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#10. Planning EBUS-TBNA of subcarinal lymph node (station 7)

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1 #10. Planning EBUS-TBNA of subcarinal lymph node (station 7)
Describe how the coronal view of a computed tomography scan can be used to help plan the procedure. What is the yield of EBUS-TBNA versus conventional TBNA for Sarcoidosis. Describe the clinical implications of granulomatous inflammation detected on nodal histology. 1

2 Case description (practical approach # 10)
A 72 year old male with a 25 pack-year history of smoking presents with cough. Past medical history: COPD (FEV1 40% predicted) and right toe amputation for melanoma 5 years earlier. Computed tomography shows a 2.5 X 2.7 cm subcarinal lymph node. PET scan = increased activity ( SUV max 6) Patient is referred for diagnosis. 2

3 Case description (practical approach #10)
Axial CT view Coronal CT view Subcarinal lymph node on axial and coronal CT views 3

4 The Practical Approach
Initial Evaluation Procedural Strategies Techniques and Results Long term Management Examination and, functional status Significant comorbidities Support system Patient preferences and expectations Indications, contraindications, and results Team experience Risk-benefits analysis and therapeutic alternatives Informed Consent Anesthesia and peri-operative care Techniques and instrumentation Anatomic dangers and other risks Results and procedure-related complications Outcome assessment Follow-up tests and procedures Referrals Quality improvement 4

5 Initial Evaluations Exam Comorbidities Support system
Decreased air entry bilaterally and prolonged exhalation WHO functional status I Comorbidities COPD Support system Lives with wife at home Patient preferences Desires diagnosis and treatment of his cough 5

6 Procedural Strategies
Indications Sample station 7(subcarina) Common differential diagnosis of mediastinal lymphadenopathy is: Metastatic primary lung carcinoma Metastatic extrapulmonary carcinoma Lymphoma Tuberculosis Sarcoidosis 6

7 Procedural Strategies
Contraindications: None Experienced team and operator Risks-benefits: No serious complications reported in the literature. Agitation, cough, and presence of blood at puncture site reported infrequently.** Benefits: accurate, safe and same day procedure. Level 7 could be sampled by conventional TBNA or Mediastinoscopy. *Chest 2004; 125:322–325 **Eur Respir J 2009; 33: 1156–1164 7

8 Techniques and results
Previous malignancy: expected results EBUS in PET positive lymph nodes N=73 lymph nodes were tested by EBUS-TBNA on 48 consecutive patients, each patient underwent to mediastinoscopy or thoracoscopy immediately after needle aspiration for histological confirmation. sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 97.4%, 100%, 100%, 87.5%, and 97.7% respectively. A cytological sampling adequate for diagnosis was obtained in 45 patients (93.7%); the three cases of inadequate sampling resulted as negative for cancer. All EBUS procedures were performed under conscious sedation; Overall, 73 lymph nodes were tested by TBNA on 48 patients. Of these patients, 38 had had non-small-cell lung cancer, 4 colonic cancers, 3 renal cancers, 1 breast and colonic cancer, 1 thyroid cancer, and 1 hepatocellular carcinoma. The mean size of lymph node tested was 17.8 mm. The lymph node stations that were explored with TBNA were 7 (52.5%), 4R (19%), 4L (14%), 3 (9.5%), and 10R (5%). There were a mean number of 1.8 needle aspirations per lymph node. Noscoti M, Surg Endoscopy, 2008 Bronchoscopy International 8

9 Techniques and results
Primary lung carcinoma: expected results Metanalysis: A total of 11 studies with 1299 patients, who fulfilled all of the inclusion criteria, were considered for the analysis. No publication bias was found. EBUS-TBNA had a pooled sensitivity of 0.93 (95% CI, 0.91–0.94) and a pooled specificity of 1.00 (95% CI, 0.99–1.00). The subgroup of patients who were selected on the basis of CT or PET positive results had higher pooled sensitivity (0.94, 95% CI 0.93–0.96) than the subgroup of patients without any selection of CT or PET (0.76, 95% CI 0.65–0.85) (p < 0.05). According to these data, the subgroup of patients selected on the basis of CT or PET positive results had higher pooled sensitivity (0.94, 95% CI 0.93–0.96) than the subgroup of patients without any selection of CT or PET (0.76, 95% CI 0.65–0.85) (p < 0.05). Bronchoscopy International EUROPEAN JOURNAL OF CANCER ( ) 9

