia ,Biomarkers ,Rats ,Liver Transplantation - Abstract
To expand the pool of organs, hypothermic oxygenated perfusion (HOPE), one of the most promising perfusion protocols, is currently performed after cold storage (CS) at transplant centers (HOPE-END). We investigated a new timing for HOPE, hypothesizing that performing HOPE before CS (HOPE-PRE) could boost mitochondrial protection allowing the graft to better cope with the accumulation of oxidative stress during CS. We analyzed liver injuries at 3 different levels. Histologic analysis demonstrated that, compared to classical CS (CTRL), the HOPE-PRE group showed significantly less ischemic necrosis compared to CTRL vs HOPE-END. From a biochemical standpoint, transaminases were lower after 2 hours of reperfusion in the CTRL vs HOPE-PRE group, which marked decreased liver injury. qPCR analysis on 37 genes involved in ischemia-reperfusion injury revealed protection in HOPE-PRE and HOPE-END compared to CTRL mediated through similar pathways. However, the CTRL vs HOPE-PRE group demonstrated an increased transcriptional level for protective genes compared to the CTRL vs HOPE-END group. This study provides insights on novel biomarkers that could be used in the clinic to better characterize graft quality improving transplantation outcomes.
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- 2022
24. The Liver Retransplantation Risk Score
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Steven J. Staffa, Johann Pratschke, Arianeb Mehrabi, Wojciech G. Polak, Daniel Cherqui, Andreas Paul, Vincent Karam, Maureen J M Werner, Vincent E de Meijer, Olivier Soubrane, René Adam, Darius F. Mirza, Mauro Salizzoni, David Zurakowski, Robert J. Porte, Michael A. Heneghan, Jürgen Klempnauer, Michael Allison, Isabel M A Brüggenwirth, Surgery, Groningen Institute for Organ Transplantation (GIOT), and Center for Liver, Digestive and Metabolic Diseases (CLDM)
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Adult ,Reoperation ,medicine.medical_specialty ,medicine.medical_treatment ,Medizin ,graft survival ,Liver transplantation ,Severity of Illness Index ,United Network for Organ Sharing ,European Liver and Intestine Transplant Association ,End Stage Liver Disease ,Liver disease ,Risk Factors ,Internal medicine ,RELT ,Humans ,Medicine ,INDEX ,Retrospective Studies ,European Liver Transplant Registry ,Transplantation ,GRAFT FAILURE ,Framingham Risk Score ,liver transplantation ,business.industry ,Hazard ratio ,risk assessment ,Original Articles ,Prognosis ,medicine.disease ,TRANSPLANT REGISTRY ,Original Article ,Graft survival ,Adult liver ,business ,Risk assessment - Abstract
Summary High‐risk combinations of recipient and graft characteristics are poorly defined for liver retransplantation (reLT) in the current era. We aimed to develop a risk model for survival after reLT using data from the European Liver Transplantation Registry, followed by internal and external validation. From 2006 to 2016, 85 067 liver transplants were recorded, including 5581 reLTs (6.6%). The final model included seven predictors of graft survival: recipient age, model for end‐stage liver disease score, indication for reLT, recipient hospitalization, time between primary liver transplantation and reLT, donor age, and cold ischemia time. By assigning points to each variable in proportion to their hazard ratio, a simplified risk score was created ranging 0–10. Low‐risk (0–3), medium‐risk (4–5), and high‐risk (6–10) groups were identified with significantly different 5‐year survival rates ranging 56.9% (95% CI 52.8–60.7%), 46.3% (95% CI 41.1–51.4%), and 32.1% (95% CI 23.5–41.0%), respectively (P, The retransplantation risk score.
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- 2021
25. Letter to the Editor: Living donor liver transplantation for people with PSC
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Melina Heinemann, René Adam, Vincent Karam, and Christoph Schramm
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Hepatology - Published
- 2023
26. Radiofrequency ablation vs surgical resection in elderly patients with hepatocellular carcinoma in Milan criteria
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Giacomo Assirati, Maria Conticchio, Giulio Cesare Vitali, Antonio Rampoldi, Taiga Wakabayashi, Nicola de’Angelis, Ferdinando M. Anelli, Tullio Piardi, Emanuele Felli, Patrick Pessaux, Paolo Magistri, Riccardo Memeo, Letizia Laera, Luca Aldrighetti, Antonella Delvecchio, Javier Briceño, Fabrizio Di Benedetto, Riccardo Inchingolo, Alexis Laurent, Daniel Cherqui, Francesca Ratti, Maximiliano Gelli, René Adam, Conticchio, M., Inchingolo, R., Delvecchio, A., Laera, L., Ratti, F., Gelli, M., Anelli, F., Laurent, A., Vitali, G., Magistri, P., Assirati, G., Felli, E., Wakabayashi, T., Pessaux, P., Piardi, T., di Benedetto, F., De'Angelis, N., Briceno&, Tild, Rampoldi, A., Adam, R., Cherqui, D., Aldrighetti, L, and Memeo, R.
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medicine.medical_specialty ,Carcinoma, Hepatocellular ,Multivariate analysis ,Hepatocellular carcinoma ,Radiofrequency ablation ,Aucun ,Milan criteria ,Severity of Illness Index ,law.invention ,End Stage Liver Disease ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,law ,Propensity score matching ,Hepatectomy ,Humans ,Medicine ,Aged ,Retrospective Studies ,Radiofrequency Ablation ,business.industry ,Proportional hazards model ,Carcinoma ,Liver Neoplasms ,Gastroenterology ,Hepatocellular ,General Medicine ,Odds ratio ,medicine.disease ,Surgery ,Elderly patients ,Neoplasm Recurrence ,Treatment Outcome ,Local ,Surgical resection ,030220 oncology & carcinogenesis ,Neoplasm Recurrence, Local ,Catheter Ablation ,030211 gastroenterology & hepatology ,business - Abstract
BACKGROUND Surgical resection and radiofrequency ablation (RFA) represent two possible strategy in treatment of hepatocellular carcinoma (HCC) in Milan criteria. AIM To evaluate short- A nd long-term outcome in elderly patients (70 years) with HCC in Milan criteria, which underwent liver resection (LR) or RFA. METHODS The study included 594 patients with HCC in Milan criteria (429 in LR group and 165 in RFA group) managed in 10 European centers. Statistical analysis was performed using the Kaplan-Meier method before and after propensity score matching (PSM) and Cox regression. RESULTS After PSM, we compared 136 patients in the LR group with 136 patients in the RFA group. Overall survival at 1, 3, and 5 years was 91%, 80%, and 76% in the LR group and 97%, 67%, and 41% in the RFA group respectively (P = 0.001). Diseasefree survival at 1, 3, and 5 years was 84%, 60% and 44% for the LR group, and 63%, 36%, and 25% for the RFA group (P = 0.001).Postoperative Clavien-Dindo IIIIV complications were lower in the RFA group (1% vs 11%, P = 0.001) in association with a shorter length of stay (2 d vs 7 d, P = 0.001).In multivariate analysis, Model for End-stage Liver Disease (MELD) score (10) [odds ratio (OR) = 1.89], increased value of international normalized ratio (1.3) (OR = 1.60), treatment with radiofrequency (OR = 1.46) ,and multiple nodules (OR = 1.19) were independent predictors of a poor overall survival while a high MELD score (10) (OR = 1.51) and radiofrequency (OR = 1.37) were independent factors associated with a higher recurrence rate. CONCLUSION Despite a longer length of stay and a higher rate of severe postoperative complications, surgery provided better results in long-term oncological outcomes as compared to ablation in elderly patients (70 years) with HCC in Milan criteria. © 2021 The Author(s). Published by Baishideng Publishing Group Inc. All rights reserved.
