Okay, guys, you can breathe a sign of relief. This is Part 3, endoscopic T/N staging and management of early stage esophageal cancer. Again, I'm Aarti Bedi. I'm one of the advanced endoscopists here at the university. Let's get started. The objectives of this section of the topic are going to be to go over available endoscopic options for therapy as well as the indications and the complications of said therapies. So as we start going into some of the topic and the meat of the discussion here, I want you to keep some of these questions in mind, so you can try to keep an eye out for the answer and what the logic is behind it. So question number one, application of endoscopic therapy for the management of esophageal cancer precludes which of the following? A, surgical management, B, chemotherapy, C, radiation therapy, or D, none of the above? Question number two. Curative endoscopic therapy can be attained in patients with, A, T1a disease, B, T1b disease, C, T2 disease as long as they are N0 status, D, both A and B. E, A, B and C. Number three, all of the following are considered high risk factors for metastatic disease except. A, submucosal involvement, B, positive margins, C, tumor size greater than two centimeters in length, D, poor differentiation on histology, and E, lympho-vascular involvement. Question number four, ways to reduce the risk of post EMR esophageal stricturing include. A, prophylactic BID PPI dosing, B, limiting resection to less than 50% of the luminal circumference, C, limiting resection to 5 centimeters or less in length, D, keeping resections to less than 3 over a 12 week period of time. Let's go ahead and get started, and we can start discussing what are the endoscopic options that we have to offer the patients whenever they present to us in the clinic. We have two categories of treatment modalities endoscopically when we talk about them. Number one is endoscopic therapy with curative intent, and number two is endoscopic therapy with palliative intent. We are going to discuss some of the palliative options in a different lecture. When we talk about curative intent, we have two categories that we break it down into. One is resection and one is ablation. When we talk about resection, we talk about EMR and ESD. EMR stands for Endoscopic Mucosal Resection, ESD for Endoscopic Submucosal Dissection. If you remember from the previous parts of this topic, we talked about EMR being offered for patients that don't have submucosal involvement, so those patients that have T1a disease or less. As soon as we get to T1b, where there's some mucosal involvement, I said we can offer endoscopic submucosal dissection, which isn't as commonplace within this country yet, but it is definitely gaining foothold and becoming more common. Whenever we talk about ablation, we have three sort of groupings here. One is photodynamic therapy with the heater probe. One is radiofrequency ablation, or RFA, and that's essentially laser therapy. And APC, which is argon plasma coagulation. We also have cryotherapy. Let's discuss resection. Resection provides large size tissue en-bloc for superior pathologic diagnosis and accuracy when staging compared to ablation. If you remember also, whenever we were talking about echoendoscopic staging, I said that US is not as accurate for staging as the EMR or surgery is, and this is exactly why. The one thing to keep in mind about resection is that it does not impact future ablative therapy. It is curative for mucosal disease. That is disease that is confined to layers that are above the submucosa. The goal is targeted removal of that superficial tissue. So one might say if you can go to surgery and get the entire esophagus taken out, and you know that it's out, one and done. Why are we even discussing or talking about endoscopic therapy, because it doesn't make sense and it might not be as good? We do actually have a great data that shows that there is decreased morbidity and mortality with an endoscopic approach as opposed to surgical management, 0% versus 39% in one report. It is equally efficacious for T1s and T1 disease. It's the similar quality adjusted life years, or the qualies, and it's less cost that is incurred. Obviously, endoscopic management, unless something goes wrong, is an outpatient procedure. We do have them come back for repeat procedures, but with all that taken into consideration, It's more cost-effective. Of course, there are cons with everything. And so some of the cons of the endoscopic therapy and endoscopic approach are like I just said, you are committing the patient to several procedures, and it is a pretty intensive long-term surveillance that we have them undergo. Not only do we take care of the tumor or the cancer tissue via EMR or EST, but we still addressed the remaining Barrett's tissue. In about 21% of patients, there is data that shows that there are meta-chronous lesions at follow-up at 63 months, meaning that there are other foci of cancer that show