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All right. So our first speaker, um I'm really happy he was able to join us. Um We did um fellowship at the same program, but we were passing ships in the night, not in the same years. Um Abu N Awal, but everyone calls him a that uh that knows him. Um did his fellowship at the Zucker North Well School of Medicine and then did interventional pulmonology um in Chicago at the Prisk School of Medicine. Um And it's been very cool seeing his uh very quick rise up um within the North organization uh where he's now the the head of IP for the entire 23 hospital system um which is uh very impressive. Um And he does a lot of work with chest. So we get to hang out um teaching ultrasound pretty often at the national conference at the headquarters. Um But he's very, very active um with the um Interventional Pulmonology Association, the American Association of Bronchology and Interventional Pulmonology, associate editor of chest pulmonary editor of uh respiratory medicine, and chief editor of the Bronchology uh podcast. Um And you've been traveling around the world teaching. Um And I'm really excited to learn what you're gonna teach us today. So, thank you so much, thank you on and uh for the kind words, of course. But uh it's especially satisfying for me to come back because all the journey, actually, I did residency at Mom Medical Center a little south of here. So it all started in New Jersey. So it all, it is very satisfying to come back and, you know, talk about a topic that is very dear and near to my heart. But uh something that we have seen significant advances in in the last uh 3 to 5 years as the field of intervention, pulmonology progresses, I do not have any conflicts of interest for this talk itself. So what we're gonna cover today is, you know, as we know, interventional pulmonology is a field that is rapidly expanding and it's hard to sometimes keep track of all the new technologies that is coming in with our support from industry as well as you know, the amazing clinical and research work that uh my colleagues are doing. Our focus today is gonna talk about how cryotherapy has helped us in these advances in terms of technology and how we have integrated cryotherapy, both in terms of diagnosis, as well as management of, you know, diseases of the lungs. So our topic is gonna talk about rigid bronchoscopy in terms of rigid bronchoscopy and the role of cryotherapy, both for cryo debulking, as well as cryos spray for benign as well as malignant diseases. We're gonna briefly at the end, talk about the role of cryotherapy in thorough disease, a very niche topic, but something that I do not wanna forget about. But I think the most relevant one is the role of cryotherapy in the diagnosis of lung disorders. And this includes diagnosis of peripheral nodules as well as diagnosis of diffuse pharyngal lung disease, which we're gonna talk about in terms of navigation, bronchoscopy, how we can integrate cryotherapy with the robotic systems or your or the older navigation systems as well as what we called EBUS guided cryobiopsy or using cryotherapy to actually, you know, get core biopsies of the lymph node itself. And this is gonna be, you know, summarized in terms of overall how it has added the diagnostic yield and now it's putting it as far with, you know, surgical techniques. So just a brief overview of the body bronchoscopy for the audience who are not used to or haven't seen the body bronchoscopy in their practice, you know, it was launched in 2017 to 2018. Now, there are three robotic systems in the market. I've had the luxury of having all three and using all three and they're all amazing. But what it entails is that it has allowed us to go from where we are with the regular bronchoscope all the way to the periphery, right? So you have increased reach and while we have an increased reach, you can see that you have increased vision, you can actually visualize where you're going and then to get to the periphery. One of our limitations was when we are doing blind navigation bronchoscopy, you think you are there, but you don't really know. And this has allowed us to reach to the periphery, visualize when you reach to the periphery and have precise control, that's a dollar bill over there. And we are navigating out of body bronchoscope. You can see how precise we can be because some of these nodules which are extremely small, it could be a millimeter or five millimeter difference in terms of getting a diagnosis or not getting a diagnosis. And especially in the future as we talk about ablation, you know, that precision is extremely important. And so there we could see that the body bronchoscopy has allowed us to reach the periphery, allow us to have vision and allows us to have control. And this was 2017 to 18 and now we have 2024. And so what has changed? And so now what we have is combining with robotic bronchoscopy, we have what we call digital tomography or tool and lesion or some centers have con ct. So once we get to the lesion, if you can't see the le lesion in real time, but there is no end bronchial component or the lung lesion is not visible, there was still that limitation that you are still relying on this virtual green ball that we have all seen in a navigation bronchoscopy. And so we have these newer systems depending upon the system you have, you can a cone beam CT which provides a high level cone beam spin or we use this galaxy system where it allows you to use your C arm to visualize the lesion. And you can see we saw the lesion, we do a spin, we confirm where we are, we then create a virtual target. And then we know that we are in the lesion itself. And we do what is called a tooling lesion tomography, meaning that the, the once the needle is in the lesion, we'll do a spin confirm that we are actually in the lesion which is akin to a CT guided or image guided biopsy and then move on from there. But the real question always is has that transferred into clinical benefit, right? So why is that relevant? Because when electromagnetic navigation BCAA became out in 2006, we were all thought that this is the next best thing. But when David did a study back in 2016, the choir study, we realized that while we think we are very good at it, the diagnostic yield was anywhere between 60 to 70%. And that is not what we aim for when we are competing with CT guided biopsies that have a diagnostic yield of 90%. So the next question is has robotic bronchoscopy then translated into an increased diagnostic yield. What they had done one of the first studies, a multicenter study out of, you know, of Chicago and a few other centers in the Midwest that had demonstrated a conservative yield of 73%. With the first generation robotic bronchoscopy. We had done a study at University of Chicago when I was a fellow over there a few years ago, uh we had demonstrated an 80% yield. So definitely an improvement in yield. Uh