On-site Cytopathology EUS-FNA

Study Overview
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Brief Summary
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This study is a multicenter prospective randomized controlled trial. Potential participants in this study include patients referred for Endoscopic Ultrasound-guided fine needle aspiration (EUS-FNA) of a solid pancreatic lesion at one of the participating centers. If the patient meets inclusion criteria and signs the informed consent, they will be randomized into one of the two study arms in a 1:1 ratio. Patients will either undergo EUS-FNA with or without an on-site cytopathologist present during EUS-FNA. Patients assigned to the on-site cytopathologist arm will have the cytopathologist dictate the number of fine needle aspiration (FNA) passes performed by the endosonographer. This number will be based on the adequacy of specimen and the ability to provide a preliminary diagnosis. In the other arm, in the absence of an on-site cytopathologist, the endosonographer will perform a predetermined number of 7 passes (standard of care in the absence of an on-site cytopathologist). The technique of performing EUS-FNA (needle type, use of stylet, suction) will be standardized among all endosonographers in order to rule out confounding factors. After EUS-FNA is performed all slides will be sent to the pathology department. The slides will be sent for review regardless of which arm the patient is randomized into, and they will be reviewed by experienced cytopathologists for the purpose of determining the final diagnoses. Future clinical intervention will be monitored for the purpose of reporting the impact EUS-FNA has on the patient's clinical course and determining diagnostic accuracy. Patients will be followed prospectively for at least one year, and the gold-standard for final diagnosis of pancreatic malignancy will be defined by the presence of malignant cytology or histologic evidence (if the patient undergoes surgery) or with clinical and/or imaging follow-up consistent with pancreatic cancer (death or clinical progression). A detailed account of medical equipment used during each procedure, procedure time, clinic visits/hospitalizations due to procedure related complications, and number of repeat procedures will be recorded systematically. The investigators hypothesize that an on-site cytopathologist during EUS-FNA for pancreatic masses improves diagnostic yield, accuracy, and lowers the duration, complications and the need for repeat procedures.

Detailed Description
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Endoscopic Ultrasound (EUS) plays an integral role in the diagnosis of suspected pancreatic cancer, and the EUS findings are crucial for determining the course of future management and potential treatment options for these patients. EUS is the most sensitive imaging modality for the detection of pancreatic masses, and has a sensitivity of greater than or equal to 90%. Furthermore, EUS-guided fine needle aspiration (EUS-FNA) plays an important role in accurate staging of pancreatic cancer with a sensitivity of 85% and specificity close to 100%. EUS-FNA is considered to be cost-effective by virtue of its impact on therapeutic management. In particular, real-time tissue sampling by EUS-FNA is possible when a cytopathologist (pathologist skilled in evaluating fine needle aspiration specimens) is able to be present at the time of FNA in order to review the biopsy slides and make a preliminary diagnosis. The availability of an on-site cytopathologist has the potential to provide quick diagnostic and predictive information to confirm the presence and staging of suspected malignancy. The rationale for an on-site cytopathologist includes increasing the adequacy and yield of biopsy tissue/aspirate which can decrease the need for additional passes to obtain a diagnostic yield of tissue. This hypothesis, however, has not been formally examined. In this proposed randomized controlled multicenter trial, the investigators hypothesize that an on-site cytopathologist during EUS-FNA for pancreatic masses improves diagnostic yield, accuracy, and lowers the duration, complications and the need for repeat procedures. This hypothesis will be explored in the context of the following specific aims. Specific aim #1: To compare the diagnostic yield of malignancy and proportion of inadequate specimens between the two groups. Specific aim #2: To compare the sensitivity, specificity and accuracy of EUS-FNA between the two groups using histologic diagnosis or cytologic diagnosis in conjunction with clinical and/or imaging follow-up as the gold standard. Specific aim #3: To compare the duration, rate of complications and repeat procedures between the two groups.