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- 2021
27. Optimal patient selection for successful two‐stage hepatectomy of bilateral colorectal liver metastases
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Marc-Antoine Allard, Hideo Baba, Katsunori Imai, and René Adam
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endocrine system ,medicine.medical_specialty ,RD1-811 ,endocrine system diseases ,Early Recurrence ,medicine.medical_treatment ,RC799-869 ,Review Article ,Disease ,Medicine ,Effective treatment ,Review Articles ,Selection (genetic algorithm) ,business.industry ,two‐stage hepatectomy ,Mortality rate ,Gastroenterology ,Diseases of the digestive system. Gastroenterology ,Surgery ,colorectal liver metastases ,Two stage hepatectomy ,Treatment strategy ,Hepatectomy ,business ,hormones, hormone substitutes, and hormone antagonists ,patient selection - Abstract
Two‐stage hepatectomy (TSH) is one of the specific surgical techniques that can expand the pool of resectable patients with initially unresectable colorectal liver metastases (CRLM). The indication of TSH for CRLM is only bilateral, multinodular disease, which cannot be resected by a single hepatectomy. TSH is nowadays considered an effective treatment for selected patients, with acceptable morbidity/mortality rates and promising long‐term outcomes. However, not all eligible patients can benefit from the TSH strategy. One of the most important issues is dropout from the strategy (failure to complete both of the two sequential procedures), because the survival of such patients is drastically worse compared with patients who can complete both stages. Another important issue is the early recurrence rate and subsequent poor survival even after completion of TSH. Thus, the selection of appropriate patients who can really benefit from the TSH strategy is crucial. This review discusses the optimal patient selection for TSH, which should be helpful for the development of treatment strategies for patients with extensive CRLM., Although two‐stage hepatectomy (TSH) for extensive colorectal liver metastases (CRLM) is nowadays considered an effective treatment for selected patients, with acceptable morbidity/mortality rates and promising long‐term outcomes, not all eligible patients can benefit from this strategy. In this review, we discuss the optimal patient selection for TSH, which should be helpful for the development of treatment strategies for patients with extensive CRLM.
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- 2021
28. De novo hepatocellular carcinoma in a non-cirrhotic allograft 27 years after liver transplantation: A case report
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Daniel Azoulay, Jocelyne Hamelin, Didier Samuel, Eric Vibert, Daniel Cherqui, C. Salloum, Nada El-Domiaty, M. Sebagh, Faouzi Saliba, and René Adam
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Transplantation ,medicine.medical_specialty ,Cirrhosis ,medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,Cancer ,030230 surgery ,Liver transplantation ,medicine.disease ,Gastroenterology ,digestive system diseases ,03 medical and health sciences ,HBcAg ,0302 clinical medicine ,Renal cell carcinoma ,Internal medicine ,Hepatocellular carcinoma ,Biopsy ,Immunology and Allergy ,Medicine ,Pharmacology (medical) ,business ,Complication - Abstract
Hepatocellular carcinoma recurrence after liver transplantation is a well-known complication but the development of de novo hepatocellular carcinoma in non-cirrhotic allograft with no previous history of hepatic malignancy either in the donor or the recipient is extremely rare. A 33-year-old man underwent deceased donor liver transplantation due to HBV-HDV cirrhosis in 1991. The donor was healthy, with negative viral serology. Pretransplant assessment and explant liver pathology revealed no tumor. He developed an 8 cm mediastinal thymus cancer in 2014, a chronic myeloid leukemia in 2015 and a 16 mm renal cell carcinoma in 2017. After 27 years, in 2018, his routine follow-up sonography showed incidentally a 37 mm hepatic nodule in segment VII which revealed after percutaneous liver guided biopsy a hepatocellular carcinoma. As no extra hepatic metastasis was noted, segmentectomy was done. The pathological report confirmed a moderately differentiated hepatocellular carcinoma nodule of 50 mm diameter with absence of microvascular invasion and the non-tumoral liver showed histological features of NASH (SAF score: S1A2F3, NAS score: A3F3 and LAFSc:5) with absence of HBsAg and HBcAg. This case emphasizes the importance of long-term close surveillance by imaging of the graft even in the absence of viral recurrence and graft cirrhosis.
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- 2021
29. Liver Transplantation for Acute Intermittent Porphyria
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Staffan Wahlin, Helena Isoniemi, Stéphanie Perrodin, Rosario Sanchez, Mattias Lissing, Olivier Boillot, Florian P. Reiter, Felix Braun, René Adam, Uta Herden, Janneke G. Langendonk, Vincent Karam, Urszula Ołdakowska-Jedynak, Laurent Gouya, Jordi Colmenero, Espen Melum, Greg Nowak, Paolo Ventura, Alexander Boyd, Elizabeth Mowlem, Wouter Meersseman, HUS Abdominal Center, IV kirurgian klinikka, Helsinki University Hospital Area, and Internal Medicine
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Male ,medicine.medical_specialty ,medicine.medical_treatment ,rare disease ,Renal function ,610 Medicine & health ,030230 surgery ,Liver transplantation ,03 medical and health sciences ,Impaired renal function ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Registries ,ELTR ,Survival rate ,Retrospective Studies ,Acute intermittent porphyria ,inherited, metabolic disease, rare disease, neuropathy, ELTR ,Transplantation ,Hepatology ,business.industry ,Original Articles ,3126 Surgery, anesthesiology, intensive care, radiology ,metabolic disease ,medicine.disease ,Liver Failure and Portal Hypertension ,Kidney Transplantation ,inherited ,Liver Transplantation ,3. Good health ,Porphyria ,Porphyria, Acute Intermittent ,Quality of Life ,Original Article ,Female ,neuropathy ,030211 gastroenterology & hepatology ,Surgery ,business ,Neurological impairment ,Rare disease - Abstract
Recurrent attacks of acute intermittent porphyria (AIP) result in poor quality of life and significant risks of morbidity and mortality. Liver transplantation (LT) offers a cure, but published data on outcomes after LT are limited. We assessed the pretransplant characteristics, complications, and outcomes for patients with AIP who received a transplant. Data were collected retrospectively from the European Liver Transplant Registry and from questionnaires sent to identified transplant and porphyria centers. We studied 38 patients who received transplants in 12 countries from 2002 to 2019. Median age at LT was 37 years (range, 18-58), and 34 (89%) of the patients were women. A total of 9 patients died during follow-up, and 2 patients were retransplanted. The 1-year and 5-year overall survival rates were 92% and 82%, which are comparable with other metabolic diseases transplanted during the same period. Advanced pretransplant neurological impairment was associated with increased mortality. The 5-year survival rate was 94% among 19 patients with moderate or no neuropathy at LT and 83% among 10 patients with severe neuropathy (P = 0.04). Pretransplant renal impairment was common. A total of 19 (51%) patients had a GFR < 60 mL/minute. Although few patients improved their renal function after LT, neurological impairments improved, and no worsening of neurological symptoms was recorded. No patient had AIP attacks after LT, except for a patient who received an auxiliary graft. LT is a curative treatment option for patients with recurrent attacks of AIP. Severe neuropathy and impaired renal function are common and increase the risk for poor outcomes. If other treatment options fail, an evaluation for LT should be performed early. ispartof: LIVER TRANSPLANTATION vol:27 issue:4 pages:491-501 ispartof: location:United States status: published
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- 2021
30. Management of disappearing colorectal liver metastases: an international survey
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Virginia Sun, René Adam, Mustafa Raoof, Yuman Fong, Laleh G. Melstrom, Thomas J. Hugh, Susanne G. Warner, Gagandeep Singh, Paul Wong, and Kenneth D. Chavin
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medicine.medical_specialty ,Preoperative planning ,Hepatology ,business.industry ,General surgery ,Liver Neoplasms ,Gastroenterology ,International survey ,MEDLINE ,Magnetic Resonance Imaging ,03 medical and health sciences ,0302 clinical medicine ,Surveys and Questionnaires ,030220 oncology & carcinogenesis ,medicine ,Content validity ,Hepatectomy ,Humans ,030211 gastroenterology & hepatology ,Colorectal Neoplasms ,business ,Chemotherapy response - Abstract
Improved chemotherapy response rates have lead to "disappearing" colorectal liver metastases (dCRLM). We aim to assess management patterns of dCRLM from an international body of hepatobiliary surgeons.A survey was designed, tested for item relevance, readability and content validity, and distributed to the AHPBA, IHPBA and ANZHPBA.The majority of 226 respondents were15 years from training (69%), practiced in academia (82%) and devoted50% of their practice to hepatobiliary (75%). Surgeons utilize CT(45%) or MRI(47%) for preoperative planning with a preferred imaging interval of6 weeks. Nearly all have experienced dCRLM (99%) and 63% of surgeons have waited a few months to assess for durability of response prior to definitive surgical/ablative therapy. Only 24% place fiducial markers for lesions1-cm prior to neoadjuvant chemotherapy. Intra-operatively, 97% of surgeons perform ultrasound, and 71% ablation. When a tumor has "disappeared," 49% elect for observation and 31% resect if the dCRLM is superficial. Of those electing observation, 87% believe there is effective treatment with progression on surveillance imaging.Nearly all surgeons have experienced dCRLM with half choosing observation over intervention due to the belief that these lesions may be re-addressed in the future.
