Clinical Evaluation Of Needle-based Confocal Laser Endomicroscopy in The Lymph Nodes Along With Masses and Cystic Tumors of the Pancreas
Clinical Evaluation Of Needle-based Confocal Laser Endomicroscopy in The Lymph Nodes Along With Masses and Cystic Tumors of the Pancreas
This study focuses on three different lesions: pancreatic cysts, lymph nodes near the
 gastrointestinal tract and pancreatic masses.

 On one hand, the results obtained during previous studies are more advanced for the
 assessment of the diagnostic performance of Cellvizio needle-based Confocal Laser
 Endomicroscopy (nCLE) system for Pancreatic cysts. Safety and technical feasibility have
 already been performed, and an interpretation criteria classification exists. On the other
 hand, results for pancreatic masses and Lymph nodes are less developed.

 The study therefore comprises two sub-studies, one on the pancreatic cysts, and another on
 pancreatic masses and lymph nodes.

 1. Cysts The primary hypothesis of the study is that using nCLE in addition to EUS-FNA and
 tissue sampling allows better characterization of pancreatic cysts and improves
 appropriate therapeutic decision-making.

 For physicians, integrating nCLE into the diagnostic algorithm of pancreatic cysts could
 impact patient management by :

 -  Ruling out malignancy for patients with benign appearing nCLE images.

 -  Characterizing more malignant tumors in the pancreas.

 2. Pancreatic masses and Lymph nodes The primary hypothesis of the study is that in vivo
 imaging of lymph-nodes near the gastrointestinal tract and pancreatic masses during
 EUS-FNA procedures is feasible and that descriptive criteria can be defined to further
 differentiate the different types of lesions.
1. Medical background Pancreatic cancer is the fourth leading cause of cancer-related death
 in the United States. This disease is associated with a high mortality rate: the 5-year
 survival rate is estimated to be 4%. This is mainly due to the fact that the disease is
 often discovered at an already advanced disease state, which carries a dismal prognosis.

 1.1. Pancreatic Cysts

 Pancreatic cysts are quite rare, but are being increasingly recognized due to the
 expanding use of cross-sectional imaging. They are classified into three main classes:

 -  Pseudocysts

 -  Serous cysts : either serous cystic neoplasms (SCN) or Solid pseudo-papillary
 neoplasm (SPN)

 -  Mucinous cystic neoplasms : either Intraductal Papillary Mucinous Neoplasm (IPMN)
 or mucinous cystadenomas/mucinous cystadenocarcinoma(MCN) Mucinous cystic neoplasms
 are considered to be malignant or pre-malignant and are considered for surgical
 resection, whereas pseudocysts and serous cysts are considered benign and with a
 low potential for malignancy. Pseudocysts and serous cysts are usually only
 considered for surgical resection when symptomatic or enlarging.

 1.2. Pancreatic masses Pancreatic solid masses can be either exocrine or endocrine
 tumors, or metastatic.Exocrine tumors are by far the most common type of pancreas
 cancer. Most of them are malignant. About 96% of cancers of the exocrine pancreas are
 adenocarcinomas, which is the most aggressive form of pancreas cancer.Endocrine tumors
 are uncommon. They represent 4% of pancreas tumors. They are known as neuroendocrine
 tumors (NETs), or islet cell tumors. These tumors can be benign or malignant.

 1.3. Lymph nodes Lymph nodes are examined in a patient with a suspicion of, or
 confirmed, cancer, as part of the staging. They may be either normal, inflammatory, or
 malignant.

 2. Clinical background

 2.1. EUSFNA Endoscopic Ultrasound (EUS) is the diagnostic method of choice when a
 pancreatic lesion is found incidentally on cross-sectional imaging. Endoscopic
 UltraSound-guided Fine Needle Aspiration (EUS FNA) (respectively Endobronchial
 Ultrasound-guided Fine Needle Aspiration (EBUS FNA)) are procedures where a target
 tissue in proximity to the GI tract (respectively the pulmonary tract) is biopsied using
 a fine needle guided in real time by an ultrasound probe fixed at the tip of an
 endoscope.It may therefore be applied to pancreatic lesions, or lymph nodes examination.

 2.2. nCLE The principle of needle-based Confocal Laser Endomicroscopy (nCLE) is to image
 organs within or adjacent to the GI or respiratory tracts with a miniprobe inserted
 through an endoscopic needle. The fundamental technology as well as the principle of
 operation of nCLE are substantially similar to pCLE.

 3. Clinical evidence More than 100 patients have already underwent an nCLE procedure, in
 the past studies. A first feasibility study enabled to define the final type of probe
 which would fit into a EUSFNA needle, and the INSPECT study enabled to define
 interpretation criteria on the micro-structure of pancreatic cysts. Less data is
 available on pancreatic masses and lymph nodes, except for a few images done in the
 first feasibility study.

 4. Objectives

 4.1. Cysts 4.1.1. The primary objective of the study is to assess the diagnostic
 performance of the Cellvizio nCLE system in diagnosing pancreatic cysts, when associated
 with other diagnostic information.

 4.1.2. The secondary objectives are to assess the potential impact of the Cellvizio nCLE
 system on patient management and validate the interpretation classification criteria
 that were created during the previous INSPECT study on cysts.

 4.2. Pancreatic masses and Lymph nodes 4.2.1. The primary objective of the study is to
 define criteria of nCLE sequences in lymph nodes and pancreatic masses.

 4.2.2. The secondary objectives are to evaluate feasibility and safety of the Cellvizio
 nCLE during EUS-FNA procedures, build an atlas of images of nCLE sequences of pancreatic
 masses and lymph nodes, and, finally, retrospectively assess the diagnostic performance
 of nCLE in the diagnosis of pancreatic masses and lymph nodes, when associated with
 other diagnostic information

 5. Design This study will be conducted in three centers in France.
Inclusion Criteria:

 -  Male or female > 18 years of age.

 -  Patient indicated for a first EUS-FNA for a pancreatic cyst, lymph node or pancreatic
 mass, or

 -  Patients who had previous non-diagnostic tissue sampling taken during a previous
 EUS-FNA for pancreatic cyst, lymph nodes, pancreatic mass, more than three months ago.

 -  Patient with known pancreatic cyst or mass detected at cross-sectional imaging or
 suspicious lymph nodes reachable via EUSFNA

 -  Willing and able to comply with study procedures and provide written informed consent
 to participate in the study.

 Add for lymph nodes:

 - any lymph node reachable with EUS-FNA

 Add for pancreatic mass:

 -  any size

 -  any location in the pancreas

 Exclusion Criteria:

 -  Subjects for whom EUS-FNA procedures are contraindicated

 -  Known allergy to fluorescein dye

 -  If female, pregnant based on a positive hCG serum or an in vitro diagnostic test
 result or breast-feeding

 Add for cysts:

 -  Subject with multiple cysts

 -  size < 20mm in diameter

 -  previous EUS-FNA procedure performed less than 3 months ago - Patients suffering
 chronic calcifying pancreatitis

 Add for lymph nodes:

 -  size < 5mm in diameter

 -  If patients present several suspicious lymph nodes, only one of them will be imaged
 during the nCLE procedure

 Add for pancreatic mass:

 - If patient present several pancreatic masses, only one of them will be imaged during the
 nCLE procedure