<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03305146</url>
  </required_header>
  <id_info>
    <org_study_id>2016-A01399-42</org_study_id>
    <nct_id>NCT03305146</nct_id>
  </id_info>
  <brief_title>Feasibility of Molecular Biology in Pancreatic Cyst Tumors</brief_title>
  <acronym>CYST-GEN</acronym>
  <official_title>Study of Feasibility and Diagnostic Profitability of Intra-cyst Fluid Molecular Biology Analysis in Pancreatic Cyst Tumors.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital St. Joseph, Marseille, France</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ramsay Générale de Santé</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Hospital St. Joseph, Marseille, France</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main objective of the study is to compare the diagnostic accuracy of intra-cystic fluid&#xD;
      DNA molecular analysis to standard diagnostics.&#xD;
&#xD;
      The secondary objective of the study is to evaluate the feasibility of intra-cystic fluid DNA&#xD;
      molecular analysis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Multicenter study to determinate the feasibility of intra-cystic fluid DNA molecular analysis&#xD;
      in patients with suspected cystic tumours of pancreas in whom EUS FNA is clinically&#xD;
      indicated.&#xD;
&#xD;
      Morphological criteria obtained by MRI and computerised tomography (tumor characterization&#xD;
      (size, metastases presence, dilatation of bile ducts), etiologic diagnosis, serious&#xD;
      symptoms), biological exams (biomarkers), cytological analysis will lead to a diagnosis and a&#xD;
      treatment.&#xD;
&#xD;
      The goal of this study is to compare this standard diagnostic modalities to diagnosis&#xD;
      obtained by intra-cystic fluid DNA molecular analysis.&#xD;
&#xD;
      Is the DNA molecular analysis improve the diagnosis accuracy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 2017</start_date>
  <completion_date type="Anticipated">January 2027</completion_date>
  <primary_completion_date type="Actual">December 2017</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>First 20 patients for pilot study to test the feasibility of the molecular analysis then 120 patients to continue the trial.</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Comparison between gene mutations found into the pancreatic cystic tumor fluid to gene mutations found into tissue specimen</measure>
    <time_frame>10 days</time_frame>
    <description>The nucleic acids of the samples will be extracted and then sequenced on a panel of about 70 genes implicated in the pancreatic tumorigenesis and targeting RAS, MAPK, AKT, JAK-STAT, WNT, TGFB, TP53 and Repair BRCA, ATM. The selected sequencing technology (HaloPlexHS ®, Agilent) will be used. A comparison of the molecular profiles between the cystic fluid and the surgical specimen will be carried out and then confronted with the pathology, biological, radiological and clinical characterization</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluate the feasibility of the molecular biology analysis of the pancreatic cystic tumor fluid to distinguish the pancreatic cysts.</measure>
    <time_frame>up to 6 months</time_frame>
    <description>The nucleic acids of the samples will be extracted from the different cyst fluids and then sequenced. A comparison of the molecular profiles between the different cystic fluids will be carried out and then confronted with the pathology, biological, radiological and clinical characterization</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">93</enrollment>
  <condition>Pancreatic Cyst</condition>
  <condition>Pancreas Cyst</condition>
  <condition>Serous Cystadenoma</condition>
  <condition>Mucinous Cystadenoma</condition>
  <condition>IPMN</condition>
  <arm_group>
    <arm_group_label>single arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>For inoperable patients with indeterminate cystic lesions of the pancreas,a EUS FNA will be performed and molecular biology analysis of pancreatic intra-cyst fluid collected by EUS FNA will be performed.&#xD;
