Episode 5: UEG Journal September Spotlight

00:00:06: Hello and welcome back to UAG Journal Podcast.

00:00:09: I'm Mohsin Subani, trainee editor at UAG Journal and a hepatologist based at Nottingham University Hospitals.

00:00:17: And I'm Maria Manuel Estrinho, trainee editor at the UAG Journal and gastroenterologist based in Porto,

00:00:23: Portugal.

00:00:24: Today we are excited to have with us Dr.

00:00:28: Juno Kehan, senior author of an important new study published in UAG Journal, the PESVIC trial.

00:00:35: which looked at pancreatic cyst and how we should think about their surveillance.

00:00:40: Juna, thank you very much for joining us and I will be grateful if you can quickly introduce yourself.

00:00:46: Thank you.

00:00:46: Thank you for having me, for inviting me.

00:00:49: Yes, my name is Juna Kahen.

00:00:50: I'm a gastroenterologist working in the Netherlands in the Osmos Medical Center in Rotterdam.

00:00:56: And my great passion is pancreatic cancer surveillance, especially focusing on pancreatic cyst surveillance for the last decade already.

00:01:06: So that's my position.

00:01:08: Wonderful, so now we are going to move to the paper.

00:01:12: We all know that pancreatic cancer is one of the deadliest cancers, with a five-year survival of just thirteen percent.

00:01:20: Hennises and pancreas are mostly discovered by chance, and because some of them progress to cancer, patients often undergo years of repeated imaging and checkups.

00:01:30: But this comes with anxiety, cause, and strain to the old care systems.

00:01:35: And that's where your study comes up to you.

00:01:38: Can you briefly explain what the Pacific Trail sets out to answer?

00:01:42: Yes, the Pacific cohort study started in guidelines were formulated because we were very much aware that these were not so much evidence-based guidelines as, in fact, you can see them as expert opinions, and we were very much interested in what the actual yield would be of pancreatic cisterines as it was suggested in these guidelines.

00:02:11: So we started to set out to assemble a large cohort and follow these individuals, thousands of individuals, for more than a decade.

00:02:21: to find some answers in that and we try to keep it a low threshold for everybody to participate.

00:02:27: and in fact we succeeded in a sense that we now have already fifty participating centres and we are almost including our three thousand patients.

00:02:39: so we're working on it but still we're assembling as much data as we can.

00:02:44: Excellent, you know that sounds very exciting.

00:02:48: Is it possible if you can highlight the key findings from your study?

00:02:52: Yes, of course.

00:02:53: The final analysis of the Pacific study has not been done yet, because we had to wait for more and larger cohorts, longer follow-up time.

00:03:02: But in fact, we are planning at first.

00:03:05: true actual interim analysis this year because we feel that the momentum is there and we cannot wait longer because of course if you wait longer you get more better quality data.

00:03:15: but we're actually caught up about.

00:03:18: we're already in a position where we feel that there's a lot of.

00:03:24: evidence pointing to the direction that we are doing too much and that we should adapt the guidelines accordingly.

00:03:32: And the study you are referring to, Mohsen, was just published in the European UIG Journal.

00:03:40: It's a study by one of our PhD students.

00:03:44: who already has done her PhD now, Iris Leving, thanks to her.

00:03:49: We analyzed a subgroup of low risk sys, actually.

00:03:54: A lot of people are focusing to identify high risk sys, but this is very difficult.

00:03:59: And we soon realized that focusing on the other side of the coin, of the very large group of very low risk sys, we may be able to stratify easier in this side of the group of patients, individuals with cysts.

00:04:16: So for this study, we looked at people with cysts that did not have any worsen features at baseline.

00:04:24: And for those who were at least two years follow up, we analyzed and looked at the lowest risk cysts compared to the high risk cysts.

00:04:33: So we looked at small cysts, smaller than one and a half centimeters, and those who remain stable in a sense that they do not grow over two and a half millimeters each year.

00:04:46: And the amazing finding, which, well, wasn't that surprising, but still it's quite shocking that those who are small and stable actually do not have an increased risk if you compare them to the general population.

