Welcome to our newly created webinar series called ASGE Global Spotlight. This series was created with our global audience in mind at a different time from our usual offerings to make sure that you all have a chance to join live. These webinars will feature global experts in their field, and I'm very excited for today's presentation. We have attendees joining us from all over the world, and the American Society for Gastrointestinal Endoscopy appreciates your participation. Today's event is entitled Management of Malignant Biliary Obstruction in the 21st Century. My name is Reddy Akova, and I will be the facilitator for this presentation. Before we get started, just a few housekeeping items. There will be a discussion at the close of the presentation. Please note that this presentation is being recorded and will be posted within two business days on GILeap, ASGE's online learning platform. You will have ongoing access to the recording in GILeap as part of your registration. And now it's my pleasure to introduce our two presenters for today. The first one is Professor Anthony Teo, who is a Deputy Director of Endoscopy and Associate Professor in the Chinese University of Hong Kong. Professor Teo received his training in many international centers around the world, and he's a winner of multiple awards such as the APDW Emerging Leaders Lectureship, the Carlos Pellegrini Traveling Fellow Award, the ASG Endoscopic Research Award, and the G.B. Ong and Lee Shields Medal, which are awards that recognize a candidate who achieved the highest mark in surgery. Professor Teo's research interests are multifold, and these include advanced interventional EOS and ERCP, minimally invasive surgery, single-site access surgery, and robotic surgery. Professor Teo currently serves on many committees in national and international organizations and is also on the editorial board for several internationally renowned journals. He has published over 100 journal papers and written many book chapters, and we are very, really, really fortunate and honored to have Professor Teo here with us today. And our other presenter is Dr. Shannon Chan, who is an Assistant Professor in the Division of Upper Gastrointestinal Metabolic Surgery of the Chinese University of Hong Kong. Dr. Chan has also completed her training in various institutions around the world, and her main research interests include upper gastrointestinal surgical oncology and advanced diagnostic and therapeutic endoscopy, especially in interventional EOS. She also has a special interest in peritoneal surface malignancy and has started a multidisciplinary team for this rare yet important group of patients. Dr. Chan has also published over 20 peer-reviewed journals and is a reviewer for digestive endoscopy and surgical endoscopy. Apart from her research interests, Dr. Chan has also devoted herself to humanitarian aid work. In 2014, she joined the Medicines Sans Frontieres, also known as Doctors Without Borders, which is an international humanitarian non-governmental organization working in war-torn and underdeveloped regions. Dr. Chan joined their surgical mission to South Sudan in 2016 and to Yemen in 2019, all the way to 2020. And presently, she continues her commitment to provide humanitarian aid to the less-developed part of the world. And again, we are very fortunate and honored to have Dr. Chan and Dr. Teo here with us today. And now, they will have a discussion at the end. Dr. Chan will start the presentation, and Dr. Teo will continue after Dr. Chan is finished. And now I will hand over the presentation to Dr. Chan. So thank you, ASG, for the invitation. And today, the talk will be split into two parts. So I will talk more about the staging, the EOS biopsy, and the ERCP part of this. And Teo will talk more about the EOS and interventional EOS side. So this is the outline of the talk. So for malignant biliary obstruction, I've divided the talk into whether the tumor is a resectable or non-resectable. For resectable tumors, I'll talk more about the pre-op localization and the need for pre-op histology and how to obtain it, and whether pre-op drainage is needed versus no drainage. And for un-resectable tumors, I'll talk more about the drainage, apodistal tumors for higher tumors, and also for tumors that are located in altered anatomies. So malignant biliary obstruction basically can occur all the way from the ampulla up to the hyla, up to the fourth order of the bowel ducts. Pancreatic cancer is the most common cause, followed by distal cholangiocarcinoma. So if you look at this diagram, the differential diagnosis also includes ampullary carcinoma, special hyla cholangios, gallbladder cancers, hyla cholangios classified according to the bismuth classification, which we'll talk more about later. So staging investigations, of course, it's according to the TNM staging. For all patients with suspected malignant biliary obstruction, usually people would perform a CT abdomen with pelvis with IV contrast. An alternative is MRI abdomen and pelvis. And apart from the M staging, the local staging is also important for pancreatic cancer, as in whether it encases the portal vein and the SMA to determine the resectability or whether it's borderline resectable or un-resectable. And for patients who come in with parameters of malignant obstructive jaundice, it's best to do a staging scan first before an ERCP drainage procedure if the patient is not septic, because if the ducts are dilated, the scans are actually easier to interpret with a better anatomy delineation. And I'll talk more about later that these tumors, if they are resectable, they may not need drainage at all. So this is the proposed algorithm from the ASGE. So for all patients with suspicion of primary pancreatobiliary malignancy, then you go for a CT scan. And for suspected resectable tumors, they advise for an EOS. And if further EOS staging on whether the SMA and portal vein are clear and this is clearly resectable, you proceed to surgery. For cases that are un-resectable, then we go for palliation. And for suspected HILA tumors, because the level of the tumor is important in determining the surgery, an MRCP is advised. So if after an MRCP it's resectable, then a surgery is indicated. And if it's not, then we go for palliation. So let's talk about some resectable tumors first. So I'll first talk about the need for histology and preoperative localization. So most of the times when we see a HILA, see a malignant biliary obstruction, we obtain brush cytology. But how accurate is this? So a recent systematic review and meta-analysis actually showed a sensitivity of only 45%, with a specificity of 99%. And the