So, as we all know, overall non-virus helper GI bleeding mortality has ranged between 1 and 11 percent over the past 10 years, about 5 percent or so now. Hemostasis, as you know, is only reserved for high-risk lesions with a classification that was initially developed for ulcer bleeding. And those include patients with active bleeding, spurting, and oozing, although you may have seen recent data and literature questioning validity as to whether oozing is indeed a high-risk lesion or not in most cases. Other lesions include non-bleeding visible vessels and the adherent clots. I remind you that for the adherent clots, you can use just a PPI, or you can go ahead and use a PPI preceded by endoscopic hemostasis. PPIs are to be considered an adjuvant to successful endoscopic hemostasis. One of the issues that remains a very timely one, pardon the pun, is endoscopy within 24 hours. This is still the current recommendation for patients, although some groups have suggested performing endoscopy earlier, particularly in sicker patients. What I hope to do over the next 12, 15 minutes or so is to go over some of these issues with you. We'll review the relevant evidence as it has emerged over the last couple of years. And where I can, I'll try and share with you some of the recommendations from the prestigious international non-variceal upper GI bleeding clinical practice guidelines group that used the GRADE methodology to grade the evidence and to weight the recommendations. So briefly, it's not really hemostasis, but it's important to emphasize the timing of endoscopy. And this is a very sobering study that was published a couple of years ago where you see the infamous U-shaped mortality curve. And this is to remind everyone that in patients who are humanically unstable with a high ASA score, you can actually harm them if you go ahead and proceed with endoscopic hemostasis or even just endoscopy early on, within 6 to 12 hours or so. So you need to keep that in mind. And indeed, when the non-variceal GI bleeding international committee looked at this, we recommended 24 hours and remained at 24 hours. We could not get to a recommendation as to an earlier endoscopy timing for patients at high risk. So keep that in mind at this point in time. Another interesting area that has emerged is that of endoscopic Doppler probe and its use in bleeding ulcer lesions. It's useful not only in predicting who should be having endoscopic hemostasis, but also predicting the outcome of the endoscopic hemostatic methods that you've used and whether you should continue or consider it a success. Dean Jensen looked at that in a cohort study and actually showed that it was better than a forced classification in predicting re-bleeding, but perhaps more importantly, actually did a randomized trial that showed that using the endoscopic Doppler probe in the context of ulcer bleeding results in decreased re-bleeding subsequently for patients. There's actually also been recently cost-effectiveness modeling that supports its use. Despite this, unfortunately, we still have limited data, and there was a lot of discussion with the consensus guidelines committee, but we felt that we did not have enough data at this point in time to recommend such a huge change in practice, but my prediction is that if people can actually get to use the endoscopic Doppler probe, it is probably a way to improve the management of endoscopic hemostasis, so something to keep in mind in time. Now, if we go ahead and talk about endoscopic hemostatic therapy specifically, I remind you that when you provide injection, it's not what you inject, but how much you inject that makes a difference. With regards to thermal methods, you have non-contact and contact methods that both have been shown to be helpful, either alone or in combination. My personal preference, and if you tease the literature out, you'll see that when you have nasty bleeders, high-risk bleeders, we recommend contact thermal coagulation, where you try and obliterate the lumen of the arteriole running in the ulcer bed, and you have the post-endoscopic hemostasis depression that you can see here. And finally, endoscopic clips. They come in all shapes and sizes, as you know, and different delivery methods. They're useful to be used either alone or in combination. Ideally, if you're going to do injection, you should first clip and then do injection. The key point is to know how to use them and to be able to make sure that the person who's assisting you when you're doing the bleeding also knows how to use them. And that may mean you need to coach them with some key words before you start the procedure if you're dealing with excess support people who don't know how to use them at night or after hours, for example. So a reminder that what is the best endoscopic hemostatic modality? That I cannot tell you, but what I can tell you is which is the worst. Unfortunately, it's injection alone, the easiest, injection of epinephrine. It's better than doing nothing, but it's inferior to all the other methods. So the