Mesopancreas Study in Pancreatic Cancer

Studien-Informationen Einschlusskriterien Studien-Rationale Studien-Arme Geprüfte Regime

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NCT-Nummer:
NCT05895214

Studienbeginn:
Juni 2023

Letztes Update:
08.06.2023

Wirkstoff:
-

Indikation (Clinical Trials):
Recurrence

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Heinrich-Heine University, Duesseldorf

Collaborator:
-

Studienleiter

Sami Alexander Safi, MD
Principal Investigator
Department of Surgery (A), University Hospital of Duesseldorf of the Heinrich Heine University Duesseldorf, Germany

Kontakt

Sami Alexander Safi, MD
Kontakt:
Phone: +4916097937947
E-Mail: safi@hhu.de» Kontaktdaten anzeigen

Studienlocations
(1 von 1)

University Hospital Duesseldorf, Heinrich Heine University
Duesseldorf
(Nordrhein-Westfalen)
Germany» Google-Maps

Studien-Informationen

Detailed Description:

For patients with a ductal adenocarcinoma of the pancreatic head (PDAC) pathological

evaluation of the pancreatoduodenectomy specimen has endured a redefined process. After the

Introduction of the pathological circumferential resection margin, residual cancer (R1

resection) was most often found in the dorsal and medial resection margins. Yet only the

medial resection margin is preoperatively evaluated by staging and utilized during assessment

of resectability. The dorsal resection margin which resides residual cancer (R1 resection) at

a similar rate compared to the medial resection margin, is not considered during preoperative

assessment for resectability. After the inclusion of the pathological LEEPP protocol true R0

resection rates have dropped to ~30%.

Next to the poor systemic tumor control and thus early detected relapse in PDAC patients,

local recurrence is evenly at risk and remains an ungoing dilemma. Revised pathological

outcome by the implemented LEEPP protocol explains the poor local tumor control.

The aim of this study is to interdisciplinary approach the circumferential infiltration

status of the PDAC concentrating foremost on the dorsal resection margin by including

anatomic and embryologic derived perspectives.

These perspectives have already been implemented by complete mesocolic and total mesorectal

excision. The mesocolon of the ascending colon is embedded dorsally by fascia sheets,

resulted by the embryologic fusion process, and the anatomic landmark of this fascia sheet

has gained significant clinical relevance for radical surgical resection (Toldt fascia for

total mesocolic excision). While surgical perspectives for the colorectal system have

included the anatomic and embryologic nature of the colon and rectum, these landmarks and the

idea of ''compartment anatomy'' are not implemented during pancreatoduodenectomy.

It seems rational to suggest that redefined surgical standards for colorectal cancer patients

with implemented fascial sheets as anatomic landmarks could be translated to the pancreas as

well. Similar to the ascending colon; the pancreas remains secondary retroperitoneal. The

Treitz fascia is a cranio-medial extension of the toldts fascia, which again is an anatomic

landmark for total mesocolic excision. The superior mesenteric artery serves as an anchor

point for the embryologic rotation process of the pancreas until it remains secondary

retroperitoneal. From an anatomic and embryologic point of view, there should not be any

doubt for the existence of a mesopancreas.

The medial resection margin after pancreatoduodenectomy is resembled mostly by the portal

confluens and does not embed any peripancreatic fat from the mesopancreas, underlining the

different embryologic anlage between the pancreas and the portal venous system. The

mesopancreas is located underneath the portal confluens, between the duodenum/pancreatic

tissue and the inferior caval vein/abdominal aorta and continually encompasses the SMA. The

dorsal resection margin during pancreatoduodenectomy resembles the mesopancreas and the aim

of this multicentric prospective study is to study the oncological relevance of the

mesopancreas.

Neoadjuvant therapy is a rising option for PDAC patients, and resectability criteria have

been implemented to adequately stage these patients prior to therapy initiation. Current

guidelines recommend to preoperatively investigate the medial vascular axis which represents

the medial vascular groove. Patients are therefore sub-grouped into primary resectable,

borderline resectable and non resectable mainly on the presumed infiltration status of the

portomesenteric system.

In summary, the infiltration status of the PDAC is mainly being concentrated on the vascular

groove. However, the dorsal resection margin, which is evenly at risk for incomplete

resection (CRM assessment), is not considered during resectability stratification. Steps to

secure or preoperatively assess this mesopancreatic area are not considered yet.

To stratify patients adequately for individualized therapy (neoadjuvant treatment vs surgery)

a circumferential assessment, is crucial. Yet a circumferential assessment of the PDAC is

provided only pathologically. In our opinion to realize a complete frame of tumor extensions

a circumferential assessment should be implemented radiographically and surgically as well.

This observational study in patients with a ductal adenocarcinoma of the pancreatic head

(PDAC) is of a prospective multicentric nature. In this study the mode of multimodal

treatment, pre-operative computed tomographic staging, biological status (CA-19-9 values) are

analyzed in a prospective consecutive treated patient cohort with respect to the infiltration

status of the mesopancreas. The infiltration status of the mesopancreas is

histopathologically analyzed while evaluating the dorsal resection margin for resection

margin status (status positive/negative, depth of invasion in mm, depth of mesopancreas in

mm, status of intact fascia sheet). No control group or placebo group exists.

