<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/NCT01734967</url>
  </required_header>
  <id_info>
    <org_study_id>herlev</org_study_id>
    <nct_id>NCT01734967</nct_id>
  </id_info>
  <brief_title>Needle-based Confocal Endomicroscopy Examination of Pancreatic Masse</brief_title>
  <official_title>Needle-based Confocal Endomicroscopy Examination of Pancreatic Masses</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Herlev Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Herlev Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Introduction: Pancreatic cancer is one of the most aggressive malignancies with only 5% of&#xD;
      patients being alive at five years. EUS (endoscopic ultra sound) is an established, sensitive&#xD;
      diagnostic tool in pancreatic cancer and for staging purposes. Additionally, EUS enables&#xD;
      guided fine needle aspiration (FNA), which is currently recommended as the first-line&#xD;
      procedure whenever a pathological diagnosis is required. However, EUS-FNA as a sampling&#xD;
      method has its drawbacks, due to a relatively low negative predictive value. Confocal laser&#xD;
      endomicroscopy has emerged in recent years as a novel method that enables in vivo microscopic&#xD;
      analysis during ongoing endoscopy. Recently, confocal laser endomicroscopy has gone beyond&#xD;
      the superficial luminal indications with the development of a new microprobe, i.e. a flexible&#xD;
      laser probe (nCLE) that can pass through a 19-gauge needle. Combined with EUS, descriptive&#xD;
      criteria for the diagnosis of pancreatic cystic neoplasm has been developed in a multicentre&#xD;
      trial. However, only a limited number of cases of solid pancreatic masses have been described&#xD;
      with nCLE.&#xD;
&#xD;
      Aim and Method: To describe confocal imaging criteria for pancreatic masses, lymph nodes or&#xD;
      liver metastases identified during EUS procedures performed for pancreatic cancer staging&#xD;
      (EUS-nCLE), while evaluating also the feasibility and safety of nCLE examination. The&#xD;
      hypothesis is that EUS-nCLE could allow targeted tissue sampling of pancreatic lesions&#xD;
      resulting in more accurate diagnosis. XX patients were included all presenting with a&#xD;
      clinical suspicion of pancreatic cancer or imaging studies showing a pancreatic mass. During&#xD;
      the procedure an nCLE preloaded 19G FNA needle was advanced into the lesion under EUS&#xD;
      guidance. A contrast agent was administered intravenously (2.5 ml fluorescein 10%). The data&#xD;
      was stored digitally for post procedural analysis. Afterwards EUS-FNA was performed for&#xD;
      cytology smears to enable a final pathological diagnosis. Correlations between the nCLE&#xD;
      images and the conventional pathology were identified.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background Pancreatic cancer is one of the most aggressive gastrointestinal malignancies with&#xD;
      mortality rates following closely the incidence rates. The incidence is increasing and the&#xD;
      prognosis is grim especially because of late diagnosis and metastatic potential. While&#xD;
      surgical treatment is currently the only potential curative intervention, 80-85% of the PC&#xD;
      cases are unfortunately detected in late unresectable stages of the disease. In spite of&#xD;
      advances in the diagnosis and management of pancreatic cancer less than 5% of patients are&#xD;
      alive at five years.&#xD;
&#xD;
      Endoscopic ultrasound (EUS) represents a highly valuable tool in the management of pancreatic&#xD;
      cancer patients. As a minimally invasive technique that enables high-resolution imaging of&#xD;
      the pancreatic parenchyma and surrounding structures it is considered the method of choice&#xD;
      for the detection of clinically suspected pancreatic tumors, with a negative predictive value&#xD;
      close to 100%. Its diagnostic sensitivity was shown by previous studies to be superior&#xD;
      compared to other imaging techniques, especially in the case of smaller tumors. Additionally&#xD;
      EUS enables guided fine needle aspiration (EUS-FNA) which is currently recommended as the&#xD;
      firs-line procedure whenever pathological diagnosis is required. However, EUS-FNA as a&#xD;
      sampling technique has its drawbacks, mainly represented by the relatively low negative&#xD;
      predictive value in diagnosing pancreatic cancer. It thus cannot reliably rule out a&#xD;
      diagnosis of malignancy and patients with high clinical suspicion usually need repeated FNA.&#xD;
&#xD;
      Confocal laser endomicroscopy has emerged in recent years as a novel technique that actually&#xD;
      enables in vivo microscopic analysis during ongoing endoscopy. Endomicroscopy can be&#xD;
      performed either with dedicated (eCLE) or with miniprobe-based systems (pCLE). It is a&#xD;
      contrast based technique, the most widely used agent being the intravenously administered&#xD;
      fluorescein. The probe-based endomicroscopy system consists of a flexible catheter probe&#xD;
      representing a bundle of optical fibers linked to a micro-objective, a laser scanning unit&#xD;
      and the control and acquisition software (Cellvizio; Mauna Kea Technology, Paris, France).&#xD;
      The flexible confocal miniprobes were specifically designed to be passed through the working&#xD;
      channels of standard endoscopes, biliary catheters or cholangioscopes and thus the pCLE&#xD;
      system can be easily integrated in any endoscopy unit. The principle of the technique is&#xD;
      based on a laser beam of defined wavelength being focused towards the targeted tissue and the&#xD;
      recaptured signal is displayed as 'optical biopsies' in a single horizontal plane.&#xD;
&#xD;
      The potential role of CLE has been explored in pathology of both upper and lower&#xD;
      gastrointestinal tract, showing good accuracy for predicting the final histopathological&#xD;
      diagnosis based on immediate evaluation of tissue and vascular patterns. Recently CLE has&#xD;
      gone beyond the superficial luminal indications with the development of a new microprobe,&#xD;
      i.e. a flexible probe thin enough that it can be passed through a 19-gauge needle. Thus under&#xD;
      EUS guidance solid organs can be accessed for real-time microscopic information. nCLE imaging&#xD;
      of abdominal organs has been so far achieved in animal models. The feasibility of the&#xD;
      technique was also proved in a clinical study and descriptive criteria for the diagnosis of&#xD;
