It's a delight for me to introduce Dr. Jessica Widmer as our next speaker. I had the honor of meeting you when you were an advanced fellow about a decade ago, so now she is the chief of endoscopy at NYU Langone Long Island Medical Center, and she is going to be talking to us about cholangiopancreatoscopy. Thank you so much for the invitation to come from both Uzma and Linda. It's a pleasure to be here, and the faculty here are outstanding, and I think the discussions that we're having are helpful for everyone. So I was tasked with the introduction to cholangiopancreatoscopy. I think I could talk all day about this, so I'll try to keep it brief, and these are my disclosures. There are so many different applications of cholangiopancreatoscopy, and so today I just want to focus on a few things. We'll be talking about management of stones in both the bile duct and the pancreas duct. We'll be talking about assessment and tissue acquisition of indeterminate strictures in both ducts. In the bile duct, we'll talk about options for treatment of biliary malignancy, and in the pancreas duct, we'll talk about assessment of main duct IPMN. So I think most of us are using the Spyglass single operator cholangioscope. It's a single operator system where we have four-way steering capability, irrigation channels. We can do both diagnostics and therapeutics with it. It's really reliable. The second generation Spyglass now has better therapeutic options, and we have all kinds of accessories to try to help us with our success for each indication. So the older generation of Spyglass was updated to a digital system, and basically looking at the improvement, procedure times are decreased, radiation exposure is decreased. It has helped modify the diagnosis in upwards of 30% of patients, those who had suspected benign strictures or long strictures. And the sensitivity is anywhere from 76% to 97%, which is quite a bit of variability, and there's been great stone clearance with this. So there are a few considerations to keep in mind, and it depends really on your center. Cost is one thing. If you're at a larger institution and you're using a lot of one company's products, you may be able to get special pricing. But you do have to think about the processor, the scopes, and all the accessories that go along with it. It might lengthen your procedure time. And we should mention the adverse events associated with this. Slightly higher than with conventional ERCP, 19% versus 14% in some studies. I'll note the increased risk of cholangitis as compared with conventional ERCP. I think most of us are given antibiotics for a few days afterwards. Slightly higher risk of pancreatitis and some increased risk of bleeding. So I'll start first to talk about difficult bile duct stones, and that's really defined as stones that are greater than 1.5 centimeters in size if they're impacted in the bile duct or the cystic duct. If there's a stricture with a stone up above it, and patients who have anatomic variants. And cholangioscopy allows us to directly visualize the bile duct and the stones, and that may reduce the injury to the bile duct wall in the midst of this. And the two ways that we have of treating difficult bile duct stones once we've kind of exhausted other options of sphincteroplasty or mechanical lithotripsy are EHL or laser lithotripsy. And what you're using, the choice may be determined based upon what you have available at your institution. I happen to have EHL, so I use that more commonly. And the way that that works is you use normal saline to irrigate the bile duct, and the sparks are discharged from the catheter and causes increased pressure waves, and that will actually fragment the stones. If you're using laser, it's short pulses of optical energy, and it creates this bubble that then bursts, and it causes a shock wave and can fragment the stones. So what are some data on difficult bile duct stones? So meta-analysis looked at over 800 patients, with success being as high as 88%, with generally low adverse events associated with it. Shortly thereafter, there were three randomized control trials that I'll just briefly talk about that were looking at either using EHL or laser as compared to conventional therapy, which was defined as mechanical lithotripsy and sphincteroplasty. In the initial study, stone clearance was improved as compared to conventional mechanisms upwards of 93%. That study was with laser lithotripsy. The second study showed no difference in success, and the third showed 100% versus 60% in patients with laser as compared to conventional. I'll just show this. These are some older studies, but if you look, there's quite a bit of variability depending on timing, but most of these cohorts had at least 80% or above in terms of ductal clearance, with generally low risks associated with it. Clangioscopy can also be used to confirm ductal clearance after you've removed stones, whether you were using it for lithotripsy or not, and that can be quite informative. Sometimes on our clangiogram, you can miss upwards of 20% of stones, actually, depending on your contrast injection, the patient's anatomy, how big the duct is. This was a retrospective study that looked