Without further ado, I will introduce our next speaker who is world-renowned. It's Horst Neuhaus, who's Professor of Medicine, Department of Internal Medicine in Dusseldorf. I won't even try to mention his institution because I won't get it right in German. But Horst is widely known in diagnostic and therapeutic endoscopy. He's past president of the ESGE, and he is a leader in ERCP and other areas, but certainly ERCP. He's going to talk to us today about indeterminability strictures and the role of pro-oral cholangioscopy. So Horst, welcome. Thank you very much for this kind introduction. I would like to thank you and Dr. Reddy and the organizers of the ESGE for inviting me. And it's a great pleasure to talk about the role of pro-oral cholangioscopy for indeterminate Baldach's strictures. So these are my disclosures. So I would like to suggest the following algorithm for indeterminability strictures. MRCP and EUS should be firstly used as non-invasive or minimally invasive diagnostic procedures to evaluate a ductal stenosis or a filling defect in particular to determine the location. And then we have to ask us, is there any clinical need for differentiation? If not, for example, if patients will undergo surgery anyway because there's a high likelihood of a malignant tumor so that you even would recommend surgery in case of a negative result of tissue acquisition. Or if it's a fragile patient, no candidate for chemotherapy or surgery, then we can directly proceed to ESCP stenting and cholangioscopy can be considered in case of failure for negotiating a stricture. Otherwise, US or PTC techniques are available for biliary drainage. However, if there is a need for differentiation, for example, if there's a candidate for neoadjuvant radio chemotherapy or if the patient is indetermined for surgery, then we have different options for tissue acquisition, which is usually needed because no surgeon, no oncologist will just rely on images. And if the tumor is in the extrapatic system, then USFNA is an excellent option, but should not be used in highly lesions because of the risk of tumor cell seeding. Otherwise, there is the open question, should we use ESCP with standard technique for tissue acquisition or directly proceed to cholangioscopy with tissue acquisition under direct visual control? So this is an example, a 68 years old female patient with epigastric pain, jaundice, cholangitis. And as we see here with the yellow arrows, MSCP and also US show a stricture of the distal CBD with upstream ductal dilatation, but there was no tumor or ductal stone and no gallbladder stones. And this patient was referred after failure of ESCP. Now cholangioscopy is difficult to perform if a tumor or stenosis is so close to the papilla. And we decided to proceed to conventional approach. So we succeeded to cannulate the CBD, the papilla was in a diverticulum, then a guide wire was advanced and we have not to fill the complete biliary system with contrast, but we focus on the stenosis and as you have seen, breast shot cytology and biopsies under fluoroscopic control were taken. Now what can we expect with this conventional ESCP approach for tissue acquisition? A recent systematic review in nine studies showed that the sensitivity in case of malignancy of brushing is 45 percent, of biopsies 48 percent, and even if you combine both techniques is less than 60 percent. So the authors conclude even a combination of both only modestly increases the sensitivity. So therefore there is obviously a need for a technique like cholangioscopy to increase the accuracy for elevation of indeterminate biliary lesions. And the aims of POCS are to visualize and to characterize lesions under direct visual control, tissue acquisition, and delineation of intraductal lesion margins. So now we would like to go back. So we have different techniques of cholangioscopy. The most commonly used are direct paroral cholangioscopy. However, the challenge is when we use, for example, a pediatric gastroscope or specially designed paroral cholangioscope to overcome the angle between the duodenum and the common bile duct. This can be facilitated with an anchoring balloon. As you can see, a balloon is filled in the left hepatic duct and then with pushing and pulling you can get the gastroscope into the bile duct. Of course, we have fantastic images, NBI, and we can use forceps through the two millimeter working channel. We get larger specimen compared to a single operator cholangioscopy. However, it's difficult to hold the position, for example, when you remove the balloon. So it has not gained wide acceptance and it's really operator dependent. On the other hand, as we have already heard in the excellent lecture from Dr. Reddy, single operator cholangioscopy is now widely available. It offers several advantages. It's a fully integrated system, can be equipped to the duodenoscope within a few minutes with a plug-in to the controller, CMOS video technologies, two LEDs, four-way deflection, as we can see are very easy to manipulate the tip, and we have a dedicated irrigation as well as aspiration