For operable patients, after the pancreatic surgery, molecular biology analysis of extemporaneous pancreatic tissue specimen biopsy will be conducted.</description>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>Molecular biology analysis of pancreatic intra-cyst fluid</intervention_name>
    <description>The EUS FNA will be performed according to the Francophone Club of Echo Endoscopy recommendations.&#xD;
For molecular biology technique, the samples will be processed within the UMR_S910 unit. Nucleic acids will be extracted from the intra-cystic fluid or, for post-operative patients, from a resected specimen that will be collected into a tube containing a nucleic acid stabilization solution (Allprotect Tissue reagent, Qiagen).&#xD;
The nucleic acids will be extracted and then sequenced. The sequencing technology chosen (HaloPlexHS, Agilent) allows a detection close to 1% in allelic frequency. This new technical approach that links high sensitivity and specificity is also suitable with degraded and/or low-volume ( &lt;50ng) DNA.</description>
    <arm_group_label>single arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient older than 18 years of age, male or female&#xD;
&#xD;
          -  Cystic tumor of the pancreas requiring a puncture under endoscopic control to&#xD;
             determine the etiologic diagnosis and gravity.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Doubts regarding the etiological diagnosis of the pancreatic cyst&#xD;
&#xD;
          -  Contraindications for the realization of a high digestive endoscopy&#xD;
&#xD;
          -  Haemorrhagic disorder, haemostasis and coagulation disorder (TP &lt;60%, TCa&gt; 40 sec and&#xD;
             platelets &lt;60000 / mm3).&#xD;
&#xD;
          -  AVK, AOD and AAP cannot be stopped&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Arthur Laquière, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>French Society of Digestive Endoscopy</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clinique de Bercy</name>
      <address>
        <city>Charenton-le-Pont</city>
        <zip>94220</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Universitaire Dupuytren</name>
      <address>
        <city>Limoges</city>
        <zip>87000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Edouard Herriot</name>
      <address>
        <city>Lyon</city>
        <zip>69003</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Mermoz</name>
      <address>
        <city>Lyon</city>
        <zip>69008</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Europeen</name>
      <address>
        <city>Marseille</city>
        <zip>13003</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Saint Joseph</name>
      <address>
        <city>Marseille</city>
        <zip>13008</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chu La Timone</name>
      <address>
        <city>Marseille</city>
        <zip>13385</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU NANTES Institut des Maladies de l'Appareil Digestif</name>
      <address>
        <city>Nantes</city>
        <zip>44000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chu L'Archet 2</name>
      <address>
        <city>Nice</city>
        <zip>06200</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Saint Joseph</name>
      <address>
        <city>Paris</city>
        <zip>75014</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Jacques Lacarin</name>
      <address>
        <city>Vichy</city>
        <zip>03207</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <reference>
    <citation>Lee KS, Sekhar A, Rofsky NM, Pedrosa I. Prevalence of incidental pancreatic cysts in the adult population on MR imaging. Am J Gastroenterol. 2010 Sep;105(9):2079-84. doi: 10.1038/ajg.2010.122. Epub 2010 Mar 30.</citation>
    <PMID>20354507</PMID>
  </reference>
  <reference>
    <citation>Farrell JJ, Fernandez-del Castillo C. Pancreatic cystic neoplasms: management and unanswered questions. Gastroenterology. 2013 Jun;144(6):1303-15. doi: 10.1053/j.gastro.2013.01.073.</citation>
    <PMID>23622140</PMID>
  </reference>
  <reference>
