Diagnostic Yield of Intranodal Forceps Biopsies in Mediastinal Adenopathy
Study Details
Study Description
Brief Summary
We will compare endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) with intranodal forceps biopsy (EBUS-IFB) as it relates to the rate of diagnosis of suspected sarcoidosis.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Detailed Description
Prospective, randomized comparative study to determine the diagnostic yield and specimen quality of endobronchial ultrasound guided intranodal forceps biopsy of patients with suspected sarcoidosis based solely on imaging. This will be a single group study and will compare transbronchial needle aspiration via 19 or 21-gauge needle with intranodal forceps biopsy.
Inclusion Criteria:
- Patients at least 18 years or older with computed tomography showing mediastinal lymphadenopathy along with parenchymal changes that is deemed suspicious for sarcoidosis by a pulmonologist or thoracic radiologist who undergo bronchoscopy
EBUS-TBNA will be performed as standard of care, 5 passes with 15-30 agitations per station. EBUS sheath dilation followed by 5 passes with three samples per pass of forceps biopsies (1.9mm alligator forceps) will then be performed at all stations at which EBUS-TBNA was performed.
Intra-patient difference in diagnostic yield and specimen quality will be compared.
Objective:
To determine the difference in diagnostic yield of 19G EBUS-TBNA and EBUS-IFB in patients with radiographic findings suspicious for sarcoidosis.
Subject Population:
Inclusion criteria:
Patients 18 years or older with CT findings of mediastinal lymphadenopathy and parenchymal changes deemed suspicious for sarcoidosis who are undergoing bronchoscopy for diagnostic purposes.
Anticipated Number of Subjects Required:
55 for α 0.05, β 0.8 and baseline EBUS-TBNA diagnostic yield ~62.5% and conservative estimate of increase in yield to 80% with IFB.
Number of Sites:
Single-center study
Funding:
None
REVIEW and RATIONALE
Intranodal forceps biopsy using 1.0mm forceps has been utilized in diagnostic bronchoscopy since 2004 (1). Herth et al furthered this technique in 2008 by showing a remarkable increase in diagnostic yield for sarcoidosis (from 49 to 88%) in subcarinal lymph nodes larger than 2.5cm with minimal increased risk (2). It should be noted that patients in these studies were under general anesthesia and underwent rigid bronchoscopy. In 2011 and 2012, two studies showed differing results with respect to difference in diagnostic yield for non-malignant disease. (3,4) Herth et al again performed a study in 2012 showing safety and efficacy with IFB, however did not compare to TBNA and used larger lymph nodes (>1.5cm) and PET avidity as inclusion criteria (5). Darwiche et al showed significant increase in diagnostic yield in non-malignant disease. Furthermore, 33% of patients with sarcoidosis were positive by IFB and non-diagnostic by TBNA (6). Ray et al performed a retrospective analysis in 2020 showing increased diagnostic yield with cautery augmented IFB with 1.9mm forceps(7).
There appears to be a lack of knowledge as to whether the diagnostic yield and specimen quality of EBUS-TBNA with a 19G needle is less than those obtained by 1.9mm or greater intranodal forceps biopsy. The study proposed here will add to the field by further elucidating whether this procedure is beneficial for the diagnosis as it pertains to suspected sarcoidosis.
RESEARCH QUESTION and DESIGN
The question that this study will answer is whether EBUS-IFB is superior to EBUS-TBNA with respect to diagnostic yield and specimen quality as it pertains to radiographically suspected sarcoidosis cases.
Patients 18 years of age or older who are already undergoing diagnostic bronchoscopy with an indication of mediastinal or hilar lymphadenopathy AND parenchymal changes suspicious for sarcoidosis will be included in the study. Exclusion criteria will be isolated lymphadenopathy, isolated pulmonary parenchymal changes, suspicion of malignancy as the primary diagnosis, or contraindications to bronchoscopy or general anesthesia. Standard of care EBUS-TBNA will be performed with 5 passes (15-30 agitations per pass) at indicated nodes with a 19-gauge EBUS needle and sent for cytopathology. Following this, IFB will be performed as follows. Ultrasonographic identification of the same suspicious nodes. An EBUS needle will be used to enter the lymph node. The EBUS sheath will be advanced to dilate the tract from the airway to the lymph node. The EBUS needle will be withdrawn. A 1.9mm fenestrated alligator forceps will be introduced through the EBUS scope, and into the lymph node under direct ultrasonographic visualization. Three bites of tissue will be taken from the proximal aspect of the node to the distal aspect of the node. A total of five passes will be performed. This tissue will be sent for cytopathology and histopathology.