but still, you know, falling short of that 90% diagnostic yield with the newer system that we have, we have been able to get close to that 90% yield. But there are few issues that still remain and that's where the role of cryobiopsy come in. You know, because whenever I try to do a biopsy and I ask my rose pathologist, hey, do you have the lesion? And then I tell them, oh, I'm in the lesion, they're like, Doctor Gerald, your tube may be in the lesion, but your lesion is not in the to unfortunately. Right. So that is the problem and that's where the role of cryobiopsy may come in because not all is about getting to the lesion. Our radiology colleagues have a core biopsy technique so they can actually cut a piece, but we may not be able to do that and that becomes even more relevant because anyone who has the navigation bronchoscopy when you get the concentric lesion, it's the happiest day, right? Your fellows are happy. You're happy you take a forcep, you do a needle, you get a nice piece. But when you have that eccentric view, now, you actually don't know if your forcep is actually going into that lesion or not. Or you know, if you're one of us who's trying to do ground glass nodules or apart solid nodules and you have no radio you and if you don't have any imaging, now it's hard to get those uh you know, those nodules biopsied. And even if you have imaging, you see on the right side bottom over there, you can actually see the lesions. Sometimes you're not able to get enough tissue because your pathologist is not gonna be able to call lipidic adenocarcinoma on a needle biopsy. What they want is a bigger piece. So they can actually look at the entire margins. So what does cry biopsy allow us to do? Well in the concentric lesion, I think it's easy. I think it's cheating. You're just getting cryobiopsy because you know you could do it. What, what happens in the eccentric lesion in the bottom center of the screen? What you're seeing is imagine this is a lesion and you have a tool and you have a forcep that's bypassing the lesion because the forcep relies on sitting in the airway. What cryobiopsy does is you'll take a 1.1 millimeter probe. But that's where you have the body bronchoscopy channel. You go close to the lesion. If you have the advantage of imaging, you're gonna do a spin to make sure you're in the lesion and they're gonna start freezing. And the advantage of freezing concentrically is that you're actually gonna freeze part of the tissue while you're freezing normal lung. And then you're gonna take a biopsy from there and that allows us uh to, you know, get pieces even in concentric lesions. And similarly, when you don't have a radio view or you have one of those ground dust nodules, now you can take a bigger piece. So a pathologist can confidently come back and tell us and anecdotally, I can tell you I saw this last week where I did needle biopsies in three ground glass nodules in the same lobe. And the pathologist was like, oh, there's nothing, oh, there's nothing, there's nothing. And I got frustrated. I'm like, ok, forget, you know what I'm gonna do. I took three grand biopsies from each of those sites and then I sent it to pathology and lo and behold, three days later, Leopard adenocarcinoma and all three of them, right? So it's not the problem with the pathologist. It's just hard to make that call needle biopsy. But, you know, with new technology, uh uh you know, when we talk about at the A VP conferences, we always talk about industry and new technology, but has that translated into clinical benefit. That is always the important question. And so this was a nice study done by our colleagues at UCLA cat A uh uh and child who actually you may remember uh as one of his co fellows who did the study, which demonstrated that when they combined cryobiopsy for peripheral pulmonary lesions with the ion system that they had and robotic bronchoscopy, the diagnostic yield was 90% and this was in the absence of integrated imaging. But what is important is the second part that they had 18% additional diagnosis with Caro biopsy. The majority of these lesions were the ones that were sent. But you forget that the third most important part and then the day and age of, you know, molecular testing and when we have EGFR mutations and lung adenocarcinoma and outcomes have changed. The third part is actually the one that is the most important because when you obtain tissue with a larger piece, when you can get a cryobiopsy, which preserves the tissue versus forceps, which can crush the tissue, you actually get increased molecular adequacy. And in this study, 100% of the patients had molecular adequacy by using this cryobiopsy technique. So again, is this something that is routine practice? You wanna make sure that you understand the risk of it, you wanna make sure that you know, when you take a bigger piece, there's gonna be increased bleeding. And so you wanna make sure that you can manage the complications. But something that is very exciting in the field of peripheral bronchoscopy where you have this additional tool. And so pathologist now cannot say, you know, doctor that to your lesion is not in your tool because we know that we're getting a big enough piece for them. And I want to switch gears a little bit as we talk about peripheral bronchoscopy. When we are doing these biopsies, we are also doing staging of the mediastinum. So this is a nice paper in E RJ. And there was a subsequent study which talked about evolving diagnostic techniques in mediastinal lymph adenopathy is mediastinal cryobiopsy. The new kid on the block, right? And there's always those inflammatory articles of this new on the block. But how can we translate into, into clinical benefit? So for those in the group who don't know what Eba says, I mean, it's pretty standard of care since 2012, ACP has recommended EBS as the first line in terms of staging and diagnosing the mediastinum. You know, there are lymph majority of the lymph nodes patients except level eight and nine, which can be accessed through the airway. And if you're somebody who does us, you know what do we call EDR, the bronchoscope and go uh in the wrong airway rather than you go in the esophagus and take biopsies, you can actually access all of the lymph nodes except the pretracheal of the prevascular lymph nodes using the cope And then if you're enterprising enough to do transvascular needle aspiration, even that is narrowed of the realm of uh you know, diagnostic success. But the limitation of ebs biopsies has been threefold. We know that when we do needle biopsies with the EBUS, it can, but it did not allow us to do core biopsies. And so therefore, when the pathologist says, oh, great adenocarcinoma and then you send it to foundation or where your local lab is Q and S right. That comes back saying not enough tissue for molecular testing. The second is if your pretest probability has lymphoma, they require