    <citation>Terris B, Ponsot P, Paye F, Hammel P, Sauvanet A, Molas G, Bernades P, Belghiti J, Ruszniewski P, Flejou JF. Intraductal papillary mucinous tumors of the pancreas confined to secondary ducts show less aggressive pathologic features as compared with those involving the main pancreatic duct. Am J Surg Pathol. 2000 Oct;24(10):1372-7. doi: 10.1097/00000478-200010000-00006.</citation>
    <PMID>11023098</PMID>
  </reference>
  <reference>
    <citation>Crippa S, Fernandez-Del Castillo C, Salvia R, Finkelstein D, Bassi C, Dominguez I, Muzikansky A, Thayer SP, Falconi M, Mino-Kenudson M, Capelli P, Lauwers GY, Partelli S, Pederzoli P, Warshaw AL. Mucin-producing neoplasms of the pancreas: an analysis of distinguishing clinical and epidemiologic characteristics. Clin Gastroenterol Hepatol. 2010 Feb;8(2):213-9. doi: 10.1016/j.cgh.2009.10.001. Epub 2009 Oct 14.</citation>
    <PMID>19835989</PMID>
  </reference>
  <reference>
    <citation>Marchegiani G, Mino-Kenudson M, Sahora K, Morales-Oyarvide V, Thayer S, Ferrone C, Warshaw AL, Lillemoe KD, Fernandez-Del Castillo C. IPMN involving the main pancreatic duct: biology, epidemiology, and long-term outcomes following resection. Ann Surg. 2015 May;261(5):976-83. doi: 10.1097/SLA.0000000000000813.</citation>
    <PMID>24979607</PMID>
  </reference>
  <reference>
    <citation>Tanaka M, Fernandez-del Castillo C, Adsay V, Chari S, Falconi M, Jang JY, Kimura W, Levy P, Pitman MB, Schmidt CM, Shimizu M, Wolfgang CL, Yamaguchi K, Yamao K; International Association of Pancreatology. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology. 2012 May-Jun;12(3):183-97. doi: 10.1016/j.pan.2012.04.004. Epub 2012 Apr 16.</citation>
    <PMID>22687371</PMID>
  </reference>
  <reference>
    <citation>Brugge WR, Lewandrowski K, Lee-Lewandrowski E, Centeno BA, Szydlo T, Regan S, del Castillo CF, Warshaw AL. Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study. Gastroenterology. 2004 May;126(5):1330-6. doi: 10.1053/j.gastro.2004.02.013.</citation>
    <PMID>15131794</PMID>
  </reference>
  <reference>
    <citation>Serikawa M, Sasaki T, Fujimoto Y, Kuwahara K, Chayama K. Management of intraductal papillary-mucinous neoplasm of the pancreas: treatment strategy based on morphologic classification. J Clin Gastroenterol. 2006 Oct;40(9):856-62. doi: 10.1097/01.mcg.0000225609.63975.6f.</citation>
    <PMID>17016145</PMID>
  </reference>
  <reference>
    <citation>Bournet B, Kirzin S, Carrere N, Portier G, Otal P, Selves J, Musso C, Suc B, Moreau J, Fourtanier G, Pradere B, Lazorthes F, Escourrou J, Buscail L. Clinical fate of branch duct and mixed forms of intraductal papillary mucinous neoplasia of the pancreas. J Gastroenterol Hepatol. 2009 Jul;24(7):1211-7. doi: 10.1111/j.1440-1746.2009.05826.x. Epub 2009 May 19.</citation>
    <PMID>19476563</PMID>
  </reference>
  <reference>
    <citation>Sugiyama M, Izumisato Y, Abe N, Masaki T, Mori T, Atomi Y. Predictive factors for malignancy in intraductal papillary-mucinous tumours of the pancreas. Br J Surg. 2003 Oct;90(10):1244-9. doi: 10.1002/bjs.4265.</citation>
    <PMID>14515294</PMID>
  </reference>
  <reference>
    <citation>Kanno A, Satoh K, Hirota M, Hamada S, Umino J, Itoh H, Masamune A, Asakura T, Shimosegawa T. Prediction of invasive carcinoma in branch type intraductal papillary mucinous neoplasms of the pancreas. J Gastroenterol. 2010 Sep;45(9):952-9. doi: 10.1007/s00535-010-0238-0. Epub 2010 Apr 10.</citation>
    <PMID>20383536</PMID>
  </reference>
  <reference>
    <citation>Crippa S, Salvia R, Warshaw AL, Dominguez I, Bassi C, Falconi M, Thayer SP, Zamboni G, Lauwers GY, Mino-Kenudson M, Capelli P, Pederzoli P, Castillo CF. Mucinous cystic neoplasm of the pancreas is not an aggressive entity: lessons from 163 resected patients. Ann Surg. 2008 Apr;247(4):571-9. doi: 10.1097/SLA.0b013e31811f4449.</citation>
    <PMID>18362619</PMID>
  </reference>
  <reference>
    <citation>Cizginer S, Turner BG, Bilge AR, Karaca C, Pitman MB, Brugge WR. Cyst fluid carcinoembryonic antigen is an accurate diagnostic marker of pancreatic mucinous cysts. Pancreas. 2011 Oct;40(7):1024-8. doi: 10.1097/MPA.0b013e31821bd62f. Erratum In: Pancreas. 2013 May;42(4):728. Turner, Brian [corrected to Turner, Brian G].</citation>
    <PMID>21775920</PMID>
  </reference>
  <reference>
