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1. Is survival influenced by metastatic site in synchronous metastatic pancreatic adenocarcinoma (PDAC)? A prospective real-world BACAP study

Author: E. Alouani, C. Canivet, B. Bournet, L. Buscail, J. Selves, B. Napoleon, L. Palazzo, N. Flori, P. Guibert, A.-C. Brunac, C. Maulat, F. Muscari, F.-Z. Mokrane, S. Gourgou, L. Roca, R. Guimbaud, N. Fares, Barbara Bournet, Cindy Canivet, Louis Buscail, Nicolas Carrere, Fabrice Muscari, Bertrand Suc, Rosine Guimbaud, Corinne Couteau, Marion Deslandres, Pascale Rivera, Anne-Pascale Laurenty, Nadim Fares, Karl Barange, Janick Selves, Anne Gomez-Brouchet, Bertrand Napoleon, Bertrand Pujol, Fabien Fumex, Jerome Desrame, Christine Lefort, Vincent Lepilliez, Rodica Gincul, Pascal Artru, Lea Clavel, Anne-Isabelle Lemaistre, Laurent Palazzo, Jerome Cros, Sarah Tubiana, Nicolas Flori, Pierre Senesse, Pierre-Emmanuel Colombo, Emmanuelle SamailScalzi, Fabienne Portales, Sophie Gourgou, Claire Honfo Ga, Carine Plassot, Julien Fraisse, Fred eric Bibeau, Marc Ychou, Pierre Guibert, Christelle de la Fouchardiere, Matthieu Sarabi, Patrice Peyrat, Severine Tabone-Eglinger, Caroline Renard, Guillaume Piessen, Stephanie Truant, Alain Saudemont, Guillaume Millet, Florence Renaud, Emmanuelle Leteurtre, Patrick Gele, Eric Assenat, Jean-Michel Fabre, Francois-Regis Souche, Marie Dupuy, Anne-Marie Gorce-Dupuy, Jeanne Ramos, Jean-Francois Seitz, Jean Hardwigsen, Emmanuelle Norguet-Monnereau, Philippe Grandval, Muriel Duluc, Dominique Figarella-Branger, Veronique Vendrely, Clement Subtil, Eric Terrebonne, Jean-Frederic Blanc, Etienne Buscail, Jean-Philippe Merlio, Dominique Farges Bancel, Jean-Marc Gornet, Daniela Geromin, Geoffroy Vanbiervliet, Anne-Claire Frin, Delphine Ouvrier, Marie-Christine SaintPaul, Philippe Berthelemy, Chelbabi Fouad, Stephane Garcia, Nathalie Lesavre, Mohamed Gasmi, Marc Barthet, Vanessa Cottet, and Cyrille Delpierre
Subjects: pancreatic cancer, survival, metastatic site, lung-only metastases, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Background: Advanced pancreatic ductal adenocarcinoma (PDAC) carries a dismal prognosis with a 5-year survival rate of 3%. While treated as an even population, previous retrospective studies suggested significantly different survival rates for patients with lung-only metastases when compared with other patients. This study aims to explore prospectively the difference in survival outcome based on initial site of metastases in synchronous metastatic PDAC. Patients and methods: This is a prospective observational study including all adult patients with synchronous metastatic PDAC in BACAP (national Anatomo-Clinical Database on Pancreatic Adenocarcinoma). Data regarding patients’ demographics, tumor characteristics and survival outcomes were analyzed. Results: Overall, 559 patients were included (52.8% male, mean age 69 years) of which 26 (4.7%), 65 (11.6%), 299 (53.5%) and 169 (30.2%) patients had lung-only, peritoneal-only, liver-only and multi-site metastases at diagnosis, respectively. The median overall survival (OS) was significantly different according to metastatic site (P < 0.001) with a median OS for lung-only, peritoneum-only, liver-only and multi-site of 12.6 months [95% confidence interval (CI) 9.7-16.9 months], 8.6 months (95% CI 5.4-11.5 months), 7.9 months (95% CI 6.5-8.9 months) and 4.5 months (95% CI 3.9-5.8 months), respectively. The median progression-free survival (PFS) was also significantly different according to metastatic site (P < 0.01) with a median PFS of 6.3 months (95% CI 2.7-9.1 months), 5.1 months (95% CI 3.7-6.2 months), 4.7 months (95% CI 3.3-5.7 months) and 3.2 months (95% CI 2.6-4.1 months), respectively. Conclusions: Patients with lung-only metastases represented 4.7% of synchronous metastatic PDAC patients and exhibited improved survival. These results suggest that a subset of patients with synchronous metastatic PDAC could benefit from more aggressive locoregional treatments.
Published: 2025
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2. Predictive genomic and transcriptomic analysis on endoscopic ultrasound-guided fine needle aspiration materials from primary pancreatic adenocarcinoma: a prospective multicentre studyResearch in context

Author: Rémy Nicolle, Cindy Canivet, Laurent Palazzo, Bertrand Napoléon, Mira Ayadi, Camille Pignolet, Jérôme Cros, Sophie Gourgou, Janick Selves, Jérôme Torrisani, Nelson Dusetti, Pierre Cordelier, Louis Buscail, Barbara Bournet, Nicolas Carrère, Fabrice Muscari, Bertrand Suc, Rosine Guimbaud, Corinne Couteau, Marion Deslandres, Pascale Rivera, Emily Alouany, Nadim Fares, Karl Barange, Anne Gomez-Brouchet, Adrian Culetto, Guillaume Le Cosquer, Marion Jaffrelot, Bertrand Pujol, Fabien Fumex, Jérôme Desrame, Christine Lefort, Vincent Lepilliez, Rodica Gincul, Pascal Artru, Léa Clavel, Anne-Isabelle Lemaistre, Sarah Tubiana, Nicolas Flori, Pierre Senesse, Pierre-Emmanuel Colombo, Emmanuelle Samalin-Scalzi, Fabienne Portales, Lise Roca, Claire Honfo Ga, Carinne Plassot, Marc Ychou, Pierre Guibert, Christelle De La Fouchardière, Mathieu Sarabi, Patrice Peyrat, Séverine Tabone-Eglinger, Caroline Renard, Guillaume Piessen, Stéphanie Truant, Alain Saudemont, Guillaume Millet, Florence Renaud, Emmanuelle Leteurtre, Patrick Gelé, Eric Assenat, Jean-Michel Fabre, François-Régis Souche, Marie Dupuy, Anne-Marie Gorce-Dupuy, Jeanne Ramos, Jean-François Seitz, Jean Hardwigsen, Emmanuelle Norguet-Monnereau, Philippe Grandval, Muriel Duluc, Dominique Figarella-Branger, Véronique Vendrely, Clément Subtil, Eric Terrebonne, Jean-Frédéric Blanc, Jean-Philippe Merlio, Dominique Farges-Bancel, Jean-Marc Gornet, Daniela Geromin, Geoffroy Vanbiervliet, Anne-Claire Frin, Delphine Ouvrier, Marie-Christine Saint-Paul, Philippe Berthélémy, Chelbabi Fouad, Stéphane Garcia, Nathalie Lesavre, Mohamed Gasmi, Marc Barthet, Vanessa Cottet, and Cyrille Delpierre
Subjects: Pancreatic cancer, RNA sequencing, Targeted DNA deep sequencing, Translational medicine, Predictive medicine, Medicine, Medicine (General), R5-920
Abstract: Summary: Background: We apply endoscopic ultrasound-guided fine needle aspiration biopsy to cytopathologically diagnose and sample nucleic acids from primary tumours regardless of the disease stage. Methods: 397 patients with proven pancreatic adenocarcinoma were included and followed up in a multicentre prospective study. DNA and mRNA were extracted from materials of primary tumours obtained by endoscopic ultrasound-guided fine needle aspiration biopsy and analysed using targeted deep sequencing and RNAseq respectively. Findings: The variant allele frequency of the KRAS mutation was used to evaluate the tumour cellularity, ranging from 15 to 20% in all cells, regardless of the tumour stage. The molecular profile of metastatic primary tumours significantly differed from other types of tumours, more frequently having TP53 mutations (p = 0.0002), less frequently having RNF43 mutations, and possessing more basal-like mRNA component (p = 0.001). Molecular markers associated with improved overall survival were: mutations in homologous recombination deficiency genes in patients who received first-line platinum-based chemotherapy (p = 0.025) and wild-type TP53 gene in patients with locally advanced tumours who received radio-chemotherapy (p = 0.01). The GemPred transcriptomic profile was associated with a significantly better overall survival in patients with locally advanced or metastatic pancreatic cancer who received a gemcitabine-based first-line treatment (p = 0.019). Interpretation: The combination of genomic and transcriptomic analyses of primary pancreatic tumours enables us to distinguish metastatic tumours from other tumour types. Our molecular strategy may assist in predicting overall survival outcomes for platinum or gemcitabine-based chemotherapies, as well as radio-chemotherapy. Funding: Institut National Du Cancer (BCB INCa_7294), CHU of Toulouse, Inserm and Ligue Nationale Contre le Cancer (CIT program).
Published: 2024
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3. Type of calcineurin inhibitor and long-term outcomes following liver transplantation in patients with primary biliary cholangitis – an ELTR study

Author: Maria C. van Hooff, Rozanne C. de Veer, Vincent Karam, Rene Adam, Pavel Taimr, Wojciech G. Polak, Hasina Pashtoun, Sarwa Darwish Murad, Christophe Corpechot, Darius Mirza, Michael Heneghan, Peter Lodge, Gabriel C. Oniscu, Douglas Thorburn, Michael Allison, Herold J. Metselaar, Caroline M. den Hoed, Adriaan J. van der Meer, Gabriel Oniscu, Johann Pratschke, Derek Manas, William Bennet, Pal-Dag Line, Emir Hot, Krzysztof Zieniewicz, Bo Goran Ericzon, Jiri Fronek, Jurgen L. Klempnauer, Allan Rasmussen, Renato Romagnoli, Petr Nemec, Arno Nordin, Andreas Paul, Paolo De Simone, R.J. Porte, Gabriela Berlakovich, Daniel Cherqui, Jacques Pirenne, Etienne Sokal, Giorgio Rossi, Daniel Candinas, Philippe Bachellier, Oleg Rummo, Karim Boudjema, Anna Mrzljak, Olivier Soubrane, Herold Metselaar, Stefan Schneeberger, Francis Navarro, Thierry Berney, Christophe Duvoux, Michele Colledan, Luciano De Carlis, Olivier Boillot, Jean Hardwigsen, Francois Rene Pruvot, Bertrand Suc, Marco Vivarelli, Pierre Alain Clavien, Hauke Lang, Maciej Kosieradzki, Frederik Berrevoet, Bruno Heyd, Matteo Cescon, Laurence Chiche, Eberhard Kochs, Umberto Baccarani, Olivier Detry, Michael Bartels, Massimo Rossi, Olivier Scatton, Vasileios Papanikolaou, Ian Alwayn, Peter Schemmer, N. Senninger, Christian Ducerf, Fabrizio Di Benedetto, Giuseppe Tisone, Silvio Nadalin, Zoltan Mathe, Marija Ribnikar, Utz Settmacher, Thomas Becker, Nuno Silva, Jorge Daniel, Irinel Popescu, Valerio Lucidi, Wolf O. Bechstein, Thomas Decaens, Jean Gugenheim, Salvatore Gruttadauria, Frausto Zamboni, Murat Zeytunlu, Jorg C. Kalff, Toomas Vali, Yaman Tokat, Ernst Klar, Julius Janek, Murat Kilic, Krum Katzarov, Lutz Fisher, Emmanuel Buc, Marco Castagneto, Tarkan Unek, Lubomir Spassov, Dirk Stippel, Christiane Bruns, Hans Schlitt, Ephrem Salame, Piotr Kalicinski, and Koray Acarli
Subjects: Calcineurin inhibitors, Graft survival, Liver Transplantation, Primary Biliary Cholangitis, Survival, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background & Aims: Tacrolimus has been associated with recurrence of primary biliary cholangitis (PBC) after liver transplantation (LT), which in turn may reduce survival. This study aimed to assess the association between the type of calcineurin inhibitor used and long-term outcomes following LT in patients with PBC. Methods: Survival analyses were used to assess the association between immunosuppressive drugs and graft or patient survival among adult patients with PBC in the European Liver Transplant Registry. Patients who received a donation after brain death graft between 1990 and 2021 with at least 1 year of event-free follow-up were included. Results: In total, 3,175 patients with PBC were followed for a median duration of 11.4 years (IQR 5.9–17.9) after LT. Tacrolimus (Tac) was registered in 2,056 (64.8%) and cyclosporin in 819 (25.8%) patients. Following adjustment for recipient age, recipient sex, donor age, and year of LT, Tac was not associated with higher risk of graft loss (adjusted hazard ratio [aHR] 1.07, 95% CI 0.92-1.25, p = 0.402) or death (aHR 1.06, 95% CI 0.90-1.24, p = 0.473) over cyclosporin. In this model, maintenance mycophenolate mofetil (MMF) was associated with a lower risk of graft loss (aHR 0.72, 95% CI 0.60-0.87, p
Published: 2024
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4. Comparing Different Methods for the Diagnosis of Liver Steatosis: What Are the Best Diagnostic Tools?

Author: Sophie Chopinet, Olivier Lopez, Sophie Brustlein, Antoine Uzel, Anais Moyon, Isabelle Varlet, Laure Balasse, Frank Kober, Mickaël Bobot, Monique Bernard, Aurélie Haffner, Michaël Sdika, Bruno Montcel, Benjamin Guillet, Vincent Vidal, Emilie Grégoire, Jean Hardwigsen, and Pauline Brige
Subjects: liver steatosis, MCD diet, CARS microscopy, MR spectroscopy, 99mTc MIBI, near-infrared spectroscopy, Medicine (General), R5-920
Abstract: Background: Due to the ongoing organ shortage, marginal grafts with steatosis are more frequently used in liver transplantation, leading to higher occurrences of graft dysfunction. A histological analysis is the gold standard for the quantification of liver steatosis (LS), but has its drawbacks: it is an invasive method that varies from one pathologist to another and is not available in every hospital at the time of organ procurement. This study aimed to compare non-invasive diagnostic tools to a histological analysis for the quantification of liver steatosis. Methods: Male C57BL6J mice were fed with a methioninecholine-deficient (MCD) diet for 14 days or 28 days to induce LS, and were compared to a control group of animals fed with a normal diet. The following non-invasive techniques were performed and compared to the histological quantification of liver steatosis: magnetic resonance spectroscopy (MRS), CARS microscopy, 99mTc MIBI SPECT imaging, and a new near-infrared spectrometer (NIR-SG1). Results: After 28 days on the MCD diet, an evaluation of LS showed ≥30% macrovesicular steatosis. High correlations were found between the NIR-SG1 and the blinded pathologist analysis (R2 = 0.945) (p = 0.001), and between the CARS microscopy (R2 = 0.801 (p < 0.001); MRS, R2 = 0.898 (p < 0.001)) and the blinded pathologist analysis. The ROC curve analysis showed that the area under the curve (AUC) was 1 for both the NIR-SG1 and MRS (p = 0.021 and p < 0.001, respectively), while the AUC = 0.910 for the Oil Red O stain (p < 0.001) and the AUC = 0.865 for the CARS microscopy (p < 0.001). The AUC for the 99mTc MIBI SPECT was 0.640 (p = 0.013), and this was a less discriminating technique for LS quantification. Conclusions: The best-performing non-invasive methods for LS quantification are MRS, CARS microscopy, and the NIR-SG1. The NIR-SG1 is particularly appropriate for clinical practice and needs to be validated by clinical studies on liver grafts.
Published: 2024
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5. Safety and feasibility of chemotherapy followed by liver transplantation for patients with definitely unresectable colorectal liver metastases: insights from the TransMet randomised clinical trialResearch in context