at 36 patients, and they had had sphincteroplasty for difficult stones. It had 86% technical success rate, and they found upwards of 20% of residual stones, so that did have a big impact and may impact, you know, you may talk about the cost of opening a clangioscope if you weren't using it already for the procedure, but if we're talking about potentially reducing the likelihood of having the need for additional procedures, that may be worthwhile. So I'll move on to biliary strictures, and they're, you know, obviously benign versus malignant. The benign are most commonly, you know, iatrogenic or inflammatory, Marazzi syndrome versus malignancy. We most commonly see pancreatic cancers, clangiocarcinomas, but also seeing gallbladder cancers, ambulary lymphoma, and of course, metastatic lesions. And our issue with this is tissue acquisition. It can be challenging. We may not be able to get a sufficient amount of tissue for a histopathologist. Sometimes it can be very difficult if there's also an inflammatory background or if the patients have already had stenting. And a lot of times, you know, at our center, all of our cases are really undergoing a multidisciplinary approach, and we're talking about what should happen first, surgery, endoscopy. And if you dig through the surgical literature, patients who undergo upfront surgery, upwards of 15 to 24 percent of those patients, and this is some old data, were actually undergoing surgery for presumed malignancy that ended up being benign. And that's a conversation that we sometimes have with our patients, depending on the clinical scenario. It's hard to decipher sometimes just based upon the clinical presentation alone or radiographic features. So a lot of the times, pre-op determination of malignancy really is going to dictate what kind of surgery they're getting if they're getting an upfront surgery. So that's where ERCP can come into play here. It can help us to assess the stricture in general, its location, the extent, and you can obtain tissue sampling for cytologic evaluations. But it's really an indirect visualization, and, you know, shapes can be deceiving. And I put this up because it's almost indistinguishable, these two cases, one which was a benign stricture and one which was malignant. So we just are not able to characterize the tissue with our fluoroscopy images. And then we're kind of blindly targeting these areas for tissue acquisition. So that's where a cholangioscopy comes in, and it's brought us back into the realm really of endoscopy for characterization of these strictures, and we have great long-term experience with them. And it's helped us to improve our distinction between benign and malignant strictures. And so these are just a couple pictures of benign strictures. They've all been treated with plastic stenting. Some of them are post-surgical strictures, and you see it's a nice, smooth stricture. There's not really the vascular abnormalities that I'll show you with malignant strictures, and there's no nodules or infiltrating masses or exophytic tissue. As compared to these images of malignant strictures where you really have an infiltrative appearance, you see a lot of ulceration here. You see abnormal tumor vessels, increased vascularity, and you often have a lot of friability. This is a study by Yang Chen back in 2011. It's a multicenter trial, one of the largest back at that time with cholangioscopy. And part of this study focused on indeterminate strictures. There were 76 patients, and you see the sensitivity with targeted biopsies was increased quite a bit from what we've been seeing in the past with just fluoroscopy-guided brushings or biopsies, which can be quite variable, like 40% to 60%. And this really brought the sensitivity up, but the specificity was interestingly quite low in this study. The adverse events associated with this were generally small. And a few years later, this is a meta-analysis that looked at 10 different studies, and you can see the sensitivity wasn't quite as good as what we were seeing in that initial one, but the specificity was much better. I think part of the issue is that a lot of the assessment that we're doing with cholangioscopy is operator-dependent, so it certainly is dependent upon the skill level, how many cases that the endoscopist is seeing. Because it can be very difficult to get a diagnosis in indeterminate strictures, you have to weigh very heavily on the endoscopist's impression. You know, if I look at it and I think it's cancer, but my path isn't showing that, I'm telling the patient that we're chasing this, or I'm talking to surgeons and we're reassessing what would be the next thing. So you weigh very heavily upon that, but a lot of studies have shown that there's quite a bit of variability upon what we think we're seeing, and there's not great agreement. So there have been a lot of different studies that are trying to look at different criteria of malignant strictures. The Mendoza criteria, this is one recent study in one of the newer classification systems that was being tested to see if we can agree on what we're reporting on cholangioscopy. And if you take a look here, where we see most agreement was when we're