diagnostic odds ratio to detect malignant biliary strictures is around 43% only. And a lot of studies have tried to address whether there are any factors affecting the positive cytology brushing. And they found that a tumor size of more than one centimeter has a higher yield, and a stricture length of more than one centimeter has also a high yield, and definitely a high yield when the stricture is more than three centimeters. And for a total bilirubin, the higher the bilirubin, the more positive the cytology is. However, even taking these into account, the sensitivity of brush cytology is also, is still very low. Of course, it's very convenient because when you do ERCP, it's just a further step more, and the risk is actually very low. But for patients who have a negative brush cytology, or an ERCP was not done altogether, experts nowadays would suggest for an EOS-guided biopsy before surgery. Because although the CT scan may tell you that there is a pancreatic mass that is highly suspicious of pancreatic cancer, there are also a number of benign differential diagnoses, including chronic pancreatitis, autoimmune pancreatitis, such as the IgG4 pancreatitis. The biopsy can aim at the primary cancer, or it can aim at the regional lymph nodes, or suspected metastatic lymph nodes. So the pros for EOS-guided biopsy is that numerous studies have shown that EOS-guided biopsy of pancreatic cancer is highly sensitive and specific. And in two meta-analyses, the results agree with each other. And the only thing is that a negative FNA does not completely exclude cancer. And there are other problems that some surgeons worry about, is that for EOS-guided biopsy, there are adverse events of bleeding, pancreatitis, perforation, and tumor seeding. For complications of bleeding, pancreatitis, and perforation, these are actually very, very rare. In a prospective study, including more than 300 patients of solid pancreatic tumors, the overall adverse event rate is less than 3%. And even with endoscopists who are less experienced, the adverse events rate of an EOS FNA is only as low as 1.1%. However, most surgeons worry about tumor seeding and the development of peritoneal cancer pneumatosis. So people have compared the method of obtaining biopsy. So EOS versus CT-guided biopsy. And of course, CT-guided biopsy has shown a high risk of peritoneal tumor. So CT-guided biopsy is out. And as for peritoneal cancer pneumatosis, a Japanese group actually compared EOS-guided FNA for pancreatic cancer versus ERCP with breast cytology. And they found that in the event of the cause of the disease, a similar amount of patients developed peritoneal cancer pneumatosis, suggesting that this might be part of the disease progression rather than related to the FNAC itself. When we consider EOS-guided biopsy, the location does make a difference. So if the lesion is located in the pancreatic head, the potential sites of seeding, including the gastric wall, is removed during a Whipple's operation. However, when the lesion is located in the body or the tail, we usually do an FNA through the stomach. The aspiration route will not be included in the resection area. So this is the location where HVP surgeons will worry about tumor seeding and incomplete surgery. But if you look in the literature, the case reports of tumor seeding is actually quite rare. Knowing that there are two case reports of a tumor seeding, and both of them are located in the pancreatic tail, and the other two of tumor seeding are also located in the body, the other at the tail of the pancreatic intraductor papillary mucinous neoplasia and metastatic melanoma. Whether this risk is increased by the needle size or the number of passes remains uncertain. So nowadays, for pancreatic head tumors, biopsy before a Whipple's operation, which is a high risk surgery associated with high morbidity and mortality, is advised. So how about for hyaluronic tumors? So for hyaluronic tumors, traditionally, the access to it is limited by CT, MRCP, ERCP, and EUS. So these are all only diagnostic ways. And a tissue acquisition by cytology, as we've mentioned, the yield is very, very low. So that is why cholangioscopy has been developed. So in the very old days, it started off with a two-operator system. So it was the electronic mother and baby scope, and then it progressed to a single operating system with Spyglass, which has now upgraded to the second version, and also the direct per-oral cholangioscopy. So for the two-operator system, the mother and baby scope, the baby scope is actually inserted into the working channel of the ERCP. And this scope has an accessory channel of 1.2 millimeters and a chip reflection of only one plane to 90 degrees. And the main application is at the bowel duct. So these are the pictures that are taken from the mother and baby scope. So if you look at it, this is cholangiocarcinoma, and this is also a cholangiocarcinoma. And this is from the PD, the main duct IPMN, and this is a normal PD, and this is a side branch IPMN. So about the single operator cholangiopancreatoscopy, the Spyglass is a single operator system. So the scope is actually mounted onto the ERCP, and the endoscopist can control both scopes at the same time. The first version of the Spyglass was reusable, but of course, the later version nowadays, it became a single-use catheter, a single-use scope. And the accessory channel can actually feed in biopsy forceps and a snare and a basket. And this scope actually has four-way chip reflection. So it's a bit like an OGD scope, where you can move in four different directions with two knobs. So the latest Spyglass system has an even higher resolution, single operator, and a bigger spy bite. And the basket and snares as accessories has been available in the new Wisdom edition. So this is a procedure with the Spyglass. So first, we need to cannulate the bile duct, perform sphincterotomy. And then we can feed in the Spyglass. So as you can see here, the scope is passing up the bile duct. So here we are at the Hyla region. So you can actually confirm your position of the scope with the X-ray. And of course, when you pass the scope, you actually know the direction, which order of bile ducts you are at. So the visibility is actually quite nice. You need to step on a lot of sodium saline for irrigation to have a better view. So in this Spyglass, we found some urethema over the Hyla region. We also found a tumor at the distal CBD region. So because these ureformatous regions are indeterminate in origin, so we took biopsy of these ureformatous lesions, because it does affect the degree of surgery that needs to be performed. So you can see that the