Without further ado, we'll move to our first section. We basically have four sections of about two hours each, and there's a lead for each section. And our first lead needs no introduction. Dr. Nagy Reddy is from Hyderabad, India, and completed his medical education at the Curnewell Medical College in India. Nagy is one of the foremost leaders and promotes endoscopy, not only in India, where he has just had an incredible impact, but subsequently internationally. He's a critical thinker. He adapts new technology, and he's pioneered so many new techniques that he has sought after everywhere. In addition to just presenting and clinical work, he is extremely prolific in publications. On top of that, he does a number of very innovative outreach programs in India and was recognized by the government of India with the Padma Bhushan, which is one of the highest civilian honors given by the president of India. It's very much a pleasure to have him. I would remind those of you that don't know that he is the Rudolf B. Schindler Award honoree for the ASG in 2021. Dr. Reddy, it's a pleasure to have you join us today. We look forward to your talk and the next two hours with you. My topic is on ERCP, a very broad-based topic. So what I'm going to do is these are my financial disclosures, none. What I'm going to do is to break up my topic into three areas, binary drainage, minimizing complications, and new devices for stones. Let's start first with biliary drainage. Of course, endoscopic biliary drainage will depend upon the cause of obstruction and the site of obstruction. Whether you're doing palliative, curative, or neoadjuvant therapy, it depends on what the cause of obstruction is. For example, for distal obstructions, it's very clear that most of these patients go for surgery. But some of them will require preoperative biliary drainage. These are mostly patients who are on neoadjuvant therapy or those who have high-grade obstructions like cholangitis, intractable pleuritis, and so on. But majority of the patients, I'd like to remind you here, are those who are low-grade obstruction and do not require any drainage. But if drainage has to be done in this group of patients, there's clear evidence now that one should use a self-expanding metal stents and not plastic stents. Now, let's come to palliative drainage in patients with distal biliary obstruction. And in fact, earlier literature suggested that in these patients who have a short lifespan, one should use plastic stents, and if you have a longer span than, say, three months, one should use a self-expanding metal stent. This concept has changed in recent years, and this was a 2015 multi-center study which came from Holland, which showed clearly that irrespective of the stage of the disease, whether it's terminal disease and so on, all patients with extra hepatic biliary obstruction benefited from self-expanding metal stents, not plastic stents, both in quality of life and in economic sense. So I think they stopped using plastic stents in majority of these patients as palliation. Now, let's come to hilar obstruction. And hilar obstruction, the more complex subject for the endoscopies, majority of these patients do not or cannot go for surgery because of various reasons and require endoscopic palliation. But before we actually palliate this patient, it's important to know what's the bismuth classification, you're dealing with type 1 to 4 type of condition, whether any of the lobes are atrophic, because draining this lobe should ultimately result in no benefit to the patients, and of course, abnormal anatomy and so on. So what we would do in majority of our patients with hilar obstruction is to get a pre-ERCP, MRCP, a so-called GPS to direct us towards the right duct. For example, in this case, the right duct would be the right anterior posterior ducts to drain and not the left. So this would sort of tell us exactly how to go about draining our patients. Again, increasingly, we are now clear that draining at least 50% of the liver is important to have effective drainage. We used to think it was 30, now it's 50%. If you drain this, then patient, of course, gets good palliation. There are several clinical questions that we as endoscopists have to go through before we actually drain these patients endoscopically. What stent should we use, plastic or metal? How many stents? Which technique? And so on. Let's start first with which stent. Should we use plastic stents or metal stents for hilar obstruction? And again, we have several studies, including a meta-analysis which suggests that using self-expanding, uncovered self-expanding metal stents is superior to plastic stents in these patients. And therefore, I think the evidence is very clear here. Rarely, very rarely, we use plastic stents, especially if the diagnosis is not certain or in a preoperative setting. But otherwise, most of these patients get palliative stenting done with an uncovered metal stent. Now, how many stents should we use? As I told you that we have to drain 50% of the liver. So to drain 50% of the liver, should we use one stent, two stents, unilateral or bilateral? Now, this is a question that's been going on for a long time. There's a recent Korean study which showed clearly that for patients having bismuth 3 or 4 high-grade obstruction, bilateral stenting was superior to unilateral stenting in terms of stent