seeing torturous dilated blood vessels. If we're seeing a raised lesion, an eccentric mass-like lesion is a clue, friability. And if a patient already has some sort of neoplastic diagnosis that's leading you to having concern for malignancy. Trying to increase our diagnostic yield and increase our sensitivity in these strictures, we couple cholangioscopy with other adjunct modalities. And some of these have kind of fallen by the wayside in the past. NBI is a big thing used in Asia. I think most of us aren't really using confocal too much in these settings and OCT. But one thing that is forging ahead is the use of AI for biliary strictures. And there's been quite a few studies and different models at this point that are being tested and trained to identify benign versus malignant lesions. And that's really what we've already kind of done with confocal and these other adjuncts. But the reason why they're not able to replace our biopsies, we still need those biopsies for diagnosis. So I think the next part of this is now kind of testing the models to see if they can help us with targeting our biopsies to the exact location. The last thing that I'll talk about in the bile duct are the options of treating therapeutically when we have malignant strictures. And there are two modalities that are being used, photodynamic therapy and RFA. I look at you, I think of you every time because our first case together was a PDT case. And live. And she gave me too many opportunities when I was losing wires. But we certainly bonded over that. And now, you know, she's a master of PDT. So I really, really admire that. But it's used exclusively for cholangiocarcinoma. And it is a pretty strong platform for paleation in these cancers. It can even be helpful in more peripheral lesions, unreachable lesions that are just peripheral to the bile duct and can be used in terms of downstaging the therapy. But it requires expertise and a dedicated team. And you know, I don't do it anymore. But when I was doing it in my fellowship, I think the biggest issue is photosensitivity. And the reality is, it's tough to convince patients that they've got to stay indoors, the use of sunscreen, protective clothing, you know, window treatments. And you know, you have a patient who may just be diagnosed with cancer, and they're very fragile at that point in time, and then, you know, you're telling them to stay away from sunshine and outdoors. And that minor thing is actually a rate-limiting step with this therapy sometimes. And the other issue is that it really requires aggressive biliary decompression and stent revisions. RFA is something that I think is a little more widespread. It can be used not only for cholangiocarcinomas, but pancreatic cancer and metastatic lesions. You can use it in patients who've had prior metal stenting. It's really for lesions that are directly obstructing the bile duct. It doesn't have the issue of photosensitivity. And initially the focus was really on, can we increase the diameter of that stricture and maybe have better patency in terms of stenting, reduce the risk of preclusions. But now with more data, there is suggestion that there may be an increase in survival as well. So just to talk about PDT in a little more detail, it's an IV administration of a photosensitizing agent. And it's activated by illumination with a non-thermal light with a specific wavelength that results in necrosis. And it's actually transmitted through the bile, which is why it can kind of reach those distal lesions, those peripheral aspects of the lesion. And it does have that immunologic effect where it's activating the tumor necrosis factor. And hopefully then has an impact on survival. You need to use plastic stents with this. You're decompressing the bile duct. You really have to be aggressive with repeated procedures every three months. But there is improved quality of life with this and improved survival. Radiofrequency ablation, as I mentioned, we're looking for improved stricture diameter and hope for longer patency. It's not, in studies, they really didn't show a significant difference as compared to stenting alone, but there was better patency of metal stents. I think if you take a look of the pictures on the left side here before RFA as compared to the second, you can see the improvement in the stricture diameter there. And as I mentioned, with more experience, we're noticing that there is improved survival with this. The thought is that there is an immunologic response and that may give us longer survival rates, especially in patients who are younger and those who are getting RFA in combination with chemotherapy. So I'm gonna switch gears now to talk a little bit about pancreatoscopy. It allows for direct visualization of the pancreatic duct. As we talked about in the bile duct, we can take targeted biopsies and we can do lithotripsy. But it also allows for the assessment of the extent of malignancy in intraductal papillary mucus neoplasms and can be helpful to refine the margins preoperatively. And in terms of using pancreatoscopy as an adjunct for lithotripsy, in some, and we'll talk about this in a little more detail, you know, it can be helpful, but it's really unclear