UEG Journal podcast Episode 12- Advances in GI disease: biomarkers, treatment outcomes, and cost-effectiveness of EUS-GE

00:00:05: Hello and welcome back to UAG Journal Podcast.

00:00:08: You will quick dive into the latest, most impactful research in gastroenterology.

00:00:14: I'm Dr Mohsen Subhanikreni, associate editor of UAG journal And a Gastroenterologist based at Nottingham University Hospital UK.

00:00:31: Today we are going to discuss three fascinating studies recently published in the UAG journal that showcase a remarkable breed of gastroenterology research.

00:00:41: We will move from molecular diagnostic, to inflammatory bowel disease therapeutics and finally have deep dive into health economics and advanced therapeutic endoscopy.

00:00:53: So, let's begin with a study entitled Molecular Traces of Gastric Cancer in saliva from tissue signatures to salivary CLC-VA as potential biomarker.

00:01:05: This study was led by Catarina Lopes and colleagues at the Portuguese Oncology Institute of Porto.

00:01:12: so it is with great pleasure that I'm going introduce you this article.

00:01:16: Henmosen, I have to say that this title immediately cuts one attention.

00:01:20: It combines three things which are very popular in biomedical research right now molecular profiling liquid biopsies and of course early cancer detection

00:01:30: Of course!

00:01:30: And i completely agree... ...and if we translate the title into question.. ..that any clinician can understand it is essentially THIS Can we detect sign-of gastric cancer through saliva?

00:01:45: almost opportunistic, but it is actually addressing a very important and clinically relevant problem.

00:01:52: Exactly!

00:01:53: Gastric cancer remains one of the leading causes of cancer related worldwide And despite advances in endoscopy and pathology we still face this same fundamental challenge.

00:02:03: Patients do much better when disease is diagnosed early.

00:02:08: The difference between early and advanced gastric cancer is dramatic.

00:02:14: The problem is that early gastrocancer is often asymptomatic or associated with very non-specific symptoms.

00:02:21: Many patients simply don't come to medical attention until it's late and cancer has progressed.

00:02:30: And while upper GI endoscopy is an excellent agnostic tool, It isn't exactly something people won't care for every year.

00:02:37: as we know

00:02:39: I have yet to meet someone who says, you know that would make my weekend better.

00:02:44: a screen and gastroscopy.

00:02:45: So are quite right Manuela?

00:02:47: Exactly.

00:02:48: Endoscopy is invasive resource intensive and difficult to implement as population-wide screening strategy especially in countries where gastric cancer incidence is lower than East Asia.

00:03:00: so far years of research has been looking for biomarker that could help identify these individuals who are at risk for gastric cancer in early stages.

00:03:11: And what I liked about this study is that investigations didn't take shortcuts, they started with

00:03:18: biology."

00:03:19: Yes!

00:03:19: That's true.

00:03:20: rather than beginning with saliva... They first asked the fundamental question… What molecular changes occur in early gastric cancers and preconceivers lesions?

00:03:29: To answer it, they used RNA sequencing on tissue samples spanning the spectrum from normal mucosa to dysplasia and early adenocastrinoma.

00:03:39: And that is important because if you're looking for a biomarker, first need understand what signal your actually trying to detect?

00:03:47: The team performed transcriptomic analysis and combined those data with machine learning approaches to identify genes that consistently differentiate disease tissue.

00:04:01: And that's one thing that impressed me.

00:04:03: Machine learning has become something of a buzzword in biomedical research, and Hindi-studied investigators did use machine learning to refine a biologically plausible signature but also then test whether the signature held up in independent cohorts.

00:04:19: Yes!

00:04:20: That was very rigorous approach.

00:04:22: The result was six gene signatures.

00:04:25: Important point is that together these genes created a molecular fingerprint associated with early gastric cancer diagnosis.

00:04:33: And the remarkably accurate one, The model achieved an area under the curve of zero point ninety six.

00:04:40: and Of course whenever I see a number like that my first reaction is usually caution.

00:04:45: And mine too because we all have seen biomarker studies That perform beautifully in discovery data sets but In real life it tell us different story

00:04:56: Exactly, but here the investigators validated this signature in an independent cohort and still observed excellent performance.

00:05:04: And of course that gives much greater confidence than they are indeed identifying a genuine biological sign.

00:05:11: For condition listening an AUC half point nine six mean that model was extremely good at distinguishing lesion tissue from a normal tissue, not perfect but approaching the level where one starts thinking about potential clinical translation.

00:05:26: One aspect of this study that received less attention which I found very interesting was analysis of metachronous gastric lesions.

00:05:36: Yes these are new lesions developed after first lesion has already been removed and clinically they

00:05:45: Exactly.

00:05:46: And many patients undergo successful endoscopy, resection and then inter-surveillance program.

