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Safety of Islet Autotransplantation After Pancreatectomy for Adenocarcinoma

Renaud, Florence, MD, PhD1,2,3; Chetboun, Mikael, MD4,5,6; Thevenet, Julien5,6; Delalleau, Nathalie5,6; Gmyr, Valery, PhD5,6; Hubert, Thomas, VetD, PhD5,6; Bonner, Caroline, PhD5,6; Messager, Mathieu, MD2,3,7; Leteurtre, Emmanuelle, MD, PhD1,2,3; Mariette, Christophe, MD, PhD2,3,7; Kerr-Conte, Julie, PhD5,6; Piessen, Guillaume, MD, PhD2,3,7; Pattou, François, MD, PhD4,5,6

doi: 10.1097/TP.0000000000002419
Original Basic Science—General
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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 explore 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. Immunocompromised mice were transplanted with pancreatic cells isolated from the nonmalignant part of the surgical specimen (experimental group). Results were compared with pancreatic tumor implants (control group). Pancreatic grafts were explanted at 6 weeks for histological analyses.

Results Nine 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 after 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.

1 CHU Lille, Institute of Pathology, Centre de Biologie Pathologie Lille, France.

2 Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, Univ Lille, Lille, France.

3 SIRIC OncoLille, Lille, France.

4 Department of Endocrine Surgery, CHU Lille, Lille, France.

5 Translational Research for Diabetes, Inserm, Lille, France.

6 European Genomic Institute for Diabetes, Univ Lille, Lille, France.

7 Department of Digestive and Oncological Surgery, CHU Lille, Lille, France.

Received 29 March 2018. Revision received 9 July 2018.

Accepted 10 July 2018.

F.R. and M.C. contributed equally to this work.

The authors declare no conflict of interest.

SIRIC ONCO Lille and European Genomic Institute for Diabetes (ANR-10-LABX-46).

F.R. participated in the research design, writing of the paper, performance of the research, data analysis. M.C. participated in the research design, writing of the paper, performance of the research, data analysis. J.T. participated in the performance of the research, data analysis. N.D. participated in the performance of the research, data analysis. V.G. participated in the research design, writing of the paper, data analysis. T.H. participated in the writing of the paper, data analysis, critical revision. C.B. participated in the writing of the article, critical revision. M.M. participated in the research design, performance of the research, data analysis. E.L. participated in the research design, writing of the paper, performance of the research, data analysis, critical revision. C.M. participated in the research design, writing of the paper, performance of the research, data analysis, critical revision. J.K.-C. participated in the research design, writing of the paper, performance of the research, data analysis. G.P. participated in the research design, writing of the paper, performance of the research, data analysis, critical revision. F.P. participated in the research design, writing of the paper, performance of the research, data analysis, critical revision.

Correspondence: François Pattou, MD, PhD, Université de Lille, Inserm, UMR 1190, Translational Research for Diabetes, European Genomic Institute for Diabetes, 1 place de Verdun 59045, Lille, France. (francois.pattou@univ-lille.fr).

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