architecture, especially for a de novo lymphoma diagnosis. You wanna have architecture to actually identify what the pathology is. What the subtype of lymphoma is. Flow cytometry may not be enough. And number three is burnt out sarcoid, right? Sarcoid, which is giant lymph nodes, you know, four centimeters. Our fellows love that they go in, you know, they have a fun day, they easy diagnosis. But when you have those one centimeter lymph nodes with a little bit of calcium. But the history of grano lung disease, maybe patient is from where I am from India with atb exposure. Is it actually truly sarcoid? You know, if there is a reason to diagnose sarcoid me always says sarcoidosis does not require a biopsy, but we live in a day and age where people want to get tissue diagnosis. Those are the times where we have trouble getting a adequate diagnosis from EBUS. And so, while we have a 90 to 96% yield with traditional diagnosis, if you look at the lab study, that was, the analysis showed a 66% diagnostic yield for lymphoma, 78% for uh the patient with previous lymphoma that was re diagnosed. If you look at the analysis for sarcoidosis, 78% diagnostic yield from uh EBUS itself. And then in terms of molecular testing, depending on which study you look at, it can range anywhere from 20% to 80%. So that's where the role of cryobiopsy can come into play. So anyone has done e you see, you know this image, but what you're seeing here is what we do is we take a needle, a 22 gauge, you know, core needle as well as a 19 gauge needle or a 21 gauge needle, a needle large enough to make a hole. We will then do a needle biopsy under direct visualization. And then once that hole is created into the in the trachea or the on the bronchi, we will then take a 1.1 millimeter cryoprobe. So it's a thin cryoprobe, it's very small, we'll pass it through that hole, we will watch it under direct visualization of this again. So you can see the probe going in right there and then we will activate a freezing cycle and we will do anywhere between a 3 to 7 2nd freezing cycle. And we will literally just take out a piece. And you can see right here now you're getting pieces which are core biopsy pieces, right? So we do this routinely. Now, if our previous probably is high for lymphoma, if you think that this is burnt out sarcoid, if our rose people tell us that all you're getting is blood and bronchial cells, or if we know that, you know, you need tissue for molecular, that may be in the setting of clinical practice or for a research where core biopsies are always needed, you know, for the research purposes. So again, another another technology and this is, you know, moving rapidly and this was a study a few years ago which I demonstrated that ear biopsy added, you know, and I I'm skeptical of the study because if you look at the diagnostic yield of TBN, uh it was 42%. But of course, there are a high population of benign disease which of course lowers the yield. Uh but you can see 97% patients had adequate molecular markers and in 83% patients, there was adequate uh diagnosis of benign diseases. But more importantly, there was this recent meta analysis which was pretty thorough. And here you can see most importantly, when I highlighted lymphoma where the diagnostic yield was 86% versus in the same group 27% using just transbronchial needle aspiration, similarly benign disease of the sarcoid is the most common 87% diagnostic yield with iva biopsy. And overall diagnostic yield is still in that 90% range. And again, whenever you see overall diagnostic yield, we are seeing more and more data, always the careful of what you're looking at. Because if you have patients with 80% 80% of the population has sarcoid and lymphoma, your diagnostic yield is gonna be low, right? Because that technology does not match up. But if 100% of the patients have cancer, your diagnostic yield is gonna be 100%. So having that prevalence is extremely important whenever you're looking at these studies, but again, a diagnostic yield that is relevant and comparable, but more importantly, a molecular yield uh that matches up uh you know to what we need and what is standard of care now. So I shift gears a little bit as we do this to through cryobiopsy and talk about, you know, the most controversial topic of cryobiopsy which has seen its peak. And now the question is, where do we stand? So, advancements in I in IP for diagnosis of what we call DPL D or diffuse paranal lung diseases. So this was uh the transbronchial biopsy for diagnosis. This was David Maldonado's paper uh that had basically summarized in uh published in chest, I believe. Now, two or three years ago, that had summarized all the studies that were present and we had demonstrated that with transbrachial cryobiopsy. And I'll go through how we do that. Specifically, the diagnostic yield for diffuse parenchymal lung disease ranged from 74 to 98% with a weighted pooled estimate of 82%. Following that. There was one of the most be best names randomized study that I've seen. It's called the Cold Eye study. You know, I was just fascinated to read the study just by the name of it. Uh But that demonstrated that an agreement of 70.8% because we remember that when we're talking about diffuse paranal lung disease pathology is not gold standard, right? What is gold standard is MDD? And so what it is important is that the MDD diagnosis is reached an agreement in 76% patients. Uh when transbronchial cryo biopsies were done, the reason it has become controversial more recently is because, you know, it is a high risk procedure. And so people have had complications, you know, major bleeding complications, patients have had air leaks. And therefore people are worried is this, you know, the right thing to do for these patients. If we look at uh you know, some paper from GO BI, they had summarized uh procedure related to mortality of 0.00 0.3 to 0.5% versus a 3% mortality for surgical lung biopsy. And we know that surgical lung biopsy is not a benign procedure. So I think the question that we wanna highlight is the, the true question is not if it is bronchial cry biopsy is better than surgical lung biopsy. I think it's a safer procedure. We'll talk about it. I think it is, you know, something that achieves a high diagnostic yield. I think it comes down to the original question of is a biopsy needed in the diffuse lung disease patient. And that question is not to be answered by data. So when we talk about hesitation with doing transbronchial biopsy, it should not be the procedural risk, but rather having an MDT discussion if a biopsy is indicated. And this is reflected in most recent IVF guidelines that were published by. You can see the difference on the left in 2018 guidelines when there is no transbronchial cry biopsy listed versus the 2022 guidelines where transbronchial cryo biopsy along with BL actually is a part of it surgical lung biopsy in terms of the next diagnostic