00:05:51: but not all patient carry the same risk of developing future lesions.

00:05:56: Yet, surveilling strategies are often relatively uniform

00:06:01: Which means some patient may be over surveyed while other might benefit from more intense follow up.

00:06:08: The authors explored whether molecular information could help refine risk prediction and personalize a surveillance program.

00:06:16: And even though the predictive performance wasn't as strong for diagnosis, The area under the curve was still around zero point seventy-four.

00:06:25: So Manila Dasmin is potentially still very useful particularly because risk prediction is generally more difficult than diagnosis.

00:06:33: Predicting future is much harder then identifying what that has already happened.

00:06:39: Yes, and with that we arrive at what is probably the most exciting part of this paper.

00:06:45: This live analysis!

00:07:08: Fair point, Manuela.

00:07:09: But biologically there's increasing evidence that tumors release molecular cargos into circulation fragments of RNA protein exocellular vesicles.

00:07:19: these can travel through the body and potentially become detectable in various biological fluids.

00:07:25: Interestingly among the six genes only one consistently showed alter expression in saliva And That was CLC-VA.

00:07:35: In a way, I found that reassuring.

00:07:37: sometimes studies claim That every signal discovered in the tissue magically appears in blood.

00:07:43: saliva are urine and probably morning coffee.

00:07:46: But biology is rarely that cooperative.

00:07:49: The fact can only one marker survived?

00:07:52: the transition from Tissue to saliva actually make finding more believable.

00:07:58: And when CLC-VV was combined with agent sex The model achieved an area under the curve of approximately zero point seventy-eight.

00:08:09: Still not enough to replace the endoscopy, but I would say this does hold some promise for future.

00:08:15: Absolutely!

00:08:16: Nobody should walk away thinking that saliva testing is ready to replace gastroscopy.

00:08:21: But it does suggest noninvasive molecular screening may be feasible.

00:08:26: and thats exciting part Because if eventually we develop reliable saliva-based tools, then this could be used to identify individuals who should go endoscopic evaluation afterwards.

00:08:40: Yes that's true!

00:08:41: Moving into the strengths one major strength of this study was design.

00:08:45: they combine discovery validation and risk prediction in a single model And then translated it into biomarker in saliva.

00:08:53: That I would say is comprehensive methodology.

00:08:57: Yes, I agree.

00:08:57: And another strength is that investigators combine molecular biology with clinical questions.

00:09:03: They weren't just cataloging genes.

00:09:06: they were asking how these findings might eventually help patients.

00:09:11: On the other hand saliva finding.

00:09:13: so when exploratory independent validation will be essential before clinical application.

00:09:18: and as exciting as SLC five A-five appears, a single promising biomarker is not the same thing as evaluated diagnostic test.

00:09:29: So Mohsen what would you say is key message from this study?

00:09:33: I'd say authors identify a robust six gene panel that's associated with early gastric cancer and precancer lesion And among those genes SLC Five A-Five emerged as potential useful saliva biomarkers.

00:09:48: but one precaution We still have this test coming up.

00:09:53: There is some distance for these to be validated into real-life practice, so we just have to watch the space and look more validation study in a new future.

00:10:02: At moment I would say that you should continue with endoscopy.

00:10:06: Yes of course.

00:10:07: So now that we've gone through it let's move from cancer biomarkers to inflammatory bowel disease.

00:10:14: Our second paper is entitled real-world effectiveness and safety of opacity lab in Crohn's disease insights from the NADL registry.

00:10:22: This study was led by Marisa Iborro, together with investigators from more than forty Spanish centers participating in NADR

00:10:30: registry.".

00:10:31: And this study that many clinician have probably been waiting for how well does Opacitinab work for Crohnís disease?

00:10:38: patient everyday clinical practice?

00:10:41: And that's a very important distinction because by the time drug reaches our clinic, we have usually already seen randomized controlled trials.

00:10:50: But what often we don't know is how the drug performs in real-world setting?

00:10:55: Exactly!

00:10:56: Clinical trials are essential – they're gold standard for establishing efficacy and safety of drugs but also carefully controlled environment.

00:11:06: Patients are selected according to strict inclusion criteria visit occur according to predefined schedules, so what we need is more real-world data especially on these important medications.

00:11:18: Yeah let's be honest the patients we see in an busy mandate clinic are not always identical to the patients enrolled in pivotal trials.

00:11:26: unfortunately

00:11:28: I would say that even close the real world tend.

00:11:32: Messier patients have failed multiple therapies.

00:11:34: They had surgeries, they have accidental gestinal manifestation comorbidities and other complicating co-existent comorbilities.

00:11:43: That's what the real world evidence is also very valuable.

00:11:47: Yes before discussing this study itself let us take a step back.