    <citation>Sahora K, Mino-Kenudson M, Brugge W, Thayer SP, Ferrone CR, Sahani D, Pitman MB, Warshaw AL, Lillemoe KD, Fernandez-del Castillo CF. Branch duct intraductal papillary mucinous neoplasms: does cyst size change the tip of the scale? A critical analysis of the revised international consensus guidelines in a large single-institutional series. Ann Surg. 2013 Sep;258(3):466-75. doi: 10.1097/SLA.0b013e3182a18f48.</citation>
    <PMID>24022439</PMID>
  </reference>
  <reference>
    <citation>Wu BU, Sampath K, Berberian CE, Kwok KK, Lim BS, Kao KT, Giap AQ, Kosco AE, Akmal YM, Difronzo AL, Yu W, Ngor EW. Prediction of malignancy in cystic neoplasms of the pancreas: a population-based cohort study. Am J Gastroenterol. 2014 Jan;109(1):121-9; quiz 130. doi: 10.1038/ajg.2013.334. Epub 2013 Oct 1.</citation>
    <PMID>24080609</PMID>
  </reference>
  <reference>
    <citation>Grobmyer SR, Cance WG, Copeland EM, Vogel SB, Hochwald SN. Is there an indication for initial conservative management of pancreatic cystic lesions? J Surg Oncol. 2009 Oct 1;100(5):372-4. doi: 10.1002/jso.21260.</citation>
    <PMID>19267387</PMID>
  </reference>
  <reference>
    <citation>Huang ES, Turner BG, Fernandez-Del-Castillo C, Brugge WR, Hur C. Pancreatic cystic lesions: clinical predictors of malignancy in patients undergoing surgery. Aliment Pharmacol Ther. 2010 Jan 15;31(2):285-94. doi: 10.1111/j.1365-2036.2009.04173.x. Epub 2009 Oct 21.</citation>
    <PMID>19845568</PMID>
  </reference>
  <reference>
    <citation>Crippa S, Bassi C, Salvia R, Malleo G, Marchegiani G, Rebours V, Levy P, Partelli S, Suleiman SL, Banks PA, Ahmed N, Chari ST, Fernandez-Del Castillo C, Falconi M. Low progression of intraductal papillary mucinous neoplasms with worrisome features and high-risk stigmata undergoing non-operative management: a mid-term follow-up analysis. Gut. 2017 Mar;66(3):495-506. doi: 10.1136/gutjnl-2015-310162. Epub 2016 Jan 7.</citation>
    <PMID>26743012</PMID>
  </reference>
  <reference>
    <citation>Springer S, Wang Y, Dal Molin M, Masica DL, Jiao Y, Kinde I, Blackford A, Raman SP, Wolfgang CL, Tomita T, Niknafs N, Douville C, Ptak J, Dobbyn L, Allen PJ, Klimstra DS, Schattner MA, Schmidt CM, Yip-Schneider M, Cummings OW, Brand RE, Zeh HJ, Singhi AD, Scarpa A, Salvia R, Malleo G, Zamboni G, Falconi M, Jang JY, Kim SW, Kwon W, Hong SM, Song KB, Kim SC, Swan N, Murphy J, Geoghegan J, Brugge W, Fernandez-Del Castillo C, Mino-Kenudson M, Schulick R, Edil BH, Adsay V, Paulino J, van Hooft J, Yachida S, Nara S, Hiraoka N, Yamao K, Hijioka S, van der Merwe S, Goggins M, Canto MI, Ahuja N, Hirose K, Makary M, Weiss MJ, Cameron J, Pittman M, Eshleman JR, Diaz LA Jr, Papadopoulos N, Kinzler KW, Karchin R, Hruban RH, Vogelstein B, Lennon AM. A combination of molecular markers and clinical features improve the classification of pancreatic cysts. Gastroenterology. 2015 Nov;149(6):1501-10. doi: 10.1053/j.gastro.2015.07.041. Epub 2015 Aug 4.</citation>
    <PMID>26253305</PMID>
  </reference>
  <reference>
    <citation>Al-Haddad MA, Kowalski T, Siddiqui A, Mertz HR, Mallat D, Haddad N, Malhotra N, Sadowski B, Lybik MJ, Patel SN, Okoh E, Rosenkranz L, Karasik M, Golioto M, Linder J, Catalano MF. Integrated molecular pathology accurately determines the malignant potential of pancreatic cysts. Endoscopy. 2015 Feb;47(2):136-42. doi: 10.1055/s-0034-1390742. Epub 2014 Oct 14.</citation>
    <PMID>25314329</PMID>
  </reference>
  <reference>
    <citation>Al-Haddad M, Wallace MB, Woodward TA, Gross SA, Hodgens CM, Toton RD, Raimondo M. The safety of fine-needle aspiration guided by endoscopic ultrasound: a prospective study. Endoscopy. 2008 Mar;40(3):204-8. doi: 10.1055/s-2007-995336. Epub 2007 Dec 4.</citation>
    <PMID>18058615</PMID>
  </reference>
  <reference>
    <citation>Boustiere C, Veitch A, Vanbiervliet G, Bulois P, Deprez P, Laquiere A, Laugier R, Lesur G, Mosler P, Nalet B, Napoleon B, Rembacken B, Ajzenberg N, Collet JP, Baron T, Dumonceau JM; European Society of Gastrointestinal Endoscopy. Endoscopy and antiplatelet agents. European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2011 May;43(5):445-61. doi: 10.1055/s-0030-1256317. Epub 2011 May 4.</citation>
