And so that's when they realized that maybe all people do not need surgical baked 40 French chest tubes. So before we talk about size of chest tubes and how that becomes relevant specific to the disease states, it is important to understand what does a chest tube size mean in terms of flow and how does drainage or flow diffusion, whatever may the theology be, happen. So just some common numbers. One French is 0.33 millimeters of outer diameter. When we talk about large bore chest tubes, there is a lot of variation in literature, but for the purpose of this talk and more of the recent guidelines, large bore is anything bigger than 16 French. Small bore is 14 or 16 French. Pigtails are smaller. So everyone remembers what's outside physics. We cannot forget that fifth day of the conference, but still. The drainage is directly proportional to the pressure gradient and 4 to the power of the radius and inversely proportional to the viscosity and the length. So when you're talking about diseases, what you're thinking about is what is the viscosity of the fluid and that may play a role and what is the size of the chest tube where the radius becomes relevant. So why is bigger not better? So this was a recent study and I'll go into more detail about the specifics of the outcomes from the study, but what they did was patients got pigtail catheter placement versus large bore surgical chest tubes in patients with hemothorax and hemoneumothorax. And what they did was they gave these patients a questionnaire and what they asked them was, number one meant it was okay, I can tolerate the chest tube, I can do this again. Number two was it was okay, but I do not want to do this again all the way down to number five, which was the worst experience of their life. And you can see on the right of your screen, it was a bad experience and some of the patients described this as the worst experience of their life and these were all large bore chest tubes versus patients who got pigtail catheter, all of them said that they're either able to tolerate it or it is okay, they would not want this again, but it was still tolerable. So this becomes relevant as we focus on patient-centric outcomes. So how do we treat these patients? And again, this is very dependent upon the etiology. And it is always important to remember why are you putting chest tubes in these patients? So for the purpose of the talk, I've divided this into three main topics. The number one on the screen is pneumothorax. And despite our beliefs, we know that the primary aim of chest tube placement in pneumothorax is not to make the picture look better, but to actually give symptom relief to the patient. And as we see more and more data coming out in primary spontaneous pneumothorax, we know that it is not necessary to achieve pleural apposition unless you're actually trying to pleuralize these patients. And we may actually be propagating and worsening these findings by subjecting these patients to continuous chest tube suction and continuous flow. In empyema patients, we can see that the primary aim is to relieve sepsis, right? So you're not actually, again, trying to make the picture look better, but you're trying to control the source itself. Complete evacuation of the space, as we have seen and we will again see, is not absolutely necessary. And it's not just about the chest tube. In addition to chest tube, you have other things that are available. In patients with empyema, you have saline flushes, you have intrapleural TPA, DNAs that is available for drainage. So you're not using chest tube by itself, but you have these tools available. In hemothorax, again, slightly different. There is an aim to completely evacuate the chest space as much as possible to make sure that they don't have a retained hemothorax and don't get a secondary empyema. And you can also consider adjunctive therapy in these patients, but the data is extremely, extremely limited. So coming on to our first bit, large bore chest tubes should be routinely used for patients with secondary spontaneous hemothorax. What does the audience think? How many support the large bore chest tube placement? Oh, clearly we don't have a lot of thoracic surgeons in this audience, but let's look at the guidelines. So this is the ACCP guidelines from 2001, which have not been updated, which say that a large bore chest tube 16 to 28 front should be used to treat patients with larger and unstable primary or secondary hemothorax. The most recent VTS guidelines that came out do not actually comment on the size of the chest tube. But we can see that recent study that was published in 2018, the systematic review, which actually included 875 patients and aggregated data from 11 studies, demonstrated that when you compare pictial catheter placements to large bore chest tube placement, you saw that the success was equal. The recurrence rate was pretty much the same without any major statistical difference. But on the right of the screen, what you can see is the rate of complications, and you can see that while the statistical difference was not major, there was a trend towards having a higher number of complications in patients with large bore chest tubes. That may be related to pain, outcome, long-term outcomes, and this favored pictial catheter placement. So summarizing this data, it is pretty convincing that large bore chest tubes in hemothorax have now become a myth, and we should not be placing large bore chest tubes in these patients unless there's a very specific single clinical scenario, which I cannot, again, imagine. So moving on to the second topic, large bore chest tube should be routinely placed for patients with empyema. Again, a poll in the audience of how many people support large bore chest tubes for empyema. One right there, surgeon? I'm kidding. Anyone else? So let's look back at the MIST trial. Again, a field that does not have a lot of data, but this is actually a retrospective review of the MIST. This is one trial that was performed. Again, we could not interpret much in terms of efficacy of the drug, but there was some important data that was published in the MIST one trial. So they had divided the patients into four groups, patients with less than 10 front chest tube, 10 to 14 front, 15 to 20 front, and greater than 20 front. And we're looking at multiple outcomes for those patients across those chest tube groups. And we can see on the left of your screen, death and surgery combined was not statistically different. Death at one year was not statistically different. Surgery at one year was not statistically different, and hospital stay was not statistically different. But again, we may say that, okay, these are short-term outcomes. This may be dependent on multiple factors. We're talking about interplural therapy. So what about long-term outcomes across these groups? Because we were not able to drain that total space completely, and maybe there was something left behind. So these were the long-term outcomes. FEV1 at three months across all those groups was exactly the same. FVC at three months was