And, you know, we have a lot of famous people at UNC Chapel Hill, but Emma is the author of the FIRES trial, right? Revolutionary, made a huge impact, was practice-changing in regards to Sentinel nodes, and I had the chance to Google that paper recently and found out that it's in the top 1% of quoted papers in, like, the universe. So we are so proud to have Emma, and I also am so thankful she took time out from her family, you know, it's like 8 o'clock at night here, to come talk with us. So anyways, thank you, Emma, for talking tonight. Well, thank you so much, Dr. Van Lee and Dr. Dinh, and everybody for inviting me to the IGCS. It's a real honor. I'm excited to share my passion with you, which is for Sentinel node biopsy, particularly for endometrial cancer. I'm going to share my screen. This talk is largely technique-driven with some theory, so I'm going to start with a video that has audio embedded, which hopefully will work well, and then we'll go to that lasts for about five minutes, and so that shows you what it looks like for those who haven't seen the technique, and then we'll talk more about the theory behind it. So I'll share my screen. And then, can everybody see that? We'll get going. In this video, we will demonstrate the UNC technique for Sentinel lymph node mapping for endometrial cancer using the robotic surgical platform as first described by the FIERS trial. After the patient is positioned, by reconstituting the lyophilized ICG with 10 cc. No video? No. So typically, when you hit share screen, if you hit share screen, if you stop sharing, there's a place that says for share screen, and before you click on what you want to hit, optimize for video clip, there's share sound and optimize for video clip. Got it. Thank you so much. No problem. All right. Let's do this. In this video, we will demonstrate the UNC technique for Sentinel lymph node mapping for endometrial cancer using the robotic surgical platform as first described by the FIERS trial. After the patient is positioned, the endocyanin green is mixed. By reconstituting the lyophilized ICG with 10 cc. of sterile water, drawing up 1 cc. of this stock solution and adding 4 cc. of sterile water to create a 0.5 milligram per milliliter concentration, 1 cc. is injected into a 1 centimeter and 1 millimeter depth at 3 and 9 o'clock of the cervix. Incisions are made in the following location at the level of the umbilicus, three or four robotic ports are placed. And then in the left upper quadrant, entry into the abdomen is performed, serving later as the assistant port. There is a common lateralized route of drainage into the external iliac or obturator sentinel lymph node and a less common subureteral route of drainage that are both important to identify. In this video, you will see examples of both. The first step is opening the right retroperitoneum parallel to the ovarian vessels above the level of the pelvic brim. This may necessitate mobilization of the cecum and appendix from its physiologic attachments in order to do so. It's important during retroperitoneal opening that hemostasis is maintained as blood in the retroperitoneum can make visualization of the sentinel lymph node channels more challenging. After the ureter is identified, a deep pararectal space development then follows. It is important that this pararectal space development is deep to the ureter and distal to the level of the uterine artery origin because this deep pararectal space development ensures that a subureteral channel is not overlooked. In this particular patient, there is no subureteral channel here on the right side but instead a lateralized channel passing to an external iliac sentinel lymph node. The next step is opening the paravesical space by skeletonizing the median umbilical ligament here on the right side. After this ligament is skeletonized, the loose areola tissue is then dissected. By opening the paravesical space, the obturator nerve is identified and skeletonized in the obturator space. This also enables skeletonization of the primary lymphatic trunk that drains ventral to the surface of the internal iliac artery and passes laterally to the side wall. Here you can see these channels identified. These reside predominantly at the level of the internal iliac artery and uterine artery origin. In this patient, multiple channels coalesce into an external iliac sentinel lymph node on the right which is then grasped and mobilized from its attachments to the external iliac vein. It is ideal to perform most if not all of this dissection in the Firefly mode because this enables clear identification of the channels including the primary channel and primary sentinel lymph node, avoid transecting these channels inadvertently and ensuring that the lymph node is removed in its entirety and not more slated or fragmented. The sentinel lymph node can then be removed using a spoon grasp or an endocatch bag. Now we will review