Endobronchial ultrasound: Indications, contraindications, and complications

INTRODUCTION — Endobronchial ultrasound (EBUS) is a bronchoscopic technique that uses ultrasound to visualize structures within the airway wall, lung, and mediastinum [1-3]. EBUS is different from endoscopic ultrasound (EUS). While both can visualize and guide sampling of mediastinal lymph nodes, EBUS is performed during bronchoscopy and EUS is performed during gastrointestinal endoscopy.

The indications, contraindications, and complications of EBUS are discussed in this topic review. Types of EBUS, technical aspects of EBUS-guided sampling, and indications for EUS are described separately. (See "Endobronchial ultrasound: Technical aspects" and "Endoscopic ultrasound-guided fine needle aspiration in the gastrointestinal tract".)

TYPES — There are two types of EBUS:

●Radial probe EBUS (RP-EBUS)

●Convex probe EBUS (CP-EBUS)

In brief, RP-EBUS typically has higher resolution than CP-EBUS such that airway structure and parenchymal lesions are visualized in better detail. However, unlike CP-EBUS, RP-EBUS cannot be used to biopsy targets in real time. Thus, for the purposes of sampling, CP-EBUS is more frequently used to acquire tissue, while RP-EBUS is often used to locate a target lesion suitable for sampling (eg, peripheral nodules). Technical details regarding the use of CP- and RP-EBUS are described separately. (See "Endobronchial ultrasound: Technical aspects", section on 'Types of EBUS'.)

INDICATIONS — EBUS in combination with transbronchial needle aspiration (EBUS-TBNA) is most commonly used as a tool to diagnose, stage, and restage patients with suspected or known non-small cell lung cancer (NSCLC). It can also be used to sample mediastinal lymphadenopathy of unknown etiology, mediastinal masses, pulmonary nodules, and endobronchial or peribronchial lesions, and can guide therapeutic procedures (eg, airway stenting). Use of EBUS may be limited by its availability and training, which is institution and provider dependent.

Diagnosis and staging of non-small cell lung cancer — EBUS has an established role in the diagnosis and staging of patients with NSCLC. In patients with NSCLC, EBUS-TBNA (with or without transesophageal endoscopic ultrasound fine needle aspiration [EUS-FNA]) is the preferred first-step procedure for sampling centrally located tumors and accessible metastases involving the mediastinum. However, because of the low negative predictive value of EBUS-TBNA in this setting, a negative sample should prompt additional sampling using alternative procedures (eg, mediastinoscopy). (See "Selection of modality for diagnosis and staging of patients with suspected non-small cell lung cancer", section on 'EBUS/EUS needle aspiration'.)

The eighth edition tumor-node-metastasis (TNM) staging system (table 1) takes into account the characteristics of the local tumor (T), the presence or absence of regional lymph node metastasis (N), and the presence or absence of distant metastases (M). The primary role of EBUS-TBNA in patients with suspected NSCLC is to determine the N component of the TNM system, and, if necessary, diagnose the primary tumor. In addition, it can also help determine the T component (see "Tumor, node, metastasis (TNM) staging system for lung cancer"):

●Primary tumor diagnosis and nodal (N) staging – In general, EBUS-TBNA is the preferred first-step procedure for sampling large, centrally located tumors and for suspicious nodal involvement in the mediastinum as well as hilar lymph nodes (2R, 2L, 3p, 4R, 4L, 7, 10R, 10L, 11R, 11L) (figure 1 and figure 2). Importantly, although diagnosis and staging can be performed simultaneously, they can also be performed sequentially. Suspicious nodes include those that are enlarged by computed tomography or metabolically active by positron emission tomography (PET). The preference for EBUS is based upon the reported high sensitivity of EBUS-TBNA to stage and diagnose NSCLC in this setting and its ability to access more nodal stations than the traditional gold standard, cervical mediastinoscopy. Multiple needle passes by an experienced operator and rapid on-site cytologic evaluation (ROSE) are suggested to increase the diagnostic yield of EBUS-TBNA samples and provide sample that is adequate for genetic analysis. The studies that describe its sensitivity for the diagnosis and staging of NSCLC are discussed separately. (See "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer", section on 'Endobronchial ultrasound' and "Selection of modality for diagnosis and staging of patients with suspected non-small cell lung cancer", section on 'EBUS/EUS needle aspiration'.)

