Episode 11: Cold Resection, Faster Sedation & Cancer Detection: What’s Changing in Endoscopy?

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

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

00:00:13: I'm Dr Mohsen Subani, trainee-associated editor of UEG journal and Gastroenterologist based at Nottingham UK

00:00:21: And i am Maria Manuel Estevino, trainee associate editor of the UEG JOURNAL AND GASTROENTOLOGIST BASED IN PORTUG PORCHEKOL.

00:00:29: And I'm pleased to say that we're back with the latest episode, with a very special guest and welcome Dr.

00:00:35: Keith Salo, UG Journal Associate Editor & Consultant Gastroenterologist.

00:00:40: Welcome on board Keith.

00:00:42: Oh thank you so much Mohsen and Manuela.

00:00:45: On behalf of UGJournal i want to thank for your wonderful work at doing for UGG Journal podcast.

00:00:51: So thanks for having me here today.

00:00:53: So, let's begin with our first paper which explores an important quality issue when we think about upper GI endoscopy.

00:01:00: That is a variation in post-endoscopy upper gastrointestinal cancer or PUGIC rates across providers in England.

00:01:07: So Keith this is really impactful national study and do you think that could start by explaining what PUGic represents?

00:01:15: And why it has such an important Quality Indicator in our Endoscopy practice?

00:01:20: Sure thanks Manuela!

00:01:22: So, Pujik stands for post-endoscopy upper GI cancer as you said.

00:01:26: This is a really important metric which refers to an upper GI Cancer diagnosed after a previously negative endoscopy typically within the last three years and this is an important patient centered outcome because this impacts the patient and this reflects either a missed cancer or a missed precancerous lesion.

00:01:47: when patients undergo an endoscopic They want to make sure that the examination has been conclusive and we haven't missed any pathology.

00:01:54: This metric measures the quality of their examination.

00:01:58: The truth is, around ten percent of cancers are post-endoscopy And we know that endoscopy can be hugely variable from one endoscopist to another... ...and this could really affect patient outcomes!

00:02:09: From colonoscopy which has its own post-colonoscopy cancer metric We now better the quality using metrics like adenoma detection rate, the lower the post-endoscopy cancer rate.

00:02:23: Thanks Keith.

00:02:24: as you highlighted the variation in uh the cancerate post-underscope across different centers could you please walk us through this study design and tell us how authors compared high versus low performing providers?

00:02:38: So this was a study by my close friends Ume Kanran.

00:02:45: They analyzed data from the UK National Endoscopy Database and they captured nearly three hundred thirty thousand diagnostic OGD procedures, gastroscopy procedures.

00:02:56: The aim to look at units with a best-and worst missed cancer rates so lowest versus highest pugic rates.

00:03:05: To look at differences So that they could direct interventions in target areas for quality improvement.

00:03:11: Units in the UK were ranked into quartiles based on the Puget rates between twenty fifteen and twenty eighteen.

00:03:18: The authors collected service-level data, looked at different factors that could be associated with Pugets.

00:03:27: Wonderful!

00:03:27: And what were the key in the scoping characteristics that are associated to providers who had lowest Pugetic rate skips?

00:03:35: So...the overall Pugete Rate was eight point six percent.

00:03:39: so this meant that eight point five percent of cancers were diagnosed in patients who had a negative gastroscopy in the preceding three years.

00:03:49: In the lowest performing centres, this was as high as ten point three percent of the highest quartile and at best performing centres with the lowest Pujit rates it's down to seven point two percent.

00:04:03: so there is range there and variation from absolute lowest to highest Pujits rate difference about three fold.

00:04:12: When the authors looked at units with a lowest puja rates, which were their absolute best performing unit in the UK They found out they shared distinct features and these included number one more training sessions.

00:04:24: So the best units trained more did more training.

00:04:28: secondly Endoscopists have higher annual endoscopy volumes so over hundred procedures.

00:04:34: A year there was doing more.

00:04:37: Thirdly procedures used intravenous sedation more and these included a combination of medazolam and fentanyl.