      pancreatic cystic neoplasm were developed from a multicentre trial. However, only a limited&#xD;
      number of cases of pancreatic solid masses have been described with nCLE.&#xD;
&#xD;
      Aim The aim of the proposed study is to describe confocal imaging criteria for pancreatic&#xD;
      masses, lymph nodes or liver metastases identified during EUS procedures performed for&#xD;
      pancreatic cancer staging (EUS-nCLE), while evaluating also the feasibility and safety of&#xD;
      nCLE examination. The hypothesis is that EUS-nCLE could allow targeted tissue sampling of&#xD;
      pancreatic lesions resulting in more accurate diagnosis. With further validation of the&#xD;
      technique real-time pathological diagnosis could be obtained with immediate initiation of the&#xD;
      adequate therapy after a single investigation.&#xD;
&#xD;
      Patients The study will prospectively include patients referred to our department for EUS and&#xD;
      EUS-FNA of suspected pancreatic masses during a 12 months period. The indication for this&#xD;
      investigation will be based on the patient's clinical history and previous imaging studies&#xD;
      (abdominal ultrasound, CT scan, MRI).&#xD;
&#xD;
      Patients will be selected according to the following criteria used throughout the study:&#xD;
&#xD;
      Data collected for each participant will include:&#xD;
&#xD;
        -  Personal data (name, surname, age, sex)&#xD;
&#xD;
        -  EUS variables (tumor characteristics)&#xD;
&#xD;
        -  Histological and immunohistochemical findings (final diagnosis)&#xD;
&#xD;
      Imaging tests All patients with a suspicion (clinical, US, CT/MRI) of pancreatic masses will&#xD;
      be evaluated by EUS, nCLE and EUS-FNA for pathological diagnosis.&#xD;
&#xD;
      For EUS examination linear instruments will be used to perform complete examination of the&#xD;
      pancreas.&#xD;
&#xD;
      Tumor characteristics (echogenicity, echostructure, size, vascular invasion) will be&#xD;
      described.&#xD;
&#xD;
      The presence of regional lymph nodes will be reported with their maximal size, echogenicity,&#xD;
      shape and margins.&#xD;
&#xD;
      Identification of liver metastasis will also be looked upon.&#xD;
&#xD;
      EUS-nCLE will be performed after EUS identification of the pancreatic tumor / lymph node /&#xD;
      liver metastasis:&#xD;
&#xD;
      The confocal microprobe will be preloaded in a 19G FNA needle as previously described and&#xD;
      advanced into the lesion under EUS guidance.&#xD;
&#xD;
      nCLE examination will follow after the intravenous administration of the contrast agent (2.5&#xD;
      ml fluorescein 10%).&#xD;
&#xD;
      Image data will be stored digitally for offline analysis. EUS-FNA will be also performed&#xD;
      after image acquisition for cytology smears and cell blocks to enable a final pathological&#xD;
      diagnosis Confocal images will be analyzed during the examination by the principal&#xD;
      investigator, with clinical and other procedural information in mind. In a second step&#xD;
      offline analysis, the correlations between representative confocal images and classical&#xD;
      hematoxylin and eosin sections will be identified.&#xD;
&#xD;
      Final diagnosis The final diagnosis will be based on EUS-FNA cytology and/or histological&#xD;
      specimens in those patients that will be further referred for surgery. Pathology samples&#xD;
      obtained from duodeno-pancreatectomies or caudal pancreatectomies done with curative intent,&#xD;
      as well as microhistological fragments obtained through EUS-FNA biopsy will be processed by&#xD;
      paraffin embedding with usual stainings (haematoxylin-eosin), with subsequent&#xD;
      immune-histochemistry where necessary.&#xD;
&#xD;
      For the patients without positive cytology or histology the diagnosis will be based on EUS&#xD;
      tumor characteristics and other relevant information (clinical, imaging tests) with follow-up&#xD;
      for at least six months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 2012</start_date>
  <completion_date type="Actual">July 2016</completion_date>
  <primary_completion_date type="Actual">July 2015</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>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Describe confocal imaging criteria for pancreatic masses, lymph nodes or liver metastases</measure>
    <time_frame>6 month</time_frame>
    <description>Tumor characteristics (EUS) (echogenicity, echostructure, size, vascular invasion) will be described.&#xD;
EUS-nCLE will be performed after EUS identification of the pancreatic tumor / lymph node / liver metastasis:&#xD;
Confocal images will be analyzed to correlate representative confocal images and classical hematoxylin and eosin sections.&#xD;
The final diagnosis will be based on EUS-FNA cytology and/or histological specimens in those patients that will be further referred for surgery. For the patients without positive cytology or histology the diagnosis will be based on EUS tumor characteristics and other relevant information (clinical, imaging tests) with follow-up for at least six months&#xD;
The outcome is fully descriptive.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety</measure>
    <time_frame>30 days</time_frame>
    <description>Number of adverse events related til the procedure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Feasibility</measure>
    <time_frame>1 day</time_frame>
    <description>Feasibility of nCLE examination measured by the number of patients, where nCLE is accomplished</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Pancreatic Neoplasms</condition>
  <condition>CHRONIC PANCREATITIS</condition>
  <arm_group>
    <arm_group_label>needle based CLE &amp; EUS-FNA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The study will prospectively include patients referred to our department for EUS and EUS-FNA of suspected pancreatic masses during a 12 months period. The indication for this investigation will be based on the patient's clinical history and previous imaging studies (abdominal ultrasound, CT scan, MRI).</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>needle based CLE</intervention_name>
    <description>EUS-nCLE will be performed after EUS identification of the pancreatic tumor / lymph node / liver metastasis:&#xD;
The confocal microprobe will be preloaded in a 19G FNA needle as previously described and advanced into the lesion under EUS guidance.&#xD;
nCLE examination will follow after the intravenous administration of the contrast agent (2.5 ml fluorescein 10%).&#xD;
Image data will be stored digitally for offline analysis.</description>
