Episode 10: UEG Journal March Spotlight

00:00:06: Hello and welcome back to UEG Journal.

00:00:08: Portocost, your quick dive into the latest and most impactful research in gastroenterology.

00:00:14: I am Dr.

00:00:15: Mohsen Subani trainee-associated editor with UEG journal And a Gastroenterologist based at Nottingham University Hospitals UK for the latest episode with a very special guest and we're pleased to welcome Dr.

00:00:38: Yusuko Maida, she is Associate Editor with UG Journal & Consultant Color Actile Surgeon at Queen Elizabeth University Hospital Glasgow.

00:00:48: Welcome on board Yasuko.

00:00:50: Thank you for having me today.

00:00:51: I'm looking forward to discussing paper with her.

00:00:54: Thanks Yasuko.

00:00:55: would like tell more about yourself?

00:00:58: Sure, so as a correct or surgeon my specialty is IBD surgery and particularly proctology.

00:01:06: So things we're going to be discussing today like perianophysiola hemorrhoid pylonoidal disease.

00:01:12: those are my specialities.

00:01:15: And I also do general surgery which includes emergency surgery.

00:01:19: Excellent, so you're the best person.

00:01:20: So today we'll be talking about the first article which is Talking About Otologous Adipose Tissue Injection in Treatment for Alunol Pouch Related Fistula.

00:01:30: Just to start with this study was actually evaluated by a patient.

00:01:37: pouch-related fistula would benefit from adipose, otologous adiposte tissue injections.

00:01:43: So we'll be discussing this in detail with our guest and hopefully will get some insights for the audience.

00:01:49: Exactly!

00:01:50: In this study investigators included twenty one patients with ileal pouch anal and osmosis and twenty nine fistulas.

00:01:57: Adipose tissue was harvested by a patient via small liposuction procedure.

00:02:06: Patients who did not achieve healing after the first injection could then undergo repeated treatment and follow-up period was around sixteen months.

00:02:15: Before coming to results, I would like ask you Yasuko Do you manage pouch complications regularly in your sociological practice right?

00:02:23: And from your perspective how significant is a problem of pouch related fistula and how challenging are they to treat with current approaches?

00:02:32: Thank you.

00:02:33: So yes, I do manage some pouch complications and it's not only limited to fistulae.

00:02:40: It could be stenosis chronic pouchitis or functional problems such as evacuation difficulties Or incontinence.

00:02:49: so there are a number of issues but here we're talking about pouch-related fistula.

00:02:55: So, in general any perianal fistula involving the sphincter muscles is challenging to manage and fistulas associated with senile or pouch are probably among most complex.

00:03:06: This because we often refer simply a pouch but every pouch is unique It's configuration.

00:03:13: most of them are these days J-shape but still the lens off the J, the anastomosis.

00:03:20: The cufflence how it is positioned whether there means entries at top or back and sometimes changes over time.

00:03:28: we now see a quite voluminous pouch over here because probably stretches.

00:03:34: I think Some patients may initially have been diagnosed with indeterminate colitis or even ulcerative colitis, which later proves to be Crohn's disease was ongoing inflammation and it becomes difficult to keep sepsis at bay.

00:03:49: So the first thing to do when managing any sort of pouch fistular or a sepses relating to is to drain it.

00:03:59: And we manage by making an incision or inserting acetone.

00:04:05: Ceton is a thread or vascular tape you may have seen, used to keep the tract open just to ensure drainage.

00:04:11: But after that we can think about definitive treatment.

00:04:14: and I think nearly all of the treatments use for idiopathic fistula.

00:04:18: so sort-of general or standard fistula has also been dried from powder related fistula.

00:04:25: some often include things like Fibring blue, advancement flap, fistula plogs, video scope laser and many other options.

00:04:35: I think really the main challenge is whether for idiopathic or pouch-related fistula it's the sphincter involvement.

00:04:42: The most definitive cure of any fistula is to lay the tract open but dividing the sphincter risks in continents.

00:04:49: So while preserving sphyncto function, we must ensure adequate drainage and somehow eradicate the

00:04:55: fistulae.".

00:04:55: And that is central difficulty with this treatment.

00:05:00: Excellent introduction!

00:05:01: Yasuko.

00:05:02: so for audience.