Official Title
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The Clinical Impact of Immediate On-site Cytopathology Evaluation During Endoscopic Ultrasound-Guided Fine Needle Aspiration of Pancreatic Mass: A Multicenter, Prospective Randomized Controlled Trial

Conditions
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Pancreatic Neoplasms, Pancreatic Cancer

Intervention / Treatment
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* Procedure: EUS-guided FNA performed with on-site Cytopathologist
* Procedure: EUS-guided FNA performed without on-site Cytopathologist


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients age: greater than or equal to 18 years Presence of a solid pancreatic mass lesion confirmed by at least a single investigational modality such as computerized axial tomography (CT) scan, magnetic resonance imaging (MRI) or Endoscopic Ultrasound (EUS) Ability to provide written informed consent Exclusion Criteria: Severe coagulopathy [International Normalized Ratio (INR) > 1.8] or thrombocytopenia (platelet count <50,000) Pure cystic lesions of the pancreas Inability to sample lesion due to the presence of intervening blood vessels Results of EUS-FNA would not impact patient management

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cytopathologist present during EUS-FNA<br>Patients assigned to the on-site cytopathologist arm will have the cytopathologist dictate the number of FNA passes performed by the endosonographer. This number will be based on the adequacy of specimen and the ability to provide a preliminary diagnosis. After EUS-FNA is performed all slides will be sent to the pathology department. The slides will be sent for review regardless of which arm the patient is randomized into, and they will be reviewed by experienced cytopathologists for the purpose of determining the final diagnoses. | Procedure: EUS-guided FNA performed with on-site Cytopathologist<br>* Patients assigned to the on-site cytopathologist arm will have the cytopathologist dictate the number of FNA passes performed by the endosonographer. This number will be based on the adequacy of specimen and the ability to provide a preliminary diagnosis.<br>|
| Cytopathologist absent during EUS-FNA<br>In the absence of an on-site cytopathologist, the endosonographer will perform a predetermined number of 7 passes (standard of care in the absence of an on-site cytopathologist). After EUS-FNA is performed all slides will be sent to the pathology department. The slides will be sent for review regardless of which arm the patient is randomized into, and they will be reviewed by experienced cytopathologists for the purpose of determining the final diagnoses. | Procedure: EUS-guided FNA performed without on-site Cytopathologist<br>* In the absence of an on-site cytopathologist, the endosonographer will perform a predetermined number of 7 passes (standard of care in the absence of an on-site cytopathologist).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the percent of patients with a positive diagnosis of malignancy in each of the two groups. | The Investigators would like to look at each of the two groups to assess whether or not having an onsite cytopathologist during EUS-FNA increases the diagnostic accuracy of pancreatic malignancies. To do this, the Investigators will compare the percent of patients in each group who were accurately diagnosed with a malignancy during EUS-FNA to see if the on-site cytopathologist group yields a higher percent of positively diagnosed malignancies. | 1 year from the time of patient enrollment | 
| Compare the percent of patients with inadequate samples (defined by an absence of cellular elements to account for a mass/lesion) between the two groups | Final slides will be reviewed by three experienced cytopathologists blinded to the patient's randomization group. The slides for each pass will be assessed for: cellularity, adequacy of specimen, contamination, amount of blood, and diagnosis. Using the cytopathologists' assessment of the FNA specimens, the Investigators will compare the percent of patients with inadequate samples in each group to see if the absence of an on-site cytopathologist corresponds with a higher percent of inadequate FNA samples. | 1-2 weeks from patient enrollment/EUS-FNA | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the sensitivity, specificity and accuracy of EUS-FNA between the two groups | Sensitivity, specificity and accuracy of EUS-FNA will be evaluated using histologic diagnosis or cytologic diagnosis in conjunction with clinical and/or imaging follow-up as the gold standard. | 1 year from patient enrollment | 
| Compare the mean number of passes in the two groups | Once all patients have been enrolled and have undergone EUS-FNA with or without an on-site cytopathologist, the Investigators will be able to compare the mean number of fine needle aspiration passes taken during EUS for patients in each group. | 1 year (length of time it takes to enroll all patients) | 
| Compare the complication rate in the two groups | The complication rates from the two groups of subjects will be evaluated when all subjects have been enrolled. | 1 year (length of time it takes to enroll all patients) | 
| Compare the EUS procedure duration in each group | The EUS procedure duration from the two groups of subjects will be evaluated when all subjects have been enrolled. | 1 year | 
| Compare the percent of patients requiring repeat procedures between the groups | The investigators will follow patients for one year after enrollment to see if they have had any repeat procedures for the purpose of diagnosing their pancreatic mass. | 1 year after the time of patient enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Biopsy, Fine-Needle, Endoscopic Ultrasonography, cytopathology