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EBUS-TBNA in patients presented with superior vena cava syndrome
Lung Cancer 77 (2012) 277–280
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Lung Cancer journal homepage: www.elsevier.com/locate/lungcan
EBUS-TBNA in patients presented with superior vena cava syndrome Matthew K. Wong, Terence C. Tam, David C. Lam, Mary S. Ip, James C. Ho ∗ Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
a r t i c l e
i n f o
Article history: Received 1 December 2011 Received in revised form 13 March 2012 Accepted 19 March 2012 Keywords: Endobronchial ultrasound Transbronchial needle aspiration Diagnostic yield Superior vena cava obstruction Lung cancer Mediastinal lymphadenopathy
a b s t r a c t Introduction: Expedient pathological diagnosis is crucial in selection of appropriate treatment in patients presented with superior vena cava syndrome (SVCS). The performance and safety of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in this setting is unknown. Methods: Over a 4-year period, patients presented with SVCS in the presence of mediastinal mass and referred for EBUS-TBNA were enrolled for the study. The procedure was performed under local anaesthesia with conscious sedation. TBNA was performed under real-time with the curvilinear probe of EBUS. Rapid on site cytological examination (ROSE) was not available. Results: Eighteen procedures of EBUS-TBNA were performed in 17 patients. Malignancy was confirmed in 16 patients (diagnostic yield 94.1%). There was no major complication including significant bleeding or pneumothorax related to the procedures. Conclusions: EBUS-TBNA has high diagnostic yield and is safe in patients presented with SVCS and mediastinal mass. © 2012 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Superior vena cava obstruction (SVCO) is caused by extrinsic compression or intraluminal blockade of the superior vena cava, due to mediastinal lymphadenopathy or right upper lobe lung tumour with mediastinal invasion. Clinically, it manifests as the distressful superior vena cava syndrome (SVCS) which is comprised of swelling of face, neck and upper limbs, headache, dyspnoea, orthopnoea and in severe cases, stridor. Over 80% of the cases of SVCO result from neoplastic causes, mostly lung cancers (75%) and lymphoma [1–4]. Not uncommonly, immediate radiotherapy may be commenced to treat SVCS before a pathological diagnosis is obtained in order to relieve severe obstructive symptoms. Nonetheless, a histological diagnosis for the cause of SVCO is preferred prior to empirical radiotherapy as some tumours, notably small cell lung cancer and non-Hodgkin’s lymphoma, are best treated with upfront systemic chemotherapy. Also, prebiopsy irradiation of the mass lesion often leads to difficult pathological interpretation of tissue samples [5], and makes further management more complicated [6–9]. Therefore, unless there are
Abbreviations: CT, computed tomography; EBUS, endobronchial ultrasound; TBNA, transbronchial needle aspiration; NPC, nasopharyngeal carcinoma; NSCLC, non-small cell lung cancer; ROSE, rapid on site cytological examination; SVCO, superior vena cava obstruction; SVCS, superior vena cava syndrome. ∗ Corresponding author at: Division of Respiratory Medicine, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong. Tel.: +852 2255 4999; fax: +852 2872 5828. E-mail addresses: [email protected], [email protected] (J.C. Ho). 0169-5002/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.lungcan.2012.03.015
alternative readily accessible tumour sites, the ability to biopsy at the mediastinal tumour causing SVCO is of utmost importance. A histological diagnosis can be obtained by conventional techniques of bronchoscopy, however, bronchoscopic biopsy in patients with evidence of SVCS is often considered to be a high-risk procedure with increased risk of bleeding [10] and airway oedema [11]. With the advent of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) as a relatively safe procedure in establishing the diagnosis of mediastinal mass, there is good clinical rationale of its application to SVCO. To date, there is yet no reported data regarding the use of EBUS-TBNA in patients suffering from SVCS due to malignant causes. The aim of this study is to review the diagnostic yield and safety of EBUS-TBNA to expedite the management of patients presented with SVCS in our institution. 2. Methods 2.1. Patients and procedures From August 2007 to August 2011, patients referred for EBUSTBNA with initial presentation of SVCS (oedema over head and neck, upper extremities, dilated collateral veins in the upper portion of the thorax and arms, and/or jugular venous distension) were recruited into the study. Contrast computed tomography (CT) scan of thorax was arranged on an urgent basis. Patients with radiological SVCO on CT scan without clinical features of SVCS on presentation were not included. Patients were also excluded if they had prior known diagnosis leading to SVCS or benign causes of
