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Keywords:

  • Bronchoscopy;
  • EBUS;
  • transbronchial needle aspiration

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Indication
  5. Instruments
  6. Methodology
  7. Anatomy
  8. Summary
  9. References

Transbronchial needle aspiration (TBNA) has been used for over three decades in the diagnosis and staging of mediastinal adenopathy and masses. Although first described in Argentina in 1949 by Dr. Eduardo Schieppati, this rigid bronchoscope technique received very little attention until 1978 at Johns Hopkins Hospital where Wang and colleagues described in detail the diagnosis of a paratracheal mass by TBNA biopsy through a rigid bronchoscope using a 25-gauge esophageal variceal needle. In 1983, a novel flexible needle that could be used with the flexible bronchoscope to perform TBNA was developed and introduced for diagnosis and staging of bronchogenic carcinoma. Immediately to follow was the expansion of its use in the diagnosis of peripheral pulmonary nodules and benign mediastinum and hilar disorders by obtaining histological core specimens. Recent development of the endobronchial ultrasound-guided TBNA is most exciting and promising. Whether this will enhance the result of TBNA and spread the TBNA technique as a standard lung cancer staging procedure is yet to be seen. TBNA is simpler and easier. Endobronchial ultrasound-guided TBNA currently is more complicated and more difficult. Its future relies on a hybrid instrument and methodology to be widely applied to the diagnosis and staging of bronchogenic carcinoma.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Indication
  5. Instruments
  6. Methodology
  7. Anatomy
  8. Summary
  9. References

Transbronchial needle aspiration (TBNA) was first described in the literature using a rigid bronchoscope and rigid needle by Dr. Eduardo Schieppati, in the Review of the Argentine Medical Association in 1949.1 This technique received very little attention at the time and only a few scattered reports of this technique appeared in the European literature until 1978, when, at Johns Hopkins Hospital, Wang and colleagues described in detail the diagnosis of a paratracheal mass by TBNA biopsy through a rigid bronchoscope using a rigid 25-gauge esophageal variceal needle.2 In 1983, a novel flexible needle that could be used with the flexible bronchoscope to successfully perform TBNA was developed and introduced for diagnosis and staging of mediastinal adenopathy and masses.3 The efficacy and utility of TBNA in the diagnosis of peripheral pulmonary nodules was published in 1984.4 In 1985, a histology needle for the flexible bronchoscope was developed and the efficacy and safety of its use in TBNA was established.5 These rapid advancements in the clinical utility and indications for TBNA continued and in 1989, Wang et al. published the results from a series of 61 patients demonstrating the effectiveness of TBNA in the histological diagnosis of sarcoidosis.6 Refinements in needle design, imaging and biopsy guidance continued, but a nationwide survey of pulmonologists in 1991 reported infrequent use of TBNA by the majority of pulmonologists7 In an effort to increase the utility of TBNA for the pulmonary community, a standard lymph node map based on computed tomography (CT) lymph node (LN) location with corresponding endobronchial puncture sites was published describing the most common lymph node locations in the mediastinum and hilar areas.8 Despite efforts to simplify and teach the technique, a 1999 survey continued to indicate that TBNA remained underutilized in practice and in fellowship training.9 Advances in imaging technology over the years have resulted in markedly improved optics but essentially the basic function and technique of the flexible bronchoscope and TBNA has remained the same. There have been many attempts to increase yields for TBNA with the use of newer imaging technologies. While fluoroscopy has been a standard imaging modality that has been used primarily with peripheral biopsies, it has also been shown to be effective in transesophageal biopsies (TENA) of mediastinal adenopathy and masses.10 The use of ultrasound in bronchoscopy is a more recent technique that originally was developed for larger endoscopes used in the gastrointestinal tract (endoscopic ultrasound (EUS)). With the development of smaller ultrasound probes that could be used in a bronchoscope's working channel, endobronchial ultrasound (EBUS) began to be used as an aid for TBNA.11 More recently, ultrasound imaging has been added to the fiber optic or video bronchoscopes allowing for real-time TBNA under EBUS guidance (convex probe EBUS-TBNA).12,13 While EBUS-TBNA has received much attention in the literature, the additional cost and training have limited its widespread use. Other technological advances for TBNA guidance such as electromagnetic navigation bronchoscopy (ENB) and CT bronchoscopy face similar challenges of added expense and training in the face of limited reimbursement. Of all of these technological advancements, EBUS appears to show the most promise for future applications in lung cancer staging. The purpose of this paper is to describe the indications and utility of standard TBNA and EBUS-TBNA or EUS-TENA for the diagnosis and staging of lung cancer.

