Surgical Approach for Adenocarcinoma of the Pancreas With Synchronous Liver Metastases

The study focuses on patients with synchronous liver metastasis from pancreatic adenocarcinoma that underwent both pancreatic and liver resection. The control group is made up of patients with resectable or borderline resectable pancreatic adenocarcinoma and synchronous liver metastasis that were excluded from surgery. Short and long-term outcomes will be compared to evaluate the safety and efficacy of simultaneous liver and pancreatic resection.

Study Overview

• Status: Completed
• Conditions: Pancreas Neoplasms; Pancreas Ductal Adenocarcinoma; Pancreatectomy; Liver Metastasis; Liver Resection; Surgery of the Pancreatic Head
• Intervention / Treatment: Procedure: Pancreatectomy and liver resection; Drug: Chemotherapy

Detailed Description

1. Summary:

   The study focuses on patients with synchronous liver metastasis from pancreatic adenocarcinoma that underwent both pancreatic and liver resection. The control group is made up of patients with resectable or borderline resectable pancreatic adenocarcinoma and synchronous liver metastasis that were excluded from surgery. Short and long-term outcomes will be compared to evaluate the safety and efficacy of simultaneous liver and pancreatic resection.

2. Introduction 2.1 Background and rationale The most common pathological pattern of pancreatic tumor is pancreatic ductal adenocarcinoma (PDAC), which accounts for approximately 90% of all cases. For digestive tract tumors such as colorectal, gastric, and pancreatic tumors, distant metastases often represent the last stage of the disease evolvement, and liver is a frequent disseminate site for metastatic tumor. Among them, only hepatic resection for metastatic disease has gained general acceptance as a potentially curative option in patients with colorectal cancer. The role of surgery for metastases from neuroendocrine tumors on long-term outcome is also well-documented. Recently, Markar et al. reported that surgical resection of hepatic metastases from gastric adenocarcinoma was associated with a significantly improved overall survival (p < 0.001). Moreover, they confirmed the additional survival benefit of solitary compared with multiple hepatic metastases (odds ratio = 0.31; p = 0.011). Liver resection showed longer survival rates also for pancreatic neuroendocrine tumor (PNET) patients.

   However, historical results regarding hepatic resection for PDAC were in conflicts and remained controversial. Furthermore, rare systematic review or meta-analysis was ever reported focusing on PDAC as a separate group. A recent meta-analysis reported that overall survival of PDAC patients can benefit from hepatic resection to some extent. It has been also recently showed that that surgical resection of pancreatic cancer with synchronous liver oligometastases is safe, and it can be associated with improved survival, providing a careful selection of patients after primary chemotherapy. Since a randomized controlled trial may be ethically questionable, a multicenter international retrospective study may clarify the role of liver resection in this cohort of patients.

   2.2 Objectives

   The primary aim is to examine recurrence free survival (RFS) and overall survival (OS) following surgical resection of synchronous hepatic metastases from PDAC, and to study the role of tumor burden and chemotherapy regimen on survival.

3. Methods:

3.1 Study design Patients underwent liver resection for synchronous metastases from pancreatic adenocarcinoma, single or multiple metastasis, will be included in the study, without any time interval limitation.

Clinical features, operative data and chemotherapy regimens will be analyzed. A control group of non-surgical patients will be included in the study for a propensity score match.

3.2 Setting

• No time interval limitation for recruitment
• No volume-based restriction for center eligibility 3.3 Participants Patients of age >18, underwent surgery for pancreatic adenocarcinoma (duodenopancreatectomy, distal pancreatectomy, total pancreatectomy) and liver resection (major or minor) for synchronous metastasis, that received neoadjuvant and/or adjuvant chemotherapy. The control group is made up of patients age >18 with resectable or borderline resectable pancreatic adenocarcinoma and synchronous liver metastasis that didn't underwent surgery.

• Study Type: Observational
• Enrollment (Actual): 90

Contacts and Locations

Study Locations

• Italy
  • Modena, Italy, 41124
    • AOU di Modena

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients underwent liver resection for synchronous metastases from pancreatic adenocarcinoma, single or multiple metastasis, will be included in the study, without any time interval limitation. Clinical features, operative data and chemotherapy regimens will be analyzed. A control group of non-surgical patients will be included in the study for a propensity score match. Setting

• No time interval limitation for recruitment
• No volume-based restriction for center eligibility

Description

Inclusion Criteria:

• Patients of age >18, underwent surgery for pancreatic adenocarcinoma (duodenopancreatectomy, distal pancreatectomy, total pancreatectomy) and liver resection (major or minor) for synchronous metastasis, that received neoadjuvant and/or adjuvant chemotherapy.
• The control group is made up of patients age >18 with resectable or borderline resectable pancreatic adenocarcinoma and synchronous liver metastasis that didn't underwent surgery.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Surgical group; Patients that underwent pancreatic and liver surgery	Procedure: Pancreatectomy and liver resection; Surgery for synchronous liver metastasis from PDAC with or without previous neoadjuvant chemotherapy
Non-surgical group; Patients that underwent CHT alone	Drug: Chemotherapy; Chemotherapy alone in potentially resectable patients with PDAC and synchronous liver metastasis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival	3 years
Recurrence-free survival	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-operative short-term outcomes 1	comprehensive complication index (using the online official CCI calculator that combines the events based on the Clavien-Dindo Classification)	90 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-operative short-term outcomes 2	ICU and in-hospital stay (days)	up to 100 weeks
Post-operative short-term outcomes 3 (histology)	surgical margin (in millimeters) and R status (R 0: no infiltration; R 1: microscopic infiltration; R 2: macroscopic infiltration) of pancreatic and hepatic specimens; nodal status (number of nodes sampled and number of positive nodes)	up to 100 weeks

Collaborators and Investigators

• Sponsor: Azienda Ospedaliero-Universitaria di Modena

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Actual): December 31, 2024
• Study Completion (Actual): December 31, 2024

Study Registration Dates

• First Submitted: April 7, 2025
• First Submitted That Met QC Criteria: May 12, 2025
• First Posted (Estimated): May 20, 2025

Study Record Updates

• Last Update Posted (Estimated): May 20, 2025
• Last Update Submitted That Met QC Criteria: May 12, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: metastases; metastasis; liver resection; PDAC; hepatectomy; synchronous; distal pancreatectomy; MIPS; whipple; RAMPS; ISLS
• Additional Relevant MeSH Terms: Endocrine System Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Neoplastic Processes; Carcinoma; Neoplasms, Second Primary; Neoplasm Metastasis; Pancreatic Neoplasms; Liver Neoplasms; Adenocarcinoma
• Other Study ID Numbers: 396/2021/OSS/AOUMO; ISLS pancreas study group (Other Identifier: ISLS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No