Hello, welcome back. We're going to now talk about the part two of our lecture series on endoscopic TN staging as well as management of early esophageal cancers. The objectives for part two are going to include basic T/N staging, when we use the echo-endoscope for staging, what are its pros, and what are some of the limitations. Development of an appropriate treatment plan, all is dependent on stage. So you can see here, the prognosis depends on local invasion and presence of spread to regional and or distant structures within the thoracic cavity. Accurate staging is critical, like we said, in establishing a treatment plan. So what do we use whenever we are trying to stage these cancers? You can do CT, you can do a PET scan, and also EUS. And staging these, we use the AJCC TNM staging system, just as it is with many other cancers. So the depth of disease is key to staging. And that is sort of one of the big take home points here. Establishing depth of invasion is critical because it also has an effect on whether or not we can offer curating endoscopic therapy. As opposed to sending the patient directly for surgical management or chemo and radiation. So mucosal malignancies, which are called T1a, and we're going to over the T staging here in just a moment, have an extremely low risk of lymph node progression. As soon as you get in to sub-mucosa, it carries a higher risk of lymph node metastasis. Metastatic disease, you can see here, is present in only about 21% of Sm1 lesion and 56% of Sm3. We're going to talk about what those mean in a moment. So before we can talk about TNM staging, we need to talk about the esophageal wall layers. So if you see here on this diagram, we have the layers of the esophagus. This side would be the luminal layer, so when you're actually eating and putting food in. And this would be the outside, which is within the [INAUDIBLE] cavity. Here, you have the epithelium. The superficial layer right here is lamina propria. That is what we are going to refer to as layer one. Layer two is the muscularis mucosa. Layer three, submucosa. Layer four, the muscularis propria. And then layer five, the adventitia. Keep in mind like we just said, the esophagus does not have a serosa like the other structures within the body. Now what does this look like on an echoendoscope? Because that is the imaging modality that we were going to be using. What you can see here, is this is the image we see whenever we put an endoscope down into the esophagus in a patient. What they are trying to see here is that oftentimes, we'll put a balloon on the tip of the echo endoscope to allow us to get good acquisition in the scope against the tissue plane. It also helps us to anchor the tissue to get a better imaging, move other structures out of the way, and what not. So what you can see here, and it's a little difficult, but this very first bright white line is actually layer 1. Now if you remember, that layer 1 was lamina propria. The second line, which is slightly darker and we call that hypoechoic, is the mascularis mucosa. The third line, which again is hyperechoic because it's bright white, is the submucosa. The forth line here again, hypoechoic, is actually the muscularis propria. And then this fifth bright white sort of thicker area right here doesn't necessarily have to be but on this image, it does look thicker is the adventitia. So let's talk about the TNM staging system. Again, this is a lot of material, you're not going to be expected to just be able to rail this off the top of your head, unless you choose to have a career and then and then let me know. But, essentially, what I want you to take away from here is, T is just a primary tumor and staging again with T staging is how deep with into this wall this is going. As soon as we get into the submucosa, you're talking about a T1 lesion. Anything going beyond the submucosa into the muscularis propria is T2. And adventitia is T3. Now again, for our purposes and what you're going to learn in the next part of this lecture, is that once you get into T2, we really aren't good at offering endoscopic curative management. You're looking primarily at catching people when they're within this T1 stage for us to offer something endocopically. If you look here really briefly with the N staging, a little easier. So if you don't see any regional lymph node metastasis, that's excluding the celiac node, that's considered N0. If you have regional lymph node metastasis, that's considered N1. And if you just can't assess for it, we call that NX. So TX is what we would write down if we just can't assess the tumor. Again, we tend to not use this phrase. This is just so that you have what the proper semantics would be. We'd just say that we were unable to do the exam, either because we couldn't get the scope down, or we just couldn't get good images. T0: there's no evidence of a primary tumor. Also, by the time it comes to us, we know there's a tumor there and so this is never an issue. Now Tis also T inside 2 is the cancer only in the epithelial layer. So it's that tissue above laminar propria or level 1. It has not started growing into the deeper layers and this is also known as high grade dysplasia. In the past, we used to call it carcinoma in situ, which is why Tis came into play. T1 is cancer growing into the tissue under the epithelium, such as the lamina propria, muscularis mucosa, or submucosa. So when we talk about T1 lesions, we further break that down into T1a, or T1b. As soon as you get into T1b, that means you're starting to affect the submucosa. And that is the tissue area where only endoscopic submucosal dissection, or ESD, can be offered. Not EMR like we're going to talk about in the part two of the structure series. If you're T1a, you're above submucosa and it's easier for us to treat that endoscopically. T2 means that you got in to level 3. I'm sorry, in level 4 now, which is the muscularis propria that thick muscle layer just beyond submucosa. T3 is now