00:05:00: Wonderful.

00:05:01: So if I understand correctly, your study suggests that these trivial things that you have just described might not need such like an aggressive surveillance, right?

00:05:11: Yes, right.

00:05:12: I mean, if you look at it this way, there's no use in surveillance.

00:05:17: And actually, you say not as aggressive as we're doing today.

00:05:21: In fact, you can also look at it the other way around and say that we even find an argument for cessation of surveillance.

00:05:28: That's good, Juna.

00:05:30: So from a practical point of view, as a physician, I work closely with this patient in HPB medicine.

00:05:38: Does it depend upon the type of cyst whether this is like IPMN or side branch IPM or any other side of like benign cyst?

00:05:47: Yeah,

00:05:48: of course, the problem is we want to stratify.

00:05:51: We want to stratify those who are at lowest risk and those who are at highest risk and to make a prediction of the risks involved.

00:06:01: And that's difficult, but now we know that very small cysts who are stable are reassuring and that we may loosen our head.

00:06:11: let them go free from surveillance.

00:06:15: And then on the other side you have the highest risk.

00:06:18: Sis which we also still have difficulty identifying.

00:06:22: but of course we still need to try and whether these are IPMS or not.

00:06:27: that's also a problem with small sis because we always.

00:06:31: talk of small cysts assuming that they are IPMNs but in fact we don't know that for sure.

00:06:36: there's a large percentage of cysts that are surveyed that in fact are probably not IPMNs but just unspecified cyst congenital cysts that don't even have a risk of malignant progression at all.

00:06:51: but it's difficult because we cannot identify those.

00:06:56: So yes the problem is that How can we identify those cysts that are risky?

00:07:02: Do you think that there are any biomarkers that we can use in our clinical practice?

00:07:06: Yes, I mean we have to continue to improve our prediction of ways to identify high risk cysts and there are actually I think two ways to go.

00:07:18: first biomarker.

00:07:20: identification is important, we have not yet established a reliable biomarker so far and in my personal opinion is that from blood.

00:07:28: it will be difficult but probably the most promising biomarker source is pancreatic juice which we are collecting in fact because it's close to the cells from which the IPMN originates so likely it will contain information.

00:07:46: about the origin of the cyst but also the grade of dysplasia because in the ideal world you would identify not so much pancreatic cancer but the stages prior to it.

00:07:58: so high grade dysplasia is actually our most wanted target to identify and so biomarker research should be a major focus which we are doing.

00:08:10: and the second of course is artificial intelligence.

00:08:13: so to have imaging being assisted by artificial intelligence, both MRCP and US is also a promising field.

00:08:24: So, Junne, thank you so much for guiding us through these important findings.

00:08:29: It is indeed a very interesting study, and I think it has very importance to our everyday clinical practice.

00:08:35: And also to our listeners, please stay tuned as we dive into the next paper.

00:08:40: Excellent.

00:08:41: Manila, I think that was a great discussion with you.

00:08:44: So let's keep the discussion out around the pancreas, but this is more exciting.

00:08:49: We're going to talk about pancreatic enzyme replacement.

00:08:52: But in this case, how this can help with diarrhea in Crohn's disease.

00:08:56: And I think that's quite close to your heart as well, one of your specialty.

00:09:00: So

00:09:01: we're going to take on our next study, which is looking into use of apencratic enzyme replacement treatment in the patient with Crohn disease who suffer with the long-term diarrhea.

00:09:11: Exactly, Mohsen.

00:09:13: And that's where the second article comes in.

00:09:15: This looks at exclusive internal nutrition or EEN, which is often used in Crohn's disease.

00:09:21: While it can really help with disease control, many patients struggle because of a side effect we don't often talk about that is diarrhea.

00:09:29: That's very right Manola and this study was published in UEG Journal recently by Ken at All and colleagues and they explored whether pancreatic enzymes replacement therapy called PERT for short could actually improve this until nutrition-related diarrhea and adult with moderate to severe Crohn's disease.