exactly the same. And even the improvement in chest radiograph when these patients came back three months later, you can see it was exactly 90% on all of the subgroups. So whatever the difference was, the chest tube size was not the difference, and therefore, we can say that there was no difference in efficacy. What about complications? So you can look at, on the left of your screen, tube insertion, on the center of tube incisor and tube removal, and you can see that comparing larger than 15 front chest tubes to smaller than 15 front chest tubes, their pain scores were much better in the smaller chest tube group, as it is very obvious to our audience. The one caveat I would give in patients with empyema is that small-bore chest tubes work, but if you look at all these studies, all of these patients had regular routine saline flushes. And Davies had done this study in 2008, which demonstrated that if you flush these chest tubes routinely, make sure that the crud is not getting stuck in the chest tube, then the tube will not get clogged, because the justification that is given in using large-bore chest tube is that you're getting thick material, fibrinous material coming out, and therefore, you would not be able to drain this. So in the presence of routine flushing, in the presence of giving intraparal TPA, if you're using the chest tube and the patient is not going to the operating room, it is reasonable to consider small-bore chest tubes in these patients. So again, coming back to our original question of large-bore chest tubes versus small-bore chest tubes, again, a myth that large-bore chest tubes are routinely necessary. In a case-by-case basis, specifically, can it be considered? Sure, but I do not think from literature there is a good enough reason to routinely pursue these in patients. Looking at guidelines and what they say, so BDS published the guidelines recently. They quoted the evidence based upon the study that I mentioned. Chest tube bore size appears to have no effect on mortality rate. Need for post-treatment thoracic surgery or the length of hospital stay or the following chest tube drainage, and if anything, it actually increases post-treatment pain, and therefore, initial drain of thoracic infection should be pursued with small-bore chest tube, which they defined as 14-bore or smaller. So coming to the elephant in the room, the hemothorax, right? That's the controversial topic. So again, same survey. How many people in the room use large-bore, or the hospitals use large-bore chest tubes for hemothorax? It's a majority of the people, or at least much more than the other two topics. So this actually comes from the ATLS guidelines from 2018, which demonstrated that perspective analysis of the studies, 28 to 32-front chest tube are effective in draining hemothorax without resulting in increased retained hemothorax, and that is what the perception was till more recently. This was the largest study that was done. This was a prospective study before the randomized control trials that I'll talk about, which actually looked at large-bore versus pigtail catheters in patients with hemothorax, and the results were surprising not only to us, but the trauma surgeons and the thoracic surgeons. So on the left of the chart, you can see non-emergent chest tube placement. On the right, you can see emergent chest tube placements, and you can see that initial output, insertion-related complications and failure rate were actually equal across all groups, and if anything, interestingly, in this paper, in the non-emergent group, the insertion-related complications were slightly higher in the pigtail catheter placement. While that may be related to technique, but still, in terms of patients requiring repeated surgery or requiring going to vats of failure rate was actually equal across both groups. The data was, again, the same in the emergent placement group, but again, the controversy was that this is a prospective study, but not really randomized, and so is it really true? So this was followed by the group performing two randomized control trials. The first, the PCAT trial, which I demonstrated earlier, which had compared the pain scores, and the second trial was from the same group, which had included not just traumatic hemothorax, but also hemoneumothorax. So on the left, you can see a multicenter study with 119 patients comparing 14 French pigtail catheters to surgical large-bore chest tubes 28 to 32 French, and you can see that the failure rate was equal across both groups. On the right, you can see the same thing, 14 French to 28 to 32 French, included hemoneumothorax, not just hemothorax, and the failure rate was the same across two groups. There are caveats to this. PCAT trial did not meet target enrollment, and in both of these groups, the patients in extremis, meaning patients who were extremely sick, were excluded. So when we tried to extrapolate some of this data, we have to be careful about that. Again, as I demonstrated earlier, the pain was more in the patients requiring large-bore chest tubes, but the one thing to remember is that unclotted blood, if there's fresh blood, it will drain despite the size of the chest tube, because while it is proportional to viscosity, if you have fresh blood in there, it does not matter, and even a 40 French chest tube will actually not be able to drain if a clot has formed in there, and these patients actually do need to go to the operating room for evacuation and control of the bleeding, right? So if anyone attended a talk on Sunday where Dr. Gillespie had talked about how to manage patients with hemothorax, the most important thing is not the size of the chest tube, but making sure that you're intervening early, placing that chest tube early, seeing if there's dramatic output which will require the patient to go to the operating room, or these patients that are at a high risk of empyema or retained hemothorax, where a surgical intervention would be indicated. So coming back to the final topic, large-bore chest tubes should be routinely used for patients with hemothorax. Again, two facts, patients who are hemodynamically stable, it is reasonable, again, the data is not convincing, to insert small-bore chest tubes for hemothorax, but the primary aim is not the size of the chest tube, but to avoid retained hemothorax, empyema, and a timely surgical intervention. So just to summarize, as I said, small-bore chest tubes may be considered as an initial treatment option for patients with primary, secondary, spontaneous or hypergenic hemothorax. Again, if you are intervening, there's data now out there that these patients may not, especially in the primary subgroup, need an intervention at all. Initial drainage of third infection should be with small-bore chest tubes, and either a large-bore or a small-bore chest tube can be considered in the patient with hemothorax, but if they can get drainage, consider small-bore chest tubes, make sure that these patients get chest tube early, and consult a thoracic surgery colleague so that they can go to the operating room in