10 Techniques and results
For lymphoma EBUS-TBNA has a: Sensitivity- 90.9% Specificity- 100% Positive predictive value- 100% Negative predictive value- 92.9% study of nodes > 5 mm and SUV max > 4 The EBUS-TBNA result was compared with a reference standard of pathological tissue diagnosis or a composite of >6 months of clinical follow-up with radiographic imaging. Nodes> 5 mm and SUV max > 4 Bronchoscopy International Kennedy MP, et al, Thorax Apr 10

11 Techniques and results
Tuberculosis: expected results No published studies on the role of EBUS-TBNA for tuberculosis as of 9/2009 Conventional TBNA, however, has a sensitivity of 83%, specificity of 100%, positive predictive value of 100% and negative predictive value of 38% Accuracy=85% Bilaceroglu S et al. Chest 2004;126:

12 Techniques and results
Sarcoidosis: expected results Oki M, Saka H, Kitagawa C et al. Real-time endobronchial ultrasound-guided Transbronchial needle aspiration is useful for diagnosing Sarcoidosis. Respirology 2007; 12(6): Yield 93% Garwood S, Judson MA, Silvestri G et al. Endobronchial ultrasound for the diagnosis of pulmonary sarcoidosis. Chest 2007; 132(4): Yield 82% Wong M, Yasufuku K, Nakajima T et al. Endobronchial ultrasound: new insight for the diagnosis of sarcoidosis. Eur Respir J 2007; 29(6): Yield 91.8%

13 Procedural Strategies
Diagnostic alternatives: EUS-FNA( esophageal ultrasound reaches station 7); Sensitivity 81-97% Specificity % ** Mediastinoscopy: considered gold standard. Bronchoscopic airway inspection would still be required VATS: most invasive of alternatives. Only provides access to ipsilateral nodes. 75% sensitivity***. Benefits include definitive lobar resection at same time if node negative. Data from studies evaluating patients with suspected/confirmed lung cancer *Chest. 2003; 123: **Lung Cancer. 2003; 41: ***Chest 2007;132; 13

14 For station 7, EBUS-TBNA and EUS-FNA have similar diagnostic rates
Am J Respir Crit Care Med Vol 171. pp , 2005

15 Procedural techniques and results Anesthesia and perioperative care
Conscious (moderate) sedation May be performed in bronchoscopy suite Cost savings compared to general anesthesia. Visualization and biopsy of smaller nodes technically more difficult than with general anesthesia. General anesthesia with LMA (#4 or 4.5 ) Better visualization of higher nodes ( station 1 and 2) compared with ET tube May not be appropriate in severe obesity or severe untreated GERD General anesthesia with ET tube (#8.5 for female and #9 for male patients) Usually performed in OR . EBUS scope directed more centrally in airway which may make biopsies more difficult J Cardiothorac Vasc Anesth 2007; 21:892–896 15 Chest 2008;134;

16 Procedural Techniques and Results
Instrumentation EBUS scope- direct real time US imaging with curved array ultrasound transducer incorporated in distal end of bronchoscope Ultrasound processor Adjustable gain and depth B mode and Doppler capabilities Needle 22 gauge acrogenic needle with stylet Needle guide system locks to scope Lockable needle and sheath Precise needle projection up to 4 cm 16

17 Procedural Techniques and Results
Anatomic dangers and other risks Major vascular structures Risk of canulating major vessel may be reduced with real time B mode and Doppler mode imaging “Minor” oozing of blood at puncture site was reported in 1 study; there have been no reports of major bleeding* Pneumothorax and pneumomediastinum** Have been reported with conventional TBNA but no reports in literature with EBUS guided FNA. Chest 2004;126; **Eur Respir J 2002; 19:356–373 17

18 Planning the procedure
Lymph node Left Atrium Pulmonary vein

19 Results Results and procedure-related complications
EBUS-TBNA was performed under general anesthesia using a 9.0 endotracheal tube. Subcarinal cytology showed granulomatous inflammation Bronchoscopic inspection : normal airway mucosa There were no complications. 19