00:09:48: Yes, and these researchers ran a randomized clinical trial with one hundred forty seven patients.

00:09:54: Everyone was on biologics plus six in weeks of exclusive internal nutrition.

00:10:00: But here's the key.

00:10:00: Eighty six developed diarrhea from the nutrition therapy and they were split into two groups.

00:10:07: One got perked, including forty three patients and the other forty three did not.

00:10:13: And the results were pretty interesting.

00:10:15: Those who go on pancreatic enzyme replacement therapy had a big reduction in daily bowel movements compared to one who didn't.

00:10:24: And their reduction in bowel frequency was as low as below five per day.

00:10:29: And that stayed stable over sixteen weeks.

00:10:32: Yes, and it wasn't just about the numbers.

00:10:34: Patients on pancreatic enzyme replacement therapy also reported a much better quality of life with improvements in both anxiety and depression scores.

00:10:44: And meanwhile, those who had diarrhea but did not get that replacement had much poorer clinical outcomes and higher dropout rates.

00:10:55: So, taking on your point, Manila, adding per... actually didn't change the endoscopic result within both groups but did show the clinical improvement in the symptom and quality of life.

00:11:09: Yes, and that really matters in real life because if patients cannot tolerate exclusive internal nutrition due to side effects, they will stop and then we will lose all the potential benefits of combining this nutrition with biologics and other advanced therapies.

00:11:25: So is it fair to say that adding pancreatic design replacement therapy in patients with Crohn disease who are on exclusive anti-nutrition can improve their symptoms and also their quality of life.

00:11:37: Yeah, completely.

00:11:39: And it's a good reminder that sometimes small supportive strategies can make a big difference in treatment success and in this case greatly improve patient adherence and of course their clinical outcomes in the end.

00:11:51: And now we will dive into new study from team in Colmar, France, led by Dr.

00:11:56: Bernard Dennis and colleagues at Pasteur Hospital.

00:11:59: They investigated how to better treat H. pylori.

00:12:02: And as we know, the H. pylori is the leading cause of gastric cancer worldwide.

00:12:08: Yes, so in France and almost everywhere, most doctors treat H. pylori infections empirically, meaning that we prescribe antibiotics without testing whether the bacteria are resistant first.

00:12:20: Yes, like shooting in the dark and hoping you hit the target and that is clinically not ideal and also in the era when we're seeing the rising resistance to a different form of antibiotics.

00:12:34: Exactly, Mohsen, and that's exactly where this study comes in.

00:12:37: These teams systematically tested patients before giving them first-line treatment.

00:12:42: They looked at PCR, histology and culture.

00:12:45: And interestingly, PCR turned out to be the winner here.

00:12:49: It had almost perfect sensitivity of ninety nine point seven percent and much superior to histology are cultures.

00:12:57: Yes, and plus PCR could quickly detect claritromycin resistance which was present in about twenty three percent of the cases and also level fluxes in resistance was pretty high nearly nineteen percent.

00:13:12: That's indeed a lot of resistance to antibiotics and important clinically.

00:13:17: But here is the cool part.

00:13:18: When treatment were guided by these susceptibility tests, the eradication rates were very high.

00:13:25: The triple therapy based on amoxicillin, chlidromycin had a ninety-eight percent success rate and amoxicillin, levofloxin and other combination could reach as high as a hundred percent eradication.

00:13:37: Yes, and in this French cohort, business protocol therapy over ten days had an eradication rate of eighty-one point three percent.

00:13:46: This is not a little lower than the ninety-five percent that was reported, for example, in the HPE Registry where that covers over twenty thousand patients across Europe.

00:13:58: And in this registry, the eradication rate with this regimen was around ninety to ninety-five percent.

00:14:05: So this is something that really kept my eye while reading this study.

00:14:09: Yes, this study shows that is the real world French practice.

00:14:13: Empirical cordial treatment may deliver only eighty percent success below the ideal of ninety percent threshold.

00:14:20: Probably the main message here for me is that optimizing adherence, single capsule regimen, as well as the setting as like checking for resistance is important when we're looking for complete eradication from Alecuberta pylori.