Spyglass actually has quite a big bite and adequate tissue for histology. So here is the two more. which, again, we took a biopsy and confirmed cholangiocarcinoma. So the other option of obtaining a pre-oblocalization and biopsy of hyalostrictus is this direct peroral cholangioscopy. So this scope is ultra-thin and ultra-long, so it can create a long loop at the stomach and enter the bowel duct, and it has superior image quality and a larger working channel. The bad thing about it is that the looping in the stomach actually makes intubation of the bowel duct quite difficult. So people actually suggested to use an overtube, or sometimes a small bowel enteroscopy overtube to assist this cholangioscopy to avoid looping at the stomach. So I'm sorry this video is actually quite an old video, so it's quite dark. So basically we passed the cholangioscopy into the stomach and into the duodenum and used the overtube to reduce the loop in the stomach and to facilitate our intubation of the bowel duct. So this is an image you can see on a direct collangioscopy. You can see that the image quality is actually much better because these are optical fibres as compared to the spyglass which is digital. So, as for the diagnostic ability of these scopes, technical success for the mother and baby system is actually quite high. The diagnostic yield is up to 70 to 80% and a multiple biopsies can be taken. And as for SPI-GLASS, of course, and its success rate is also very high. The sensitivity is over 70% with a specificity of 100% and the adverse events of cholangitis and abscess formation is actually quite rare. And same for the overtube-assisted ultrathin direct per-oral and cholangioscopy. The technical success rate is high and the sensitivity and specificity is also quite high. So, in this more recent review on the new SPI-GLASS and SPI-BYTE version, they actually compared the diagnostic accuracy of a visual impression of hyalostricture, so you can see the negative predictive value is very high. And as for the SPI-BYTE biopsy, of course, then the positive predictive value is high, meaning that the biopsy that they have taken is actually quite accurate. And the negative predictive value, however, is only at 70%. And also a recent version of this per-oral cholangioscopy was developed. So this scope is special in that this is a multiband scope. So there are actually two bands right here that can turn 290 degrees that helps in the intubation of the bowel duct. And this scope has two accessory channels of a 2.2 millimetres. So this accessory channel size is very high. So this is a photo that you can obtain from this scope. In this cohort study, the technical success rate is up to 90%. With after intubation, the procedure time is only about three minutes where they can examine the entire bowel duct. So as for the NBR and confocal imaging for cholangioscopy, these are still under investigation and the role still needs to be defined. So after determining that tumours are resectable, as they presented with malignability obstruction, should we or should we not drain it first before surgery? So I'm sure all of you know about this landmark study from New England Journal of Medicine called the DROP trial. So they compared preoperative drainage versus surgery within one week. And they showed a significant difference in complications and the drainage group had more complications than the early surgery group. So because of this trial, all patients who have a resectable distal cancer with malignability obstruction, early surgery within one week is the advised management protocol. Then of course, this study has been criticised for its exceptionally high complication rates associated with the preoperative bowel drainage. If you can see, this study is actually published more than 10 years ago. So over the past decade, people have been trying to use different methods of endoscopic drainage, percutaneous drainage, metal stents, plastic stents. So in the end, the conclusion is that the outcomes of plastic stents and fully covered metal stents were similar. And considering the cost-effectiveness, then plastic stents may be more preferable. And in this forearm network meta-analysis, they compared patients without pre-op drainage, patients with drainage with metal stent, patients with drainage with a plastic stent, and patients with a percutaneous drainage. And the result of this study is that, again, early surgery with no drainage is preferred. And as in how to drain the endoscopic, there is no obvious benefit of percutaneous over endoscopic or either way, but given the quality of life would be better for endoscopic drainage, they also suggested that endoscopic drainage is preferred. And as to endoscopic drainage, there is no difference in the outcomes on whether you use metal stents or plastic stents. So let's now talk about the un-resectable tumors. So patients who have malignant biliary obstruction, un-resectable tumors. So first we'll start with distal tumors. So the consideration that you need to think about is whether you want to do an ERCP or an EOS procedure. So I believe Teal will talk more about the EOS procedure later. So now I'll focus more on the ERCP and also what kind of stents you want to use. So the factors we need to consider as a factors of tumor ingrowth, overgrowth, sludge formation, and a stent-induced hyperplasia and a stent migration. So we need to consider the material, the covering, so whether it's uncovered or fully covered or partially covered, the cutting of it and whether it has any anti-migratory properties. So as mentioned, the stents that we can choose from are uncovered stents. So for uncovered stents, we have the consideration of a tumor ingrowth. For fully covered, then maybe more sludge formation or tumor overgrowth. And for partially covered, then it's a combination of both the uncovered and fully covered. So a lot of studies has been performed and meta-analysis is out every one to two years comparing these two methods. And they have a lot of conflicting results. So these are the stents that are available, the types of fully covered and partially covered stents that are currently available with different materials, sizes, and diameter, and the coverings. So in this meta-analysis, comparing fully covered and uncovered stents, fully covered stents provide longer stent patency, longer stent survival, but with a problem of a higher stent migration and a higher tumor overgrowth and sludge formation. So and in another meta-analysis that actually showed very similar results. So again, fully covered stents has a higher migration rate, higher tumor overgrowth, and of course, then a lower tumor ingrowth. So