00:04:46: Fourth, the biopsy rates were actually lower in higher performing units And then finally In the best-performing units The intensity Of half day sessions Were lower.

00:05:00: So this included A point system that we have uniquely in UK.

00:05:05: so Units with lowest Puget Rates Had Nine or less points per list.

00:05:13: It's important to note that this study did not look at factors such as inspection time, endoscope quality considering

00:05:41: everyday clinical practice.

00:05:44: So units that use more sedation, especially in conjunction with opioids had lower Puget rates and this really makes sense because it's hard to do good endoscopy when the patient is moving or trying to pull out of the scope And good sedation allows the endoscopist take time To look properly?

00:06:03: To clean the mucosa without any pressure!

00:06:06: Some societies actually recommend spending an inspection of seven minutes or more to examine the mucosa and this can be an awfully long time without any sedation.

00:06:18: Regarding biopsies, it's interesting to see that endoscopists in better units took less biopsys but they actually took more targeted biopses when they really mattered for high-risk lesions And I think this reflects practitioners taking on a more targeted approach rather than just a random shotgun approach of better lesion recognition abilities.

00:06:42: for instance, endoscopy as we know now is a really visual sport which should spend more time looking rather than taking biopsies.

00:06:51: Yes that's very interesting Keith and also this study allows us to look for modifiable factors right?

00:06:59: From your perspective, what are the key takeaway messages that we should take from this study?

00:07:05: That will allow us to improve our endoscopy quality and also reduce the amount of missed cancers.

00:07:11: So firstly volume is important.

00:07:13: We need be doing a critical mass of volumes And according to this study it's about one hundred procedures or more per year.

00:07:21: Secondly hospital bookings teams need avoid packing lists with patients so that there is time to perform good quality inspection and minimise fatigue.

00:07:31: Thirdly, training is good for patients.

00:07:34: Training procedures benefit from an extra pair of eyes And probably greater vigilance From the trainer.

00:07:39: It really makes us up our game.

00:07:42: I think units should be a bit more welcoming To trainees.

00:07:45: There should be more focus on optical diagnosis.

00:07:48: Finally we need use that time to inspect more.

00:07:51: Use that time look Clean Photodocument Use near-focus Optical enhancement, perhaps take a second look.

00:07:59: And this is really important to spot pre-cancerous legions like gastriatrophy, barizosophagus or suspicious ulcers.

00:08:06: Don't just take random biopsies but take targeted biopsys and if we're really in doubt bring patients back for a second Look.

00:08:14: overall the lesson here Is that the miscancer?

00:08:17: It's actually a complication of a procedure and Patients need to be consented for this as should be safety netted appropriately.

00:08:25: Excellence of this all highlights the variation in technique, tronic and workload on how it can impact risk-of missing cancer in apogee endoscopy.

00:08:34: And interestingly one key theme here is how endoscopic techniques and approach influence detection & outcome of these procedures.

00:08:44: This brings up to our next paper a randomized front row trial comparing cold vs hot resection techniques for intermediate size cell cell serrated lesions.

00:08:55: So Mohsen, this is a really practical question for our everyday endoscopy.

00:08:59: Could you start by briefly reminding us what makes sessile serrated lesions so important?

00:09:06: Absolutely!

00:09:07: Sessile-serated lesion or we also call them SSLs are not recognized as an important precursor in serrated pathway to colorectal cancer particularly for right sided lesions.

00:09:20: they can be quite subtle often flat pale and indistinct borders, which makes them very difficult to recognize and identify.

00:09:31: And also pulpectomy make it hard in certain cases.

00:09:35: so getting both detection and resection right in these cases is an effective way for future cancer prevention.

00:09:43: Yes, that's true.

00:09:44: And in terms of resection strategy indeed many of us have traditionally learned that these religions should be respected towards OTMR.

00:09:53: so kids could you briefly outline what this trial sets out to compare?

00:09:59: Thanks Manuela!

00:10:00: So we've had lots of randomized trials there compared the section techniques for adenomas but very few for SSLs which makes it really unique.

