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

NCT03820531 | Completed

• 1 other identifier: ZYSTEUS-Study
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pancreas Cyst

Keywords

DNA Mutational Analysis; Cyst Fluid; Pancreas

Outcome Measures

Primary Outcomes (2)

• Patients with a mucinous pancreas cyst

  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

  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

Study Arms (1)

Suspected mucinous pancreas cyst

EXPERIMENTAL

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; Diagnostic Test: CEA and lipase; Diagnostic Test: Cytology; Diagnostic Test: Histology of resected pancreas cyst

Interventions

Next Generation Sequencing DIAGNOSTIC_TEST

DNA Mutational Analysis in pancreas cyst fluid concerning KRAS/GNAS-mutations and mutations in tumor supressor genes

Suspected mucinous pancreas cyst

CEA and lipase DIAGNOSTIC_TEST

Measuring CEA and lipase level in pancreas cyst fluid: CEA \> 192 ng/ml and lipase \> 200 U/l = mucinous cyst

Suspected mucinous pancreas cyst

Cytology DIAGNOSTIC_TEST

Cytology in pancreas cyst fluid: mucinous versus non-mucinous cyst; LGD versus HGD/Carcinoma

Suspected mucinous pancreas cyst

Histology of resected pancreas cyst DIAGNOSTIC_TEST

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

Suspected mucinous pancreas cyst

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• patients who are not fit for surgery

Sponsors & Collaborators

• Theresienkrankenhaus und St. Hedwig-Klinik GmbH: lead
• University Hospital Heidelberg: collaborator

Study Sites (1)

Tertiary referral hospital: Theresienkrankenhaus und St. Hedwig Hospital, Academic

Mannheim, 68165, Germany

Location

Related Publications (6)

• Felsenstein M, Noe M, Masica DL, Hosoda W, Chianchiano P, Fischer CG, Lionheart G, Brosens LAA, Pea A, Yu J, Gemenetzis G, Groot VP, Makary MA, He J, Weiss MJ, Cameron JL, Wolfgang CL, Hruban RH, Roberts NJ, Karchin R, Goggins MG, Wood LD. IPMNs with co-occurring invasive cancers: neighbours but not always relatives. Gut. 2018 Sep;67(9):1652-1662. doi: 10.1136/gutjnl-2017-315062. Epub 2018 Mar 2.

  PMID: 29500184 BACKGROUND

• Kanda M, Sadakari Y, Borges M, Topazian M, Farrell J, Syngal S, Lee J, Kamel I, Lennon AM, Knight S, Fujiwara S, Hruban RH, Canto MI, Goggins M. Mutant TP53 in duodenal samples of pancreatic juice from patients with pancreatic cancer or high-grade dysplasia. Clin Gastroenterol Hepatol. 2013 Jun;11(6):719-30.e5. doi: 10.1016/j.cgh.2012.11.016. Epub 2012 Nov 28.

  PMID: 23200980 BACKGROUND

• Singhi AD, McGrath K, Brand RE, Khalid A, Zeh HJ, Chennat JS, Fasanella KE, Papachristou GI, Slivka A, Bartlett DL, Dasyam AK, Hogg M, Lee KK, Marsh JW, Monaco SE, Ohori NP, Pingpank JF, Tsung A, Zureikat AH, Wald AI, Nikiforova MN. Preoperative next-generation sequencing of pancreatic cyst fluid is highly accurate in cyst classification and detection of advanced neoplasia. Gut. 2018 Dec;67(12):2131-2141. doi: 10.1136/gutjnl-2016-313586. Epub 2017 Sep 28.

  PMID: 28970292 BACKGROUND

• Rosenbaum MW, Jones M, Dudley JC, Le LP, Iafrate AJ, Pitman MB. Next-generation sequencing adds value to the preoperative diagnosis of pancreatic cysts. Cancer Cytopathol. 2017 Jan;125(1):41-47. doi: 10.1002/cncy.21775. Epub 2016 Sep 20.

  PMID: 27647802 BACKGROUND

• Amato E, Molin MD, Mafficini A, Yu J, Malleo G, Rusev B, Fassan M, Antonello D, Sadakari Y, Castelli P, Zamboni G, Maitra A, Salvia R, Hruban RH, Bassi C, Capelli P, Lawlor RT, Goggins M, Scarpa A. Targeted next-generation sequencing of cancer genes dissects the molecular profiles of intraductal papillary neoplasms of the pancreas. J Pathol. 2014 Jul;233(3):217-27. doi: 10.1002/path.4344.

  PMID: 24604757 BACKGROUND

• Volckmar AL, Endris V, Gaida MM, Leichsenring J, Stogbauer F, Allgauer M, von Winterfeld M, Penzel R, Kirchner M, Brandt R, Neumann O, Sultmann H, Schirmacher P, Rudi J, Schmitz D, Stenzinger A. Next generation sequencing of the cellular and liquid fraction of pancreatic cyst fluid supports discrimination of IPMN from pseudocysts and reveals cases with multiple mutated driver clones: First findings from the prospective ZYSTEUS biomarker study. Genes Chromosomes Cancer. 2019 Jan;58(1):3-11. doi: 10.1002/gcc.22682. Epub 2018 Oct 17.

  PMID: 30230086 BACKGROUND

MeSH Terms

Conditions

Pancreatic Cyst

Interventions

Cytological Techniques

Condition Hierarchy (Ancestors)

Cysts; Neoplasms; Pancreatic Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Christel Weiß, Prof.Dr.

  University of Heidelberg, Department of Medical Statistis

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: DNA-mutation analysis by Next Generation Sequencing is performed to identify IPMN pancreas cysts with LGD versus HGD/Carcinoma. Controls: non-neoplastic pancreas cysts and chronic pancreatitis with main duct dilation

Study Record Dates

• First Submitted: January 25, 2019
• First Posted: January 29, 2019
• Study Start: January 1, 2018
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2022
• Last Updated: December 20, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)