patency and survival probability, both increased with bilateral stenting. So I think now the jury's out that actually better to stent as many ducts as possible in these patients so that you can get at least 50% of the liver obstruction out. Just to summarize what I said and to sort of give an immediate reckoner, in general, if you have bismuth 1 or bismuth 2 or bismuth 3b, a single stent is enough to drain 50% of the liver. If you have bismuth 3a or bismuth 4, one would have to use either two stents or three stents, especially in this category, 3a, one had to use three stents to drain more than 50% of the liver. But what is important is to look at which lobe of the liver is atrophic before you put in the stents. Now, which technique should we use? There are two techniques when you put in multiple metal stents, either side-by-side or stent-in-stent technique. Again, it's very clear that most endoscopists tend to use side-by-side stent because when you want to re-intervene, it's much easier. In Asia and most parts of the East, we tend to use more stent-in-stent technique, although there are no good studies comparing both the techniques to show which is more advantageous. So whatever you're used to, you can. But it's also important to remember that although endoscopy is useful for type 1, type 2, and sometimes type 3 patients, for type 4 patients, endoscopy can often become difficult. And wherever expertise is available in terms of interventional radiology, percutaneous ability drainage or percutaneous stenting may be more advantageous in these patients. So this is something that we have to keep in mind, depending upon the local expertise that's available. Now, let's come to the other angle. This is the benign stent, the benign strictures. For benign strictures, especially those in the distal part, again, endoscopic therapy can be quite useful. And for several years, we've been following the costomagnetic technique of putting in multiple stents, plastic stents, at three-month interval, so that these strictures, especially the ones less than one centimeter, can open up completely. And after one year, these stents are removed with 80% resolution rates. But we have now seen that a similar result can be obtained with a completely covered self-expanding metal stent. So this is a multicentric study that was done in several centers in Europe and India, where using a completely covered, self-expanding wall-flex stent, we found that putting these stents in and removing them at six to 12 months resulted in an 80% resolution of the stricture, which followed up to three or five years, the effect remained the same. So therefore, we believe that instead of plastic stents, one could use metal stents too. Even when you follow up these patients for a longer period of time, we found that this efficacy still remains in up to 60% of the patients. We have recently demonstrated that when you have patients with chronic pancreatitis with strictures, believe it's strictures, of less than three centimeters in size, absence of head mass, or absence of calcification, you can treat these patients either with multiple plastic stents or fully covered self-expanding stents. And in this randomized study, we have stents put in for 12 months, followed up for 12 months. After two years, you see that the stricture resolution is similar, overall side effects are similar. What is important is the number of ERCPs when you use a covered self-expanding metal stent is much less than we use a plastic stent, where when you increase the number of ERCPs, there's always a potential for cholangitis and so on. Therefore, we believe that in patients with distal benign biliary obstruction, a completely covered self-expanding metal stent may be adequate in most of these patients. Now, let's come to the second topic. And this is, I think, extremely important for the ERCPs, that is minimizing post-ERCP complications. We know that ERCP, the fairly aggressive procedure associated with complications of which pancreatitis is more dreaded and most common. There are others like cholangitis, bleeding, and so on. What we also know now is that there are certain risk factors which are responsible for these post-ERCP complications. And in pancreatitis, we know that, for example, if you have a suspected SOD in a female patient with normal LFT, the chance of producing a post-ERCP pancreatitis is almost 50%. So based on this, we can now weed out our patients who are likely to develop complications and, of course, decrease the chance of a post-ERCP complication problem. So for a variety of complications, there are a variety of risk factors, and these can be looked at, and we can minimize the complications. But pancreatitis is the most important. And we now have a lot of evidence over several years to show us how to decrease this incidence of post-ERCP pancreatitis, starting from pharmacological agents, stents, IV hydration, and so on. This is a landmark study from Indiana, which showed that in patients with high risk for ERCP, most of these patients actually were SOD patients, using rectal endometriosis in 100 milligrams after ERCP decreased all cases of post-ERCP pancreatitis, but more importantly, decreased those cases which are severe or moderately severe and, of course, without increased side effects. And therefore, clear evidence that rectal NSAIDs can decrease post-ERCP