recommendations actually remain that if you want to go and do endoscopic hemostasis, you should consider doing a thermal method alone, a clip method alone, or a combination of either with epinephrine injection. And finally, I remind you, routine second look endoscopy is not indicated as a routine procedure, but can be reserved for patients at particular high risk because of the lesion, location, size of lesion, or if you're concerned that you didn't do as good a job as you would like to, which is absolutely fair to come back at a later time. With regards to the endoscopic therapy, so the International Consensus Guidelines Group looked at this and tried to update some of the recommendations and came to the following conclusions. So for patients with acute bleeding ulcer with high risk stigmata, we recommend endoscopic therapy with thermal coagulation or sclerosant injection. We didn't discuss sclerosant. It's not used much in Western countries, but there are good data to support it. This was a strong recommendation based on low to moderate quality evidence. In addition, with regards to endoscopic therapy, they recommend through-the-scope clips, which was based on conditional recommendation, based on very low quality evidence. So the picture there has not changed, really, compared to what we know of before, and surprisingly few new data in this important area. Now, another modality that's been looked at, interestingly, with quite a bit of good support of evidence in the literature, although it was not tackled by any recommendation by the group, was use of hemostatic forceps with soft-mode coagulation. Indeed, it's been shown to be superior to injection with conventional thermal coagulation, either alone or with injection. It's non-inferior to injection when compared to the APC, and both was either non-inferior or superior to clips in two other randomized trials, something that you may want to consider along the way. Now, the nucleotide block for the United States, available over the past year even though it's been available for probably four, four-and-a-half, five years in various areas of the world, are the hemostatic powders. And I show you here an example in malignant bleeding of the use of the hemo spray. So TC325 powder or hemo spray adsorbs the water, concentrates blood cells and cloning factors, and forms a mechanical tamponade to terminate bleeding, and I emphasized to you, at the active bleeding site. It only works if there's active bleeding. You cannot use it in non-actively bleeding lesions. The evidence there is not bad, however, you need to know when to use it, and the limitation of it is in peptic ulcer bleeding, and the problem of it is its residency time. So there's a bunch of publications on this, over 80, including three randomized trials, thousands of patients treated for various indications used both as primary, adjunct, or rescue therapy. The take-home message is I think it's one of the best endoscopic hemostatic methods that you have to provide immediate hemostasis, and certainly in Canada, we have it on the cart, because we know that if the tip of the catheter and the powder can reach the bleeding lesion, chances are you will stop that bleeding. The problem is the residency time. We've done a number of studies looking at this, and through second-look endoscopy cohort studies, we find that the powder only remains on the bleeding lesion site 12 to 24 hours, which of course is not enough for ulcery bleeding, which you know extends beyond that, much beyond that, 72 hours, and even more with patients on antiplatelet agents. So this is why the randomized trial data, looking at the hemo spray, showed the following. Initial hemostasis, very good initial hemostatic rates of stopping the bleeding, as I told you before, but the problem is re-bleeding up to 30 percent. So if you're going to use it in peptic ulcer bleeding, you need to use a second modality in addition to the hemo spray, either at the same setting or at second-look endoscopy. There are a number of other randomized trials that have looked at hemo spray, suggesting non-inferiority versus CLPS for varying indications, and there are two randomized trials, one completed, one ongoing, that suggest that it may be promising in malignant bleeding, which is a difficult area for us to treat, so something to keep in mind. Finally, there are cost-effectiveness data that have been looked at and suggesting that it is helpful if used with another modality, but again, not in the context of peptic ulcer bleeding. The endoclot is another slightly different chemical compound, but also a hemostatic powder on which there are much fewer data available in literature, as you see here with two ongoing randomized trials in this. So the recommendation from the International Consensus Guidelines Group with regards to the use of TC325 or hemo spray will be that in patients with actively bleeding ulcers, we suggest using TC325 or hemo spray as a temporizing therapy to stop bleeding when conventional endoscopic therapies are not available or