identification of a subuteral channel here on the right side. This schema demonstrates the typical location. As mentioned before, this can occur in 15% of patients and may harbor metastatic disease. Here on the right side, the pyrorectal space is developed and identification of this subuteral channel is made possible here deep to the ureter. This is emptying into a pre-sacral sentinel lymph node. The ideal approach to a pre-sacral sentinel lymph node on the right side is a medial approach, transperitoneally, rather than attempting to resect this lymph node retroperitoneally. In order to do so, the ovarian vessels with the ureter are retracted anteriorly and laterally and a peritoneal window is made, overlying the pre-sacral space lateral to the sigmoid colon. Here the sentinel lymph node becomes immediately apparent with opening the peritoneal window. Once the ureter has been mobilized laterally, the structure to be concerned about is the left common iliac vein which resides immediately deep to this sentinel lymph node structure. Therefore care must be made during dissection Therefore care must be made during dissection to avoid deep dissection into this vascular structure. A retex sponge kept close at hand serves both to retract the sigmoid colon medially from this dissection plane, but also to be present and available for assistance in hemostasis should there be bleeding from this dissection. All right, so we'll talk a little bit then about the theory about this. So now that you've seen what it looks like for those who haven't, so which patients would you consider candidates for an endometrial sentinel node biopsy? You'd want to consider basically all patients with clinical stage one disease. So they shouldn't have grossly positive nodes, which effectively are a sentinel node. They shouldn't have gross cervical involvement or obvious stage four disease. But any cell type of endometrial cancer is a candidate, including high grade and non-endometriate cell types. We'll talk about that in a moment. Where do you inject? Well, really the best place to inject that most would agree on is in the cervix. And the cervix is a very good delivery agent for the tracer for the uterus. So most lymphatic drainage from the uterus actually passes down through the lower uterine segment, out through the parametrial trunks, and then into those two different directions that you saw in the video, and that we'll talk about in a moment. Injection in the uterus through hysteroscopic techniques can be cumbersome. It actually has lower rates of finding a sentinel node. And the accuracy studies that have been done, certainly the largest accuracy studies, have all used cervical injections. So we know it's accurate in finding metastatic disease. And we like to inject at 3 and 9 o'clock of the cervix at a 1 centimeter depth and 1 millimeter depth to pick up maximally on those lymphatic trunks. What dye do you use? Well, there's two different types of tracers, two different groups of tracers. You can either use the colored dyes. That's called calorimetric techniques. That means you just use your naked eye to visualize colored nodes and channels. Or you can use image-guided techniques like radiolabeled colloid or ICG, which is what the video showed, where you need special imaging cameras to be able to see the dye. So the calorimetric techniques are great because they're very low-tech. And the blue sulfan blue was designed specifically for the purpose of sentinel node biopsy. The challenge with it is it can be expensive, and it can be associated with anaphylactic allergic reactions in about 1% of patients. And so for that reason, a lot of surgeons who are using blue dye will instead use methylene blue as it's less expensive with a lower allergic reaction risk, but it is an off-label use. What has come about in more recent years, particularly from a lot of work done in China, is black dye, carbon nanoparticle suspension. And this has been published in both cervical cancer and endometrial cancer sentinel node mapping techniques, using both open and minimally invasive techniques to find the dye. And it seems to be from those studies that it may be easier and better to find with higher detection rates than blue dye. Here's a picture that was published in the European Journal of Gynecological Oncology, showing a left external iliac sentinel lymph node that stained dye with carbon nanoparticle suspension. So no additional technology for that either. My preferred technique is with the ICG endocyanide green, very non-toxic water-soluble dye that's actually been designed for perfusion imaging with intravascular injection, but that's not how we use it. We use it off-label by injecting into the tissues. When you do that, it lasts in the lymph nodes for more than 24 hours. And the real benefit and the virtue of this technique is that the signal is able to penetrate through fatty tissue, which particularly