a timely fashion. And I'll be happy to take questions at the end. All right. Thank you. Thank you all for closing down the conference with us. Still loading, still loading. All right, while we're loading, question on large-bore and more small-bore tubes. How many of you all work in a place where nursing staff will flush pigtails routinely? Okay, impressive. How did you manage that? Yeah, we are, you know, there's policies that no one can show us that this is not a nursing procedure. I think this is a little different than across the pond, where it is predominantly accepted as a nursing duty. So anyway, we're interested in this flushing issue. Okay, more on that later. Okay, so I'm gonna go through spontaneous pleurodesis after IPC placement. So fairly narrow topic here, but one that is important, because it's a thing we talk to our patients about a lot, is we're trying to go through options for managing specifically malignant pleural fusion, sometimes other things as well. This is me. I do not have any pertinent disclosures. Okay, if we wanna, yeah, if you all wanna, I guess they added this slide for me. I have one question that we can do if you wanna do the audience response here. That's a good one. Okay. All right, so spontaneous pleurodesis, or autopleurodesis, is a phenomenon after IPC placement, where eventually fluid stops accumulating, and generally this is less than 50 cc's per drainage. Sometimes it's 100, but low volume. And then despite not draining, the patient is well palliated. The symptom, you know, shortness of breath does not recur. And when you're imaging, ultrasound, x-ray, whatever CT shows that there's no significant reaccumulation of fluid. In some of this literature, there's partial pleurodesis where there is significant residual pleural fluid, but it doesn't seem to expand over time when the patient is well palliated. So that is also allowable. So this is fairly accepted. And purportedly, this is most of the time due to the fact that you have spontaneously pleurodesed. You've fused the pleural membranes in at least the majority of the surface area involved. There are other situations that can present like this, like you've had disease response, and they might not have fused, there just might not be impetus to create the molecular infusion anymore. Some of this literature gets to it, some it doesn't. Okay, here's the one question. All right, so you have a patient, malignant infusion. They had one tap a few weeks ago at another hospital. They felt better afterwards, but three weeks later now, they're short of breath again. You don't know what their post-film looked like. They don't remember why the aspiration was stopped. So you don't really have much of a clue as opposed to the underlying physiology here. So what do you tell this patient about the likelihood that this IPC is gonna come back out because they spontaneously pleurodesed? So most patients, we put these in, we get spontaneous pleurodesis within a few months, it comes back out. Or if you really wanna get this out, we can do some things like daily drainage or add some talc to it. And then when we do that thing, most of the time we get this thing out within a few months. Or we can do these things that are pretty aggressive, but still, it's only about a coin flip that we get this IPC removed in a timely manner. Let's move on, let's see. All right, yeah, leading question here. So I will tell you that my discussion with patients has gone through all three of those iterations and now is firmly in the third one, as I'll show you here in a second. But I think we've had a bit of a rosy opinion of spontaneous pleurodesis because we want it to be true. Spontaneous pleurodesis after an IPC is having our cake and eating it, too. We get to do a thing to a patient that helps them breathe better, that doesn't require admission like traditional pleurodesis does, and so patients like that. And then in the end, they don't have a tube after very long. And so we very much want spontaneous pleurodesis to happen. And unfortunately, it doesn't happen as much as we might have thought. Okay, so going quickly through the evidence here. So this was the initial randomized trials of Putnam and Light, two of my former colleagues. In 1999, this was, I think it was called the Denver Catheter, this was the original pleural catheter, pleurox catheter. So this is RCT, and they found that 46% of folks spontaneously pleurodesed within a month, which is pretty good. Now, after this RCT, many moons go by before there is further robust data on this topic. There are lots of single center retrospective series that come out. There are lots of reviews and editorials that have fairly rosy opinions of the literature at that time. This particular review claimed a spontaneous pleurodesis rate of 70%, citing the Putnam paper, which was definitely not 70%. So, I mean, this is a phenomenon that we know happens. This happened with robotic bronchoscopy, I think, where there was not much robust data for a while, and a litany of reviews and letters and things. So we're all excited about a new thing. This sounds good. Again, we want to have our cake and eat it too. And so this gets put out into the milieu. Here are the early, some, not all. These are some of the early trials or series, case series, largely cohort studies, to give you a sense for things. Generally reporting pretty good spontaneous pleurodesis rates, 40 to 60%. And then there's a smattering of these crazy high numbers, even in benign effusions. So this 100% pleurodesis rate in benign effusions. So the literature has a bunch of this in it too. Systemic review, sorry, systematic review, 46%. This was about 15 years ago now. And then another one that showed something pretty similar. So again, about 50%. So people are still feeling pretty good about this. But are these estimates accurate? And there's a lot of problems with these studies. Their definition of pleurodesis varied pretty widely. Some of them excluded patients where they took the IPC out and two months later the effusion was back. That patient didn't pleurodese. But most of these studies didn't. They just kind of censored when it came out. They said pleurodese done, go away, and success. There's a lot of selection bias. Some of these studies, some of these trials kicked out the patients with trapped lung and didn't include them in their retrospective analyses. Some of these patients got tout. Some had pleural infection that was not terribly well reported, how often that was going on. But if you're pleurodesing mostly for patients by way of empyema, it's probably not the way that we should be doing it. So anyways, obviously we all know that the issues with retrospective literature, it all plagued this literature as well. All right, so let's go with some more robust evidence now. This is up to the current day. These are all the RCPs involving tunneled indwelling pleural catheters that really started coming out in the last 10-ish years or so. Still pretty modest number of patients overall. But we looked at this literature because the outcomes are well