00:11:51: Why has there been so much interest in Uppala city new?

00:11:54: Opalacetany belongs to the family of genuskinase inhibitors or jaginibiters and unlike biological therapies that target extracellular molecules, Jaginibitors work inside immune cells by interrupting senoling pathways involved in inflammation.

00:12:10: I would say one thing that immediately stood out for me while treating this study was steady population.

00:12:16: these were not biologically naive patients.

00:12:19: In fact they are already exposed other treatments.

00:12:22: Yes, that's true not at all.

00:12:24: In fact in ninety-eight percent of patients had already received prior GTNF therapy and nearly sixty percent have received three or more advanced therapies.

00:12:33: In other words if you want to design difficult to treat cohort You would probably end up with something very similar towards the others included here.

00:12:42: That is exactly right.

00:12:43: these patient has already traveled a long therapeutic journey.

00:12:47: And what did they investigations?

00:12:49: Maya can tell us Manila?

00:12:51: Yeah, so here the investigators followed three hundred patients.

00:12:56: Most patients were treated for active luminal Crohn's disease although the cohort also included patient-treated for extranetestinal manifestations and smaller groups receiving combination therapy.

00:13:06: Here disease activity was assessed using several complementary measures clinical symptoms where evaluated using the RV retro index.

00:13:15: inflammation Was monitored?

00:13:16: Using C reactive protein in fecal coprotectin and endoscopic outcomes were assessed where never follow-up endoscopy was available.

00:13:25: Which reflects the real world practice, not every patient undergoes protocolized endoscopies at fixed time.

00:13:31: so Maniola can you highlight some of other important findings?

00:13:35: Yeah!

00:13:36: So let's start with the headline.

00:13:38: finding corticosteroid free clinical remission was achieved in approximately sixty percent patients at weeks twelve twenty four and fifty two And I found that remarkably reassuring, not just because the remission rates were high but also means stable over time.

00:13:56: That is an important point.

00:13:57: sometimes IBD therapeutics show impressive induction results then gradually being off and patients often struggle to get durable long-term control.

00:14:08: Yes and durability really what we as physicians care about.

00:14:13: Achieving remission is wonderful staying in a remission even better!

00:14:17: When aspect I particularly appreciated was the emphasis on objective inflammatory markers.

00:14:23: We are increasingly moving away from reliable, solely-on symptoms so that is very important.

00:14:29: Because symptom don't always tell whole story.

00:14:32: patient can feel despite having ongoing inflammation and vice versa.

00:14:37: In this study CRP normalization increase from sixty four percent at week twelve to seventy four percent a week.

00:14:44: fifty two Fecal coprotectin normalization improved from forty-eight percent to sixty four percents.

00:14:51: There are encouraging findings because they suggest that UpaCityNAP was not simply improving symptom, it also reducing underlying inflammatory activity.

00:15:01: And now let's talk about endoscopy as we know that mucosal healing remains one of our key therapeutic goals.

00:15:07: Followup in the oscopy wasn't of course a failure for everyone as this is a real-world registry, but among patients with paradevaluations nearly half demonstrated endoscopic improvements and sixteen percent achieved endoscopical remission.

00:15:23: And while at first glance some listeners may think that sixteen per cent sounds modest, context mirrors —and here we are talking about exceptionally treatment experienced population— these were not patients at the beginning of their disease score.

00:15:37: so sixty percent remains a very decent, I would say percentage.

00:15:43: Exactly!

00:15:43: A completely agree patient who achieved clinical admission at week twelve performed more likely to remain in remission at week fifty-two.

00:15:51: the odds ratio was greater than eight

00:15:54: and that's a powerful message because it leaves clinicians a practical decision point

00:15:59: an unlike many predicted biomarker It does require complex boilable retestings based on patients actual response.

00:16:08: Yes, and another aspect we are discussing is extraintestinal manifestations because as you all know, Crohn's disease isn't just an extraintesinal disorder.

00:16:17: And here in this study many patients add joint symptoms, skin manifestations, eye involvement... ...and also other inflammatory complications that we now really impact their quality of life.

00:16:29: The patient treated primarily for extraintestein manifestation achieved partly higher mission rates & excellent treatment persistence.

00:16:37: Yes, and these findings of course reinforce the idea that check inhibitors may be effective beyond DIN testing itself.

00:16:45: And of course whenever we discuss checked inhibitors safety inevitably enters a conversation.

00:16:52: In this cohort adverse events occurred in approximately twelve percent Of the patient.

00:16:56: most were infections or dermatological.

00:16:59: even The safety provided was largely consistent with what has been observed previously in clinical trials.

00:17:07: But of course, this study also has limitations.

00:17:09: First there is no control group and the scopic assessments weren't standardized And treatment decisions remained at description Of individual physicians.