connection and a 1.3 millimeter working channel. So I would like to show a case which was referred with PSC, 25 years old female patient, elevated laboratory parameters, again, first step MRCP showing multiple intrapartic strictures and dominant strictures of the CBD and the right hepatic duct with suspicion of proximately located intrapartic stones. So the aims of cholangioscopy are firstly to evaluate this dominant strictures to exclude malignant lesions, secondly, of course, ESCP for dilatation of the strictures and also to remove the intrapartic stones. So the first challenge was to overcome, to negotiate this very tight and angulated stricture at the distal part of the CBD. So we used several guide wires and different techniques, but we failed. And this is the first advantage of cholangioscopy under direct vision here using the single operator cholangioscope, we could identify the tiny orifice by the way you see this typical changes of PSC, so whitish tissues, scars in the common bile duct, and then we could advance the wire over the stenosis, then the cholangioscope has been removed. We use six millimeter balloon to dilate the stricture, allows now characterization, does not look malignant, so we don't see the typical signs for malignancy. This is the cystic duct orifice, the left hepatic duct, the right hepatic duct, which looks quite normal here. But when, now we approach the very tight stenosis to the anterior lobe of the right liver, and you see a very tight stenosis, and you can imagine this is the opening of the stricture. This would be probably impossible to pass it with conventional ESCP techniques. But under direct vision, we can identify this tiny opening into the stricture, and we use ultrathin hydrophilic guide wires and can change the direction due to the excellent angulation capability of the cholangioscope, which is now removed. We dilate the stricture again to six millimeters, and then we see the typical aspect of a benign stricture and the intrapathic stones, and these cannot be removed with conventional ESCP techniques, but here we use the cholangioscopic technique for EHL, for electrohydraulic lithotropy under direct vision, followed by balloon extraction of the stones, and finally we characterize the two dominant strictures. As I said, so visualization unknown is not enough. We don't see the typical aspect of torturous vessels, for example, in malignancy, but we combined the endoscopic aspect with tissue acquisition, which didn't show a malignant lesion here. So a recent prospective multicenter registry from Almerdi reported on the results of using SOC for discrimination of indeterminability of lesions in 289 patients and showing that the visual impression was correct in malignancy in 87 percent, as again no surgeon and oncologist will just rely on visual impression, but also the sensitivity for biopsies was higher compared to standard ESCP techniques, 75 percent with a high specificity, so false negative results are extremely rare, NPV 77 percent and the overall QSC 77 and 87 percent respectively. However, we have to consider that all of these uncontrolled trials may have been biased because usually the endoscopist is already informed, is not unblinded on the results of previous examinations and therefore we recently reported on the first randomized controlled trial which we did together with the center of Nagy Reddy and the team in Hong Kong because we randomized patients with indeterminability lesions to undergo either ESCP guided brush tissue acquisition or spyglass guided biopsies. Patients were randomized in these two groups, a small study but nevertheless showing a higher sensitivity for visualization, for spyglass and also the overall accuracy was 87 percent versus 66 percent. The sensitivity of single operator guided biopsies versus brush cytology was 68 percent versus 21 percent, surprisingly low, lower than in previous reports, but nevertheless we see this superiority in terms of the sensitivity. There was no difference on specificity, PPV, NPV and rates of adverse events. So how to take biopsies? This is an example of a patient with a filling defect in the left hepatic duct. This is the hepatic confluence, this is the exit to the right hepatic duct and here we can already suspect a lesion in the left hepatic duct. It would be very difficult to approach this area just with ESCP techniques. We don't inject contrast because we have all the information of the ducts by MRCP but we insert a guide wire and the direction shows this was segment three, this is segment two, so we exactly know where the changes are located and you see the typical aspect, so irregular vessels, friable tissue and then we take at least three biopsies under direct vision from the same spot. A recent study from the group in Orlando showed a randomized control design when they compared on-site versus off-site specimen processing by using single operator cholangioscopy for indeterminate biliary lesions in a relatively small group of patients. There was no significant difference. Again, we can appreciate the sensitivity of 77 