Prognostic Outcomes of Total Mesopancreas Excision for Pancreatic Head Cancer (TMpE)

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.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Ductal Adenocarcinoma; Pancreatic Head Cancer
• Intervention / Treatment: Procedure: Total Mesopancreas Excision (TMpE)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Saleh K Saleh, MD; Phone Number: +2 01201765401; Email: salehkhairy@mu.edu.eg

Study Locations

• Egypt
  • Minya Governorate
    • Minya, Minya Governorate, Egypt, 61519
      • Recruiting
      • Liver and GIT hospital , Minia University
      • Contact: Saleh K Saleh, MD; Phone Number: +2 01201765401; Email: salehkhairy@mu.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Total Mesopancreas Excision (TMpE); Patients with resectable or borderline resectable pancreatic head cancer undergoing pancreaticoduodenectomy with curative intent.

Procedure: Total Mesopancreas Excision (TMpE); All patients undergo pancreaticoduodenectomy with total mesopancreatic excision (TMpE) and Adjuvant chemotherapy. -Meticulous dissection and en bloc removal of the fatty tissue and perineural lymphatic layer located between the head of the pancreas and the superior mesenteric vessels (superior mesenteric artery and portal vein) and the celiac axis, performed during pancreaticoduodenectomy.; Other Names: TMpE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-Free Survival (DFS)	Time from surgery to first evidence of local recurrence, distant metastases, or death from any cause, whichever occurs first.	24 months post-surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
R0 Resection Rate	Complete microscopic removal of the tumor with all surgical margins (including mesopancreatic margin) free of tumor cells. Assessed according to standardized protocols (e.g., College of American Pathologists guidelines). The status of all margins (proximal, distal, circumferential, and mesopancreatic) will be recorded.	Within 30 days post-surgery (Pathology report)
Lymph Node Yield and Ratio	To quantify the total number of lymph nodes harvested and the ratio of positive to total lymph nodes.	Within 30 days post-surgery (Pathology report)
Completeness of Mesopancreas Excision	Assessment through detailed pathological evaluation.	Within 30 days post-surgery (Pathology report)
Overall Survival (OS)	Time from surgery to death from any cause.	Up to 24 months post-surgery
Prognostic Factors	Identification of factors (preoperative, intraoperative,and pathological) associated with DFS and OS.	Up to 24 months post-surgery
Recurrence-Free Survival (RFS)	Time from the date of surgery to the date of first recurrence (local, regional, or distant).Calculated in months from the date of surgery. Recurrence will be confirmed by imaging (CT/MRI), biopsy, or clinical assessment. Patients without recurrence will be censored at the last follow-up date.	Up to 2 years post-surgery
Local Disease Control	Defined as tumor recurrence in the pancreatic bed, retroperitoneum, or regional nodes (via CT/MRI/ positron emission tomography (PET)-CT). Assessed by RECIST 1.1 criteria. Time-to-recurrence was calculated from surgery date to detection date.	Up to 2 years post-surgery (assessed at 3, 6, 12, 18 and 24 months).]

Collaborators and Investigators

• Sponsor: Minia University
• Investigators: Principal Investigator: Saleh K Saleh, MD, Minia University

Publications and helpful links

General Publications

• Safi SA, Haeberle L, Fluegen G, Lehwald-Tywuschik N, Krieg A, Keitel V, Luedde T, Esposito I, Rehders A, Knoefel WT. Mesopancreatic excision for pancreatic ductal adenocarcinoma improves local disease control and survival. Pancreatology. 2021 Jun;21(4):787-795. doi: 10.1016/j.pan.2021.02.024. Epub 2021 Mar 17.
• Xu J, Tian X, Chen Y, Ma Y, Liu C, Tian L, Wang J, Dong J, Cui D, Wang Y, Zhang W, Yang Y. Total mesopancreas excision for the treatment of pancreatic head cancer. J Cancer. 2017 Sep 30;8(17):3575-3584. doi: 10.7150/jca.21341. eCollection 2017.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 20, 2027

Study Registration Dates

• First Submitted: November 13, 2025
• First Submitted That Met QC Criteria: November 15, 2025
• First Posted (Estimated): November 18, 2025

Study Record Updates

• Last Update Posted (Actual): December 2, 2025
• Last Update Submitted That Met QC Criteria: November 30, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Pancreatic Cancer; Pancreaticoduodenectomy; DFS; R0 Resection; TMpE; Total Mesopancreas Excision
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: 1702/09/2025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No