Indication

  1. Top of page
  2. Abstract
  3. Introduction
  4. Indication
  5. Instruments
  6. Methodology
  7. Anatomy
  8. Summary
  9. References

TBNA is indicated for biopsy of lesions adjacent and within the needle's reach outside the lumen of the tracheobronchial tree. TBNA is used primarily for obtaining mediastinal or hilar lymph node tissue for the diagnosis and staging of bronchogenic and other metastatic carcinomas. Other important indications include the diagnosis of lymphoma, granulomatous, and inflammatory and infectious diseases located in the mediastinum and lungs. Biopsy of some endobronchial lesions using TBNA may offer a less traumatic method for biopsy and minimize bleeding risk resulting from the biopsy. TBNA is also an effective method for draining cyst or fluid collections adjacent to the tracheobronchial tree.

Instruments

  1. Top of page
  2. Abstract
  3. Introduction
  4. Indication
  5. Instruments
  6. Methodology
  7. Anatomy
  8. Summary
  9. References

Since its development in 1983, the flexible transbronchial needle has been the worldwide standard for performing TBNA. While there have been many variations and sizes developed, essentially all needle designs follow the basic fundamental design of the original needles. The basic flexible needle apparatus is a needle attached to a wire, all encased in a sheath. The needle is retracted in the sheath and extended by pushing the wire at the proximal end of the sheath. The bronchoscope channel is protected from the needle tip by a hub on the distal end of the sheath. The proximal end has a connection for suction to be applied with a syringe. Typically the gauges range from 19-gauge to 22-gauge. The 19-gauge needles are used primarily for histology while the smaller gauges are used for cytology. Stiffness of the needle varies with the diameter of the wire and/or stylet. The stiffer needles tend to be better for puncturing the endobronchial wall because more force can be applied without the sheath bending. While this seems desirable, the trade-off is less ability to bend the distal end of the bronchoscope resulting in less angulation for penetrating the endobronchial wall. A shallower angle of penetration decreases the perpendicular depth of the needle penetration and the likelihood of maximal lymph node sampling. Lymph nodes in very accessible areas such as the anterior carina, main bronchus, and subcarina need little maneuvering of the bronchoscope to perform a TBNA and a stiffer needle can be easily used. For areas requiring more extreme flexing of the bronchoscope, such as the left paratracheal station or the aorta-pulmonary (AP) window station, a more flexible needle might be easier to maneuver and perform the TBNA.

Larger gauge needles (19-gauge) are usually used for histology, although all of the needles can combine specimens from multiple biopsies into a cellblock that can be processed histologically. Core biopsies are most reliably obtained with a 21-gauge needle within a 19-gauge needle. For histology core biopsies, the needle tip shape is a significant factor. A shorter slope of the needle tip with an inward cutting edge will result in a more cylindrical core, while a needle with a penetrating tip will leave less of a hole in the mucosal wall, but is less likely to provide as solid or core biopsy. In the combined needle, the smaller needle functions as a trocar to prevent plugging and the outer needle is used for cutting the core.

Needles designed specifically for the EBUS bronchoscopes currently are longer than standard TBNA needles and are produced in 22-gauge and 21-gauge sizes. While the added length increases the distance the needle can be extended to reach the target lesion and the amount of specimen that can be obtained with each pass, the angle that the needle exits the scope is fixed and often a lesion may be unreachable due to needle stiffness and a lack of flexibility of the bronchoscope to achieve the necessary angle to penetrate the endobronchial wall and reach the target. This is particularly evident with the larger and stiffer 21-gauge EBUS needles. The number of passes and the depth of passes back and forth inside the lesion determine the quantity of specimen obtained.