Author: René Adam, David Badrudin, Laurence Chiche, Petru Bucur, Olivier Scatton, Victoire Granger, Michel Ducreux, Umberto Cillo, François Cauchy, Mickael Lesurtel, Jean-Yves Mabrut, Chris Verslype, Laurent Coubeau, Jean Hardwigsen, Emmanuel Boleslawski, Fabrice Muscari, Heithem Jeddou, Denis Pezet, Bruno Heyd, Valerio Lucidi, Karen Geboes, Jan Lerut, Pietro Majno, Lamiae Grimaldi, Nadjia Boukhedouni, Céline Piedvache, Maximiliano Gelli, Francis Levi, and Maïté Lewin
Subjects: Colorectal liver metastases, Liver transplantation, Chemotherapy, Randomised clinical trial, Medicine (General), R5-920
Abstract: Summary: Background: Despite the increasing efficacy of chemotherapy (C), the 5-year survival rate for patients with unresectable colorectal liver metastases (CLM) remains around 10%. Liver transplantation (LT) might offer a curative approach for patients with liver-only disease, yet its superior efficacy compared to C alone remains to be demonstrated. Methods: The TransMet randomised multicentre clinical trial (NCT02597348) compares the curative potential of C followed by LT versus C alone in patients with unresectable CLM despite stable or responding disease on C. Patient eligibility criteria proposed by local tumour boards had to be validated by an independent committee via monthly videoconferences. Outcomes reported here are from a non-specified interim analysis. These include the eligibility of patients to be transplanted for non resectable colorectal liver metastases, as well as the feasibility and the safety of liver transplantation in this indication. Findings: From February 2016 to July 2021, 94 (60%) of 157 patients from 20 centres in 3 countries submitted to the validation committee, were randomised. Reasons for ineligibility were mainly tumour progression in 50 (32%) or potential resectability in 13 (8%). The median delay to LT after randomisation was 51 (IQR 30–65) days. Nine of 47 patients (19%, 95% CI: 9–33) allocated to the LT arm failed to undergo transplantation because of intercurrent disease progression. Three of the 38 transplanted patients (8%) were re-transplanted, one of whom (3%) died post-operatively from multi-organ failure. Interpretation: The selection process of potential candidates for curative intent LT for unresectable CLM in the TransMet trial highlighted the critical role of an independent multidisciplinary validation committee. After stringent selection, the feasibility of LT was 81%, as 19% had disease progression while on the waiting list. These patients should be given high priority for organ allocation to avoid dropout from the transplant strategy. Funding: No source of support or funding from any author to disclose for this work. The trial was supported by the Assistance Publique – Hôpitaux de Paris (AP-HP).
Published: 2024
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6. Inevitability of disease recurrence after liver transplantation for NAFLD cirrhosis

Author: François Villeret, Sébastien Dharancy, Domitille Erard, Armand Abergel, Louise Barbier, Camille Besch, Olivier Boillot, Karim Boudjema, Audrey Coilly, Filomena Conti, Christophe Corpechot, Christophe Duvoux, François Faitot, Stéphanie Faure, Claire Francoz, Emiliano Giostra, Jean Gugenheim, Jean Hardwigsen, Marie-Noëlle Hilleret, Jean-Baptiste Hiriart, Pauline Houssel-Debry, Nassim Kamar, Guillaume Lassailly, Marianne Latournerie, Georges-Philippe Pageaux, Didier Samuel, Claire Vanlemmens, Faouzi Saliba, and Jérôme Dumortier
Subjects: liver transplantation, NASH, metabolic syndrome, NAFLD recurrence, Bariatric surgery, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background & Aims: Liver transplantation (LT) is the only available treatment for end-stage non-alcoholic fatty liver disease (NAFLD) (related decompensated cirrhosis and/or hepatocellular carcinoma). The aim of our study was to evaluate the risk of disease recurrence after LT and the factors influencing it. Method: This retrospective multicenter study included adults transplanted for NAFLD cirrhosis between 2000 and 2019 in 20 participating French-speaking centers. Disease recurrence (steatosis, steatohepatitis and fibrosis) was diagnosed from liver graft biopsies. Results: We analyzed 150 patients with at least one graft liver biopsy available ≥6 months after transplantation, among 361 patients transplanted for NAFLD. The median (IQR) age at LT was 61.3 (54.4-64.6) years. The median follow-up after LT was 4.7 (2.8-8.1) years. The cumulative recurrence rates of steatosis and steatohepatitis at 5 years were 80.0% and 60.3%, respectively. Significant risk factors for steatohepatitis recurrence in multivariate analysis were recipient age at LT
Published: 2023
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7. AFP score and metroticket 2.0 perform similarly and could be used in a 'within-ALL' clinical decision tool

Author: Federico Piñero, Charlotte Costentin, Helena Degroote, Andrea Notarpaolo, Ilka FSF. Boin, Karim Boudjema, Cinzia Baccaro, Aline Chagas, Philippe Bachellier, Giuseppe Maria Ettorre, Jaime Poniachik, Fabrice Muscari, Fabrizio Dibenedetto, Sergio Hoyos Duque, Ephrem Salame, Umberto Cillo, Sebastián Marciano, Claire Vanlemmens, Stefano Fagiuoli, Flair Carrilho, Daniel Cherqui, Patrizia Burra, Hans Van Vlierberghe, Quirino Lai, Marcelo Silva, Fernando Rubinstein, Christophe Duvoux, Filomena Conti, Olivier Scatton, Pierre Henri Bernard, Claire Francoz, Francois Durand, Sébastien Dharancy, Marie-lorraine Woehl, Alexis Laurent, Sylvie Radenne, Jérôme Dumortier, Armand Abergel, Louise Barbier, Pauline Houssel-Debry, Georges Philippe Pageaux, Laurence Chiche, Victor Deledinghen, Jean Hardwigsen, J. Gugenheim, M. altieri, Marie Noelle Hilleret, Thomas Decaens, Paulo Costa, Elaine Cristina de Ataide, Emilio Quiñones, Margarita Anders, Adriana Varón, Alina Zerega, Alejandro Soza, Martín Padilla Machaca, Diego Arufe, Josemaría Menéndez, Rodrigo Zapata, Mario Vilatoba, Linda Muñoz, Ricardo Chong Menéndez, Martín Maraschio, Luis G. Podestá, Lucas McCormack, Juan Mattera, Adrian Gadano, Jose Huygens Parente García, Giulia Magini, Lucia Miglioresi, Martina Gambato, Cecilia D’Ambrosio, Alessandro Vitale, Michele Colledan, Domenico Pinelli, Paolo Magistri, Giovanni Vennarecci, Marco Colasanti, Valerio Giannelli, Adriano Pellicelli, Callebout Eduard, Iesari Samuele, Dekervel Jeroen, Schreiber Jonas, Pirenne Jacques, Verslype Chris, Ysebaert Dirk, Michielsen Peter, Lucidi Valerio, Moreno Christophe, Detry Olivier, Delwaide Jean, Troisi Roberto, and Lerut Jan Paul
Subjects: Prediction, reclassification, recurrence, transplantation, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background & Aims: Two recently developed composite models, the alpha-fetoprotein (AFP) score and Metroticket 2.0, could be used to select patients with hepatocellular carcinoma (HCC) who are candidates for liver transplantation (LT). The aim of this study was to compare the predictive performance of both models and to evaluate the net risk reclassification of post-LT recurrence between them using each model’s original thresholds. Methods: This multicenter cohort study included 2,444 adult patients who underwent LT for HCC in 47 centers from Europe and Latin America. A competing risk regression analysis estimating sub-distribution hazard ratios (SHRs) and 95% CIs for recurrence was used (Fine and Gray method). Harrell’s adapted c-statistics were estimated. The net reclassification index for recurrence was compared based on each model’s original thresholds. Results: During a median follow-up of 3.8 years, there were 310 recurrences and 496 competing events (20.3%). Both models predicted recurrence, HCC survival and survival better than Milan criteria (p
Published: 2023
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8. The white test for intraoperative screening of bile leakage: a potential trigger factor for acute pancreatitis after liver resection—a case series

Author: Sophie Chopinet, Emilie Bollon, Jean-François Hak, Laurent Reydellet, Valéry Blasco, Farouk Tradi, Guillaume Louis, Emilie Grégoire, and Jean Hardwigsen
Subjects: Acute pancreatitis, White test, Hepatectomy, Bile leakage, Case series, Surgery, RD1-811
Abstract: Abstract Background Acute pancreatitis after liver resection is a rare but serious complication, and few cases have been described in the literature. Extended lymphadenectomy, and long ischemia due to the Pringle maneuver could be responsible of post-liver resection acute pancreatitis, but the exact causes of AP after hepatectomy remain unclear. Cases presentation We report here three cases of AP after hepatectomy and we strongly hypothesize that this is due to the bile leakage white test. 502 hepatectomy were performed at our center and 3 patients (0.6%) experienced acute pancreatitis after LR and all of these three patients underwent the white test at the end of the liver resection. None underwent additionally lymphadenectomy to the liver resection. All patient had a white-test during the liver surgery. We identified distal implantation of the cystic duct in these three patients as a potential cause for acute pancreatitis. Conclusion The white test is useful for detection of bile leakage after liver resection, but we do not recommend a systematic use after LR, because severe acute pancreatitis can be lethal for the patient, especially in case of distal cystic implantation which may facilitate reflux in the main pancreatic duct.
Published: 2021
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9. R3-AFP score is a new composite tool to refine prediction of hepatocellular carcinoma recurrence after liver transplantation

Author: Charlotte Costentin, Federico Piñero, Helena Degroote, Andrea Notarpaolo, Ilka F. Boin, Karim Boudjema, Cinzia Baccaro, Luis G. Podestá, Philippe Bachellier, Giuseppe Maria Ettorre, Jaime Poniachik, Fabrice Muscari, Fabrizio Dibenedetto, Sergio Hoyos Duque, Ephrem Salame, Umberto Cillo, Sebastian Marciano, Claire Vanlemmens, Stefano Fagiuoli, Patrizia Burra, Hans Van Vlierberghe, Daniel Cherqui, Quirino Lai, Marcelo Silva, Fernando Rubinstein, Christophe Duvoux, Filomena Conti, Olivier Scatton, Pierre Henri Bernard, Claire Francoz, Francois Durand, Sébastien Dharancy, Marie-lorraine Woehl, Alexis Laurent, Sylvie Radenne, Jérôme Dumortier, Armand Abergel, Louise Barbier, Pauline Houssel-Debry, Georges Philippe Pageaux, Laurence Chiche, Victor Deledinghen, Jean Hardwigsen, J. Gugenheim, M. Altieri, Marie Noelle Hilleret, Thomas Decaens, Aline Chagas, Paulo Costa, Elaine Cristina de Ataide, Emilio Quiñones, Sebastián Marciano, Margarita Anders, Adriana Varón, Alina Zerega, Alejandro Soza, Martín Padilla Machaca, Diego Arufe, Josemaría Menéndez, Rodrigo Zapata, Mario Vilatoba, Linda Muñoz, Ricardo Chong Menéndez, Martín Maraschio, Lucas McCormack, Juan Mattera, Adrian Gadano, Ilka S.F. Fatima Boin, Jose Huygens Parente García, Flair Carrilho, Giulia Magini, Lucia Miglioresi, Martina Gambato, Fabrizio Di Benedetto, Cecilia D’Ambrosio, Alessandro Vitale, Michele Colledan, Domenico Pinelli, Paolo Magistri, Giovanni Vennarecci, Marco Colasanti, Valerio Giannelli, Adriano Pellicelli, Cizia Baccaro, Callebout Eduard, Iesari Samuele, Dekervel Jeroen, Schreiber Jonas, Pirenne Jacques, Verslype Chris, Ysebaert Dirk, Michielsen Peter, Lucidi Valerio, Moreno Christophe, Detry Olivier, Delwaide Jean, Troisi Roberto, and Lerut Jan Paul
Subjects: Liver transplantation, Liver cancer, Recurrence, Explants pathology, Prediction, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background & Aims: Patients with hepatocellular carcinoma (HCC) are selected for liver transplantation (LT) based on pre-LT imaging ± alpha-foetoprotein (AFP) level, but discrepancies between pre-LT tumour assessment and explant are frequent. Our aim was to design an explant-based recurrence risk reassessment score to refine prediction of recurrence after LT and provide a framework to guide post-LT management. Methods: Adult patients who underwent transplantation between 2000 and 2018 for HCC in 47 centres were included. A prediction model for recurrence was developed using competing-risk regression analysis in a European training cohort (TC; n = 1,359) and tested in a Latin American validation cohort (VC; n=1,085). Results: In the TC, 76.4% of patients with HCC met the Milan criteria, and 89.9% had an AFP score of ≤2 points. The recurrence risk reassessment (R3)-AFP model was designed based on variables independently associated with recurrence in the TC (with associated weights): ≥4 nodules (sub-distribution of hazard ratio [SHR] = 1.88, 1 point), size of largest nodule (3–6 cm: SHR = 1.83, 1 point; >6 cm: SHR = 5.82, 5 points), presence of microvascular invasion (MVI; SHR = 2.69, 2 points), nuclear grade >II (SHR = 1.20, 1 point), and last pre-LT AFP value (101–1,000 ng/ml: SHR = 1.57, 1 point; >1,000 ng/ml: SHR = 2.83, 2 points). Wolber’s c-index was 0.76 (95% CI 0.72–0.80), significantly superior to an R3 model without AFP (0.75; 95% CI 0.72–0.79; p = 0.01). Four 5-year recurrence risk categories were identified: very low (score = 0; 5.5%), low (1–2 points; 15.1%), high (3–6 points; 39.1%), and very high (>6 points; 73.9%). The R3-AFP score performed well in the VC (Wolber’s c-index of 0.78; 95% CI 0.73–0.83). Conclusions: The R3 score including the last pre-LT AFP value (R3-AFP score) provides a user-friendly, standardised framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials for HCC not limited to the Milan criteria. Clinical Trials Registration: NCT03775863. Lay summary: Considering discrepancies between pre-LT tumour assessment and explant are frequent, reassessing the risk of recurrence after LT is critical to further refine the management of patients with HCC. In a large and international cohort of patients who underwent transplantation for HCC, we designed and validated the R3-AFP model based on variables independently associated with recurrence post-LT (number of nodules, size of largest nodule, presence of MVI, nuclear grade, and last pre-LT AFP value). The R3-AFP model including last available pre-LT AFP value outperformed the original R3 model only based on explant features. The final R3-AFP scoring system provides a robust framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials, irrespective of criteria used to select patients with HCC for LT.
Published: 2022
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10. International study on the outcome of locoregional therapy for liver transplant in hepatocellular carcinoma beyond Milan criteria

Author: Helena Degroote, Federico Piñero, Charlotte Costentin, Andrea Notarpaolo, Ilka F. Boin, Karim Boudjema, Cinzia Baccaro, Aline Lopes Chagas, Philippe Bachellier, Giuseppe Maria Ettorre, Jaime Poniachik, Fabrice Muscari, Fabrio Di Benedetto, Sergio Hoyos Duque, Ephrem Salame, Umberto Cillo, Adrián Gadano, Claire Vanlemmens, Stefano Fagiuoli, Fernando Rubinstein, Patrizia Burra, Daniel Cherqui, Marcelo Silva, Hans Van Vlierberghe, Christophe Duvoux, Filomena Conti, Olivier Scatton, Pierre Henri Bernard, Claire Francoz, Francois Durand, Sébastien Dharancy, Marie-lorraine Woehl, Alexis Laurent, Sylvie Radenne, Jérôme Dumortier, Armand Abergel, Louise Barbier, Pauline Houssel-Debry, Georges Philippe Pageaux, Laurence Chiche, Victor Deledinghen, Jean Hardwigsen, J. Gugenheim, M. Altieri, Marie Noelle Hilleret, Thomas Decaens, Aline Chagas, Paulo Costa, Elaine Cristina de Ataide, Emilio Quiñones, Sebastián Marciano, Margarita Anders, Adriana Varón, Alina Zerega, Alejandro Soza, Martín Padilla Machaca, Diego Arufe, Josemaría Menéndez, Rodrigo Zapata, Mario Vilatoba, Linda Muñoz, Ricardo Chong Menéndez, Martín Maraschio, Luis G. Podestá, M. Fauda, A. Gonzalez Campaña, Lucas McCormack, Juan Mattera, Adrian Gadano, Ilka S.F. Fatima Boin, Jose Huygens Parente García, Flair Carrilho, Giulia Magini, Lucia Miglioresi, Martina Gambato, Fabrizio Di Benedetto, Cecilia D’Ambrosio, Alessandro Vitale, Michele Colledan, Domenico Pinelli, Paolo Magistri, Giovanni Vennarecci, Marco Colasanti, Valerio Giannelli, Adriano Pellicelli, Cizia Baccaro, Callebout Eduard, Iesari Samuele, Dekervel Jeroen, Schreiber Jonas, Pirenne Jacques, Verslype Chris, Ysebaert Dirk, Michielsen Peter, Lucidi Valerio, Moreno Christophe, Detry Olivier, Delwaide Jean, Troisi Roberto, and Lerut Jan Paul
Subjects: Hepatocellular carcinoma, Downstaging, UCSF downstaging protocol, All-comers, Alpha-foetoprotein, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background & Aims: Good outcomes after liver transplantation (LT) have been reported after successfully downstaging to Milan criteria in more advanced hepatocellular carcinoma (HCC). We aimed to compare post-LT outcomes in patients receiving locoregional therapies (LRT) before LT according to Milan criteria and University of California San Francisco downstaging (UCSF-DS) protocol and ‘all-comers’. Methods: This multicentre cohort study included patients who received any LRT before LT from Europe and Latin America (2000–2018). We excluded patients with alpha-foetoprotein (AFP) above 1,000 ng/ml. Competing risk regression analysis for HCC recurrence was conducted, estimating subdistribution hazard ratios (SHRs) and corresponding 95% CIs. Results: From 2,441 LT patients, 70.1% received LRT before LT (n = 1,711). Of these, 80.6% were within Milan, 12.0% within UCSF-DS, and 7.4% all-comers. Successful downstaging was achieved in 45.2% (CI 34.8–55.8) and 38.2% (CI 25.4–52.3) of the UCSF-DS group and all-comers, respectively. The risk of recurrence was higher for all-comers (SHR 6.01 [p
Published: 2021
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11. Comparison of different feeding regimes after pancreatoduodenectomy - a retrospective cohort analysis