step and you know, the the group adequately. Uh and eloquently pointed out that in the current day and age, while in 2018, they did not have enough data to actually recommend routine transbronchial cryobiopsy in 2022. Based upon the data and the evolving data, you can consider transbronchial cryobiopsy, but they put a very important caveat, it should be done at centers with expertise and centers of excellence. And the reason is because in the right hands, it could be done in a safe manner, but you don't have experience, it can lead to a significant amount of complications. However, we integrated that into our practice. This is abstract that our fellow had just submitted to a VP that's gonna be uh presented in Charlotte in August this year. And so what we do in our practice and there are three ways of doing a cryo biopsy is we do a rigid bronchoscopy. So we intubate the patient with a rigid bronchoscope, we then pass a flexible bronchoscope and we pass a radial probe in the area of interest. It tends to be the middle of the lower lobe. We make sure that there is no large vessel in that area that we, that that's a safe area to biopsy. Once we do that, then we advance a ob balloon or a blocker through the rigid bronchoscope. And that's the reason we're using a rigid bronchoscope. So we have a large working channel. We pass that uh pho and park it in the lower lobe or the middle lobe. Whenever we are intending to do the cryo biopsy, and we deflate the balloon, we actually do two people. So that way you have enough hands in the room and then the other procedure list comes and basically goes through that area of interest, process the cryoprobe all the way until you feel resistant. Just like your traditional uh transbronchial forceps biopsy pulls like a centimeter. That way we're making sure that we are away from the pleura itself. We have already made sure that there is no significant vasculature in that area. And then we do anywhere between a 3 to 7 2nd freezing cycle depending upon how you get it. As we take the piece out, the second person immediately inflates the balloon. And also we have isolated the lung in that area, right. So the balloon is inflated, the person comes out, the bronchoscope comes out if they take the piece, you know, you get about a anywhere between a seven millimeter to a 1.2 centimeter piece, the balloon is inflated. We then take the cryoprobe out. We insert the bronchoscope again, we leave the balloon inflated anywhere between 30 seconds to a minute and then slowly deflate the balloon and make sure there's no bleeding. And if there is bleeding, we immediately reinflate the balloon in our experience. Uh We just got the data that we showed. Uh since Doctor Murre joined us, we have ramped up our program. We have done about 25 patients. So far, 15 were submitted for this uh abstract itself. And we have had a bleeding complication of one patient. And that was a grade two bleeding, meaning no significant bleeding, requiring any major intervention. That patient requires some epinephrine and oxamic acid and zero pneumothorax. That's not to say that this is a benign procedure. All it tells you is that if you do it in the right setting with the right hands and if it is indicated and all of those patients were done after the MDD discussion at North Health, we have ILD board that discusses all these patients. And more importantly, we wanna make sure that is that translating into diagnostic yield. So this is just some of three examples that I had. So this is a 49 year old patient with shortness of breath with abnormal chest ct, you can again see, you know, uh the concern, this was uh labeled as intermediate risk or indeterminate uh for U IP diagnosing NSIP. In this patient. Similarly, on the patient with, you know, 68 year old patient, you could see lower low predominant disease. They had suspected IPF in this patient, but they were not sure they did not want to treat because the clinical history actually did not uh the progression did not fit with IPF uh And the biopsy demonstrated chronic hypersensitivity pneumonitis uh which is, you know, the difference when we talk about a ui pattern and another patient, 84 year old, not a candidate for a surgical lung biopsy because of comorbidities. Um and was found to have NSIP again. And this was actually very interesting. It was drug related uh plus post COVID and sip with combined with organizing pneumonia. Uh something that we have noted more and more for a post COVID patients. So again, to summarize, I wanna highlight that very important fact, most patients do not need a tissue diagnosis for ILD, right? You have your radiologist, you have the clinical history, you have, you know your patient, if you talk to them, you have their doctors and you can achieve a diagnosis of ILD by MDD. The decision should be based upon a multidisciplinary discussion. It should involve a pulmonologist, the LD team, the thoracic radiologist, the hematologist, you know, to make sure that this is something your pathology is comfortable reading a thoracic surgeon in terms of assessing surgical candidacy. But in the studies that have been done, the risk profile is superior. It is safer than surgical lung biopsy, surgical lung and open lung biopsy does remain gold standard. So if you need a biopsy and you do not achieve a diagnosis, the transbronchial cryobiopsy, those patients we did uh for one patient in our group, for a confirmatory sld because the final pathology was discordant with the clinical picture. And actually, and the whole the surgical pathology showed the same thing. But as we are evolving, that trust factor takes time. So just to show you that even at the center where we do high volume, sometimes there is, you know, there is that lack of, you know, conviction and therefore some of these patients may end up with a surgical lung biopsy, but that it should be a shared decision making and we should not forget the patient, right? Every patient that we do a transbronchial cryobiopsy, I tell them exactly the risk uh that is involved with it because, you know, it is a procedure that is riskier than a transbronchial forceps biopsy. So, shifting gears a little bit again, from diagnosis to management. And this is again, you know, something that is close to my heart as an interventional pulmonologist, something that we like to manage in terms of both benign and malignant disease and cryotherapy. As uh some of my colleagues tell me is cheating, right? It makes your life so much easier than trying to do the traditional. So I'm gonna talk about why cryosurgery or cryotherapy can be used, right? So, we know that cryotherapy can be used in benign stenosis. I'll talk about that in malignant area, obstruction, we'll talk about cryotherapy for granulation tissue, you know, post tracheostomy, granulation, tissue, poststenosis, granulation, tissue, post stent granulation tissue. We tend to use cryotherapy routinely uh