DNA-mutation Analysis in Cyst Fluid of Suspected Intraductal Papillary Mucinous Neoplasia of the Pancreas

December 17, 2022 updated by: Theresienkrankenhaus und St. Hedwig-Klinik GmbH

DNA-mutation Analysis by Next Generation Sequencing in Cyst Fluid of Suspected Intraductal Papillary Mucinous Neoplasia of the Pancreas Obtained by Endoscopic Ultrasound-guided Fine Needle Aspiration (ZYSTEUS-Study)

Diagnostic tools are needed to identify mucinous cysts for further evaluation or follow-up respectively to identify cysts with HGD or invasive cancer at an early stage for surgical resection. Molecular genetic analysis of pancreatic cyst fluid is a new but rapidly evolving method to identify KRAS/GNAS oncogenic driver mutations in mucinous cysts and to identify tumour suppressor gene mutations which are involved in advanced cysts with HGD or carcinoma. The ongoing ZYSTEUS-study tries to implement DNA mutation analysis by Next Generation Sequencing in the diagnostic algorithm of pancreas cyst evaluation. The first aim is to distinguish mucinous from non-mucinous cysts. The second aim is to define relevant tumour suppressor gene mutations which are relevant to distinguish between LGD and HGD/carcinoma in mucinous cysts.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Intraductal papillary mucinous neoplasm (IPMN) with low grade dysplasia (LGD) can progress to high grade dysplasia (HGD) or invasive cancer. Main duct IPMN, mixed type IPMN or branch duct IPMN with high risk stigmata are highly predictive for malignancy. Therefore, patients in good general state should be considered for surgical resection. Guidelines like the International Fukuoka Consensus Guidelines from 2017 or the European evidence-based Guidelines on Pancreatic cyst neoplasms from 2018 provide detailed recommendations on the management of IPMNs by focusing on clinical characteristics, image morphology, cytology and laboratory parameters. However, these applied guidelines still lead to surgical overtreatment of pancreas cysts based on the pathologic outcomes as neither HGD nor carcinoma is found in up to 82.1 % of the resected cysts. Cyst fluid sent for cytology usually provides adequate cellular material for analysis in only 31% of the cases and Endoscopic Ultrasound-guided forceps biopsy has not yet shown to be better than fine needle aspiration. Hence, further diagnostic tools are needed to identify mucinous cysts for further evaluation or follow-up respectively to identify cysts with HGD or invasive cancer at an early stage for surgical resection. Molecular genetic analysis of pancreatic cyst fluid is possibly able to identify KRAS/GNAS oncogenic driver mutations in mucinous cysts and to identify tumour suppressor gene mutations which are involved in advanced cysts with HGD or carcinoma. This workgroup described a high sensitive method of targeted Next Generation Sequencing in pancreas cyst fluid with a limit of detection of allele frequency down to 0.01 %. Further investigations of the ongoing ZYSTEUS-study are focused on the implementation of DNA mutation analysis by NGS in the diagnostic algorithm of pancreas cyst evaluation. The first aim is to reliably distinguish mucinous from non-mucinous cysts respectively main duct IPMN from chronic pancreatitis with main duct dilatation as the absence of KRAS/GNAS-mutations is highly predictive for non-mucinous diseases. The second aim is to define relevant tumour suppressor gene mutations which are relevant to differentiate LGD from HGD/carcinoma in mucinous cysts. DNA mutation analysis will be compared with already established peroperative diagnostic tests of pancreas cyst fluid: Measurement of CEA and lipase as well as cytology.

Study Type

Interventional

Enrollment (Actual)

150

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Mannheim, Germany, 68165
        • Tertiary referral hospital: Theresienkrankenhaus und St. Hedwig Hospital, Academic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • pancreas cysts with cyst size > 15mm
  • pancreas with main duct dilation > 5mm

Exclusion Criteria:

  • patients who are not fit for surgery

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Suspected mucinous pancreas cyst
In all pancreas cysts > 15mm and/or pancreas duct dilatation > 5mm in patients who are fit for surgery EUS-guided pancreas cyst fluid aspiration is conducted. In cyst fluid CEA and lipase examination, cytology and Next Generation Sequencing is performed. After that, the pancreas cyst will be resected and histopathologically analysed.
Diagnostic test: Next Generation Sequencing
DNA Mutational Analysis in pancreas cyst fluid concerning KRAS/GNAS-mutations and mutations in tumor supressor genes
Diagnostic test: CEA and lipase

Measuring CEA and lipase level in pancreas cyst fluid:

CEA > 192 ng/ml and lipase > 200 U/l = mucinous cyst

Diagnostic test: Cytology

Cytology in pancreas cyst fluid:

mucinous versus non-mucinous cyst; LGD versus HGD/Carcinoma

Diagnostic test: Histology of resected pancreas cyst
Histology of resected pancreas cyst concerning mucinous versus non-mucinous cyst, IPMN versus non-IPMN and LGD versus HGD/Carcinoma

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Patients with a mucinous pancreas cyst
Time Frame: From EUS-guided fine needle aspiration of pancreas cyst fluid up to seven days
Number of patients with the preoperative diagnosis of a mucinous pancreas cyst (numerator) in correlation with the number of patients with a mucinous pancreas cyst confirmed by surgery (denominator)
From EUS-guided fine needle aspiration of pancreas cyst fluid up to seven days
Pancreas cyst with HGD or carcinoma
Time Frame: From EUS-guided fine needle aspiration of pancreas cyst fluid up to seven days
Number of patients with the preoperative diagnosis of a HGD/carcinoma pancreas cyst (numerator) in correlation with the number of patients with a HGD/carcinoma pancreas cyst confirmed by surgery (denominator)
From EUS-guided fine needle aspiration of pancreas cyst fluid up to seven days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Theresienkrankenhaus und St. Hedwig-Klinik GmbH

Collaborators

University Hospital Heidelberg

Investigators

  • Study Chair: Christel Weiß, Prof.Dr., University of Heidelberg, Department of Medical Statistis

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2018

Primary Completion (Actual)

December 1, 2022

Study Completion (Actual)

December 1, 2022

Study Registration Dates

First Submitted

January 25, 2019

First Submitted That Met QC Criteria

January 25, 2019

First Posted (Actual)

January 29, 2019

Study Record Updates

Last Update Posted (Actual)

December 20, 2022

Last Update Submitted That Met QC Criteria

December 17, 2022

Last Verified

December 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ZYSTEUS-Study

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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