    <PMID>21547880</PMID>
  </reference>
  <reference>
    <citation>Dumonceau JM, Polkowski M, Larghi A, Vilmann P, Giovannini M, Frossard JL, Heresbach D, Pujol B, Fernandez-Esparrach G, Vazquez-Sequeiros E, Gines A; European Society of Gastrointestinal Endoscopy. Indications, results, and clinical impact of endoscopic ultrasound (EUS)-guided sampling in gastroenterology: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Endoscopy. 2011 Oct;43(10):897-912. doi: 10.1055/s-0030-1256754. Epub 2011 Aug 12.</citation>
    <PMID>21842456</PMID>
  </reference>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>June 14, 2017</study_first_submitted>
  <study_first_submitted_qc>October 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 9, 2017</study_first_posted>
  <last_update_submitted>April 13, 2022</last_update_submitted>
  <last_update_submitted_qc>April 13, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hospital St. Joseph, Marseille, France</investigator_affiliation>
    <investigator_full_name>Arthur Laquiere</investigator_full_name>
    <investigator_title>Principal Investigator Dr Arthur LAQUIERE</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cysts</mesh_term>
    <mesh_term>Pancreatic Cyst</mesh_term>
    <mesh_term>Cystadenoma</mesh_term>
    <mesh_term>Cystadenoma, Mucinous</mesh_term>
    <mesh_term>Cystadenoma, Serous</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03305146
org study id: 2016-A01399-42
nct id: NCT03305146
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The main objective of the study is to compare the diagnostic accuracy of intra-cystic fluid
      DNA molecular analysis to standard diagnostics.

      The secondary objective of the study is to evaluate the feasibility of intra-cystic fluid DNA
      molecular analysis.
Multicenter study to determinate the feasibility of intra-cystic fluid DNA molecular analysis
      in patients with suspected cystic tumours of pancreas in whom EUS FNA is clinically
      indicated.

      Morphological criteria obtained by MRI and computerised tomography (tumor characterization
      (size, metastases presence, dilatation of bile ducts), etiologic diagnosis, serious
      symptoms), biological exams (biomarkers), cytological analysis will lead to a diagnosis and a
      treatment.

      The goal of this study is to compare this standard diagnostic modalities to diagnosis
      obtained by intra-cystic fluid DNA molecular analysis.

      Is the DNA molecular analysis improve the diagnosis accuracy.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: First 20 patients for pilot study to test the feasibility of the molecular analysis then 120 patients to continue the trial.
primary purpose: Diagnostic
masking: None (Open Label)
measure: Comparison between gene mutations found into the pancreatic cystic tumor fluid to gene mutations found into tissue specimen
time frame: 10 days
description: The nucleic acids of the samples will be extracted and then sequenced on a panel of about 70 genes implicated in the pancreatic tumorigenesis and targeting RAS, MAPK, AKT, JAK-STAT, WNT, TGFB, TP53 and Repair BRCA, ATM. The selected sequencing technology (HaloPlexHS ®, Agilent) will be used. A comparison of the molecular profiles between the cystic fluid and the surgical specimen will be carried out and then confronted with the pathology, biological, radiological and clinical characterization
measure: Evaluate the feasibility of the molecular biology analysis of the pancreatic cystic tumor fluid to distinguish the pancreatic cysts.
time frame: up to 6 months
description: The nucleic acids of the samples will be extracted from the different cyst fluids and then sequenced. A comparison of the molecular profiles between the different cystic fluids will be carried out and then confronted with the pathology, biological, radiological and clinical characterization
arm group label: single arm
arm group type: Experimental
description: For inoperable patients with indeterminate cystic lesions of the pancreas,a EUS FNA will be performed and molecular biology analysis of pancreatic intra-cyst fluid collected by EUS FNA will be performed.