00:10:07: This was a randomized controlled trial from Taiwan by group called themselves The Takus Working Group and they set out to compare three different techniques from removing intermediate-sized sarsal serrated lesions, so those that measured between ten and twenty millimeters.

00:10:23: The three methods compared were cold snapylopectomy called EMR which is endoscopic mucosal resection and hot EMR.

00:10:32: the primary outcome was complete histological resection And this is defined as having horizontal and vertical resection.

00:10:39: margins are completely clear of tumor.

00:10:42: Other outcomes studied include on-block perception rates, procedure time complications including delayed bleeding and perforation.

00:10:50: Thanks Keith!

00:10:51: So thanks for taking us through the methodology of this trial And authors included actually intermediate size SSLs so roughly between ten up to nineteen millimeters in size.

00:11:03: Would you mind just highlighting some key findings from these trials?

00:11:08: So in total, a hundred and twenty patients were randomized into each of the three groups.

00:11:12: We had about forty patients per group.

00:11:15: The mean polyps size per group was about fourteen millimeters.

00:11:19: Both cold methods were proven to be non-invivier To hot EMR.

00:11:24: They complete histological research.

00:11:25: rates Were about ninety percent for each group.

00:11:29: Cold snare polypectomy resulted In significantly shallower vertical reception depth Compared to Hot EMR or cold EMR.

00:11:38: On average this was about nought point five millimeters clearance for cold snare versus one millimeter clearance for hot snare.

00:11:46: Unsurprisingly, cold snare polypectomy led to lower unblocked reception rates.

00:11:51: This is about seventy percent of the cold snare vs nearly eighty percent for cold EM R and ninety percent for hot EMR.

00:11:58: However, Cold Snare was by far the fastest.

00:12:01: It reduced Polypectomy times by three minutes and total procedure times by ten minutes compared to hot EMR.

00:12:08: I think overall, the study provides strong evidence that supports current guidelines from ESGE that recommend cold resection techniques for intermediate-sized SSLs proving they can avoid risks of thermal injury while maintaining comparable efficacy.

00:12:26: So it

00:12:32: looks like efficacy was quite comparable but safety is where things may differ, right?

00:12:39: Could you please expand on the Safety Outcomes reported in this study Keith.

00:12:43: I think that this study was underpowered to look at safety outcomes considering there were only forty polyps per group.

00:12:51: There are no perforations encountered and there're no differences in immediate or delayed leading between groups.

00:12:57: so these three methods were comparatively are safe as each other.

00:13:02: Great, so from a practical point of view Keith how do you think we should be advising clinicians?

00:13:08: How should the clinician taking findings into account while performing clonoscopy ?

00:13:13: We finally have three-way RCT that supports use cold resection techniques for intermediate sized SSLs.

00:13:21: It shows that the cold snare method is fast and it shaves off up to ten minutes of procedure time but my concern and lower oblock recession rates.

00:13:34: However, before we can conclude that these three methods are the same We need to remember key study limitations.

00:13:40: The fact is this a small study.

00:13:43: There was no follow-up colonoscopy data To look at post polypectomy recurrence rates And it's also unclear whether those results Can be influenced by underwater EMR method which most of us routinely do.

00:14:01: That's really interesting Keith, and do you think there are any particular situations where we would still favor EMR over a cold approach?

00:14:10: Personally for SSLs under ten millimeters I think cold snare will do the job.

00:14:15: For those that larger than ten millimeters i prefer cold EMR And this is supported by this study... ...and I find it more reassuring because the lift better defines the borders And you can be sure that if we remove the polyp in its entirety.

00:14:29: Luckily SSLs are usually softer and more superficial lesions than adenomas, these could be removed without heat.

00:14:36: The only exception for me where I favour hot EMR is when there's a high risk lesion such as in Cessal serrated polyposis syndrome or an SSL with dysplasia.

00:14:50: In this case i prefer on block reception Adenomas.

00:14:53: however they're different beasts.

00:14:55: These are more resistant, they have higher recurrence rates and it's really important that we ensure when we resect them to give them clear horizontal and vertical margins.