percent and 75 percent, so this can be seen in several series which is undoubtedly higher compared with all previous ESCP-based techniques, so no difference. That means you can evaluate the specimen even if you don't have the pathologist on-site and the study also showed if you take at least three biopsies from the same area then you can expect the correct diagnosis for 90 percent of the cases. A recent systematic review and meta-analysis confirmed these results from expert centers, so they analyzed studies for digital single operator cholangioscopy, so the digital system was introduced in October 2015 and they analyzed the results until April 2020. Only studies that used the control arm and studies with at least 10 cases and therefore the meta-analysis is based on 11 studies with more than 350 patients diagnosed through biopsies, so not visualization, and the results again show sensitivity of 74 percent for tissue-based diagnosis, specificity 98 percent, positive likelihood ratio 10.5 and negative likelihood ratio 0.3, so very promising results. So another example, let's go back, so 84 years old patient, painless jaundice since four weeks and MRCP shows perihyalis strictures either bismuth 3a or 4, suspicious for cholangiocasinoma, and this is another role now for cholangioscopy, so these are the MRCP images and you will see we directly proceed to cholangioscopy. We do not need anymore to inject a lot of contrast because we know the anatomy, but we want firstly to reconfirm the suspicion of cancer by taking biopsies, but also we would like to evaluate the interluminal spread of the suspected cholangiocasinoma, so this is very important for the surgeon with the question, is this still a candidate for extended right hemipatectomy or is the tumor also invading the left hepatic duct so that we have bismuth 4 and this would then we know for no candidate for surgery. So therefore we performed sphincterotomy and then we approach the hepatic confluence with a cholangioscope, we see again very suspicious lesions here, we inject a little bit contrast to reconfirm that this is the right hepatic duct, the anterior lobe, but now we advance the wire through a small opening here, suspicious for the exit to the left hepatic duct. Under direct visual control we inject a little bit contrast to confirm that we are in the left side and then we advance the wire in segment 2. Now we inject contrast because we will finally drain the left liver lobe and then we pass the cholangioscope over the wire upstream of the stenosis showing normal epithelium, then we pull it carefully back and this is now the junction between segment 2 and segment 3 and to reconfirm that we are correct we advance the wire now in segment 3 you see the anterior part. So we have a very precise information now for the surgeon this is the proximal tumor margin that there are just maybe 7 to 8 millimeters between the proximal tumor margin and the junction between segment 2 and 3 and based on these results the surgeon can decide if this is still a candidate for right extended amyopatectomy and this concept mapping of biliopancreatic neoplasia for determination of resection margin was recently studied by Tyberg, 118 patients and as you can see the results most of these patients had cholangiocarcinoma, some IPM and the surgical plan was changed in one third of the patient either by avoiding surgery less or more extensive surgeries so it seems to be worthwhile of course based on the interdisciplinary discussion before starting with these invasive techniques. So finally the economic impact of using cholangioscopy for indeterminate biliary lesions. These are results based on a model on clinical data and resource consumption in Belgium published by DEPRE and they assumed that malignancy is expected in about 70% of the cases and based on the results I showed you ESCP plus brushing 45% SOC guided biopsies 86% and they also calculated that in case of false negative cases procedures would be repeated and surgery would be done for malignancy and definitely false negative cases and based on this model SOC determined a decrease of number of procedures by 31% and also cost by 5%. So I would like to conclude with conclusion one. So an invasive diagnostic approach is only justified if the results lead to a therapeutic consequence. Tissue acquisition is needed for surgical and oncological decisions. ESCP techniques are false negative in about 40% of malignant lesions and SOC is the cholangioscopic method of choice because of the high efficacy and safety. SOC is more accurate than ESCP for tissue acquisition. I showed you the data. It allows targeted cannulation of difficult structures and determination of introductory tumor extension and the cost effectiveness depends on expertise of the endoscopist, consequences of false negative results of standard techniques and reimbursement issues. Thank you very much for your kind attention.

pro-oral cholangioscopy

indeterminate biliary strictures

diagnosis and treatment

cholangioscopy techniques

single operator cholangioscopy

interdisciplinary discussions