Endobronchial Ultrasound Needle Aspiration With and Without Suction

Study Overview
=================
Brief Summary
-----------------
The main purpose of the present study is to compare the diagnostic yield of different aspiration techniques in Ultrasound-guided Transbronchial Needle Aspiration (EBUS-TBNA) in the diagnosis of hilar/mediastinal adenopathy

Detailed Description
-----------------
The role of ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for the diagnosis of hilar/mediastinal adenopathy is well established. However, different aspiration techniques are available and it's not clear if there's a significant difference between suction vs no suction aspiration. Of great interest is the role of different aspiration techniques in EBUS-TBNA in determining the diagnostic yield for histopathological evaluation, including molecular biology and PD-L1 amplification assessment in lung cancer diagnosis. In this context, no comparative studies between suction and no suction aspiration have been performed; moreover, considering only suction techniques, no studies evaluated if there's a difference between aspiration with EBUS dedicated syringe and manual aspiration through Cameco syringe. It is very important for clinical practice to definitively assess the non inferiority of no suction techniques in EBUS-TBNA in terms of diagnostic yield, and to provide information regarding the quality of histologic sample to define the best diagnostic strategy. The study is focused on a minimum of 306 patients who have at least one hilar/mediastinal lymph node > 1 cm on CT scan or hypermetabolic on FDG-PET in at least one approachable lymph nodal station for which a diagnostic cyto-histological assessment is required for clinical purpose. Patients will be randomized 1:1:1 (no suction : passive suction with EBUS dedicated syringe : manual suction with Cameco syringe) by a computer-generated random-allocation system to undergo EBUS-TBNA with one of the three different aspiration techniques. The pathologist provides a final diagnosis and, as secondary endpoint, a qualitative assessment of the sample quality using both a binary and a semi-quantitative score.

Official Title
-----------------
Diagnostic Accuracy of Endobronchial Ultrasound Needle Aspiration With and Without Suction: a Single-center Randomized Controlled Trial

Conditions
-----------------
ALK Translocation, Mediastinal Lymphadenopathy, Hilar Lymphadenopathy, Lymphoma, Lung Neoplasms, Sarcoidosis, Tuberculosis, EGF-R Positive Non-Small Cell Lung Cancer, PDL1 Gene Mutation, ROS1 Gene Mutation

Intervention / Treatment
-----------------
* Procedure: No suction EBUS-TBNA
* Procedure: Passive suction through dedicated EBUS-TBNA syringe
* Procedure: Manual applied suction EBUS-TBNA through a pistol-grip syringe holder


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: age ≥ 18years; presence of at least one hilar/mediastinal adenopathy >1 cm on short axis assessed by contrast-enhanced CT scan and/or hypermetabolic adenopathy assessed by FDG-PET; ability to give an informed consent Exclusion Criteria: coagulopathy or bleeding diathesis that cannot be corrected; severe refractory hypoxemia; unstable hemodynamic status; inability to give an informed consent

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: No suction EBUS-TBNA<br>In this technique the stylet is slowly removed without any kind of device in order to avoid active suction. | Procedure: No suction EBUS-TBNA<br>* The needle is moved from a side to side of the lymphnode for 15 times. Each lymphnode is sampled three times. The samples obtained will be examined on-site by experienced blinded cytopathologist.All specimens obtained will be send to definitive cytological and histological evaluation and the final diagnosis will be collected and reported on CRFs.<br>|
| Active Comparator: Passive suction through dedicated EBUS-TBNA syringe<br>After rapid stylet removal, suction is applied through a vacuteiner syringe, without active aspiration. | Procedure: Passive suction through dedicated EBUS-TBNA syringe<br>* The needle is moved from a side to side of the lymphnode for 15 times. Each lymphnode is sampled three times. The samples obtained will be examined on-site by experienced blinded cytopathologist.All specimens obtained will be send to definitive cytological and histological evaluation and the final diagnosis will be collected and reported on CRFs.<br>|
| Active Comparator: Manual applied suction EBUS-TBNA through a pistol-grip syringe holder<br>After rapid stylet removal, suction is applied through Cameco syringe pistol, that can apply active suction manually. | Procedure: Manual applied suction EBUS-TBNA through a pistol-grip syringe holder<br>* The needle is moved from a side to side of the lymphnode for 15 times. Each lymphnode is sampled three times. The samples obtained will be examined on-site by experienced blinded cytopathologist.All specimens obtained will be send to definitive cytological and histological evaluation and the final diagnosis will be collected and reported on CRFs..<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the diagnostic yield of active suction vs passive suction vs no suction EBUS-TBNA in the diagnosis of hilar/mediastinal adenopathies | The diagnostic yield is defined as the rate of diagnoses/total of cases. Assuming that the best technique provides a diagnostic yield of 94%, the non inferiority is defined if the difference between the best and the worst method is less than 3% with a non-inferiority limit of 10%. | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adeguacy for molecular assessment in lung cancer | Considering only the lung cancer diagnoses, the sample is considered adeguated is if provides all the available molecular evaluations included PD-L1 iperexpression | 36 months | 
| Qualitative evaluation of the sample by the pathologist | The sample is evaluated by a pathologist that provides a semi-quantitative assessment of the sample, through a cell count: the sample is adeguate only if it contains more than diagnostic 100 cells. | 36 months |