the use of the fully covered metal stents, the benefit is still very highly unclear. So in this other more recent meta-analysis, the results are very, very similar. So in the latest meta-analysis in 2018, included 11 RCTs. And again, the stent migration is more common in the fully covered stents, more sludge formation and a higher rate of tumor overgrowth with a lower tumor ingrowth. So these are the 11 RCTs that were included in this meta-analysis. So these four studies are studies that favor fully covered stents. So if we look into them one by one, they actually use different types of fully covered stents and the indication for drainage is different. So in this study by Isayama, it was a partially covered polyurethane stent that they used. And they actually showed, in terms of the survival of the patient, it's similar, but the cover stents has a higher stent patency rate. In this other study, using this new stent with anti-migratory property, it actually showed that stent patency is higher with the fully covered stents in pancreatic cancer. And the same results was reproduced in patients with the cholangiocarcinoma. In this other study by Catano, they again compared covered and uncovered stents and covered stents also has a higher stent patency rate. So all in all, all these studies conclude that a fully covered stent and uncovered stents have their benefits and their disadvantages. So at this point of time, which kind of stent you use is still up to the endoscopist's preference with no citing to which stent to use for each pathology. So some people then studied whether the use of chemo-irradiation would help with the stent patency. And in this study, comparing a fully covered stent with chemo-RT and a plastic stent with or without chemo-RT, the difference then is in the stent material rather than in the difference of chemo-RT. So showing that chemo-RT itself is not helpful in maintaining stent patency. And the reasons for stent dysfunction mainly is due to a sludge formation for the fully covered stents and also the plastic stents. So for highly strictures, most of the causes is a cause by clad skin tumor, which is a primary bile duct cancer involving the hilum. Second most common cause is gallbladder cancer, and then it's metastatic cancer. All these patients usually have a dismal survival with only 5% in five years, and only one fifth of them is resectable. Surgery is the only chance of cure, but even with surgery, the five-year survival is only up to 40%. So hyaluronic cholangios can be classified according to the bismuth classification, which I'm sure all of you are very familiar, from type 1 to type 4. So the issue then first is to drain or not to drain, how to drain, either we drain it percutaneously or endoscopically, and what stents do we drain, and whether we drain one side or two sides. So this study in 2009 has already showed us that percutaneous drainage with stems offered a higher stent patency rate than the endoscopic drainage. In this more recent meta-analysis and systematic review, the pooled odds ratio for successful biliary drainage in PTBD was actually much higher than that of the endoscopic drainage. Then of course a problem with PTBD is because these are higher strictures, patients may need more than one percutaneous catheter, and in the light of being unresectable and palliative in nature, a lot of endoscopists would try to do endoscopic drainage to provide a better quality of life. So if we are to do endoscopic stenting, should we put in one stent or two stents? So of course it's technically easier with one stent. You probably have a lesser incidence of sepsis because less contrast is needed and less time is needed to cannulate the other side. And then the thinking is that only a small volume of liver needs to be drained for relief of jaundice. So is it really necessary to drain both sides of the highly stricture? So in this study, comparing drainage with plastic stents, one side versus two sides, you can see that the successful stent insertion, one side of course the successful rate is significantly higher. However, if you look at the successful drainage to insert two stents, the successful rate is actually less than that of one sided, and the incidence of cholangitis is much higher if you tend to insert two stents. In this other very, very old study, it showed us that it tried to address a question of whether we should drain only the opacified duds and not drain the non-opacified duds. So group A is a patient with only one lobe opacified and drained. Group B is both lobes opacified and both drained. And C is both lobes opacified but only one drained. So you can see that the survival in group C is significantly lower. So this gives us the idea that if we should drain all lobes that are opacified. And if we are to drain both sides, there are actually different types of metastats we can choose from to palliate the malignant highly obstruction. So in this multicenter study with 35 patients, the insertion of this bilateral metastat insertion, the technical success rate is quite high. In this very recent large multicenter parallel study from China, they tried to address all questions in one study. So they have four groups of patients, one with unilateral metastat, one with unilateral plastic stents, and one with bilateral metastat, and one group with bilateral plastic stents. So you can see here, in terms of clinical success, bilateral metastat is the best. In terms of the reintervention, bilateral metastat, the reintervention rate is the lowest. And the incidence of cholangitis, it's also the lowest with bilateral metastat. So in conclusion, compared to plastic stent placement, metastat placements achieved higher success in all outcome parameters, and bilateral stent placement was superior to unilateral stent placement in terms of clinical success, stent patency, and overall survival. So if we decide to insert bilateral metastats, there are two ways of inserting it. So you can either insert what we call the side-by-side technique. So you cannulate both duds and insert metal stents separately in each dud. So second is the stent-in-stent method. So if you use the stent-in-stent method, you will need a special type of metal stent, where in the mid-stent, they have larger pores where you can cannulate the contralateral bowel duds and insert a stent through these large pores. So this is a video showing the side-by-side insertion of the plastic stents. So of course, to do this, a prerequisite is you need to be able to cannulate both sides of the stricture. So after the first cannulation, then you need to insert another guide wire to the contralateral side. You can