    <arm_group_label>needle based CLE &amp; EUS-FNA</arm_group_label>
    <other_name>nCLE</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>EUS-FNA</intervention_name>
    <description>Endoscopic ultrasound (EUS) is an established tool in pancreatic masses used both for diagnosis, but also for staging purposes. Additionally, EUS enables guided fine needle aspiration (FNA), which is currently recommended as the first-line procedure whenever a pathological diagnosis is required.</description>
    <arm_group_label>needle based CLE &amp; EUS-FNA</arm_group_label>
    <other_name>Endoscopic ultrasound with fine-needle aspiration</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria&#xD;
&#xD;
          -  Age &gt; 18 years old, male or female&#xD;
&#xD;
          -  Patients diagnosed with solid pancreatic masses with an indication for EUS-FNA&#xD;
&#xD;
          -  Signed informed consent for EUS with FNA and nCLE examination&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
          -  Failure to provide informed consent&#xD;
&#xD;
          -  Patients with a contraindication for EUS-FNA&#xD;
&#xD;
          -  Known allergy to fluorescein&#xD;
&#xD;
          -  Pregnant or breast-feeding patients&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>john G Karstensen, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Copenhagen University Hospital at Herlev</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Copenhagen University Hospital Herlev</name>
      <address>
        <city>Herlev</city>
        <zip>2730</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Center of Gastroenterology and Hepatology,</name>
      <address>
        <city>Craiva</city>
        <zip>200349,</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
    <country>Romania</country>
  </location_countries>
  <reference>
    <citation>Vincent A, Herman J, Schulick R, Hruban RH, Goggins M. Pancreatic cancer. Lancet. 2011 Aug 13;378(9791):607-20. doi: 10.1016/S0140-6736(10)62307-0. Epub 2011 May 26.</citation>
    <PMID>21620466</PMID>
  </reference>
  <reference>
    <citation>Sharma C, Eltawil KM, Renfrew PD, Walsh MJ, Molinari M. Advances in diagnosis, treatment and palliation of pancreatic carcinoma: 1990-2010. World J Gastroenterol. 2011 Feb 21;17(7):867-97. doi: 10.3748/wjg.v17.i7.867.</citation>
    <PMID>21412497</PMID>
  </reference>
  <reference>
    <citation>Saftoiu A, Vilmann P. Role of endoscopic ultrasound in the diagnosis and staging of pancreatic cancer. J Clin Ultrasound. 2009 Jan;37(1):1-17. doi: 10.1002/jcu.20534.</citation>
    <PMID>18932265</PMID>
  </reference>
  <reference>
    <citation>DeWitt J, Devereaux B, Chriswell M, McGreevy K, Howard T, Imperiale TF, Ciaccia D, Lane KA, Maglinte D, Kopecky K, LeBlanc J, McHenry L, Madura J, Aisen A, Cramer H, Cummings O, Sherman S. Comparison of endoscopic ultrasonography and multidetector computed tomography for detecting and staging pancreatic cancer. Ann Intern Med. 2004 Nov 16;141(10):753-63. doi: 10.7326/0003-4819-141-10-200411160-00006.</citation>
    <PMID>15545675</PMID>
  </reference>
  <reference>
    <citation>Iglesias Garcia JJ, Larino Noia J, Alvarez Castro A, Cigarran B, Dominguez Munoz JE. Second-generation endoscopic ultrasound elastography in the differential diagnosis of solid pancreatic masses. Pancreatic cancer vs. inflammatory mass in chronic pancreatitis. Rev Esp Enferm Dig. 2009 Oct;101(10):723-30. doi: 10.4321/s1130-01082009001000009. English, Spanish.</citation>
    <PMID>19899942</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>
  <reference>
    <citation>Becker V, Wallace MB, Fockens P, von Delius S, Woodward TA, Raimondo M, Voermans RP, Meining A. Needle-based confocal endomicroscopy for in vivo histology of intra-abdominal organs: first results in a porcine model (with videos). Gastrointest Endosc. 2010 Jun;71(7):1260-6. doi: 10.1016/j.gie.2010.01.010. Epub 2010 Apr 24.</citation>
    <PMID>20421104</PMID>
  </reference>
  <reference>
    <citation>Konda VJ, Aslanian HR, Wallace MB, Siddiqui UD, Hart J, Waxman I. First assessment of needle-based confocal laser endomicroscopy during EUS-FNA procedures of the pancreas (with videos). Gastrointest Endosc. 2011 Nov;74(5):1049-60. doi: 10.1016/j.gie.2011.07.018. Epub 2011 Sep 15.</citation>
    <PMID>21924718</PMID>
  </reference>
  <verification_date>February 2018</verification_date>
  <study_first_submitted>November 19, 2012</study_first_submitted>
  <study_first_submitted_qc>November 22, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 28, 2012</study_first_posted>
  <last_update_submitted>February 21, 2018</last_update_submitted>
  <last_update_submitted_qc>February 21, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">February 23, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Herlev Hospital</investigator_affiliation>
    <investigator_full_name>John Gasdal Karstensen</investigator_full_name>
    <investigator_title>M.D.</investigator_title>
  </responsible_party>
  <keyword>confocal laser endomicroscopy</keyword>
  <keyword>Pancreatic Neoplasms</keyword>
  <keyword>CHRONIC PANCREATITIS</keyword>
  <keyword>Endoscopic ultrasound</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pancreatic Neoplasms</mesh_term>
    <mesh_term>Pancreatitis</mesh_term>
    <mesh_term>Pancreatitis, Chronic</mesh_term>
  </condition_browse>
  <!-- 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/NCT01734967
org study id: herlev
nct id: NCT01734967
lead sponsor: 
has dmc: Yes
Introduction: Pancreatic cancer is one of the most aggressive malignancies with only 5% of
      patients being alive at five years. EUS (endoscopic ultra sound) is an established, sensitive
      diagnostic tool in pancreatic cancer and for staging purposes. Additionally, EUS enables
      guided fine needle aspiration (FNA), which is currently recommended as the first-line
      procedure whenever a pathological diagnosis is required. However, EUS-FNA as a sampling
      method has its drawbacks, due to a relatively low negative predictive value. Confocal laser
      endomicroscopy has emerged in recent years as a novel method that enables in vivo microscopic
      analysis during ongoing endoscopy. Recently, confocal laser endomicroscopy has gone beyond
      the superficial luminal indications with the development of a new microprobe, i.e. a flexible
      laser probe (nCLE) that can pass through a 19-gauge needle. Combined with EUS, descriptive
      criteria for the diagnosis of pancreatic cystic neoplasm has been developed in a multicentre
      trial. However, only a limited number of cases of solid pancreatic masses have been described
      with nCLE.