00:05:03: autologous adipose tissues contain mesenchymal stem cells and regenerative factors that may sport healing.

00:05:10: So from surgical, biological endpoint what do you think about the rationale behind using this in this clinical context?

00:05:19: Because of challenges I mentioned earlier also considering anatomical space which we operate.

00:05:25: so treatment is inherently difficult for these conditions.

00:05:29: For example even a normal anal canal internal anal sphincter is only few millimeters thick and then the space between internal and external sphincter is just a few millimeters more.

00:05:41: So we're there for working within an extremely confined space, And in addition fish to attract often fibrosis or still has some inflavations which are very difficult to handle as tissues.

00:05:54: so from surgical perspective I think any treatment that's meaningfully improved symptom is welcome.

00:06:02: If I may add another surgical point, fat injection has been used for a range of indications and many people are familiar with its role in cosmetic surgery for tissue bulking.

00:06:12: But it is also known to soften scar tissue.

00:06:15: so whether this benefit arises from misenchymals themselves that isn't the fact issue or from regenerative or gross factors Is unclear.

00:06:24: but surgical experience over many years suggests that fat grafting can be beneficial.

00:06:29: In terms of the underlying science i do not think the mechanism has been fully elucidated.

00:06:36: as you mentioned some have proposed a regenerative effect.

00:06:39: however evidence from many fields not limited to fish treatment shows that regeneration does not occur automatically.

00:06:47: it requires specific biological conditioning such as oxygen level or nutrients.

00:06:53: So for that reason, maybe overly optimistic to assume that injected fat cells simply grow into sphincter muscle and mucosa?

00:07:04: I think a more plausible explanation is a paracrine effect whereby process fat contains not only mesenchymal cell cells but also growth factors and other bioactive components that may promote healing or stimulate local cells.

00:07:19: We're still quite far from understanding exactly what triggers the successful response.

00:07:26: Thank you for this explanation, Iazuku.

00:07:28: And well the reported dealing rates are quite promising especially when repeated injections are allowed.

00:07:35: and how do you believe that these results compare with other treatments we currently use for pouch-related fistula?

00:07:42: For example sitans advancement flops or revisional pouch surgery?

00:07:48: Sure, so am.

00:07:49: acetone is a temporalizing option.

00:07:52: it allows to drain sepsis and in some complex cases where the fish is deep enough amenable definitive treatment.

00:07:59: It may be only way control infection or recurrent infections at least.

00:08:04: however this definitely not a curative approach.

00:08:07: An advancement flap is essentially a technique in which small sort of part of mucosa or rectal wall is mobilized to cover the interlopening, so you stretch tissue to cover whole.

00:08:20: And this can be effective but when the rectum inflamed and that's often case with pouch related or other IBD associated fistula procedure may not be feasible And for example in a pouch with stenosis is the physical narrowing so it's not really accessible to raise a flap.

00:08:37: now how?

00:08:38: revision is another potential option but it isn't major operation.

00:08:44: And given that fistula formation often stems from chronic inflammation, advancing or revising the pouch may not prevent recurrence.

00:08:52: In addition re-operation on a pouch is technically demanding because it lies deep within the pelvis and is frequently surrounded by dense scarring which is often not feasible in the context of fistula an ongoing infection.

00:09:08: As far

00:09:10: as I understand, this is minimally invasive and sphincter-preserving treatment.

00:09:15: So in your opinion which patient would have maximum benefit from it?

00:09:21: And can you highlight any of the characteristics related to fistula when we identify a patient for these treatments?

00:09:28: First and foremost i think the fistula that could be considered for this treatment needs.

00:09:35: What it means is that, it must be adequately drained and there's no ongoing severe infection or active inflammation.

00:09:42: And the tract should probably well-established because when with this procedure you inject sort of a column of fat around the fish to attract then you have to close the opening so don't want any residual brewing infections within them.

00:10:00: And then also in order to close that hole or internal opening the mucosa must be healthy and so this is the most optimal curative scenario.

00:10:11: On the other hand from discussion i have had with the authors group I think technique can use dinner in a sort of palliative context meaning just focusing on symptom control.

00:10:21: So put patient was persistent discharge or severe scarring for multiple previous operations, you know, these scarring could be associated with quite significant pain.

00:10:31: So softening this probiotic tissue or reducing inflammation through fat injection may alleviate some of the symptoms and make the condition more manageable.