for the Northern American and European populations is very beneficial, where we see very high rates of obesity, particularly in our endometrial cancer population. There's a much lower risk for allergic reaction. There's some concern among patients who have an iodine allergy because it's an iodide-containing product, but the risk of allergic reaction is substantially lower than for the blue dye. The problem with it is that it requires fancy technology that requires your hospital to purchase, and that can be a barrier for some. It doesn't have to require a robot. There are platforms available for conventional laparoscopy as well as for open surgery. There are open images that can be used that you can do open surgery, albeit in the dark, to find the sentinel nodes. As you saw from the video, we tend to use it robotically at our institution. I mentioned in the video how to mix up the dye. The critical point is dilution, dilution beyond the conventional solution that's used for intravascular injection. That really just helps with better visualization because when it's mixed, when it's not diluted, the strength is too strong and tends to make it very hard for you to find those discrete channels. Then you wait about 10 minutes after injecting before you look to give it a chance to get to those sentinel nodes. As I mentioned, the ICG or the green dye has the virtue over blue dye in that it has higher rates of detection of a sentinel node. You're more likely to find a node and not need to do a complete lymph node dissection. That's what that translates to. In the film trial, which randomized about 180 patients to either green dye mapping first or blue dye mapping first, they found that there was a significantly higher rate of overall mapping and mapping on both sides, as I've highlighted on the right side of the screen, with the ICG or the green dye. They used a conventional laparoscopic camera made by the company Stryker for this study. Here's a study that was done in New York at Memorial Sloan Kettering, where they looked at as patients' body mass index increased, what was the likelihood of finding a sentinel lymph node on both sides of the pelvis, and as body mass index increased, particularly with the blue dye, there was a sharp drop off in being able to find lymph nodes on both sides. With the green dye, that drop off was somewhat attenuated. It was just easy to find it on both sides in obese patients. So why is it so important to find a sentinel lymph node on both sides of the pelvis? Well, most of the studies that looked at the ability of sentinel nodes to find cancer or find metastatic disease showed pretty recurrently a theme that the sentinel lymph node on one side of the pelvis could only predict what was going on with metastatic disease on that same side of the pelvis. It couldn't tell you what was happening with metastatic disease on the contralateral side. And so if a patient only maps on one side, the recommendation from this well-established algorithm is that the surgeon should proceed by performing a complete lymph node dissection on the side that did not map. And obviously, if our goal is to minimize full pelvic lymph node and or pariotic lymph node dissections for patients, obviously failed mapping means we're still exposing our patients to those risks and morbidity. So that's why bilateral mapping is so important. So some little tips about finding the sentinel lymph node. Most of these you saw in the video. How do you locate it? Well, the most common locations are on the medial surface of the external iliac vein and in the most proximal obturator space right at the bifurcation of the internal external iliac vein. This less commonly but importantly found some uncommon sentinel lymph node locations in the presacral common iliac space. Some of these are in locations that we don't normally remove with our conventional complete lymphadenectomies, but they can harbor metastatic disease. And so it's really important to completely open up those retroperitoneal spaces and identify the main lymphatic trunks that's leaving the parametria to identify the first in-chain sentinel lymph node and to make sure you're not overlooking one of those atypical or less common channels. So once again, this is that diagram, courtesy of Dr. Abu Rastam from Memorial Sloan-Kettering, showing the most common route of drainage passing from medial to lateral through the parametria, ventral to the ureter, ventral to the internal iliac artery, and then passing into the proximal obturator sentinel lymph node and or an external iliac sentinel lymph node. And this is that less common subureteral route of drainage, which instead passes from caudad to cephalad, deep to the ureter, depositing into either a presacral or common iliac sentinel lymph node. So where are you most likely to find sentinel lymph nodes? Well, this is data from the FIRES trial that showed the most common site that they