pancreatitis. So now that we have evidence, should we use this only in high-risk patients or in all patients going for ERCP? This was a study that came from UPenn, which showed that in all patients going for ERCP, irrespective of whether it's post-spintrotomy or those with pancreatic adenocarcinoma or actually those with low risk for pancreatitis, you can actually decrease the incidence of post-ERCP pancreatitis by using rectal endometriosis. Of course, this was a retrospective analysis, but still significant evidence because of the large number of cases that are actually analyzed. So I believe, based on this and other evidence, the ESG, the latest guidelines which came out last year, suggested that NSAIDs, either diclofenac or endometrazine, should be used rectally in all patients going for ERCP unless there's a contraindication. And the contraindications are usually pregnancy, renal failure, or a GI bleed. When should we actually use this NSAIDs in these patients? And this is very interesting because should we use it before ERCP, after ERCP? And this very well-conducted multi-center study from six Chinese hospitals seemed to answer this question. There were 2,600 patients who were randomized into two groups. One group received pre-procedure endomethacin. Another group was stratified into high-risk and average risk. High-risk patients, again, received endomethacin after the procedure, post-procedure. And then they looked at the data. They showed clearly that the incidence of post-ERCP pancreatitis with the pre-procedure was 4% compared to 8% when it was after the procedure. But more importantly, we looked at high-risk patients in both the groups. They showed very clearly that you can actually decrease the post-ERCP pancreatitis by 50% by using endomethacin before ERCP. So I think it's fairly clear now that if you use endomethacin 30 minutes before ERCP, you could actually have the most efficacy with rectal endomethacin. However, it is not always possible in clinical practice exactly timing it that way. But in general, rectal endomethacin before ERCP would be ideal in most patients in this situation. And what about the route? Of course, unfortunately, both intramuscular and oral routes don't seem to work. Why rectal is better, we do not know. But this is a route that we would have to use in our patients. Coming to pancreatic stents now to prevent post-ERCP pancreatitis, it's clear evidence that pancreatic stents can decrease the incidence of post-ERCP pancreatitis. And of course, again, ESG guidelines suggested that we should use pancreatic stenting, especially in high-risk patients. Small plastic stents are used, especially in high-risk patients. It's fairly significant evidence, and of course, great recommendation. Now, how effective are these stents? I think, again, there's several meta-analysis reviews which suggest that these stents are definitely very effective to prevent post-ERCP pancreatitis in patients with high risk for this. Now, which stent should we use? There are many, many studies. I summarized this very quickly into saying that the ideal stent would be to use a 5-french, 5-centimeter stent. Of course, there are some who use longer 3-french stents. Again, arguments for and against. I don't want to go into this. Maybe we can take it up in the questions. But in general, a single-pigtail, 5-french, 5-centimeter stent is ideal in these patients. These stents tend to drop off after a week or 10 days' time, although some have to be removed. And when should we use this? Because we're using the equilibrium stent already, when should we use pancreatic stents? Of course, I would personally suggest that these should be used in certain high-risk situations. A double guidewire of pancreatic cannulation more than three times or too much of contrast in the pancreatic duct. But mostly for high-risk patients. For example, if you are doing an amphilectomy, one would always put a pancreatic stent to prevent post-ARCP pancreatitis. In a situation like this, where we are doing a double guidewire technique, after the procedure is over, I would always place a pancreatic stent to prevent post-ARCP pancreatitis. Similarly, if the pancreatic duct is completely filled and is not draining, it may be wise to finish off your procedure with a pancreatic stent. Now, if you combine a pancreatic stent with NSAID, will it be more useful? Of course, synergetically they should be. But unfortunately, this meta-analysis showed it does not work. For some reason, a combination therapy using both of these doesn't have a synergistic effect. So one of these can be used. Of course, what happens is most of these patients get an NSAID before the ERCP. If you have a very difficult cannulation or if you are doing an amphilectomy, you would add an additional pancreatic stent to these patients. In patients in whom you can't use a pancreatic stent or NSAIDs, in these patients it's been shown that sublingual glyceryl trinitrate, 5 mg prior to ERCP, may be beneficial in decreasing post-ARCP pancreatitis. The other important concept that's come in recent years is IV hydration. And again, it's increasingly being used in our patients. So this was a Korean randomized controlled study. We showed clearly that patients who underwent vigorous hydration with ringlectate, usually a 10 ml per kg bolus before the procedure, 3 ml during the procedure, and 10 ml after