Prognostic Outcomes of Total Mesopancreas Excision for Pancreatic Head Cancer

Prognostic Outcomes of Total Mesopancreas Excision During Pancreaticoduodenectomy for Pancreatic Head Cancer

Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis due to high recurrence rates after standard pancreaticoduodenectomy (PD). The concept of Total Mesopancreas Excision (TMpE), analogous to total mesorectal excision, aims to improve oncological outcomes by achieving higher R0 resection rates through the comprehensive removal of retroperitoneal connective tissue surrounding major peripancreatic vessels. This single arm prospective study will evaluate the prognostic outcomes, primarily Disease- Free Survival (DFS) at 24 months, of a standardized TMpE technique performed during pancreaticoduodenectomy for resectable pancreatic head cancer. Secondary objectives include assessing Overall Survival (OS), R0 resection rates, recurrence patterns, and perioperative outcomes in 90 consecutive patients.

Pancreatic duct adenocarcinoma (PDAC) is one of the most aggressive malignancies, with a 5-year overall survival rate of approximately 20-25% even after curative resection. Standard pancreaticoduodenectomy (PD, or Whipple procedure) often results in high rates of local recurrence (up to 40-50%) due to incomplete clearance of peripancreatic tissues, leading to R1 resections in 15-35% of cases. The concept of the "mesopancreas" was introduced by Gockel et al. in 2007 as an anatomical entity analogous to the mesorectum in rectal cancer surgery. Excision of the mesopancreas aims to achieve total en bloc removal of retroperitoneal tissues harboring lymphatic, neural, and vascular pathways for tumor spread, potentially improving R0 resection rates (to 80-90%), reducing local recurrence (to 15-20%), and enhancing survival. Existing retrospective and meta-analyses suggest that total mesopancreatic excision (TMpE) increases R0 rates and reduces locoregional recurrence while maintaining acceptable safety. However, prospective data are limited, and no large randomized trials exist. This study prospectively evaluates TMpE in resectable PDAC to assess its impact on local control and survival . Objectives

Primary Objectives:

• To determine disease-free survival (DFS).

Secondary Objectives:

• To assess the impact of TMpE on overall survival (OS).
• To evaluate R0 resection rates and surgical morbidity.
• To identify predictors of recurrence and survival through preoperative,intraoperative, and postoperative data.

DEFINITION OF MESOPANCREAS The mesopancreas is defined as the retropancreatic tissue located posterior to the pancreatic head, encompassing:

• Anatomical boundaries: Inverted triangle with apex at the origins of celiac trunk (CT), hepatic artery, and superior mesenteric artery (SMA), and base at the posterior aspect of superior mesenteric vein(SMV) and portal vein(PV)
• Tissue components: Adipose tissue, peripheral nerves and plexuses, vascular structures, lymphogenic structures, and locoregional lymph nodes
• Alternative nomenclature: "Pancreatic head plexus", "retroportal lamina", "mesopancreatoduodenum"
• Surgical margins: Includes retroperitoneal, uncinate, posterior, and portal vein groove margins This structure is the primary site for positive resection margins (R1) in PDAC and is implicated in locoregional spread.
• Level of Dissection: The extent of mesopancreatic dissection can vary:
• Level 1: Dissection close to the pancreatic capsule.
• Level 2: Dissection along the superior mesenteric vein and portal vein.
• Level 3 (Total Mesopancreas Excision): it involves dissecting along the entire length of the SMA and celiac axis, removing all lymphatic and neural tissue surrounding these vessels.
• Mesopancreatic Excision (TMpE, Level 3):
• After pancreatic neck transection, focus on posterior dissection.
• Identify the mesopancreas as the retroperitoneal fibro-fatty tissue posterior to the pancreatic head.
• Dissect along the right aspect of the SMA, exposing its origin from the aorta.
• Extend dissection to the celiac trunk and right celiac ganglion, resecting nerve plexuses (e.g., plexus pancreaticus I and II).
• Clear the aorto-caval groove laterally, including para-aortic lymph nodes (stations 16a2/b1 if involved).
• En bloc removal of the mesopancreas: triangular resection bounded by portal vein /SMV (medial), SMA/celiac axis (posterior), and pancreatic head (anterior). Includes all lymphatic, neural, and fatty tissues up to the anterior aortic surface.
• Ensure circumferential margin clearance: frozen section if needed for pancreatic neck, bile duct, and posterior margins.
• Vascular skeletonization: clear adventitia of SMA and celiac trunk.

Inclusion Criteria:

• Age ≥18 years.
• Patients scheduled to undergo pancreaticoduodenectomy with planned mesopancreatic excision.
• Histologically confirmed PDAC of the pancreatic head (via endoscopic ultrasound-guided biopsy).
• Resectable disease per National Comprehensive Cancer Network(NCCN) guidelines (no distant metastases, no arterial involvement >180°, venous involvement reconstructable).
• Eastern Cooperative Oncology Group(ECOG) performance status 0-2.
• Adequate organ function (e.g., bilirubin <1.5x upper limit of normal(ULN), creatinine clearance >50 mL/min).
• Informed consent.

Exclusion Criteria:

• Irresectable PDAC.
• Distant metastases.
• Periampullary tumors other than pancreatic adenocarcinoma
• Prior neoadjuvant chemotherapy or radiotherapy (to isolate TMpE effect;may be amended for subgroups).
• Active second malignancy.
• Severe comorbidities precluding surgery (e.g., uncontrolled cardiac disease).
• Pregnancy or lactation.
• Patients who have received prior radiotherapy to the abdomen.
• Patients unwilling or unable to provide informed consent.