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- 2021
31. Predicting the risk of post-hepatectomy portal hypertension using a digital twin: A clinical proof of concept
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Florian Joly, Maïté Lewin, D. Castaing, Quentin Nicolas, Prisca Combari, Daniel Cherqui, Didier Samuel, Chloe Audebert, Antonio Sa Cunha, Eric Vibert, Marc-Antoine Allard, Irene E. Vignon-Clementel, René Adam, and N. Golse
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Male ,0301 basic medicine ,medicine.medical_specialty ,Cardiac output ,Portal venous pressure ,medicine.medical_treatment ,Clinical Decision-Making ,03 medical and health sciences ,Postoperative Complications ,0302 clinical medicine ,Liver Function Tests ,Risk Factors ,Internal medicine ,Hypertension, Portal ,Hepatectomy ,Humans ,Medicine ,Prospective Studies ,Aged ,Hepatology ,Portal Vein ,business.industry ,Liver failure ,Middle Aged ,Models, Theoretical ,Prognosis ,medicine.disease ,Magnetic Resonance Imaging ,Portal Pressure ,030104 developmental biology ,Cohort ,Cardiology ,Feasibility Studies ,Portal hypertension ,Female ,030211 gastroenterology & hepatology ,business ,Complication ,Liver Failure ,Major hepatectomy ,Follow-Up Studies - Abstract
Background & Aims Despite improvements in medical and surgical techniques, post-hepatectomy liver failure (PHLF) remains the leading cause of postoperative death. High postoperative portal vein pressure (PPV) and portocaval gradient (PCG), which cannot be predicted by current tools, are the most important determinants of PHLF. Therefore, we aimed to evaluate a digital twin to predict the risk of postoperative portal hypertension (PHT). Methods We prospectively included 47 patients undergoing major hepatectomy. A mathematical (0D) model of the entire blood circulation was assessed and automatically calibrated from patient characteristics. Hepatic flows were obtained from preoperative flow MRI (n = 9), intraoperative flowmetry (n = 16), or estimated from cardiac output (n = 47). Resection was then simulated in these 3 groups and the computed PPV and PCG were compared to intraoperative data. Results Simulated post-hepatectomy pressures did not differ between the 3 groups, comparing well with collected data (no significant differences). In the entire cohort, the correlation between measured and simulated PPV values was good (r = 0.66, no adjustment to intraoperative events) or excellent (r = 0.75) after adjustment, as well as for PCG (respectively r = 0.59 and r = 0.80). The difference between simulated and measured post-hepatectomy PCG was ≤3 mmHg in 96% of cases. Four patients suffered from lethal PHLF for whom the model satisfactorily predicted their postoperative pressures. Conclusions We demonstrated that a 0D model could correctly anticipate postoperative PHT, even using estimated hepatic flow rates as input data. If this major conceptual step is confirmed, this algorithm could change our practice toward more tailor-made procedures, while ensuring satisfactory outcomes. Lay summary Post-hepatectomy portal hypertension is a major cause of liver failure and death, but no tool is available to accurately anticipate this potentially lethal complication for a given patient. Herein, we propose using a mathematical model to predict the portocaval gradient at the end of liver resection. We tested this model on a cohort of 47 patients undergoing major hepatectomy and demonstrated that it could modify current surgical decision-making algorithms.
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- 2021
32. Ideal Surgical Margin to Prevent Early Recurrence After Hepatic Resection for Hepatocellular Carcinoma
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Hidetoshi Nitta, Daniel Cherqui, Henri Bismuth, Eric Vibert, Mylène Sebagh, Marc-Antoine Allard, Hideo Baba, Nicolas Golse, Gabriella Pittau, Antonio Sa Cunha, Denis Castaing, René Adam, and O. Ciacio
- Subjects
medicine.medical_specialty ,Surgical margin ,business.industry ,Odds ratio ,030230 surgery ,Vascular surgery ,medicine.disease ,Surgery ,Cardiac surgery ,03 medical and health sciences ,0302 clinical medicine ,Margin (machine learning) ,Cardiothoracic surgery ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,medicine ,business ,Abdominal surgery - Abstract
Postoperative early recurrence after hepatic resection for hepatocellular carcinoma (HCC) poses a challenge to surgeons, and the effect of a surgical margin is still controversial. This study aimed to identify an ideal margin to prevent early recurrence. A total of 226 consecutive patients who underwent primary curative hepatic resection for solitary and primary HCC were enrolled. The definition of early recurrence was determined using the minimum P value approach. Logistic regression analysis was used to identify the risk factors of early recurrence. The receiver-operating characteristic (ROC) curve was used to identify the optimal cut-off of the surgical margin and early recurrence. Recurrence within 8 months induced the poorest overall survival (P = 2×10−15). ROC analysis showed that the optimal cut-off value of the surgical margin was 7 mm. The risk factors of early recurrence (≤ 8-month recurrence) were preoperative alpha-fetoprotein levels ≥ 100 ng/ml (Odds ratio [OR] 4.92 [2.28–10.77], P 7-mm margin is important to prevent early recurrence. Patients with HCC and alpha-fetoprotein levels > 100 ng/ml, non-capsule formation, or microvascular invasion may have a survival benefit from a ≥ 7-mm margin.