00:15:08: We should be opting for Hock EMR in these

00:15:10: cases.".

00:15:11: This all is very interesting and shows how defining endoscopic techniques can meaningfully impact on both safety outcomes how we can optimize colorectal cancer prevention strategies.

00:15:28: Exactly, and that brings up to our next paper which takes a step back and looks at screening approaches more broadly comparing colonoscopy and fecal immunochemical testing with outcomes stratified by age and sex.

00:15:42: This paper takes a broader view of colorector cancer prevention.

00:15:46: this is the post-op analysis of clonoprev study looking at outcome of clonoscopy versus fit testing and stratified by age and sex.

00:15:57: Nila, could you start briefly reminding us of what original study showed?

00:16:02: And why this follow-up analysis is important?

00:16:05: Of course!

00:16:06: So the original colon pref trial was a landmark randomized study comparing a one time screening colonoscopy with biennial fits in average risk individuals aged between fifty and sixty nine.

00:16:19: It showed that fit based screening was non-inferior to colonoscopy in terms of colorectal incidence, cancer incidents and mortality largely because more people participated in fit screening.

00:16:31: And it is important to emphasize this.

00:16:33: what this analysis does Is?

00:16:35: That he doesn't dig deeper asking whether these outcomes differ depending on sex age which is highly relevant as we move towards more personalized training strategies.

00:16:48: Thanks for summarizing it.

00:16:49: So Keith, would you mind walking through the design of this analysis and what specific outcomes authors looked at?

00:16:56: And why they are important?

00:16:58: Of course as you say This was a post hoc analysis of The Coulomb Prep Study which specifically

00:17:04: compared

00:17:05: fit testing versus one-off colonoscopy.

00:17:08: In this trial or in this post hop study that authors looked out the impact of gender and age on patient outcomes The primary outcome was cancer mortality, ten years down the line.

00:17:20: And the secondary outcomes included participation rates and cancer

00:17:23: incidents.".

00:17:24: So Keith as you were highlighting around age and sex.

00:17:29: so their trial included over fifty thousand individuals.

00:17:33: that most age groups are between fifty to fifty nine in the second group between six two sixty-nine.

00:17:39: can you take us through the key finding from

00:17:42: So, at ten years the risk of colorectal cancer for men was one point five percent and women this is one per cent.

00:17:50: The risk of man being affected by post-envolvement cancer was nearly fifty percent higher And because of these men also had higher cancer related mortality rates than woman.

00:18:03: so there's three in a thousand versus one point.

00:18:07: Unsurprisingly, patients in their sixties had higher risk of cancer outcomes than those screened in the fifties.

00:18:13: Overall when matched by age and gender screening with two-yearly fit testing was not inferior to a one off colonoscopy.

00:18:21: it's worth noting that the colonoscopy group found more polyps but this did not change tenure mortality

00:18:30: Okay!

00:18:30: And one of most striking aspects we have here is consistency.

00:18:36: Mohsen, what does the study tell us about how effective these screening strategies are across different demographic groups?

00:18:44: So interestingly Manuela that both strategies performed similarly regardless of age or sex.

00:18:51: The reduction in colorectal cancer incidence and mortality were consistent across all groups suggesting that overall effectiveness of screening doesn't really depend on this factors.

00:19:03: However, there were still important baseline differences.

00:19:06: Men and older individuals had higher cancer incidence mortality And that was despite screening.

00:19:13: so screening perhaps helps but does not completely eliminate underlying risk differences.

00:19:19: Yes then participation is a key part of this story as well Of course.

00:19:23: So kids?

00:19:24: what did the study show about uptake of screening between fit and colonoscopy?

00:19:31: I have to say that the participation in this study and the compliance of screening was quite limited.

00:19:38: So, this was about forty percent for fit testing... ...and thirty-two percent for colonoscopy And the participation were slightly lower in men.. ..and these where their population with a higher risk of cancer & high immortality.

00:19:55: Of course there are protective effects on colorectal cancer.

00:19:58: screenings can only apply to people who turn up.

00:20:28: Yes, that's completely right.