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SVCS such as the catheter-related (e.g. Hickman, haemodialysis) thrombosis without abnormal mediastinal lesion on CT scan. Written informed consent was obtained from all participants. During the interview for informed consent, alternative clinical approaches including other means of obtaining tissue diagnosis or empirical treatment with radiotherapy would be discussed. This study has been approved by the Institutional Review Board (HKU/HA HKW). Prior to EBUS, hydrocortisone 100 mg was given intravenously as steroid cover for patients who received systemic steroid prior to bronchoscopy. Patients were lying in semi-reclined position for comfort before given conscious sedation, while the monitoring was the same as those undergoing routine conventional bronchoscopy. EBUS-TBNA was performed with a flexible ultrasonic bronchoscope with a curvilinear ultrasound probe of frequency of 7.5 MHz (XBFUC260F-OL8, Olympus, Tokyo, Japan) under conscious sedation by intravenous injection of pethidine with or without midazolam. Airway was anaesthetized with doses (2 ml each) of 2% lignocaine, delivered through the bronchoscope. Suspicious lesions over the paratracheal, hilar and subcarinal regions were scanned. Power Doppler was performed before needle puncture with a designated 22-Guage needle under real-time guidance. One to five passes were made at each region. Both cytology and histology specimens were sent for pathological analysis in addition to microbiological studies including acid-fast bacilli and fungus. Rapid on-site cytological examination (ROSE) was unavailable during the study. Subsequently, conventional bronchoscopy was performed for airway assessment and endobronchial biopsy was performed if appropriate in the same setting. Complications related to EBUS-TBNA and conventional flexible fibreoptic bronchoscopy were recorded accordingly, in particular oxygen desaturation and major bleeding. Major bleeding was defined as haemorrhage that required haemostasis such as application of topical adrenaline and/or cold saline. Chest X-ray was performed to rule out pneumothorax after the procedure. 2.2. Statistical analysis The baseline characteristics were performed with descriptive statistics. The diagnostic yield was defined as the percentage of patients diagnosed by EBUS-TBNA. 3. Results EBUS-TBNA was first introduced in our centre since August 2006. Eighteen EBUS-TBNA procedures were performed in 17 consecutive patients presented with SVCS from August 2007 to August 2011. Although our patients included in this study were having SVCS, they were otherwise not critically ill. All had lesions at the right lower paratracheal region while 9 out of 17 (52.9%) had lesions (>1 cm) at the subcarinal region. A median of 1 region per patient (range 1–3) was aspirated with a median of 3 needle passes per node (range 1–4) (Table 1). Although EBUS-TBNA was introduced in our institution since 2006, EBUS-TBNA was performed in 7 out of 17 (41.2%) patients as the first pathological diagnostic investigation. One patient had prior nondiagnostic thoracentesis. Nine patients (52.9%) had conventional bronchoscopy (without blind TBNA) and two of them required additional thoracentesis, which were all non-diagnostic, before referral for EBUS-TBNA. In cases where endobronchial lesion was initially suspected based on CT findings, pathological diagnosis could only be reached in 3/17 (17.6%) patients with conventional bronchoscopy. The diagnosis was confirmed with EBUS-TBNA in 16 out of 17 (94.1%) patients presented with SVCS, while one patient had EBUS-TBNA performed twice and no patient required mediastinoscopy. None except one patient had received upfront
Table 1 Clinical data of 17 patients undergoing EBUS-TBNA. Age (mean ± SD) Gender (M:F) Size of target lesion on CT scan Right paratracheal area, cm (mean ± SD) Subcarinal area, cm (mean ± SD) Procedure (total 18) Premedication with steroid cover (n [%]) Use of pethidine ± midazolam (n [%]) Stations sampled (median [range]) Needle aspirated per station (median [range]) Diagnostic yield Procedures (n = 18), (no [%]) Patients (n = 17), (no [%]) Final diagnosis (total 17) Lung cancer (n [%]) Small cell carcinoma Adenocarcinoma Squamous cell carcinoma NSCLC, poorly differentiated Non-pulmonary malignancy (n [%]) (breast, endometrium, NPC) Carcinoma, not otherwise specified (n [%]) No diagnosis (no [%]) Complications Increased oxygen supplement during procedure (n [%]) Significant bleeding (requiring haemostatic measures)
63 ± 12 13:4 3.53 ± 1.33 1.14 ± 1.21 13 [72.2%] 18 [100%] 1 [1–3] 3 [1–4] 16 [88.9%] 16 [94.1%] 12 [70.6%] 5 4 2 1 3 [17.6%] 1 [5.9%] 1 [5.9%] 5 [27.8%] 0
radiotherapy prior to EBUS-TBNA in which non-small cell carcinoma (not otherwise specified) was obtained. Six patients (35.3%) had history of extrathoracic malignancy but only three (50%) of them had SVCS caused by the same malignancy as in the past (Table 2). There was no significant bleeding associated with EBUS-TBNA whereas three patients (17.6%) had significant bleeding with conventional bronchoscopy (two from endobronchial biopsy and one from transbronchial lung biopsy), requiring topical adrenaline and/or cold saline for haemostasis. Transient increase in supplemental oxygen was required in five (27.8%) procedures undergoing EBUS-TBNA. There was no procedure-related mortality. 4. Discussion Timely establishment of the underlying diagnosis of SVCS is imperative for starting appropriate treatment so that patients can have effective chemotherapy especially if small cell carcinoma or lymphoma is confirmed. In our series, five patients (30%) were confirmed small cell carcinoma that allowed timely systemic treatment and even in patients diagnosed to have NSCLC, the appropriate choice of chemotherapy was largely dictated by the exact cell type (adenocarcinoma versus squamous cell carcinoma) [12]. Upfront radiotherapy may not be the optimal treatment since sampling of the irradiated lesion precludes proper pathological classification in 40% of cases [5]. Among all patients confirmed with malignancy, EBUS-TBNA revealed diagnosis of specific cell type and origin of primary lesion except one who had upfront radiotherapy prior to tissue sampling, in which a pathologically non-specific carcinoma made subsequent chemotherapy challenging. Both the primary site of malignancy and duration prior to EBUS-TBNA appeared unrelated to the final diagnosis (Table 2). Bronchogenic carcinoma is by far the commonest cause of SVCS and conventional bronchoscopic forceps biopsy appears to be a reasonable approach to this condition. However, the diagnostic yield is suboptimal ranging from 40 to 67% [2,4,13–15] and may be explained by the extrinsic compression of the bronchus without endobronchial invasion. Also, bleeding complication after the initial forceps biopsy may prohibit further sampling and therefore affect the diagnostic performance as suggested in our present study. To the best of our knowledge, this is the first report that describes the