for its ablation effect. And also in patients with recurrent respiratory papillomatosis. Uh the disadvantage of using thermal ablation is you aerosolize the particles versus cryotherapy. And again, in malignant senti obstruction, carcinoid syndrome is one of those or carcinoid tumor rather is one of those where you can use cryotherapy uh pretty frequently with some amazing uh you know, outcomes. How does cryotherapy work in these patients in terms of benign or malignant disease? So, again, it, it is similar to thermal ablation in terms of cell death. But the advantage is that it preserves that extracellular matrix and that's the difference between, you know, if anyone has an ablation, we know that once you burn the tissue, there's gonna be fibrosis, there's gonna be granulation tissue, there's gonna be a reaction and then that's gonna heal with the fibrosis. And so whenever we treat our patients with uh thermal ablation, you know, that may be electro arter and plasma coagulation. The concern is that they're gonna heal with a scar again. And what cryotherapy theoretically allows us to do is preserve that extracellular matrix and therefore not heal with a scar and you know, promote normal healing. What is the mechanism of action? There are, you know, these are all proposed mechanisms of action. There's actually a lot of controversy in terms of what is the exact mechanism of action, but some of it makes intuitive sense, right, like intracellar ice formation, extrasellar ice formation as you do as you rapidly freeze something, there's gonna be cell dehydration. There's gonna be, you know, all the electrolytes are gonna go into that tissue. There's gonna be that thermal shock from the change in the temperature and that's gonna lead to the deration of the lipid complexes and that itself that rapid cooling effect where you're taking that tissue from body temperature down all the way to negative 1 50 60 or negative 90 depending on which stool you're using, that will allow for destruction of tissue itself. How do we use that in benign stenosis? So this is just an example of what we call spray cryotherapy. So if you have a tral stenosis patient, that is, you know, requiring frequent interventions, it's not a surgical candidate requires endoscopic intervention in that right, preselected patient. What we do is we go inside, we identify the tissue and then we take this cryos spray, it is basically liquid nitrogen which is rapidly converted into a gas at high volume. Um and we make sure that the catheter is pointing towards the lesion. We can also use this in carcinoma in sits and then we fire and we do a either a five second or 12th freezing cycle. And what is important to see is you can see that gas coming out of the patient's mouth, right? So it is very important to make sure that you have an open system because you are taking a high volume of liquid nitrogen and then actually converting into ra gas rapidly. And what that does is there's expansion, there's a 70 times expansion of gas. And what will happen if 70 times gas expands into the airway and your upper airway is blocked, that air, that gas is gonna go into the lung and cause a pneumothorax, right. So whenever you're doing X ray cryotherapy, we make sure that it's an open system, we tend to use a rigid bronchoscope. If it's extremely high tracheal stenosis where a rigid bronchoscope is not gonna be stable, then we use a LMA with an open system or we use the endotracheal tube without the, you do not inflate the cuff. Um So something if you are gonna be bringing spray cryotherapy to your practice, to be extremely mindful of that, the complications of spray therapy cryotherapy don't come from the local effect but come from the, you know, the effect of expansion of gas itself. So, does that again translate into clinical benefit? Uh This was a study published uh in the, in the cardic surgery journal uh that demonstrated a 35 center patient series. And if you could see at the bottom, you know that patients who have tral stenosis require repeat endoscopic interventions. If you look at the largest studies that was published in Jama Ent uh by the group in Vanderbilt, they demonstrated that these patients, you know, about 50 to 60% of these patients require repeated interventions. And these interventions could be as frequently as one month or every three months. And so you can see here that at the median follow up of 8.2 months, 33% of the patients remain asymptomatic and 48.5% of the patients have improved symptoms. Again, this is a caveat of a retrospective study. And whenever you're looking at a retrospective study in a symptomatic outcome, there is a high risk of a bias. This is who I believe is in New Jersey. Now, uh this was his study uh that demonstrated, you know, a retrospective case series. Again, 48 sessions of spray cryotherapy and these patients had grade three and grade four stenosis. And you can again see that these patients require uh you know, less interventions. And especially in these patients with GP required fewer CT uh procedures. And that's relevant because while when you talk about post intubation or post tracheostomy stenosis, there's, you know, surgical surgery is a good option. When we talk about uh connective tissue disorder related to tracheal stenosis, uh it could become challenging because these patients have the highest risk of recurrence after surgery. And if they respond to systemic therapy such as riTUXimab, that's great. But if they don't respond to therapy, this could be your significantly challenging subgroup of patients itself. Talking about safety, there's an ongoing actually study that is uh primarily based out of Vanderbilt but involves about 14 centers. Uh uh And what they've demonstrated was that in that large study, 100 and two patients around 65 procedures in alleviating our concerns of the safety. And they, they only had one patient with postoperative hypoxemia, four patients uh with a pneumothorax requiring two thost in two patients. Uh and no instances of air embolism, which is one of the concerns when gas is rapidly expanding hemodynamic compromise as well as any procedure related mortalities. And uh we are awaiting that data in terms of efficacy, which I think is gonna be the game changer if cryotherapy could be routinely used in patients with uh you know, benign tracheal stenosis, taking that to the next step. There's actually a rejuvenator or device company that actually does meter dose cryotherapy for chronic bronchitis. Uh This is on the phase three trial right now, what they are doing is, you know, in chronic bronchitis trying to destroy the tissue that is leading to chronic bronchitis. So they, you take a meter dose, dry spray, go out to the airway. So you can think about it as bronchial thermoplasty, but not the same. It's, you know, the freezing version of it and COPD. Um so you do a flash freeze causing instant cell death, you preserve extracellular