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- 2021
33. Clinical practice guidelines for the management of liver metastases from extrahepatic primary cancers 2021
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H. Takeda, Tomohiko Ukai, Masakazu Yamamoto, Makoto Ueno, Steven M. Strasberg, René Adam, Mariano E Giménez, Takuro Mizukami, Naohiro Okano, Palepu Jagannath, Ho-Seong Han, Katsunori Sakamoto, Masato Ozaka, Takayuki Ueno, Susumu Hijioka, Koji Asai, Yoo Seok Yoon, Keita Wada, Keiji Sano, Toru Beppu, Satoru Shikata, Takako Eguchi Nakajima, Tsutomu Tabata, Shingo Yamashita, Do Youn Oh, Yoichi Naito, Tadahiro Takada, Taizo Hibi, Junji Furuse, Masayuki Ohtsuka, Koichi Hayano, Tsann Long Hwang, Hee-Jung Wang, Masahiro Yoshida, Teijiro Hirashita, Nozomu Sakai, Shao Ciao Luo, Hisato Kawakami, Yukio Iwashita, Ryusei Matsuyama, Michael G. Sarr, Olivier Scatton, and Yasuhisa Mori
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medicine.medical_specialty ,medicine.medical_treatment ,Population ,030230 surgery ,Malignancy ,Systemic therapy ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Hepatectomy ,Humans ,education ,Grading (tumors) ,education.field_of_study ,Hepatology ,business.industry ,General surgery ,Standard treatment ,Liver Neoplasms ,medicine.disease ,Clinical trial ,Systematic review ,030220 oncology & carcinogenesis ,Surgery ,business - Abstract
Background Hepatectomy is standard treatment for colorectal liver metastases; however, it is unclear whether liver metastases from other primary cancers should be resected or not. The Japanese Society of Hepato-Biliary-Pancreatic Surgery therefore created clinical practice guidelines for the management of metastatic liver tumors. Methods Eight primary diseases were selected based on the number of hepatectomies performed for each malignancy per year. Clinical questions were structured in the population, intervention, comparison, and outcomes (PICO) format. Systematic reviews were performed, and the strength of recommendations and the level of quality of evidence for each clinical question were discussed and determined. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations. Results The eight primary sites were grouped into five categories based on suggested indications for hepatectomy and consensus of the guidelines committee. Fourteen clinical questions were devised, covering five topics: (1) diagnosis, (2) operative treatment, (3) ablation therapy, (4) the eight primary diseases, and (5) systemic therapies. The grade of recommendation was strong for one clinical question and weak for the other 13 clinical questions. The quality of the evidence was moderate for two questions, low for 10, and very low for two. A flowchart was made to summarize the outcomes of the guidelines for the indications of hepatectomy and systemic therapy. Conclusions These guidelines were developed to provide useful information based on evidence in the published literature for the clinical management of liver metastases, and they could be helpful for conducting future clinical trials to provide higher-quality evidence.
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- 2020
34. Efficacy and safety of chronomodulated irinotecan, oxaliplatin, 5‐fluorouracil and leucovorin combination as first‐ or second‐line treatment against metastatic colorectal cancer: Results from the International <scp>EORTC</scp> 05011 Trial
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Sylvie Giacchetti, Carlo Garufi, Pasquale F. Innominato, Christian Focan, Angela Torsello, Abdoulaye Karaboué, Ayhan Ulusakarya, René Adam, Francis Lévi, Philippe Chollet, and Mohamed Bouchahda
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Oncology ,Cancer Research ,medicine.medical_specialty ,Chemotherapy ,Colorectal cancer ,business.industry ,FOLFIRINOX ,medicine.medical_treatment ,medicine.disease ,Oxaliplatin ,Irinotecan ,03 medical and health sciences ,Regimen ,0302 clinical medicine ,Fluorouracil ,030220 oncology & carcinogenesis ,Internal medicine ,Toxicity ,medicine ,business ,medicine.drug - Abstract
The triplet combination of irinotecan, oxaliplatin and fluorouracil is an active frontline regimen in metastatic colorectal cancer, but scarce data exist on its use as salvage treatment. We aimed at assessing its safety and efficacy profiles with its circadian-based administration (chronoIFLO5) as either first- or second-line treatment, within the time-finding EORTC 05011 trial. Five-day chronoIFLO5 was administered every 3 weeks in patients with PS 0, 1 or 2. It consisted of chronomodulated irinotecan (180 mg/sqm), oxaliplatin (80 mg/sqm) and fluorouracil-leucovorin (2800 and 1200 mg/sqm, respectively). For our study, toxicity and antitumour activity were evaluated separately in first- and second-line settings. Primary endpoints included Grade 3-4 toxicity rates, best objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). One-hundred forty-nine and 44 patients were treated in first-line and second-line settings, respectively, with a total of 1138 cycles with median relative dose intensities of about 90%. Demographics were comparable in the two groups. Thirty-six (24.7%) and 10 (22.2%) patients experienced at least one episode of severe toxicity in first line and second line, respectively. Frontline chronoIFLO5 yielded an ORR of 62.3% [95% CI: 54.2-70.4] and resulted in median PFS and OS of 8.7 months [7.5-9.9] and 19.9 months [15.4-24.5]. Corresponding figures in second line were 37.5% [22.5-52.5], 6.7 months [4.8-8.9] and 16.3 months [11.8-20.8]. International and prospective evaluation revealed the favourable safety and efficacy profiles of chronoIFLO5, both as frontline and as salvage treatment against metastatic colorectal cancer. In particular, encouraging activity in second line was observed, with limited haematological toxicity.
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- 2020
35. Liver Graft Hypothermic Static and Oxygenated Perfusion (HOPE) Strategies: A Mitochondrial Crossroads
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Raquel G. Bardallo, Rui T. Da Silva, Teresa Carbonell, Carlos Palmeira, Emma Folch-Puy, Joan Roselló-Catafau, René Adam, Arnau Panisello-Rosello, and European Commission
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AMPK ,Succinate ,Transplants ,Trasplantament hepàtic ,Glycocalyx ,Catalysis ,Inorganic Chemistry ,Humans ,Physical and Theoretical Chemistry ,Molecular Biology ,Spectroscopy ,ALDH2 ,Glycoproteins ,Aldehyde Dehydrogenase, Mitochondrial ,Organic Chemistry ,Succinates ,General Medicine ,Organ Preservation ,Computer Science Applications ,Liver Transplantation ,Oxygen ,Perfusion ,Liver ,Glicolípids ,Liver graft preservation ,Glycolipids ,Hepatic transplantation ,Glicoproteïnes - Abstract
Marginal liver grafts, such as steatotic livers and those from cardiac death donors, are highly vulnerable to ischemia–reperfusion injury that occurs in the complex route of the graft from “harvest to revascularization”. Recently, several preservation methods have been developed to preserve liver grafts based on hypothermic static preservation and hypothermic oxygenated perfusion (HOPE) strategies, either combined or alone. However, their effects on mitochondrial functions and their relevance have not yet been fully investigated, especially if different preservation solutions/effluents are used. Ischemic liver graft damage is caused by oxygen deprivation conditions during cold storage that provoke alterations in mitochondrial integrity and function and energy metabolism breakdown. This review deals with the relevance of mitochondrial machinery in cold static preservation and how the mitochondrial respiration function through the accumulation of succinate at the end of cold ischemia is modulated by different preservation solutions such as IGL-2, HTK, and UW (gold-standard reference). IGL-2 increases mitochondrial integrity and function (ALDH2) when compared to UW and HTK. This mitochondrial protection by IGL-2 also extends to protective HOPE strategies when used as an effluent instead of Belzer MP. The transient oxygenation in HOPE sustains the mitochondrial machinery at basal levels and prevents, in part, the accumulation of energy metabolites such as succinate in contrast to those that occur in cold static preservation conditions. Additionally, several additives for combating oxygen deprivation and graft energy metabolism breakdown during hypothermic static preservation such as oxygen carriers, ozone, AMPK inducers, and mitochondrial UCP2 inhibitors, and whether they are or not to be combined with HOPE, are presented and discussed. Finally, we affirm that IGL-2 solution is suitable for protecting graft mitochondrial machinery and simplifying the complex logistics in clinical transplantation where traditional (static preservation) and innovative (HOPE) strategies may be combined. New mitochondrial markers are presented and discussed. The final goal is to take advantage of marginal livers to increase the pool of suitable organs and thereby shorten patient waiting lists at transplantation clinics., This study was supported by the European Commission H2020-MSCA-ITN-ETN-2016 “FOIE GRAS—Metabolism and the Liver-Gut Axis in Non-Alcoholic Fatty Liver Disease” and the Marie Curie Fellow to Rui Teixeira da Silva.