      Aim and Method: To describe confocal imaging criteria for pancreatic masses, lymph nodes or
      liver metastases identified during EUS procedures performed for pancreatic cancer staging
      (EUS-nCLE), while evaluating also the feasibility and safety of nCLE examination. The
      hypothesis is that EUS-nCLE could allow targeted tissue sampling of pancreatic lesions
      resulting in more accurate diagnosis. XX patients were included all presenting with a
      clinical suspicion of pancreatic cancer or imaging studies showing a pancreatic mass. During
      the procedure an nCLE preloaded 19G FNA needle was advanced into the lesion under EUS
      guidance. A contrast agent was administered intravenously (2.5 ml fluorescein 10%). The data
      was stored digitally for post procedural analysis. Afterwards EUS-FNA was performed for
      cytology smears to enable a final pathological diagnosis. Correlations between the nCLE
      images and the conventional pathology were identified.
Background Pancreatic cancer is one of the most aggressive gastrointestinal malignancies with
      mortality rates following closely the incidence rates. The incidence is increasing and the
      prognosis is grim especially because of late diagnosis and metastatic potential. While
      surgical treatment is currently the only potential curative intervention, 80-85% of the PC
      cases are unfortunately detected in late unresectable stages of the disease. In spite of
      advances in the diagnosis and management of pancreatic cancer less than 5% of patients are
      alive at five years.

