Αρχειοθήκη ιστολογίου

Παρασκευή 17 Αυγούστου 2018

Safety of Islet Autotransplantation Following Pancreatectomy for Adenocarcinoma

Background total pancreatectomy with intraportal islet autotransplantation (TPIAT) rather than partial pancreatectomy could represent a major shift in the management of patients with resectable pancreatic ductal adenocarcinoma (PDAC) when risks of postoperative pancreatic fistula are well identified. This approach provides a theoretical risk of tumor cell dissemination when islet cells are transplanted into the portal vein. Our objective was to demonstrate the safety of TPIAT in PDAC in a mouse preclinical model of subcutaneous xenotransplantation of human cells isolated from pancreatic specimen during partial pancreatectomy performed for PDAC. Methods patients requiring pancreatectomy for PDAC were prospectively included. Immunocompromized mice were transplanted with pancreatic cells isolated from the nonmalignant part of the surgical specimen (experimental group). Results were compared to pancreatic tumor implants (control group). Pancreatic grafts were explanted at 6 weeks for histological analyses. Results 9 patients were included and 31 mice were transplanted. In the experimental group, explants were microscopically devoid of tumor cell and no metastasis was observed. In the control group, all explants were composed of tumor. Conclusions we report in a preclinical model the absence of local and distant spreading of malignant cells following pancreatic islets xenograft isolated from PDAC patients. These data supports the oncological safety of TPIAT as valuable alternative to partial pancreatectomy for PDAC patients with a high risk of postoperative pancreatic fistula. *The authors contributed equally to this work Corresponding author: François Pattou, Université de Lille, Inserm, UMR 1190, Translational Research for Diabetes, European Genomic Institute for Diabetes, 1 place de Verdun 59045, Lille, France, Tel: (+33)3 20 62 69 63; francois.pattou@univ-lille.fr Conflicts of interest: The authors have no conflict of interest to disclose. Funding: SIRIC ONCO Lille and European Genomic Institute for Diabetes (ANR-10-LABX-46). Authorship page Florence Renaud: research design, writing of the paper, performance of the research, data analysis Mikael Chetboun: research design, writing of the paper, performance of the research, data analysis Julien Thevenet: performance of the research, data analysis Nathalie Delalleau: performance of the research, data analysis Valery Gmyr: research design, writing of the paper, data analysis Thomas Hubert: writing of the paper, data analysis, critical revision Caroline Bonner: writing of the paper, critical revision Mathieu Messager: research design, performance of the research, data analysis Emmanuelle Leteurtre: research design, writing of the paper, performance of the research, data analysis, critical revision Christophe Mariette†: research design, writing of the paper, performance of the research, data analysis, critical revision Julie Kerr-Conte: research design, writing of the paper, performance of the research, data analysis Guillaume Piessen: research design, writing of the paper, performance of the research, data analysis, critical revision François Pattou: research design, writing of the paper, performance of the research, data analysis, critical revision Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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