whether it has a productive role in patients with chronic painful pancreatitis. So a few things to think about. Pancreatoscopy often requires pancreatic sphincterotomy and we kind of started the conversation in the last presentation about those risks with pancreatic sphincterotomies. But there's an increased risk of pancreatitis as a result of that. And you're also, you know, doing contrast injection within the duct. So make sure you're talking to your patients about that risk. Talk to the, make sure you're giving rectal endomethysin. We are placing pancreatic duct stents in those patients and make sure they're getting adequate hydration with lactated ringers. So let's talk a little bit about the diagnostic role of pancreatoscopy. And this is often used in main duct IPMN. And it allows us to both visualize the duct itself, looking for, you know, any ductal abnormalities, which we'll talk about in a minute. And it allows for a mapping for the extent of neoplasia that can be very helpful for the surgeons prior to considering a resection in these patients. Sometimes you have ductal dilation, and it's difficult to figure out if this is related to, if this is truly main duct IPMN or chronic pancreatitis. So I think it can be used as another modality that's probably best to be coupled with EUS. It can help to confirm the diagnosis in equivocal cases, patients that you're unclear if they truly have malignancy or looking for the extent. So when you do pancreatoscopy for main duct IPMN, and I think that, you know, there's not a lot of data out there that's reported. And I think it's really institutionally dependent. And I often do it at the request of, I don't necessarily do it on my own, but more so at the request of the surgeons in terms of planning. But what we're looking for are, you can see in the first, well, in the first picture, you can see the lining of the pancreatic duct is just finely granular. In type two, you start to see those classic fish eggs that we talk about that are a suggestive of main duct IPMN. And the third picture shows the same thing, but the difference is that there's vascular involvement. You can kind of see those red little dots in the center. Type four shows the villus protrusions. And then of course, type five shows an actual, you know, vegetative type protrusion, like a polyploid lesion. And type three, four, and five are a little more sensitive and specific for malignancy. Not great upwards of around 70%. It can be used, as I mentioned, for a presurgical mapping. And not a lot of data out there, a few studies. One looks... Okay, okay, great, thanks. And eight of those patients had a change in plan based upon pancreatoscopy in terms of the surgery. Four required a more extensive surgery. I found it interesting, four had a less extensive surgery, but on evaluation pathologically, two had high-grade dysplasia on the surgical margins. It was a pretty short-term follow-up, but those patients had not, at the time of the study, required subsequent surgery and was just undergoing surveillance. Some places, they're also doing intraoperative pancreatoscopy. I've done this a couple times. I too am in the camp where I don't ever wanna go to the OR, but every once in a while, you have a case. I mean, I had a patient who had... It's a very interesting case, actually. It was a patient who had chronic pancreatitis and had a huge stone in the head of the pancreas. We weren't able to really get around due to large cystic lesions in the head as well. Kind of getting the spy scope can sometimes get just stuck if you have a large cyst there and you can't get towards the genu as you'd like to. And he was having recurrent pancreatitis, and so the decision was made from a multidisciplinary approach to consider surgery. But what was interesting is we decided to take a look at the time at the minor papilla to see if maybe we could get better access that way. And he had what looked like a fish-mouth appearance of the papilla. And we went in that way with pancreatoscopy, and I didn't see any kind of high-risk features. The duct looked normal. But with all of those findings, we decided to consider having surgical intervention. And so in that patient, because we wanted to further define what was happening distally and try to do mapping, and I couldn't get the scope beyond, that was somebody that we ended up doing an intraoperative pancreatoscopy. So every once in a while, it has its place. I did find one retrospective study of 21 patients. Eight of those patients had occult IPMN that was not known prior to the surgical assessment. And five patients, the plan was modified based upon pancreatoscopy, so value there. I think the one thing that I would say before I move on is these patients, if you're doing it for mapping prior to surgery, you do have to have a talk with them and with your surgeon that the risk of pancreatitis is there, and that may also affect timing of surgery. So it's not without adverse events. So that has to be part of the conversation as well. And as we mentioned, some of these patients will require pancreatic sphincterotomy when there's a fish mouth appearance of the papilla. You often don't, and I definitely stent these