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Table 2 Patients with SVCS with known malignancy prior to EBUS-TBNA. Primary malignancy
Number of years prior to EBUS
Diagnosis by EBUS-TBNA
Same origin of primary malignancy as revealed by EBUS-TBNA
Laryngeal carcinoma Carcinoma of breast Nasopharyngeal carcinoma Heptaocellular carcinoma Carcinoma of rectum Carcinoma of endometrium
20 13 9 4 3 2
Adenocarcinoma of lung Carcinoma of breast Nasopharyngeal carcinoma Carcinoma, NOSa Squamous cell carcinoma of lung Carcinoma of endometrium
No Yes Yes Indeterminateb No Yes
a b
NOS: not otherwise specified. This patient received upfront irradiation of lesion prior to EBUS-TBNA. Indeterminate: pathological diagnosis could not definitely determine the origin.
role of EBUS-TBNA in SVCS due to a mediastinal mass. As there is no standard protocol on the workflow of investigations for SVCS, various methods were adopted as first-line investigation. From our experience, seven patients (41.2%) had EBUS-TBNA as their first investigation which turned out to be diagnostic in all. The rest of our cohort had EBUS-TBNA as the subsequent investigation after unrevealing workup, e.g. conventional bronchoscopy or thoracentesis. The overall diagnostic yield of EBUS-TBNA in SVCS was found to be 94.1%. If available, rapid on-site cytological examination (ROSE) is preferred in ensuring adequate tissue obtained during the procedure and minimizing the number of needle passes. In most cases, the compression of SVC is caused by lesions in the mediastinum, right paratracheal or precarinal areas [16], which can be readily accessible by conventional TBNA with diagnostic yield of 67–96% [17,18]. In contrast to EBUS-TBNA, conventional TBNA without EBUS guidance resulted in premature termination of procedures due to haemorrhage or loss of adequate bronchoscopic view in 7.7–13.3% [17,18]. In addition, the opening of collateral vessels might increase risk for excessive bleeding during biopsy [18]. EBUS has the built-in power Doppler which allows real-time identification of any prominent vasculature next to or within the target lesion, especially important with distorted anatomy due to the huge mediastinal mass (Fig. 1). There was no major bleeding in our patients undergoing EBUS-TBNA, but the complication was more commonly encountered with forceps biopsy. EBUS-TBNA was performed twice in one patient suffering from nasopharyngeal carcinoma (NPC), as the first procedure could only yield squashed lymphoid tissue. He was later diagnosed as having metastatic disease to the mediastinum from nasopharyngeal carcinoma on second EBUS-TBNA. Only one patient ultimately received no pathological diagnosis after EBUS-TBNA and extensive investigations including conventional bronchoscopy, thoracentesis and pleural biopsy, who died 2 months after presentation. Both patients illustrated the examples of sampling error for needle biopsy of enlarged lymph nodes. Although EBUS-TBNA can be performed with the needle passing away from the cystic necrosis inside the grossly enlarged lymph node, a newer EBUS processor system might be able to further elucidate the necrotic centre within the targeted lymph node [19]. Surgical approach under general anaesthesia was shown to have high diagnostic yield [20], however, only limited number of patients were considered suitable for these procedures with major complications including major haemorrhages and airway obstructions in up to 13% [20]. In addition, surgery should better be avoided in these unresectable patients with SVCS, who might not even be able to assume supine position during the operation. On the other hand, the use of needle aspiration in obtaining the pathological diagnosis with SVCS was reported with transthoracic approach under ultrasound guidance [6,21,22]. However, only 33% [21] to 42% [22] of patients presented with SVCS were suitable for this approach. The inherent limitation of transthoracic approach under ultrasound guidance is the inability of visualizing the lesion
when it is not abutting or invading the chest wall, which can still be reached with EBUS-TBNA. The additional advantage of bronchoscopic approach includes the ability to assess the airways for endobronchial stenting and biopsy of endobronchial lesion. Endovascular stenting of SVC has emerged as a feasible treatment option for SVCS, with rapid symptomatic relief and improvement of quality of life. Two of our patients had endovascular stenting performed 1 week and 1 month before EBUS-TBNA. Both of them received low molecular weight heparin after stenting and were withheld temporarily prior to EBUS-TBNA. No bleeding or
Fig. 1. (A) Power Doppler sonogram showing the tumour mass (dotted line) that invaginates into the brachiocephalic artery (BCA). (B) Computed tomography scan of the same patient showing the tumour that invades into the mediastinum.