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- 2022
36. Patient with unresectable colorectal liver metastases and asymptomatic primary tumor: end of the debate!
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Marc-Antoine Allard and René Adam
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Original Investigation - Abstract
IMPORTANCE: The role of primary tumor resection (PTR) in synchronous patients with metastatic colorectal cancer (mCRC) who had unresectable metastases and few or absent symptoms of their primary tumor is unclear. Studying subgroups with low postoperative mortality may identify patients who potentially benefit from PTR. OBJECTIVE: To determine the difference in 60-day mortality between patients randomized to systemic treatment only vs PTR followed by systemic treatment, and to explore risk factors associated with 60-day mortality. DESIGN, SETTING, AND PARTICIPANTS: CAIRO4 is a randomized phase 3 trial initiated in 2012 in which patients with mCRC were randomized to systemic treatment only or PTR followed by systemic treatment with palliative intent. This multicenter study was conducted by the Danish and Dutch Colorectal Cancer Group in general and academic hospitals in Denmark and the Netherlands. Patients included between August 2012 and December 2019 with histologically proven colorectal cancer, unresectable metastases, and a primary tumor with few or absent symptoms were eligible. INTERVENTIONS: Systemic treatment, consisting of fluoropyrimidine-based chemotherapy with bevacizumab vs PTR followed by fluoropyrimidine-based chemotherapy with bevacizumab. MAIN OUTCOMES AND MEASURES: The aim of the current analysis was to compare 60-day mortality rates in both treatment arms. A secondary aim was the identification of risk factors for 60-day mortality in the treatment arms. These aims were not predefined in the study protocol. RESULTS: A total of 196 patients were included in the intention-to-treat analysis (112 [57%] men; median [IQR] age, 65 [59-70] years). Sixty-day mortality was 3% (95% CI, 1%-9%) in the systemic treatment arm and 11% (95% CI, 6%-19%) in the PTR arm (P = .03). In a per-protocol analysis, 60-day mortality was 2% (95% CI, 1%-7%) vs 10% (95% CI, 5%-18%; P = .048). Patients with elevated serum levels of lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, and/or neutrophils who were randomized to PTR had a significantly higher 60-day mortality than patients without these characteristics. CONCLUSIONS AND RELEVANCE: Patients with mCRC who were randomized to PTR followed by systemic treatment had a higher 60-day mortality than patients randomized to systemic treatment. Especially patients randomized to the PTR arm with elevated serum levels of lactate dehydrogenase, neutrophils, aspartate aminotransferase, and/or alanine aminotransferase were at high risk of postoperative mortality. Final study results on overall survival have to be awaited. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01606098
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- 2022
37. Development of Ex Situ Normothermic Reperfusion as an Innovative Method to Assess Pancreases After Preservation
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Arnau Panisello-Roselló, Emma Folch-Puy, Joan Roselló-Catafau, and René Adam
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Transplantation - Published
- 2022
38. Proposal of a New Comprehensive Notation for Hepatectomy
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Shoji Kawakatsu, Sung-Gyu Lee, Itaru Endo, Massimo Malagó, Eduardo de Santibañes, Antonio D Pinna, Ronald P. DeMatteo, Wojciech G. Polak, Olivier Soubrane, René Adam, David A. Geller, Alfredo Guglielmi, Karim Boudjema, Tomoki Ebata, Tomoaki Kato, Silvio Nadalin, Michelle L. DeOliveira, Peter Lodge, Hauke Lang, Jiahong Dong, Bryan M. Clary, Daniel Cherqui, William C. Chapman, Pierre-Alain Clavien, Masato Nagino, Luca Aldrighetti, Nagino, M., Dematteo, R., Lang, H., Cherqui, D., Malago, M., Kawakatsu, S., Deoliveira, M. L., Adam, R., Aldrighetti, L., Boudjema, K., Chapman, W., Clary, B., de Santibanes, E., Dong, J., Ebata, T., Endo, I., Geller, D., Guglielmi, A., Kato, T., Lee, S. -G., Lodge, P., Nadalin, S., Pinna, A., Polak, W., Soubrane, O., Clavien, P. -A., Aichi Cancer Center Hospital, University of Pennsylvania [Philadelphia], University Medical Center [Mainz], Hôpital Paul Brousse, University College of London [London] (UCL), University hospital of Zurich [Zurich], CHU Pontchaillou [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), University of California [San Diego] (UC San Diego), University of California, Nagoya University, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), University of Verona (UNIVR), Columbia University [New York], University of Ulsan, Cleveland Clinic, Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Pennsylvania, Université de Rennes (UR), University of California (UC), Università degli studi di Verona = University of Verona (UNIVR), and Surgery
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Liver surgery ,[SDV]Life Sciences [q-bio] ,medicine.medical_treatment ,MEDLINE ,030230 surgery ,computer.software_genre ,Notation ,Terminology ,03 medical and health sciences ,0302 clinical medicine ,Terminology as Topic ,terminology ,Humans ,Hepatectomy ,Medicine ,ComputingMilieux_MISCELLANEOUS ,business.industry ,Liver ,030220 oncology & carcinogenesis ,nomenclature ,Surgery ,Artificial intelligence ,business ,computer ,Natural language processing - Abstract
International audience
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- 2021
39. Hepatobiliary scintigraphy and kinetic growth rate predict liver failure after ALPPS: a multi-institutional study
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Michael Linecker, Dario Bruzzese, François-René Pruvot, Rimma Axelsson, Ernesto Sparrelid, Yves D'Asseler, René Adam, Federico Tomassini, Pierre-Alain Clavien, Stéphanie Truant, Thomas M. van Gulik, Carlos Castro-Benitez, Valerio Lucidi, Mariano Cesare Giglio, Karen Geboes, Thiery Chapelle, Roberto Troisi, Roberto Montalti, P.B. Olthof, Matteo Serenari, University of Zurich, Troisi, Roberto I, Academic Medical Center, Amsterdam Gastroenterology Endocrinology Metabolism, Surgery, Tomassini, F., D'Asseler, Y., Linecker, M., Giglio, M. C., Castro-Benitez, C., Truant, S., Axelsson, R., Olthof, P. B., Montalti, R., Serenari, M., Chapelle, T., Lucidi, V., Sparrelid, E., Adam, R., Van Gulik, T., Pruvot, F. -R., Clavien, P. -A., Bruzzese, D., Geboes, K., and Troisi, R. I.