up apart from the area that we treated as far out as 63 months. We cannot optimally address larger, longer, or deeper lesions. And there's always a concern, and we've discussed at length with patient's missing disease, missing lesions, or burying disease. Especially whenever we start addressing the remaining Barrett's tissue, and we start ablating that tissue. So whenever we talk to patients, we always like to break them up into whether they have a high risk lesion or not. Cancers associated with higher risk of metastatic disease have the following features. There's submucosal involvement. There's lympho-vascular invasion. You have poor histologic differentiation, and you have positive margins. So let's talk about EMR, endoscopic mucosal resection. Methods of raising neoplastic mucosal tissue off of the sub-mucosal and muscular layers and then resecting it. All of that, when we want to talk about it make it sound fancy and say it's endoscopic mucosal resection or EMR, we are essentially cutting out the cancer. It can be used for staging and curative intents. So like I just said, whenever we have a patient, and we are not able to tell with any degree of comfort whether or not this patient is T1A or T1B, we often will have them undergo a staging EMR. Because again, if it is truly a T1A lesion, we could have that patient offered endoscopic curative therapy as opposed to sending them for a surgical management. So we go in, we resect the lesion, we give that tissue en-bloc to the pathologist and let them look at it and see how deep the tumor is invading into the esophageal wall. Staging EMR upstages in about 30% of cases. Again, it shows that giving tissue en-bloc to the pathologist is the way to go, even trumping US. And so this is the most accurate assessment of T staging. Again, we're giving tissue to the pathologist to work with. Who do we offer a EMR for? Patients that have T1a, so neoplastic tissue extending into possibly the Muscularis Mucosa but not beyond into the submucosa. As soon as you start getting tumor invading into the submucosa, it becomes difficult for us to raise that Muscularis Mucosa layer up off of the submucosa and resect, because you have tissue anchoring it to the deeper layer. We usually use this in T1a lesions that are less than or equal to two centimeters in diameter and less than one-third of the wall circumference. Again, this a very soft rule, and we always take into consideration the patient, comorbidities, the age, whether or not they would be a good surgical candidate or not. And often time, people undertake EMR resection in patients with much bigger lesions if after we talked to our surgical colleagues, we come away with the understanding after of course discussing with the patient that they would not survive or have a much rougher time with surgery, then they would if we were to try to do this endoscopically. Patients that have flat Barrett's with this high grade dysplasia are also considered for EMR. In conjunction, that is with ablation. So either cryo or RFA to eradicate all the present Barrett's esophagus. Patients that have nodular Barrett's esophagus are not amenable to some of our ablative techniques such as RFA. And so oftentimes, we will go in, and we will do EMR of those sections of tissue not only to remove them but also to have pathology review and evaluate to make sure that we're not missing our focus on neoplastic tissue. So what is EMR and how do we do it? Here you can see, there are two different methods or techniques of EMR. The method on the left is the cap technique, and the method on the right is band ligation. So what you can see here is we have our image whenever we go down, and unfortunately, you don't really see it on this image. You can get a sneak peak and a cheek here. You have a cap, just a plastic ring that's on the end of our scope. We identify what tissue we want to address. And here, again, you can see this very salmon-colored abnormal looking tissue, and you've got nice pink happy tissue, which would be our normal squamous lining. This was the area that was targeted for resection in this case. They go up to the area in question, and you apply suction. That brings this tissue up into your cap of your scope. With suction applied and maintained, you then put your snare down. Here, you can see if you use your imagination, there's a metallic looking ring right here, and that is the snare being placed around this little mound of tissue that is being suctioned up into your endoscopic cap. And this is the post image, so you see burn and cautery effect right here, and then you've got this divot of remaining where the tissue was previously resected off. This is one technique, it's called the cap technique. Here we have the band technique, same thing. We've got a cap on the end of our scope, and what we do is we go down, we identify the tissue that we want to resect. We suction it up just like this into the tip of the scope, and we apply a rubber band, which is