      Endoscopic ultrasound (EUS) represents a highly valuable tool in the management of pancreatic
      cancer patients. As a minimally invasive technique that enables high-resolution imaging of
      the pancreatic parenchyma and surrounding structures it is considered the method of choice
      for the detection of clinically suspected pancreatic tumors, with a negative predictive value
      close to 100%. Its diagnostic sensitivity was shown by previous studies to be superior
      compared to other imaging techniques, especially in the case of smaller tumors. Additionally
      EUS enables guided fine needle aspiration (EUS-FNA) which is currently recommended as the
      firs-line procedure whenever pathological diagnosis is required. However, EUS-FNA as a
      sampling technique has its drawbacks, mainly represented by the relatively low negative
      predictive value in diagnosing pancreatic cancer. It thus cannot reliably rule out a
      diagnosis of malignancy and patients with high clinical suspicion usually need repeated FNA.

      Confocal laser endomicroscopy has emerged in recent years as a novel technique that actually
      enables in vivo microscopic analysis during ongoing endoscopy. Endomicroscopy can be
      performed either with dedicated (eCLE) or with miniprobe-based systems (pCLE). It is a
      contrast based technique, the most widely used agent being the intravenously administered
      fluorescein. The probe-based endomicroscopy system consists of a flexible catheter probe
      representing a bundle of optical fibers linked to a micro-objective, a laser scanning unit
      and the control and acquisition software (Cellvizio; Mauna Kea Technology, Paris, France).
      The flexible confocal miniprobes were specifically designed to be passed through the working
      channels of standard endoscopes, biliary catheters or cholangioscopes and thus the pCLE
      system can be easily integrated in any endoscopy unit. The principle of the technique is
      based on a laser beam of defined wavelength being focused towards the targeted tissue and the
      recaptured signal is displayed as 'optical biopsies' in a single horizontal plane.