00:14:35: And in this case, I think this study set the merits.

00:14:38: And interestingly, the study also showed that PCR guided approach was more cost effective, about thirty nine percent cheaper compared to relying on immunosubchemistry, which doesn't even tell you that the bug is resistant.

00:14:52: So I would say it's right to pass on the message to colleagues that prior to starting any treatment for etymology, testing the susceptibility based on PCR could change their education and improve the cure rate.

00:15:07: Yes, exactly.

00:15:08: The message from this study is clear.

00:15:10: In regions where eye resistance rates are likely, for example, in France, susceptibility-guided therapy should move from the exception, probably, if possible, to standard practice.

00:15:21: So we should always aim to tailor the antibiotics so that we will be able to cure my patients, avoid unnecessary drugs, endoscopies, and of course, even save money.

00:15:31: So, so far this protocol has been very exciting.

00:15:34: We'll be discussing about pancreas and also H. pylori and leading cause of gastric cancer.

00:15:39: Now, let's move on to liver ducts and me being a hepatologist quite keen about this article.

00:15:45: This study was done in Milan where Dr.

00:15:47: Di Amico and colleagues at San Rafael Hospital teamed up with the international network to explore what happened when inflammatory bowel disease comes hand in hand with the PSC.

00:15:59: So, Mohsen, we all know IBD is already at a frithe.

00:16:03: Crohn's oral sororative colitis can seriously affect quality of life.

00:16:07: But what happens if you add PSE into the mix?

00:16:11: Well, according to this study, almost over four hundred thousand patients from two thousand three to two twenty twenty three things actually get on a rough ride.

00:16:22: After carefully matching patient with IBD alone to those with both IBD and PSC, researchers found PSCs increases the risk of both mortality and morbidity in this cohort.

00:16:34: Yeah, right.

00:16:35: The composite outcomes that included that hospitalizations or colactomy was reached by fifty-four percent of patients with both IBD and PSC compared to forty-two percent in IBD alone.

00:16:49: And this is a thirty-two percent higher risk.

00:16:52: That's very frightening.

00:16:53: Actually, mortality was almost as high as seventy percent if you had PSC in addition to IBD and hospitalization strikingly in rows by a third.

00:17:04: Yeah, that's true, Mohsen.

00:17:05: But interestingly, colactomy rates were not very different between groups, and perianal surgeries were actually lower in chronic disease patients with PSE.

00:17:15: So, I believe that PSE does not necessarily make the gut surgery worse.

00:17:20: That's true, but overall survival was clearly poorer.

00:17:24: In ulcerative colitis with PSC, nearly seventeen percent died over the falloff compared to just under nine percent in ulcerative colitis alone.

00:17:33: In Crohn's with PSC, the difference was even sharper, seventeen percent versus eight percent.

00:17:39: That's pretty stark.

00:17:40: So the takeaway here is that PSC is not just a bystander.

00:17:44: It meaningfully worsens prognosis in diabetes patients.

00:17:49: Exactly.

00:17:49: It highlights the need for closer monitoring, possible more aggressive.

00:17:53: treatment and regular cancer surveillance since PSC is linked to high risk of colorectal and bile duct cancers.

00:18:01: So it really likes that.

00:18:02: PSC is like the uninvited guest that appears in the party.

00:18:07: No one wants him to be really there.

00:18:09: Yes, definitely not the guest you want hanging around.

00:18:13: Absolutely not.

00:18:14: So there you have it.

00:18:15: PSC in IBD is just not a side note.

00:18:17: It significantly raises the stakes, increasing mortality and hospitalization risks.

00:18:23: And these authors conclude that patients with both conditions should be followed with extra care, guided by tailored strategies and of course with strict surveillance.

00:18:32: Great, thank you very much listener for Stengas with this exciting episode.

00:18:37: Please stay tuned and don't forget to subscribe, share and like our podcast and stay up to date with the latest advancement in the field of GI research.

00:18:48: Thank you very much.