00:20:29: So when we look to our real-world practice effectiveness isn't just about test performance but whether people do engage or not with screening.

00:20:38: Keith how should these findings influence?

00:20:40: are we design our personalized screenings programs?

00:20:44: That is an important question because the engagement rate here is much lower than other countries.

00:20:50: The highest we see in Finland was around eighty percent for fit and the Verna apps include UK and Netherlands with bowel cancer screening compliance of just over seventy percent.

00:21:00: For the US, which is primarily colonoscopy based this level was about two-thirds.

00:21:05: so these countries are doing a great job!

00:21:08: Of note Sweden uses different fit thresholds for men and women.

00:21:12: The threshold there for Men is eighty and then forty for Women.

00:21:16: I think the Fit Threshold used in this trial as about fifteen for comparison And These improve concordance with testing.

00:21:24: For a bowel cancer screening program to succeed, you need the really well-oiled team.

00:21:29: There needs be a centralized programme of mailing and in this era texts emails... ...and possibly even social media notifications.

00:21:36: Patients need to understand why they need The test so that They can actually adhere To them or recognise the importance of going off turning up.

00:21:46: So education is really important.

00:21:47: Reminders help as our endorsements from GPs and personalized human contact for non-responders?

00:21:55: Absolutely, so what this study suggests?

00:21:58: that we don't have to perhaps in this age group personalize the screening strategies just based on ages sex but probably need to look into other factors.

00:22:08: And maybe we need to learn from other nations where the screening program is performing better regarding adherence to both like screening program and there was also a lot of learning from latest vaccination programs.

00:22:23: So overall, this other wing force is the message that both colonoscopy and feet are effective but their success depends on how they're implemented at the population level.

00:22:33: And ultimately improving uptake may be just as important as improving our technique.

00:22:40: With these we'll move onto final paper.

00:22:43: Now turn to sedation something that underpins almost every endoscopic procedure we do.

00:22:49: So this study is a multi-center randomized controlled trial comparing remu mesolin with midazolin for diagnostic hypergastrointestinal endoscopy.

00:22:59: so Mohsen could you start by briefly explaining us what makes remu mezzolin different from the sedatives?

00:23:05: We are more familiar

00:23:07: with?

00:23:07: absolutely, so remu memezol is relatively new but an ultra short acting benzodiazepine Like medazolam, it works on GABA receptor but has much shorter half-life and is rapidly metabolized by tissue astrosis.

00:23:22: This essentially means faster onset & fast recovery which makes it an attractive option for procedural sedation particularly in endoscopy where efficacy and turnovers are really important.

00:23:35: And kids could you all go through the design of this trial

00:23:39: please?

00:23:39: Sure So this trial involved seven endoscopy centers in South Korea.

00:23:43: They randomized patients undergoing routine gastroscopy to either medazolam or remimasolam.

00:23:49: Patients were eligible if they were fit, so ASA score of one-to-two.

00:23:53: If they were young—so between nineteen and sixty And had a BMI between eighteen point five and thirty —they were excluded... ...if needed anything more complicated done….

00:24:03: …so therapeutic endoscopies Or if there was any significant liver kidney or respiratory comorbidity.

00:24:09: Patients received loading doses of either drug, and that's five milligrams for Mimazolam.

00:24:15: And two milligrams from Medazolamb... ...and had regular top-ups every two minutes until they were moderately sedated using an MOAA score or three or less.

00:24:24: You can lift it up on the paper.

00:24:26: The primary outcome was total procedure time.

00:24:29: So this is a time from first sedation dose to discharge.

00:24:33: Other outcomes they looked at included Time to maximal sedation Adverse events and patient satisfaction.

00:24:40: Yes,

00:24:41: thank you Keith!

00:24:42: And what were the main findings?

00:24:45: So sixty-six patients were involved into each group.

00:24:48: The average dose of Ramimazlam was seven point five milligrams... ...and for Medazlam it was five milligrams.

00:24:55: Ramimazzlam was a clear winner here.