      The potential role of CLE has been explored in pathology of both upper and lower
      gastrointestinal tract, showing good accuracy for predicting the final histopathological
      diagnosis based on immediate evaluation of tissue and vascular patterns. Recently CLE has
      gone beyond the superficial luminal indications with the development of a new microprobe,
      i.e. a flexible probe thin enough that it can be passed through a 19-gauge needle. Thus under
      EUS guidance solid organs can be accessed for real-time microscopic information. nCLE imaging
      of abdominal organs has been so far achieved in animal models. The feasibility of the
      technique was also proved in a clinical study and descriptive criteria for the diagnosis of
      pancreatic cystic neoplasm were developed from a multicentre trial. However, only a limited
      number of cases of pancreatic solid masses have been described with nCLE.

      Aim The aim of the proposed study is to describe confocal imaging criteria for pancreatic
      masses, lymph nodes or liver metastases identified during EUS procedures performed for
      pancreatic cancer staging (EUS-nCLE), while evaluating also the feasibility and safety of
      nCLE examination. The hypothesis is that EUS-nCLE could allow targeted tissue sampling of
      pancreatic lesions resulting in more accurate diagnosis. With further validation of the
      technique real-time pathological diagnosis could be obtained with immediate initiation of the
      adequate therapy after a single investigation.

