Inclusion criteria  Inclusion criteria are composed of preoperative conditions validated by intraoperative confirmation to plan an exit of the protocol if the pancreas does not finally appear with a high-risk of CR-POPF.  Age ≥ 18 years Locale resectable invasive adenocarcinomas located in the cephalic region of the pancreas documented by endoscopic ultrasonography with fine-needle aspiration biopsy pancreatic adenocarcinoma; duodenal adenocarcinoma; ampullary adenocarcinoma; and IPMNs with adenocarcinoma degeneration; A potentially curative strategy with primary tumor resection approved by a multidisciplinary expert team  A high-risk of CR-POPF  Suspected during preoperative evaluation by the presence of 2 or more of the following criteria (screening criteria of inclusion) : sex male;an obesity (BMI ≥ 30 kg/m2);a main pancreatic duct diameter ≤ 3 mm on preoperative endoscopic ultrasonography a visceral obesity (i.e. a visceral fat area > 84 cm2) ; a sarcopenia (i.e. a skeletal muscle index < 43 cm2/m2 in men with a BMI of <25 kg/m2 or <53 cm2/m2 in men with a BMI of ≥25 kg2/m2, and <41 cm2/m2 in women) and validated during intraoperative evaluation (finale inclusion) by a probability score above or equal to 20% on the validated updated alternative Fistula Risk Score ua-FRS for pancreaticoduodenectomy (ua-FRS) based of pancreas texture, duct size, BMI, sex . Women of childbearing potential should only be included after a confirmed menstrual period, and a negative highly sensitive urine or serum pregnancy test and must agree to be subjected to a monthly pregnancy test (urine or blood) until the end of the relevant systemic exposure to chemotherapy agents, in accordance with current CTFG recommendations (Recommendations related to contraception and pregnancy testing in clinical trials); Women of child-bearing potential and male subjects must agree to use a birth control methods which may be considered as highly effective (failure rate of less than 1% per year ) as recommended by the CTFG (Cinical Trials Facilitation and Coordination Group, version 1.1). These recommandations related to contraception and pregnancy testing in clinical trials suggested such method (see below) that will be use during chemotherapy exposure for included women of child-bearing potential and woman of child-bearing potential when partner of included male : combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal) ; progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable) ; intrauterine device (IUD) ; intrauterine hormone-releasing system ( IUS) ; bilateral tubal occlusion; vasectomised partner ;sexual abstinence For included male partner of a women of child-bearing potential, contraception with condom.  Contraception will be perform during the relevant systemic exposure to chemotherapy agents and will be extended by 6 months for women of childbearing potential and by 1 month for men included as recommended by the CTFG  Patient covered by a health insurance system Patient who provides a written informed consent to participate to the study  Exclusion criteria  Patient will be screened and excluded if they present a preoperative diabetes defined by a stimulated C-peptide < 0.5 ng/mL relative to blood glucose > 2 g/dL, at 2 hours in post prandial Patients with a known or highly suspected genetic syndrome associated with a risk of pancreatic adenocarcinoma: familial pancreatic cancer, multiple familial melanoma, Peutz-Jeghers syndrome, hereditary chronic pancreatitis, cystic fibrosis, familial breast Ovarian Cancer, Lynch syndrome, adenomatous polyposis family, Li Fraumeni syndrome, Multi-endocrine disorder type I; Multifocal pancreatic adenocarcinomas identified during preoperative evaluation; Performance status and comorbidity profile inappropriate for a major abdominal surgery; Contraindication for autologous islet intraportal transplantation Current or indicated/scheduled neoadjuvant chemotherapy; Extra pancreatic metastasis identified during preoperative evaluation (high-definition cross-sectional imaging with thorax-abdomen-pelvis multi-detection computed tomography or abdominal MRI with T1, T2 and diffusion weighted sequences) or during intraoperative assessment (clinical examination and ultrasonography); Need for complex vascular reconstructions (endovascular treatment or release of the arcuate ligament will be not considered as complex vascular reconstructions), major vein reconstructions will exclude the patients because of the over-risk of portal thrombosis following islet intraportal infusion. evident macroscopically or biologically proved post biliary drainage pancreatitis that jeopardize islet isolation Known infection or positive serology performed at screening for human immunodeficiency virus (HIV) infection, Hepatitis B or C virus infection, HTLV infection or syphilis infection. Active infection for SARS-CoV-2 virus (positive PCR), which will require rescheduling of the intervention 30 days later. Pregnant or breastfeeding woman Dihydropyrimidine dehydrogenase total deficiency  Ethics / regulatory criteria :  Person unable to understand purposes, benefits and risks of the study and/or unable to provide a written informed consent. Person unable to comply with the whole study schedule. Person not covered by a health insurance system. Person kept in detention and/or receiving psychiatric medical care and/or patients admitted in a social or medical sanatorium. Person in an emergency situation.