help yourself sometimes with the angulation with a sphincter tome or with a balloon. So once you've got two guide wires in, there are two ways of doing this. So in this video, the stents are inserted one after the other. We use the six French silver stent by Koch because it has the smallest delivery system of six French, and it can easily pass highly strictures. And because you need to put in two stents, space is a very important consideration. So you can see that the first stent is being deployed. And after deploying the first stent, then you can insert the second stent. So a potential risk of this is that you might move the first stent while you insert the second stent. Because of very, very tight height restrictions, passing two stents may be difficult. So there are experts who would suggest to insert both stents first and deploy them together. So the good thing about this is that you will not migrate the first stent. And second, the distal end of the stents can be put in parallel so that in future reintervention, it would be easier to reintervene. So now you see that we always try to put both ends of the stents quite close to each other, the level quite close to each other to facilitate future cannulation for reintervention. So there are a lot of cohort studies comparing the side-by-side and stent-in-stent method. And up till now, there's still no consensus on which is better. So it depends on your center's expertise and, of course, then the stents available. So this was the six French silver stent that I talked about with the small delivery system, which can easily pass into these height restrictions. So the last part is we'll talk about unresectable tumors with altered anatomy. So it will be very brief, because I believe Teal will be talking about EOS drainage. So for tumors that are determined to be unresectable, with altered anatomy, it includes patients who had a gastrectomy before with a BRF2 reconstruction, a Rheum-Y reconstruction, patients who had a Whipple's operation, and patients who actually has a concomitant duodenal obstruction. So for patients who have altered anatomy, one option is to do an enteroscopy-assisted ERCP, where you first use a short-type single or double balloon scope to first pass the scope to the papilla and cannulate the native papilla. Another option is to do an EOS-guided drainage. So it can either be a hepatogastrostomy. So in this picture, I was in HGS with a geoball. Or the second option is EOS-guided antigrade stenting. And you can use whatever stent you want, because these are just the normal ERCP stents. So Dr. Mohan Kashyap has actually compared between the enteroscopy-guided ERCP versus the EOS biliary drainage. And he found that for EOS-guided biliary drainage, it has a significantly shorter time and a higher success rate in terms of technical success and clinical success rate. However, somehow they had a longer length of hospital stay. In terms of adverse events, they are similar. So in the post-hoc analysis, he found that EOS-guided biliary drainage is the only factor that is found to be a predictive factor for success of biliary drainage. And in terms of adverse events, it was also found that EOS-guided biliary drainage has a higher adverse events rate. So I guess for patients with altered anatomy, it really depends on the expertise you have on enteroscopy-guided ERCP or EOS-guided biliary drainage. So let me summarize the first half of the lecture. It's that in patients with a malignant biliary obstruction who are deemed to be resectable, for pancreatic head tumors, an EOS-guided biopsy is advised. For higher strictures, a cholangioscopy is advised for better pre-op localization and also for a biopsy before surgery. And for patients who has a resectable distal cholangiocarcinoma or pancreatic cancer, we advise for no pre-op drainage and early surgery within one week. For unresectable tumors, for distal obstructions, there is still no consensus on whether covered or uncovered stent should be used. And for higher strictures, if you're given the choice and you can cannulate both sides, it's better to drain both sides and to drain it with a metal stent. For altered anatomy, whether you do EOS-guided biliary drainage or enteroscopy-assisted ERCP depends on the expertise available. So I'll hand over the time to Teo. Thank you, Shannon, for your very comprehensive review. So I'll pick it up from here and talk more about other aspects of draining unresectable cancers. These are my disclosures. So in terms of ERCP, recently there has also been a lot of interest on seeing what we can do more apart from just drainage. So can we do some endoscopic ablative therapy to potentially improve patency as well as survival? So a number of different modalities has recently been described. PDT has been around for almost 10, 15 years. And in the recent five years, endobiliary RFA has also become available. The technique of intraluminal brachytherapy has also been described, but it's not extremely popular. So potential benefits, improved patency, prolonged survival. So this was the original paper published by Ortner and Gastroenterology 2003. So it was, at that time, a very exciting paper, although the sample size was very small. But it showed clearly that PDT plus stenting, versus stenting alone, provided a clear survival benefit. The idea of photodynamic therapy is that they used a sensitizing agent, which is tamoporphine. And they used a diode laser system to activate this substrate. So the sensitizing agent needs to be injected 48 hours before the procedure. It can either be photofritin or Foscan. A diode laser system will be used, and it will induce a tumor necrosis around 4 to 6 millimeters. So with the sensitizing agent, after the tumor is exposed to the laser, it will lead to a number of cellular changes, resulting in apoptosis, necrosis, and also activation of the immune response. So the procedure is similar to NIRCP. Most of the time, these patients already have a stent. So the stent needs to be removed, a guide wire placed, and a catheter to guide the laser to be inserted, to the position will be inserted here. And then the laser fiber will be inserted to the tumor's level. But the problem with this procedure is that because after injection of the Foscan, any exposure to light may potentially affect the patient. So actually, even with the ERC procedure, it needs to be performed with all the lights out. And patients need to be stayed in a room without light for a few days. So in terms of outcomes, most of these studies have shown benefit of PDT. So original study, Otna, prolonged survival. Michelle Kahale also showed a study with a prolonged survival. In