the tissue got into level 5, which is the adventisia. And T4 meaning is going into nearby structures. That could be the pericardium and the aorta for example. When they talk about T4 again to further break it down in terms of semantics this tends to not really be used in clinical practice. T4a is growing into the pleura, pericardium, or the diaphragm. T4b is growing into other structures, such as the aorta, the spine, the trachea. Once you get to T4, whether it's a or b, doesn't really have too much of an impact whenever we are describing that to our surgical and our oncologist colleagues. So I tried to tie these together when we're talking about all this structures. And I'll show you something on an echoendoscope scope. So when we put the scope down, again, this is going to be the luminal surface where your food is going to be passing. And this is the deeper structures where the thoracic cavity and the mediastinum being out over here. You have the epithelium. And you have high grade dysplasia. This was the TIS or [INAUDIBLE]. This has not yet affected layer one which is the lamina propria right here. As soon as you get into layer one, you're now looking at T1 intramucosal solution. This is the same thing as T1-A. This is showing that it's either affecting the lamina propria, or it's also getting into the muscularis mucosae, which is layer two. T1, submucosa, or T1 B, is now showing that it's affecting this third layer. And this is the tumor that we have a harder time, and we cannot address it with endoscopic mucosal resection. It can be addressed with endoscopic submucosal dissection which is gaining ground at the United States but it's not as commonly done as the EMR techniques. T2 means that we've now gone beyond submucosa into layer of level 4. T3 is showing that it's going beyond the muscularis propria into eventation. Then T4 is showing that it's invading an adjacent structure here. It's the aorta, so theoretically, it would be T4 B. Here, this is trying to show you neural metastases, no neural involvement or normal happy looking sort of draping lymph node as opposed to an enlarged irregular lymph node that we see here in the new stage as N1. So let's talk about EUS as a modality for staging. EUS or endoscopic ultra sound is now considered the most accurate imaging modality to establish T stage. It is better than CT or MRI for pre-operative T staging. And if you look at the percentages there are about 76% to 89% versus 49% to 59% accuracy. Obviously if the tumor size increases and gets larger, it's better for us, because we have more accurate, we have more tissue to work with. And we get a clearer image whenever we're trying to stage these lesions. When we talk about N staging, EUS can accurately determine N staging in about 90%, of superficial and partially obstructing lesions. Whenever we talk about lymph nodes on endoscopic ultra sound, we talk about the acoustic characteristics that can make it either seem more malignant or more benign. So things that will tip us off or raise our antenna about this lymph node looking abnormal and possibly being a malignant node, is a size greater than one centimeter or ten millimeters. If it's a very round and smooth, very clearly defined bordered node, the proximity, obviously, to the primary tumor, and if it's hypoechogenic. We'll talk about in the next slide what we see with a normal or benign-looking lymph node and you can sort of compare between the two. The accuracy of applying these acoustic characteristics approaches 80%. And if we do an FNA, which is a fine needle aspirate of the lymph node in question, we can increase that accuracy from 80% going up to 92% to 98%. You can see here on two ultrasound images, we have a benign lymph node here. It's very hazy bordered. It's what we call, I wouldn't say it's hypoechoic, but it's more isoechoic, an iso, meaning same echogenicity, as what we compared to as the liver. You have a very sort of bean-shaped, we call it draping or triangular node. The size you can't really tell here, but not a terribly large size, it's more isoechoic. Whereas if you see this malignant lymph node right here, it's dark, it's hypoechoic, it's very well defined. You can very clearly see what the borders are, which is why they've tried to also show this right here, compared to this very sort of hazy looking thing. It's more round. It's not sort of bean or draping or triangular shaped. Like we will often describe. Note, these two don't necessarily correlate here because we're talking about benign with this image and malignant with this image. But you can see how we describe it. So if we describe a node that's sort of draping, like I said, or triangular, fuzzy margined or hyper or isoechoic, you're probably talking about a benign node. Whenever you start worrying is if it's hypoechoic, it's very sharp margined, round or oval, and obviously, the size is greater than one centimeter. So the utility of EUS when we're using it to determine pre-treatment staging and to identify cases, obviously talking about jaw cancer, that may or may not be amenable to our minimally invasive endoscopic therapies is sought of why EUS is superior it cannot only be used to diagnostic tool. But theoretically at the time, we can even while we have the scope down, provide therapy as well. EUS can also be used to determine response to chemotherapy. Now this is going to be a little different here, whenever it comes to radiation. And then we're going to talk about that in a moment. EUS staging, the accuracy, like I said, decreases in cases when we can't get our EUS scope down beyond the tumor. There used to be a practice of going down and dilating these patients in order to get the endoscopic ultrasound scope down. That carries a really high perforation rate, up to 24% and a high mortality. So that is not a practice that, at least here at the University of Michigan, that we routinely carry out. Partial staging of the accessible area, meaning the area we can actually