Para-aortic Lymphnodes Removal During Upfront Pancreaticoduodenectomy

NCT ID: NCT04571294

Last Updated: 2024-10-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-26
• Study Completion Date: 2025-05-31

Brief Summary

Pancreaticoduodenectomy (PD) associated with lymphadenectomy is the only curative option for patients affected by pancreatic ductal adenocarcinoma (PDAC). In 2014, the International Study Group on Pancreatic Surgery (ISGPS) defined the "standard lymphadenectomy", that is mandatory during PD for PDAC. Lymphadenectomy should include the removal of the hepatoduodenal ligament nodes (stations 5, 6, 12b1, 12b2, 12c according the classification of Japanese Pancreas Society), nodes along the hepatic artery (station 8a), the posterior surface of the pancreatic head (station 13a and 13b), the superior mesenteric artery (14a right lateral side, 14b right lateral side) and nodes of the anterior surface of the pancreatic head (stations 17a and 17b). The inclusion of para-aortic lymphnodes (PALN) (station 16) in standard lymphadenectomy is still matter of debate. Moreover, some retrospectives or prospective studies reported that the presence of PALN metastases has a significant negative prognostic impact. Until now, no randomized studies comparing PD associated with standard lymphadenectomy with or without removal of PALN have been published. The aim of this study is to evaluate if the removal of station 16 should be routinely included in standard lymphadenectomy during PD for PDAC.

Detailed Description

Pancreaticoduodenectomy (PD) with lymphadenectomy is the current treatment of pancreatic ductal adenocarcinoma (PDAC). The optimal lymphadenectomy during PD (standard versus extended) has been largely debated during the last two decades. Four randomized controlled trials (RCTs) published afterward reported no survival benefit, and no arguments could be presented based on the evidence of these studies to support the role of extended lymphadenectomy during PD. A similar conclusion was underlined also in two meta-analyses, the first from Michalski et al., in which 3 RCTs were analyzed, and the second from Iqbal et al., in which both RCTs and cohort studies were included, both of which showed no benefit of extended lymphadenectomy. However, the definition of lymphadenectomy varied considerably between the RCTs. For this reason, in 2014, the International Study Group on Pancreatic Surgery (ISGPS) defined the "standard lymphadenectomy" during PD for PDAC. Lymphadenectomy should include the removal of the hepatoduodenal ligament nodes (stations 5, 6, 12b1, 12b2, 12c according the classification of Japanese Pancreas Society), nodes along the hepatic artery (station 8a), the posterior surface of the pancreatic head (station 13a and 13b), the superior mesenteric artery (14a right lateral side, 14b left lateral side) and nodes of the anterior surface of the pancreatic head (stations 17a and 17b). Para-aortic lymph nodes (PALN; station 16) are considered as "extra-regional" lymph nodes. Some questions about PALN still remain open: a) should the removal of station 16 be routinely included in the standard lymphadenectomy during PD for PDAC? b) in case of removal of station 16 and intraoperative demonstration of PALN metastases at frozen section, should PD be avoided ? Several retrospective reports described that the prognosis of patients with metastatic PALN is significantly worse if compared with patients with negative PALN. Two recent-metaanalyses have been published on this topic, confirming that PALN metastases correlated with poor prognosis in patients with PDAC. However, these meta-analyses concluded that, due to the presence of some long survivors even in cases of PALN metastases, the definitive avoidance of PD in these cases needs further investigation. Until now, no consensus in case of intraoperative metastatic PALN has been reached. Moreover, it's not still clear if the removal of PALN during PD should be routinely performed. Until now, no randomized studies comparing PD with or without removal of PALN have been published. In 2014, during the consensus meeting of ISGPS, there was extensive discussion about PALN removal: no strong recommendation was formulated on dissecting station 16 routinely and it was not included in standard lymphadenectomy. For this reason, we decided to plan this multicentric RCT that compares upfront PD with and without the removal of PALN, in order to evaluate if their removal should be routinely included in standard lymphadenectomy during PD for PDAC.

Conditions

Pancreas Cancer; Pancreaticoduodenal Lymphadenopathy; Pancreas Adenocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

group A

PALN removal

Group Type: EXPERIMENTAL

removal of para-aortic lymphnodes (PALN)

Intervention Type: PROCEDURE

During pancreaticoduodenectomy, para-aortic lymphnodes (PALN) will be removed for the surgeon

group B

No PALN removal

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

removal of para-aortic lymphnodes (PALN)

During pancreaticoduodenectomy, para-aortic lymphnodes (PALN) will be removed for the surgeon

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• pre-operative radiological or histological diagnosis of pancreatic head PDAC, including PDAC arising from IPMN (invasive-IPMN) (in case of not confirmation of PDAC at final pathological examination, the case will be considered as a "drop out" and excluded from the study);
• upfront PD associated with standard lymphadenectomy.

Exclusion Criteria

• PD performed after neoadjuvant treatment;
• PALN metastases diagnosed by a pre-operative PET-FDG (if performed);
• intraoperative distant metastases;
• R2 resection.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Humanitas Hospital, Italy

OTHER

Sponsor Role: lead

Responsible Party

Alessandro Zerbi

Professor of Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Humanitas Research Hospital

Rozzano, Italy/Milan, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Gennaro Nappo, MD

Role: CONTACT

gennaro.nappo@humanitas.it

00393471926757

Facility Contacts

Gennaro Nappo, MD

Role: primary

gennaro.nappo@humanitas.it

+39(0)282247701

Other Identifiers

451/20

Identifier Type: -

Identifier Source: org_study_id