00:17:19: And for me The key message that could pass into the lab Demonstrated meaningful durable and effectively high response rate in otherwise refractive Crohn disease population.

00:17:31: Yes!

00:17:31: And perhaps even more important Is that highly responsive week twelve emerged as a strong predictor of long-term success, a finding that clinicians can potentially use tomorrow morning in practice.

00:17:45: And speaking of practical decision making our final paper asks the question that health care systems around world are increasingly asking not just whether treatment work but also weather.

00:17:58: it provides value

00:17:59: and over final paper today will be And if we

00:18:18: translate that title into everyday language, the question is surprisingly simple.

00:18:23: When treating malignant gastric outlet obstruction as a newer endoscopic approach actually worth money

00:18:31: And that's the question we are hearing more and more often in medicine, not only does it works but also is it worth using resources to deliver?

00:18:41: Exactly.

00:18:41: I think this study highlights something becoming increasingly important in gastroenterology.

00:18:46: We now have remarkable technologies but healthcare systems have finite resources so clinical effectiveness and economic effectiveness are increasingly intertwined.

00:18:56: Let's start with the clinical context.

00:18:58: Malignant gastric outlet obstruction is one of the most distressing complications of advanced upper-gm lignancies, particularly pancreatic cancer.

00:19:08: Yes patients often develop persistent nausea vomiting early society and an inability to tolerate oral intake.

00:19:16: And beyond physical symptoms there are also profound psychological burden.

00:19:21: Food, as we know is such a central part of our daily life that losing the ability to eat normally can have huge impacts on quality-of-life for patients and family.

00:19:31: Historically treatment options include antler feeding and surgical gastrogenostomies.

00:19:38: Antler stents are relatively straightforward to place and patient often move quickly but downside is that reinvention rates are very high.

00:19:47: Yes, Mohsen.

00:19:48: On the other hand surgical gastrogeostomy sits at the other end of the spectrum.

00:19:54: It is generally durable and effective but surgery comes with its own costs risks And of course a recovery period.

00:20:03: Exactly over the last several years we have seen emergence.

00:20:07: EUS guided gastrogenosomies Technique essentially creates a bypass around obstruction using a lumen-opposing metal stent, also called lamps which is endoscopic ultrasound guided.

00:20:22: Before discussing the economic analysis it is worth remembering that this study was built upon the Endurorandomized Trail.

00:20:30: This clinical trail has already demonstrated several important findings patients undergoing EOSG resumed oral intake more rapidly hospital stays were shorter, and outcomes where at least comparable to surgery regarding recurrent obstruction.

00:20:47: So clinically US gastroentrostomy was already looking very attractive.

00:20:53: the question became whether those clinical advantages translated into economic advantages?

00:21:00: The investigators analyzed.

00:21:02: ninety-eight patients enrolled in randomized indoor trial across twelve Dutch hospitals.

00:21:33: Now let's head to the first major finding.

00:21:35: the procedure itself was actually more expensive when performed endoscopically.

00:21:40: The average procedural cost for USGE was approximately four thousand and forty-hundred euros, while for surgery it was about three thousand and four hundred.

00:21:54: so one thousand difference between two

00:21:56: procedures.".

00:21:58: And that's what exactly many economic discussions stop.

00:22:01: but fortunately the investigator didn't stop here.

00:22:04: Once the hospital costs were included, the picture changed dramatically.

00:22:08: Average in-hospital cost was around fifty two hundred after USGE compared to more than ten thousand after surgery.

00:22:17: So it will be almost double for surgery and The primary reason was shorter Hospitalizations.

00:22:24: patients risk recovered faster And returned to oral intake sooner when USGE was applied The more expensive procedure actually resulting in lower overall L-card expenditure.

00:22:37: Of course cost alone is not enough, we also need to know whether patient are doing well or hopefully better.

00:22:44: that's where the quality of life adjusted years are.

00:22:47: quality come into picture for listeners who do not routinely think and quality.

00:22:52: they're essentially a way combining both quantity & quality of Life into single mayor.

00:22:58: this study showed a modest advantage in favor of EUSGE?

00:23:02: Yes,

00:23:03: and another result that really stood out to me was the bootstrapping analysis.

00:23:08: Ninety-nine point.

00:23:09: nine percent of simulations favored USGE In terms of cost And That's an extraordinarily consistent final.

00:23:20: So what would be your take home from this study?

00:23:22: Maniola

00:23:24: US guided gastroenterostomy appears not only to be clinically effective but also economically attractive.

00:23:31: Although the procedure itself costs more, around one thousand year or more.

00:23:37: those costs are more than compensated for shorter hospitalization and lower overall health care use.

00:23:44: And perhaps more broadly This study reminds us that innovation should not be judged only by technical success, but also by the value it delivers to patients and healthcare systems.