20 Procedural Techniques and Results
Aspirate cytology Adequate/representative: in presence of frankly malignant cells, lymphocytes, lymphoid tissue, or clusters of anthracotic pigment-laden macrophages* Inadequate/nonrepresentative: if there are no cellular components, scant lymphocytes (defined as <40 per HPF) blood only, or cartilage or bronchial epithelial cells only* ** A quantitative cut off value of at least 30% of cellularity composed of lymphocytes has been arbitrarily proposed by some experts*** Higher yield may be obtained by obtaining aspirates from the periphery of nodes**** *Am J Clin Pathol 2008;130: **Chest 2008;134; ; ***Chest 2004;126; ****Techniques in GI Endoscopy, Vol 2, No 3, 2000: pp

21 In some cases of nodal replacement by granulomatous or metastatic disease, lymphoid tissue might not be seen In addition, the presence and quantity of bronchial cells may have no bearing on adequacy because these cells are found in the majority of samples, without correlation with the number of lymphocytes. Am J Clin Pathol 2008;130: Bronchoscopy International

22 Long-term Management Plan
Outcome assessment Adequate specimen obtained but no specific diagnosis Follow-up tests and procedures Mediastinoscopy was deferred. Computed tomography was scheduled in 3 months to re-evaluate the mediastinal lymphadenopathy Work up for sarcoidosis Fungal antibodies to rule out infection as a cause of the granulomatous inflammation Referrals Oncology to re-evaluate for possible melanoma recurrence and potentially obtain full body PET/CT Quality improvement No confident diagnosis was made on EBUS-TBNA 22

23 Q 1: Describe how the coronal view of a computed tomography scan can be used to help plan the procedure.

24 Subcarina (Station 7): definition based on IASLC map
Upper border: the carina of the trachea Lower border: the upper border of the lower lobe bronchus on the left; the lower border of the bronchus intermedius on the right (J Thorac Oncol. 2009;4: 568–577)

25 Bronchoscopy International
CT views Bronchoscopy International 25 25

26 Bronchoscopy International
CT views: coronal A coronal (aka frontal) plane is perpendicular to the ground, which (in humans) separates the anterior from the posterior, the front from the back, the ventral from the dorsal Bronchoscopy International 26 26

27 Bronchoscopy International
CORONAL AXIAL 27 Bronchoscopy International 27

28 Which CT view is most useful for planning EBUS-TBNA for 7?
12 9 Drawing modified from Herth F et al. J Bronchol Volume 13, Number 2, 2006 Bronchoscopy from head of patient EBUS scope in the RMB with the probe facing medially towards 9 o’clock

29 The coronal CT view identifies the EBUS scanning plane
cephalad caudal P. vein Left Atrium LN Drawing modified from Herth F et al. J Bronchol Volume 13, Number 2, 2006 Bronchoscopy International 29 29 29

30 Simultaneous coronal CT view and EBUS image at station 7
The EBUS image at station 7 shows this pattern Subcarinal (station 7) lymph node on coronal CT view

31 Bronchoscopy International
To understand the use of coronal CT view one must understand the reference points on the EBUS image caudal cephalad The EBUS image is projected on the monitor as if the scope is horizontal The green dot on the monitor represents the point where the needle exits the scope and corresponds to the superior (cephalad) aspect of the body This dot is by default towards the 1’o’clock position of the screen Bronchoscopy International 31 31 31

32 While the coronal CT view is displayed as if the scope is vertical
cephalad caudal P. vein Left Atrium cephalad caudal P. vein Left Atrium Several adjustments can be made to the coronal CT image in order to bring the scope to a horizontal position, the green dot cephalad (towards the 1 o’clock position on the screen) to match the EBUS image… Bronchoscopy International 32 32 32

33 Bronchoscopy International
cephalad caudal P. vein Left Atrium Step by Step cephalad caudal P. vein Atrium Left 1. Print out a single frame of the CT image 2. Rotate the CT image clockwise in order to horizontalize the scope and bring the green dot cephalad towards the 1 o’clock position. Bronchoscopy International 33 33 33

34 The two images now correlate and show all structures in the same locations
cephalad caudal Left Atrium LN caudal cephalad LN Left Atrium See how easy it is to identify the anatomic structures now ! This is a characteristic EBUS view of the subcarinal node Bronchoscopy International 34 34 34