Korea, they have Qian, Li, Hong, Park, all showed a prolonged survival of PDT. So it was actually a very exciting technology. And then another study looking at PDT plus palliative chemo, again, showing improved outcomes with PDT plus palliative chemo. But still, we don't see a very widespread usage of photodynamic therapy. The agent itself is quite expensive. It's maybe $2,000 to $3,000 per injection. Photosensitivity can be up to six weeks. The patient needs to live like a Batman. So they can only come out at night. They can't even have sunlight in the rooms. There are some reports of serious phototoxicity requiring oral cortisol treatment or even erythema multiforme. And as I mentioned, we need to do the ERCP with the room completely dimmed. So this is a picture showing you some sort of phototoxic reaction, 24 hours PDT. So as a result, people started looking for alternatives to a local ablative therapy. And then came endobiliary radiofrequency. This is available from two main companies now. One is in, and both of them are available in US. So the Boston acquired the Habib endobiliary probe. So this is a probe that has two electrodes. So the radiofrequency waves travels from one electrode to the other. This is the ALRA probe from Taiwan. And the radiofrequency travels through all the four electrodes. Both of these come with a propriety machine that activates the probe. So with RFA, the idea is that it produces heat at 60 degrees. In theory, there should be a water system inside the catheter, which cools the electrode and prevents it from overheating. So if it gets too hot, it generates char, and it prevents heat from traveling beyond the char. The other thing that we need to be aware is the tumor needs to be in good contact with the probe. So in the bile ducts, it is not uncommon to see some spaces, dead spaces between the probe and the tumor. And this may impair the transfer of energy from the probe to the tumor. So this is one of these patients that we did a while back in our own study. This was actually a patient with pancreatic cancer with distal burea obstruction. This is the probe that was being inserted. Insertion is usually quite easy. The size of the probe is a little bit larger than the synchrotron. And for a long structure, we can have multiple applications. So for the Habib probe shown in this video, we applied it for one minute for two times. And then afterwards, we placed a metal stand. So here, you can see the ablated tissue appearing white in the endoscopic image. So in terms of RA results, most of these are not comparative studies. These are just cohort studies, mainly showing you technical success and also a safety profile. Recent meta-analysis comparing RFA versus stent-only group didn't show any survival benefit. But there was improved stent patency data. From our own experience, we haven't been able to show any benefit in the stent patency data. But I think the case selection is very important. So I think it probably works better with primary and secondary stent patency with primary bright bowel cancers, cholangiocancers, and not pancreatic cancers. This is another from STRAND comparing EBRFA versus PDT. So quite interesting, because there was no significant difference between the two modalities. And as you may remember just now, there was a clear benefit of PDT versus stent-only. So maybe the two modalities may be comparable. Some endoscopists also apply radiofrequency in patients with occluded stems from tumor engrowth. So in this study comparing RFA versus control group, they were able to show an improved stent patency in 90 days, and whereas the stent patency time is longer in the RFA group. Sometimes after ampulectomy, there will be some residual adenomas. And these are often problematic, because these are difficult to remove, especially in the scarred area. So in this study, they look at the potential use of an endobiliary RFA to apply to these residue adenomas. So 20 patients had this procedure performed. And some of these patients were able to achieve a long-term cure. But of course, in patients with high grade dysplasia, the risk of recurrence is still quite high. Intramural therapy I'm not going to talk too much about. I think this is just only one study that has been talked about. We need to apply the brachytherapy from an oral biliary route. And it is not readily available in many centers. And only one such small study have described this technique showing some success. So in terms of ablative therapies, both PDT as well as eBRA showed some promising modalities. But what we are lacking are randomized trials, but to compare the efficacy. And also, we need to know more in terms of which type of bowel cancers are more effective in terms of these technologies. As Shannon has mentioned, another big area, and also my research area, is in US biliary drainage. For those who are listening to this talk, I think most of you are still fellows or trainees. So I'll give you just a quick overview because time is running out. If you want to know more about US biliary drainage, you can check out this guideline we've published about three years ago. This is the first consensus guideline by the 18 years group on interventional US procedures and biliary drainage is one of these procedures that we reviewed. In terms of indications, currently, USPD is still mainly indicated in patients with failed ERCP or anticipated difficult ERCP, such as those with an accessible papilla in altered anatomy or prior delusional stenting or obstruction. Of course, the alternative is with percutaneous drainage, but with the percutaneous tube, many patients would complain to you because they have a lot of problems like leakage, infection, blockade, and so on. So to be able to do US biliary drainage does confer some advantages, like better clinical success, reduce adverse events, and also reduce intervention rates. In terms of approaches, USPD also allows you to have many different options. You can do a trans-papillary drainage, such as the Hongdevu or integrated drainage, or a transmural type of drainage, which involves creation of a new tract, which is either a colorectal duodenostomy, CDS, versus hepatic gastrostomy, HGS. So yes, Hongdevu, for me, mainly for benign disease with failed ERCP. So this is a patient with acute pancreatitis, failed CBD cannulation. You can see I was using the US image. It's a bit narrow. This is a forward-viewing scope. The bile duct is narrow, usually, in these cases. You can see the angulation of the forward-viewing scope is much bigger than a regular linear scope. So if you have this scope, I would suggest you to use this scope because it does give you a