Welcome back. This is part two of our series of many lectures on image directed tissue sampling for lymph node staging in lung cancer. So in part two, we'll be talking about medical techniques. Just to reiterate our objectives for this series of many lectures is to review the different methods of lymph node sampling that are available to our team. And to show how imaging can help direct the best methods of sampling in any individual patient. So in the first part we went over the surgical techniques, namely, mediastinoscopy, chamberlain procedure, and a VATS procedure. Today, we will be talking about medical techniques for lymph node biopsies, including transbronchial needle aspiration biopsy, abbreviated TBNA and sometimes called a Wang procedure. We'll go over endobronchial ultrasonography, sometimes called EBUS, as well as endoscopic ultrasonography, or EUS. Let's first go over a pre-lecture question. And we'll have you answer this, and then we'll get back to this at the end of the talk. This was a 50-year-old man who had a left upper lobe lung cancer. We see on his CT scan that there is a prominent lymph node over here in station 4L. So if you wanted to biopsy this 4L lymph node let's talk about what would be the least optimal way to sample a 4L lymph node. So you can choose from transbronchial needle aspiration biopsy. Endobronchial ultrasound, or endoscopic ultrasonography. So again, choose the least optimal way to sample this 4L lymph note. We will get back to that question at the end. Let's now get started with the talk, and we'll begin with transbronchial needle aspiration biopsy. This technique is done via the bronchoscope. So here is the bronchoscope going down the trachea and we can see the biopsy needle protruding out of the end of the instrument through the wall of the trachea into this adjacent lymph node. This type of biopsy is essentially done blindly by the bronchoscopist meaning that he or she can see the lumen of the airway but cannot see the lymph node outside the wall of the air way. So what's done is the needle is placed using internal airway land marks without knowing exactly where the lymph node is and if the needle is going into it. So the lymph node itself is not visualized. This technique is good for bulky lymph nodes that touch, or nearly touch the outer airway wall. And this yields a cytologic sample, in other words a fine-needle aspiration biopsy. As opposed to the surgical techniques which yield large tissue samples. What station or stations are suitable for transbronchial needle aspiration biopsy? The major station that we go after is station 7, the subcarinal lymph nodes. The bronchoscopist will put the scope down the trachea, generally go just passed carina, and then angle medially into the subcarinal region. So if we see a lymph node like this one in station 7 just below the carina, that would be potentially reachable with a TBNA technique. Occasionally, we can use this technique for the upper and lower paratracheal lymph nodes, for example, this 2R lymph node. This is more difficult, however, because the scope has to be angulated to go through the wall to reach this lymph node. And also there are no internal landmarks for the bronchoscopist to know where to do that angulation and where to place the needle. So we generally reserve TBNA for subcarinal lymph nodes. That is our segue into our next medical technique, which is endobronchial ultrasonography, abbreviated EBUS, which is essentially an add-on to TBNA. So TBNA with EBUS is also done using a bronchoscope, but it's a special bronchoscope, which also has an ultrasound transducer on the end of it, which we can see over here. So while the bronchoscopist is looking down the endoscope, the transducer can be turned on. And then they can see the ultrasound beam, which shows the lymph node just outside the wall of the airway. And they can watch the needle going into the lymph node. So, as they're doing the biopsy, they can watch and make sure they are in the right place. The lymph nodes do not actually have to touch the outer airway wall. That is because the needle is about 5 centimeters long and there is about a 5 centimeter visualization depth with ultrasound. So what stations are reachable using EBUS? Well, the bronchoscopist can get to the upper and lower paratracheal lymph nodes, stations 2 and 4, also station 7, as well as multiple stations in the pulmonary hila, 10, 11, and 12, so very wide coverage using EBUS. Generally at our institution we only use EBUS for abnormal lymph nodes. In other words for lymph nodes that are big on CT scan or they're FDG avid on PET scanning. However, complete nodal sampling is possible using this technique, so you could put the scope down, turn on the ultrasound beam, and sample any lymph node that you find, whether the lymph node is large or not large. We don't do that at our institution, but some other practices do that. We do have to keep in mind that EBUS is not universally available. You need the special equipment and you need the local expertise. We are lucky to have this in our university hospital. However, if I were at a community hospital, or out in the country side, or maybe in a different country, I might not have access to this technique for my patients. TBNA with EBUS is very accurate in the setting of staging lung cancer. Sensitivity reported to be almost 90% with a similar negative predictive value. Here's an example of an EBUS technique. The slide was given to me by Dr. Arenberg, who you'll be hearing from as part of this entire lecture series. We see the scope going down the central airway, here is the ultrasound transducer in this diagram, this represents the balloon on the end which is insufflated to seat the ultrasound transducer in the airway. The green dot shows where the needle comes out. Here is the needle going into this lymph node. And let me just point out that they can turn on Doppler and that will light up the vessels so they're sure they're not going into a vascular structure. And this just illustrates how the needle would come out where that green dot is and usually it'll take several cytologic samples. Let's look at an example of a patient we saw at our weekly tumor board meeting. This was a 65 year old man who had a central left upper lobe squamous cell cancer which we see over here. On PET scanning, this central lung cancer was extremely FDG avid. Images at a slightly different level show multiple small meaty Steinel lymph nodes. None of these are enlarged using CT criteria. However, this lymph node over here was very FDG avid. So that lymph node was suspicious for a nodal metastasis. We decided we needed to get a sample of that lymph node to help stage the tumor. So we first had to think about what station this lymph node was in. And this would be station 4L. So here's our question. How would we biopsy this small FDG avid 4L lymph node? So we could choose mediastinoscopy, transbronchial needle aspiration