patients, and I try to do a longer stent beyond the genu, and I keep the flange on so that I make sure there's no concern for risk of migration of the stent too early on. So we'll talk a little bit about indeterminate strictures within the bile duct, and pancreatoscopy can be helpful to differentiate between benign and malignant disease. Excuse me. And it allows us to get a little better look at the duct and can help us with our targeted biopsies. And these are often patients with chronic pancreatitis. So we're looking at a retrospective analysis of upwards of almost 80 patients at a single center, and they found 64% of these patients had indeterminate pancreatic duct strictures, 36% had a suspected IPMN. The technical success rate in these patients was 99%, so really great technical success. They found neoplasia in 33 of the patients. 12 of those actually had cancer, 21 had main duct IPMN. 40 had benign strictures, and five had just branch duct IPMN. Pancreatoscopy, which is interesting and maybe a little bit different, I think, than the data that we're seeing in the bile duct, was 87% accurate in distinguishing the neoplasia from non-neoplastic-type lesions with a ferrous sensitivity upwards of 87% and specificity of 86%. Patients who had discordant visual pancreatoscopy and the final diagnosis were those with chronic pancreatitis, and that was only five patients. So findings on pancreatoscopy that were more frequent in patients with main duct IPMN or adenocarcinoma are tumor vessels. You know, similar stuff that we've talked about with the bile duct, tumor vessels, ulceration, friability, and infiltrative-type stricture or protruding lesions, but also the addition of mucin. Benign stricture is more likely to have a band-like scarring, kind of smooth but scarred, maybe an atrophic mucosa and some blurred blood vessels, but you're not expecting those tumor vessels that you see with malignancy. It can be helpful with tissue acquisition. Like we talked about, a few studies are showing that there is improved diagnostic yield. One study looked at 26 patients with known IPMN and pancreatoscopy-guided biopsies were 100% specific, but still with that low sensitivity for being able to differentiate an adenocarcinoma. One study looked at pancreatoscopy-assisted biopsies, 87% sensitive, 100% specific, so not bad there, but overall looks a little more promising than what we're seeing in the bile duct. I'll just go through this very quickly. These were a number of studies that were looking at findings within the pancreatic duct, and we've kind of talked about the various findings that you're looking for in main duct IPMN, what we see in cancer, but also chronic pancreatitis, just those benign strictures that are smooth and as a smooth narrowing and maybe some scarring. I think what comes into question a little bit is about ductal clearance and painful chronic pancreatitis. We know that pancreatic duct obstruction and hypertension plays a role in pain. I think the data is better for using Aswell in combination with the ERCP for the treatment of these stones, but pancreatoscopy with intraductal lithotripsy is an option, especially depending on what you have available at your center, the expertise for Aswell. It can be challenging if you're trying to do Aswell in conjunction with a urologist if you don't have a dedicated person in your hospital who can do it for pancreatic duct stones. So in that setting, certainly we have success with intraductal lithotripsy. And again, we've kind of talked about the mechanisms of EHL and laser, and we know that using direct visualization with it helps to reduce injury to the wall, whether it's causing leaks or an increased risk of pancreatitis and scarring that can lead to stricturing. The data is sparse, and when I say sparse, it's not, there are quite a few studies about it, but when you're looking at the number of patients that are being reported over the years, there's only a few that really have a decent amount of patients that are greater than 10. And in terms of success, it's anywhere from 70 to 100%, and clinical success is defined by a reduction in pain score, a reduction in opiate use, and that's seen in upwards of 75%. So just to summarize, cholangioscopy with EHL or laser lithotripsy is safe and effective to treat bile duct stones. Indeterminate biliary strictures really still can be a challenge at times for diagnosis, but we're seeing some progress when we're using direct visualization, we're doing targeted biopsies, and perhaps with the addition of adjunct modalities, and AI is probably the most promising one coming down the pike at this point. PDT and RFA are therapeutic interventions that can be offered to patients who have malignant biliary strictures. Pancreatoscopy is a good tool for determining benign versus malignant pancreatic duct strictures, and data is promising in terms of pancreatoscopy for main duct IPMM, particularly in mapping prior to considering a surgical resection. And pancreatoscopy-guided lithotripsy is effective, but its role as compared to using as well still needs to be clarified.

cholangiopancreatoscopy

stones

strictures

malignancies

bile ducts

pancreatic ducts

lithotripsy