much better angulation and allows a better direction of puncture and passage of Gaia wire down the common bile duct. So afterwards, after the wire is in the duodenum, then you can have the option of either cannulating alongside the wire or trying to catch it with a snare or a micro forceps. So after catching the wire, I would usually catch it at the junction between the hydrophilic tip and the metal part of the wire because sometimes even with a snare, it still slips. And if you catch it, you can put it back in the channel and then afterwards change it with a regular ERCP. And after changing into your regular ERCP, you can pull the wire and then re-cannulate the bile duct and then perform cannulation as per usual. And then insert your stent. But for most of these melanin patients, actually a transmutability gene is much preferred. So either a CDS called the gluconeostomy or hepatogastrostomy. So with a luminal pulsing stent, the cautery-enhanced luminal pulsing stent, the bile duct version should be available in US very soon. This is the eight and six millimeter bile duct luminal pulsing stent. This is the first procedure of one of my trainees done a long time ago. In the bile duct, I usually recommend first to puncture with a needle and not direct puncture because the bile duct is much more narrower and the window of safety is much smaller. So it's better to put in a wire first and then exchange with a cautery-enhanced luminal pulsing stent. So the single step system is very good, especially in terms of learning because you can see even with this first procedure by a trainee, it reduces the need of exchange of devices. So we can burn and insert the stent and then deploy the distal flange first under US guidance, followed by deployment of the proximal flange in the channel, and then pushing it out from the scope. So the entire procedure can be done in a very controlled, safe, and gradual manner. So this is the beauty of luminal pulsing stent, and it may potentially reduce the learning curve. And also quickly, I'll show you the HGS stent. So in this patient, the segment 3 duct is dilated. Again, we first puncture with a needle, followed by contrast injection. The patient already had a previous B-Restent inserted, which was obstructed again. Insert a wire, followed by a 6-franc systotome, and then placement of this hepatical gastrostomy. I'm sorry. So deployment of the distal part, followed by deployment of the stent in the channel, and then pushing it out from the scope afterwards. All right. So which approach do we use? So if you look at the literature, actually it's quite complicated. In this study by Park, my good friend, he tried to decide his method depending on whether the papilla is accessible or not. If the papilla is accessible, he would use a trans-papillary method like Hongde Vu. If it's not, then he would employ the transmural method like CDS and HGS. For those who are more experienced, there are other considerations. Etiology is very important, benign versus malignant, and also your own outcomes as well experience. So if you are familiar with all types of biliary drainage procedures, then I would consider the etiology and also the idea of stent patency. So for malignant conditions who are unresectable, in general we will prefer a transmural stenting because we can place the stent away from tumor and potentially have improved stent patency. All right. So now we are also seeing some studies looking at the potential role of primary USBD drainage for malignant biliary obstruction. Again, the rationale is to avoid placing the stems across tumor. Potential advantage included improved stent patency, reduced procedure time, no risk of pancreatitis, but of course there is a risk of adverse events and also it's expensive. So the first study to show that USBD may be beneficial over ERCP is this current study, again by my good friend Park. He compared ERCP versus primary USCDS or HGS. They show that the over adverse events is similarly better. Pancreatitis rate is zero, re-intervention rate was 15% versus 42%, and stent patency was better at one year, 63% versus 36%. This is the Kepler-Meier graph and my only criticism is that in this study the stent patency in the ERCP is unusually low. So at one year it's only around 40%. So if you look at most studies they would report about 80, 90, 80 or 70% percent. So I'm not sure why, but this is my main criticism. So we have also recently completed this study comparing USCDS versus ERCP. So CDS was performed by the Cautery Enhanced Immunoprostein stent. We just presented the results in this year's DDW plenary. The technical success is certainly better with the CDS procedure. In patients with ERCP they failed because of failure of cannulation, they failed because of duodenal obstruction. Procedural time was significantly faster in the CDS arm. In terms of other outcomes, many of these patients still haven't reached their endpoint. So the one year stent patency is still being collected, but right now we haven't been able to show any differences. So in terms of US bleed drainage, I think a US guided bleed drainage is gaining popularity as an alternative to PDBD. The approach is opening to new possibilities in endoscopy and evidence in suggesting that it may provide some benefits over ERCP is accumulating. So in the interest of time, I'm going to conclude this webinar. And in conclusion, I think Shannon has showed us a very comprehensive lecture in terms of how we could approach malignant bleed obstruction in the 21st century, going from diagnosis, work of the patient, obtaining tissue diagnosis, to the decision of drain or no drain in receptor cancers, how to drain in unreceptor cancers. And I also followed up in terms of what more can be done in terms of endoscopic ablated treatment, as well as if ERCP fails, how can we achieve drainage with a US guided approach. So we are happy to take questions from the floor. So hi. Sure, I probably cut into your time a little bit, but I want to ask, you did show us the EOS CDS with the axial stent, and then a study showing that our primary EOS drainage has a higher technical success rate and a shorter procedure time as compared to ERCP, right? So do you think this result would be reproducible if we use other stents that are not cautery enhanced? Oh, so yeah. So in terms of the technical success, as I mentioned, I think it's more of a characteristic of the EOS procedure because for EOS, we do not need to cannulate the tumor. So in quite a number of these patients, the tumor is so obstructing that cannulation was impossible. And also in a number of patients, they do have duodenal obstruction. Although we do allow