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thrombotic complication was found. It has been shown that needle aspiration was safe even in patients who had risk of bleeding including vascular carcinoid tumours in the presence of coagulopathy [2]. Our preliminary experience suggests that endovascular stenting prior to EBUS-TBNA to the mediastinal tumour may be a reasonable approach for those with very symptomatic SVCS. Nonetheless, majority (88.2%) of our patients underwent EBUS-TBNA smoothly without preceding endovascular stenting of SVC. In fact, one patient failed to have endovascular stenting because of the complete intraluminal obstruction of SVC. Although percutaneous stenting of SVC has been reported to have high success rate and low morbidity, serious complications like cardiac tamponade have occurred [23]. As only patients referred for EBUS-TBNA were recruited, patients who underwent other methods to establish pathological diagnosis such as direct surgical exploration, imaging guided transthoracic needle aspiration were not investigated, which did not allow direct comparison of different diagnostic modalities in our study. The size of the paratracheal lymph nodes in our cohort was huge, in which smaller sized lymph nodes might be less accessible, though the average size of subcarinal lymph nodes in our series was only around 1 cm. However, our findings would strongly support the safety and high diagnostic yield of EBUS-TBNA in SVCS. When there is no readily accessible tumour site for tissue diagnosis such as supraclavicular lymph node or pleural fluid, EBUS-TBNA is often the least invasive and yet highly diagnostic investigation in SVCS, allowing high quality specimens for exact pathological classification and molecular profiling. Conflict of interest statement All authors in this manuscript have no financial and personal relationships with other people or organizations that could inappropriately influence our work. None of the authors have conflict of interest to declare. Acknowledgements There is no funding source to declare. No writing assistance was sought in the preparation of this report. References [1] Bell DR, Woods RL, Levi JA. Superior vena caval obstruction: a 10-year experience. Med J Aust 1986;145:566–8. [2] Schraufnagel DE, Hill R, Leech JA, Pare JA. Superior vena caval obstruction. Is it a medical emergency? Am J Med 1981;70:1169–74.
[3] Parish JM, Marschke Jr RF, Dines DE, Lee RE. Etiologic considerations in superior vena cava syndrome. Mayo Clin Proc 1981;56:407–13. [4] Yellin A, Rosen A, Reichert N, Lieberman Y. Superior vena cava syndrome. The myth—the facts. Am Rev Respir Dis 1990;141:1114–8. [5] Loeffler JS, Leopold KA, Recht A, Weinstein HJ, Tarbell NJ. Emergency prebiopsy radiation for mediastinal masses: impact on subsequent pathologic diagnosis and outcome. J Clin Oncol 1986;4:716–21. [6] Ko JC, Yang PC, Yuan A, Chang DB, Yu CJ, Wu HD, et al. Superior vena cava syndrome. Rapid histologic diagnosis by ultrasound-guided transthoracic needle aspiration biopsy. Am J Respir Crit Care Med 1994;149:783–7. [7] Varma S, Varma N, Dhar S, Jain A, Rajwanshi A, Dash S, et al. Cytodiagnosis of granulocytic sarcoma presenting as superior vena cava syndrome in acute myeloblastic leukemia. A case report. Acta Cytol 1992;36:371–2. [8] Adler OB, Rosenberger A. Reevaluation of transthoracic fine needle aspiration biopsy in diagnosing superior vena cava syndrome. Rofo 1988;149: 470–2. [9] Cosmo L, Haponik EF, Darlak JJ, Summer WR. Neoplastic superior vena caval obstruction: diagnosis with percutaneous needle aspiration. Am J Med Sci 1987;293:99–102. [10] British Thoracic Society Bronchoscopy Guidelines Committee, a Subcommittee of Standards of Care Committee of British Thoracic Society. British Thoracic Society guidelines on diagnostic flexible bronchoscopy. Thorax 2001;56(Suppl. 1):i1–21. [11] Prakash U, Utz JP. Bronchoscopic lung biopsy. Cambridge, MA: Blackwell Science; 1995. [12] Scagliotti G, Brodowicz T, Shepherd FA, Zielinski C, Vansteenkiste J, Manegold C, et al. Treatment-by-histology interaction analyses in three phase III trials show superiority of pemetrexed in nonsquamous non-small cell lung cancer. J Thorac Oncol 2011;6:64–70. [13] Painter TD, Karpf M. Superior vena cava syndrome: diagnostic procedures. Am J Med Sci 1983;285:2–6. [14] Armstrong BA, Perez CA, Simpson JR, Hederman MA. Role of irradiation in the management of superior vena cava syndrome. Int J Radiat Oncol Biol Phys 1987;13:531–9. [15] Chen JC, Bongard F, Klein SR. A contemporary perspective on superior vena cava syndrome. Am J Surg 1990;160:207–11. [16] Wan JF, Bezjak A. Superior vena cava syndrome. Emerg Med