●Tumor (T) staging – Accurate determination of the distance from the carina to the proximal portion of the tumor is easily performed using radial probe-EBUS (RP-EBUS). Measuring this distance (table 1) distinguishes a T2 from a T4 lesion, which, in turn, partly determines suitability for surgical resection. (See "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer", section on 'Endobronchial ultrasound'.)

Real-time EBUS-TBNA using the convex probe EBUS (CP-EBUS) allows real-time sampling of mediastinal and hilar lesions. Prior to the development of the CP-EBUS, the RP-EBUS had been used to perform RP-EBUS-guided TBNA (RP-EBUS-TBNA), which was not a real-time procedure. With CP-EBUS now available for EBUS-TBNA, RP-EBUS-TBNA is not widely performed. Both improve the diagnostic yield, compared with conventional TBNA (ie, TBNA without ultrasound guidance). (See "Endobronchial ultrasound: Technical aspects", section on 'Lymph nodes' and "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer", section on 'Endobronchial ultrasound'.)

Sonographic findings of lymph nodes may help to predict nodal metastases [4,5]. In one retrospective analysis of 1061 images of lymph nodes in patients with lung cancer, round shape, distinct margin, heterogenous echogenicity, and the presence of necrosis were independent predictors of malignant involvement [4]. When none of these features were present, 96 percent of lymph nodes were pathologically proven to be benign.

Mediastinal lymphadenopathy of unclear etiology — EBUS can visualize and sample mediastinal and hilar lymphadenopathy to distinguish benign from malignant lesions (other than NSCLC) (table 2). The most common use for CP-EBUS-guided TBNA (CP-EBUS-TBNA) in this setting is in patients with bilateral hilar adenopathy to distinguish sarcoidosis from lymphoma. The value of EBUS-TBNA in obtaining tissue to diagnose benign lesions other than sarcoidosis (eg, tuberculosis, fungal disease) has also been reported. Detailed discussion of the role of EBUS-TBNA in this setting is provided separately. (See "Bronchoscopy: Transbronchial needle aspiration", section on 'Mediastinal and hilar lymphadenopathy'.)

One 2012 meta-analysis of 12 studies totaling 1658 patients reported a sensitivity of 92 percent and specificity of 100 percent for EBUS-TBNA of mediastinal lymph nodes, although interpretation of this analysis should be limited because only small, retrospective studies of patients with suspected NSCLC were analyzed [6].

Advances in EBUS imaging technology (eg, second-generation CP-EBUS) may also allow blood vessels inside lymph nodes to be visualized and identify the direction of flow, which may distinguish malignant from benign nodal disease [7,8].

Sampling parenchymal pulmonary nodules — During the diagnostic evaluation of a solitary parenchymal pulmonary nodule, clinical features, radiographic features, and, occasionally, quantitative models are used to determine the likelihood that the nodule is malignant. RP-EBUS is the bronchoscopic procedure of first choice in patients who have a nodule at intermediate risk (5 to 65 percent) for malignancy or in patients who are at high risk (>65 percent) who are not surgical candidates. Additional indications may include patients in whom a benign diagnosis is suspected that requires therapy (eg, fungal or mycobacterial disease), or, rarely, for patients at low risk of malignancy who place a high value on diagnostic certainty. (See "Diagnostic evaluation of the incidental pulmonary nodule", section on 'Initial evaluation'.)

EBUS-TBNA is best used in those with large, centrally located lesions adjacent to major airways, while RP-EBUS is an option for peripherally located nodules/masses [9-14]. The technical aspects of using a RP-EBUS-guided sheath to locate smaller peripheral nodules and detailed discussion on the sensitivity of EBUS-TBNA for the diagnosis of cancer in pulmonary nodules are discussed separately. (See "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer", section on 'Endobronchial ultrasound' and "Bronchoscopy: Transbronchial needle aspiration", section on 'Lung nodules or masses' and "Endobronchial ultrasound: Technical aspects", section on 'Parenchymal lesions'.)

