Thank you, Norio, for the kind introduction. So it's my great pleasure to be here today. So it's a great honor for me to kick off this conference with my talk. And then I'm going to talk about the fundamentals of ESD and the appropriate patient selection. So this is my disclosure. So I'm going to show some quick history of the ESD. So this is the first case report of the endoscopic resection with a needle knife. So this was published back in 1999, over 23 years ago. And then by Dr. Gotowada and Dr. Ono's group. So they basically developed a new needle knife with the ceramic ball at the tip to safely perform the peripheral mucosal incision. And then they performed the peripheral mucosal incision around this early gastric cancer. And then they used a snare to remove it. So this is the procedure called pre-cut DML at this moment. But this is the first case report of the endoscopic resection using the needle knife. And then this was followed by Dr. Yamamoto's group's publication, which was published in Endoscopy in 2002. Dr. Yamamoto developed a tapered tip attachment cap to safely perform the submucosal entry. And he also used the hyaluronic acid for the first time in the world to safely perform the pure ESD case. So this is one of the first case report of the pure ESD procedures. So I'm going to show some landscape of the ESD history. So as I said, Dr. Gotoda and Dr. Ono's group developed the IT knife back in 1999. And then this was followed by hook knife by Dr. Oyama, ST foot by Dr. Yamamoto, and flex knife, later jaw knife by Dr. Yahagi, and also the triangle knife, Dr. Inoue. So all of these new knives were developed by the ESD pioneers at this time. And then finally, this procedure was named Endoscopic Submucosal Dissection ESD at the consensus meeting at the 67th JGES meeting. And then this procedure was named ESD. And then Dr. Toyonaga developed flash knife in 2005. And then it was 10 years after this, like everything happened, that all of these ESD knives were finally approved in the United States by the FDA. It was 2008. And then the ASG first held this ASG JGES ESD poem course at this IT&T Center in 2013. And I had the honor of being the assistant for Dr. Yahagi as a junior faculty at that time. And then since then, because of a lot of ESD courses in the United States, the ESD was adopted by more and more physicians in the United States. So recently, we had a lot of publications. In this two or three years, there are a lot of publications about the March Center study from the United States in gastro and also CGH, endoscopy and GIE. So I think that ASG is currently working on developing an ESD guideline. And also, hopefully, CPT code will be assigned to ESD in a few years from now. So I'm going to show some quick overview of ESD. I think the technical aspect will be covered by other Japanese faculties. So I'm going to just quickly show the procedure itself. So ESD has multi-steps. So one, the ESD starts with the marking. So we typically use the needle knife, the tip of the needle knife to delineate the border of the region. So it's usually like a 3 to 5 millimeter outside the region borders. And this is followed by submucosal injection. This is to safely perform the peripheral mucosal incision. We used to use the high viscosity solution, but we can use the injection capability knife. So we no longer need to use a very high amount of the high viscosity solution. And this is the peripheral mucosal incision. So this is to separate or isolate the region from the peripheral healthy mucosal. And then once the region is isolated, we perform the submucosal dissection. You can see this gauzy blue tissue. So this is the submucosal tissue. This is the target tissue for the submucosal dissection step. And then once the region is removed and unblocked, we use the hypostatic forceps to cauterize those blood vessels to prevent any delayed bleeding. So these are the major steps in the ESD. And then we usually spread out the tissue on the cork board or dental wax, and then submit this specimen to the pathology. So I'm going to move on to the indication of ESD. So most important part is that you understand the basic knowledge in the surgical oncology. Because the ESD is just a local incision, so we cannot remove any lymph nodes which are located outside the GI tract. So those just has the limited or minimal risk of the lymph node metastasis. Those are the good indication for ESD. So such as low-grade dysplasia or high-grade dysplasia, intramucosal cancer, or superficial submucosal cancer. Those are the good indication of the ESD because of the minimal risk of the lymph node metastasis. However, those lesions with the higher risk of the lymph node metastasis, you have to send the patient to surgery for the segmental organ resection with the lymph node dissection. So I'm going to talk about the details of the current JGS guideline. I want