Author: Théophile Guilbaud, David Jérémie Birnbaum, Sandrine Loubière, Julien Bonnet, Sophie Chopinet, Emilie Grégoire, Stéphane Berdah, Jean Hardwigsen, and Vincent Moutardier
Subjects: Pancreaticoduodenectomy, Gastrojejunostomy tube, Enteral nutrition, Postoperative pancreatic fistula, Delayed gastric empty, Cost savings, Nutrition. Foods and food supply, TX341-641, Nutritional diseases. Deficiency diseases, RC620-627
Abstract: Abstract Background Delayed gastric emptying (DGE) is the most frequent pancreatic specific complication (PSC) after pancreaticoduodenectomy (PD). Several gastric decompression systems exist to manage DGE. Patients with a pancreatic tumor require prolonged nutrition; however, controversies exist concerning nutrition protocol after PD. The aim of the study was to assess the safety and efficacy of nasogastric (NG), gastrostomy (GT), and gastrojejunostomy (GJ) tubes with different feeding systems on postoperative courses. Methods Between January 2013 and March 2016, 86 patients underwent PD with pancreaticogastrostomy. Patients were divided into three groups: GJ group with enteral nutrition (EN, n = 12, 14%), NG (n = 31, 36%) and GT groups (n = 43, 50%), both with total parenteral nutrition (TPN). Results Patients in the GJ (n = 9, 75%) and GT (n = 18, 42%) groups had an American Society of Anesthesiologists (ASA) score of 3 more often than those in the NG group (n = 5, 16%, p ≤ 0.01). Multivariate analysis identified the GT tube with TPN as an independent risk factor of severe morbidity (p = 0.02) and DGE (p
Published: 2017
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12. Cold Preservation of Human Adult Hepatocytes for Liver Cell Therapy

Author: Cedric Duret, Daniel Moreno, Anangi Balasiddaiah, Solene Roux, Phillipe Briolotti, Edith Raulet, Astrid Herrero, Helene Ramet, Christine Biron-Andreani, Sabine Gerbal-Chaloin, Jeanne Ramos, Francis Navarro, Jean Hardwigsen, Patrick Maurel, Rafael Aldabe, and Martine Daujat-Chavanieu
Subjects: Medicine
Abstract: Hepatocyte transplantation is a promising alternative therapy for the treatment of hepatic failure, hepatocellular deficiency, and genetic metabolic disorders. Hypothermic preservation of isolated human hepatocytes is potentially a simple and convenient strategy to provide on-demand hepatocytes in sufficient quantity and of the quality required for biotherapy. In this study, first we assessed how cold storage in three clinically safe preservative solutions (UW, HTS-FRS, and IGL-1) affects the viability and in vitro functionality of human hepatocytes. Then we evaluated whether such cold-preserved human hepatocytes could engraft and repopulate damaged livers in a mouse model of liver failure. Human hepatocytes showed comparable viabilities after cold preservation in the three solutions. The ability of fresh and cold-stored hepatocytes to attach to a collagen substratum and to synthesize and secrete albumin, coagulation factor VII, and urea in the medium after 3 days in culture was also equally preserved. Cold-stored hepatocytes were then transplanted in the spleen of immunodeficient mice previously infected with adenoviruses containing a thymidine kinase construct and treated with a single dose of ganciclovir to induce liver injury. Engraftment and liver repopulation were monitored over time by measuring the blood level of human albumin and by assessing the expression of specific human hepatic mRNAs and proteins in the recipient livers by RT-PCR and immunohistochemistry, respectively. Our findings show that cold-stored human hepatocytes in IGL-1 and HTS-FRS preservative solutions can survive, engraft, and proliferate in a damaged mouse liver. These results demonstrate the usefulness of human hepatocyte hypothermic preservation for cell transplantation.
Published: 2015
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13. Further characterization of HDAC and SIRT gene expression patterns in pancreatic cancer and their relation to disease outcome.

Author: Mehdi Ouaïssi, Françoise Silvy, Céline Loncle, Diva Ferraz da Silva, Carla Martins Abreu, Emmanuelle Martinez, Patrick Berthézene, Sophie Cadra, Yves Patrice Le Treut, Jean Hardwigsen, Bernard Sastre, Igor Sielezneff, Liliane Benkoel, Jean Delgrande, Ali Ouaissi, Juan Iovanna, Dominique Lombardo, and Eric Mas
Subjects: Medicine, Science
Abstract: Ductal adenocarcinoma of the pancreas is ranking 4 for patient' death from malignant disease in Western countries, with no satisfactory treatment. We re-examined more precisely the histone deacetylases (HDAC) and Sirtuin (SIRT) gene expression patterns in pancreatic cancer with more pancreatic tumors and normal tissues. We also examined the possible relationship between HDAC gene expression levels and long term disease outcome. Moreover, we have evaluated by using an in vitro model system of human pancreatic tumor cell line whether HDAC7 knockdown may affect the cell behavior. We analyzed 29 pancreatic adenocarcinoma (PA), 9 chronic pancreatitis (CP), 8 benign pancreatic (BP) and 11 normal pancreatic tissues. Concerning pancreatic adenocarcinoma, we were able to collect biopsies at the tumor periphery. To assess the possible involvement of HDAC7 in cell proliferation capacity, we have generated recombinant human Panc-1 tumor which underexpressed or overexpressed HDAC7. The expression of HDAC1,2,3,4,7 and Nur77 increased in PA samples at levels significantly higher than those observed in the CP group (p = 0.0160; 0.0114; 0.0227; 0.0440; 0.0136; 0.0004, respectively). The expression of HDAC7, was significantly greater in the PA compared with BP tissue samples (p = 0.05). Mean mRNA transcription levels of PA for HDAC7 and HDAC2 were higher when compared to their counterpart biopsies taken at the tumor periphery (p = 0.0346, 0.0053, respectively). Moreover, the data obtained using confocal microscopy and a quantitative method of immunofluorescence staining strongly support the HDAC7 overexpression in PA surgical specimens. The number of deaths and recurrences at the end of follow up were significantly greater in patients with overexpression of HDAC7. Interestingly, the rate of growth was significantly reduced in the case of cell carrying shRNA construct targeting HDAC7 encoding gene when compared to the parental Panc-1 tumor cells (p = 0.0015) at 48 h and 96 h (p = 0.0021). This study strongly support the notion that HDAC7play a role in pancreatic adenocarcinoma progression.
Published: 2014
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14. Long‐term outcome of liver transplantation for autoimmune hepatitis: A French nationwide study over 30 years

Author: Yasmina Chouik, Olivier Chazouillères, Claire Francoz, Eleonora De Martin, Olivier Guillaud, Armand Abergel, Mario Altieri, Louise Barbier, Camille Besch, Filomena Conti, Christophe Corpechot, Sébastien Dharancy, François Durand, Christophe Duvoux, Jean Gugenheim, Jean Hardwigsen, Marie‐Noëlle Hilleret, Pauline Houssel‐Debry, Nassim Kamar, Delphine Maucort‐Boulch, Anne Minello, Martine Neau‐Cransac, Georges‐Philippe Pageaux, Sylvie Radenne, Olivier Roux, Faouzi Saliba, Olivier Serée, Didier Samuel, Claire Vanlemmens, Marie‐Lorraine Woehl‐Jaegle, Vincent Leroy, Jean‐Charles Duclos‐Vallée, and Jérôme Dumortier
Subjects: Hepatology
Published: 2023
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15. Liver transplantation for autoimmune hepatitis: Pre‐transplant does not predict the early post‐transplant outcome

Author: Yasmina Chouik, Claire Francoz, Eleonora De Martin, Olivier Guillaud, Armand Abergel, Mario Altieri, Louise Barbier, Camille Besch, Olivier Chazouillères, Filomena Conti, Christophe Corpechot, Sébastien Dharancy, François Durand, Christophe Duvoux, Jean Gugenheim, Jean Hardwigsen, Marie‐Noëlle Hilleret, Pauline Houssel‐Debry, Nassim Kamar, Anne Minello, Martine Neau‐Cransac, Georges‐Philippe Pageaux, Sylvie Radenne, Olivier Roux, Faouzi Saliba, Didier Samuel, Claire Vanlemmens, Marie‐Lorraine Woehl‐Jaegle, Vincent Leroy, Jean‐Charles Duclos‐Vallée, Jérôme Dumortier, Hospices Civils de Lyon (HCL), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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 (UPCité), 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 Edouard Herriot [CHU - HCL], Clinique de la Sauvegarde [Lyon], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Les Hôptaux universitaires de Strasbourg (HUS), CHU Strasbourg, Hôpital de Hautepierre [Strasbourg], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Henri Mondor [Créteil], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de Néphrologie et Transplantation d'organes [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), and Fondation Léon Bouchut
Subjects: early infection, MESH: Liver Transplantation, immunosuppression, MESH: Humans, Hepatology, MESH: Hepatitis, Autoimmune, fulminant hepatitis, MESH: Adult, MESH: Retrospective Studies, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, survival, sepsis, MESH: Massive Hepatic Necrosis, MESH: Female, MESH: Sepsis
Abstract: Background and aims: Autoimmune hepatitis (AIH) is a rare indication (
Published: 2023
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16. The white test for intraoperative screening of bile leakage: a potential trigger factor for acute pancreatitis after liver resection—a case series

Author: V. Blasco, Jean-François Hak, Farouk Tradi, Emilie Bollon, Jean Hardwigsen, Sophie Chopinet, Emilie Gregoire, Laurent Reydellet, G. Louis, Département de chirurgie générale et viscérale [Hôpital de la Timone - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE), Laboratoire d'Imagerie Interventionnelle Expérimentale (LIIE), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Européen de Recherche en Imagerie médicale (CERIMED), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-École Centrale de Marseille (ECM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Centre National de la Recherche Scientifique (CNRS), Department of Neuroradiology, APHM La Timone, Marseille, France, Service d'anesthésie et de réanimation [Hôpital de la Timone - APHM], and Département de Radiologie [Hôpital de la Timone - APHM]
Subjects: medicine.medical_specialty, RD1-811, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, medicine.medical_treatment, Ischemia, Case Report, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Bile leakage, Bile, Humans, Medicine, Hepatectomy, Case series, Pancreatic duct, business.industry, Reflux, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, General Medicine, medicine.disease, White test, Surgery, Acute pancreatitis, medicine.anatomical_structure, Liver, Pancreatitis, Acute Disease, Cystic duct, Lymphadenectomy, business, Complication
Abstract: Background Acute pancreatitis after liver resection is a rare but serious complication, and few cases have been described in the literature. Extended lymphadenectomy, and long ischemia due to the Pringle maneuver could be responsible of post-liver resection acute pancreatitis, but the exact causes of AP after hepatectomy remain unclear. Cases presentation We report here three cases of AP after hepatectomy and we strongly hypothesize that this is due to the bile leakage white test. 502 hepatectomy were performed at our center and 3 patients (0.6%) experienced acute pancreatitis after LR and all of these three patients underwent the white test at the end of the liver resection. None underwent additionally lymphadenectomy to the liver resection. All patient had a white-test during the liver surgery. We identified distal implantation of the cystic duct in these three patients as a potential cause for acute pancreatitis. Conclusion The white test is useful for detection of bile leakage after liver resection, but we do not recommend a systematic use after LR, because severe acute pancreatitis can be lethal for the patient, especially in case of distal cystic implantation which may facilitate reflux in the main pancreatic duct.
Published: 2021
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17. Liver transplantation for NAFLD cirrhosis: Age and recent coronary angioplasty are major determinants of survival

Author: François Villeret, Sébastien Dharancy, Domitille Erard, Armand Abergel, Louise Barbier, Camille Besch, Olivier Boillot, Karim Boudjema, Audrey Coilly, Filomena Conti, Christophe Corpechot, Christophe Duvoux, François Faitot, Stéphanie Faure, Claire Francoz, Emiliano Giostra, Jean Gugenheim, Jean Hardwigsen, Marie‐Noëlle Hilleret, Jean‐Baptiste Hiriart, Pauline Houssel‐Debry, Nassim Kamar, Guillaume Lassailly, Marianne Latournerie, Georges‐Philippe Pageaux, Didier Samuel, Claire Vanlemmens, Faouzi Saliba, and Jérôme Dumortier
Subjects: Adult, Aged, 80 and over, Liver Cirrhosis, Male, Carcinoma, Hepatocellular, Hepatology, Angioplasty, Liver Neoplasms, Liver Transplantation, End Stage Liver Disease, Treatment Outcome, Non-alcoholic Fatty Liver Disease, Humans, Retrospective Studies
Abstract: Liver transplantation (LT) is the treatment of end-stage non-alcoholic liver disease (NAFLD), that is decompensated cirrhosis and/or complicated by hepatocellular carcinoma (HCC). Few data on long-term outcome are available. The aim of this study was to evaluate overall patient and graft survivals and associated predictive factors.This retrospective multicentre study included adult transplant patients for NAFLD cirrhosis between 2000 and 2019 in participating French-speaking centres.A total of 361 patients (69.8% of male) were included in 20 centres. The median age at LT was 62.3 years [57.4-65.9] and the median MELD score was 13.9 [9.1-21.3]; 51.8% of patients had HCC on liver explant. Between 2004 and 2018, the number of LT for NAFLD cirrhosis increased by 720%. A quarter of the patients had cardiovascular history before LT. Median follow-up after LT was 39.1 months [15.8-72.3]. Patient survival at 1, 5 and 10 years after LT was 89.3%, 79.8% and 68.1% respectively. The main causes of death were sepsis (37.5%), malignancies (29.2%) and cardiovascular events (22.2%). In multivariate analysis, three risk factors for overall mortality after LT were recipient pre-LT BMI 32 kg/mSurvival after LT for NAFLD cirrhosis is good at 5 years. Donor and recipient age, and cardiovascular history, are major prognostic factors to consider.
Published: 2022