Clin North Am 2009;27:243–55. [17] Selcuk ZT, Firat P. The diagnostic yield of transbronchial needle aspiration in superior vena cava syndrome. Lung Cancer 2003;42:183–8. [18] Kelly PT, Chin Jr R, Adair N, Burroughs A, Haponik EF. Bronchoscopic needle aspiration in patients with superior venacaval disease. J Bronchology 1997;4:290–3. [19] Nakajima T, Shingyouji M, Nishimura H, Lizasa T, Kaji S, Yasufuku K, et al. New endobronchial ultrasound imaging for differentiating metastatic site within a mediastinal lymph node. J Thorac Oncol 2009;4:1289–90. [20] Dosios T, Theakos N, Chatziantoniou C. Cervical mediastinoscopy and anterior mediastinotomy in superior vena cava obstruction. Chest 2005;128: 1551–6. [21] Reyes CV, Thompson KS, Massarani-Wafai R, Jensen J. Utilization of fine-needle aspiration cytology in the diagnosis of neoplastic superior vena caval syndrome. Diagn Cytopathol 1998;19:84–8. [22] Koegelenberg CF, Bolliger CT, Plekker D, Wright CA, Brundyn K, Louw M, et al. Diagnostic yield and safety of ultrasound-assisted biopsies in superior vena cava syndrome. Eur Respir J 2009;33:1389–95. [23] Da Ines D, Chabrot P, Motreff P, Alfidja A, Cassagnes L, Filaire M, et al. Cardiac tamponade after malignant superior vena cava stenting: two case reports and brief review of the literature. Acta Radiol 2010;51:256–9.
Contents lists available at SciVerse ScienceDirect
Lung Cancer journal homepage: www.elsevier.com/locate/lungcan
EBUS-TBNA in patients presented with superior vena cava syndrome Matthew K. Wong, Terence C. Tam, David C. Lam, Mary S. Ip, James C. Ho ∗ Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
a r t i c l e
i n f o
Article history: Received 1 December 2011 Received in revised form 13 March 2012 Accepted 19 March 2012 Keywords: Endobronchial ultrasound Transbronchial needle aspiration Diagnostic yield Superior vena cava obstruction Lung cancer Mediastinal lymphadenopathy
a b s t r a c t Introduction: Expedient pathological diagnosis is crucial in selection of appropriate treatment in patients presented with superior vena cava syndrome (SVCS). The performance and safety of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in this setting is unknown. Methods: Over a 4-year period, patients presented with SVCS in the presence of mediastinal mass and referred for EBUS-TBNA were enrolled for the study. The procedure was performed under local anaesthesia with conscious sedation. TBNA was performed under real-time with the curvilinear probe of EBUS. Rapid on site cytological examination (ROSE) was not available. Results: Eighteen procedures of EBUS-TBNA were performed in 17 patients. Malignancy was confirmed in 16 patients (diagnostic yield 94.1%). There was no major complication including significant bleeding or pneumothorax related to the procedures. Conclusions: EBUS-TBNA has high diagnostic yield and is safe in patients presented with SVCS and mediastinal mass. © 2012 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Superior vena cava obstruction (SVCO) is caused by extrinsic compression or intraluminal blockade of the superior vena cava, due to mediastinal lymphadenopathy or right upper lobe lung tumour with mediastinal invasion. Clinically, it manifests as the distressful superior vena cava syndrome (SVCS) which is comprised of swelling of face, neck and upper limbs, headache, dyspnoea, orthopnoea and in severe cases, stridor. Over 80% of the cases of SVCO result from neoplastic causes, mostly lung cancers (75%) and lymphoma [1–4]. Not uncommonly, immediate radiotherapy may be commenced to treat SVCS before a pathological diagnosis is obtained in order to relieve severe obstructive symptoms. Nonetheless, a histological diagnosis for the cause of SVCO is preferred prior to empirical radiotherapy as some tumours, notably small cell lung cancer and non-Hodgkin’s lymphoma, are best treated with upfront systemic chemotherapy. Also, prebiopsy irradiation of the mass lesion often leads to difficult pathological interpretation of tissue samples [5], and makes further management more complicated [6–9]. Therefore, unless there are
Abbreviations: CT, computed tomography; EBUS, endobronchial ultrasound; TBNA, transbronchial needle aspiration; NPC, nasopharyngeal carcinoma; NSCLC, non-small cell lung cancer; ROSE, rapid on site cytological examination; SVCO, superior vena cava obstruction; SVCS, superior vena cava syndrome. ∗ Corresponding author at: Division of Respiratory Medicine, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong. Tel.: +852 2255 4999; fax: +852 2872 5828. E-mail addresses: [email protected], [email protected] (J.C. Ho). 0169-5002/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.lungcan.2012.03.015