RP-EBUS imaging can provide additional information to help support a clinician’s assessment of whether a pulmonary nodule is benign or malignant [1]. In one retrospective study of 124 patients, based upon the appearance of the nodule, three classes of peripheral nodules were distinguished [15]:

●Type I – A homogeneous nodule

●Type II – A nodule with hyperechoic dots and linear arcs

●Type III – A heterogeneous nodule

Approximately 92 percent of the type I lesions were benign, and 99 percent of the type II and III lesions were malignant.

Sampling endobronchial or peribronchial lesions — EBUS-TBNA can be used to sample lesions that are located endobronchially or peribronchially:

●Endobronchial – Regardless of whether or not a visible endobronchial lesion appears benign or malignant, it is typically sampled (the exception may be highly vascular lesions). In most cases, EBUS offers no extra advantage over conventional bronchoscopy (ie, without ultrasound guidance) for biopsy of the lesion itself; however, it can be useful for sampling other coexisting lesions (eg, lymph nodes) that are not directly visible. (See "Diagnostic evaluation of the incidental pulmonary nodule", section on 'Bronchoscopic techniques' and "Bronchoscopy: Transbronchial needle aspiration", section on 'Airway lesions'.)

●Peribronchial – The yield of conventional procedures such as forceps biopsy and brushing tends to be much lower in submucosal and peribronchial disease. Under such circumstances, the addition of EBUS-TBNA to obtain submucosal or peribronchial samples may increase the diagnostic yield. (See "Bronchoscopy: Transbronchial needle aspiration", section on 'Peribronchial and submucosal disease'.)

Sampling mediastinal masses — Case reports suggest that EBUS-TBNA may be of value in the evaluation of mediastinal lesions including anterior mediastinal masses of unclear etiology or bronchogenic cysts [16,17]. Accessing mediastinal masses in such cases is limited by the ability of EBUS to access the anterior and superior mediastinum only. In general, some posterior and middle mediastinal masses may not be adequately accessed using EBUS. (See "Approach to the adult patient with a mediastinal mass" and 'Other' below.)

Guidance of therapeutic procedures — EBUS can impact therapy by its ability to determine the following:

●The depth of tumor invasion into the airway wall prior to an intervention – RP-EBUS has been shown to impact whether a patient is deemed a candidate for local endobronchial therapy or should be referred for an alternative intervention [18,19].

●The local effects of the intervention – This may prompt changes during the procedure (eg, terminate tumor debridement to avoid bronchial wall or vessel perforation) [18].

As examples:

●One prospective cohort study followed 1174 patients who underwent EBUS-guided therapeutic bronchoscopy for a variety of indications, including mechanical tumor debridement, airway stenting, argon plasma coagulation, Neodymium:yttrium aluminum garnet (Nd:YAG) laser therapy, brachytherapy, foreign body removal, and abscess drainage [18]. Approximately 45 percent of the procedures were altered by EBUS findings. Changes included referral for surgical interventions rather than endoscopic treatment (28 percent), adjustment of stent dimensions, and termination of tumor debridement because the procedure was encroaching upon blood vessels.

●In another study of 43 patients with lung cancer, RP-EBUS (with or without electromagnetic bronchoscopy [ENB]) was used to facilitate placement of fiducial markers (FMs) for stereotactic radiosurgery (SRS) [20]. FMs were successfully placed in 31 patients using EBUS alone; ENB was used with EBUS in 12 patients with peripheral tumors.

INVESTIGATIONAL

Detection of early airway malignancy — Small or early endobronchial lesions that are radiographically inapparent may be detected during EBUS performed for any reason. Other optional investigations for this indication include fluorescence bronchoscopy, high-magnification bronchovideoscopy, optical coherence tomography, and narrow band imaging [21-25]. (See "Detection of early lung cancer: Autofluorescence bronchoscopy and investigational modalities".)

