Safety of Islet Autotransplantation After Pancreatectomy for Adenocarcinoma.


Journal

Transplantation
ISSN: 1534-6080
Titre abrégé: Transplantation
Pays: United States
ID NLM: 0132144

Informations de publication

Date de publication:
01 2019
Historique:
pubmed: 17 8 2018
medline: 29 5 2019
entrez: 17 8 2018
Statut: ppublish

Résumé

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. 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. 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. 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.

Sections du résumé

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.

Identifiants

pubmed: 30113997
doi: 10.1097/TP.0000000000002419
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

177-181

Auteurs

Florence Renaud (F)

CHU Lille, Institute of Pathology, Centre de Biologie Pathologie Lille, France.
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, Univ Lille, Lille, France.
SIRIC OncoLille, Lille, France.

Mikael Chetboun (M)

Department of Endocrine Surgery, CHU Lille, Lille, France.
Translational Research for Diabetes, Inserm, Lille, France.
European Genomic Institute for Diabetes, Univ Lille, Lille, France.

Julien Thevenet (J)

Translational Research for Diabetes, Inserm, Lille, France.
European Genomic Institute for Diabetes, Univ Lille, Lille, France.

Nathalie Delalleau (N)

Translational Research for Diabetes, Inserm, Lille, France.
European Genomic Institute for Diabetes, Univ Lille, Lille, France.

Valery Gmyr (V)

Translational Research for Diabetes, Inserm, Lille, France.
European Genomic Institute for Diabetes, Univ Lille, Lille, France.

Thomas Hubert (T)

Translational Research for Diabetes, Inserm, Lille, France.
European Genomic Institute for Diabetes, Univ Lille, Lille, France.

Caroline Bonner (C)

Translational Research for Diabetes, Inserm, Lille, France.
European Genomic Institute for Diabetes, Univ Lille, Lille, France.

Mathieu Messager (M)

Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, Univ Lille, Lille, France.
SIRIC OncoLille, Lille, France.
Department of Digestive and Oncological Surgery, CHU Lille, Lille, France.

Emmanuelle Leteurtre (E)

CHU Lille, Institute of Pathology, Centre de Biologie Pathologie Lille, France.
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, Univ Lille, Lille, France.
SIRIC OncoLille, Lille, France.

Christophe Mariette (C)

Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, Univ Lille, Lille, France.
SIRIC OncoLille, Lille, France.
Department of Digestive and Oncological Surgery, CHU Lille, Lille, France.

Julie Kerr-Conte (J)

Translational Research for Diabetes, Inserm, Lille, France.
European Genomic Institute for Diabetes, Univ Lille, Lille, France.

Guillaume Piessen (G)

Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, Univ Lille, Lille, France.
SIRIC OncoLille, Lille, France.
Department of Digestive and Oncological Surgery, CHU Lille, Lille, France.

François Pattou (F)

Department of Endocrine Surgery, CHU Lille, Lille, France.
Translational Research for Diabetes, Inserm, Lille, France.
European Genomic Institute for Diabetes, Univ Lille, Lille, France.

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