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11 #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.

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1 11 #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. 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. What is the yield of EBUS- TBNA versus conventional TBNA for Sarcoidosis. Describe the clinical implications of granulomatous inflammation detected on nodal histology. Describe the clinical implications of granulomatous inflammation detected on nodal histology. Bronchoscopy.org

2 2 2 Case description (practical approach # 10) A 72 year old male with a 25 pack-year history of smoking presents with cough. 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. 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. Computed tomography shows a 2.5 X 2.7 cm subcarinal lymph node. PET scan = increased activity ( SUV max 6) PET scan = increased activity ( SUV max 6) Patient is referred for diagnosis. Patient is referred for diagnosis.

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

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

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

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

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

8 8Bronchoscopy International Techniques and results Previous malignancy: expected results Previous malignancy: expected results EBUS in PET positive lymph nodes 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. 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. sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 97.4%, 100%, 100%, 87.5%, and 97.7% respectively. Noscoti M, Surg Endoscopy, 2008

9 9Bronchoscopy International Techniques and results Primary lung carcinoma: expected 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. 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). 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). 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). EUROPEAN JOURNAL OF CANCER ( )

10 10Bronchoscopy International For lymphoma EBUS-TBNA has a: For lymphoma EBUS-TBNA has a: Sensitivity- 90.9% Sensitivity- 90.9% Specificity- 100% Specificity- 100% Positive predictive value- 100% Positive predictive value- 100% Negative predictive value- 92.9% Negative predictive value- 92.9% study of nodes > 5 mm and SUV max > 4 study of nodes > 5 mm and SUV max > 4 Kennedy MP, et al, Thorax Apr Techniques and results

11 Tuberculosis: expected results Tuberculosis: expected results No published studies on the role of EBUS-TBNA for tuberculosis as of 9/2009 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% Conventional TBNA, however, has a sensitivity of 83%, specificity of 100%, positive predictive value of 100% and negative predictive value of 38% Accuracy=85% Accuracy=85% Bronchoscopy.org11 Bilaceroglu S et al. Chest 2004;126:

12 Techniques and results Sarcoidosis: expected 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): 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% Yield 93% Garwood S, Judson MA, Silvestri G et al. Endobronchial ultrasound for the diagnosis of pulmonary sarcoidosis. Chest 2007; 132(4): Garwood S, Judson MA, Silvestri G et al. Endobronchial ultrasound for the diagnosis of pulmonary sarcoidosis. Chest 2007; 132(4): Yield 82% 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): 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% Yield 91.8% Bronchoscopy.org12

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

14 For station 7, EBUS-TBNA and EUS-FNA have similar diagnostic rates Bronchoscopy.org14 Am J Respir Crit Care Med Vol 171. pp , 2005

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

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

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

18 Bronchoscopy.org18 Planning the procedure Lymph node Left Atrium Pulmonary vein

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

20 20 Procedural Techniques and Results Aspirate cytology Aspirate cytology Adequate/representative: in presence of frankly malignant cells, lymphocytes, lymphoid tissue, or 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* ** Inadequate/nonrepresentative: if there are no cellular components, scant lymphocytes (defined as <40 per HPF) blood only, or cartilage or bronchial epithelial cells only* ** *Am J Clin Pathol 2008;130: ** Chest 2008;134; ; *** Chest 2004;126; ****Techniques in GI Endoscopy, Vol 2, No 3, 2000: pp

21 21Bronchoscopy International 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. 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:

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

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

24 definition based on IASLC map 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 25 Bronchoscopy International CT views

26 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 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

27 27 Bronchoscopy International CORONALAXIAL

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

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

30 Simultaneous coronal CT view and EBUS image at station 7 Bronchoscopy.org30 The EBUS image at station 7 shows this pattern Coronal Subcarinal (station 7) lymph node on coronal CT view

31 31Bronchoscopy International To understand the use of coronal CT view one must understand the reference points on the EBUS image 1.The EBUS image is projected on the monitor as if the scope is horizontal 2.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 3.This dot is by default towards the 1oclock position of the screen caudalcephalad

32 32Bronchoscopy International While the coronal CT view is displayed as if the scope is vertical 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 oclock position on the screen) to match the EBUS image… cephalad caudal P. vein Left Atrium cephalad caudal P. vein Left Atrium

33 33Bronchoscopy International 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 oclock position. Step by Step cephalad caudal P. vein Left Atrium cephalad caudal P. vein Left Atrium

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

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

36 36Bronchoscopy International Conventional vs. EBUS TBNA for Sarcoidosis EBUS-TBNA to standard 19-gauge TBNA in patients with mediastinal adenopathy and a clinical suspicion of 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) 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 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% an absolute increase of 29.5% Tremblay A et al. Chest Aug;136(2):340-6.

37 37 Bronchoscopy International EBUS-TBNA vs. Conventional TBNA for Sarcoidosis Tremblay A et al. Chest Aug;136(2):340-6.

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

39 39Bronchoscopy International 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: 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.

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 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 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%) 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. 8/153 (5.2%) patients with new mediastinal lymphadenopathy and no prior history of cancer had a clinical syndrome consistent with sarcoidosis. Bronchoscopy.org40 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 The diagnosis of sarcoidosis or sarcoid like lymphadenopathy was made if clinico-radiological findings were supported by histopathologic findings from EBUS-TBNA histopathologic findings from EBUS-TBNA appropriate exclusion of other granulomatous diseases 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 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 Bronchoscopy.org41 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 therapy 1. Attributing radiographic findings such as mediastinal lymphadenopathy without tissue confirmation as cancer recurrence can lead to unnecessary and toxic therapy 1. 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 progression 2 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 progression 2 Bronchoscopy.org42 (1). Kok TC et al. Cancer 1991, 68: (2). Kennedy MP et al. Journal of Cardiothoracic Surgery 2008, 3:8

43 43 Bronchoscopy.org 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

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


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