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Combined hepatocellular-cholangiocarcinoma compared to hepatocellular carcinoma and intrahepatic cholangiocarcinoma: Different survival, similar recurrence: Report of a large study on repurposed databases with propensity score matching |
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Surgery. 2023 Nov 17:S0039-6060(23)00710-9. doi: 10.1016/j.surg.2023.09.040.Online ahead of print.
Boris Amory 1, Claire Goumard 2, Alexis Laurent 3, Serena Langella 4, Daniel Cherqui 5, Ephrem Salame 6, Louise Barbier 6, Olivier Soubrane 7, Olivier Farges 8, Christian Hobeika 8, Takayuki Kawai 9, Jean-Marc Regimbeau 10, François Faitot 11, Patrick Pessaux 12, Stéphanie Truant 13, Emmanuel Boleslawski 13, Astrid Herrero 14, Jean-Yves Mabrut 15, Laurence Chiche 16, Marcello Di Martino 17, Rami Rhaiem 18, Lilian Schwarz 19, Vivian Resende 20, Julien Calderaro 21, Jérémy Augustin 21, Stefano Caruso 21, Daniele Sommacale 22, Stefan Hofmeyr 23, Alessandro Ferrero 4, David Fuks 24, Eric Vibert 5, Guido Torzilli 25, Olivier Scatton 2, Raffaele Brustia 26; AFC-ICC-2009, AFC-LLR-2018, and PRS-2019 Study Group
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Author information
Collaborators
- AFC-ICC-2009, AFC-LLR-2018, and PRS-2019 Study Group:
Julio Abba, René Adam, Mustapha Adham, Pietro Addeo, Marc-Antoine Allard, Giuliana Amaddeo, Ahmet Ayav, Daniel Azoulay, Philippe Bachellier, Pierre Balladur, Julien Barbieux, Emmanuel Boleslawski, Karim Boudjema, M Bougard, Emmanuel Buc, Petru Bucur, Antoine Carmelo, François Cauchy, Denis Chatelain, Jean Chauvat, Zineb Cherkaoui, 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, Álvaro Gancedo Quintana, Brice Gayet, Alessandro Giacomoni, Jean-Francois Gigot, 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, Philippe Leourier, Emilie Lermite, Mikael Lesurtel, Christian Letoublon, Paul Leyman, Mickael Lesurtel, Jean Lubrano, Jean-Yves Mabrut, Georges Mantion, Ugo Marchese, Elena Martín-Pérez, Benjamin Menahem, Maxime Meunier, Guillaume Millet, Kayvan Mohkam, André Mulliri, Fabrice Muscari, Francis Navarro, Francisco Nolasco, Takeo Nomi, Jean Nunoz, Gennaro Nuzzo, Shinya Okumura, Nassima Oudafal, Gerard Pascal, Guillaume Passot, Damiano Patrono, François Paye, Fabiano Perdigao, Niccolo Petrucciani, Gabriella Pittau, François-René Pruvot, Artigas Raventos, Hélène Regnault, Michel Rivoire, Renato Romagnoli, Didier Roulin, Antonio Sa-Cunha, Michel Scotte, François-Regis Souche, Bertrand Suc, Alexandre Thobie, Boris Trechot, Stéphanie Truant, Olivier Turini, Shinji Uemoto, Xavier Unterteiner, Charles Vanbrugghe, Jean Zemour
Affiliations
- 1Department of Digestive and Hepato-pancreatic-biliary Surgery, AP-HP, Hôpital Henri-Mondor, Paris Est Créteil University, UPEC, France; Assistance Publique-Hôpitaux de Paris, Créteil, France.
- 2Department of Hepatobiliary and Liver Transplantation Surgery, AP-HP, Hôpital Pitié Salpêtrière, CRSA, Sorbonne Université, Paris, France.
- 3Department of Digestive and Hepato-pancreatic-biliary Surgery, DMU CARE, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, Créteil, France; Paris Est Créteil University, UPEC, France; Team "Pathophysiology and Therapy of Chronic Viral Hepatitis and Related Cancers," INSERM U955, Créteil, France; Assistance Publique-Hôpitaux de Paris, Créteil, France.
- 4Department of General and Oncological Surgery, Ospedale Mauriziano, Torino, Italy.
- 5Center Hepato-Biliaire, AP-HP Paul Brousse Hospital, Paris-Saclay University, Villejuif, France.
- 6Department of Digestive Surgery and Liver Transplantation, University Hospital of Tours, University of Tours, France; FHU Support, Tours, France.
- 7Department of Digestive, Oncological, and Metabolic Surgery, Institut Mutualiste Montsouris, Paris, France.
- 8Department of HPB Surgery and Liver Transplantation, AP-HP Beaujon Hospital, University of Paris, Clichy, France.
- 9Department of Surgery, Medical Research Institute, Kitano Hospital, Osaka and Graduate School of Medicine, Kyoto University, Japan.
- 10SSPC (Simplification of Surgical Patients Care) - Clinical Research Unit, University of Picardie Jules Verne, Amiens, France; Department of Digestive Surgery, Amiens University Medical Center, France.
- 11Service de Chirurgie Hépato-Biliaire et Transplantation Hépatique, Hôpital de Hautepierre, Strasbourg, France.