For operable patients, after the pancreatic surgery, molecular biology analysis of extemporaneous pancreatic tissue specimen biopsy will be conducted.
intervention type: Genetic
intervention name: Molecular biology analysis of pancreatic intra-cyst fluid
description: The EUS FNA will be performed according to the Francophone Club of Echo Endoscopy recommendations.
For molecular biology technique, the samples will be processed within the UMR_S910 unit. Nucleic acids will be extracted from the intra-cystic fluid or, for post-operative patients, from a resected specimen that will be collected into a tube containing a nucleic acid stabilization solution (Allprotect Tissue reagent, Qiagen).
The nucleic acids will be extracted and then sequenced. The sequencing technology chosen (HaloPlexHS, Agilent) allows a detection close to 1% in allelic frequency. This new technical approach that links high sensitivity and specificity is also suitable with degraded and/or low-volume ( <50ng) DNA.
arm group label: single arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Arthur Laquière, MD
role: Principal Investigator
affiliation: French Society of Digestive Endoscopy
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: France
citation: Lee KS, Sekhar A, Rofsky NM, Pedrosa I. Prevalence of incidental pancreatic cysts in the adult population on MR imaging. Am J Gastroenterol. 2010 Sep;105(9):2079-84. doi: 10.1038/ajg.2010.122. Epub 2010 Mar 30.
PMID: 20354507
citation: Farrell JJ, Fernandez-del Castillo C. Pancreatic cystic neoplasms: management and unanswered questions. Gastroenterology. 2013 Jun;144(6):1303-15. doi: 10.1053/j.gastro.2013.01.073.
PMID: 23622140
citation: Terris B, Ponsot P, Paye F, Hammel P, Sauvanet A, Molas G, Bernades P, Belghiti J, Ruszniewski P, Flejou JF. Intraductal papillary mucinous tumors of the pancreas confined to secondary ducts show less aggressive pathologic features as compared with those involving the main pancreatic duct. Am J Surg Pathol. 2000 Oct;24(10):1372-7. doi: 10.1097/00000478-200010000-00006.
PMID: 11023098
citation: Crippa S, Fernandez-Del Castillo C, Salvia R, Finkelstein D, Bassi C, Dominguez I, Muzikansky A, Thayer SP, Falconi M, Mino-Kenudson M, Capelli P, Lauwers GY, Partelli S, Pederzoli P, Warshaw AL. Mucin-producing neoplasms of the pancreas: an analysis of distinguishing clinical and epidemiologic characteristics. Clin Gastroenterol Hepatol. 2010 Feb;8(2):213-9. doi: 10.1016/j.cgh.2009.10.001. Epub 2009 Oct 14.
PMID: 19835989
citation: Marchegiani G, Mino-Kenudson M, Sahora K, Morales-Oyarvide V, Thayer S, Ferrone C, Warshaw AL, Lillemoe KD, Fernandez-Del Castillo C. IPMN involving the main pancreatic duct: biology, epidemiology, and long-term outcomes following resection. Ann Surg. 2015 May;261(5):976-83. doi: 10.1097/SLA.0000000000000813.
PMID: 24979607
citation: Tanaka M, Fernandez-del Castillo C, Adsay V, Chari S, Falconi M, Jang JY, Kimura W, Levy P, Pitman MB, Schmidt CM, Shimizu M, Wolfgang CL, Yamaguchi K, Yamao K; International Association of Pancreatology. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology. 2012 May-Jun;12(3):183-97. doi: 10.1016/j.pan.2012.04.004. Epub 2012 Apr 16.
PMID: 22687371
citation: Brugge WR, Lewandrowski K, Lee-Lewandrowski E, Centeno BA, Szydlo T, Regan S, del Castillo CF, Warshaw AL. Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study. Gastroenterology. 2004 May;126(5):1330-6. doi: 10.1053/j.gastro.2004.02.013.
