"Pancreatic cancer, especially pancreatic ductal adenocarcinoma, is one of the most serious and deadly cancers. Its outlook is very poor, with fewer than 10% of patients surviving five years after diagnosis. This is largely because the disease is often discovered at a late stage and because it frequently comes back even after surgery.

When the tumor is located in the head of the pancreas, the only treatment that can potentially cure the disease is a major operation called a pancreaticoduodenectomy, also known as the Whipple procedure. This surgery is now safely performed in specialized hospitals, but it remains complex and carries a high risk of complications. Importantly, even after surgery, cancer cells often remain, leading to a high rate of local recurrence.

A newer surgical technique, known as the "artery-first" approach, changes the order of the operation. By carefully exposing a major blood vessel near the pancreas at the beginning of the surgery, surgeons can better assess whether the tumor can be completely removed and can improve the precision of the operation.

This research protocol aims to compare this artery-first technique with the standard surgical approach. The goal is to determine whether starting the operation by addressing the artery allows for more complete tumor removal and reduces the risk of cancer coming back in patients with pancreatic cancer of the head of the pancreas."

"Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second leading cause of cancer death in the United States and Europe by 2030. It remains the worst prognostic gastrointestinal cancer, with a 7-9% five-year overall survival (OS) rate. The majority of patients are diagnosed at an advanced stage, i.e., locally advanced (30%) or metastatic (50%), and more than 60% of the operated patients relapse within 3 years after surgery.

Pancreaticoduodenectomy: standard approach Pancreaticoduodenectomy (PD) is the only potentially curative technique for PDAC of the pancreatic head. The procedure, commonly named the Whipple procedure, was described in 1935 when O.Whipple reported the previously modified technique by A.Codinivillan and W.Keusch. In its current form, the Whipple procedure owes its evolution to many physicians and surgeons' groundbreaking and innovative work. The procedure is now performed with an acceptable mortality rate of < 4% in expert centers and and nevertheless 30% morbidity.

Pancreaticoduodenectomy: SMA first approach, peri-adventitial dissection Whipple procedure with mesenteric first approach is a technique described and validated in surgery for pancreatic adenocarcinoma. This technique, which involves dissecting the peri-adventitial tissues of the superior mesenteric artery, has been reported mainly in borderline or locally advanced tumors of the head of the pancreas, to control the artery and improve the quality of the resection. This technique allows exposure of the right hemicircumference of the artery and clearance of the origin of the celiac trunk before sectioning the key elements of the duodenopancreatectomy cephalic.

Six surgical approaches that can be considered as "artery first" have been reported by Sanjay et al. Two approaches to avoid technical biases in SMA dissection and arterial margins will be considered: the right posterior approach and the anterior approach.

Although PD is mature, the low R0 resection rate remains a major issue, and most patients will develop a local recurrence, as demonstrated by autopsy studies.

The investigators hypothesise that the SMA first approach (SMA-PD) improves R0 resection margins compared to the standard procedure (ST-PD) during PD in patients with pancreatic head adenocarcinoma."

Inclusion Criteria:

1. Primary resectable or borderline with isolated veinous contact pancreatic adenocarcinoma (according to the NCCN classification and international consensual definition of Isaji 2018): resectability is evaluated on arterial-phase and portal-phase IV contrast-enhanced multislice CT scan of the pancreas (slice thickness: 2.5 mm), and assessed in a multidisciplinary staff meeting including at least one radiologist and one expert surgeon.
2. CT-scan of the thorax and abdomen confirming non-metastatic PAC at least 45 days before inclusion
3. MRI of the liver without metastasis performed maximum one month before inclusion
4. CA 19.9 (carbohydrate antigen) level ≤ 500 U/mL at the time of inclusion (in absence of cholestasis or biliary drainage)
5. Age 18 or over
6. Grade 0 or 1 Performans Status (ECOG)
7. Normal renal and liver function at the time of inclusion (According to Cockroft and Gault's equation Glomerular Function Rate > 50ml/min/m2; Prothrombin Time > 70%)
8. Absolute neutrophil count > 1,500/mm3, platelet count > 100,000/mm3, haemoglobin level > 10 g/dl (transfusions are authorized) at time of inclusion
9. Adequate contraception on fertile women
10. "Women of childbearing potential (defined as under 50 years of age and without a history of hysterectomy or tubal ligation) must not self-report being pregnant on the day of inclusion."
11. Patient who provides a signed written informed consent form
12. Patient having the rights to French social insurance

Exclusion Criteria:

1. Pancreatic adenocarcinoma defined as "borderline" with arterial contact, locally advanced, non-resectable, or metastatic.

2. Surgical or anesthesiologic contra-indications:

   Non-controlled congestive heart failure - non-treated angina - recent myocardial infarction (in the previous year) - non-controlled AHT (SBP >160 mm or DBP > 100 mm, despite optimal drug treatment), long QT

3. Major non-controlled infection

4. Major comorbidity that may preclude the surgery

5. Severe liver failure

6. Any medical, psychological, or social situation that (in the investigator's opinion) could limit (i) the patient's compliance with the protocol or (ii) the ability to obtain or interpret data

7. Pregnant or breastfeeding women and women of childbearing age not using effective means of contraception

8. Curatorship or guardianship or patient placed under judicial protection

9. Participation in other interventional research type 1, clinical investigation or clinical trial during the study

Secondary exclusion criterion (during surgery):

1. Evaluation of abdominal cavity, presenting infra-radiologic metastasis
2. Positive tumoral invasion at frozen section after picking on the inter-aortic lymph nodes performed before any irrevocable organ section.
3. Anasthaesiologic complication (induction allergy or unprevisible heart disease at induction)
4. For fertile women: serological pregnancy test positive before surgery