A wide variety of flexible needle types and variations are available for conventional TBNA. Continued emphasis and focus on development of simpler, easier to use and more effective needles for TBNA with or without EBUS bronchoscopes is needed.

Methodology

  1. Top of page
  2. Abstract
  3. Introduction
  4. Indication
  5. Instruments
  6. Methodology
  7. Anatomy
  8. Summary
  9. References

The elegance and simplicity of TBNA is most evident in the methodology for performing the procedure. The bronchoscope is maneuvered to the biopsy puncture site, the flexible needle is inserted into the working channel of the bronchoscope and the needle is then used by the bronchoscopist to puncture the tracheal or bronchial wall to sample the lymph node or mass. The needle is then withdrawn from the lesion and bronchoscope and the specimen is prepared on a glass slide as a smear or in a fluid form for examination.

Several of these techniques for puncturing the tracheal or bronchial wall are very effective, either alone or in a combination. The first is a simple jabbing technique. Once the needle hub is visible at the bronchoscope's distal end, the needle is extended and locked, with the needle tip minimally visible it is directed to the target site. The operator uses a free hand at the bronchoscope working channel to quickly advance the needle catheter in a jabbing movement to force the needle tip to penetrate the mucosal wall. Another technique is to keep the needle retracted and position the needle sheath hub on the mucosal wall at the puncture site and extend the needle at this point to puncture the wall. This is often referred to as the “hub against the wall” technique. An alternative approach is to extend the needle from its sheath and lock with the hub still visible and then fix the needle sheath at the working channel proximal end and advance the distal end of the bronchoscope with the needle towards the desired puncture site as one unit and push the needle through the wall with the force of the scope. This technique provides a force that reliably achieves needle penetration. Patient participation can also assist in needle puncture. Having the patient produce a forceful cough while using one of the above techniques will often provide the force needed to puncture the wall when other techniques have failed. Having the nurse or technician fix the scope at the nose while the bronchoscopist uses the jabbing technique or having the catheter fixed at the proximal end in the pushing technique may be necessary to puncture hard lesions or tough tracheobronchial wall. It is essential that the hub of the needle be visualized against the mucosal wall to ensure actual penetration of the bronchial wall.

Choosing the appropriate puncture site will be covered in detail in the anatomy section below. In general, avoiding cartilage is important to minimize difficulty in wall puncture and avoiding plugging of the needle before the target is reached. As mentioned earlier, the angle of the needle for TBNA is ideally perpendicular to the tracheal or bronchial wall. While this is not always possible, a 45° to 90° penetration of the needle through the wall will maximize the length of needle in the target lesion. Too shallow an angle of penetration may result in missing the target and/or a bronchial wall biopsy.

Once the needle has fully penetrated the wall with appropriate angulation, suction should be applied with a syringe attached to the proximal end of the needle sheath. A 20 ml syringe is used to apply suction while the needle is in the lesion. If the syringe is not a locking syringe, it is important that the person applying the suction does not allow the syringe plunger to move forward once suction is applied to avoid dislodging the specimen from the needle.

With suction applied the needle should be moved in a back and forth motion by advancing and withdrawing the needle sheath at the proximal end of the working channel with the intent of advancing the needle through the target lesion multiple times without allowing the needle tip to exit the mucosal wall. One style of performing this part of the procedure is to do this back and forth motion very quickly in a high frequency fashion with very small excursion of each stroke. Another method is to withdraw and advance the needle a greater length each stroke but at a lower frequency. This method is done by changing the orientation of the needle tip by rotating and altering the angulation of the bronchoscope slightly with each advancement. For histology core biopsies the slower method with longer strokes is more desirable. In EBUS-TBNA this can be accomplished under ultrasound visualization and is more effective because of the greater length and rigidity of the needle. In EBUS-TBNA, the needle is moved in and out within the outer catheter that has been fixed to the scope.

Before withdrawal of the needle from the target, the syringe used for suction is disconnected from the needle sheath, removing suction at the needle tip. The needle is then withdrawn into the sheath; the bronchoscopist straightens the scope tip and smoothly pulls the needle out of the working channel. Once out of the bronchoscope, the needle is extended and locked, and the specimen is pushed out of the needle shaft either with air, saline, or a stylet.