this black thing right here. After we identify, and we suction up, and we applied the rubber band, you have this nice little target, this little mound. We then go down with a snare. Under direct visualization, we place the snare, and we try to place the snare right underneath this rubber band. We apply our heat therapy, and this whole chunk will come falling off. We go and retrieve it and submit that to pathology for review. But you see here, there's a divot where you have the underlying tissue. In this case, you could see submucosal reticular fibers. Oftentimes prior to this step, we will inject a fluid solution with epinephrine, methylene blue, and saline to lift these two layers off of the submucosa. And it also provides staining of the submucosa so that whenever we evaluate our resection site, we can see if there's perforation or anything we need to be concerned about. We usually like to see a very nice blue, uniform reticular layer, which shows us that we have an intact submucosa underneath where we just cut. So there's actually a great video that I'll play here that shows this sort of inaction in an animated form, because it makes a little bit more sense if you're seeing it in real time. So here, you see our scope tip go down. We identified an area, and what you're seeing there is suctioning up, into the tip of the scope, the tissue that is in question. A rubber band is deployed right there and you have this nice little mushroom looking piece of tissue that is going to be the target for our snare to go around for resection. Here, you see the snare coming out of the tip of the scope. We're applying it, hopefully, underneath that rubber band, applying heat therapy, and that tissue falls off. And now, here you can see, again, like I was talking about, you see a reticulated layer of fibrous tissue, which gives a tip that this is intact submucosa. This is visual inspection, and then again, applying another band, resecting more tissue in continuity with the previous area to resect the entire area of question and concern. And here, you can just see that this is all superficial mucosal tissue, and this is the underlying submucosal layer. When we apply this rubber band, this is what we're getting into our scope and see what we are resecting. Which makes it safe, safer in terms of preventing a perforation. What we do is whenever we inject fluid prior to performing any of this, which they didn't show in this cartoon and in this video is the fluid is injected here. And so both of these two layers are raised off of the submucosal layer, and you almost have this, I like to think of it as a little water balloon buffer into which we might cut into a little bit. But it protects underneath submucosal layer, and thus, further reduces the risk of perforation. So just like anything else that we do to a patient, there are ways, a pros, but there are also a cons, and we need to make sure the patient understands what the potential complications are of endoscopic mucosal resection. Number one, bleeding. We are going in and cutting, almost like surgery, and so we can always encounter bleeding, which can be uncontrolled in certain circumstances. Whenever we encounter this, we are very good about managing this phenomenon in this event endoscopically via injection, via clip. But sometimes, we get into bleeding that we cannot control, and then that patient has to be sent to our interventional radiology or surgical colleagues. We usually see this immediately in about 10% of cases. Delayed bleeding is less common, but it can happen, especially in our population of patients that is on intake regulation for one reason or the other. We always discuss perforation. We do say it's less than 1%. And again, the techniques that we use with both injection of saline to lift the mucosal layers off of the submucosal tissue as well as the rubber band and band ligation, we quote less than 1%. Stricture formation occurs in about 25% of cases. It's dependent on the circumference and the length of mucosa that we have to remove. So the more tissue that we're removing and the greater the amount of circumference that is involved at any one point, the higher the risk of stricture formation. The good thing is that whenever we do encounter restructures, we are able to manage those really successfully via endoscopic dilation. We usually try to limit performing EMR and more than 50% of the luminal circumference at anyone point at any given time. And that is pretty good at reducing the risk of stricture formation. So now, you've been introduced to what EMR is, what are the options in terms of ablation and resection therapies, as well as how does EMR and endoscopic resection compare to what the standard of care was and still is for some patients in terms of surgical management. In the next part, we're going to discuss ESD as well as some of the ablative therapies in a bit more detail when we apply them and how we apply them, and finally wrap everything up for you.