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medicine.medical_specialty ,medicine.medical_treatment ,610 Medicine & health ,030230 surgery ,Scintigraphy ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Hepatectomy ,Humans ,2715 Gastroenterology ,Stage (cooking) ,Radionuclide Imaging ,Retrospective Studies ,10217 Clinic for Visceral and Transplantation Surgery ,Receiver operating characteristic ,medicine.diagnostic_test ,Hepatology ,business.industry ,Portal Vein ,Liver Neoplasms ,Liver failure ,Retrospective cohort study ,Liver ,030220 oncology & carcinogenesis ,2721 Hepatology ,Liver function ,Human medicine ,business ,Liver Failure - Abstract
Background: Post hepatectomy liver failure (PHLF) after ALPPS has been related to the discrepancy between liver volume and function. Pre-operative hepatobiliary scintigraphy (HBS) can predict postoperative liver function and guide when it is safe to proceed with major hepatectomy. Aim of this study was to evaluate the role of HBS in predicting PHLF after ALPPS, defining a safe cut-off. Methods: A multicenter retrospective study was approved by the ALPPS Registry. All patients selected for ALPPS between 2012 and 2018, were evaluated. Every patient underwent HBS during ALPPS evaluation. PHLF was reported according to ISGLS definition, considering grade B or C as clinically significant. Results: 98 patients were included. Thirteen patients experienced PHLF grade B or C (14%) following ALPPS-2. The HBS and the daily gain in volume (KGRFLR) of the future liver remnant (FLR) were significantly lower in PHLF B and C (p = .004 and .041 respectively). ROC curves indicated safe cut-offs of 4.1%/day (AUC = 0.68) for KGRFLR, and of 2.7 %/min/m(2) (AUC = 0.75) for HBSFLR. Multivariate analysis confirmed these cut-offs as variables predicting PHLF after ALPPS-2. Conclusion: Patients presenting a KGRFLR
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- 2020
40. Liver Resection for Early Hepatocellular Carcinoma
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Daniel Cherqui, Maximiliano Gelli, Antonio Sa Cunha, Eric Vibert, Raphaël Porcher, René Adam, Olivier Rosmorduc, Elena Romanelli, D. Castaing, M. Sebagh, and Didier Samuel
- Subjects
Male ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,medicine.medical_treatment ,Salvage therapy ,Liver transplantation ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,medicine ,Carcinoma ,Hepatectomy ,Humans ,Survival rate ,Aged ,Salvage Therapy ,business.industry ,Patient Selection ,Liver Neoplasms ,Hazard ratio ,Middle Aged ,medicine.disease ,Confidence interval ,Liver Transplantation ,Survival Rate ,Transplantation ,030220 oncology & carcinogenesis ,Female ,030211 gastroenterology & hepatology ,Surgery ,Neoplasm Recurrence, Local ,business - Abstract
Background and aims LR and LT are the standard curative options for early HCC. LT provides best long-term survival but is limited by organ shortage. LR, readily available, is hampered by high recurrence rates. Salvage liver transplantation is an efficient treatment of recurrences within criteria. The aim of the study was to identify preoperative predictors of non transplantable recurrence (NTR) to improve patient selection for upfront LR or LT at initial diagnosis. Study design Consecutive LR for transplantable HCC between 2000 and 2015 were studied. A prediction model for NTR based on preoperative variables was developed using sub-distribution hazard ratio after multiple imputation and internal validation by bootstrapping. Model performance was evaluated by the concordance index after correction for optimism. Results A total of 148 patients were included. Five-year overall survival and recurrence free survival were 73.6% and 29.3%, respectively (median follow-up 45.8 months). Recurrence rate was 54.8%. NTR rate was 38.2%. Preoperative model for NTR identified >1 nodule [sub-distribution hazard ratio 2.35 95% confidence interval (CI) 1.35-4.09], AFP >100 ng/mL (2.14 95% CI 1.17-3.93), and F4 fibrosis (1.93 95% CI 1.03-3.62). The apparent concordance index of the model was 0.664 after correction for optimism. In the presence of 0, 1, and ≥2 factors, NTR rates were 2.6%, 22.7%, and 40.9%, respectively. The number of prognostic factors was significantly associated with the pattern of recurrence (P = 0.001) and 5-year recurrence free survival (P Conclusions Cirrhosis, >1 nodule, and AFP >100 ng/mL were identified as preoperative predictors of NTR. In the presence of 2 factors or more upfront transplantation should be probably preferred to resection in regard of organ availability. Other patients are good candidates for LR and salvage liver transplantation should be encouraged in eligible patients with recurrence.
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- 2020
41. Delivery of hepato-pancreato-biliary surgery during the COVID-19 pandemic
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Frederik Berrevoet, Stefan Heinrich, Susanne G. Warner, A. Balakrishnan, Andrea Laurenzi, Martin Smith, Kevin C. Conlon, Mert Erkan, Mickael Lesurtel, René Adam, Bodil Andersson, José Manuel Ramia, Tom K. Gallagher, Isabella Frigerio, Ajith K. Siriwardena, Wojciech G. Polak, Shailesh V. Shrikhande, Stefan W.M. Olde Damink, Marc G. Besselink, A. Serrablo, Erkan, Murat Mert (ORCID 0000-0002-2753-0234 & YÖK ID 214689), Balakrishnan, A., Lesurtel, M., Siriwardena, A.K., Heinrich, S., Serrablo, A., Besselink, M.G.H., Andersson, B., Polak, W.G., Laurenzi, A., Olde Damink, S.W.M., Berrevoet, F., Frigerio, I., Ramia, J.M., Gallagher, T.K., Warner, S., Shrikhande, S.V., Adam, R., Smith, M.D., Conlon, K.C., E-AHPBA Scientific and Research Committee, School of Medicine, RS: NUTRIM - R2 - Liver and digestive health, Surgery, MUMC+: MA Heelkunde (9), and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism
- Subjects
Male ,medicine.medical_specialty ,Cross-sectional study ,Service delivery framework ,Pneumonia, Viral ,MEDLINE ,Article ,03 medical and health sciences ,Betacoronavirus ,0302 clinical medicine ,Pancreatic cancer ,Pandemic ,Medicine ,Humans ,Personal protective equipment ,Pandemics ,Digestive System Surgical Procedures ,Societies, Medical ,Hepatology ,business.industry ,SARS-CoV-2 ,Liver Neoplasms ,Gastroenterology ,Cancer ,COVID-19 ,medicine.disease ,Surgery ,Europe ,Pancreatic Neoplasms ,Biliary Tract Neoplasms ,Cross-Sectional Studies ,Surgical oncology ,General surgery ,Trainee ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Africa ,030211 gastroenterology & hepatology ,Female ,business ,Coronavirus Infections ,Delivery of Health Care - Abstract
Background: the extent of the COVID-19 pandemic and the resulting response has varied globally. The European and African Hepato-Pancreato-Biliary Association (E-AHPBA), the premier representative body for practicing HPB surgeons in Europe and Africa, conducted this survey to assess the impact of COVID-19 on HPB surgery. Methods: an online survey was disseminated to all E-AHPBA members to assess the effects of the pandemic on unit capacity, management of HPB cancers, use of COVID-19 screening and other aspects of service delivery. Results: overall, 145 (25%) members responded. Most units, particularly in COVID-high countries (>100,000 cases) reported insufficient critical care capacity and reduced HPB operating sessions compared to COVID-low countries. Delayed access to cancer surgery necessitated alternatives including increased neoadjuvant chemotherapy for pancreatic cancer and colorectal liver metastases, and locoregional treatments for hepatocellular carcinoma. Other aspects of service delivery including COVID-19 screening and personal protective equipment varied between units and countries. Conclusion: this study demonstrates that the COVID-19 pandemic has had a profound adverse impact on the delivery of HPB cancer care across the continents of Europe and Africa. The findings illustrate the need for safe resumption of cancer surgery in a “new” normal world with screening of patients and staff for COVID-19., NA
- Published
- 2020
42. Indocyanine Green Fluorescence Imaging to Predict Graft Survival After Orthotopic Liver Transplantation: A Pilot Study
- Author
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Muga Terasawa, Quentin Nicolas, Eric Vibert, René Adam, Marc-Antoine Allard, Chady Salloum, Oriana Ciacio, Nicolas Golse, Daniel Cherqui, Didier Samuel, Gabriella Pittau, Antonio Sa Cunha, Irene E. Vignon-Clementel, Damien Dousse, Luis Cano, Hôpital Paul Brousse, Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital de Rangueil, CHU Toulouse [Toulouse], Numerical simulation of biological flows (REO), Sorbonne Université (SU)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jacques-Louis Lions (LJLL (UMR_7598)), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and BOPA_BERNOULLI
- Subjects
Indocyanine Green ,Orthotopic liver transplantation ,[SDV]Life Sciences [q-bio] ,medicine.medical_treatment ,Pilot Projects ,Near-infrared fluorescence ,030230 surgery ,Liver transplantation ,Revascularization ,Modelling ,Indocyanine green dye ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Primary non-function ,Humans ,Medicine ,Prospective Studies ,Prospective cohort study ,Transplantation ,Hepatology ,business.industry ,Graft Survival ,Optical Imaging ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Liver Transplantation ,3. Good health ,Fluorescence intensity ,chemistry ,030211 gastroenterology & hepatology ,Surgery ,Graft survival ,Graft function ,business ,Nuclear medicine ,Indocyanine green ,Indocyanine green fluorescence - Abstract
Introduction: The incidence of primary non-function (PNF) after liver transplantation (LT) remains a major concern with the increasing use of marginal grafts. Indocyanine green (ICG) fluorescence is an imaging technique used in hepatobiliary surgery and LT. Because few early predictors are available, we aimed to quantify in real time the fluorescence of grafts during LT to predict their 3 months survival. Patients and methods: After graft revascularization, ICG was intravenously injected, then the fluorescence of the graft was captured with a near infrared camera and postoperatively quantified. A multi-parametric modelling of the parenchymal fluorescence intensity curve was proposed, and a predictive model of graft survival was tested. Results: Between July 2017 and May 2019, 76 LT were included, among which 6 recipients were re-transplanted (re-LT+ ). No side effects of ICG injection were observed. The parameter a150 (temporal course of fluorescence intensity) was significantly higher in the group re-LT+ group (0.022s-1 [0.016-0.035] versus 0.012s-1 [0.009-0.015], p=0.01). This parameter was the only independent predictive factor of graft survival at 3 months (OR=2.4 CI95% [1.05-5.5] p=0.03). The best cut-off for the parameter a150 (0.0155s-1 ) predicted the graft survival at 3 months with a sensitivity of 83% and a specificity of 79% (AUC=0.82 [0.67-0.98], p=0.01). Conclusion: Quantitative assessment of intraoperative ICG fluorescence on the graft was feasible to predict graft survival at 3 months with a good sensitivity and specificity. Further prospective studies should validate these results over larger cohorts and evaluate the clinical impact of this tool.