the procedure, decreased the incidence of post-ERCB pancreatitis. And this is again something that's becoming a routine in our ERCB practices. And finally, the most important problem that actually most important technique related to decrease incidence of post-ERCB pancreatitis is the so-called guidewire-assisted biliary cannulation that is now increasingly being used. And again, several studies, several meta-analysis showed that if you use selective guidewire cannulation, you decrease post-ERCB pancreatitis. And of course, the number of times you're trying to cannulate, if it is more than five or more than eight times, then the chance of post-ERCB pancreatitis increase. So techniques are very important. And these techniques, of course, better techniques decrease the incidence of post-ERCB pancreatitis. Bleeding can occur in some of these patients, although not very high incidence, but there's certain risk factors like use of anticoagulants and so on. It's now recommended that patients are on antiplatelet agents or anticoagulants. They should be stopped or non-spintrotomy techniques like dilatation should be used. Aspirin can, however, continue with these patients. But sometimes bleeding can occur in an unexpected way. For example, this was a patient with portal hypertension in whom we are doing an ERCB, removing the stones in the bile duct. And you can see what happens is as soon as we remove the stones, they are ruptured one of the varices in the bile duct and the torrential bleed that can occur secondary. These bleeds were difficult to stop initially, but we now know how to stop these bleeds very easily. And what we now do is to put in a completely covered, self-expanding metal stem so the bleed will stop. Post-ERCB related perforation can occur because of a variety of reasons. The most common is one secondary to spintrotomy or a pre-cut, which can often be managed with clipping. But if you have an endoscope causing the perforation and cannot be closed by an overscore or so on, these patients would often require surgery. Of course, cholangiitis is another problem. I don't want to delve too much into this. Probably we can discuss data because of this resistant organism that are coming in now and the issue of disposable scopes and so on. And finally, I come to this area of new devices for stones. It's almost 40 years since Kawai and Klassen described the technique of removal of CBD stones. And since then, this technique has become standard. But there are difficulties sometimes, especially when large CBD stones, stones behind a stricture or Mirzi's syndrome, intrahepatic stones, these are not so easy to remove. We're getting a lot of new devices. For example, these tough rotatable baskets or spintrotomes along with a balloon, them are coming in. But I think the standard technique now, which is becoming very common for these difficult stones, especially those larger than one centimeter, is to do a combination of endoscopic spintrotomy, partial endoscopic spintrotomy. And this is a very common technique followed by a large balloon dilatation. And we have found that with this technique, majority of these so-called large stones up to 1.5 centimeters can be very easily extracted. And there are over nine RCTs and several series which have shown that this to be true. So this has become an important armamentarium in our endoscopic techniques to try and remove this very large CBD stone. You can see here, once we readily break the spinter, very large stones appear, which can't be taken out by the standard techniques, can be very easily taken out if you're using a balloon to remove this stone. The AAGE recommends, based on the evidence in literature, that if you actually compare papillary balloon dilatation with spintrotomy versus spintrotome alone, you can see the efficacy rates of balloon dilatation with spintrotomy is much higher, with a much lower need for mechanical lithography. I think this is very important, and therefore this has become the standard. Now, what has also become standardized is how long to dilate the balloon, what balloon size to use. We always use the balloon which is sized along with the lower end of the CBD and the stone size, never more than 15 millimeters. The duration is 60 seconds. And of course, if we can't do a spintrotomy for some reason, we always put a pancreatic stent in these patients to avoid post-RCT pancreatitis. But once you do a large opening and still can't remove the stones, we have some options. One of them is mechanical lithography. Although mechanical lithography is a very old technique, is very effective, unfortunately, if the stone size is more than two centimeters or if the duct is smaller in size, it's not very effective methods. And therefore, the other techniques in recent years which are coming in, which are being used in our patients, and the most important, of course, is a parole cholangoscopy guided lithography, either using laser or EHL. There is, I think, considerable evidence of high quality and, of course, recommendations from various societies that this should be the next step in our patients. There have been three series recently which have reported its efficacy. What we, of course, would do is to use this, you can see here that it's a very simple technique. It's an adjuvant that occurs to ERCP now, putting in a cholangoscope and then, of course, using laser