18. Endovascular therapy for hepatic artery stenosis after liver transplantation: a retrospective study of 17 patients

Author: Idir KHATI, Alexis JACQUIER, Mathieu GRABER, Axel BARTOLI, Farah CADOUR, Jean HARDWIGSEN, Farouk TRADI, and Pierre Antoine BARRAL
Abstract: Purpose:To evaluate the efficiency of endovascular therapy in hepatic artery stenosis.Methods:A retrospective review of all endovascular interventions for hepatic artery stenosis (HAS) after liver transplantation that occurred between June 2013 and November 2020 was performed at a single institution in France. The treatment consisted of dilation with a balloon or stent. We analyzed short-term (technical success and complications) and long-term outcomes (liver function, arterial patency, graft survival at 12 months (GS), and reintervention). We also compared percutaneous balloon angioplasty (PBA) with stent placement.A total of 18 stenoses were suspected on the basis of routine surveillance duplex ultrasound imaging (peak systolic velocity >200 cm/s, systolic accelerating time >10 ms and resistive index Results:Seventeen patients were included (14 males, mean age 57 years; and three females, mean age 58 years). Interventions were performed in 17 cases (95%) with PBA only (5/17), stent only (5/17) or both (4/17). In four cases no treatment was possible.Immediate technical success was 100%. Major complications occurred in 1 of 17 cases (5.8%), consisting of target vessel dissection. Follow up occurred from 1 month to 4 years (median 15 months). The analysis of the three (groups PBA only, stent only or both) showed the same procedural success (100%), GS (100%) and normal liver function after the procedures but different rates of complications (20% vs. 0% vs. 0%), arterial patency at 12 months (60% vs. 80% vs. 85%), early stenosis (40% vs. 80% vs. 0%) or late stenosis (60% vs. 20% vs. 100%) and requirement for reintervention (40% vs. 20% vs. 14%).Conclusion:PBA alone, stent placement only or both (PBA + stent) produced the same results in the treatment of HAS. The results may depend on the type of lesion and anatomy of the artery. Our study did not show any significant difference in prognosis between early and late stenosis. It is probably not a definitive answer, but these treatments are safe and effective for extending graft survival in the context of graft shortages.
Published: 2022
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19. Five-year outcomes in liver transplant patients receiving everolimus with or without a calcineurin inhibitor: Results from the CERTITUDE study

Author: Faouzi Saliba, Christophe Duvoux, Sébastien Dharancy, Jérôme Dumortier, Yvon Calmus, Jean Gugenheim, Nassim Kamar, Ephrem Salamé, Martine Neau‐Cransac, Claire Vanlemmens, François Durand, Georges‐Philippe Pageaux, Jean Hardwigsen, Yasmina Benkhatar, François Derquenne, and Filomena Conti
Subjects: Graft Rejection, Carcinoma, Hepatocellular, Hepatology, Calcineurin Inhibitors, Graft Survival, Liver Neoplasms, Humans, Everolimus, Immunosuppressive Agents, Tacrolimus, Liver Transplantation
Abstract: To report 5-year outcomes of the CERTITUDE study.An observational study in patients with liver transplantation (LTx) compared the long-term impact of immunosuppression (with/without a calcineurin inhibitor) on renal function, cancers, major cardiovascular events (MACEs) and other safety parameters. All patients completing the 6-month SIMCER study were recruited and analysed according to treatment received at randomization and actual treatment received during the follow-up.Of the 143 enrolled patients, 119 completed the 5-year follow-up (everolimus [EVR], n = 55; tacrolimus [TAC], n = 64). The mean absolute change in estimated glomerular filtration rate was not statistically different between both groups (TAC, -15.53 ml/min/1.73 mThe CERTITUDE study demonstrated that EVR- and TAC-based regimens have comparable efficacy, safety and tolerability up to 5 years post-LTx.
Published: 2022

20. Long-term abdominal wall benefits of the laparoscopic approach in liver left lateral sectionectomy: a multicenter comparative study

Author: Jean-Yves Mabrut, Jean Hardwigsen, Mickael Lesurtel, Olivier Soubrane, François Cauchy, Jean-Marc Regimbeau, Kayvan Mohkam, Stéphanie Truant, Daniel Cherqui, Emmanuel Boleslawksi, Guillaume Millet, Benjamin Darnis, Christophe Laurent, J. Dembinski, Philippe Bachelier, Eric Vibert, Nicolas Golse, Clinique de la Sauvegarde [Lyon], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, SImulations en Médecine, BIOtechnologie et ToXicologie de systèmes multicellulaires (SIMBIOTX ), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Centre Hépato-Biliaire [Hôpital Paul Brousse] (CHB), Hôpital Paul Brousse-Assistance Publique - Hôpitaux de Paris, Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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 (UPCité), Service de Gastroentérologie [Hôpital Beaujon], Chirurgie digestive [CHU Amiens], CHU Amiens-Picardie, Simplification des soins chez les patients complexes - UR UPJV 7518 (SSPC), Université de Picardie Jules Verne (UPJV), Service de Chirurgie, Assistance Publique - Hôpitaux de Marseille (APHM)-Hospices Civiles de Marseille-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), CHU Strasbourg, Centre interuniversitaire de recherche et d'ingenierie des matériaux (CIRIMAT), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT), CHU Lille, Université de Lille, Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])
Subjects: medicine.medical_specialty, medicine.diagnostic_test, business.industry, Incisional hernia, [SDV]Life Sciences [q-bio], Incidence (epidemiology), Hepatology, medicine.disease, Surgery, Abdominal wall, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Internal medicine, Medicine, 030211 gastroenterology & hepatology, Hernia, business, Laparoscopy, Complication, Abdominal surgery
Abstract: International audience; Background Laparoscopy is nowadays considered as the standard approach for hepatic left lateral sectionectomy (LLS), but its value in the prevention of incisional hernia (IH) has not been demonstrated. Methods Between 2012 and 2017, patients undergoing laparoscopic (LLLS) or open LLS (OLLS) in 8 centers were compared. Patients undergoing a simultaneous major abdominal procedure were excluded. The incidence of IH was assessed clinically and morphologically on computed tomography (CT) using inverse probability of treatment weighting (IPTW) and multivariable regression analysis. Results After IPTW, 84 LLLS were compared to 48 OLLS. Compared to OLLS, LLLS patients had reduced blood loss (100 [IQR: 50-200] ml vs. 150 [IQR: 50-415] ml,p = 0.023) and shorter median hospital stay (5 [IQR: 4-7] days vs. 7 [6-9] days,p < 0.001), but experienced similar rate of postoperative complications (mean comprehensive complication index: 12 +/- 19 after OLLS versus 13 +/- 20 after LLLS,p = 0.968). Long-term radiological screening was performed with a median follow-up of 27.4 (12.1-44.9) months. There was no difference between the two groups in terms of clinically relevant IH (10.7% [n = 9] after LLLS, 8.3% [n = 4] after OLLS,p = 0.768). The rate of IH detected on computed tomography was lower after LLLS than after OLLS (11.9% [n = 10] versus 29.2% [n = 14],p = 0.013). On multivariable analysis, the laparoscopic approach was the only independent factor influencing the risk of morphological IH (OR = 0.290 [95% CI: 0.094-0.891],p = 0.031). The 2 preferential sites for specimen extraction after LLLS were Pfannenstiel and midline incisions, with rates of IH across the extraction site of 2.3% [n = 1/44] and 23.8% [n = 5/21], respectively (p = 0.011). Conclusion The laparoscopic approach for LLS decreases the risk of long-term IH as evidenced on morphological examinations, with limited clinical impact. Pfannenstiel's incision should be preferred to midline incision for specimen extraction after LLLS.
Published: 2020
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21. Influence de 4 solutions de préservation sur la durée de réanimation, la survie du greffon et du patient après transplantation hépatique

Author: 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
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22. Impact of Hyperoxia after Graft Reperfusion on Lactate Level and Outcomes in Adults Undergoing Orthotopic Liver Transplantation

Author: Laurent Reydellet, Audrey Le Saux, Valery Blasco, Cyril Nafati, Karim Harti-Souab, Romain Armand, Ariane Lannelongue, Emilie Gregoire, Jean Hardwigsen, Jacques Albanese, and Sophie Chopinet
Subjects: liver transplantation, hyperoxia, ischemia–reperfusion injury, lactate level, General Medicine
Abstract: Background: Hyperoxia is common during liver transplantation (LT), without being supported by any guidelines. Recent studies have shown the potential deleterious effect of hyperoxia in similar models of ischemia–reperfusion. Hyperoxia after graft reperfusion during orthotopic LT could increase lactate levels and worsen patient outcomes. Methods: We conducted a retrospective and monocentric pilot study. All adult patients who underwent LT from 26 July 2013 to 26 December 2017 were considered for inclusion. Patients were classified into two groups according to oxygen levels before graft reperfusion: the hyperoxic group (PaO2 > 200 mmHg) and the nonhyperoxic group (PaO2 < 200 mmHg). The primary endpoint was arterial lactatemia 15 min after graft revascularization. Secondary endpoints included postoperative clinical outcomes and laboratory data. Results: A total of 222 liver transplant recipients were included. Arterial lactatemia after graft revascularization was significantly higher in the hyperoxic group (6.03 ± 4 mmol/L) than in the nonhyperoxic group (4.81 ± 2 mmol/L), p < 0.01. The postoperative hepatic cytolysis peak, duration of mechanical ventilation and duration of ileus were significantly increased in the hyperoxic group. Conclusions: In the hyperoxic group, the arterial lactatemia, the hepatic cytolysis peak, the mechanical ventilation and the postoperative ileus were higher than in the nonhyperoxic group, suggesting that hyperoxia worsens short-term outcomes and could lead to increase ischemia–reperfusion injury after liver transplantation. A multicenter prospective study should be performed to confirm these results.
Published: 2023
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23. Peri-operative risk factors of chronic kidney disease after liver transplantation

Author: Emilie Gregoire, Laurent Reydellet, Valérie Moal, Claire Decoster, Mickaël Bobot, Emilie Bollon, Jean Hardwigsen, V. Blasco, René Gerolami, Sophie Chopinet, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Microbes évolution phylogénie et infections (MEPHI), and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Nephrology, medicine.medical_specialty, medicine.medical_treatment, Renal function, Kidney failure, Liver transplantation, Severity of Illness Index, law.invention, End Stage Liver Disease, Liver disease, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, law, Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Chronic kidney disease, medicine, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Renal replacement therapy, Renal Insufficiency, Chronic, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, business.industry, Acute kidney injury, medicine.disease, Intensive care unit, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Post-operative outcomes, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, business, Kidney disease, Glomerular Filtration Rate
Abstract: International audience; Background Chronic kidney disease (CKD) is a frequent long-term complication after liver transplantation (LT) and is associated with poor long-term survival. The aim of our study was to identify the risk factors of developing post-transplant CKD at 1 year, during the pre-operative, peri-operative, and post-LT phases. Methods All consecutive patients who underwent primary LT between July 2013 and February 2018 were analyzed. To assess the impact of peri- and post-operative factors on renal function at 1 year we performed a propensity score matching on gender, age of the recipient, Model for End-Stage Liver Disease (MELD) score, etiology of the hepatic disease, and estimated Glomerular Filtration Rate (eGFR) at baseline. Results Among the 245 patients who underwent LT, 215 had available data at one year (Y1), and 46% of them had CKD. Eighty-three patients in the CKD group and 83 in the normal renal function group were then matched. The median follow-up was 35 months (27-77). Patients with CKD at Y1 had a decreased 5-year survival compared to patients with normal renal function at one year: figures were 62% and 90%, respectively, p = 0.001. The independent predictors of CKD at Y1 were major complications (OR = 2.2, 95% CI [1.2-4.2]), p = 0.015, intensive care unit (ICU) stay > 5 days (OR = 2.2, 95% CI [1.3-5.1]), p = 0.046, ICU serum lactate level at 24 h >= 2.5 mmol/L (OR = 3.8 95% CI [1.1-8]), p = 0.034, need for post-LT renal replacement therapy (OR = 6.4 95% CI [1.4-25]), and MELD score >= 20 (OR = 2.1 95% CI [1.1-3.9]), p = 0.019. Conclusions The peri-operative period has a major impact on CKD incidence. Early recognition of patients at high risk of CKD may be critical for implementation of nephroprotective measures. Graphic abstract
Published: 2022
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24. Recurrence of primary sclerosing cholangitis after liver transplantation: a french cohort study including 571 patients

Author: Florian Veyre, Eleonora De Martin, Domitille Erard, Claire Francoz, Laure Elkrief, Camille Besch, Olivier Boillot, Karim Boudjema, Filomena Conti, Sebastien Dharancy, Christophe Duvoux, Jean Gugenheim, Jean Hardwigsen, Marie-Noëlle Hilleret, Isabelle Ollivier-Hourmand, Maryline Debette-Gratien, Pauline Houssel-Debry, Nassim Kamar, Jean-Baptiste Hiriart, Stéphanie Faure, Faouzi Saliba, Didier Samuel, Claire Vanlemmens, Christophe Corpechot, Olivier Chazouillères, and Jérôme Dumortier
Subjects: Hepatology
Published: 2022
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25. Liver transplantation for hepatocellular carcinoma with extended criteria: performance and applicability of the AFP score after official adoption by the French Organ Sharing Organization ABM: 5-year outcomes

Author: Christophe Duvoux, Mathilde Petiet Dumont, Georges-Philippe Pageaux, Ephrem Salamé, Jérôme Dumortier, Sylvie Radenne, Sébastien Dharancy, Pauline Houssel-Debry, Philippe Bachellier, Laurence Chiche, Francois Durand, Fabrice Muscari, Jean Gugenheim, Filomena Conti, Jean Hardwigsen, Christian Jacquelinet, Corinne Antoine, Norbert Ngongang, Vincent Leroy, Thomas Decaens, Daniel Cherqui, and Nadia Oubaya
Subjects: Hepatology
Published: 2022
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26. Prevention of biliary fistula after partial hepatectomy by transcystic biliary drainage: randomized clinical trial

Author: Patrick Pessaux, J.-M. Regimbeau, J.R. Delpero, Jean Hardwigsen, Jacques Belghiti, Bertrand Suc, C. Maulat, Eric Vibert, E Tournay, Fabrice Muscari, E Buc, C Arnaud, Emmanuel Boleslawski, Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Programme hospitalier de recherche clinique (PHRC)
Subjects: Male, medicine.medical_specialty, Biliary Fistula, medicine.medical_treatment, 030230 surgery, Partial hepatectomy, law.invention, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Randomized controlled trial, Risk Factors, law, Clinical endpoint, Hepatectomy, Humans, Medicine, Biliary drainage, Intention-to-treat analysis, business.industry, Surrogate endpoint, Biliary fistula, Middle Aged, medicine.disease, 3. Good health, Surgery, 030220 oncology & carcinogenesis, Drainage, Female, Bile Ducts, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Biliary fistula is one of the most common complications after hepatectomy. This study evaluated the effect of transcystic biliary drainage during hepatectomy on the occurrence of postoperative biliary fistula.This multicentre RCT was carried out from 2009 to 2016 in nine centres. Patients were randomized to transcystic biliary drainage or no transcystic drainage (control). Patients underwent hepatectomy (more than 2 segments) of non-cirrhotic livers. The primary endpoint was the occurrence of biliary fistula after surgery. Secondary endpoints were morbidity, postoperative mortality, duration of hospital stay, reoperation, readmission to hospital, and complications caused by catheters. Intention-to-treat and per-protocol analyses were performed.A total of 310 patients were randomized. In intention-to-treat analysis, there were 158 patients in the transcystic group and 149 in the control group. Seven patients were removed from the per-protocol analysis owing to protocol deviations. The biliary fistula rate was 5·9 per cent in intention-to-treat and 6·0 per cent in per-protocol analyses. The rate was similar in the transcystic and control groups (5·7 versus 6·0 per cent; P = 1·000). There were no differences in terms of morbidity (49·4 versus 46·3 per cent; P = 0·731), mortality (2·5 versus 4·7 per cent; P = 0·367) and reoperations (4·4 versus 10·1 per cent; P = 1·000). Median duration of hospital stay was longer in the transcystic group (11 versus 10 days; P = 0·042). The biliary fistula risk was associated with the width and length of the hepatic cut surface.This randomized trial did not demonstrate superiority of transcystic drainage during hepatectomy in preventing biliary fistula. The use of transcystic drainage during hepatectomy to prevent postoperative biliary fistula is not recommended. Registration number: NCT01469442 ( http://www.clinicaltrials.gov).La fístula biliar es una de las complicaciones más comunes después de la hepatectomía. Este estudio evalúa el efecto del drenaje biliar transcístico durante la hepatectomía en la aparición de una fístula biliar postoperatoria. MÉTODOS: Este ensayo prospectivo aleatorizado y multicéntrico (Clinical Trial NCT01469442) con dos grupos de estudio (grupo transcístico versus grupo control) se llevó a cabo de 2009 a 2016 en 9 centros. Los pacientes fueron sometidos a una hepatectomía (≥ 2 segmentos) en hígados no cirróticos. El resultado principal fue la aparición de una fístula biliar después de la cirugía. Los resultados secundarios fueron la morbilidad, la mortalidad postoperatoria, la duración de la estancia hospitalaria, la reintervención, la necesidad de reingreso y las complicaciones causadas por los catéteres. Se realizaron análisis por intención de tratamiento y por protocolo.Un total de 310 pacientes fueron randomizados. Por intención de tratamiento, 158 pacientes fueron aleatorizados al grupo transcístico y 149 al grupo control. Siete pacientes fueron excluidos del análisis por protocolo por desviaciones del protocolo. La tasa de fístula biliar fue del 5,9% en el análisis por intención de tratamiento y del 6,0% en el análisis por protocolo. Esta tasa fue similar para el grupo transcístico y para el grupo control: 5,7% versus 6,0% (P = 1). No hubo diferencias en términos de morbilidad (49,4% versus 46,9%, P = 0,731), mortalidad (2,5% versus 4,7%, P = 0,367) y reintervenciones (4,4% versus 10,1%, P = 1). La mediana de la duración de la estancia hospitalaria fue mayor para el grupo transcístico (11 versus 10 días, P = 0,042). El riesgo de fístula biliar se correlacionó con el grosor y la longitud de la transección hepática. CONCLUSIÓN: Este ensayo aleatorizado no demuestra la superioridad del drenaje transcístico durante la hepatectomía para prevenir la fístula biliar. No se recomienda el uso de drenaje transcístico durante la hepatectomía para prevenir la fístula biliar postoperatoria.
Published: 2020
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27. The technique and outcomes of central hepatectomy by the Glissonian suprahilar approach