00:10:40: it May also be considered as a last resort option for patients who wish to avoid proctectomy removing anus completely.

00:10:51: Many of these individuals have experienced multiple septic episodes and repeated operation, maybe facing the prospect of removing everything altogether.

00:11:01: And some are however keen to preserve it.

00:11:05: in such circumstances I think this approach can be offered as a final attempt.

00:11:12: there's really not many alternatives at this stage

00:11:16: Yes, and of course this study was still a relatively small cohort so we need to take that into account.

00:11:24: And from the research perspective what would you like to see next?

00:11:27: Do think it should go to larger trials comparative studies or perhaps integrate these with other therapies for example?

00:11:36: What do you think?

00:11:38: So I think your raise is an interesting point.

00:11:41: You know, although this treatment along with other stem cell based therapies for fistula has been available for decades.

00:11:47: It is only relatively recently that it has been investigated consistently by the same group of hosts across both idiopathic and iberid related fistula And I understand that they have a large clinical trial in the pipeline.

00:12:01: Uh, and as we gain a clearer understanding of the underlying mechanism there may be opportunities to develop combined treatment approaches such as biologics but i think We just don't know at this stage.

00:12:13: That's great.

00:12:14: So finally Yasuko has a handling editor and from your clinical practice What do you think are key?

00:12:20: take home for our gastroenterologist?

00:12:23: When you dealt with study what was the key strengths that came out?

00:12:27: I think there are many positives out of this study, although as you mentioned it is a small pilot's study.

00:12:33: The simplicity of otologous fat grafting is quite appealing particularly when compared with commercial allogeneic stem cell therapies which are prohibitively expensive.

00:12:44: I think they also say experience in delivering this treatment and report their data quite openly.

00:12:48: It's a small study, but i think that they've been honest with all the outcome And i think... That is particular strengths of this nature.

00:12:59: We should watch the space for long-term outcomes and hopefully further basic science studies to elucidate the underlying mechanism.

00:13:06: Excellent, that's great Yasukun Thank you very much for your insight.

00:13:10: So let us move on our second paper titled Ten-year follow up after a nine six week treatment with Pagylator interferon plus tenor four in hepatitis D or delta.

00:13:20: This was hidden to study by Anika rank at all as we all know that chronic hepatitis d remain the most severe form of viral hepatitis.

00:13:29: until recently treatment options have been quite limited with Pagellated interferon alpha historically being The man Treatment available.

00:13:37: however long term impact of this treatment are less explored and this study provides important insight in the long-term follow up of this cohort.

00:13:46: Exactly, these studies are a long term followup analysis offered by IDITS to randomized clinical trial.

00:13:53: In the original trial patients with chronic hepatitis delta received ninety six weeks of pagylated infernal alpha two A either in combination with tenophobia deproxial fumarate or with placebo.

00:14:06: For this analysis, the authors followed patients who had completed treatment and at least one follow-up visit in total.

00:14:14: One hundred and seven patients were included with fifty-one receiving combination therapy and fifty six receiving infran alone.

00:14:22: Patients were then followed for a mean of around eight point four years, allowing the initiators to assess long-term outcomes such as apathetic decompensation, epitocellular carcinoma liver transplantation or liver related death.

00:14:38: So what did they find?

00:14:39: So overall about twenty four percent patient developed at least one liver related clinical endpoint during their follow up duration.

00:14:47: but importantly risk was significantly lower.

00:14:50: in combination treatment group.

00:14:52: Patient treated with Pagylated Interferon plus Tenono Fever had liver-related even in fourteen percent of cases compared to thirty four percent single interferon related treatment.

00:15:04: The study also showed that virological response mattered greatly.

00:15:08: patient who achieved undetectable RNA or loss of hepatitis B surface antigen has significantly better long term outcomes.

00:15:19: additionally Factors such as older age, cirrhosis and higher baseline mark for liver disease were associated with worse clinical outcomes.

00:15:29: Yes!

00:15:29: And another interesting observation was that HDV RNA decline during therapy and control of HPV replication also appeared to influence long-term prognoses.

00:15:39: So even though in front-based therapy does not achieve sustained responses in all patients, those who do achieve a logical suppression seem to gain meaningful long term clinical benefits.

00:15:52: What does this mean for clinical practice?