Specimen preparation is largely dependent on the institution's pathology service. Cytology is the most common specimen type. Histology is usually obtained as a core biopsy or in cellblock format prepared as a histological specimen. The preparation of the specimen can affect the diagnostic yield.14 The clot or “jello” cellblock technique is a method that has been used in traditional TBNA, but is more heavily used in EBUS-TBNA and has optimized diagnostic results.

EBUS-TBNA does have some notable differences to traditional TBNA. The most obvious is that the target lesion can be visualized real-time and needle penetration and successful positioning of the needle tip in the target can be confirmed prior to taking the specimen. The EBUS-TBNA needle is considerably longer than conventional TBNA needles and, as mentioned in the instruments section, has a greater range for biopsy past the mucosal wall. This added range does not always correlate to success in reaching targets as the added length, increased stiffness and fixed exit angle from the bronchoscope may all contribute to an inability to achieve the angle necessary for a safe path for the needle. Once in the target, the added length and stiffness does allow for more efficient and deeper back and forth strokes within the lesion, thus allowing for the collection of more biopsy material. The EBUS-TBNA needle is more cumbersome than the standard TBNA needles and the need to remove the inner stylet completely before applying suction is a nuisance and a risk. With the EBUS-TBNA needles, the bronchoscopist is limited to 22-gauge or 21-gauge needles. Continued development of the EBUS-TBNA scope and needles to reflect the simplicity and effectiveness of the standard TBNA technique will greatly enhance the potential for future widespread use of EBUS-TBNA.

Anatomy

  1. Top of page
  2. Abstract
  3. Introduction
  4. Indication
  5. Instruments
  6. Methodology
  7. Anatomy
  8. Summary
  9. References

Even with the best instruments and technique, TBNA will not be effective if the appropriate puncture site for the needle is not selected. Historically, radiographic imaging and airway branching was used to guide selection of biopsy sites. Occasionally using fluoroscopy during the procedure, the area of abnormality could be identified and biopsied. CT scan is used to identify the abnormality in relation to some recognizable landmarks in the airway. The proximal airways are relatively fixed in relation to mediastinal and hilar structures so distances measured from airway bifurcations such as the carina can be reliably made and used to guide biopsies. Over time, experienced bronchoscopists recognized the consistent endobronchial location for common mediastinal lymph node chains. In 1994, Wang published a map of the mediastinal and hilar lymph node stations with CT and endobronchial correlations for each of the stations. Wang identified 11 endobronchial locations that allowed for TBNA biopsy of the mediastinum in areas accessible from the airways.8

These 11 nodal stations were selected because they can be sampled easily and safely with the TBNA technique. They are also consistently involved with metastatic tumor. TBNA is not recommended for the sampling of para-aortic or parapulmonary artery lymph nodes. Lymph nodes in the AP window, like the left paratracheal and subaortic lymph nodes, are in reach of TBNA. AP lymph nodes lateral to the tracheal wall can be reached by a longer or telescopic needle. Fortunately, lymph nodes along the side of the aorta, pulmonary artery, or between these vessels but too far from the tracheobronchial wall, can also easily be sampled by percutaneous needle aspiration (PCNA). In our experience, mediastinotomy is rarely necessary. Lesions in the above areas are relatively fixed and non-mobile during respiration. The aortic knob, left main bronchus, and pulmonary artery can easily be used as landmarks for PCNA under fluoroscopy or CT scan. Paraesophageal lymph nodes distant from the bronchial tree may be sampled by transesophageal needle aspiration. Pulmonary ligament lymph nodes are difficult to locate with CT imaging and are rarely the only lymph nodes involved. Some of the station 10, or sub-subcarinal nodes may include the paraesophageal to pulmonary ligament lymph nodes.