00:24:57: It significantly reduced total procedure time compared to Medazalam dropping the average time from forty eight point five minutes to thirty point three minutes.

00:25:06: Patients who had family meslam achieved not only a deeper level of sedation, but they got to it faster too.

00:25:12: So then they've got steeper sedation within three minutes compared six minutes for medazolam and They also recovered faster.

00:25:20: patients receiving very mazalan required less top-up doses And twenty percent were adequately sedated with just the initial loading doses Whereas almost all patients in the midasalam group needed atop up dose.

00:25:32: So in practical terms, patient was sedated more quickly and were ready to leave sooner which has clear implication for endoscopy practice and day-to-day capacity management.

00:25:44: What about safety, Keith?

00:25:45: Was there any concerns around safety

00:25:47: so that they will know significant differences in adverse events?

00:25:51: but there were provisional signals In terms of lower hypertension rates Lower rates of bradycardia in the Remy Mazalan group And this is quite surprising considering that they were sedated at a deeper level.

00:26:06: So, we are potentially gaining efficacy without compromising safety and that's very important?

00:26:12: Correct!

00:26:13: And patient experience is also an important aspect here right so Keith what did the study report in terms of patient satisfaction.

00:26:22: I've always said being awake during endoscopy is overrated... ...and patients have more ideas to thank me for being asleep than being awake.

00:26:31: Overall, patients on Venomazolam were more likely to report a positive patient experience.

00:26:37: That's very interesting!

00:26:38: The patient reported higher satisfaction but that probably as you highlighted Keith shows the fact there is deeper sedation compared with average sedation we used.

00:26:47: How do think this would impact both quick recovery and possible smoother sedation overall?

00:26:55: I think having drug which allows patients recover faster it great.

00:27:00: having a smoother sedation profile where patients have better comfort is also great and allows endoscopists to do more thorough job.

00:27:10: Yeah, so taking this all together how will you see that Remy Maiseland will fit into our routine clinical practice in the coming years?

00:27:19: I think we're privileged to have this trial on our journal And data for Remy Maslamm is really promising.

00:27:26: but i'll have to heed caution here!

00:27:30: in patients with comorbidity, when the meslam doesn't rely on a liver for metabolism compared to metasalam.

00:27:37: So it should be theoretically safer for patients with liver disease.

00:27:41: so we might even be an advantage of procedures like ERCP or various bleeding related procedures.

00:27:48: and important limitation here is that the patient's hair were all healthy And also patients didn't have fentanyl co-administration which pretty much my practice.

00:27:58: there was a cost implication in the UK where madzlam is about fifteen times more expensive, but this could be offset by a faster turnaround time.

00:28:06: For midazlam users like me ,this study has quite eye-opening and number of ways.

00:28:11: Midazlam takes three minutes to start working And six minutes for maximum effect.

00:28:17: So we need give it some work.

00:28:19: The average dose of medazlam needed was five milligrams But this range from two milligrams to twelve milligrams which means that insufficient amounts of sedation to our patients.

00:28:31: And bringing us back whole circle, the first study we talked about.

00:28:36: adequate sedation is really vital for high quality endoscopy and this includes giving it a right dose, time-to work perhaps even selecting the right sedative.

00:28:48: Wonderful.

00:28:49: So this study really highlights how even small changes in sedation strategy can have a meaningful impact, right?

00:28:56: And as the demand for endoscopy continues to grow these kind of innovations could become increasingly important.

00:29:03: Thank you very much Keith for this excellent overview of these articles.

00:29:09: so let's wrap up todays episode.

00:29:11: In this episode we've explored how variation and endoscope practice can influence cancer detection How evolving a resection technique can improve safety and how innovation and sedation may enhance both efficacy and patient experience.

00:29:26: Together, these studies highlight the common theme that incremental improvement in how we perform everyday endoscopy can translate into meaningful gains for patients.

00:29:38: Thank you to our guest again For sharing his insight And thank you all for listening.

00:29:44: Stay tuned for more science from UAG German.

00:29:47: Join us next time on UG General Photocast as we continue to bring you the latest and most impactful research in gastrointotology.