35 Q 2: Describe the yield of EBUS-TBNA versus conventional TBNA for sarcoidosis.

36 Conventional vs. EBUS TBNA for Sarcoidosis
EBUS-TBNA to standard 19-gauge TBNA in patients with mediastinal adenopathy and a clinical suspicion of sarcoidosis. N= 50 ( 24 EBUS, 26 conventional) The primary outcome measure of diagnostic yield was 53.8% versus 83.3% in favor of the EBUS-TBNA group an absolute increase of 29.5% After blinded research pathology review, diagnostic yield was 73.1% versus 95.8%, in favor of the EBUS-TBNA group, an absolute increase of 22.7 %. Sensitivity and specificity were 60.9% and 100% in the standard TBNA group and 83.3% and 100% in the EBUS-TBNA group (22.5% absolute increase in sensitivity; p=0.085; 95% CI -3.2% to 44.9%), respectively. pathological mediastinal or hilar adenopathy (>1 cm short axis). Transbronchial needle aspiration was the only positive test in 10/26 (38.5%) and 11/24 (45.8%) cases in the standard TBNA versus EBUS-TBNA, respectively (p>0.05). This resulted in a high overall diagnostic rate for bronchoscopy including EBUS-TBNA of 91.7% in a patient group with a high prevalence of stage I disease. 36 Bronchoscopy International Tremblay A et al. Chest Aug;136(2):340-6. 36 36

37 EBUS-TBNA vs. Conventional TBNA for Sarcoidosis
The aim of this study was to compare the diagnostic yield of EBUS-guided TBNA to TBNA performed with a standard 19-gauge needle in patients with mediastinal adenopathy and a clinical suspicion of Sarcoidosis Rapid on-site cytological evaluation (ROSE) was not performed. Bronchoscopy International 37 Tremblay A et al. Chest Aug;136(2):340-6. 37 37

38 Q3:Describe the clinical implications of granulomatous inflammation detected on EBUS-TBNA specimens

39 Granulomatous inflammation can coexist with malignancy and may be an epiphenomenon
Lymph nodes harboring both necrotizing and nonnecrotizing granulomas and metastatic malignancies have been reported: Laurberg P. Sarcoid reactions in pulmonary neoplasms. Scand J Respir Dis. 1975;56:20-27. Cohen PR, Kurzrock R. Sarcoidosis and malignancy. Clin Dermatol. 2007;25: Pandey M, Abraham EK, Chandramohan K, et al. Tuberculosis and metastatic carcinoma coexistence in axillary lymph node: a case report. World J Surg Oncol. 2003;1:3. Bronchoscopy International 39

40 Clinical implication of granulomatous inflammation on EBUS-TBNA specimens
N=153 patients with mediastinal lymphadenopathy on CT imaging at a cancer institution and noncaseating granulomas seen on EBUS-TBNA Non-caseating granuloma in 17/153 (11%) patients in patients w/o any evidence of cancer 8/153 (5.2%) had sarcoid like lymphadenopathy mimicking cancer recurrence (5/5 PET positive) 8/153 (5.2%) patients with new mediastinal lymphadenopathy and no prior history of cancer had a clinical syndrome consistent with sarcoidosis. Kennedy MP et al. Journal of Cardiothoracic Surgery 2008, 3:8

41 Clinical implication of granulomatous inflammation on EBUS-TBNA specimens
The diagnosis of sarcoidosis or sarcoid like lymphadenopathy was made if clinico-radiological findings were supported by histopathologic findings from EBUS-TBNA appropriate exclusion of other granulomatous diseases a composite of clinical history, follow-up and laboratory results including tissue staining for fungi and acid fast bacilli (AFB), fungal and mycobacterial cultures and serum fungal antibody titers Kennedy MP et al. Journal of Cardiothoracic Surgery 2008, 3:8

42 Take home messages Attributing radiographic findings such as mediastinal lymphadenopathy without tissue confirmation as cancer recurrence can lead to unnecessary and toxic therapy1. If granulomatous inflammation is identified by EBUS-TBNA in a patient with suspected cancer recurrence, a reasonable clinical approach is to follow the patient radiographically without additional invasive testing, unless there is radiographic progression2 (1). Kok TC et al. Cancer 1991, 68: (2). Kennedy MP et al. Journal of Cardiothoracic Surgery 2008, 3:8

43 All efforts are made by Bronchoscopy International to maintain currency of online information. All published multimedia slide shows, streaming videos, and essays can be cited for reference as: Bronchoscopy International: Practical Approach, an Electronic On-Line Multimedia Slide Presentation. Published 2009 (Please add “Date Accessed”). Thank you 43

44 Prepared with the assistance of Septimiu Murgu M. D
Prepared with the assistance of Septimiu Murgu M.D., University of California, Irvine 44

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