biopsy, EBUS procedure, or CT guided biopsy. So, go ahead and choose your one or more best answers here. Well, the best answers here would be mediastinoscopy as well as EBUS. We really couldn't get to this with a Wang procedure. It's too small. We wouldn't be able to know what we're going after because we couldn't see it. With CT guided biopsy, we really can't get there. There are too many vital structures in the way. So we could pick mediastinoscopy or EBUS. This patient ended up having an EBUS procedure. Here's an image from that procedure. This is where the needle will come out. Here is the lymph node. And here, we see the needle within the lymph node itself and the pathology came back metastatic non-small cell lung cancer. So the take home point for this case is that EBUS enables sampling of even small lymph nodes. They do not have to be enlarged. Let's move on to our last medical technique, and that's endoscopic ultrasonography, often called EUS. This type of procedure is done using a curvilinear echoendoscope just like the echoendoscope used for an EBUS. So for an EBUS, the instrument goes down through the trachea. But for an EUS, the instrument goes down the esophagus as we see here. And here, we can see the ultrasound transducer showing the operator this lymph node outside the esophageal wall, and the needle extending through the wall of the esophagus into this lymph node. So the operators can watch real time as the biopsy is being done. This procedure, not surprisingly, is suitable for lymph nodes near the esophagus. This yields a cytologic sample. So again, the surgical techniques yield big tissue samples. The medical techniques generally will yield fine needle aspiration samples. Just like with EBUS, EUS is not universally available. It requires the appropriate equipment as well as the appropriate expertise. Many of us our familiar with endoscopic ultrasonography and biopsy for patients with esophageal cancer, in order to enable regional nodal staging as we see in this diagram. But more and more EUS is being used to stage lung cancer patients. And in this setting it is reported to have very high sensitivity, and particularly this is true when we are trying to sample in large lymph nodes. So what stations can we get to with EUS? Well, what we think about generally is station eight. Those are the para esophageal lymph nodes. But essentially EUS can get to any lymph nodes that touch or nearly touch the esophagus. So stations 7, 8, and 9, station 3p, as we see here next in the esophagus, and 4L. In some patients, however, we can get to lots of other stations as well. Maybe the upper and lower paratrachial lymph nodes, sometimes even 3a. It just depends on the individual patient whether or not those lymph nodes happen to be near the esophagus. So here's a station 8 lymph node next to the esophagus, that one is entirely suitable for an EUS biopsy. Keep in mind, that other lesions can also sometimes be biopsied with EUS. In our institution endoscopic ultrasound biopsy through the esophagus is done by the gastroenterologist. So they go down through the esophagus, they get to the stomach and sometimes they'll see abnormalities in the abdomen and then they can sample those. So for example, this patient has a left adrenal nodule and in the setting of lung cancer that's suspicious for metastasis, and death can be biopsied right to the stomach. Occasionally enlarge mesenteric lymph nodes are seen, and those can also be sampled at the same sitting. Here's an example of the patient who had non-small cell lung cancer. We see a necrotic appearing lymph node here in the mediastinum on CT scanning. On PET scanning this lymph node was extremely FDG avid. This lymph node is in between the left mainstem bronchus and the esophagus. So we have to think about which station this is. And I would say you could call this maybe a low station 7, a low subcarinal or perhaps a high station 8 lymph node, paraesophageal. But more importantly, how would we access this suspicious looking lymph node? Let's choose from mediastinoscopy, VATS procedure, chamberlain procedure or endoscopic ultrasonography. Go ahead and pick your best choice here. And I would say the best choice here would be endoscopic ultrasonography. You can't get to a lymph node in this location easily with mediastinoscopy. It's a little bit on the low side. VATS might work if you could come in through the right pleural space that might be a little difficult. Chamberlain can't get there at all, but EUS would be the best choice for this patient. And here's an image from the endoscopic ultrasonography exam as we see here, and the biopsy came back positive for non-small cell lung cancer. Using our techniques, our medical techniques, we can do pre-operative total nodal sampling, in other words, we can sample not just abnormal appearing lymph nodes on our scans, but also normal lymph nodes. And that can be done with a combination of EBUS and EUS. So essentially what would happen is the scope would be put down the central airway. And any visible lymph nodes near the central airway would be biopsied with EBUS, and then the scope would be withdrawn and inserted down the esophagus. And any additional lymph node stations that were visible and accessible could be biopsied that way there by sampling the vast majority of the mediastinal lymph node stations. We don't do this at our institution, but some practices do. So again, that's using the same endoscope. This type of total nodal sampling is reported to have very high sensitivity and perfect specificity. Well that brings us back to the question we started off with at the beginning of the lecture. So here's our post lecture question. We have a 50-year-old man who had a left upper lobe lung cancer and a prominent station 4L lymph node. So, if we wanted to sample this lymph node, what would be the least optimal way to get a tissue sample? So, go ahead and pick your least optimal choice. The least optimal choice in this patient would be transbronchial needle aspiration biopsy because the bronchoscopus would not be able to see what here she is going after and might be hard to ungulate the skull, you could potentially get to this lymph node with EBUS or with EUS. Okay, that brings us to our take home points. First of all, medical techniques enable preoperative or non-operative sampling of most mediastinal and hilar regions. The exception to this would be stations five and six. We can sample lymph nodes near the central airways or the esophagus using these techniques. And the techniques are successful not just for enlarged lymph nodes but also for small lymph nodes. Keep in mind that a combinations of EBUS and EUS may be combined for a total pre-operative nodal sampling. Well that will finishes our talk on medical techniques. Next lecture will be about image guided techniques, including CT and ultrasound guided biopsies, and I look forward to talking to you next time. Thanks for your attention.