the Japanese faculty to correct me if I'm wrong, but I hope this is correct. So if you look at these green parts, you can see that the risk of the lymph node metastasis is very low. So these are the target region for ESD, which is the squamous cell cancer in esophagus, which confined to the lamina propria, and also the T1A adenocarcinoma in esophagus, and also the T1A in gastric cancer. And then T1A, T1 submucosal invasion with a superficial invasion in the colorectal cancer. Those are the good indication for the ESD according to the JGS guideline. However, there's a change in the esophageal ESD guideline recently, which described, recommends the staging ESD for the squamous cell cancer in esophagus, even if there's a small chance for the submucosal invasion to avoid unnecessary esophagectomy, because the pre-ESD, EOS, or NVI might be sometimes wrong. So to prevent any unnecessary invasive esophagectomy, we should try the staging ESD. So this is the JGS guideline. At the same time, we have the guideline from NCCN in the United States. We also need to understand what the NCCN guideline says at this moment. So NCCN guideline is more forgiving in terms of the submucosal invasion. So specifically, squamous cell cancer in esophagus, T1A, T1B, adenocarcinoma in the esophagus, and gastric cancer smaller than 2 centimeter in the stomach, and also the colorectal cancer with the superficial submucosal invasion. So they think that the endoscopic resection can be used as a staging purpose. So they are more forgiving for the preoperative possibility of the submucosal invasion. So these are a little bit of the difference between the two guidelines. So I'm going to dig into a little details of the gastric ESD guidelines. So as you know, there are expanded indication for gastric ESD. So these red parts used to be the expanded indication for gastric ESD. However, there are two important JCOG studies from Japan, which specifically looked at the survival rate for the expanded indication for the ESD. And they showed over 95% of the survival rate, validating that those expanded indication can be changed to the absolute indication. So there is no longer expanded indication in the gastric ESD guideline. However, if you look at the NCCN guideline, it's still conservative. ESD can be used for gastric cancer only when the tumor is smaller than 2 centimeter intestinal type, well or moderately differentiated, and T1A or superficial T1B. So there is a difference between the two guidelines at this moment. So I'm going to move on to giving you the advantage of ESD. So there are three major advantages of ESD. So the first thing is the unblock resection of the tumor, regardless of the tumor size. So if you see these like large, laterally springing tumors, there are two options to remove these lesions. So the first one is ESD. So we can provide unblock resection by removing the tumor in one piece. However, there is also the chance that we can remove it in a piecemeal with the EMR. So traditional EMR techniques. So however, what happens after the piecemeal EMR? So this is a study from Australia, looking at the local recurrence rate after the piecemeal corrector EMR. And they showed that there's a 25% chance of the local recurrence at the 18 months from the index of EMR. And also, if you look at the high risk, larger lesions, measuring over 35 millimeters, there is a 35% of the local recurrence. So there is a significant difference between the ESD and the EMR in terms of the local recurrence rate. So this is a corrector. And if you look at the spasmodic EMR versus ESD, this is the study from Dr. Abbott's group, looking at the outcomes of the EMR versus ESD for the spasmodic cancer at the G-junction. So this study also showed the significant difference between the two groups. 13% and 0.4%. So this is a significant difference in terms of the local recurrence after EMR. So we need to understand why this ESD unblocked resection is better than EMR. So this leads to the basic principle of the surgical oncology, which is unblocked resection with negative resection margins. So if you look at this picture, you can see that there's a tumor at the center of this specimen. And then you can see the negative horizontal margin. So this is the basic principle of the cancer treatment. So we need to understand this is the basic principle to reduce the local recurrence. So I'm going to show one case. She's a 40-year-old female with a history of Lynch syndrome. And she originally had the nodule in the rectum, which was removed with the piecemeal polypectomy technique. And as you can see here, what you see is that a small residual adenomatous island. If you leave it behind, so this is a next year, you can see the small scar. And right next to it, there's a local recurrence. And then this was removed in a piecemeal polypectomy technique again. And then if you look at the area, you