The aim of this study is to analyze the oncological relevance of mesopancreatic fat

infiltration both in upfront resected and neoadjuvant treated PDAC patients and to evaluate

the feasibility of computed tomographic staging and preoperative serologic CA 19-9 values to

predict the mesopancreatic infiltration status.

The histopathological analysis in each study center is an obligatory tool in order to

postoperatively stage the PDAC. For this instance, the mesopancreatic fat infiltration status

is analyzed in each respective study center. The radiographic analysis of the mesopancreas

has yet not been standardized. For this mater, preoperative and peri-chemotherapeutic CT

slides are centrally evaluated by the leading study initiators.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- All patients age ≥18 years who are admitted for primary surgery or patients who

Received neoadjuvant therapy prior to surgery

- CRM analysis through Pathologic Institute in study centre already implemented (see

LEEPP protocol Menon et al (2009) Impact of margin status on survival following

pancreatoduodenectomy for cancer: the Leeds Pathology Protocol (LEEPP). HPB

11(1):18-24)

- Preoperative computed-tomographic Imaging (biphasic) prior to surgery (if resected

without neoadjuvant treatment)

- Pre-chemotherapeutic computed-tomographic and post-chemotherapeutic

computed-tomographic if neoadjuvantly treated (biphasic).

- indepth information of surgical procedure (pancreatic tail preserved:yes/no, pylorus

preserved resection: yes/no, venous resection: complete/partial/no, arterial

resection: complete/partial/no)

Exclusion Criteria:

- Palliation

- Abort of operative procedure

- No preoperative computed-tomography for staging

- No pathological CRM Implementation according to the LEEPP

Studien-Rationale

Primary outcome:

1. Rate of mesopancreatic infiltration in a multicentric setting. (Time Frame - through study completion, an average of 1 year):
Rate of mesopancreatic fat infiltration

2. Statistical comparison of the mesopancreatic infiltration status with known oncologically relevant histopathological staging factors: is there a more aggressive tumor biology or an unfavorable tumor topography (Time Frame - through study completion, an average of 1 year):
Status of MP infiltration (pathologically analysed) vs. UICC and AJCC staging system (questionnaire from pathological staging reporting)

3. Statistical comparison of mesopancreatic infiltration status with the CRM of the dorsal resection margin and with the entire CRM (Time Frame - through study completion, an average of 1 year):
Status of MP infiltration (pathologically analysed) vs. R-status (R0CRM- vs. R0CRM+/R1)(questionnaire from pathological staging reporting)

4. Prediction value of density analyses in computed tomography (Hounsfield Unit) with mesopancreatic infiltration status in primary and neoadjuvantly patients (Time Frame - through study completion, an average of 1 year):
Density score of mesopancreas (HU) vs. Infiltration status of MP (Hounsfield Unit scale resembles the density assessment during computed tomography)(Hypothesis: higher HU measurements indicate higher risk for mesopancreatic fat infiltration) (minimum HU value: air -1000HU, maximum HU value: gold +30000 HU)

Secondary outcome:

1. Rate of mesopancreatic infiltration in primary and borderline resectable pancreatic head carcinomas (classification of resectability using the well-known ABC scheme) (Time Frame - through study completion, an average of 1 year):
Status of MP infiltration vs. resectability status

2. Incidence rate of mesopancreatic infiltration between neoadjuvant treated and primary resected patients (matched-pairs analysis: both patient groups (neoadjuvant vs. primary resected) must have similar resectability criteria). (Time Frame - through study completion, an average of 1 year):
Status of MP infiltration vs. treatment protocol (matched pair analysis)

Studien-Arme

patients who received primary surgery
preoperative CT scans available for assessing resectability criteria and presumed mesopancreatic infiltration status (CT scans are centrally evaluated) UICC 8th edition staging including CRM Tumor size in mm measured twice perpendicular Age Sex CA 19-9 values (preoperative) ECOG status BMI Type of PD (tail preserved vs total PD) simultaneous vessel resection (complete, partial; combined arterial and venous)
patients who received neoadjuvant treatment prior to surgery
Peri-therapeutic CT scans available for assessing resectability criteria and presumed mesopancreatic infiltration status (CT scans are centrally evaluated) UICC 8th edition staging including CRM Tumor size in mm measured twice perpendicular Age Sex CA 19-9 values (peri-therapeutic) ECOG status BMI Type of neoadjuvant Therapy Type of PD (tail preserved vs total PD), simultaneous vessel resection (complete, partial; combined arterial and venous) Tumor response according to CAP

Geprüfte Regime

oncological relevance of the mesopancreas:
Invasion status Invasion depth in mm Depth of mesopancreas in mm Treitz fascia intact (histopathological examination)

Quelle: ClinicalTrials.gov

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