fail. It's very helpful in this context. However, suggested against using it as a single therapeutic strategy when dealing with patients who are talking here about active bleeding ulcers, not other lesions, versus conventional endoscopic therapy, which is the gamut of the techniques I've talked to you about before. Let's move on. Before I finish, let's talk about refractory lesions, predictors of re-bleeding. In this case, include hemodynamic instability of the patient, spurting or oozing, large ulcers, and the ulcers, as James Lau says, that live in areas where you have big arteries that have names in textbooks. So be aware of that. The posterior adrenal ulcer is one, and higher and lesser curvature of the stomach is the other. The recommendations, if re-bleeding, is to repeat endoscopy with the endoscopic modalities that we've previously discussed. And in select patients, you may want to consider transarterial embolization, and much more rarely surgery today, depending on what available resources you have at your practicing institution. So there's an interesting study I want to share with you from James Lau out of Hong Kong that actually looked at prophylactic embolization, prophylactic, post-endoscopic hemostatic therapy. This is a large study of 241 patients where he compared standard endoscopic hemostasis versus that usual hemostasis we do, followed by prophylactic angiographic embolization. He included patients that are very high risk for re-bleeding, large ulcers over two centimeters in size, spurting bleeding, hypotensive shock, or hemoglobin under nine grams per deciliter. And looking at endoscopy versus the endoscopy followed by the prophylactic embolization, unfortunately there was no difference in 30-day re-bleeding or re-intervention or death, but a post-hoc analysis suggested that embolization did reduce recurrent bleeding, but only in patients who had large ulcers. Interestingly, although this study is underpowered, I think it highlights the fact that there is room for improvement in peptic ulcer bleeding on the current management that we have at this point in time. Of course, another method would be the over-the-scope clip. You may have seen the very nicely done randomized trial published in Gastroenterology. So briefly, they randomized, and these are patients who are at high risk of re-bleeding, who had re-bleeding, recurrent peptic ulcer bleeding in 66 patients. When they had re-bleeding, these patients were randomized to either hemostasis with the over-the-scope clip versus standard therapy. And there was a difference in primary endpoint favoring the over-the-scope clip with regards to further bleeding that you can see here, 15 versus 57 percent. There were no differences in any of the secondary endpoints. There are usual other endpoints, mortality, surgery, embolization, hospital stay transfusions, complications. However, this is interesting. It's still preliminary. The guidelines consensus group felt that this was not enough to recommend a change in practice at this point in time because there are very limited data, but certainly highlights an additional modality that you may want to consider in select refractory patients. Before I finish, just in a qualitative way, I just want to mention a couple of other methods of endoscopic hemostasis. This would be radiofrequency ablation that has been reported in a number of areas, but including GAVE. I think Greg mentioned it as well. Cryotherapy, again, also a little bit recommended for a number of areas, but published in randomized trial data in GAVE. And finally, endoscopic suturing, where there's a small cohort of, I think, 10 patients where they used it in bleeding ulcers with some success, but no recommendation that we can do. So just a little bit of further information as to emerging potentially beneficial modalities of endoscopic hemostasis. So in finishing, concluding, a few practice pearls with regards to upper GI endoscopic hemostasis. First of all, let's remember the basics. Adequate resuscitation before anything else, especially in high-risk patients. Remember that U-shaped curve I showed you. Do not perform injection or adrenaline alone. We recommend thermal or eclipsalone or in combination with adrenaline. Consider using the hemostatic forceps with self-coagulation if you have some experience in it in other areas, as you see perhaps in ESD. Understand indications and limitations of the hemospray powder, which should not be used alone for ulcer bleeding. In refractory patients, repeat endoscopic approaches are indicated, and some high-risk patients with ulcer-free bleeding may benefit from over-the-scope CLIP. But finally, and I usually conclude this way, but I think it is important that we remind ourselves, despite all the beautiful videos we see here, that you should only perform procedures that you're comfortable doing in the appropriate clinical setting with adequate Thank you very much for your attention.

endoscopic hemostasis

upper gastrointestinal bleeding

endoscopy timing

hemostatic methods

refractory lesions