matrix and then intact ECM allows healing. And so we know that for our patients with the emphysema variant of COPD D, we have multiple options available. Now, apart from, you know, surgical lung volume reduction, we have bronchoscopic lung volume reduction for those phenotypes where you have emphysema or hyperinflation. But for patients that have chronic bronchitis phenotype for COPD, you know, that have been optimized in medical management and not responding, there's limited options available. So this is something that is on the phase three trial. And I think the nearest center of here, I think this temple uh that can do it. So again, an option that may be available in the future, but you know more to come on that. So keep an eye out for that. I think the brand name is called rejuvenator and I don't have, I don't have any conflicts of interest with them. So, coming to, you know, malignant Elway disorders and you can, you know, this is uh every interventional pulmonologist, dream and nightmare at the same time, right? Uh When you get called at 2 a.m. for a patient that has a central area, obstruction with a 5% room and is having stridor and you have to come in. Um and cryotherapy itself, I could say, you know, has been one of the game changer in terms of how we manage those patients when I was a fellow and we had just gotten the cryoprobe. I remember sitting down, you know, using the laser trying to make sure the tissue gets denatured, make sure that it gets devascularized and taking the rigid forceps and slowly pulling it out and an hour and a half later, I'm like, oh my God, I'm still here and it's 10 p.m. already, right. As a fellow, I remember that and where cryotherapy has allowed us is to uh you know, do that in an expedited manner, but still in a safe manner. Same concept as we talked about previously, local vasoconstriction, thrombosis, uh extracellular intercellular ice formation and immune mediated. So there is both immediate effect and delayed effect and the immune mediated is a delayed effect. All of this leading to uh cell death. We tend to primarily malignant disease. Use it for what I call cryo recanalization or cryo debulking. So we basically literally touch the tissue, make sure we freeze it, we allow it to get destroyed and then we pull the tissue out and that has allowed us to save time on the procedure. And why is that important? Well, it's not that I wanna get home early, but these patients are hypoxemic, right? These patients are getting symptomatic from post obstructive symptoms. You have allergic bronchoscope in them to control the bleeding. And the anesthesiologist is getting nervous by the minute as you are not able to ventilate these patients. So allowing that rapid speed of recanalize that airway using cryo debulking. In addition to other tools has been a game changer for us. There's also contact cryotherapy. If there is a small amount of tissue, that is just so we will freeze it and allow it to uh you know, have immune media that sell that, that would allow that over time. And then we use spray cryotherapy for carcinoma in C. Um At ABP, we present a bigger paper that talks about the role of, you know, of uh definitive ablation. And uh for patients who are either not surgical candidates, which tends to be rare in these patients or are not radiation candidates. Uh spray cryotherapy along with photodynamic therapy is a good option uh for carcinoma in situ again, you know, a rare disease, maybe I've done about five cases in the last two years for a CIS, but a a good tool to have in our momenta and then my favorite uh foreign body aspiration, right? So I remember our thoracic surgeons now call us because uh they don't wanna sit there trying to fish out these foreign bodies for, you know, hours and end and I are very jealous and I call it, you know, I described to my fellows, this is the tongue to the light pole effect, right? You literally go to the foreign body as long as there is a water content in the foreign body. Or sometimes I will even squirt saline on the object to allow it to have some water content. You let you touch the probe. You could see that was one of my first foreign bodies I removed as a tending a nice plantar peanut sitting in the right main bronchus for about a month, you touch, you allow counter cryotherapy, you freeze it, you don't let go of the pedal, you make sure you don't touch any of the surrounding structures and you remove the foreign body. And we do this routinely. Uh you know, if the, if the foreign body does not have a metal content, I mean a water content, it's metallic. Then we use the basket. But for every other foreign body, uh we use that tongue to the light pole effect. Uh you know, to great advantage and then switching gears in terms of cryotherapy of pleural disease. Again, a limited role. Uh I just wanna highlight the role of IP in pleural disease management. You know, we know that we could put chest Tues, all of us, you know, as pulmonologists for chest Tues, we could aspirate fluid, we could aspirate air, but very interventional pulmonology can be your partner's is, you know, doing the pleural biopsy. We use a eight millimeter uh incision. So it's basically, I what I call a glorified surgical chest tube, right? And then we put a, put a small port through it and then we put a camera through that and what that, what that that allow you can see on the left of your screen. This is a thoracoscopy in a patient uh that had a 35 year old patient, I believe with a recurrent effusion uh history of breast cancer. And you can see, you know, uh malignant nodules everywhere in the pleura itself. And so you can do a biopsy. Uh Those are pretty easy to do, but it can get challenging when you're talking about what we call diffuse pachypleuritis. And now you can see that on the right of the screen where what you have is the pleura itself is diffusely inflamed. It doesn't really obviously look malignant, but you're really concerned based upon the clinical scenario, you have this exudative effusion that is lymphocytic, predominant. Uh and then your concerned and what we do with cryotherapy is if for some reason we cannot use the rigid forceps. So we are not able to peel off the tissue in an adequate manner in an area of interest because we are using a single port, we're not using multiple ports. And so if it is a challenging angle, what we do with the cryoprobe is we literally take one of the semi flexible uh pleuroscope, go to that area, freeze the tissue gently, peel it off the wall and take a biopsy itself. And what does that allow us to do? Well, we have achieved the diagnosis on, you know, frozen section or rapid onsite cytology. Once we know it's malignant, um we tend to do the rapid pleurodesis protocol. Uh There's a randomized study called tactic trial that's ongoing in the UK. Right now, this concept was originated by Chuck Reddy's group uh at University of Utah. Uh where, what you do