The following is a detailed description of the 11 nodal stations, their location on CT scan, their recommended puncture site by TBNA, and their relationship to the existing International Association for the Study of Lung Cancer (IASLC)15 nodal system. At the carinal level, there are six nodal stations: 1, anterior carina; 2, posterior carina; 3, right paratrachea; 4, left paratracheal or AP window; 5, right main bronchus; and 6, left main bronchus. Anterior carina lymph nodes are defined as lymph nodes in front of the carina. Carina is defined on the CT scan by the change of shape of the trachea to triangular or oval or the appearance of the carina tip, which divides the bronchus into right and left. This area usually is at the same level as the azygos arch. The lymph node in this area is often called the azygos node when it is lateral with the trachea, or the pretracheal node when it is more anterior. We propose to call the lymph node in this area anterior carina, although sometimes it is not exactly in front of the tip of the carina but slightly to the right. Lymph nodes inferior and lateral to the anterior carina are called right main bronchus nodes, and lymph nodes more superior and lateral to the anterior carina are defined as right paratracheal. The right paratracheal lymph node is above the superior border of the azygos arch and is anterior and lateral to the trachea and posterior and medial to the superior vena cava. Stations 1, 3, and 5 are defined as the right mediastinal lymph nodes. It can be difficult to separate one node from the other, and often all are involved.

To sample the anterior carina node, the needle is placed between the space of the first tracheal cartilage ring and the first bronchial cartilage ring, anteriorly and slightly toward the right. For right paratracheal lymph node, the second to the fourth tracheal intercartilage space above the carina is punctured anterolaterally. This avoids the azygos arch. The needle tip is not long enough to reach the superior vena cava. For the right main bronchus lymph node, the space between the first two bronchial cartilage rings anteriorly is punctured. The posterior carina node is exactly posterior to the anterior carina. Often it is more posterior to the right main bronchus; the puncture site is at the medial posterior wall of the right main bronchus. No major vessels are in this area. In the absence of lymph nodes, however, the azygoesophageal recess may be punctured, possibly resulting in pneumothorax. The left paratracheal lymph node is defined as the lymph node lateral to the left lower trachea. When it is below the aortic arch and above the pulmonary artery, it is also called the AP window lymph node. The AP window lymph nodes also include lymph nodes lateral to the left main bronchus. Sampling of this group of lymph nodes is accomplished at the lateral aspect of the left lower trachea or proximal left main bronchus. When sampling the AP window, if the needle is placed too high, the aorta may be punctured and if placed too low, the pulmonary artery may be punctured. For this reason, the needle must be placed very close to the tracheobronchial angulation as horizontal as possible to the trachea. Station 6 lymph nodes are anterior to the left main bronchus. The puncture site for these nodes is anterior to the space between the first two bronchial cartilages. Stations 4 and 6 are considered the left mediastinum lymph nodes. The second major landmark is the right upper lobe bronchus. Two nodal stations exist in this area. First, in front of and between the right upper lobe and bronchus intermedius, is the right upper hilar lymph node station. Second, the lymph node next to the medial wall of the right main bronchus is defined as the subcarinal lymph node. The subcarinal lymph node is between the right and left main bronchus at the level of the right upper lobe bronchus. When it extends downward, distal to the right upper lobe bronchus, it is called the sub-subcarinal node. When it extends above the right upper lobe bronchus, it often moves more posterior and becomes the posterior carina lymph node. The puncture site for the right upper hilar is at the anterior aspect of the right upper lobe spur. The puncture site of the subcarina is at the medial wall of the right main bronchus, proximal to the right upper lobe orifice. The third landmark is the bronchus intermedius. At this level, the lymph node at the anterior lateral aspect of the bronchus intermedius is defined as right lower hilar and the lymph node medial to the bronchus intermedius is defined as the sub-subcarina lymph node The puncture site for the right lower hilar is at the right anterior lateral wall of the bronchus intermedius and the puncture site for sub-subcarina is at the medial posterior wall of the bronchus intermedius. Often, lymph node stations 9 and 10 can be seen on CT scan to extend below the right middle lobe bronchus. These are still defined as sub-subcarina and right lower hilar. Puncture sites should be at the level of the right middle lobe orifice. Right upper hilar and right lower hilar puncture can often result in bloody aspiration because of the proximity to the superior pulmonary vein in the right upper hilar and the right main pulmonary artery in the right lower hilar. Subcarina and sub-subcarina are away from major vessels and left atrium. The last station is at the left upper lobe spur. The lymph node in between the left upper and lower lobe bronchi is named the left hilar node, station 11. The puncture site is at the mid lateral wall of the left lower lobe bronchus, proximal to the superior segment orifice. Unless the needle is placed too posterior, bloody aspiration is uncommon at this site in comparison with the right lower hilar. If blood is aspirated from the right hilar station, the puncture site should be moved more posterior to avoid the vessel.