were found was that medial surface of the external iliac vein, probably because that's the easiest place to find them, truthfully. But because the place that was most likely to contain metastatic disease was actually the proximal obturator sentinel lymph node. So that's the very, very important sentinel lymph node to make sure you don't miss. How do you optimize mapping, particularly failed mapping, failed bilateral mapping? Well, with experience. So surgeon experience is the single greatest factor associated with failed mapping. There is a learning curve. People do get better at finding nodes with time. Advanced cancer is thought to be a factor to clog up the lymphatics and prevent movement of your dye out to the lymph node spaces. So advanced cancer can be can be present if your patient's not mapping. Also, obesity, as I mentioned before, and use of the blue dye alone. So you'll often look in there and see multiple lymph nodes that are colored with your dye. And so how do you know which is the sentinel node? It's critically important that you do that dissection all the way down to that primary parametrial trunk to find that channel and determine that, in fact, the primary trunk is leading to this is lower sentinel node. And then the other sentinel node is actually what we call an upper echelon node. But sometimes when you do that dissection, you find that the primary trunk passes into both of the nodes equally, in which case it's important to remove both of them because they're both true sentinel lymph nodes. Is it accurate? The short answer is yes. And we know that from a couple of big trials that have been published over the last few years. We talked about the FIRES trial that included nearly 400 patients with endometrial cancer. About one third of them had one quarter to one third of them had high grade cancer. There were 36 patients who had node positive disease who mapped a sentinel node. And among those, only one patient had a false negative sentinel node, which resulted in a false negative rate of less than three percent. So that's actually less than what the false negative rate is for sentinel node biopsy for breast cancer, most melanoma cancer, for vulva cancer. So it's lower than the rate of false negative rate for most established sentinel node or cancers which we treat with sentinel node biopsy. More recently was published the results of the CENTOR trial. The CENTOR trial looked exclusively at high grade endometrial cancer, essentially the same study design as the FIRES trial. All patients received both sentinel node biopsy and full node dissection. But these patients had high grade cancers, including the non endometrioid cell types. And this trial similarly found a very low false negative rate of four percent. So the final thing I'll briefly mention is ultra stagings of sentinel lymph nodes because that's a bit of a controversy. And this is what happens to the node once it leaves your operating room. It goes to the pathology lab. Now, this is a picture of my schema of a lymph node with a tiny subcapsular metastasis in red. Traditional lymphadenectomy specimens are typically the node is bivalved by the pathologist. And you can see here that would miss this tiny net. In sentinel nodes, the pathologists have fewer nodes to look at and they apply this bread loaf sectioning of the sentinel node. And that allows potentially the pathologist to identify, to pick up on one of those sections, this tiny subcapsular metastasis. They also apply immunohistochemistry stains to AE1 and AE3, which further helps them find these really tiny metastases. In this case here on the left, that's called isolated tumor cells. And here on the right is an example of a micrometastasis, which means it's between 0.2 and 2 millimeters. So are they clinically significant or are we picking up effectively false positives with this ultra staging technique? Well, in truth, we don't completely know, but we do think that those micrometastases are real and we should treat them. Why? Because we always did used to treat them. We just didn't call them micrometastases when we found them before on conventional sectioning. And the data would support that the prognosis of those patients mirrors that of patients with macrometastases. But isolated tumor cells are likely to be a different picture. Most of the early retrospective small series data shows that when untreated, these patients do better than patients who have micrometastases or macrometastases. And really, we should probably rely on uterine factors when making a determination about adjuvant therapy rather than treating the ITC specifically. And that's all I have. Well, I have more to talk about if anybody has questions. That's all I have time for in my lecture, but I'm happy to field questions. Thank you. No, thank you.

sentinel lymph node mapping

endometrial cancer

robotic surgical platform

ICG

detection rate

sentinel node biopsy