Author: Sophie Chopinet, Emilie Gregoire, Jules A. Giuly, Jean-Robert Delpero, Yves Patrice Le Treut, Régis Fara, and Jean Hardwigsen
Subjects: Adult, Male, Central Hepatectomy, medicine.medical_specialty, Blood transfusion, medicine.medical_treatment, Iatrogenic Disease, Operative Time, Blood Component Transfusion, 030230 surgery, Metastasis, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, medicine, Hepatectomy, Humans, Intrahepatic Cholangiocarcinoma, Aged, Retrospective Studies, Bile duct, business.industry, Liver Neoplasms, Retrospective cohort study, General Medicine, Perioperative, Length of Stay, Middle Aged, medicine.disease, Surgery, Survival Rate, medicine.anatomical_structure, Oncology, Hepatocellular carcinoma, Female, 030211 gastroenterology & hepatology, business
Abstract: Central hepatectomy (CH) is technically challenging and seldom-used to treat centrally located tumors. However, CH is a parenchyma-sparing resection that may decrease the risk of postoperative liver failure. This retrospective study presents our technique of CH and assesses the outcomes.All CH performed in our department over two decades (1997-2017) were identified. Indications and short-term outcomes were compared between the two decades. Long-term outcomes were assessed.Sixty-four patients underwent CH using a suprahilar approach for hepatocellular carcinoma (HCC: n = 30), metastasis (n = 23), intrahepatic cholangiocarcinoma (IHCCA: n = 9) or other diseases (n = 2). CH represented 6% of 1004 major hepatectomies, (7.4% (n = 35) before 2007 vs 5.4% (n = 29) after 2007). The mean operating time was 219 ± 56 min. A perioperative blood transfusion was required in 14 patients (22%). Intraoperative bile duct injuries occurred in 5 patients (8%), and they were repaired. One patient died postoperatively (1,5%). Ten patients (16%) experienced a major complication. Nine patients (14%) suffered from bile leakage, of which 6 healed spontaneously. Only one patient had low grade liver failure. The R0-resection rate was 69%. After 2007, there were no bile duct injuries (0/29 vs 5/35, p 0.05), and the average hospital stay was shorter but not significantly (11 vs 14 days). Actuarial 5-year survival was 56% for HCC patients and 34% for those with colorectal metastasis CONCLUSIONS: CH is associated with significant biliary morbidity and may increase positive surgical margins. Nevertheless, it should be recommended in selected patients to avoid the risk of postoperative liver failure.
Published: 2019
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28. An ordinal model to predict the risk of symptomatic liver failure in patients with cirrhosis undergoing hepatectomy

Author: Jean-Marc Regimbeau, Mathieu Prodeau, Jean-Yves Mabrut, Eric Vibert, François-René Pruvot, Guillaume Lassailly, Olivier Farges, Alain Duhamel, Emmanuel Boleslawski, Jean Hardwigsen, René Adam, Olivier Soubrane, and Elodie Drumez
Subjects: Blood Platelets, Liver Cirrhosis, Male, Risk, 0301 basic medicine, medicine.medical_specialty, Carcinoma, Hepatocellular, Cirrhosis, medicine.medical_treatment, Blood Loss, Surgical, Gastroenterology, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Laparotomy, Internal medicine, medicine, Clinical endpoint, Hepatectomy, Humans, Prospective Studies, Stage (cooking), Laparoscopy, Aged, Univariate analysis, Models, Statistical, Hepatology, medicine.diagnostic_test, business.industry, Liver Neoplasms, Middle Aged, Prognosis, medicine.disease, Blood Cell Count, Treatment Outcome, 030104 developmental biology, Hepatocellular carcinoma, Female, 030211 gastroenterology & hepatology, business, Liver Failure, Forecasting
Abstract: Background & Aims Selection criteria for hepatectomy in patients with cirrhosis are controversial. In this study we aimed to build prognostic models of symptomatic post-hepatectomy liver failure (PHLF) in patients with cirrhosis. Methods This was a cohort study of patients with histologically proven cirrhosis undergoing hepatectomy in 6 French tertiary care hepato-biliary-pancreatic centres. The primary endpoint was symptomatic (grade B or C) PHLF, according to the International Study Group of Liver Surgery's definition. Twenty-six preoperative and 5 intraoperative variables were considered. An ordered ordinal logistic regression model with proportional odds ratio was used with 3 classes: O/A (No PHLF or grade A PHLF), B (grade B PHLF) and C (grade C PHLF). Results Of the 343 patients included, the main indication was hepatocellular carcinoma (88%). Laparoscopic liver resection was performed in 112 patients. Three-month mortality was 5.25%. The observed grades of PHLF were: 0/A: 61%, B: 28%, C: 11%. Based on the results of univariate analyses, 3 preoperative variables (platelet count, liver remnant volume ratio and intent-to-treat laparoscopy) were retained in a preoperative model and 2 intraoperative variables (per protocol laparoscopy and intraoperative blood loss) were added to the latter in a postoperative model. The preoperative model estimated the probabilities of PHLF grades with acceptable discrimination (area under the receiver-operating characteristic curve [AUC] 0.73, B/C vs. 0/A; AUC 0.75, C vs. 0/A/B) and the performance of the postoperative model was even better (AUC 0.77, B/C vs. 0/A; AUC 0.81, C vs. 0/A/B; p Conclusions By accurately predicting the risk of symptomatic PHLF in patients with cirrhosis, the preoperative model should be useful at the selection stage. Prediction can be adjusted at the end of surgery by also considering blood loss and conversion to laparotomy in a postoperative model, which might influence postoperative management. Lay summary In patients with liver cirrhosis, the risk of a hepatectomy is difficult to appreciate. We propose a statistical tool to estimate this risk, preoperatively and immediately after surgery, using readily available parameters and on online calculator. This model could help to improve the selection of patients with the best risk-benefit profiles for hepatectomy.
Published: 2019
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29. Predictive factors of tumor recurrence after liver transplantation for hepatocellular carcinoma: analysis of a multicenter prospective study including 371 patients

Author: Thomas Decaens, René Adam, Sébastien Dharancy, Laurent Sulpice, Didier Samuel, Emmanuel Boleslawski, Marianne Latournerie, Georges-Philippe Pageaux, Olivier Scatton, Sylvie Radenne, Eric Savier, Claire Francoz, Claire Vanlemmens, Pierre-Henri Bernard, Jean Hardwigsen, Jean Gugenheim, Christophe Duvoux, and Nadia Oubaya
Subjects: Hepatology
Published: 2022
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30. Laparoscopic versus open liver resection for intrahepatic cholangiocarcinoma: Report of an international multicenter cohort study with propensity score matching

Author: Raffaele Brustia, Alexis Laurent, Claire Goumard, Serena Langella, Daniel Cherqui, Takayuki Kawai, Olivier Soubrane, Francois Cauchy, Olivier Farges, Benjamin Menahem, Christian Hobeika, Rami Rhaiem, Daniele Sommacale, Shinya Okumura, Stefan Hofmeyr, Alessandro Ferrero, François-René Pruvot, Jean-Marc Regimbeau, David Fuks, Eric Vibert, Olivier Scatton, Julio Abba, René Adam, Mustapha Adham, Marc-Antoine Allard, Ahmet Ayav, Daniel Azoulay, Philippe Bachellier, Pierre Balladur, Louise Barbier, Julien Barbieux, Emmanuel Boleslawski, Karim Boudjema, M. Bougard, Emmanuel Buc, Petru Bucur, Antoine Carmelo, Denis Chatelain, Jean Chauvat, Zineb Cherkaoui, Laurence Chiche, Mircea Chirica, Oriana Ciacio, Tatiana Codjia, Fabio Colli, Luciano De Carlis, Jean-Robert Delpero, Nicolas Demartines, Olivier Detry, Marcelo Dias Sanches, Momar Diouf, Alexandre Doussot, Christian Ducerf, Mehdi El Amrani, Jacques Ewald, Jean-Marc Fabre, Hervé Fagot, Simone Famularo, Léo Ferre, Francesco Fleres, Gilton Marques Fonseca, Brice Gayet, Alessandro Giacomoni, Jean-Francois Gigot, E. Girard, Nicolas Golse, Emilie Gregoire, Jean Hardwigsen, Paulo Herman, Thevi Hor, François Jehaes, Ali-Reza Kianmanesh, Shohei Komatsu, Sophie Laroche, Christophe Laurent, Yves-Patrice Le Treut, K. Lecolle, Philippe Leourier, Emilie Lermite, Mikael Lesurtel, Christian Letoublon, Paul Leyman, Jean Lubrano, Jean-Yves Mabrut, Georges Mantion, Ugo Marchese, Riccardo Memeo, Guillaume Millet, Kayvan Mohkam, André Mulliri, Fabrice Muscari, Francis Navarro, Francisco Nolasco, Takeo Nomi, Jean Nunoz, Gennaro Nuzzo, Nassima Oudafal, Gerard Pascal, Guillaume Passot, D. Patrice, Damiano Patrono, François Paye, Fabiano Perdigao, Patrick Pessaux, Niccolo Petrucciani, Gabriella Pittau, C. Ratajczak, Artigas Raventos, Lionel Rebibo, Vivian Resende, Michel Rivoire, Renato Romagnoli, Didier Roulin, Antonio Sa-Cunha, Ephrem Salame, Astrid Schielke, Lilian Schwarz, Michel Scotte, François-Regis Souche, Bertrand Suc, Michele Tedeschi, Alexandre Thobie, Boris Trechot, Stéphanie Truant, Olivier Turini, Shinji Uemoto, Xavier Unterteiner, Charles Vanbrugghe, and Jean Zemour
Subjects: medicine.medical_specialty, Cholangiocarcinoma, Cohort Studies, Postoperative Complications, Open Resection, medicine, Hepatectomy, Humans, Propensity Score, Intrahepatic Cholangiocarcinoma, Retrospective Studies, business.industry, Proportional hazards model, Hazard ratio, Perioperative, Confidence interval, Surgery, Bile Ducts, Intrahepatic, Treatment Outcome, Bile Duct Neoplasms, Liver, Propensity score matching, Laparoscopy, business, Cohort study
Abstract: Intrahepatic cholangiocarcinoma is a rare disease with a poor prognosis. In patients where surgical resection is possible, outcome is influenced by perioperative morbidity and lymph node status. Laparoscopic liver resection is associated with improved clinical and oncological outcomes in primary and metastatic liver cancer compared with open liver resection, but evidence on intrahepatic cholangiocarcinoma is still insufficient. The primary aim of this study was to compare overall survival for a large series of patients treated for intrahepatic cholangiocarcinoma by open or laparoscopic approach. Secondary objectives were to compare disease-free survival, predictors of death, and recurrence.Patients treated with laparoscopic or open liver resection for intrahepatic cholangiocarcinoma from 2000 to 2018 from 3 large international databases were analyzed retrospectively. Each patient in the laparoscopic resection group (case) was matched with 1 open resection control (1:1 ratio), through a propensity score calculated on clinically relevant preoperative covariates. Overall and disease-free survival were compared between the matched groups. Predictors of mortality and recurrence were analyzed with Cox regression, and the Textbook Outcomes were described.During the study period, 855 patients met the inclusion criteria (open liver resection = 709, 82.9%; laparoscopic liver resection = 146, 17.1%). Two groups of 89 patients each were analyzed after propensity score matching, with no significant difference regarding pre- and postoperative variables. Overall survival at 1, 3, and 5 years was 92%, 75%, and 63% in the laparoscopic liver resection group versus 92%, 58%, and 49% in the open liver resection group (P = .0043). Adjusted Cox regression revealed severe postoperative complications (hazard ratio: 10.5, 95% confidence interval [1.01-109] P = .049) and steatosis (hazard ratio: 13.8, 95% confidence interval [1.23-154] P = .033) as predictors of death, and transfusion (hazard ratio: 19.2, 95% confidence interval [4.04-91.4] P.001) and severe postoperative complications (hazard ratio: 4.07, 95% confidence interval [1.15-14.4] P = .030) as predictors of recurrence.The survival advantage of laparoscopic liver resection over open liver resection for intrahepatic cholangiocarcinoma is equivocal, given historical bias and missing data.
Published: 2021

31. Oncological relevance of major hepatectomy with inferior vena cava resection for intrahepatic cholangiocarcinoma

Author: Emilie Gregoire, Yves Patrice Le Treut, Jean-Robert Delpero, Olivier Turrini, Anaïs Palen, Christian Hobeika, Jacques Ewald, Jonathan Garnier, Jean Hardwigsen, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de Chirurgie Oncologique [Institut Paoli-Calmettes, Marseille], Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)
Subjects: medicine.medical_specialty, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Vena Cava, Inferior, 030230 surgery, Inferior vena cava, Resection, Cholangiocarcinoma, 03 medical and health sciences, 0302 clinical medicine, Text mining, medicine, Hepatectomy, Humans, education, Severe complication, Intrahepatic Cholangiocarcinoma, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, education.field_of_study, Hepatology, business.industry, Gastroenterology, Surgery, Bile Ducts, Intrahepatic, medicine.vein, Bile Duct Neoplasms, 030220 oncology & carcinogenesis, Propensity score matching, cardiovascular system, business, Major hepatectomy
Abstract: Background This study aimed to investigate the short- and long-terms outcomes of patients undergoing major hepatectomy (MH) with inferior vena cava (IVC) resection for intrahepatic cholangiocarcinoma (ICC). Methods Data from all patients who underwent MH for ICC with or without IVC resection between 2010 and 2018 were analysed retrospectively. Postoperative outcomes, overall survival (OS), and recurrence-free survival (RFS) were compared in the whole population. A propensity score matching (PSM) analysis and an inverse probability weighting analysis (IPW) were performed to assess the influence of IVC resection on short- and long-terms outcomes. Results Among the 78 patients who underwent MH, 20 had IVC resection (IVC patients). Overall, the mortality and severe complication rate were 8% and 20%, respectively. IVC patients required more extended hepatectomies (p = 0.001) and had increased rates of transfusions (p = 0.001), however they did not experience increased postoperative morbidity, even after PSM. The 1-, 3- and 5-years OS and DFS were 78%, 45%, and 32% and 48%, 20%, and 16%, respectively. IVC was not associated with decreased OS (p = 0.52) and/or RFS (p = 0.85), even after IPW. Conclusion MH with IVC resection for ICC seems to provide acceptable short- and long-term results in a selected population of patients.
Published: 2020
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32. Immediate preoperative renal artery embolization in the resection of complex renal tumors (UroCCR-48 Reinbol study)