described and described in advance. And what they did with the catheters is well documented. Was this daily drainage? Was this every other day? Was this three times a week or two times a week? And did we do anything else like put tout in them? So I'm gonna break this down a little bit because it's a busy table, into the ones where it was kind of more usual or less aggressive management of these IPCs. This is drainage every other day or less. Some just PRN drainage without doing anything else in particular trying to get the spontaneous pleural diseases to happen versus some of the arms of these trials did do some things like daily drainage, ASAP and AMPL2, or IPC plus with tout, ambulatory tout. And then broken down a different way and kind of aggregated, these are the numbers that we're seeing. So this is the best evidence we have on the actual, or the best estimates we have on the true rate of spontaneous pleural disease after IPC placement. If you're doing kind of usual, routine, non-aggressive care with this, less than a third, about 30%. And if you are doing things like daily drainage or putting a tout, still just scratching 50%. So less robust certainly than we were hoping for as we thought about these procedures or as we tell patients, hey, this tube is great, we should do it because you're likely to get it back out. Okay, and then just a word on this. So these more aggressive measures are not free. This is a cost effectiveness analysis looking at IPC plus tout or daily drainage. And daily drainage is expensive. So yes, the data is reasonably good that it will help these spontaneous pleural disease, but it comes at a cost, either to the patient or to society. This is a small study we did at our institution. So this is very preliminary. But just to put the thought out there that half of the patients that we put these IPCs in, at least in a small cohort, had to pay at least something for these. And it was not necessarily small for folks on a fixed income, 200, 250 bucks a month. And that's just with routine, non-aggressive drainage. So you can imagine if you're having these patients drain every day instead of three times a week, that cost goes up quite a bit. Okay, so what are we doing now, or what is being explored to try to promote spontaneous pleural disease after IPCs? Again, we'd like to have our pick and need it to, and we're still trying to figure out a way to make that happen. And the other subtitle here is, why is it that we can't spontaneously pleural disease more? So, there are some new directions in, we have not yet studied IPC plus TALC plus daily drainage together. IPC plus was kind of as needed drainage. ASAP and AMPLE2 were just daily drainage without TALC. And so, AMPLE3 and TACTIC, two ongoing recruiting trials, will give us our first data on this TALC plus daily drainage combination. And we'll see what that does. They're both versus other arms, but we'll get some data here. There's been some interest in some background data here on elastance, and whether we ought to be looking at pleural elastance as we're deciding our management strategies regarding IPC or other things. And then catheter alterations to promote pleurodesis, I'll touch on here briefly as well. So, there are a couple papers out, one from our group, and one from Chopra's group, in the last couple years, looking at the concordance between radiographic expansion, which is what we use when typically, most folks are not doing routine manometry. So, we use the x-ray after pleural fluid aspiration to estimate, or try to get a sense for, are they expandable? Is the elastance hopefully normal? If the elastance is abnormal, the visceral pleura is gonna recoil away from the chest wall. Fluid will come in to fill that space here. I'm a harder time pleurodesing that patient, because they're not making contact. And then, this classic land paper from 1997, pleurodesis failure was predicted if the elastance was greater than or equal to 19 centimeters of water per liter. Per liter's not there. And this is Light's original description of the three classic normal, entrapped, entrapped elastance pattern. So, these are the two, the results from these two recent papers. So, Chopra did, I think it was a prospective observational trial. They did manometry on these patients, got x-rays after. They used a fairly stringent definition of re-expandable. You had to have 90% pleural apposition to be considered radiographically expanded. Even with that more stringent definition, 30% of patients who looked expanded had abnormal elastance. And on the other side of that, about the same proportion, 34%, had normal elastance by manometry, but their x-ray didn't look normal afterwards. You wouldn't have recognized that the elastance was actually okay. So, there was a 30% discordance rate, which is pretty remarkable. In the study that we did, this was a post-hoc analysis of the manometry arm from a manometry trial. We used what IPC Plus used in their inclusion or exclusion criteria. So, if you had 75% pleural apposition, you were considered not trapped and you could be in this trial of pleurosis. And so, using that more lax definition, 71% of patients that looked expanded actually had abnormal terminal elastance, which is pretty remarkable. And the positive predictive value of radiographic re-expansion for their elastance actually being normal was 24%. So, the x-ray clearly doesn't tell us what the elastance is doing, and that might be important for our attempts at pleurodesis. It probably also explains in part why these pleurodesis trials have had pretty lackluster results of late. Pre-edit came out a few years ago. I don't know that edit is actually a thing, but this was using manometry to say if your elastance was abnormal, you went to IPC placement and usual drainage. If your elastance was normal, you went to top pleurodesis as a strategy. So, the first trial I'm aware of that actually tried to use elastance in a pleurodesis situation involving acne, I don't know that that's gonna move forward. And then just a brief word on catheter alterations throughout pleurodesis. We're all fairly excited about these silver nitrate coated catheters that perform pretty poorly when we actually, you know, the pilot looked spectacular, pilots usually do, but the full trial, these catheters did not perform very well. So, we're kind of back to the drawing board, but the idea is sound. Can we do it? Can we coat this tube? We've changed the tube in some way to try to promote spontaneous pleurodesis. I think that is all that I have on my, thank you all. Thank you. All right, so the next talk will be one given by me. I'm gonna be talking about the role of pleuroscopy in patients with empyema. Now, pleuroscopy is also known as medical thoracoscopy, and I'm sort of gonna focus on that, but also give out empyema management algorithm that I sort of think is the best way to manage these patients. So, I don't have any non-intellectual conflicts of interest to disclose. I'm talking about myths over here, so clearly I don't believe that pleuroscopy has a role in patients with