is you do a one stop shop for these patients because majority of the discomfort from these patients, if you're doing pleurodesis comes from a long hospital stay, they require chest tube through that phase, then they have to stay in the hospital, then they go home, they're in pain. Otherwise some of these patients get a pleurx catheter, but now they have this pleura or the C IPC for months and months and end and they're doing a procedure on themselves for every, in every other day or every day. And so what we do is a rapid pleurodesis. If we have confirmed intraoperatively that this is a malignant diffusion. And we have discussed prior to the procedure with the patient that this is what we're gonna do. We will uh you know pace of pleura in these patients under direct visualization through us the second single entry. And then we will do thoracoscopic talc drop. So we will basically this is the small storm pattern that we call it. We will take TP and literally insufflate it into the pleural space. And what that allows us to do is once the patient, the procedure is completed from that single incision, the patient can then uh you know, be extubated or if we do it with sedation. If there's no reason to do a bronchoscopy, they go to the recovery room, they take that chest tube out if they have to put one in and these patients then can go home with pleural fluid drainage with the pleura, right. So now, instead of having that chest tube for the longer period of time, they're just draining through the pleura itself. And so they can keep the space dry, they achieve adequate apposition and uh still have that 70 to 80% success rate of again, that data comes from uh you know, retrospective studies. And so we can get away data from the tactic trial from me months to, to actually see if that truly translates uh into, you know, reduced length of ST for the patients, increased satisfaction, increased, uh decreased time of pleurodesis, increased incidence of pleuritides for this patient. But what cryotherapy allows us to do is diagnose these patients get adequate tissue in that diagnostic phase. So we can combine and do all of this in a single setting. Therefore, you know, uh shortening the path both to diagnosis treatment and optimal management for these patients. So again, it was a whirlwind tour and I'm happy to answer any questions, you know, in the break time. Uh but uh just to go over what we talked about, you know. So from the diagnostic standpoint navigation, bronchoscopy, robotic bronchoscopy, if you're doing peripheral bronchoscopy, you can use a 1.1 millimeter cryoprobe to increase the diagnostic yield. Uh If you're frustrated by your rose team, sometimes, you know, something to consider caveat is that there is increased risk of bleeding. So the advantage with any of the navigation system is you actually have an automatic tampon out. Your scope is to this 7th 8th generation segment, but be prepared to deal with that bleeding. Uh If it happens in that rare circumstance with EBUS prior biopsy, again, you know, actually, no increased risk of complications compared to traditional EBUS, apart from a slightly nonclinically significant incidence of uh from the slightly larger hole. Uh but again, a significant increase in diagnostic yield. So this is something we always have in our es procedures. If you are suspecting lymphoma, we go upfront for it. If you are suspecting lung cancer, we don't like to waste $400 disposable devices. Uh you know, if they're not needed. And so we do the needle biopsy if it's not adequate or if it's not enough tissue, uh or if the tissue is not similar enough, we'll do cryo biopsies, diffuse parenchymal lung disease. Again, not something we do for every patient I get more. You know, our, our patient number of patients that I see to that end up with a cryobiopsy. Uh transbronchial for paranal lung disease is about 30 to 40%. So we are very, very selective. Each of the patients that comes to us gets uh you know, discussed at the Multidisciplinary ILD conference. And if then this patient is indicated for a cryobiopsy, we'll take them and perform cryo biopsies, rigid bronchoscopy and c debridement as well as spray cryotherapy. Again, a tool to have for inner for benign and malignant disease and the disease, you know, limited role, but still helps us in our diagnostic heel. So you can see how cryobiopsy for the interventional palmo and all the procedures that we do uh you know, plays a significant role and has come along a long way. Uh Happy to answer any questions by email, uh tag me on Twitter or you know, find me here in person. Thank you. She any questions in the audience? Yeah. No trick questions like I know, you know me. So uh thanks for that. It, it sounds like the things there's no longer on. Um are pretty much the diagnostic you um is much better. And the, the question is, do you still need to put a bridge if it's all central and you're cooling it? And the from the central process is less because we kind of see sometimes it just go less. So great question. Uh You know, I'll answer it in two parts in terms of the oh, so the questions is a two part question. The first question is, is there any role of transbronchial forceps biopsies? And I'm hoping doctor at me is not on the line because uh you chime in and tell me uh that's the best tool available. And that's the second part of the question is, do we still need to do rigid bronchoscopy? Given the fact that we have cryotherapy, uh you know, available and therefore the bleeding risk would be lower. So to answer your first question, II still think there's a role for transbronchial forces biopsy because the risk profile is increased. And so there are certain disease scenarios where organizing pneumonia, uh you know, and some others where transbronchial forces biopsy can be done and still get you an adequate diagnosis. Again, people do transplant forces labs in very different ways. Uh If you talk about the traditional transplant forces, labs done with alligator forces with a 2.8 millimeter, a working channel that gets you a bigger piece. And if you're doing it in the right way, lung transplantation is another group of patients that have a very high diagnostic yield. Uh Are we gonna slowly transition from transbronchial forces biopsy to transbronchial cryobiopsy? I think with the advent of the 1.1 millimeter probe where we are still not getting, you know, giant chunks of tissue and therefore, the bleeding risk is not as high. I think that is something you know, possible in the future. In my practice, I do that if I am not getting good enough pieces with the forcep and sometimes that happens when you have a very bronchiectatic airway. There is bronchiectatic all the way to the periphery. And therefore, you actually never get a good piece of tissue, right? You actually go and you never feel that close and that resistance because the so bronchiectatic all the way to the periphery in