00:15:54: Firstly the study reinforces that virological response in hepatitis delta is clinically meaningful and it translates into fewer liver related complication over time.

00:16:05: secondly suggests combining Interfront-based treatment with tenoverphyr may improve long term outcome, even if the short term viral garylapse occurs.

00:16:14: And finally these findings highlight the importance of early treatments and long term monitoring in patients with hepatitis delta related infection especially those with advanced liver disease.

00:16:25: And as new therapies for Hepatitis Delta such as entry inhibitors or other antiviral approaches continue to emerge Studies like these provide an important benchmark for long-term outcomes and also do help us to understand what meaningful treatment success really looks like.

00:16:43: Absolutely, a decade of follow up data is rare in this type of research and provides valuable guidance we move towards more effective treatments near future.

00:16:55: Yes, thanks Mohsen.

00:16:56: So now let's move to our next paper titled five-year experience of nationwide implementation of colorectal cancer screening in Sweden which was published in the UAJ Journal recently.

00:17:09: and this study This paper evaluates the first five years of implementing this nationwide population-based colorectal cancer screening program across Sweden.

00:17:21: And rather than a clinical trial, these is indeed real world implementation study and allows us to understand how screening programs perform at national

00:17:30: level.".

00:17:31: Exactly!

00:17:32: In terms of methods individual between age of sixty to seventy four years were invited participate through mail invitation that included A fecal immunochemical test are called FIT tests.

00:17:44: This test detect occult blood in the stool which can indicate colorectal cancer or advanced adenoma including few other differential diagnosis.

00:17:53: between twenty nineteen and twenty-twenty two over eight hundred thousand individuals were invited those with positive fit tests for effort for clonoscopy an outcome recorded in centralized national screening and colonoscopic registry.

00:18:06: The investigator assessed participant rates test positivity, clonoscopy adherence diagnostic yield and quality indicators.

00:18:15: And so what did they find?

00:18:16: Overall participation was about sixty-four percent which is quite strong for a population based training program.

00:18:23: this participation was slightly higher among women and older individuals and somewhat lower in regions with lower population density.

00:18:32: Defeat positivity rate was two point seven percent and of souls with a positive test around eighty-two percent then underwent colonoscopy.

00:18:42: And when we looked at diagnostic yield the results are clinically meaningful.

00:18:46: among those who underwent clonoscopy after a positive fit, colorectal cancer was detected in about six point six per cent.

00:18:54: advanced nuoplasm including advanced adenoma and cancer was found.

00:18:58: nearly thirty percent of cases among these positively detected patients.

00:19:04: The adenomal detection rate was close to fifty-percent which reflects strong clonoscopy performance, quality indicators were reshoring as well, adequate bowel proportion around ninety eight per cent a procedure and high secal intubation rates are relatively low.

00:19:17: complication rates

00:19:19: Yes!

00:19:19: And in terms of limitations we need take them into account.

00:19:23: This analysis reflects early implementation and some regions were still scaling up in the program.

00:19:30: We can see here that colonoscopy adherence, while good did not reach ideal targets and varied by sex and region.

00:19:37: Also importantly this study does NOT provide long-term outcomes such as state shift or mortality reduction.

00:19:45: And of course part of the study period overlapped with a COVID-IX pandemic which may also have influenced participation patterns.

00:19:53: So what are the implications of a clinical practice?

00:19:56: First, this study demonstrated that a nationwide fit-based colorectal cancer screening program is feasible and effective in routine care.

00:20:04: And I'm aware UK there's lots such data which they're looking to cut off And that would be interesting to look at.

00:20:11: Second, it highlights the high-quality clonoscopy infrastructure which is essential for such screening programmes.

00:20:17: and third, it underscores importance of addressing disparities in participation and follow up to maximise population level benefit.

00:20:26: Yes overall Sweden's first five years provide an important benchmark for countries planning or refining their national colorectal cancer screening programs, showing that real-world implementation at scale can indeed achieve strong participation and also a very meaningful diagnostic yield.

00:20:45: And as long term data emerge we will better understand the full impact on colorexal cancer incident and mortality.

00:20:53: So, that's all for today's episode.

00:20:55: Thank you all for listening to us and we will see you next time... ...for another deep drive into emerging research in gastroenterology published in your favorite journal.