PMID: 15131794
citation: Serikawa M, Sasaki T, Fujimoto Y, Kuwahara K, Chayama K. Management of intraductal papillary-mucinous neoplasm of the pancreas: treatment strategy based on morphologic classification. J Clin Gastroenterol. 2006 Oct;40(9):856-62. doi: 10.1097/01.mcg.0000225609.63975.6f.
PMID: 17016145
citation: Bournet B, Kirzin S, Carrere N, Portier G, Otal P, Selves J, Musso C, Suc B, Moreau J, Fourtanier G, Pradere B, Lazorthes F, Escourrou J, Buscail L. Clinical fate of branch duct and mixed forms of intraductal papillary mucinous neoplasia of the pancreas. J Gastroenterol Hepatol. 2009 Jul;24(7):1211-7. doi: 10.1111/j.1440-1746.2009.05826.x. Epub 2009 May 19.
PMID: 19476563
citation: Sugiyama M, Izumisato Y, Abe N, Masaki T, Mori T, Atomi Y. Predictive factors for malignancy in intraductal papillary-mucinous tumours of the pancreas. Br J Surg. 2003 Oct;90(10):1244-9. doi: 10.1002/bjs.4265.
PMID: 14515294
citation: Kanno A, Satoh K, Hirota M, Hamada S, Umino J, Itoh H, Masamune A, Asakura T, Shimosegawa T. Prediction of invasive carcinoma in branch type intraductal papillary mucinous neoplasms of the pancreas. J Gastroenterol. 2010 Sep;45(9):952-9. doi: 10.1007/s00535-010-0238-0. Epub 2010 Apr 10.
PMID: 20383536
citation: Crippa S, Salvia R, Warshaw AL, Dominguez I, Bassi C, Falconi M, Thayer SP, Zamboni G, Lauwers GY, Mino-Kenudson M, Capelli P, Pederzoli P, Castillo CF. Mucinous cystic neoplasm of the pancreas is not an aggressive entity: lessons from 163 resected patients. Ann Surg. 2008 Apr;247(4):571-9. doi: 10.1097/SLA.0b013e31811f4449.
PMID: 18362619
citation: Cizginer S, Turner BG, Bilge AR, Karaca C, Pitman MB, Brugge WR. Cyst fluid carcinoembryonic antigen is an accurate diagnostic marker of pancreatic mucinous cysts. Pancreas. 2011 Oct;40(7):1024-8. doi: 10.1097/MPA.0b013e31821bd62f. Erratum In: Pancreas. 2013 May;42(4):728. Turner, Brian [corrected to Turner, Brian G].
PMID: 21775920
citation: Sahora K, Mino-Kenudson M, Brugge W, Thayer SP, Ferrone CR, Sahani D, Pitman MB, Warshaw AL, Lillemoe KD, Fernandez-del Castillo CF. Branch duct intraductal papillary mucinous neoplasms: does cyst size change the tip of the scale? A critical analysis of the revised international consensus guidelines in a large single-institutional series. Ann Surg. 2013 Sep;258(3):466-75. doi: 10.1097/SLA.0b013e3182a18f48.
PMID: 24022439
citation: Wu BU, Sampath K, Berberian CE, Kwok KK, Lim BS, Kao KT, Giap AQ, Kosco AE, Akmal YM, Difronzo AL, Yu W, Ngor EW. Prediction of malignancy in cystic neoplasms of the pancreas: a population-based cohort study. Am J Gastroenterol. 2014 Jan;109(1):121-9; quiz 130. doi: 10.1038/ajg.2013.334. Epub 2013 Oct 1.
PMID: 24080609
citation: Grobmyer SR, Cance WG, Copeland EM, Vogel SB, Hochwald SN. Is there an indication for initial conservative management of pancreatic cystic lesions? J Surg Oncol. 2009 Oct 1;100(5):372-4. doi: 10.1002/jso.21260.
PMID: 19267387
citation: Huang ES, Turner BG, Fernandez-Del-Castillo C, Brugge WR, Hur C. Pancreatic cystic lesions: clinical predictors of malignancy in patients undergoing surgery. Aliment Pharmacol Ther. 2010 Jan 15;31(2):285-94. doi: 10.1111/j.1365-2036.2009.04173.x. Epub 2009 Oct 21.