also see the small residual islands. And then if you leave it for two years, she came back with a large local recurrence at the same location. And then unfortunately, this was removed in a piecemeal technique with a lot of local residual adenomatous islands, as you can see here. And then she came for another surveillance colonoscopy. And as you can see here, there's a large, laterally spreading local recurrence with the central severe scar. So she was originally sent to a surgery, but she wanted to avoid the surgery. So I performed EST to remove this lesion unblocked. And then, so she, I just met her last week. And then there's a very clean scar. And then there's no local recurrence. Under NEBI, you don't see any recurrence. So this is the big difference between the EMR and the EST. So the other thing is the accurate histopathological analysis. So there are two goals of the EST. So one is the therapeutic tool, which is the treatment. So we can provide the patient with the R0 resection to avoid the local recurrence. The other option is to use the EST as a diagnostic tool, which is the staging. So we can perform the accuracy staging. So why this is necessary? So this is a study from MD Anderson Cancer Center, looking at the accuracy of the pre-EST or EMR EUS. So this study showed that the 50% of the T1A tumors were overstaged at T1B to T3, as well as the 26.4% of the T1B tumors were understaged to the superficial cancers. So my concern is that those cases, so if you over-diagnose those patients, the patient would have the unnecessary spondectomy. So there's uncertainty of the pre-endoscopic treatment diagnosis with the EUS. And also, if you look at the diagnostic accuracy of the J-NET classifications, so basically the J-NET type 1 corresponds to hyperplastic or SSP. Type 2A corresponds to low-grade dysplasia. And then type 3 corresponds to the deep submucosal invasive cancer, which is not amenable to endoscopic resection. So basically, the type 2B would be the good candidate for correct EUSD. However, if you look at the number of cases included in the type 2B, in the J-NET classification, it includes low-grade dysplasia, high-grade dysplasia, T1A, and T1B. Like 20% cases were T1B. So there's also uncertainty. And we do not have the ability to perform the magnifying chromoendoscopy after this J-NET classification. So that way, the T-staging with the endoscopic treatment is very important in the United States. So the unblocked specimen allows for accurate T-staging. So we usually ask the pathologist to make sections every 2 to 3 millimeters and not to miss any small cancerous foci. And also, the unblocked specimen from EUSD can provide a lot of very important information, including margins, invasion depth, LVI, and the tumor budding. So the unblocked specimen from EUSD can provide a definitive pathological assessment, unlike piecemeal specimens. So this is one of the advantages of the unblocked resection with EUSD. So to summarize this section, so when to consider EUSD over EMR? So first of all, regions with the suspected submucosal invasion, such as large, bulky, protruding areas of nodularity, like Paris 1S in large, the G-junction, and also the LSD-G mixed type with the large nodule. And also, the depressed region, like Paris 2S or, sorry, Paris 2C, and also the LSD-NG depressed. And the possible T1B or EUS. So this is not a definite diagnosis. So we need to do the staging ESD to accurately measure the invasion depth for these cases. And also, there might sometimes have the patient with an equivocal index biopsy, which describes the biopsy as at least intramucosal cancer. So to give a definitive diagnosis, the ESD would be very more advantageous than the EMR. So basically, for these regions, ESD will work for diagnostic, as well as the therapeutic tools. And also, the other advantage is the large, other indication would be large advanced regions, not ideal for PSME resection, such as biopsy-proven cancer or high-grade dysplasia. So if you do PSME resection, recurrence would occur as a cancer or high-grade dysplasia, and which makes the following treatment very difficult. And also, the regions with the submucosal fibrosis, because of the previous EMR attempts. So those cases are a good indication for ESD. So ESD would work only for the therapeutic purpose for those cases. Okay, so this is my last advantage of ESD, so which is the curative resection for superficial cancers. So to understand the curative resection, so what is the curative resection? So we need to go back to the basic principle of the surgical oncology. So if you look at the curative surgery, so this is defined as a surgery to remove all malignant tissue, to remove all malignant tissue, which is meant to cure the disease. So this includes removing part of the cancerous organ and a small amount of the healthy tissue around it. So this is the basic principle, which is