Tissue will be analyzed on both per-patient and per-nodal bases. Patient-level diagnosis of sarcoidosis will be defined as noncaseating granulomas in the absence of infection. If there are differences in pathologic diagnoses, a single, blinded pathologist will be asked to review all specimens for the patient. Specimen quality will be assessed by the amount of cellular material, background blood, degree of cellular degeneration and trauma, and retention of normal architecture. Quality in each subdomain will be scored on an ordinal 0 to 2 scale where higher scores reflect higher quality, resulting in an overall score ranging from 0 to 8.
The rate of diagnostic yield will be calculated taking the number of patients determined to have the disease with the respective approaches EBUS-TBNA or EBUS-IFB as the numerator and the total number of patients determined to have that disease from all approaches as the denominator (including endobronchial biopsies and transbronchial biopsies).
The anticipated required enrollment is 55 patients to achieve an α of 0.05 and β of 0.2. This assumes an unassisted diagnostic yield of 62.5% with standard of care EBUS-TBNA as reported in Ray et al, and a diagnostic supplementation to 80% yield with intranodal forceps biopsies.
References
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Oki, M., Saka, H., & Sako, C. (2004). Bronchoscopic miniforceps biopsy for mediastinal nodes. Journal of Bronchology & Interventional Pulmonology, 11(3), 150-153.
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Herth FJ, Morgan RK, Eberhardt R, Ernst A. Endobronchial ultrasound-guided miniforceps biopsy in the biopsy of subcarinal masses in patients with low likelihood of non-small cell lung cancer. Ann Thorac Surg. 2008 Jun; 85(6):1874-8.
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Chrissian A, Misselhorn D, Chen A. Endobronchial-ultrasound guided miniforceps biopsy of mediastinal and hilar lesions. The Annals of Thoracic Surgery. 2011;92(1):284-288.
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Franke KJ, Bruckner C, Szyrach M, Ruhle KH, Nilius G, Theegarten D. The contribution of endobronchial ultrasound-guided forceps biopsy in the diagnostic workup of unexplained mediastinal and hilar lymphadenopathy. Lung. 2012;190(2):227-232.
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Herth FJF, Schuler H, Gompelmann D, et al. Endobronchial ultrasound-guided lymph node biopsy with transbronchial needle forceps: a pilot study. European Respiratory Journal. 2012;39(2):373-377.
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Darwiche K, Freitag L, Nair A, et al. Evaluation of a novel endobronchial ultrasound-guided lymph node forceps in enlarged mediastinal lymph nodes. Respiration. 2013;86(3):229-236.
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Ray AS, Li C, Murphy TE, et al. Improved diagnostic yield and specimen quality with endobronchial ultrasound-guided forceps biopsies: a retrospective analysis. The Annals of Thoracic Surgery. 2020;109(3):894-901
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: EBUS-TBNA These will be the patient who undergo EBUS-TBNA only without EBUS-IFB |
Procedure: Endobronchial Ultrasound-Guided Intranodal Forceps Biopsy
Patients with mediastinal adenopathy will undergo EBUS-IFB and EBUS-TBNA during the same procedure to compare the yield of this procedure with EBUS-TBNA alone.
Other Names:
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| Experimental: EBUS-TBNA + EBUS-IFB These will be the individuals who undergo EBUS-TBNA followed by EBUS-IFB in the same procedure |
Procedure: Endobronchial Ultrasound-Guided Intranodal Forceps Biopsy
Patients with mediastinal adenopathy will undergo EBUS-IFB and EBUS-TBNA during the same procedure to compare the yield of this procedure with EBUS-TBNA alone.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Diagnostic Yield [1 year]
Diagnostic yield of EBUS-TBNA + EBUS-IFB compared to EBUS-TBNA alone
Secondary Outcome Measures
- Duration of Procedure [1 year]
Duration of combined EBUS-TBNA +IFB procedure compared to TBNA alone
- Complications [1 year]
Complications of EBUS-TBNA +IFB procedure compared to TBNA alone
Eligibility Criteria
Criteria
Inclusion Criteria:
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Radiologic evidence of mediastinal and/or hilar lymphadenopathy
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Attending radiologist or pulmonologist reports a possible diagnosis of sarcoidosis
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Age 18 years or older
Exclusion Criteria*:
These are the characteristics that a participant must NOT have in order to be eligible to participate in the study.
Order Number Criteria
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Severe pulmonary hypertension
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Inability to undergo general anesthesia
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Severe coagulopathy or bleeding diathesis
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Previously diagnosed sarcoidosis
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Patient presently taking clopidogrel
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Patient deemed to be high risk for general anesthesia per anesthesiologist
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Hemodynamic instability
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Mediastinitis
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Acute Hypercarbic Respiratory Failure (pCO2 >55mmHg)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The George Washington University Hospital | Washington | District of Columbia | United States | 20037 |
Sponsors and Collaborators
- George Washington University
Investigators
- Study Director: Mardi Gomberg, MD, The George Washington University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NCR224078