Visualization of radiographically inapparent lesions with radial probe EBUS (RP-EBUS) improves prediction of whether such lesions are malignant [2,26-28]. As an example, in a prospective cohort study, 74 patients with positive fluorescence bronchoscopy (but negative white-light bronchoscopy) had the lesion further imaged using RP-EBUS [28]. Malignant lesions were correctly predicted by autofluorescence bronchoscopy alone in 69 percent of patients, which increased to 97 percent when RP-EBUS was added. Benign lesions were correctly predicted by autofluorescent bronchoscopy alone in 55 percent of patients, which increased to 97 percent when RP-EBUS was added. Among the patient population, 46 percent had malignant lesions, and 54 percent had benign lesions. (See "Detection of early lung cancer: Autofluorescence bronchoscopy and investigational modalities".)

Extent of airway tumor invasion — Detection of tumor in the airway wall may help to distinguish airway invasion from external compression. One prospective cohort study compared computed tomography with RP-EBUS for the evaluation of airway wall invasion in 131 patients who had either invasion or external compression of an airway by an adjacent tumor that was histologically proven [27]. RP-EBUS was associated with superior sensitivity (89 versus 75 percent), specificity (100 versus 28 percent), and accuracy (94 versus 51 percent) for the detection of airway wall invasion.

Other — Case reports have described the use of EBUS for the detection of left atrial myxoma or intracardiac masses, pulmonary artery hydatid cysts, pulmonary embolism, as well as for draining infected mediastinal bronchogenic cysts and staging of thyroid cancer [29-35]. EBUS may have some value in measuring cartilage or airway wall thickness in patients with tracheobronchomalacia [36-38] and chronic asthma [39], respectively.

CONTRAINDICATIONS — Contraindications to EBUS are the same as contraindications to bronchoscopy. Similarly, contraindications to EBUS-guided sampling (eg, transbronchial needle aspiration) are the same as contraindications to the sampling procedure. (See "Bronchoscopy: Transbronchial needle aspiration" and "Flexible bronchoscopy in adults: Indications and contraindications", section on 'Contraindications'.)

COMPLICATIONS — EBUS alone is associated with the usual complications of bronchoscopy, while EBUS-guided transbronchial needle aspiration (TBNA) is associated with the usual complications of both bronchoscopy and TBNA. Complications are procedure- and sedation-related. (See "Bronchoscopy: Transbronchial needle aspiration", section on 'Complications' and "Flexible bronchoscopy in adults: Preparation, procedural technique, and complications", section on 'Complications' and "Flexible bronchoscopy in adults: Overview" and "Procedural sedation in adults in the emergency department: General considerations, preparation, monitoring, and mitigating complications", section on 'Anticipating and mitigating Complications'.)

EBUS-TBNA is generally an extremely safe procedure [9,10,40-46]. A systematic review of 18 observational studies (1782 patients) reported no serious complications of the use of the convex probe EBUS (CP-EBUS) for EBUS-TBNA of regional lymph nodes [40]. Minor complications included agitation, cough, and blood at the puncture site. Studies of radial probe EBUS-guided transbronchial biopsy of peripheral pulmonary nodules reported moderate bleeding in 1 percent of procedures and pneumothorax in less than 4 percent [9,10,41,46,47]. Infection (eg, alveolitis mediastinitis, adenitis) and fistula formation are rare [42-44,47,48]. (See "Image-guided bronchoscopy for biopsy of peripheral pulmonary lesions", section on 'Complications'.)

TRAINING — Acquiring the necessary skills for performing EBUS depends upon a fundamental understanding of normal and abnormal airway anatomy to avoid inadvertent sampling of structures that should not be biopsied (eg, aorta) [49-51]. Although no specific criteria have been established, it is appropriate that clinicians be trained in institutions with expertise in the performance of EBUS (eg, institutions with interventional bronchology expertise and/or in thoracic surgery). Likewise, it is crucial to understand the staging system for lung cancer and we recommend sampling N3 nodes first, followed by N2 and then N1 in order to eliminate false up-staging of patients (figure 2).