      Patients The study will prospectively include patients referred to our department for EUS and
      EUS-FNA of suspected pancreatic masses during a 12 months period. The indication for this
      investigation will be based on the patient's clinical history and previous imaging studies
      (abdominal ultrasound, CT scan, MRI).

      Patients will be selected according to the following criteria used throughout the study:

      Data collected for each participant will include:

        -  Personal data (name, surname, age, sex)

        -  EUS variables (tumor characteristics)

        -  Histological and immunohistochemical findings (final diagnosis)

      Imaging tests All patients with a suspicion (clinical, US, CT/MRI) of pancreatic masses will
      be evaluated by EUS, nCLE and EUS-FNA for pathological diagnosis.

      For EUS examination linear instruments will be used to perform complete examination of the
      pancreas.

      Tumor characteristics (echogenicity, echostructure, size, vascular invasion) will be
      described.

      The presence of regional lymph nodes will be reported with their maximal size, echogenicity,
      shape and margins.

      Identification of liver metastasis will also be looked upon.

      EUS-nCLE will be performed after EUS identification of the pancreatic tumor / lymph node /
      liver metastasis:

      The confocal microprobe will be preloaded in a 19G FNA needle as previously described and
      advanced into the lesion under EUS guidance.

      nCLE examination will follow after the intravenous administration of the contrast agent (2.5
      ml fluorescein 10%).

      Image data will be stored digitally for offline analysis. EUS-FNA will be also performed
      after image acquisition for cytology smears and cell blocks to enable a final pathological
      diagnosis Confocal images will be analyzed during the examination by the principal
      investigator, with clinical and other procedural information in mind. In a second step
      offline analysis, the correlations between representative confocal images and classical
      hematoxylin and eosin sections will be identified.

      Final diagnosis The final diagnosis will be based on EUS-FNA cytology and/or histological
      specimens in those patients that will be further referred for surgery. Pathology samples
      obtained from duodeno-pancreatectomies or caudal pancreatectomies done with curative intent,
      as well as microhistological fragments obtained through EUS-FNA biopsy will be processed by
      paraffin embedding with usual stainings (haematoxylin-eosin), with subsequent
      immune-histochemistry where necessary.