alternative readily accessible tumour sites, the ability to biopsy at the mediastinal tumour causing SVCO is of utmost importance. A histological diagnosis can be obtained by conventional techniques of bronchoscopy, however, bronchoscopic biopsy in patients with evidence of SVCS is often considered to be a high-risk procedure with increased risk of bleeding [10] and airway oedema [11]. With the advent of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) as a relatively safe procedure in establishing the diagnosis of mediastinal mass, there is good clinical rationale of its application to SVCO. To date, there is yet no reported data regarding the use of EBUS-TBNA in patients suffering from SVCS due to malignant causes. The aim of this study is to review the diagnostic yield and safety of EBUS-TBNA to expedite the management of patients presented with SVCS in our institution. 2. Methods 2.1. Patients and procedures From August 2007 to August 2011, patients referred for EBUSTBNA with initial presentation of SVCS (oedema over head and neck, upper extremities, dilated collateral veins in the upper portion of the thorax and arms, and/or jugular venous distension) were recruited into the study. Contrast computed tomography (CT) scan of thorax was arranged on an urgent basis. Patients with radiological SVCO on CT scan without clinical features of SVCS on presentation were not included. Patients were also excluded if they had prior known diagnosis leading to SVCS or benign causes of
278
M.K. Wong et al. / Lung Cancer 77 (2012) 277–280
SVCS such as the catheter-related (e.g. Hickman, haemodialysis) thrombosis without abnormal mediastinal lesion on CT scan. Written informed consent was obtained from all participants. During the interview for informed consent, alternative clinical approaches including other means of obtaining tissue diagnosis or empirical treatment with radiotherapy would be discussed. This study has been approved by the Institutional Review Board (HKU/HA HKW). Prior to EBUS, hydrocortisone 100 mg was given intravenously as steroid cover for patients who received systemic steroid prior to bronchoscopy. Patients were lying in semi-reclined position for comfort before given conscious sedation, while the monitoring was the same as those undergoing routine conventional bronchoscopy. EBUS-TBNA was performed with a flexible ultrasonic bronchoscope with a curvilinear ultrasound probe of frequency of 7.5 MHz (XBFUC260F-OL8, Olympus, Tokyo, Japan) under conscious sedation by intravenous injection of pethidine with or without midazolam. Airway was anaesthetized with doses (2 ml each) of 2% lignocaine, delivered through the bronchoscope. Suspicious lesions over the paratracheal, hilar and subcarinal regions were scanned. Power Doppler was performed before needle puncture with a designated 22-Guage needle under real-time guidance. One to five passes were made at each region. Both cytology and histology specimens were sent for pathological analysis in addition to microbiological studies including acid-fast bacilli and fungus. Rapid on-site cytological examination (ROSE) was unavailable during the study. Subsequently, conventional bronchoscopy was performed for airway assessment and endobronchial biopsy was performed if appropriate in the same setting. Complications related to EBUS-TBNA and conventional flexible fibreoptic bronchoscopy were recorded accordingly, in particular oxygen desaturation and major bleeding. Major bleeding was defined as haemorrhage that required haemostasis such as application of topical adrenaline and/or cold saline. Chest X-ray was performed to rule out pneumothorax after the procedure. 2.2. Statistical analysis The baseline characteristics were performed with descriptive statistics. The diagnostic yield was defined as the percentage of patients diagnosed by EBUS-TBNA. 3. Results EBUS-TBNA was first introduced in our centre since August 2006. Eighteen EBUS-TBNA procedures were performed in 17 consecutive patients presented with SVCS from August 2007 to August 2011. Although our patients included in this study were having SVCS, they were otherwise not critically ill. All had lesions at the right lower paratracheal region while 9 out of 17 (52.9%) had lesions (>1 cm) at the subcarinal region. A median of 1 region per patient (range 1–3) was aspirated with a median of 3 needle passes per node (range 1–4) (Table 1). Although EBUS-TBNA was introduced in our institution since 2006, EBUS-TBNA was performed in 7 out of 17 (41.2%) patients as the first pathological diagnostic investigation. One patient had prior nondiagnostic thoracentesis. Nine patients (52.9%) had conventional bronchoscopy (without blind TBNA) and two of them required additional thoracentesis, which were all non-diagnostic, before referral for EBUS-TBNA. In cases where endobronchial lesion was initially suspected based on CT findings, pathological diagnosis could only be reached in 3/17 (17.6%) patients with conventional bronchoscopy. The diagnosis was confirmed with EBUS-TBNA in 16 out of 17 (94.1%) patients presented with SVCS, while one patient had EBUS-TBNA performed twice and no patient required mediastinoscopy. None except one patient had received upfront