- Published
- 2020
43. Sex‐dependent least toxic timing of irinotecan combined with chronomodulated chemotherapy for metastatic colorectal cancer: Randomized multicenter EORTC 05011 trial
- Author
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Philippe Chollet, Pasquale F. Innominato, Mohamed Bouchahda, Annabelle Ballesta, Abdoulaye Karaboué, Sylvie Giacchetti, Francis Lévi, Christian Focan, Carlo Garufi, Qi Huang, and René Adam
- Subjects
Male ,0301 basic medicine ,Cancer Research ,Leucovorin ,Gastroenterology ,law.invention ,0302 clinical medicine ,Randomized controlled trial ,law ,Antineoplastic Combined Chemotherapy Protocols ,gender ,Neoplasm Metastasis ,Original Research ,Morning ,Sex Characteristics ,education.field_of_study ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Prognosis ,Europe ,Oxaliplatin ,Survival Rate ,Exact test ,Oncology ,030220 oncology & carcinogenesis ,Female ,Fluorouracil ,medicine.symptom ,Colorectal Neoplasms ,medicine.drug ,Adult ,medicine.medical_specialty ,Drug-Related Side Effects and Adverse Reactions ,Population ,colorectal cancer ,Anorexia ,Neutropenia ,Irinotecan ,lcsh:RC254-282 ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,education ,Adverse effect ,Aged ,Dose-Response Relationship, Drug ,chronotherapy ,business.industry ,Clinical Cancer Research ,toxicity ,medicine.disease ,circadian ,030104 developmental biology ,business ,Follow-Up Studies - Abstract
The least toxic time (LTT) of irinotecan varied by up to 8 hours according to sex and genetic background in mice. The translational relevance was investigated within a randomized trial dataset, where no LTT stood out significantly in the whole population. 130 male and 63 female eligible patients with metastatic colorectal cancer were randomized to receive chronomodulated Irinotecan with peak delivery rate at 1 of 6 clock hours staggered by 4 hours on day 1, then fixed‐time chronomodulated Fluorouracil‐Leucovorin‐Oxaliplatin for 4 days, q3 weeks. The sex‐specific circadian characteristics of grade (G) 3‐4 toxicities were mapped with cosinor and time*sex interactions confirmed with Fisher's exact test. Baseline characteristics of male or female patients were similar in the six treatment groups. Main grade 3‐4 toxicities over six courses were diarrhea (males vs females, 39.2%; vs 46.0%), neutropenia (15.6% vs 15.0%), fatigue (11.5% vs 15.9%), and anorexia (10.0% vs 7.8%). They were reduced following irinotecan peak delivery in the morning for males, but in the afternoon for females, with statistically significant rhythms (P, In this randomized international trial, the hematologic and clinical toxicities of irinotecan were least following dosing in the morning for men and in the afternoon for women with colorectal cancer. Sex‐specific least toxic times of anticancer drugs need further identification in prospective clinical trials.
- Published
- 2020
44. Liver transplantation in elderly patients: what do we know at the beginning of 2020?
- Author
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Marc Antoine Allard, René Adam, Shimon Dolnikov, and Daniel Cherqui
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Male ,medicine.medical_specialty ,Population ageing ,Tissue and Organ Procurement ,medicine.medical_treatment ,Nutritional Status ,Comorbidity ,Review Article ,030230 surgery ,Liver transplantation ,Asymptomatic ,03 medical and health sciences ,0302 clinical medicine ,Surgical oncology ,Humans ,Medicine ,Intensive care medicine ,Aged ,Aged, 80 and over ,Frailty ,business.industry ,Patient Selection ,Age Factors ,Nutritional status ,General Medicine ,Elderly patients ,Transplantation ,Treatment Outcome ,Survival benefit ,Female ,030211 gastroenterology & hepatology ,Surgery ,medicine.symptom ,business - Abstract
An aging population has prompted us to evaluate the indications of liver transplantation (LT) in elderly patients more frequently. In this review, we summarize the short- and long-term results after LT in elderly patients and also discuss the criteria used to select patients and how recipient age can challenge current allocation systems. Briefly, the feasibility and early outcomes of LT in elderly patients compare favorably with those of younger patients. Although long-term survival is less than satisfactory, large-scale studies show that the transplant survival benefit is similar for elderly and younger patients. Therefore, age alone does not contraindicate LT; however, screening for cardiopulmonary comorbidities, and asymptomatic malignancies, evaluating nutritional status, and frailty, is crucial to ensure optimal results and avoid futile transplantation.
- Published
- 2020
45. Influence de 4 solutions de préservation sur la durée de réanimation, la survie du greffon et du patient après transplantation hépatique
- Author
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Astrid Herrero, Laurence Chiche, L. Barbier, Emmanuel Boleslawski, M. Rayar, K. Mohkam, R. Brustia, François-René Pruvot, Jean-Christophe Vaillant, C. Chardot, C B Lim, M. Chirica, Oriana Ciacio, Francis Navarro, Emilie Gregoire, J.-L. Golmard, Samir Jaber, Pietro Addeo, Christian Letoublon, René Adam, Bertrand Suc, J. Abba, Olivier Soubrane, E. Salame, A. Sepulveda, Jean-Yves Mabrut, Emmanuel Buc, Philippe Bachellier, F. Jeune, Eric Savier, K. Boudjema, Gabriella Pittau, C. Maulat, François Faitot, Philippe Compagnon, O. Boilot, B. Heyd, Y.P. Le Treut, A. Mallet, P. Houssel-Debry, Christophe Laurent, C. Salloum, F. Perdigao, A. Merdignac, T. Dao, Safi Dokmak, Jean Gugenheim, B. Trechot, G. Rousseau, S. Branchereau, Daniel Cherqui, Jean Hardwigsen, Olivier Scatton, F. Dondero, A. Mulliri, Jean-Michel Siksik, and G.-P. Pageaux
- Subjects
Surgery - Abstract
Resume But de l’etude Le but de l’etude etait d’evaluer le role pronostique de 4 solutions de conservation en transplantation hepatique (TH). Patients et methodes Il s’agit d’une etude retrospective a partir de toutes les TH de tous les centres francais (n = 22) enregistrees dans la base de donnees prospective de l’Agence de la Biomedecine (Cristal) entre 2008 et 2013. Les solutions de preservation utilisees etaient : Celsior, IGL-1, SCOT 15 ou UW. Les criteres d’exclusion etaient : solution inconnue ou inhomogene ou solution HTK (3 % seulement des TH). Le critere principal de jugement etait la survie des patients. Les criteres secondaires etaient la survie des greffons et la duree de reanimation. Resultats Parmi 6347 TH realisees, 4928 ont ete incluses pour lesquelles la solution de preservation utilisee etaient Celsior (30 %), IGL-1 (44 %), SCOT 15 (10 %) et UW (16 %). La survie des patients etait de 86 %, 80 % et 74 % a 1, 3 et 5 ans, respectivement, sans difference entre les 4 solutions (p = 0,78). La survie des greffons etait respectivement de 82 %, 75 % et 69 % a 1, 3 et 5 ans, sans difference entre les 4 solutions (p = 0,80). Le sejour en reanimation etait different selon la solution utilisee en analyse univariee (p Conclusion Le type de solution de conservation utilisee (Celsior, IGL-1, SCOT 15 ou UW) n’a pas d’influence sur la survie des patients ou des greffons apres TH.