Author: F. Michel, Vincent Vidal, Eric Lechevallier, Pierre Bigot, Gilles Karsenty, Jean Hardwigsen, C. Alegorides, Marc Andre, J-C. Bernhard, Romain Boissier, A. Riberi, Bastien Gondran-Tellier, and Michael Baboudjian
Subjects: Nephrology, Male, medicine.medical_specialty, Time Factors, Urology, medicine.medical_treatment, 030232 urology & nephrology, Median artery, 030204 cardiovascular system & hematology, Nephrectomy, 03 medical and health sciences, 0302 clinical medicine, Renal Artery, Renal cell carcinoma, Internal medicine, Preoperative Care, medicine, Humans, Local anesthesia, Embolization, Thrombus, Carcinoma, Renal Cell, Aged, Neoplasm Staging, Retrospective Studies, business.industry, Perioperative, Middle Aged, medicine.disease, Embolization, Therapeutic, Kidney Neoplasms, Surgery, medicine.anatomical_structure, Treatment Outcome, Feasibility Studies, Female, business
Abstract: We evaluated the feasibility and outcomes of immediate preoperative renal artery embolization (IPRAE) before complex nephrectomy for locally advanced RCC ± inferior vena cava thrombus (IVCT). A comparative retrospective (2007–2017) multicenter study which included 145 patients with locally advanced RCC ± IVCT: 99 radical nephrectomies vs. 46 radical nephrectomies with IPRAE identified in the prospective UroCCR national database (CNIL DR 2013–206; NCT03293563). IPRAE was performed under local anesthesia the day of nephrectomy (
Published: 2020

33. Long-term abdominal wall benefits of the laparoscopic approach in liver left lateral sectionectomy: a multicenter comparative study

Author: Benjamin, Darnis, Kayvan, Mohkam, Nicolas, Golse, Eric, Vibert, Daniel, Cherqui, François, Cauchy, Olivier, Soubrane, Jean-Marc, Regimbeau, Jeanne, Dembinski, Jean, Hardwigsen, Philippe, Bachelier, Christophe, Laurent, Stéphanie, Truant, Guillaume, Millet, Mickaël, Lesurtel, Emmanuel, Boleslawksi, and Jean-Yves, Mabrut
Subjects: Liver, Abdominal Wall, Hepatectomy, Humans, Incisional Hernia, Laparoscopy, Length of Stay, Retrospective Studies
Abstract: Laparoscopy is nowadays considered as the standard approach for hepatic left lateral sectionectomy (LLS), but its value in the prevention of incisional hernia (IH) has not been demonstrated.Between 2012 and 2017, patients undergoing laparoscopic (LLLS) or open LLS (OLLS) in 8 centers were compared. Patients undergoing a simultaneous major abdominal procedure were excluded. The incidence of IH was assessed clinically and morphologically on computed tomography (CT) using inverse probability of treatment weighting (IPTW) and multivariable regression analysis.After IPTW, 84 LLLS were compared to 48 OLLS. Compared to OLLS, LLLS patients had reduced blood loss (100 [IQR: 50-200] ml vs. 150 [IQR: 50-415] ml, p = 0.023) and shorter median hospital stay (5 [IQR: 4-7] days vs. 7 [6-9] days, p 0.001), but experienced similar rate of postoperative complications (mean comprehensive complication index: 12 ± 19 after OLLS versus 13 ± 20 after LLLS, p = 0.968). Long-term radiological screening was performed with a median follow-up of 27.4 (12.1-44.9) months. There was no difference between the two groups in terms of clinically relevant IH (10.7% [n = 9] after LLLS, 8.3% [n = 4] after OLLS, p = 0.768). The rate of IH detected on computed tomography was lower after LLLS than after OLLS (11.9% [n = 10] versus 29.2% [n = 14], p = 0.013). On multivariable analysis, the laparoscopic approach was the only independent factor influencing the risk of morphological IH (OR = 0.290 [95% CI: 0.094-0.891], p = 0.031). The 2 preferential sites for specimen extraction after LLLS were Pfannenstiel and midline incisions, with rates of IH across the extraction site of 2.3% [n = 1/44] and 23.8% [n = 5/21], respectively (p = 0.011).The laparoscopic approach for LLS decreases the risk of long-term IH as evidenced on morphological examinations, with limited clinical impact. Pfannenstiel's incision should be preferred to midline incision for specimen extraction after LLLS.
Published: 2020

34. Partial splenectomy in children undergoing liver transplantation or venous shunt for severe hypersplenism: A case control comparative study

Author: Olivier, Boillot, Sophie, Chopinet, Emilie, Gregoire, Laurent, Milot, Philippe, Petit, Barbara, Rohmer, Bertrand, Roquelaure, Anne, Dariel, Nicoleta, Panait, Jean, Hardwigsen, and Jérôme, Dumortier
Subjects: Liver Cirrhosis, Hepatology, Splenomegaly, Splenectomy, Gastroenterology, Humans, Child, Hypersplenism, Liver Transplantation, Retrospective Studies
Abstract: Hypersplenism is a consequence of portal hypertension and splenomegaly secondary to cirrhosis or portal cavernoma in children. In order to avoid persistent hypersplenism and splenomegaly after liver transplantation (LT) or venous shunt (VS), partial splenectomy (PS) may represent a relevant therapeutic option. The aim of this retrospective study was to evaluate the results of PS performed in children presenting hypersplenism.The following end-points were evaluated: (1) reversion of hypersplenism and its durability over time, (2) postoperative outcome, (3) courses of spleen size and volume and (4) comparison to a control group in which PS was not performed.Between 1996 and 2020, 16 children underwent PS associated with LT (8 cases) for cirrhosis or VS (8 cases) for portal cavernoma. From Day 0 to 1 month, mean platelet and white blood cell counts (WBC) dramatically improved from 48 ± 19 at day 0 to 176 ± 70 × 10PS appears to be effective for treatment of hypersplenism and splenomegaly in combination with LT or VS without compromising outcome.
Published: 2022
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35. Postoperative Bleeding After Laparoscopic Pancreaticoduodenectomy: the Achilles’ Heel?

Author: Yves-Patrice Le Treut, Sophie Chopinet, Christian Lamer, Jean Hardwigsen, Brice Gayet, Emilie Gregoire, Julien Massol, Mathieu Rinaudo, Ajay Belgaumkar, and David Fuks
Subjects: medicine.medical_specialty, education.field_of_study, business.industry, General surgery, medicine.medical_treatment, Population, Perioperative, Vascular surgery, medicine.disease, Pancreaticoduodenectomy, Cardiac surgery, Surgery, 03 medical and health sciences, 0302 clinical medicine, Cardiothoracic surgery, Pancreatic fistula, hemic and lymphatic diseases, 030220 oncology & carcinogenesis, medicine, 030211 gastroenterology & hepatology, business, education, Abdominal surgery
Abstract: Laparoscopic pancreaticoduodenectomy (LPD) is technically demanding, and its impact on postoperative outcomes remains controversial. To compare short-term outcomes between laparoscopic versus open pancreaticoduodenectomy (OPD) in order to assess the safety of LPD. From 2002 to 2014, all consecutive patients undergoing LPD or OPD at two tertiary centers were retrospectively analyzed. Patients were matched for demographics, comorbidities, pathological diagnosis, and pancreatic texture. Results for the two groups were compared for postoperative outcomes. Sixty-five LPD were performed and compared to 290 OPD. In the whole population, postoperative pancreatic fistula (PF) was higher in the LPD group, but the proportion of ampullary adenocarcinoma (25 vs. 10%, p = 0.004) and soft pancreatic parenchyma (52 vs. 38%, p = 0.001) were higher in the LDP group. After matching (n = 65), LPD was associated with longer operative time (429 vs. 328 min, p
Published: 2017
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36. Intensive Early Rehabilitation in the Intensive Care Unit for Liver Transplant Recipients: A Randomized Controlled Trial

Author: Laurence Bienvenu, Laurent Bensoussan, Emilie Gregoire, Jacques Albanèse, Pierre Maffei, Sandrine Wiramus, Mohamed Fathallah, Y. Patrice Le Treut, Sophie Morange, Eric Haddad, Jean Hardwigsen, and Jean-Michel Viton
Subjects: Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Psychological intervention, Physical Therapy, Sports Therapy and Rehabilitation, Liver transplantation, law.invention, Treatment and control groups, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Humans, Medicine, Postoperative Period, Prospective Studies, Medical prescription, Adverse effect, Physical Therapy Modalities, Rehabilitation, business.industry, 030208 emergency & critical care medicine, Length of Stay, Middle Aged, Intensive care unit, Liver Transplantation, Intensive Care Units, 030228 respiratory system, Physical therapy, Female, business
Abstract: Objective To validate the feasibility and tolerance of an intensive rehabilitation protocol initiated during the postoperative period in an intensive care unit (ICU) in liver transplant recipients. Design Prospective randomized study. Setting ICU. Participants Liver transplant recipients over a period of 1 year (N=40). Interventions The "usual treatment group" (n=20), which benefited from the usual treatment applied in the ICU (based on physician prescription for the physiotherapist, with one session a day), and the experimental group (n=20), which followed a protocol of early and intensive rehabilitation (based on a written protocol validated by physicians and an evaluation by physiotherapist, with 2 sessions a day), were compared. Main Outcome Measures Our primary aims were tolerance, assessed from the number of adverse events during rehabilitation sessions, and feasibility, assessed from the number of sessions discontinued. Results The results revealed a small percentage of adverse events (1.5% in the usual treatment group vs 1.06% in the experimental group) that were considered to be of low intensity. Patients in the experimental group sat on the edge of their beds sooner (2.6 vs 9.7d; P =.048) and their intestinal transit resumed earlier (5.6 vs 3.7d; P =.015) than patients in the usual treatment group. There was no significant difference between the 2 arms regarding length of stay (LOS), despite a decrease in duration in the experimental group. Conclusions The introduction of an intensive early rehabilitation program for liver transplant recipients was well tolerated and feasible in the ICU. We noted that the different activities proposed were introduced sooner in the experimental group. Moreover, there is a tendency to decreased LOS in the ICU for the experimental group. These results now need to be confirmed by studies on a larger scale.
Published: 2017
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37. Liver transplantation for hepatocellular carcinoma after down staging with sorafenib: a monocentric case-matched series

Author: Anaïs Palen, Emilie Gregoire, Patrick Borentain, Sophie Chopinet, René Gerolami, Jean Hardwigsen, Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'hépato-gastro-entérologie [Hôpital de la Timone -APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Service de Chirurgie, Assistance Publique - Hôpitaux de Marseille (APHM)-Hospices Civiles de Marseille-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), and Assistance Publique - Hôpitaux de Marseille (APHM)-Hospices Civiles de Marseille-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION )
Subjects: Male, Sorafenib, Oncology, medicine.medical_specialty, Carcinoma, Hepatocellular, medicine.medical_treatment, Down staging, MEDLINE, Eligibility Determination, Antineoplastic Agents, Liver transplantation, Glypicans, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Preoperative Care, Biomarkers, Tumor, medicine, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, ComputingMilieux_MISCELLANEOUS, Neoplasm Staging, Series (stratigraphy), [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, business.industry, Liver Neoplasms, Gastroenterology, Middle Aged, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Liver Transplantation, Tumor Burden, 3. Good health, Outcome and Process Assessment, Health Care, Case-Control Studies, Hepatocellular carcinoma, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, alpha-Fetoproteins, business, medicine.drug
Abstract: International audience
Published: 2020
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38. Risk factors of de novo malignancies after liver transplantation: a French national study on 11004 adult patients

Author: Christophe Duvoux, Mario Altieri, Nassim Kamar, Jean Gugenheim, Sébastien Dharancy, Filomena Conti, Armand Abergel, Olivier Sérée, Georges-Philippe Pageaux, Ephrem Salamé, Jean Hardwigsen, Karim Boudjema, Pascal Lebray, Philippe Segol, Camille Besch, Vincent Leroy, Didier Samuel, Guy Launoy, Claire Vanlemmens, Sylvie Radenne, Maryline Debette-Gratien, Olivier Chazouillères, Xavier Blaizot, Martine Neau-Cransac, Claire Francoz, Marianne Latournerie, Jérôme Dumortier, Audrey Coilly, Pauline Houssel-Debry, François Durand, Olivier Boillot, Faouzi Saliba, Thierry Lobbedez, CCSD, Accord Elsevier, Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, 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, Centre Hépato-Biliaire [Hôpital Paul Brousse] (CHB), Hôpital Paul Brousse-Assistance Publique - Hôpitaux de Paris, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Centre de Référence des Maladies Rares - Maladies Inflammatoires des Voies Biliaires et Service d’Hépatologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges], CHU Limoges, Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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 (UPCité), Hôpital Henri Mondor, Ecole Polytechnice Universitaire de Nice (EPU Nice -Polytech'Nice-Sophia), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital de la Timone [CHU - APHM] (TIMONE), Service de Néphrologie - Immunologie Clinique [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-PRES Université de Toulouse, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hospices Civils de Lyon (HCL), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), and CHU Strasbourg
Subjects: Oncology, Adult, Male, medicine.medical_specialty, MESH: Liver Transplantation, Liver tumor, medicine.medical_treatment, Liver transplantation, Malignancy, Primary sclerosing cholangitis, 03 medical and health sciences, Liver disease, 0302 clinical medicine, MESH: Liver Neoplasms, MESH: Risk Factors, Risk Factors, Internal medicine, medicine, Humans, MESH: Incidence, Lung cancer, Retrospective Studies, MESH: Humans, Hepatology, business.industry, Incidence, Liver Neoplasms, Gastroenterology, Retrospective cohort study, MESH: Adult, MESH: Retrospective Studies, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Competing risk, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: Male, Liver Transplantation, 030220 oncology & carcinogenesis, Population study, 030211 gastroenterology & hepatology, business, Liver transplantationde novomalignancies
Abstract: International audience; Background: After liver transplantation (LT),de novo malignancies are one of the leading causes of late mortality. The aim of the present retrospective study was to identify the risk factors of de novo malignancies in a large cohort of LT recipients in France, using Fine and Gray competing risks regression analysis.Methods: The study population consisted in 11004 adults transplanted between 2000 and 2013, who had no history of pre-transplant malignancy, except primary liver tumor. A Cox model adapted to the identification of prognostic factors (competitive risks) was used.Results: From the entire cohort, one (or more)de novo malignancy was reported in 1480 L T recipients (13.45%). The probability to develop a de novo malignancy after LT was 2.07% at 1 year, 13.30% at 5 years, and 28.01% at 10 years. Of the known reported malignancies, the most common malignancies were hematological malignancy (22.36%), non-melanoma skin cancer (19.53%) and lung cancer (12.36%). According to Fine and Gray competing risks regression multivariate analysis, were significant risk factors for post-LT de novo malignancy: recipient age (Subdistribution Hazard Ratio (SHR) = 1.03 95%CI 1.03-1.04), male gender (SHR = 1.45 95%CI 1.27-1.67), non-living donor (SHR = 1.67 95%CI 1.14-2.38), a first LT (SHR = 1.35 95%CI 1.09-1.69) and the type of initial liver disease (alcohol-related liver disease (SHR = 1.63 95%CI 1.22-2.17), primary sclerosing cholangitis (SHR = 1.98 95%CI 1.34-2.91), and primary liver tumor (SHR = 1.88 95%CI 1.41-2.54)). Initial immunosuppressive regimen had no significant impact.Conclusion: The present study confirms that LT recipient characteristics are associated with the risk ofde novo malignancy and this underlines the need for personalized screening in order to improve survival.
Published: 2020
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39. Influence of 4 preservation solutions on ICU stay, graft and patient survival following liver transplantation