empyema, so that's my bias. So, the objective, of course, is to see why people even consider medical thoracoscopy in patients with empyema. So, we'll discuss the rationale, the purpose, and the data that's out there. So, what's the rationale, right? Medical thoracoscopy is a very safe procedure. It's done under local anesthesia. It's effective, and it's a day case. The patients go home right after the procedure. So, it should be a suitable alternative to VATS. However, this is extrapolation from the diagnostic medical thoracoscopy data. So, where you see that, you know, on the left-hand side of the screen is a review of 47 studies where there was a mortality rate of only 0.3% and most of those cases were also where they used therapeutic ungraded talc that is no longer done. So it's a very safe procedure and it's very effective in getting us a diagnosis. So extrapolating this to say that medical theracoscopy is a safe and effective procedure for a therapeutic indication like a decortication which is traditionally performed by vats is a little far stretched. And then what about it being under local anesthesia? That's great but a lot of patients who need decortication need excessive work so you're going to need high amounts of sedation in these patients. So the role of a potential pleuroscopy in patients who are undergoing a decortication is a little exaggerated. And then what about the benefit of a day case? Empyema patients are already admitted to the hospital. So that benefit is already scratched off here. So when we do a vats in someone with empyema, what's your goal? Your goal is to evacuate all the infected material and if the lung does not expand all the way, you want to expand the lung. Now hopefully this leads to better outcomes and quicker discharge because you are draining all the infected septic material in the space. This is what is done during a vats. So initially when you get into this complex space, you are going to see a lot of fibrinous rinds or pleural deposits which you can take off pretty easily with blunt dissection as is being done here with a suction catheter. This is accomplishable with medical thoracoscopy, however getting to every nook and corner is something that is hard to do with one port. So you might have to use multiple ports to achieve this. The next thing you want to do is free up the lung in the costophrenic recess, free up the diaphragm because we know that that has great impact on patient palliation and symptom burden. And then if the visceral pleura is stuck up, you want to debride and decorticate the visceral pleura. Now this is something we cannot do. So this is I am talking about a gray zone here which I will talk about in just a bit that there are three stages to empyema and it is not clear always as to which stage the patient presents in. So debriding and decorticating the visceral pleura and taking off the strip is something that we cannot accomplish during medical thoracoscopy. So what can we accomplish during medical thoracoscopy? We can clear the infected material provided that we can get to most corners and break down all the septicians and adhesions and peel off a parietal pleural fiber in its deposit. That too likely not in its entirety. So at best what we are achieving with the medical thoracoscopy is a partial decortication and the question is, is that sufficient or not? And we do not know that yet. What are other rationale to do a thoracoscopic procedure? We say that we can put a well-positioned chest tube. Now that is highly exaggerated because any chest tube with a communicating pleural space is well-positioned in patients with empyema, especially because these patients are going to be on suction and not water seal. And the second rationale is to perform pleural biopsies. It is great to have biopsy information. We know that from the audio trial which was a pilot trial that the pleural, parietal pleural biopsies showed a 25% greater yield in giving us the infectious organism in empyema compared to the pleural fluid itself. But then there was a STORPITS trial which told us what we already knew based on 16S RNA data that 80% of these infections are polymicrobial. So unless you have strep pneumo growing, which tends to be monomicrobial, you really cannot de-escalate antibiotics all the way based on your culture data. You can probably de-escalate to a less potent antibiotic, but you cannot, for example, take away anaerobic coverage because 80% of these are polymicrobial, 80% have coexisting anaerobes in there. So knowing the culture information is great, it is great for future studies, but it may not have that awesome impact on the patient in front of you in every case. Now what is the next question? Let us say we want to intervene, we want to do a decortication, right. So you want to do a medical thoracoscopy or a VATS or you want to do medical treatment. Which one should we do first? What is the first salvage? And we go back to two of the pioneers in the medical and surgical space, right. So on the left is William Osler, a guru in the space of medicine, and he said that Empyma needs three inches of cold steel instead of the fool of a physician. And this comes from a physician. And on the right is Dr. Dukweitran, who is a famous surgeon, you know, one of the pioneers in surgery, and he had Empyma too, and he says that I prefer to die by the hand of God than with the help of a surgeon. So both of them are basically dissing their own professions, and unfortunately both of them died making the wrong decision, probably. William Osler actually died of post-op complications, post-op hemorrhage on day five post-op. So the question is when to operate, when do we need to do an intervention? And I'll tell you how I'm going to, you know, link this together with medical thoracoscopy. Now if you look at the MIS-2 data in the tPA DNAs group, and I mention MIS-2 even though it's more than 10 years old now, because it's still the only randomized controlled trial that exists in the space. There's a lot of prospective data that comes after this, but non-randomized. So in MIS-2, 4% of the patients in the tPA DNAs group needed surgery. What that means is if you routinely subject patients to decortication, no matter how you decide to do it, you're probably going to be operating on almost 90% of the patients who would never need the intervention. So really, surgical intervention, no matter how you do it, should be reserved at this point in my opinion for medical treatment failure, or in those patients who show up in a very advanced stage of empyema where they have this fibrotic pleural rhine and are unlikely to get good clearance of their space with just medical therapy. And those patients are hard to identify because there's a gray zone clinically, you know, everyone's not a clear stage 2 or stage 3 empyema. And then let's talk about the timing of when we do surgeries if we decide to do it. It's important to do it early because you see here that if you wait a week or longer and you go into week 2, the rate of conversion from VATs to thoracotomy is really exponentially