Table 1 Clinical data of 17 patients undergoing EBUS-TBNA. Age (mean ± SD) Gender (M:F) Size of target lesion on CT scan Right paratracheal area, cm (mean ± SD) Subcarinal area, cm (mean ± SD) Procedure (total 18) Premedication with steroid cover (n [%]) Use of pethidine ± midazolam (n [%]) Stations sampled (median [range]) Needle aspirated per station (median [range]) Diagnostic yield Procedures (n = 18), (no [%]) Patients (n = 17), (no [%]) Final diagnosis (total 17) Lung cancer (n [%]) Small cell carcinoma Adenocarcinoma Squamous cell carcinoma NSCLC, poorly differentiated Non-pulmonary malignancy (n [%]) (breast, endometrium, NPC) Carcinoma, not otherwise specified (n [%]) No diagnosis (no [%]) Complications Increased oxygen supplement during procedure (n [%]) Significant bleeding (requiring haemostatic measures)
63 ± 12 13:4 3.53 ± 1.33 1.14 ± 1.21 13 [72.2%] 18 [100%] 1 [1–3] 3 [1–4] 16 [88.9%] 16 [94.1%] 12 [70.6%] 5 4 2 1 3 [17.6%] 1 [5.9%] 1 [5.9%] 5 [27.8%] 0
radiotherapy prior to EBUS-TBNA in which non-small cell carcinoma (not otherwise specified) was obtained. Six patients (35.3%) had history of extrathoracic malignancy but only three (50%) of them had SVCS caused by the same malignancy as in the past (Table 2). There was no significant bleeding associated with EBUS-TBNA whereas three patients (17.6%) had significant bleeding with conventional bronchoscopy (two from endobronchial biopsy and one from transbronchial lung biopsy), requiring topical adrenaline and/or cold saline for haemostasis. Transient increase in supplemental oxygen was required in five (27.8%) procedures undergoing EBUS-TBNA. There was no procedure-related mortality. 4. Discussion Timely establishment of the underlying diagnosis of SVCS is imperative for starting appropriate treatment so that patients can have effective chemotherapy especially if small cell carcinoma or lymphoma is confirmed. In our series, five patients (30%) were confirmed small cell carcinoma that allowed timely systemic treatment and even in patients diagnosed to have NSCLC, the appropriate choice of chemotherapy was largely dictated by the exact cell type (adenocarcinoma versus squamous cell carcinoma) [12]. Upfront radiotherapy may not be the optimal treatment since sampling of the irradiated lesion precludes proper pathological classification in 40% of cases [5]. Among all patients confirmed with malignancy, EBUS-TBNA revealed diagnosis of specific cell type and origin of primary lesion except one who had upfront radiotherapy prior to tissue sampling, in which a pathologically non-specific carcinoma made subsequent chemotherapy challenging. Both the primary site of malignancy and duration prior to EBUS-TBNA appeared unrelated to the final diagnosis (Table 2). Bronchogenic carcinoma is by far the commonest cause of SVCS and conventional bronchoscopic forceps biopsy appears to be a reasonable approach to this condition. However, the diagnostic yield is suboptimal ranging from 40 to 67% [2,4,13–15] and may be explained by the extrinsic compression of the bronchus without endobronchial invasion. Also, bleeding complication after the initial forceps biopsy may prohibit further sampling and therefore affect the diagnostic performance as suggested in our present study. To the best of our knowledge, this is the first report that describes the
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Table 2 Patients with SVCS with known malignancy prior to EBUS-TBNA. Primary malignancy
Number of years prior to EBUS
Diagnosis by EBUS-TBNA
Same origin of primary malignancy as revealed by EBUS-TBNA
Laryngeal carcinoma Carcinoma of breast Nasopharyngeal carcinoma Heptaocellular carcinoma Carcinoma of rectum Carcinoma of endometrium
20 13 9 4 3 2
Adenocarcinoma of lung Carcinoma of breast Nasopharyngeal carcinoma Carcinoma, NOSa Squamous cell carcinoma of lung Carcinoma of endometrium
No Yes Yes Indeterminateb No Yes
a b
NOS: not otherwise specified. This patient received upfront irradiation of lesion prior to EBUS-TBNA. Indeterminate: pathological diagnosis could not definitely determine the origin.