- 12Unité Chirurgie HBP, Pôle hépato-digestif Nouvel Hôpital Civil, Strasbourg, France; Institut of Viral and Liver Disease, Inserm U1110, Strasbourg, France.
- 13Department of Digestive Surgery and Transplantation, University Hospitals, Lille, France.
- 14Department of HBP Surgery and Liver Transplantation, Montpellier University Hospital, University of Montpellier, France.
- 15Croix Rousse University Hospital, Department of General Surgery and Liver Transplantation, Lyon, France; Cancer Research Center of Lyon, INSERM U1052, France.
- 16Department of Hepato-Bilio-Pancreatic Surgery and Liver Transplantation, Haut Lévêque Hospital, Center Hospitalier Universitaire de Bordeaux, France; Inserm UMR 1312-Team 3 "Liver Cancers and Tumoral Invasion," Bordeaux Institute of Oncology, University of Bordeaux, France.
- 17HPB Unit, Department of General and Digestive Surgery, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), Madrid, Spain.
- 18Department of Hepatobiliary, Pancreatic, and Digestive Surgery, Robert Debré University Hospital, Reims, France; University Reims Champagne-Ardenne, France.
- 19Department of Genomic and Personalized Medicine in Cancer and Neurological Disorders, Rouen University Hospital, UNIROUEN, UMR 1245 INSERM, Normandie Rouen University, France.
- 20Federal University of Minas Gerais School of Medicine, Belo Horizonte, Brazil.
- 21Université Paris Est Créteil, INSERM, IMRB, Créteil, France; Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Department of Pathology, Créteil, France; Inserm, U955, Team 18, Créteil, France.
- 22Department of Digestive and Hepato-pancreatic-biliary Surgery, DMU CARE, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, Créteil, France; Paris Est Créteil University, UPEC, Créteil, France; Team "Pathophysiology and Therapy of Chronic Viral Hepatitis and Related Cancers," INSERM U955, Créteil, France; Assistance Publique-Hôpitaux de Paris, Créteil, France.
- 23Division of Surgery, Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg Academic Hospital, Cape Town, South Africa.
- 24Department of Hepato-Pancreatic-Biliary and Endocrine Surgery, Hopital Cochin, Assistance Publique-Hôpitaux de Paris, France; Université Paris Cité, France.
- 25Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas Research Hospital - IRCCS, Humanitas University, Rozzano, Milan, Italy.
- 26Department of Digestive and Hepato-pancreatic-biliary Surgery, DMU CARE, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, Créteil, France; Paris Est Créteil University, UPEC, France; Team "Pathophysiology and Therapy of Chronic Viral Hepatitis and Related Cancers," INSERM U955, Créteil, France; Assistance Publique-Hôpitaux de Paris, Créteil, France. Electronic address: raffaele.brustia@aphp.fr.
Abstract
Background: Combined hepatocholangiocarcinoma is a rare cancer with a grim prognosis composed of both hepatocellular carcinoma and intrahepatic cholangiocarcinoma morphologic patterns in the same tumor. The aim of this multicenter, international cohort study was to compare the oncologic outcomes after surgery of combined hepatocholangiocarcinoma to hepatocellular carcinoma and intrahepatic cholangiocarcinoma.
Methods: Patients treated by surgery for combined hepatocholangiocarcinoma, hepatocellular carcinoma, and intrahepatic cholangiocarcinoma from 2000 to 2021 from multicenter international databases were analyzed retrospectively. Patients with combined hepatocholangiocarcinoma (cases) were compared with 2 control groups of hepatocellular carcinoma or intrahepatic cholangiocarcinoma, sequentially matched using a propensity score based on 8 preoperative characteristics. Overall and disease-free survival were compared, and predictors of mortality and recurrence were analyzed with Cox regression after propensity score matching.
Results: During the study period, 3,196 patients were included. Propensity score adjustment and 2 sequential matching processes produced a new cohort (n = 244) comprising 3 balanced groups was obtained (combined hepatocholangiocarcinoma = 56, intrahepatic cholangiocarcinoma = 66, and hepatocellular carcinoma = 122). Kaplan-Meier overall survival estimations at 1, 3, and 5 years were 67%, 45%, and 28% for combined hepatocholangiocarcinoma, 92%, 75%, and 55% for hepatocellular carcinoma, and 86%, 53%, and 42% for the intrahepatic cholangiocarcinoma group, respectively (P = .0014). Estimations of disease-free survival at 1, 3, and 5 years were 51%, 25%, and 17% for combined hepatocholangiocarcinoma, 63%, 35%, and 26% for the hepatocellular carcinoma group, and 51%, 31%, and 28% for the intrahepatic cholangiocarcinoma group, respectively (P = .19). Predictors of mortality were combined hepatocholangiocarcinoma subtype, metabolic syndrome, preoperative tumor markers alpha-fetoprotein and carbohydrate antigen 19-9, and satellite nodules, and recurrence was associated with satellite nodules rather than cancer subtype.
Conclusion: Despite data limitations, overall survival among patients with combined hepatocholangiocarcinoma was worse than both groups and closer intrahepatic cholangiocarcinoma, whereas disease-free survival was similar among the 3 groups. Future research on immunophenotypic profiling may hold more promise than traditional nonmodifiable clinical characteristics (as found in this study) in predicting recurrence or response to salvage treatments.
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