      For the patients without positive cytology or histology the diagnosis will be based on EUS
      tumor characteristics and other relevant information (clinical, imaging tests) with follow-up
      for at least six months.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Describe confocal imaging criteria for pancreatic masses, lymph nodes or liver metastases
time frame: 6 month
description: Tumor characteristics (EUS) (echogenicity, echostructure, size, vascular invasion) will be described.
EUS-nCLE will be performed after EUS identification of the pancreatic tumor / lymph node / liver metastasis:
Confocal images will be analyzed to correlate representative confocal images and classical hematoxylin and eosin sections.
The final diagnosis will be based on EUS-FNA cytology and/or histological specimens in those patients that will be further referred for surgery. For the patients without positive cytology or histology the diagnosis will be based on EUS tumor characteristics and other relevant information (clinical, imaging tests) with follow-up for at least six months
The outcome is fully descriptive.
measure: Safety
time frame: 30 days
description: Number of adverse events related til the procedure
measure: Feasibility
time frame: 1 day
description: Feasibility of nCLE examination measured by the number of patients, where nCLE is accomplished
arm group label: needle based CLE & EUS-FNA
arm group type: Experimental
description: The study will prospectively include patients referred to our department for EUS and EUS-FNA of suspected pancreatic masses during a 12 months period. The indication for this investigation will be based on the patient's clinical history and previous imaging studies (abdominal ultrasound, CT scan, MRI).
intervention type: Device
intervention name: needle based CLE
description: EUS-nCLE will be performed after EUS identification of the pancreatic tumor / lymph node / liver metastasis:
The confocal microprobe will be preloaded in a 19G FNA needle as previously described and advanced into the lesion under EUS guidance.
nCLE examination will follow after the intravenous administration of the contrast agent (2.5 ml fluorescein 10%).
Image data will be stored digitally for offline analysis.
arm group label: needle based CLE & EUS-FNA
other name: nCLE
intervention type: Procedure
intervention name: EUS-FNA
description: Endoscopic ultrasound (EUS) is an established tool in pancreatic masses used both for diagnosis, but also for staging purposes. Additionally, EUS enables guided fine needle aspiration (FNA), which is currently recommended as the first-line procedure whenever a pathological diagnosis is required.
arm group label: needle based CLE & EUS-FNA
other name: Endoscopic ultrasound with fine-needle aspiration
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: john G Karstensen, M.D.
role: Principal Investigator
affiliation: Copenhagen University Hospital at Herlev
facility: 
facility: 
country: Denmark
country: Romania
citation: Vincent A, Herman J, Schulick R, Hruban RH, Goggins M. Pancreatic cancer. Lancet. 2011 Aug 13;378(9791):607-20. doi: 10.1016/S0140-6736(10)62307-0. Epub 2011 May 26.
PMID: 21620466
citation: Sharma C, Eltawil KM, Renfrew PD, Walsh MJ, Molinari M. Advances in diagnosis, treatment and palliation of pancreatic carcinoma: 1990-2010. World J Gastroenterol. 2011 Feb 21;17(7):867-97. doi: 10.3748/wjg.v17.i7.867.
PMID: 21412497
citation: Saftoiu A, Vilmann P. Role of endoscopic ultrasound in the diagnosis and staging of pancreatic cancer. J Clin Ultrasound. 2009 Jan;37(1):1-17. doi: 10.1002/jcu.20534.
PMID: 18932265
citation: DeWitt J, Devereaux B, Chriswell M, McGreevy K, Howard T, Imperiale TF, Ciaccia D, Lane KA, Maglinte D, Kopecky K, LeBlanc J, McHenry L, Madura J, Aisen A, Cramer H, Cummings O, Sherman S. Comparison of endoscopic ultrasonography and multidetector computed tomography for detecting and staging pancreatic cancer. Ann Intern Med. 2004 Nov 16;141(10):753-63. doi: 10.7326/0003-4819-141-10-200411160-00006.
PMID: 15545675
citation: Iglesias Garcia JJ, Larino Noia J, Alvarez Castro A, Cigarran B, Dominguez Munoz JE. Second-generation endoscopic ultrasound elastography in the differential diagnosis of solid pancreatic masses. Pancreatic cancer vs. inflammatory mass in chronic pancreatitis. Rev Esp Enferm Dig. 2009 Oct;101(10):723-30. doi: 10.4321/s1130-01082009001000009. English, Spanish.
PMID: 19899942
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
citation: Becker V, Wallace MB, Fockens P, von Delius S, Woodward TA, Raimondo M, Voermans RP, Meining A. Needle-based confocal endomicroscopy for in vivo histology of intra-abdominal organs: first results in a porcine model (with videos). Gastrointest Endosc. 2010 Jun;71(7):1260-6. doi: 10.1016/j.gie.2010.01.010. Epub 2010 Apr 24.
PMID: 20421104
citation: Konda VJ, Aslanian HR, Wallace MB, Siddiqui UD, Hart J, Waxman I. First assessment of needle-based confocal laser endomicroscopy during EUS-FNA procedures of the pancreas (with videos). Gastrointest Endosc. 2011 Nov;74(5):1049-60. doi: 10.1016/j.gie.2011.07.018. Epub 2011 Sep 15.
PMID: 21924718
responsible party type: Principal Investigator
investigator affiliation: Herlev Hospital
investigator full name: John Gasdal Karstensen
investigator title: M.D.
mesh term: Pancreatic Neoplasms
mesh term: Pancreatitis
mesh term: Pancreatitis, Chronic