fibers, which are directed with saline around the stone to break, fragment the stones into small bits. And again, with a very high success rates. The first study, which came from a Los Angeles, James Boxwong unit, which showed very clearly that compared to a standard clearance of the mechanical lithography, a cholangoscopy guided laser lithography resulted in a much higher success rate with similar complication rates. This was the first study that came in. And then, subsequently, a study from Thailand. These were patients who had a papillary balloon dilatation, but their stones could not be extracted for a variety of reasons. And in these patients, were randomized to either mechanical lithography or laser lithography. And you can see very clearly the difference in the success rates when these two techniques were used. So therefore, again, confirming that laser cholangoscopy guided lithography is superior to mechanical lithography. And finally, this was a study that came from Sham Vardarajan's unit in Orlando, which randomized 66 patients with stones that exceeded the diameter of the extra-phytic bile duct, usually more than 1.5 centimeters. And you can see that when they compared the single-operated cholangoscope with a large balloon dilatation as the control, you can see a much higher success rate with a single-operated cholangoscopy. And therefore, I think this is now recommended as a technique, especially if you have a stone which is more than 2 centimeters in size, unusual location, and a distal fixture below the stone, it would be better directly to go and try and use a cholangoscopic laser lithography or EHL rather than other techniques like mechanical lithography and trying to take out these stones. And of course, it is now increasingly becoming aware that radiation has its complications, especially in patients, for example, with pregnancy. And what is now being tried, and of course, we now know that using the new cholangoscopes with better vision and so on, you can do a completely radiation-free removal of CPT stones. And this is an example of a patient, pregnancy, and you can see that no radiation is being used. A spintrotomy is done after the guide wire is put deep into the bile duct. And of course, once you see the stone, we now have baskets which can be passed through this cholangoscope, and then the stone can be extracted. The whole procedure done without any radiation. I think this is going to the future, a radiation-free RCP. Of course, we're going to develop better devices and so on for this. The other technologies coming in, this is the direct cholangoscope, which is not commercially available, but some of the models that are available now, you can see that this can be inserted directly into the bile duct. And a dilated bile duct, this has certain advantages in removing the large stones, or even doing DHL or laser trypsin in these patients. In patients who have very large stones which can't be removed by any of these techniques, in our unit and some European units, increasingly an extracorporeal shock laser trypsin is being used. And you can see how effective it is. This was actually a four centimeter stone, and how it can be pulverized into very small bits using a nasobiliary catheter, continuous irrigation, these stones can be removed. So this is, of course, available in certain centers. And finally, just to summarize what we would do in a difficult or a large stone more than 1.5 centimeters, if the stone is not impacted, these patients would first have a preliminary sphintotomy followed by a large balloon dilatation. And if the stone-to-CBD ratio is less than one centimeter, less than one, then these stones can be removed by mechanical atrophy. If this is unsuccessful, or if the stone-to-CBD ratio is more than one, then one would have to use a cholangoscope with DHL or laser to clear these stones. And of course, if these can't be cleared, we can do a temporary biliary stenting and come back and finish the procedure at a later date. So finally, my take home messages in this subject are, for biliary drainage, whether you're dealing with benign strictures or malignant strictures, uncovered or covered self-expanding metal stents seem to be superior to plastic stents. Of course, we're starting to use cholangoscopy for indeterminate stricture, another topic I don't want to dwell into details, but for pre-op drainage, again, covered cell solutions. Minimizing complications is now possible with rectal endometriosis and pancreatic stents in given situations. And finally, in patients who have difficult biliary stones, papillary balloon dilatation, either initial therapy, and in case this fails, one should go on cholangoscopic electroplasty to remove the stones. Thank you very much for your attention. Dr. Reddy, fantastic talk. Much appreciated. You can cover a lot of ground in a short time. And we also know that you practice what you preach. So, to remind the audience, put your questions not in your chat box, but address your questions through the Q&A at the bottom of your Zoom screen. We could ask questions, I think, to Dr. Reddy all day long, but a couple would have come up. Can you just touch on your pre-procedure antibiotic protocol? What type of antibiotics do you use? Who do you use them on prior to an ERCP? I think this is a good question. All patients with obstructive jaundice, so undergoing biliary