increasing. So you have to keep this in mind in medical thoracoscopy too. You know, if I do a medical thoracoscopy on somebody and I decide, oh my god, this space is too complex, this patient needs a thoracotomy, I can't convert on table, but a thoracic surgeon can. So it's important to remember that these patients, if operated upon, should be operated upon early before they get into that advanced stage 3. And if they are operated upon, it should probably be with a VATs because there is that, you know, leverage that you can switch to with a thoracotomy if need be. The goal is of course to avoid the thoracotomy, right, that's where the morbidity and the mortality comes in from the procedure. So doing this early and doing it from the right pair of hands really makes a big difference. Now what do you do first is something what I just presented as my opinion, but there is no good head-to-head data and there are several ongoing studies that will tell us what is the first salvage. That's important because everyone should not be subjected to either of these two. Every patient with empyema should come and get a chest tube, get saline flushes, see if they drain, get antibiotics, and if they feel that, as subsequent therapy, you can consider one of these two. Which one is better? We don't know based on, because of the lack of randomized data yet. If we are trying to intervene on these patients in an operative way, you don't want to wait until they get into that stage three, so you want to be, you want to try to avoid surgery, but if you are doing something, you want to catch them in that stage two phase so that everything is easier for your surgeon as well. So let's look at the data that comes from medical thoracoscopy. So there are six studies that have looked at the role of medical thoracoscopy in empyema and the success rates vary between 75 and 85 percent. Now all these studies did medical thoracoscopy for these indications. So either the chest tube failed or they did it as a first line. Patient came with empyema, let's take you for medical thoracoscopy. And this is not the way I think empyema should be managed. A patient should get a chest tube, flush it, start antibiotics. If it doesn't work, then maybe your first line should be tPA-DNAs, because even if you believe that surgery is better than tPA-DNAs, no one is being rushed to the OR the same day. So you want to give tPA-DNAs a trial at the very least. So this is incorrect use for all the studies, all the studies have incorrectly used medical thoracoscopy. So they do not answer the question whether it should be used in these patients. So even if you use it for their indications, you can see that there is almost a 15 to 20 percent failure rate. So the question is, is it really effective? You are putting someone through a surgical procedure and you are failing in 1 in 5 almost. And you are doing it with the rationale that this is a safe procedure. But look at the complication rates in each of these studies, which is listed in the red down below. So if I have to pool all of this together, it seems that if you do medical thoracoscopy for empyema, 1 in 4 will either have a complication or fail. So it's not really safe and it's not really effective in my opinion. There was one trial, the one on the extreme right, which was randomized. All the other data is non-randomized. The randomized trial looked at two arms. It looked at intraplural enzyme therapy, tPA-DNAs, versus medical thoracoscopy. Now there's two issues with these trials in my opinion. Number one is I think they are asking the wrong question. The question is, is medical thoracoscopy as good as surgery? Not whether it compares to intraplural enzyme therapy or not. So I think that's the first mistake. And the second is the outcome. The outcome looks at length of stay. And when one intervention arm is a 3-day intervention, I think it's unfair to look at length of stay as your primary outcome. Anyway, that's what they did. And patients who got medical thoracoscopy stayed in the hospital for 2 days versus 4 days in the intraplural enzyme therapy group. These are extraordinary numbers. It's very rare that empyema patients can stay in the hospital for such short periods. Also these patients got one to two ports. It wasn't a true thoracoscopy, you know. We usually do it with one port. These patients got one to two ports, had a large pore tube in place, and there was no assessment of pain and other patient quality metrics reported in this small study of 16 patients in each arm. So summarizing all of this, is there a role for thoracoscopy in empyema? Rarely is my answer. Maybe in an early stage 2 empyema, which is hard to identify in all cases, when intraplural enzyme therapy fails and the patient is not a candidate for VATS, it could be considered in expert hands. But short of this extremely rare scenario, I don't think medical thoracoscopy has any role in empyema at this point of time. So how should we manage empyema in my opinion? Patient comes in, you put a chest tube in, again you put a small port chest tube in as was highlighted earlier today, you start antibiotics and you start flushing the tube. Once you start flushing the tube, you know within an hour or two whether this tube is going to drain the space or not. You don't have to wait 24 hours to make any decisions. Within an hour you know this tube is working or this tube is not working. And if this tube is not working, you go on to the next step, which is start tPA DNAs. Now tPA DNAs does not have to be six doses. I won't go into the details of that right now in this talk. But tPA DNAs can be up to a couple of doses, two to three doses, and you know whether it's working or not. And if it is working, keep going as long as you're seeing persistent improvement. If you've already seen improvement, stop it. But within 24 to 48 hours, within two to four doses, you know whether it's going to work or not. And if it's not working, you move on to vats. Okay. Now the definition of working is not getting complete radiological resolution. You want to get a partial radiological resolution and clinical deferences. That's the key. Don't focus on the x-ray, focus on the patient. So really in this algorithm, medical thoracoscopy really doesn't fit in. It only fits in when tPA DNAs fails and they're not a surgical candidate. So all your decision making should happen within the first 24 to 48 hours because if you are following this, your surgical decisions are made within the first 72 hours and patients should hit the operating room within the first five days so that your thoracotomy conversion rates are much lower. And I think that's my last slide. Thank you. All right. So this is a first for me. I hope you guys have all enjoyed the conference and I hope you've had time to see Hawaii. This is actually across from Colubo Ranch. I have a 10-year-old and we had to go there because they filmed Jurassic Park there. So I thought it was appropriate to use this in my presentation. So I'm going to talk to you about the diagnostic approach or diploidal effusion. I have no