see upstream, where our scope can go risks under staging the lesion. What I mean by that is what we see up top may not be what actually is happening throughout the lesion and its sort of more distill into the area that we can't put our scope. So we may staged something as T2 or T3 and further down there actually is a T4 lesion. One thing that has been shown in terms of it being evidence-based is when we can not pass our EUS scope through the stenotic tumor, T3 disease was present in 89% of those patients. And N2/N3 disease was present in about 63%. So when we sort of hit this barrier whenever we're doing our procedure on a patient that's being sent to us for treatment staging. If we can't pass the scope down, we do not dilate. We just abort the procedure and we send the patient for likely neo-adjuvant therapy. But mostly likely back to the referring surgeon or oncologist. What are the limitations of EUS because I'm singing about all the glories. But every imaging motarility has it's limitations and you keep those in mind and never discuss that with patient as well as interpreting the data. Obviously endoscopic ultrasound then imaging study just like in the titanium ultrasound is operator dependent. It is not as optimal as EMR or surgery for T staging. Now what I mean by that is these are all images that we are getting and we're seeing. And for somebody that has been doing this for 15, 20, 30 years, they can sometimes be duped by not correctly identifying what layer may or may not be hazy, let alone for you, who's looking at this likely for the first time. And can't make heads or tails of the dark line, or the black line, or the white line. So whenever you are able to do EMR, or surgery, you're giving the pathologist tissue and block. They're actually looking at this under a microscope and they can see Tissue in front of them, to determine how deep and how accurate that would be, in terms of neoplastic tissue going into the esophageal layers. Now one thing to keep in mind with EUS, is that staging and re-staging after neo-adjuvant chemo and radiation, it is not accurate. Radiation totally destroys all of our mucosal planes and there's no way for us to distinguish in the vast majority of cases whether it's residual disease or whether it's radiation induced mucosal injury. Oftentimes we go down and everything just looks obliterated. We can't make heads or tails of what is there, what's not. So whenever we're talking about T staging in these patients that have had chemo and radiation, you're getting a 29-60%, which is a huge range. But again, it just goes to show you that it's not the optimal test for T staging these patients. 38 to 71% for N staging. And we can get about to a 78% whenever we're actually doing an FNA of an abnormal-looking lymph node. Again, we're getting tissue for the pathologist to look at, which is why we can get that accuracy. But whenever you have a patient that is post-chemo radiation, sending them for restaging via EUS is not the way to go. The most optimal imaging modality for that is a PET scan. So, in other words, we're at the end of part one here, what are the things that I want you to be able to take away from this as you walk away from this lecture? I want you to know the esophageal walls layers. Because that is critical whenever you are talking about staging and whenever you're talking about whether or not a patient's going to be amendable to endoscopic curative therapy. There are five layers, lamina propria, muscularis mucosa, submucosa, muscularis propria, and the adventitia. Keep in mind, the esophagus does not have a serosal layer. Accurate staging is critical when we're developing a treatment plan, and for prognostic information for the patient in anybody with esophageal cancer. EUS is the imaging modality to go to whenever you're trying to talk about T staging in these patients. It's better than a CT or MRI. And obviously our T staging improves as the tumor size increases. If the echo-endoscope can't pass, it's likely a T3 lesion, we do not dilate, we do not do further therapy to try to get the echo-endoscope down, we call a T3 and we send the patient out. EUS N staging, which is nodal staging improves, obviously, with FNA which is fine needle aspirate. We're actually going in, sucking out cells, and giving it to our pathologist to look at. When you have a patient post radiation treatment, the evaluation is best left to a PET scan, not in EUS. So let's go back to the questions that I showed you at the beginning of the lecture, and see if we can now identify what the correct answer is. So, number one, what was the correct esophageal wall anatomy from the luminal side to the mediastinal side? Now we see that the answer is c, lamina propria, muscularis mucosa, submucosa, muscularis propria and adventitia. Number 2, all of the following are risk factors for esophageal adenocarcinoma except. And we see alcohol is the answer here. Number 3, the most optimal assessment of treatment effect in a patient post radiation therapy and chemotherapy would be what? And we know that's going to be a PET scan, not an ultrasound, even though that's what I'm plugging here. Number 4, tumor extending into the submucosa would be staged as? That would be a T1b lesion. Number 5, the most accurate way to obtain information on pre-treatment T staging is. And that would be EUS. All right, so I will see you guys in part two of this lecture theories. Hopefully, that made sense and we'll be able to tie it together a little bit more in part two when we actually talk about What are endoscopic curative therapies are and discuss those in a little bit more detail. If you want more information, one of the better references here is the ASGE Guideline which I would recommend and they discuss the role of endoscopy in the management and assessment of patients with esophageal cancer. It's a phenomenal resource and you can get a little bit more information if you're interested in that and I'll see you shortly.