role of EBUS-TBNA in SVCS due to a mediastinal mass. As there is no standard protocol on the workflow of investigations for SVCS, various methods were adopted as first-line investigation. From our experience, seven patients (41.2%) had EBUS-TBNA as their first investigation which turned out to be diagnostic in all. The rest of our cohort had EBUS-TBNA as the subsequent investigation after unrevealing workup, e.g. conventional bronchoscopy or thoracentesis. The overall diagnostic yield of EBUS-TBNA in SVCS was found to be 94.1%. If available, rapid on-site cytological examination (ROSE) is preferred in ensuring adequate tissue obtained during the procedure and minimizing the number of needle passes. In most cases, the compression of SVC is caused by lesions in the mediastinum, right paratracheal or precarinal areas [16], which can be readily accessible by conventional TBNA with diagnostic yield of 67–96% [17,18]. In contrast to EBUS-TBNA, conventional TBNA without EBUS guidance resulted in premature termination of procedures due to haemorrhage or loss of adequate bronchoscopic view in 7.7–13.3% [17,18]. In addition, the opening of collateral vessels might increase risk for excessive bleeding during biopsy [18]. EBUS has the built-in power Doppler which allows real-time identification of any prominent vasculature next to or within the target lesion, especially important with distorted anatomy due to the huge mediastinal mass (Fig. 1). There was no major bleeding in our patients undergoing EBUS-TBNA, but the complication was more commonly encountered with forceps biopsy. EBUS-TBNA was performed twice in one patient suffering from nasopharyngeal carcinoma (NPC), as the first procedure could only yield squashed lymphoid tissue. He was later diagnosed as having metastatic disease to the mediastinum from nasopharyngeal carcinoma on second EBUS-TBNA. Only one patient ultimately received no pathological diagnosis after EBUS-TBNA and extensive investigations including conventional bronchoscopy, thoracentesis and pleural biopsy, who died 2 months after presentation. Both patients illustrated the examples of sampling error for needle biopsy of enlarged lymph nodes. Although EBUS-TBNA can be performed with the needle passing away from the cystic necrosis inside the grossly enlarged lymph node, a newer EBUS processor system might be able to further elucidate the necrotic centre within the targeted lymph node [19]. Surgical approach under general anaesthesia was shown to have high diagnostic yield [20], however, only limited number of patients were considered suitable for these procedures with major complications including major haemorrhages and airway obstructions in up to 13% [20]. In addition, surgery should better be avoided in these unresectable patients with SVCS, who might not even be able to assume supine position during the operation. On the other hand, the use of needle aspiration in obtaining the pathological diagnosis with SVCS was reported with transthoracic approach under ultrasound guidance [6,21,22]. However, only 33% [21] to 42% [22] of patients presented with SVCS were suitable for this approach. The inherent limitation of transthoracic approach under ultrasound guidance is the inability of visualizing the lesion
when it is not abutting or invading the chest wall, which can still be reached with EBUS-TBNA. The additional advantage of bronchoscopic approach includes the ability to assess the airways for endobronchial stenting and biopsy of endobronchial lesion. Endovascular stenting of SVC has emerged as a feasible treatment option for SVCS, with rapid symptomatic relief and improvement of quality of life. Two of our patients had endovascular stenting performed 1 week and 1 month before EBUS-TBNA. Both of them received low molecular weight heparin after stenting and were withheld temporarily prior to EBUS-TBNA. No bleeding or
Fig. 1. (A) Power Doppler sonogram showing the tumour mass (dotted line) that invaginates into the brachiocephalic artery (BCA). (B) Computed tomography scan of the same patient showing the tumour that invades into the mediastinum.
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thrombotic complication was found. It has been shown that needle aspiration was safe even in patients who had risk of bleeding including vascular carcinoid tumours in the presence of coagulopathy [2]. Our preliminary experience suggests that endovascular stenting prior to EBUS-TBNA to the mediastinal tumour may be a reasonable approach for those with very symptomatic SVCS. Nonetheless, majority (88.2%) of our patients underwent EBUS-TBNA smoothly without preceding endovascular stenting of SVC. In fact, one patient failed to have endovascular stenting because of the complete intraluminal obstruction of SVC. Although percutaneous stenting of SVC has been reported to have high success rate and low morbidity, serious complications like cardiac tamponade have occurred [23]. As only patients referred for EBUS-TBNA were recruited, patients who underwent other methods to establish pathological diagnosis such as direct surgical exploration, imaging guided transthoracic needle aspiration were not investigated, which did not allow direct comparison of different diagnostic modalities in our study. The size of the paratracheal lymph nodes in our cohort was huge, in which smaller sized lymph nodes might be less accessible, though the average size of subcarinal lymph nodes in our series was only around 1 cm. However, our findings would strongly support the safety and high diagnostic yield of EBUS-TBNA in SVCS. When there is no readily accessible tumour site for tissue diagnosis such as supraclavicular lymph node or pleural fluid, EBUS-TBNA is often the least invasive and yet highly diagnostic investigation in SVCS, allowing high quality specimens for exact pathological classification and molecular profiling. Conflict of interest statement All authors in this manuscript have no financial and personal relationships with other people or organizations that could inappropriately influence our work. None of the authors have conflict of interest to declare. Acknowledgements There is no funding source to declare. No writing assistance was sought in the preparation of this report. References [1] Bell DR, Woods RL, Levi JA. Superior vena caval obstruction: a 10-year experience. Med J Aust 1986;145:566–8. [2] Schraufnagel DE, Hill R, Leech JA, Pare JA. Superior vena caval obstruction. Is it a medical emergency? Am J Med 1981;70:1169–74.
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