- Published
- 2020
46. What is the Prognostic Value of a Discordant Radiologic and Pathologic Response in Patients Undergoing Resection of Colorectal Liver Metastases After Preoperative Chemotherapy?
- Author
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Christelle Blot, Maïté Lewin, Antonio Sa Cunha, Stéphane Benoist, Thierry Lazure, Antoine Brouquet, Mathilde Gayet, C. Penna, René Adam, Marc-Antoine Allard, and Mylene Sebbagh
- Subjects
medicine.medical_specialty ,Multivariate analysis ,medicine.medical_treatment ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Major Pathologic Response ,Surgical oncology ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Hepatectomy ,Humans ,Medicine ,Preoperative chemotherapy ,Clinical significance ,In patient ,Retrospective Studies ,business.industry ,Liver Neoplasms ,Retrospective cohort study ,Prognosis ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Surgery ,Colorectal Neoplasms ,business - Abstract
The clinical significance of discordant radiological and pathological response to preoperative chemotherapy of colorectal liver metastases (CLM) is unknown. From 2011 to 2016, all eligible patients undergoing resection for CLM after preoperative chemotherapy were included at two centres. Patients were categorized according to radiologic response using RECIST as Rad-responders (complete/partial response) or Rad-non responders (stable disease) and according to Blazer et al. pathologic response grade as Path-responders (complete/major response) or Path-non responders (minor response). Survival outcome was analysed according to radiologic and pathologic response. Among 413 patients undergoing resection of CLM, 119 fulfilled the inclusion criteria. Among these, 52 (44%) had discordant radiologic and pathologic response including 27 Rad-non responders/path responders and 25 Rad-responders/Path-non responders. Rad-non responders/path responders and Rad-responders/Path-non responders had similar characteristics except for the proportion receiving more than 6 cycles of preoperative chemotherapy (7/27 vs 16/25; P = 0.017). Median disease-free survival was not different in patients with or without discordant radiologic and pathologic responses (P = 0.195) but the type of discordance had an impact on oncologic outcome as median disease-free survival was 13.9 months (95% CI 5.7–22.2 months) in Rad-non responders/Path responders and 8.6 (6.2 – 10.9 months) in Rad-responders/Path-non responders (P = 0.034). Univariate and multivariate analysis showed that major pathologic response was associated with improved disease-free survival (OR 0.583, 95% CI 0.36–0.95, P = 0.031). A discordant radiologic and pathologic response is common after preoperative chemotherapy for CLM. In these patients, pathologic response drives oncologic outcome.
- Published
- 2020
47. Impact of COVID-19 on liver transplantation in Europe: alert from an early survey of European Liver and Intestine Transplantation Association and European Liver Transplant Registry
- Author
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Giacomo Germani, Christophe Duvoux, Pavel Taimr, Ulrich Baumann, Christian Toso, Luca S. Belli, Roberto Troisi, Krzysztof Zieniewicz, Vincent Karam, René Adam, Silvio Nadalin, Wojciech G. Polak, Constantino Fondevila, Polak, W, Fondevila, C, Karam, V, Adam, R, Baumann, U, Germani, G, Nadalin, S, Taimr, P, Toso, C, Troisi, R, Zieniewicz, K, Belli, L, Duvoux, C, and Surgery
- Subjects
Scarce data ,2019-20 coronavirus outbreak ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,SARS-Cov-2 ,medicine.medical_treatment ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Crude incidence ,030230 surgery ,Liver transplantation ,COVID-19, liver recipient, liver transplantation, mortality, SARS-CoV-2, survey ,liver recipient ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,survey ,Transplantation ,Intestine transplantation ,ddc:617 ,liver transplantation ,business.industry ,SARS-CoV-2 ,COVID-19 ,mortality ,030211 gastroenterology & hepatology ,business - Abstract
There are scarce data on the impact of COVID-19 pandemic on liver transplantation (LT) in Europe. The aim of this study was to obtain a preliminary data on incidence, management, and outcome of COVID-19 in liver transplant recipients and candidates in Europe. An Internet-based survey was sent to the centers affiliated with European Liver Transplant Registry (ELTR). One hundred nine out of 149 (73%) of ELTR centers located in 28 European countries (93%) responded. Ninety-four (86%) of the centers tested all donors, and 75 (69%) centers tested all LT recipients for SARS-CoV-2. Seventy-three (67%) centers selected recipients for LT in the COVID-19 pandemic, whereas 33% did not. Eighty-eight centers reported COVID-19 infection in 57 LT candidates and in 272 LT recipients. Overall crude incidence of COVID-19 among LT candidates and recipients was estimated 1.05% (range 0.5–20%) and 0.34% (range 0.1–4.8%), respectively, and it was significantly higher among candidates (P'0.001). Crude rate of death was 18% (10/57) among candidates and 15% (36/244) among recipients. This first large-scale European snapshot study clearly shows that both LT candidates and recipients are at a high risk for COVID-19. These results plead for an early and pro-active screening of COVID-19 symptoms in these populations.
- Published
- 2020
48. The Use of a Single, Novel Preservation Solution in Split Liver Transplantation and Hypothermic Oxygenated Machine Perfusion
- Author
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Arnau Panisello-Roselló, Rui T. da Silva, Emma Folch-Puy, Teresa Carbonell, Carlos M. Palmeira, Constantino Fondevila, Joan Roselló-Catafau, and René Adam
- Subjects
Perfusion ,Transplantation ,Organ Preservation ,Liver Transplantation - Published
- 2022
49. Morbid obesity increases death and dropout from the liver transplantation waiting list: A prospective cohort study
- Author
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Claire, Delacôte, Mathilde, Favre, Medhi, El Amrani, Massih, Ningarhari, Elise, Lemaitre, Line Carolle, Ntandja-Wandji, Pierre, Bauvin, Emmanuel, Boleslawski, Guillaume, Millet, Stephanie, Truant, Philippe, Mathurin, Alexandre, Louvet, Valérie, Canva, Gilles, Lebuffe, François René, Pruvot, Sébastien, Dharancy, Guillaume, Lassailly, and René, Adam
- Subjects
Oncology ,Waiting Lists ,Gastroenterology ,Humans ,Prospective Studies ,Risk Assessment ,Liver Transplantation ,Obesity, Morbid - Abstract
Liver transplant (LT) candidates with a body mass index (BMI) over 40 kg/mData between January 2007 and December 2017 were extracted from the French prospective national database: CRISTAL. Competing risk analyses were performed to evaluate predictors of receiving LT. Competitive events were (1) death/WL removal for disease aggravation or (2) improvement. The link between grade obesity, grafts propositions, and reason for refusal was studied.15,184 patients were analysed: 10,813 transplant, 2847 death/dropout for aggravation, 748 redirected for improvement, and 776 censored. Mortality/dropout were higher in BMI over 35 (18% vs. 14% 1 year after listing) than in other candidates. In multivariate analysis, BMI35, age, hepatic encephalopathy, and ascites were independent predictors of death/dropout. Candidates with a BMI ≥ 35 kg/mBMI over 35 kg/m
- Published
- 2022
50. Liver Transplantation for Colorectal Cancer Liver Metastases
- Author
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Maximiliano Gelli and René Adam
- Published
- 2022
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