dilatation of the tumor before the ERCP, but sometimes these can still be very difficult. So in terms of this area, I think EOS is advantageous. In terms of procedural time, I think yes, cautery enhanced luminal pulsing stent would significantly improve the time. I think in US and Europe, most of the stenters that would perform CDS would still be using this device. So I think in terms of this aspect, it is quite applicable to the situation. And in US, actually, the 6-frame systotome is not available. So it's difficult for them to perform a CDS with a 6-frame systotome followed by a 4 millimeter balloon dilatation. So yes, I think that's my answer. So I think there are some questions for you. Is there a risk of cystic duct blockage with fully covered mineral stents in ERCP? Yes, thank you for your question. Of course, there is a potential risk, but the risk itself is actually very low. So most of the time, the patient has cystic duct blockage usually due to the cancer itself. So the cancer involves the cystic duct origin rather than really the stent itself obstructing it. But it is a potential risk, and the patient may need a PTC drainage or US drainage of the gallbladder after this procedure. I also want to follow up on this question. So from your presentation, you mentioned that covered versus uncovered stent is still a big controversy. And you have mentioned that if there is a covered stent that can have anti-migratory properties like those that were described, then it can improve patency, right? So what is your choice now? So which stent do you use and why? Well, in general, I would try to look at the etiology of the malignant obstruction. So if it is a luminal obstruction, like in cholangiocarcinoma, the risk of stent in-growth is much higher. And usually, these have a very, very tight structure. So I would insert a partially covered stent. So hoping that the top uncovered part would prevent stent migration and at the same time prevent stent in-growth. But for etiologies like extrinsic compression from lymph nodes or primary pancreatic cancer, then I would consider the use of uncovered stents because the theoretical chance of tumor in-growth should be lower in these extraluminal compressions. So I see that there is a second question in the Q&A. So Teo, what is your practice for choice of metal stents in inoperable hilar lesions, partially covered or uncovered? I think most endoscopists would choose an uncovered stent for hilar lesions because in the hilum, it's not only just two ducts. You have primary, secondary, or tertiary ducts. If you place a fully covered stent, then you may potentially block all these tributaries. So I think most endoscopists would choose an uncovered stent. But I think the bigger discussion on hilar stenting would be, I think Shannon just now mentioned the single versus bilateral stent. But even with bilateral stenting, there are different choices like side-by-side or a wide stent. So what is your preference? Do you have any preference? And is there any difference between the two methods? Well, in general, I would place a side-by-side stent because cannulation through the large pore in the middle part of the stent is actually quite technically demanding. So after cannulation of both ducts, logistically, it's actually easier to place it side-by-side, I think. What about you? I agree. But I think recently there has been a number of Korean studies showing that the wide stent has actually better patency. So if you have a stricture, if you put two metal stents, then actually the two stents won't be able to expand as well at the highlight area. So if you have a wide stent, then you have one lumen. So the stent won't be sort of like fighting each other. So I guess that's the idea. But I do agree that if you have a very tight stricture, cannulation through the large cell may be difficult. And actually the re-intervention is actually more difficult, right? Yes. Re-intervention is of course more difficult because if you have a wide stent, then if one side gets obstructed, if you have to go through the mesh to put in additional metal or plastic stent, it can be a nightmare. So is there a role of antibiotics in reducing early cholangitis post-stent placement for hyaluronatumus? You're asking me? Would you like to answer it? So of course antibiotics, we do give prophylactic antibiotics. If you look at the ASG guideline, they actually suggest that antibiotics is not needed in the post-ERCP management if adequate drainage can be obtained. So going along those lines, so if the hyaluronatumus are well drained in theory, or the dirty bowel could be drained. But I think as many endocrinologists would tell you, in trying to cannulate hyaluronatumus, try not to inject contrast because once you inject contrast and if you couldn't drain that sediment, then you will induce cholangitis. So I think more importantly is your technique of cannulation. So always use a wide guided method to try to cannulate that part of the duct. If you can't cannulate with a wire, if you really have to use contrast, then you need to make sure that you provide adequate drainage. And finally, nowadays with the US method, if you cannot cannulate with ERCP, then a very common situation is you end up placing a metal stand either on the left or right duct with ERCP and you can drain the other side with US guided drainage. So I think that is the latest approach. All right, we've finished all the answers. So ready? I think, are we happy to close this session? You still want us to keep talking? This is perfect. Thank you again, Professor Teo and Professor Chan for these excellent and informative presentations and again for being here with us today. I know it's getting late in Hong Kong, so we appreciate it. And as a final reminder, please do check ASG's calendar of events as we will continue to feature relevant sessions to our global spotlight series. Our next event is scheduled for Thursday, July 29th at 8 a.m. Central Daylight Time, same as today. Save the date and look out for registration link to come out soon. In closing, thank you again to Professor Teo and Professor Chan for these excellent presentations and the discussion. It was very lively. And thank you to our audience for making this session interactive. We hope this information has been useful to you and your practice. And with this, we'll conclude our presentation. Thank you. Thank you so much. Thank you.

malignant biliary obstruction

21st century

ASGE Global Spotlight

tissue diagnosis

brush cytology

endoscopic ultrasound-guided biopsy

resectable tumors

preoperative drainage

choice of stents

endoscopic ablative therapy

altered anatomy