those subgroup of patients. I'm still careful. I'd make sure that I go in a diffuse disease to the lateral segment of the right middle lobe or the anterior segment of the left lower lobe. But I can visualize my probe going all the way to the periphery. So as to not, you know, inadvertently puncture the pleural itself. But then I do use the smaller 1.1 millimeter probe, which is a lower bleeding risk and therefore through the tube, if I'm doing a true transbronchial cryobiopsy for DPL LD, where they actually need enough tissue to identify UI or the specific pattern that requires a bigger piece and therefore we use a 1.7 millimeter probe. I still feel that I do see bleeding enough times even if it is mild that it would be prudent to not do it routinely unless indicated and do it in the safest manner possible at a center where, you know, you've been doing this routinely and can manage complications to answer your second question of rigid bronchoscopy, um, with immediate cryotherapy, even though it does cause this tissue destruction, they're still bleeding. Uh I've had enough tissues that I will pull out. Uh So the patients do bleed. Uh Do I work to bronchoscope and et tube? Yes, it depends upon availability. If I have three cases back to back that have central area obstruction, I think the, the highest risk one with the ridge bronchoscope, the ridge bronchoscope, the advantage of r bronchoscope is not just related to the bleeding control. Well, that's great because I could pass a second tool. So, you know, for those who don't do bronchoscopy, what that allows me to do is I, I'm using the 1112 mill working channel, it will allow me to then put a flexible bronchoscope to freeze and pull. But at the same time, put a suction or it will allow me to, you know, put a in the distal to it or if I'm operating in the right main bronchus and I'm worried about bleeding into the left mainstream bronchus. I'll pass a PBO next to it park it right at the carina as I'm taking a piece, even if it bleeds, it doesn't spill into it. But the other advantage of a rigid bronchoscope is if you run into trouble, for whatever reason, the rigid bronchoscope allows you to bypass the stenosis in the central area, especially in the trachea. And so I could core the tissue out at rapid speed by just a blade of the rigid bronchoscope. And it also allows me to place a stent at the same time in a rapid speed. So that's where I think it, it is a rigid bronchoscope is as much a tool as it is a conduit as well. And so we use it as a larger conduit because you no anesthesia is gonna put an 11 millimeter E ET tube uh when using a six millimeter bronchoscope. And if you use a six millimeter bronchoscope through 8.5 et tube, you really can't do much. Some of my colleagues do that, you know, they pass a catheter next to the at tube. So there are ways around it, but I still think there is a role for them. I just step out in terms of that. It seems like even within an institution like uh disparity in what first procedure for a patient is gonna be. And we see a pattern which I share with you that even within our division, which is in a, I would say a center, some of us kind of stop doing because rather our, I do this because we don want a patient on going through procedures because we try, then we can do the advance procedure, the patient patients. I wanna be our family member. But now I go through procedures in a month and you're saying that the city puls are referring patients for the first attempt to them. Um But then I'm wondering about, you know, regional or national disparity or, or all the audience that's on the zoom uh national. Anyone look at what the variation and within a, within eight institution and seeing what is the disparity in patient who is the operator? It's a great question, you know, and so and very relevant and this came up recently uh as we were talking about not uh ra bronchoscopy or biopsy, the pleural disease management, right? So this becomes relevant in definite pleural disease management. In our pleural disease consortia meeting, we talked about, you know, in, in San Francisco, one of my colleagues gets patients from six hours of it that has had 1015 th and the lack of definitive management, right? So, I mean, there is only about 600 interventional pulmonologists growing at 3040 maybe a year, right? So there's not enough uh interventional pulmonologist present to, you know, serve the needs. We have pathways through our society of advanced diagnostic bronchoscopies or advanced procedures, right? And there are certain procedures that are limited to what IP does like bronchoscopy or pleuroscopy, but everything else in the right hands, um you know, so in terms of coming to disparity, I think there is a disparity by appearance as even quantified that, you know, we are actually working on that in terms of pleural disease management. How many definitive, how early can a patient get a definitive procedure when they are a tertiary center versus when they are, you know, six hours away from a tertiary center? I think that is the truth, but I think the importance is to have awareness, right? Because the first step of any improvement is to have awareness that actually what is standard of care, right? So when we if people don't know what is available, then they're not gonna know what to do for it, right? Because it's not out of ignorance that this comes, it, it comes out of a lack of awareness as we go to areas. And then the second part is the lack of expertise. And so as our societies are working on, you know, formalizing IP is now a CGM approved specialty. Hopefully soon enough ABM approved specialty as we grow the community itself, you know, we want to partner with our colleagues from Pulmonary, are people who actually are pulmonologists that are interested in advanced diagnostic bronchoscopy. ABP has a pathway to actually allow you to do all of the procedures short of rigid bronchoscopy, take that certificate to your uh hospital and do that as long as it is done in the right manner. So I think in the short run, the disparities can be sorted in, in when you talk about other countries. I think there are more people performing these procedures as a general pulmonologist in other countries than in the United States. But one of the problems with specialization is that, you know, everything gets streamlined uh to that specialty and there are upsides of that, but there are downsides of that, that lack of access being one. So I think we have to work as a community itself to expand the field itself. And as you know, keep up with industry and make sure that when we are keeping up with industry, we align our goals for patient specific outcomes because that is not always the case with industry, right, the industry's job is to uh the sell the technology, but it's our job to make sure that that actually truly translated into patient clinical benefits. So we have to do the twos for them.