drainage, we use pre-procedure antibiotics. We prefer to use cephalosporins, but I think it also depends upon the type of bacteria you have in individual units, so it depends on your microbiologist. But for us, the first choice is cephalosporins. We use a single shot of cephalosporins, and if the drainage is successful, we don't follow it up with further. But if you have a complex situation like a high-load stricture where we have to do multiple stentings, then we continue to use these antibiotics for another 24 hours. Yeah, so presumably, you need to know your local resistance patterns, and one shot of Cipro and three days of Cipro afterwards may not cut it for many units. Is that correct? Yeah, exactly. And for stone disease, of course, we're now not using antibiotics so much, unless you do a cholangoscopic stone, then you might have to use an antibiotic, at least a single shot. Question about the spy basket. What size of stone can you get into that spy basket? I think you stimulated a lot of thought with the spy basket removing a stone. How big of a stone can you go after with that basket? Yeah, with a spy basket, you can get out stones which are about eight millimeters, the maximum of eight millimeters. Rarely, even one centimeter stone we could catch and get out, but generally, stones which are less than one centimeter, larger stones you can't get out. With the current spy baskets, they're developing newer ones which open up much further, and maybe larger stones can be caught with that. But currently, I would say anything below one centimeter. Would you consider diclofenac as an equivalent substitution for indomethacin prophylaxis? Yeah, I think there is evidence in literature to suggest that where indomethacin is not available, diclofenac can be used with similar efficacy. And great questions, by the way, from the audience. Will you have a threshold to place a pancreatic stent? This is always difficult. Is it one cannulation, two inadvertent cannulations? Is it no cannulations in a high-risk patients? What is your threshold? I assume it's relatively low, given the evidence. Yeah, so my threshold is actually getting lower as I'm becoming older. I'm very concerned about what happens to this patient in terms of post-TRCB pancreatitis. If the patient had a difficult cannulation, and I think that this patient requires a pre-cut, even with the first pancreatic ductal cannulation, I put in a pancreatic stent, because I always like to do a pre-cut on a pancreatic stent and won't like without a pancreatic stent. But if the patient has like a large CBD stone, and we know that we're going to get in very easily, then I'd wait at least for three cannulations, that is three times the vial going in, and then I'd put a pancreatic stent in these patients. Okay, and one last question, management of post-liver transplant common bile duct stones above an anastomotic stricture. So I guess that's altered anatomy, stones up high. What is your thought process on those? Actually, very often post-anastomotic strictures of a liver transplant are very easy to dilate. These strictures can be dilated very easily, and following that, we would go in with a cholangioscope if the stones are large, or if they're not large, just with a standard basket, and invariably one can clear them. They're also very soft stones, so you have a combination of a soft stricture and a soft stone, so very often you can clear them easily. I'll do one more. Needle knife, you've mentioned it a couple times. How quickly to move to a needle knife? You probably don't have to use a needle knife very often because you're very skilled and have high volumes, but how quickly do you go to a needle knife sphincterotomy, doing something early as opposed to waiting until you have repeated cannulation of a pancreatic duct? Yeah, again, we tend to go in very early. If you can't, three attempts, if you can't go in, we go in for needle knife. The reason is that early on, when we started ERCP very early in 1980s, we didn't have these kind of accidents, and now the need for needle knife has come down dramatically. Very little indication for needle knife, and when you can't go in, we would very quickly go to needle knife because there's evidence that early needle knife has a decreased incidence of post-ERCP pancreatitis. Okay, and I keep going last, but for palliation of common bile duct strictures, i.e. pancreatic cancer or even higher, non-covered versus covered? Yeah, so in general, for palliation, we tend to use uncovered stents. The reason, of course, is because of less migration and less chance of complications like polycystitis. There have been many randomized control trials, especially in patients with pancreatic cancer, looking at covered versus uncovered stents, showing that there are advantages and disadvantages, but in general, especially, of course, for high-large, it's always uncovered. For distal CBD strictures, for palliation, pure palliation, I tend to use uncovered, but if these patients are likely to go for chemotherapy, neoadjuvant therapy, or potential surgery later on, one could still think of using either a completely covered or a partially covered stent. Okay, and I think we'll close it there for the Q&A. We'll have more time for Q&A later.

ERCP

biliary drainage

metal stents

post-ERCP pancreatitis

complications

stone removal

healthcare professionals