Author: L. Barbier, Emmanuel Boleslawski, J.-M. Siksik, E. Savier, A. Mulliri, K. Boudjema, Gabriella Pittau, René Adam, O. Boilot, Jean-Yves Mabrut, A. Sepulveda, Astrid Herrero, G.-P. Pageaux, J.-L. Golmard, Christophe Laurent, Philippe Bachellier, F. Dondero, François Faitot, Emilie Gregoire, C. Salloum, E. Salame, Laurence Chiche, Jean Hardwigsen, Christian Letoublon, M. Rayar, R. Brustia, Philippe Compagnon, F. Jeune, Y.P. Le Treut, Jean Gugenheim, Samir Jaber, Bertrand Suc, Olivier Scatton, A. Mallet, J. Abba, P. Houssel-Debry, C. Maulat, E. Buc, C B Lim, F. Perdigao, Safi Dokmak, François-René Pruvot, M. Chirica, Oriana Ciacio, B. Trechot, G. Rousseau, S. Branchereau, C. Chardot, Pietro Addeo, K. Mohkam, Jean-Christophe Vaillant, Francis Navarro, A. Merdignac, T. Dao, Olivier Soubrane, Daniel Cherqui, B. Heyd, MORNET, Dominique, Service de Chirurgie Digestive, Hépato-Bilio-pancréatique et Transplantation Hépatique [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département de Biostatistiques [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Paul Brousse, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de Hautepierre [Strasbourg], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi], Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Hôpital de la Timone [CHU - APHM] (TIMONE), Service de pédiatrie médicale et médecine de l'adolescent [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hôpital Henri Mondor, Centre Hospitalier Universitaire [Grenoble] (CHU), Département de chirurgie digestive et de l'urgence, CHU Grenoble-Hôpital Michallon, Hôpital Claude Huriez [Lille], CHU Lille, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Bicêtre, CHU Necker - Enfants Malades [AP-HP], Agence de la Biomédecine, Service de chirurgie digestive et hépato-bilio-pancréatique [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], CHU Pitié Salpêtrière, CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Unité de Transplantation, CHU Cochin [AP-HP], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, CHU Saint-Eloi-Université de Montpellier (UM), Department of Hepatobiliary Surgery, Hôpital Conception, Hôpital Claude Huriez, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Hôpital de Rangueil, CHU Toulouse [Toulouse], UPMC Université Paris 06, 75012 Paris, France., Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Mère Enfant Edouard Herriot, 69677 Bron, France. 2, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Université Clermont Auvergne, and Hôpital Bicêtre, AP-HP, 94275 Le Kremlin-Bicêtre, France.
Subjects: Male, Adenosine, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Liver transplantation, Disaccharides, Electrolytes, 0302 clinical medicine, Glutamates, Preservation solutions, Insulin, Mannitol, Registries, ComputingMilieux_MISCELLANEOUS, Univariate analysis, Graft Survival, General Medicine, Prognosis, Glutathione, Multicenter study, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, Human, medicine.medical_specialty, Critical Care, Allopurinol, Organ Preservation Solutions, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, 03 medical and health sciences, Raffinose, Intensive care, medicine, Humans, Icu stay, Histidine, Retrospective Studies, business.industry, Significant difference, Retrospective cohort study, Patient survival, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Length of Stay, Survival Analysis, Preservation solution, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Surgery, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Follow-Up Studies
Abstract: International audience; Objective - The goal of this study was to evaluate the prognostic role of four preservation solutions in liver transplantation (LT). Patients and methods - This is a retrospective study originating from 22 French centers performing LT, registered in the prospective databank of the Cristal Biomedicine Agency between 2008 and 2013. The preservation solutions used were Celsior (CS), Institut Georges Lopez (IGL)-1, Solution de Conservation des Organes et des Tissus (SCOT) 15 and University of Wisconsin (UW) solutions. Exclusion criteria were preservation with unknown or inhomogeneous solutions, or Histidine-tryptophan-ketoglutarate (HTK) solution (representing only 3% of LT). Patient survival was the main endpoint. Secondary endpoints were graft survival and duration of stay in intensive care. Results - Of 6347 LT performed, 4928 were included in this study, for which the distribution of preservation solution was CS (30%), IGL-1 (44%), SCOT 15 (10%) and UW (16%). Patient survival was 86%, 80% and 74% at 1, 3 and 5 years after LT, respectively, without any statistically significant difference between the four solutions (P=0.78). Graft survival was 82%, 75% and 69% at 1, 3 and 5 years after LT, respectively, without any statistically significant difference between the four solutions (P=0.80). Duration of intensive care was different according to the solution used in univariate analysis (P
Published: 2020
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40. Early Switch From Tacrolimus to Everolimus After Liver Transplantation: Outcomes at 2 Years

Author: Vincent Leroy, Christophe Duvoux, Claire Vanlemmens, Malka Tindel, Ephrem Salamé, Georges Philippe Pageaux, Yvon Calmus, Faouzi Saliba, Filomena Conti, François Durand, Hakam Gharbi, Jean Gugenheim, Jérôme Dumortier, Nassim Kamar, Jean Hardwigsen, Martine Neau-Cransac, Sébastien Dharancy, Cécile Masson, Hôpital Paul Brousse, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, CHU Henri Mondor, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Archet 2 [Nice] (CHU), CHU Toulouse [Toulouse], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital Beaujon [AP-HP], CHU Saint-Eloi, Hôpital Michallon, Hôpital de la Timone [CHU - APHM] (TIMONE), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de Rangueil, Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Graft Rejection, Male, medicine.medical_specialty, Basiliximab, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Posttransplant Care, Urology, 030230 surgery, Liver transplantation, Severity of Illness Index, Tacrolimus, Mycophenolic acid, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Everolimus, Prospective Studies, Renal Insufficiency, Chronic, Aged, Randomized Controlled Trials as Topic, Sirolimus, Transplantation, Hepatology, Drug Substitution, business.industry, Graft Survival, Original Articles, Middle Aged, medicine.disease, Liver Transplantation, 3. Good health, Discontinuation, Calcineurin, Treatment Outcome, Feasibility Studies, Original Article, Female, 030211 gastroenterology & hepatology, Surgery, business, Immunosuppressive Agents, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies, medicine.drug, Kidney disease
Abstract: International audience; The observational CERTITUDE study follows liver transplant patients who completed the SIMCER trial. SIMCER randomized patients at month 1 after transplant to everolimus (EVR) with stepwise tacrolimus (TAC) withdrawal or to standard TAC, both with basiliximab induction and mycophenolic acid ± steroids. After completing SIMCER at 6 months after transplant, 65 EVR-treated patients and 78 TAC-treated patients entered CERTITUDE. At month 24 after transplant, 34/65 (52.3%) EVR-treated patients remained calcineurin inhibitor (CNI) free. Mean estimated glomerular filtration rate (eGFR) was significantly higher with EVR versus TAC during months 3-12. At month 24, eGFR values were 83.6 versus 75.3 mL/minute/1.73 m2 , respectively (P = 0.90) and adjusted mean change in eGFR from randomization was -8.0 versus -13.5 mL/minute/1.73 m2 (P = 0.15). At month 24, 45.9%, 31.1%, and 23.0% of EVR-treated patients had chronic kidney disease stages 1, 2, and 3, respectively, versus 25.7%, 45.7%, and 28.6% of TAC-treated patients (P = 0.05). Treated biopsy-proven acute rejection affected 4 EVR-treated patients and 2 TAC patients during months 6-24. Adverse events led to study discontinuation in 15.4% and 7.7% of EVR-treated and TAC-treated patients, respectively. Grade 3 or 4 hematological events were rare in both groups. A CNI-free EVR-based maintenance regimen appears feasible in approximately half of liver transplant patients. It preserves renal function effectively with good efficacy without compromising safety or hematological tolerance.
Published: 2019
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41. Closed Cyst Resection for Liver Hydatid Disease: a New Standard

Author: Anaïs Palen, Yves Patrice Le Treut, Stéphane Bourgouin, Jean Hardwigsen, and Clément Julien
Subjects: medicine.medical_specialty, Echinococcosis, Hepatic, Multivariate analysis, Disease, Resection, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Recurrence, medicine, Humans, Cyst, Major complication, Retrospective Studies, business.industry, Cysts, Gastroenterology, Reference Standards, medicine.disease, Surgery, Single centre, Time to recurrence, 030220 oncology & carcinogenesis, Operative time, 030211 gastroenterology & hepatology, business
Abstract: Although radical resections are recommended for the surgical management of liver hydatid disease (LHD), whether closed (CCR) or opened (OCR) cyst resections should be performed remains unclear. The aim of this study was to compare the postoperative and long-term outcomes of CCR and OCR for primary and recurrent LHD. Medical charts of patients who underwent surgery at a single centre were retrospectively reviewed and compared with respect to major postoperative complications and recurrence rates. Seventy-nine CCRs and 37 OCRs were included. The major morbidity rates were 19% and 5% in the OCR and CCR groups, respectively (P = 0.036). In multivariate analysis, OCR (P = 0.030, OR = 5.37) and the operative time (P
Published: 2019

42. Incidence of Venous Thromboembolism in Patients With Newly Diagnosed Pancreatic Cancer and Factors Associated With Outcomes

Author: Corinne Frere, Barbara Bournet, Sophie Gourgou, Julien Fraisse, Cindy Canivet, Jean M. Connors, Louis Buscail, Dominique Farge, Nicolas Carrère, Fabrice Muscari, Bertrand Suc, Rosine Guimbaud, Corinne Couteau, Marion Deslandres, Pascale Rivera, Anne-Pascale Laurenty, Nadim Fares, Karl Barange, Janick Selves, Anne Gomez-Brouchet, Bertrand Napoléon, Bertrand Pujol, Fabien Fumex, Jérôme Desrame, Christine Lefort, Vincent Lepilliez, Rodica Gincul, Pascal Artru, Léa Clavel, Anne-Isabelle Lemaistre, Laurent Palazzo, Jérôme Cros, Sarah Tubiana, Nicolas Flori, Pierre Senesse, Pierre-Emmanuel Colombo, Emmanuelle Samail-Scalzi, Fabienne Portales, Claire Honfo Ga, Carine Plassot, Frédéric Bibeau, Marc Ychou, Pierre Guibert, Christelle de la Fouchardière, Matthieu Sarabi, Patrice Peyrat, Séverine Tabone-Eglinger, Caroline Renard, Guillaume Piessen, Stéphanie Truant, Alain Saudemont, Guillaume Millet, Florence Renaud, Emmanuelle Leteurtre, Patrick Gele, Eric Assenat, Jean-Michel Fabre, François-Régis Souche, Marie Dupuy, Anne-Marie Gorce-Dupuy, Jeanne Ramos, Jean-François Seitz, Jean Hardwigsen, Emmanuelle Norguet-Monnereau, Philippe Grandval, Muriel Duluc, Dominique Figarella-Branger, Véronique Vendrely, Clément Subtil, Eric Terrebonne, Jean-Frédéric Blanc, Etienne Buscail, Jean-Philippe Merlio, Jean-Marc Gornet, Daniela Geromin, Geoffroy Vanbiervliet, Anne-Claire Frin, Delphine Ouvrier, Marie-Christine Saint-Paul, Philippe Berthelémy, Chelbabi Fouad, Stéphane Garcia, Nathalie Lesavre, Mohamed Gasmi, Marc Barthet, Vanessa Cottet, Cyrille Delpierre, CCSD, Accord Elsevier, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Unité de biostatistiques, CRLCC Val d'Aurelle - Paul Lamarque, Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), McGill University Health Center [Montreal] (MUHC), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), and CHU Toulouse [Toulouse]
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, Time Factors, medicine.drug_class, Low molecular weight heparin, Pancreatic Cancer, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Clinical endpoint, medicine, Humans, Cumulative incidence, cardiovascular diseases, Progression-free survival, Prospective Studies, Aged, Neoplasm Staging, Aged, 80 and over, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Hepatology, business.industry, Prognostic Factor, Incidence (epidemiology), Incidence, Hazard ratio, Gastroenterology, Venous Thromboembolism, Middle Aged, medicine.disease, Primary tumor, Confidence interval, Progression-Free Survival, 3. Good health, Pancreatic Neoplasms, 030104 developmental biology, 030211 gastroenterology & hepatology, Female, Blood Clot, France, business, Complication, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Carcinoma, Pancreatic Ductal, Follow-Up Studies
Abstract: International audience; Background & aims: Pancreatic ductal adenocarcinoma (PDAC) is associated with the highest incidence of venous thromboembolism (VTE) of any cancer type. However, little is known about risk factors for VTE or its outcomes in patients with PDAC.Methods: We collected data from a prospective, observational study performed at multiple centers in France from May 2014 through November 2018 (the Base Clinico-Biologique de l'Adénocarcinome Pancréatique [BACAP] study) linked to a database of patients with a new diagnosis of PDAC of any stage. Data were collected from 731 patients at baseline and during clinical follow-up or in the event of symptoms. The primary endpoint was the onset of VTE during follow-up. The secondary endpoints were progression-free survival (PFS) and overall survival (OS) times.Results: During a median follow-up of 19.3 months, 152 patients (20.79%) developed a VTE. The median time from PDAC diagnosis to the onset of VTE was 4.49 months. Cumulative incidence values of VTE were 8.07% (95% confidence interval [CI], 6.31-10.29) at 3 months and 19.21% (95% CI, 16.27-22.62) at 12 months. In multivariate analysis, PDAC primary tumor location (isthmus vs head: hazard ratio [HR], 2.06; 95% CI, 1.09-3.91; P = .027) and stage (locally advanced vs resectable or borderline: HR, 1.66; 95% CI, 1.10-2.51, P = .016; metastatic vs resectable or borderline: HR, 2.50; 95% CI, 1.64-3.79; P < .001) were independent risk factors for the onset of VTE. Patients who developed VTE during follow-up had shorter times of PFS (HR, 1.74; 95% CI, 1.19-2.54; P = .004) and OS (HR, 2.02; 95% CI, 1.57-2.60; P < .001).Conclusion: In an analysis of data from the BACAP study, we found that frequent and early onsets of VTE after diagnoses of PDAC are associated with significant decreases in times of PFS and OS. Studies are needed to determine whether primary prophylaxis of VTE in patients with PDAC will improve morbidity and mortality related to VTE. (ClinicalTrials.gov, Number: clinicaltrials.gov as number NCT02818829).
Published: 2019
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43. Hépatectomie majeure et résection de la veine cave pour cholangiocarcinome intrahépatique

Author: O. Turrini, Jean Hardwigsen, Anaïs Palen, Jonathan Garnier, Jacques Ewald, Emilie Gregoire, Y.P. Le Treut, and J.R. Delpero
Subjects: Surgery
Abstract: Objectif Evaluer les suites operatoires et la survie de patients operes d’hepatectomie majeure (HM) avec resection de la veine cave inferieure (VC) pour cholangiocarcinome intrahepatique (CIH). Materiel et methode Entre 2010 et 2018, 18 patients ont eu une HM avec resection de la VC (groupe VC) et ont ete compares aux patients operes d’HM pour CIH (n = 60) durant la meme periode. Les resultats postoperatoires, la survie globale (SG) et sans recidive (SSR) ont ete analysees. Resultats Douze patients ont eu une resection laterale et 6 patients un remplacement cave prothetique. Les suites operatoires ainsi que la mortalite a 90 jours etaient comparables. Seule la transfusion postoperatoire etait identifiee comme facteur de risque de mortalite a 90 jours (p = 0,015). La mediane de survie dans le groupe VC et controle n’etait pas differente statistiquement (48 mois vs 27 mois p = 0,32) de meme que le taux de SG a 1-, 3- et 5 ans (85/81 %, 50/23 %, et 30/8 %). La mediane de SSR etait de 11 mois dans les 2 groupes. L’atteinte ganglionnaire etait le seul facteur de risque de diminution de la survie globale (p = 0,042). Conclusion La resection de la VC au cours d’une HM pour CIH ne pejore pas les resultats a court et long terme.
Published: 2020
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44. Longterm Risk of Solid Organ De Novo Malignancies After Liver Transplantation: A French National Study on 11,226 Patients