the R0 resection. And also, the curative surgery only works best for localized cancer. So what is the localized cancer? So we need to understand the localized cancer by looking at the steps in the cancer metastasis. So first of all, the cancer invades into the submucosa. Here, as you can see here. And then as a next step, the cancer cells leave the original tumor, main tumor, and they create the cancer sprouts. So this is called tumor budding. And then the cancer start to penetrate into the lymphobascular structure. So this is called LVI. And then finally, these cancer cells travel through this lymphobascular structure and then create the cancer nest. So this is the metastasis. So all of these are the risk factor of the cancer metastasis, which can be seen by the pathologist. So the curative resection can be defined as R0 resection with no risk factors, which is the poor differentiation and deep cancer invasion and the tumor budding and the lymphobascular invasion. So this table, it's a busy slide, but it summarizes the current guideline of the definition of the curative resection in terms of the each organs. So first of all, the ESD needs to, the specimen needs to satisfy these all conditions, which includes R0 resection, no deep invasion and not poorly differentiated and no tumor budding and no LVI. And then there is a definition of the superficial cancer invasion, which is SM1 here. So basically those green parts in the indication corresponds to the curative resection according to the guideline. But I need to mention two parts. So first of all, the skeletal cell cancer with the invasion into the musculoskeletal mucosa with no LVI. So recent study showed that there's no risk of the lymph node metastasis. So the guideline recommends to discuss this case at the tumor board to decide the next steps. And then for the gastric cancer with the less than five microns invasion into the submucosa with no LVI and the smaller than three centimeter. So this is considered as EQRB. So we need to have the close follow-up for those cases with the EGD as well as EOS and a CAT scan. So these are the difference from the indication. And then if you look at the NCCN guideline, there's a little of the difference between the two guidelines. So as I said, the NCCN guidelines are a little more forgiving in terms of the deep submucosal invasion. So basically the superficial submucosal invasion is considered as a gray zone. So you need to discuss those cases at the tumor board. If you see the submucosal invasion in the adenocarcinoma, in the esophagus, in the stomach, in the colon. So it's a case-by-case basis discussion. And then also the NCCN thinks the T1A as squamous cell cancer can be completely cured with the endoscopic treatment at this moment. As long as there's no LVI. So let's look at the curative clinical outcomes of the spasio-EMR versus ESD. So this is the multicenter study from Dr. Abbott group. Recently published in Endoscopy looking at the clinical outcomes of the EMR versus ESD for the advanced barrett-associated neoplasia. We only included high-grade dysplasia and cancer. And as you can see here, the ESD resulted in much higher, significantly higher unblocked resection rate, zero resection rate, and a curative resection rate, as well as the comparative adverse event rates compared to the EMR. And also, if you look at the colorectal ESD, so this is the recently published paper from Japan, which was prospective multicenter trial from Japan, including over 1,800 cases superficial of a colorectal tumor, and including over 700 high-grade dysplasia and 371 colorectal cancers, which showed 97% unblocked resection rate and over 90% of the curative resection rate, and with minimal perforation rate or bleeding risk. So this is my summary slide. So there are a lot of advantage of ESD over EMR in the surgery. So in terms of the EMR, ESD provides a higher unblocked resection rate and a curative treatment for the cancer, and a lower recurrence rate compared to EMR. So the patient doesn't need to have the follow-up endoscopy very often. Compared to the surgery, because the ESD is a no-scar surgery, so it's an organ-sparing treatment, and we do the ESD as the outpatient procedure, so no hospital stay for the patient, and minimal adverse events, and then with the same treatment outcomes. Okay, thank you very much. Thank you. Thank you. Just to confirm, the SM-1 criteria you mentioned, the esophagus is glamorous, right? 200 micron? 200, yes. But I think it's still not determined by the JGS guideline, 200. The adenocarcinoma is supposed to be 500. Yes, for the adenocarcinoma, it's 500. But I think it's still not determined by the JGS guideline, 200. The adenocarcinoma is supposed to be 500. The adenocarcinoma is supposed to be 500, yes.

Endoscopic Submucosal Dissection

ESD

cancer treatment

needle knives

patient outcomes

histopathological analysis