disclosures, but I'm a clinical educator, here to learn from my panel, here to learn from you. So excited to hear about any feedback you may have. Here is a QR code. It will be the same one that Rob had up, but go ahead and click on it. And I just have one question. And that is actually what we will start with. So I actually have the five myths that I'm supposed to bust or discuss. And so which one of these is true? You can go ahead and vote. Okay. Let's see what the answer is. Okay. And the one that we think it may be most true in the audience is pleural effusion drainage and malignant pleural effusion. And so we're going to talk about these, and then we'll answer it at the end. So first one is pleural fluid cytology has a high diagnostic sensitivity. And so back in the day, we were told that the more that you studied the fluid, your yield would increase. So if you didn't get an answer the first time, then you should go around another time. But you know, in honesty, this really varies by the tumor type itself. It can range from 40% to 80%, and it really depends on what the tumor is. There's a nice meta-analysis. There's several studies that look at this, and there's a nice meta-analysis that shows that it's pretty modest, pretty good with lung adenocarcinoma, breast, and ovarian, but poor with other malignancies such as mesothelioma and squamous cell carcinoma. This is a study from the English group. First author was Arnold, and they studied 921 patients. They sent 40 cc's on every pleural fluid sample, and they did immunohistochemistry staining. And so it's nice because you can see from this graph the yield for diagnostic yield for these cancers are quite high, and you see how low mesothelioma is. Lymphoma and other hematologic malignancies can be improved if you send flow cytometry. This is definitely something to keep in mind. It's also, and when you send the fluid off, you want to send at least 50 cc's off, or 25 to 50 is what the BTS guidelines say. You know, I would encourage you to talk to whatever center you're sending that fluid off in and talk to your pathologist, because they can actually make cell blocks and do the immunohistochemical staining. But it's important to have that conversation. We tend to send the whole vat. Whatever we bring, we send, so they can do whatever markers they want. These are some of the immunohistochemical stains that are important. They can provide additional data. And of course, in those with unclear ideology, we would say go straight to biopsy. Now, this obviously is an older diagram. Back in the day, I'm not going to date myself, but when we did closed pleural biopsies with Abrams and Koch needles, the limitation of that is if you don't have diffuse inflammation in your pleura, you're not necessarily going to get the answer, right? And a lot of the imaging that we do now, we see discrete lesions. And so image-guided biopsy, be it ultrasound or CT or with medical thoracoscopy, is going to increase your yield. In some cases in our institution, instead of even doing a thoracentesis, we'll go straight to either drainage with biopsy or even a fluoroscopy straight up. I have the advantage of working with five interventional pulmonologists, so I know that different places you do different things, so I'm a little privileged to have that available. But you can always work with your surgeons or interventional pulmonologists or even learn how to do the pleural ultrasound guided biopsies. This is just an example of where it would be useful. This was an 84-year-old woman who had a history of lymphoma and then developed squamous cell carcinoma of the right lung, received radiation and had a recurrent exudative effusion. So we did a fluoroscopy on her, and she showed a lot of exuberant mesothelial cell hyperplasia. There was a lot of chronic inflammation but no cancer, so no lymphoma and no squamous cell. And you could see that the radiation field kind of lined up where it could affect the radiation as well, and she actually had radiation pleuritis. But in cases like this, it can definitely change management. The other thing to be careful of is pleural effusion cytology in hematologic malignancies, specifically in acute leukemia, you can get malignant effusions. It's not as common. The most common is lymphoma, but of course I work in a cancer center, so we see this a lot. In the first two diagrams, you see malignant effusion related to ALL and the second one, AML, and you can see a lot of lymphoblasts and a lot of myeloblasts. But in some of these cases, you may get blasts within the cytology that may be red, but those can also be contamination from your initial stick. So it's important to kind of clinically correlate in some of these patients. And again, if you can send flow cytometry and connect with your pathologist, it's quite helpful. So the second myth was pleural fluid, if it's a transidate, then it's not necessarily cancer related. And I think we have to go back to how does a tumor cause pleural effusion. It can be either direct or indirect. So directly, if there's interference with the integrity of the lymphatic system, anywhere between the parietal pleura and the mediastinal lymph nodes, or direct involvement with the pleura, you can get pleural effusion. And it can be indirect, right? So if you have a local inflammatory response related to tumor invasion, you can get increased capillary permeability. Really, the post-mortem studies that have been done also show that this can be embolic. And pretty much most of the pleural metastasis arise from tumor emboli to the visceral pleural surface with secondary seeding to the parietal pleura. Now, transidates can also occur just with malignant pleural effusion, and about 5% of these can be transidates. And about 17% of pleural effusions can be transidates, or they can be paramalignant. And so this was a term coined by Dr. Son, where effusions are not the direct result of neoplastic involvement, but related to the primary tumor. So if you have a tumor, you can have local effects. So if you're having lymphatic obstruction, bronchial obstruction, traplon, chylothorax, superior vena cava, those are all related to the cancer, right? So you may get recurrent transidative effusions related to that. You can have systemic effects, poor nutrition, pulmonary embolism. And even the ones with poor nutrition or hyperalbuminemia sometimes can be challenging to treat. And finally, you can have treatment effects. So it can be radiation, or it can be chemotherapies, or other target therapies. What we see notoriously is gemcitabine and dasatinib often. So the next myth, which I think a lot of people did select, was limit chlorofluid drainage to less than 1.5 liters at a time. And how many of you guys limit your drainage to that? What do you guys use to limit? Do you look at symptoms, show of hands? Okay. Do any of you guys use manometry? Okay. So I often teach about pleura and talk to others about pleura, and one limitation that most people give is that 1.5 limit. And even in interventional radiology, you'll get a report from outside and almost