Author: Guy Launoy, Pascal Lebray, Olivier Chazouillères, Claire Francoz, Thierry Lobbedez, Sylvie Radenne, Nassim Kamar, Maryline Debette-Gratien, Sébastien Dharancy, Marie-Lorraine Woehl-Jaegle, Dominique Debray, Olivier Sérée, Jean Gugenheim, Marianne Latournerie, Vincent Leroy, Martine Neau-Cransac, Pauline Houssel-Debry, Jean Hardwigsen, Mario Altieri, Faouzi Saliba, Geraldine Hery, Olivier Boillot, Alessandra Mazzola, Rémy De Mil, Filomena Conti, Claire Vanlemmens, Georges-Philippe Pageaux, Elodie Guillaume, Philip Robinson, Emmanuel Jacquemin, Christophe Duvoux, François Durand, Ephrem Salamé, Philippe Segol, Didier Samuel, Jérôme Dumortier, Armand Abergel, Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hospices Civils de Lyon (HCL), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Hôpital Edouard Herriot [CHU - HCL], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Pathologies biliaires, fibrose et cancer du foie [CRSA], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges], CHU Limoges, Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de pédiatrie multidisciplinaire [Hôpital de la Timone Enfants - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Henri Mondor [Créteil], Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital Universitaire Pontchaillou, Intéractions cellulaires et physiopathologie hépathique (Orsay, Essonne) UMRS 1174 (ICPH ), Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, Equipe EPICAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre hépato-biliaire (CHB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie et traitement des maladies du foie, Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépatologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Pôle des Pathologies Digestives Hépatiques et Transplantation [Hôpital Hautepierre-Strasbourg], Hôpital de Hautepierre [Strasbourg], Pathologies biliaires, fibrose et cancer du foie [CHU Saint-Antoine], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Université de Limoges (UNILIM)-CHU Limoges, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), CHU Henri Mondor, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), CHU Saint-Eloi, Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Paul Brousse-Université Paris-Sud - Paris 11 (UP11), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), and UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER
Subjects: Adult, Male, Alcoholic liver disease, medicine.medical_specialty, Time Factors, medicine.medical_treatment, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, 030230 surgery, Liver transplantation, Gastroenterology, Risk Assessment, Liver transplantation (LT), End Stage Liver Disease, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Risk Factors, Internal medicine, Neoplasms, medicine, Humans, education, Liver Diseases, Alcoholic, Transplantation, education.field_of_study, Hepatology, business.industry, Incidence (epidemiology), Incidence, Absolute risk reduction, Middle Aged, medicine.disease, Confidence interval, 3. Good health, Liver Transplantation, Standardized mortality ratio, Treatment Outcome, 030211 gastroenterology & hepatology, Surgery, Female, France, Risk assessment, business, Follow-Up Studies
Abstract: IF 3.756; International audience; De novo malignancies are one of the major late complications and causes of death after liver transplantation (LT). Using extensive data from the French national Agence de la Biomédecine database, the present study aimed to quantify the risk of solid organ de novo malignancies (excluding nonmelanoma skin cancers) after LT. The incidence of de novo malignancies among all LT patients between 1993 and 2012 was compared with that of the French population, standardized on age, sex, and calendar period (standardized incidence ratio; SIR). Among the 11,226 LT patients included in the study, 1200 de novo malignancies were diagnosed (10.7%). The risk of death was approximately 2 times higher in patients with de novo malignancy (48.8% versus 24.3%). The SIR for all de novo solid organ malignancies was 2.20 (95% confidence interval [CI], 2.08‐2.33). The risk was higher in men (SIR = 2.23; 95% CI, 2.09‐2.38) and in patients transplanted for alcoholic liver disease (ALD; SIR = 2.89; 95% CI, 2.68‐3.11). The cancers with the highest excess risk were laryngeal (SIR = 7.57; 95% CI, 5.97‐9.48), esophageal (SIR = 4.76; 95% CI, 3.56‐6.24), lung (SIR = 2.56; 95% CI, 2.21‐2.95), and lip‐mouth‐pharynx (SIR = 2.20; 95% CI, 1.72‐2.77). In conclusion, LT recipients have an increased risk of de novo solid organ malignancies, and this is strongly related to ALD as a primary indication for LT.
Published: 2018
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45. Portal vein stenosis preconditioning of living donor liver in swine: early mechanisms of liver regeneration and gain of hepatic functional mass

Author: Vincent Vidal, Théophile Guilbaud, Jean Hardwigsen, Eric Guedj, Christophe Buffat, Anaïs Palen, Guillaume Gorincour, Emilie Gregoire, Sophie Chopinet, Pauline Brige, Benjamin Guillet, Anaïs Moyon, Geraldine Hery, Laboratoire d'Imagerie Interventionnelle Expérimentale (LIIE), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pédiatrie multidisciplinaire [Hôpital de la Timone Enfants - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE), Aix-Marseille Université - Faculté de médecine (AMU MED), Aix Marseille Université (AMU), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Aix-Marseille Université - Faculté de pharmacie (AMU PHARM), Centre recherche en CardioVasculaire et Nutrition (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Chirurgie, Assistance Publique - Hôpitaux de Marseille (APHM)-Hospices Civiles de Marseille-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Service Central de Biophysique et de Médecine Nucléaire, Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Informatique de Lens (CRIL), Université d'Artois (UA)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Assistance Publique - Hôpitaux de Marseille (APHM)-Hospices Civiles de Marseille-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Service de médecine nucléaire [Marseille], Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Imagerie MOléculaire pour applications THéranostiques personnalisées (IMOTHEP), Institut FRESNEL (FRESNEL), and Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE)
Subjects: Models, Anatomic, STAT3 Transcription Factor, medicine.medical_specialty, Swine, Physiology, medicine.medical_treatment, Portal vein, liver preconditioning, Living donor, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Physiology (medical), Living Donors, Animals, Hepatectomy, Medicine, portal stenosis, Ischemic Preconditioning, liver regeneration, Ligation, ComputingMilieux_MISCELLANEOUS, Hepatology, Left portal vein, Interleukin-6, Portal Vein, Tumor Necrosis Factor-alpha, business.industry, Gastroenterology, Organ Size, Recovery of Function, medicine.disease, Peptide Fragments, Liver regeneration, Liver Transplantation, major hepatectomy, 3. Good health, Surgery, Stenosis, Liver, 030220 oncology & carcinogenesis, Models, Animal, 030211 gastroenterology & hepatology, LDLT, business, Major hepatectomy, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: To reduce the morbidity and mortality risk for the donor in living donor liver transplantation (LDLT), we previously identified 20% left portal vein (LPV) stenosis as an effective preconditioning method to induce cell proliferation in the contralateral lobe without downstream ipsilateral atrophy. In this study, we report the pathways involved in the first hours after preconditioning and investigate the changes in liver volume and function. Fourteen pigs were used this study. Five pigs were used to study the genetic, cellular and molecular mechanisms set up in the early hours following the establishment of our preconditioning. The remaining nine pigs were equally divided into three groups: sham-operated animals, 20% LPV stenosis, and 100% LPV stenosis. Volumetric scanning and 99 mTc-Mebrofenin hepatobiliary scintigraphy were performed before preconditioning and 14 days after to study morphological and functional changes in the liver. We demonstrated that liver regeneration triggered by 20% LPV stenosis in the contralateral lobe involves TNF-α, IL-6, and inducible nitric oxide synthase 2 by means of STAT3 and hepatocyte growth factor. We confirmed that our preconditioning was responsible for an increase in the total liver volume. Finally, we demonstrated that this volumetric gain was associated with an increase in hepatic functional capacity. NEW & NOTEWORTHY We describe a new preconditioning method for major hepatectomy that is applicable to hepatectomy for donation. We identified 20% left portal vein stenosis as effective preconditioning that is capable of inducing cell proliferation in the contralateral lobe without the downstream ipsilateral atrophy. In this study, we report the pathways involved in the first hours following preconditioning, and we confirm that 20% left portal vein stenosis is responsible for an increase in the functional capacity and total liver volume in a porcine model.
Published: 2018
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46. Authors' Reply: Postoperative Bleeding After Laparoscopic Pancreaticoduodenectomy: The Achilles' Heel?

Author: Sophie Chopinet, Brice Gayet, Jean Hardwigsen, David Fuks, and Emilie Gregoire
Subjects: medicine.medical_specialty, Heel, business.industry, Anastomosis, Surgical, Vascular surgery, Postoperative Hemorrhage, Surgery, Cardiac surgery, Pancreaticoduodenectomy, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Pancreatectomy, Cardiothoracic surgery, 030220 oncology & carcinogenesis, Medicine, Humans, 030211 gastroenterology & hepatology, Laparoscopy, business, Laparoscopic pancreaticoduodenectomy, Abdominal surgery
Published: 2018

47. Short-term outcomes after major hepatic resection in patients with cirrhosis: a 75-case unicentric western experience

Author: Anaïs Palen, Jean-François Hak, Yves-Patrice Le Treut, Vincent Vidal, Jean Hardwigsen, Sophie Chopinet, Emilie Bollon, and Emilie Gregoire
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, Multivariate analysis, Cirrhosis, Blood transfusion, Carcinoma, Hepatocellular, medicine.medical_treatment, Disease, Gastroenterology, Postoperative Complications, Risk Factors, Internal medicine, medicine, Hepatectomy, Humans, Stage (cooking), Aged, Retrospective Studies, Hepatology, business.industry, Liver Neoplasms, Perioperative, Middle Aged, medicine.disease, digestive system diseases, Survival Rate, Treatment Outcome, Hepatocellular carcinoma, Female, business, Liver cancer
Abstract: Background The benefit of performing major hepatic resection (MHR) for hepatocellular carcinoma (HCC) in patients with cirrhosis remains controversial because of its high risk of posthepatectomy liver failure (PHLF). This study was conducted to assess the risk of MHR for HCC in patients with cirrhosis. Methods Patients with Child-Pugh A or B cirrhosis and HCC who underwent MHR from January 2000 to June 2014 were retrospectively identified. Risk factors for postoperative morbidity and mortality using univariate and multivariate analyses were evaluated. Results Seventy patients with Child-Pugh A (93%) and 5 (7%) with Child-Pugh B cirrhosis underwent MHR for HCC. Thirteen (17%) had Barcelona Clinic Liver Cancer (BCLC) stage A, 39 (50%) had BCLC B, and 23 (32%) had BCLC C disease. A perioperative blood transfusion was performed in 18 patients (24%). Ninety-day postoperative mortality was 9% (n=7). Major complications occurred in 16 patients (21%), including PHLF in 9 patients (12%). A multivariate analysis showed that perioperative blood transfusion was the main independent factor associated with mortality (OR= 6.5) and major morbidity (OR=10). Conclusion In selected patients with HCC and cirrhosis, MHR is feasible and has acceptable mortality, but careful perioperative management and limiting blood loss are required.
Published: 2018

48. Réponse aux commentaires : duodénectomie subtotale pour envahissement secondaire du duodénum

Author: Jean Hardwigsen, Y.P. Le Treut, Emilie Gregoire, and M. Baboudjian
Subjects: Surgery
Published: 2019
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49. Minimal portal vein stenosis is a promising preconditioning in living donor liver transplantation in porcine model

Author: Vincent Vidal, Jean Hardwigsen, Y.P. Le Treut, Emilie Gregoire, Pauline Brige, Louise Barbier, Pierre H. Rolland, Christophe Buffat, and A. Coppola
Subjects: medicine.medical_specialty, medicine.medical_treatment, Sus scrofa, Hemodynamics, Liver transplantation, Hepatic Artery, Risk Factors, Internal medicine, Living Donors, medicine, Animals, Hepatectomy, Ischemic Preconditioning, Ligation, Cell Proliferation, Hepatology, Portal Vein, business.industry, Organ Size, medicine.disease, Liver regeneration, Liver Regeneration, Liver Transplantation, Surgery, Stenosis, medicine.anatomical_structure, Cardiology, Ischemic preconditioning, business, Liver Circulation, Artery
Abstract: Background & Aims The main hindrance in promoting living donor liver transplantation remains the morbi-mortality risk for the donor. Considering the opposed remodeling influence of portal and hepatic artery flows, our working hypothesis was to identify a lobar portal vein stenosis capable of inducing a contralateral liver mass compensatory enlargement, without the downstream ipsilateral atrophic response. Methods Twenty-four pigs entered this study. Six of them were used to establish hemodynamic changes following a progressive left portal vein (LPV) stenosis, in blood flow, pressure and vessel diameter of the LPV, main portal vein and hepatic artery. Sixteen pigs were divided into 4 groups: sham operated animals, 20% LPV stenosis, 50% LPV stenosis, and 100% LPV stenosis. Daily liver biopsies were collected until post-operative day 5 to investigate liver regeneration and atrophy (Ki67, STAT3, LC3, and activated caspase 3) according to the degree of LPV stenosis. Finally, changes in liver volumetry after 20% LPVS were investigated. Results A 20% LPV stenosis led to dilatation of the hepatic artery and a subsequent four-fold increase in hepatic arterial flow. Concomitantly, liver regeneration was triggered in the non-ligated lobe and the cell proliferation peak, 5days after surgery, was comparable to that obtained after total LPV ligation. Moreover, 20% LPV stenosis preconditioning did not induce left liver atrophy contrary to 50 and 100% LPV stenosis. Conclusions A 20% LPV stenosis seems to be the adequate preconditioning to get the remnant liver of living donor ready to take on graft harvesting without atrophy of the future graft.
Published: 2014
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50. Long term results of liver transplantation for Wilson’s disease: Experience in France

Author: Olivier Guillaud, Jérôme Dumortier, Rodolphe Sobesky, Dominique Debray, Philippe Wolf, Claire Vanlemmens, François Durand, Yvon Calmus, Christophe Duvoux, Sébastien Dharancy, Nassim Kamar, Karim Boudjema, Pierre Henri Bernard, Georges-Philippe Pageaux, Ephrem Salamé, Jean Gugenheim, Alain Lachaux, Dalila Habes, Sylvie Radenne, Jean Hardwigsen, Olivier Chazouillères, Jean-Marc Trocello, France Woimant, Philippe Ichai, Sophie Branchereau, Olivier Soubrane, Denis Castaing, Emmanuel Jacquemin, Didier Samuel, Jean-Charles Duclos-Vallée, service d'Hépato-gastro-entérologie, Hospices Civiles de Lyon-Hôpital Edouard Heriault, Service de Chirurgie Générale et Transplantation Multi Organes, CHU Strasbourg, Service d'hépatologie, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz-Université de Franche-Comté (UFC), Service de Chirurgie Digestive, CHU Cochin [AP-HP], Pôle Recherche Clinique-Santé Publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri-Mondor, Hôpital Claude Hurriez, Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Foie, métabolismes et cancer, 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)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département Digestif, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital de l'Archet, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Service de Chirurgie, Assistance Publique - Hôpitaux de Marseille (APHM)-Hospices Civiles de Marseille-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Service d'hépatologie [Saint-Antoine], CHU Saint-Antoine [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de neurologie [Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Service de neurologie [Univ. Paris VII], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Centre National de Référence pour la maladie de Wilson (CNR wilson), CNR Wilson, Service de Neurologie, Hôpital Lariboisière, Pathogénèse et traitement de l'hépatite fulminante et du cancer du foie, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hépato-biliaire (CHB), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de chirurgie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Service de chirurgie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse, Service d'hépato-gastro-entérologie pédiatrique, Virus Hépatotropes et Cancers, Université Paris-Sud - Paris 11 (UP11)-IFR89-EA 3541, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Assistance Publique - Hôpitaux de Marseille (APHM)-Hospices Civiles de Marseille-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Male, Reoperation, medicine.medical_specialty, Adolescent, [SDV]Life Sciences [q-bio], Fulminant, medicine.medical_treatment, Renal function, Liver transplantation, Chronic liver disease, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Fulminant hepatic failure, Hepatolenticular Degeneration, Internal medicine, medicine, Humans, Child, Survival rate, Aged, Retrospective Studies, Immunosuppression Therapy, Hepatitis, Hepatology, business.industry, Graft Survival, Middle Aged, medicine.disease, Liver Transplantation, 3. Good health, Surgery, Wilson's disease, Treatment Outcome, Female, 030211 gastroenterology & hepatology, France, business, 030217 neurology & neurosurgery
Abstract: International audience; BACKGROUND & AIMS: Liver transplantation (LT) is the therapeutic option for severe complications of Wilson's disease (WD). We aimed to report on the long-term outcome of WD patients following LT. METHODS: The medical records of 121 French patients transplanted for WD between 1985 and 2009 were reviewed retrospectively. Seventy-five patients were adults (median age: 29 years, (18-66)) and 46 were children (median age: 14 years, (7-17)). The indication for LT was (1) fulminant/subfulminant hepatitis (n = 64, 53%), median age = 16 years (7-53), (2) decompensated cirrhosis (n = 50, 41%), median age = 31.5 years (12-66) or (3) severe neurological disease (n = 7, 6%), median age = 21.5 years (14.5-42). Median post-transplant follow-up was 72 months (0-23.5). RESULTS: Actuarial patient survival rates were 87% at 5, 10, and 15 years. Male gender, pre-transplant renal insufficiency, non elective procedure, and neurological indication were significantly associated with poorer survival rate. None of these factors remained statistically significant under multivariate analysis. In patients transplanted for hepatic indications, the prognosis was poorer in case of fulminant or subfulminant course, non elective procedure, pretransplant renal insufficiency and in patients transplanted before 2000. Multivariate analysis disclosed that only recent period of LT was associated with better prognosis. At last visit, the median calculated glomerular filtration rate was 93 ml/min (33-180); 11/93 patients (12%) had stage II renal insufficiency and none had stage III. CONCLUSIONS: Liver failure associated with WD is a rare indication for LT (\textless1%), which achieves an excellent long-term outcome, including renal function.
Published: 2014
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