Overall, the various classifications for mediastinal and hilar lymph node staging in lung cancer from the past 20 years show much more agreement than discord. One of the most crucial determinations that needed to be clarified with the involved lymph nodes is whether or not they are hilar or mediastinal. The current IASLC15,16 classifications effectively resolve the distinction between mediastinal and hilar lymph nodes in the distal trachea and proximal main bronchi as well as the subcarina. More specifically, 4R is defined superiorly by the intersection of the caudal margin of the innominate vein with the trachea and inferiorly by the lower border of the azygos vein and moving the midline to the lateral border of the trachea (Fig. 1). This coincides with the concept of stations 3, 1, and 5 (right paratracheal, anterior carina and right main bronchus lymph nodes) in the Wang system or right mediastinum. The 4L station is defined by the upper margin of the aortic arch and inferiorly by the upper rim of the left pulmonary artery (Fig. 2). This definition includes lymph nodes that are at the proximal left main bronchus. In the Wang system, the left side mediastinal lymph nodes are station 4 and 6 (AP window and proximal left main bronchus, respectively). Extending the mediastinum lymph node borders downward, the subcarina lymph node is now consistent with the Wang lymph node stations 8 and 10, and both are central mediastinum lymph nodes. It is important to highlight that the new IASLC has included the proximal main bronchi lymph nodes as mediastinum (lower border of 4R and 4L). While the original Wang system was developed from an endobronchial view with CT correlation to aid in biopsy, the new changes to the IASLC nodal system now is in concordance with the Wang system for mediastinal and hilar nodal classification. From the perspective of endobronchial biopsy, the Wang system is much more specific and descriptive. (Table 1)

image

Figure 1. Correlation between Wang and International Association for the Study of Lung Cancer (IASLC) 4R nodal station. Ao,aorta; Az, azygous vein, LPa, left pulmonary artery.

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image

Figure 2. Correlation between Wang and International Association for the Study of Lung Cancer (IASLC) 4L nodal station. Ao,aorta; Az, azygous vein, LPa, left pulmonary artery.

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Table 1.  Correlation between Wang and new IASLC nodal stations
IASLC LN stationWang LN station
  1. IASLC, International Association for the Study of Lung Cancer; L, left; LN, lymph node; R, right.

4R1,3,5
4L4,6
72,8,10
11R7,9
11L11

Summary

  1. Top of page
  2. Abstract
  3. Introduction
  4. Indication
  5. Instruments
  6. Methodology
  7. Anatomy
  8. Summary
  9. References

These exciting new technologies have refocused the pulmonary specialist community on TBNA and we should capitalize on this by increasing efforts to improve training quality and availability for standard TBNA as well as EBUS-TBNA. Objective clarification for the role for each of these techniques is still needed. In our experience with over 200 patients undergoing both standard TBNA and EBUS-TBNA, only in five cases did EBUS-TBNA add to the diagnosis, all of which were normal sized lymph nodes. It appears EBUS-TBNA has the utility to increase the yield in smaller lesions and avoid bloody aspirations in hilar lesions.17 In the future, we will likely be required to justify the cost of TBNA and provide the best value to the patient and health care system for our diagnostic procedures. The vision for the future should include applying technological advances to revolutionize our instruments and techniques with ultrasound capability, focusing on accuracy and safety and developing a simpler instrument and easier methodology for TBNA to minimize patient discomfort and cost so it can be widely applied for the diagnosing and staging of lung cancer.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Indication
  5. Instruments
  6. Methodology
  7. Anatomy
  8. Summary
  9. References