like they stopped at 1.5. It's never above, right? So this is something that's kind of been propagated. And the reason for it is in this study, Dr. Light actually was monitoring pleural pressures, and their recommendation on this study was actually to stop at if greater than 1 liter is removed, then monitor pleural pressures. And the reason for that is patient comfort. You don't want to get a side effect of the fatal, which could be potentially fatal, re-expansion pulmonary edema. And obviously, as Dr. Lentz or Rob discussed, success for pleurodesis eventually, right? And so re-expansion pulmonary edema can happen. A lot of times you can get your X-ray that shows something, but the patient's fine. So there has to be both. You have to have radiographic alveolar infiltrates and along with the clinical picture with dyspnea and hypoxemia. It's thought to be related to excessive negative interpleural pressure with an increase in pulmonary capillary permeability, reperfusion injury. But honestly, nobody knows. We speculate this. But really, you can't predict it. When it happens, oxygen, positive pressure therapy, and diuresis can help. Rarely, intubation. And rarely, it can be fatal. So it's definitely something you want to look for. I won't talk too much about pleuromanometry because we've kind of touched it already. I will highlight this study that we've done from our institution where we looked at symptom-limited. And so basically, if they developed cough, shortness of breath, or chest pain, we stopped draining. We had about 10,000 thoracentesis. And these were all symptom-limited with suction draining. And our incidence of re-expansion pulmonary edema was actually 0.08%. About 20% of our patients had greater than 1.5 liters drained. And so what we concluded from the study was that it was safe to drain if you use symptom limitation with large volumes and even ipsilateral shift. One thing we did find is those with performance status that was like an ECOG 3 or 4, those are the ones that may have had issues or complications, and those are the ones that we exercise more caution with in terms of stopping draining sooner. Because they're not moving, they may not sense when it's time to stop. So those are cases where we'll be cautious. All right, so the most popular answer, which was malignant pleural effusion and hematologic malignancies are low risk. And it makes sense that people think this, right? Because unlike the Lent score calculation, malignant pleural effusions related to hematologic malignancies are categorized as low. In this initial study, however, there were actually only 35 patients that actually had hematologic malignancies, and they were mostly lymphoma. I'm showing you a diagram from our retrospective study that we did with pleural catheters in hematologic malignancies. There's actually two in the literature. One's multicenter and one's retrospective. So I'm focusing on ours because we also looked at survival curves in these patients, both from the time of their cancer diagnosis and when they had the pleural catheter placed. So let's just focus on this one. So you can see that those that have lymphoma and chronic leukemia that are both kind of lymphocytic, they tend to do better. However, those with acute leukemia and multiple myeloma tend to do worse. Of course, there's a limitation on this study that these are the patients that had pleural effusions. So keep that in mind. So you can take that with a grain of salt. We followed that up with a study that this was research I actually did when I was a fellow that we later published, looking at the significance of pleural effusions in acute leukemia. And what we found was even within acute leukemia itself, the survival curves were different. Those that had ALL tended to do better, but AML and MDS and myeloproliferative tended to do worse. The most frequent etiology, though, in hematologic malignancies, both in the old autopsy studies and now, tends to be infection. So make sure you look for that. Malignancy, drug, and the other stuff like volume and renal dysfunction. What we found, that older age, AML or MDS, were associated with a shorter-mean survival, and survival was actually determined by the response of treatment to the hematologic malignancy, not necessarily the presence of the pleural effusion alone. All right, so our third one. No, third or fourth. I think we're on fourth. Drainage of pleural effusion significantly impacts oxygenation. And so we know that a sense of breathlessness emerges from having a pleural effusion, and there are several possible pathophysiologic explanations. One is compression of the lung by fluid. You can have interpulmonary shunting. You can have reduced cardiac output. You can have alteration of diaphragmatic mechanics, and you can have neuromechanical uncoupling. And so this was a nice study done where it was a meta-analysis of five randomized trials with about 553 patients looking at all of those that underwent interventions for malignant pleural effusion, and they used a visual analog scale to assess their level of breathlessness. And what they found is those with a sense of breathlessness at baseline and even after intervention correlated to how their survival was. So definitely that can impact your prognosis, and it's important to pay attention to their symptoms. This is a recent study done by Gary Lee and his group, and it's called the PLEASE study, and I thought it was really cool. So what they did is they had patients that had pleural effusions. They wanted to characterize a mechanical and physiologic response post-pleural fluid drainage. So they looked at symptom scores, they looked at walk tests, and they also looked at PFTs. And what they found was that breathlessness and exercise tolerance did improve in most patients with only a small mean improvement in spirometry and no change at all in oxygenation. And so the point from this study was really if these patients have significant hypoxemia, then it's really important to look for alternate etiologies. I'm sure a lot of you guys have gotten calls from the emergency room who are like, you need to tap them now, they're really hypoxic. It's really important that you make sure you do a CT angio and looking for other things that could cause it. Of course, tapping the effusions can help them, but it's not necessarily the etiology. So, in conclusion, sensitivity of pleural fluid cytology can vary by tumor. It's important if you have exudative effusion and you think something's going on, proceed with obtaining a biopsy. Paramellic infusions may be transidates and result from cancer. Symptom-limited drainage is safe, but be cautious of their performance status and just pay attention to your patient. Survival with hematologic malignancies in pleural effusion can vary. And drainage of pleural effusion can help with breathlessness, but if significant hypoxia, then it's important to look for alternate etiologies. Great. Thank you.

pleural effusion

fluid accumulation

transudate

cancer related

diagnostic sensitivity

drainage

oxygenation

hypoxemia

tumor type