SUMMARY AND RECOMMENDATIONS

●Endobronchial ultrasound (EBUS) is a bronchoscopic technique that uses ultrasound to visualize structures within the airway wall, lung, and mediastinum. There are two types of EBUS: radial probe EBUS (RP-EBUS) and convex probe EBUS (CP-EBUS). Real-time EBUS-guided transbronchial needle aspiration (EBUS-TBNA) using the CP-EBUS allows real-time sampling of mediastinal and hilar lesions. Prior to the development of the CP-EBUS, the RP-EBUS had been used to perform RP-EBUS-guided TBNA (RP-EBUS-TBNA) which was not a real-time procedure. With CP-EBUS now available for EBUS-TBNA, RP-EBUS-TBNA is not widely performed. (See 'Introduction' above and "Endobronchial ultrasound: Technical aspects", section on 'Types of EBUS'.)

●CP-EBUS-guided TBNA (CP-EBUS-TBNA) is most commonly used as a tool to diagnose and stage patients with suspected or known non-small cell lung cancer (NSCLC). It can also be used to sample mediastinal lymphadenopathy of unknown etiology, mediastinal masses, pulmonary nodules, endobronchial or peribronchial lesions, and can guide therapeutic procedures (eg, airway stenting) (see 'Indications' above):

•CP-EBUS-TBNA is the preferred first-step procedure for sampling large, centrally located tumors and for suspicious nodal involvement in the mediastinum as well as hilar lymph nodes (2R, 2L, 3p, 4R, 4L, 7, 10R, 10L, 11R, 11L) (figure 1 and figure 2). (See 'Diagnosis and staging of non-small cell lung cancer' above.)

•CP-EBUS-TBNA is commonly used to visualize and sample mediastinal lymphadenopathy of unknown etiology. The most common use for EBUS-TBNA in this setting is in patients with bilateral hilar adenopathy where sarcoidosis needs to be distinguished from lymphoma. The value of EBUS-TBNA in obtaining tissue to diagnose benign lesions other than sarcoidosis (eg, tuberculosis, fungal disease) has also been reported. (See 'Mediastinal lymphadenopathy of unclear etiology' above and "Bronchoscopy: Transbronchial needle aspiration", section on 'Mediastinal and hilar lymphadenopathy' and 'Sampling endobronchial or peribronchial lesions' above.)

•RP-EBUS is the procedure of first choice to guide sampling in patients who have a nodule at intermediate risk (5 to 65 percent) for malignancy or in patients who are at high risk (>65 percent) who are not surgical candidates. Additional indications may include patients in whom a benign diagnosis is suspected that requires therapy (eg, mycobacterial disease). We prefer CP-EBUS-TBNA for sampling large, centrally located lesions adjacent to major airways. RP-EBUS can be used as an option for sampling peripheral lung lesions, when local expertise is available. (See "Diagnostic evaluation of the incidental pulmonary nodule", section on 'Bronchoscopic techniques' and 'Sampling parenchymal pulmonary nodules' above.)

•CP-EBUS-TBNA may also be used to sample mediastinal masses and to guide local endobronchial therapies including tumor debridement and sheath placement, although such indications are only supported by case reports and small case series. (See 'Sampling mediastinal masses' above and 'Guidance of therapeutic procedures' above.)

●Contraindications to EBUS are the same as contraindications to bronchoscopy. Similarly, contraindications to EBUS-guided sampling (eg, TBNA) are the same as contraindications to the sampling procedure. (See "Bronchoscopy: Transbronchial needle aspiration" and "Flexible bronchoscopy in adults: Indications and contraindications", section on 'Contraindications' and 'Contraindications' above.)

●EBUS is, in general, a safe procedure, and complications are uncommon. (See 'Complications' above and "Flexible bronchoscopy in adults: Overview".)

●EBUS should only be performed by appropriately trained clinicians who have a fundamental understanding of airway anatomy. (See 'Training' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Takehiko Fujisawa, MD, PhD, who contributed to earlier versions of this topic review.