PMID: 19845568
citation: Crippa S, Bassi C, Salvia R, Malleo G, Marchegiani G, Rebours V, Levy P, Partelli S, Suleiman SL, Banks PA, Ahmed N, Chari ST, Fernandez-Del Castillo C, Falconi M. Low progression of intraductal papillary mucinous neoplasms with worrisome features and high-risk stigmata undergoing non-operative management: a mid-term follow-up analysis. Gut. 2017 Mar;66(3):495-506. doi: 10.1136/gutjnl-2015-310162. Epub 2016 Jan 7.
PMID: 26743012
citation: Springer S, Wang Y, Dal Molin M, Masica DL, Jiao Y, Kinde I, Blackford A, Raman SP, Wolfgang CL, Tomita T, Niknafs N, Douville C, Ptak J, Dobbyn L, Allen PJ, Klimstra DS, Schattner MA, Schmidt CM, Yip-Schneider M, Cummings OW, Brand RE, Zeh HJ, Singhi AD, Scarpa A, Salvia R, Malleo G, Zamboni G, Falconi M, Jang JY, Kim SW, Kwon W, Hong SM, Song KB, Kim SC, Swan N, Murphy J, Geoghegan J, Brugge W, Fernandez-Del Castillo C, Mino-Kenudson M, Schulick R, Edil BH, Adsay V, Paulino J, van Hooft J, Yachida S, Nara S, Hiraoka N, Yamao K, Hijioka S, van der Merwe S, Goggins M, Canto MI, Ahuja N, Hirose K, Makary M, Weiss MJ, Cameron J, Pittman M, Eshleman JR, Diaz LA Jr, Papadopoulos N, Kinzler KW, Karchin R, Hruban RH, Vogelstein B, Lennon AM. A combination of molecular markers and clinical features improve the classification of pancreatic cysts. Gastroenterology. 2015 Nov;149(6):1501-10. doi: 10.1053/j.gastro.2015.07.041. Epub 2015 Aug 4.
PMID: 26253305
citation: Al-Haddad MA, Kowalski T, Siddiqui A, Mertz HR, Mallat D, Haddad N, Malhotra N, Sadowski B, Lybik MJ, Patel SN, Okoh E, Rosenkranz L, Karasik M, Golioto M, Linder J, Catalano MF. Integrated molecular pathology accurately determines the malignant potential of pancreatic cysts. Endoscopy. 2015 Feb;47(2):136-42. doi: 10.1055/s-0034-1390742. Epub 2014 Oct 14.
PMID: 25314329
citation: Al-Haddad M, Wallace MB, Woodward TA, Gross SA, Hodgens CM, Toton RD, Raimondo M. The safety of fine-needle aspiration guided by endoscopic ultrasound: a prospective study. Endoscopy. 2008 Mar;40(3):204-8. doi: 10.1055/s-2007-995336. Epub 2007 Dec 4.
PMID: 18058615
citation: Boustiere C, Veitch A, Vanbiervliet G, Bulois P, Deprez P, Laquiere A, Laugier R, Lesur G, Mosler P, Nalet B, Napoleon B, Rembacken B, Ajzenberg N, Collet JP, Baron T, Dumonceau JM; European Society of Gastrointestinal Endoscopy. Endoscopy and antiplatelet agents. European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2011 May;43(5):445-61. doi: 10.1055/s-0030-1256317. Epub 2011 May 4.
PMID: 21547880
citation: Dumonceau JM, Polkowski M, Larghi A, Vilmann P, Giovannini M, Frossard JL, Heresbach D, Pujol B, Fernandez-Esparrach G, Vazquez-Sequeiros E, Gines A; European Society of Gastrointestinal Endoscopy. Indications, results, and clinical impact of endoscopic ultrasound (EUS)-guided sampling in gastroenterology: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Endoscopy. 2011 Oct;43(10):897-912. doi: 10.1055/s-0030-1256754. Epub 2011 Aug 12.
PMID: 21842456
responsible party type: Principal Investigator
investigator affiliation: Hospital St. Joseph, Marseille, France
investigator full name: Arthur Laquiere
investigator title: Principal Investigator Dr Arthur LAQUIERE
mesh term: Cysts
mesh term: Pancreatic Cyst
mesh term: Cystadenoma
mesh term: Cystadenoma, Mucinous
mesh term: Cystadenoma, Serous
sharing ipd: No