0:01 [snorts] What's up, ninja nerds? In this video today, we're going to be talking about lung cancer. And this is part of our clinical medicine section. If you guys really do like these videos and they're helping you, please support us. There's a bunch of different ways that you can do it. Hitting the like button, commenting down in the comment section, subscribing, all of those things go a long way with the good old algorithm. So, please do that. Also, I really suggest this down in the description box below. We got links to our website. On our website, we'll have things like notes, illustrations, quiz questions, so many things that can we can offer you that'll truly help you to understand that concept. So, go check that out. Without further ado, done with my sales pitch. Let's get right into the pathophys. All right. So, let's discuss the pathophys and we'll discuss some causes when it comes to lung cancer. When we discuss pathophys, the two big things that I want you guys to understand is the types, right? So, there's the subtypes of um you know, lung cancer. We say small cell non small cell and we really can define this yes based upon the actual hystopathology. 1:04 When you look at these cells they look small they look hyperchromatic they're poorly differentiated but the other really important thing for small versus non small cell is very very rapid aggressive growth. This one it's not going to be as rapid. It may be slower kind of progressive growth. That's the real big difference between these is again yes it is going to be small oval round hypochromatic cells but these things proliferate like rabbits. This one not as fast not as proliferative and as rapid key difference. Now we talk about small cell and really any of these lung cancers we got to know where they're located or where they actually start to form because one is it actually helps us with the exam. If you read in the exam and you say, "Oh, there's a central mass." There's really only two types of lung cancers that most likely present within the central portion of the lung. If you think peripheral, then there's some other ones. So, that's really really helpful for your exam and in the in the actual wards. So, small cell lung cancer, it prefers the central airways. So, a central hiler mass is 2:04 going to be what you want to really be looking for. So, central hiler mass. So, for example, we'll represent this in like a pink color. Let me get my pink marker here. We're going to say here is going to be a bronchus and we're going to have some cells that malignantly transform and these things start growing like crazy. And here I have a big mass in the central part of my airways near the hilum because the hilum is that entryway where what the primary bronchi, the pulmonary artery and veins kind of come in and out of the lung. So that's going to be my central location. When I zoom in on this one, so hisystopathology wise, when I take a biopsy, so this one I would do a broncoscopy. I would take and I would biopsy this tissue. After I do a biopsy, what would you be looking for? And you're probably like, "Zack, why in the heck are we talking about diagnostics here?" Well, I think it's crucial that we get some headway into actually having 3:04 some identifiers or classifiers that things that when we look under the microscope, this is a little bit more of the initial step one stuff that you think about how would I see under the microscope the types of cells that represent small cell, adno, large cell, etc. So for small cell, the cells that this actually deres from, if you took a piece of the epithelium, you'd have these blue cells, what are those? pseudoratified ciliated columnar. You'd have these green cells. Those are your gobble cells. They make a lot of mucin. You have these red cells which are your basil cells. They're the progentor cells and they can make really any of these. And then you got these little pink buggers. These little sons of guns. These little freckles right here are called the neuroindocrine cells. What are they called? They're called the neuroendocrine cells. Now we also give them what's called the kchitsky kchitsky cells. Now these cells the neuroendocrine cells that happens is is these guys are really the problematic 4:04 issue. They undergo malignant transformation. Maybe you smoke maybe it's some radon exposure some asbestous whatever it is they undergo some mutations. When they mutate they gain that capacity to either shut off tumor suppressor genes or turn on protoonco genes. And guess what starts happening, man? These things start rapidly, rapidly proliferating. And that's the really important thing to consider with this one. So again, I want you to know which are the cells that are really going to be the problematic issue here. And it's those neuroendocrine cells or the kulchitsky cells that undergo this malignant transformation and make this big mass that we see. All right. So when you look at these, they're going to be the kchitsky cells. which when you look at these cells under microscopy, they're small round kind of like hyper chromatic cells. That's a really important thing. Now, the other thing is when you take these cells and you do what's called aminoistochemistry, you try to look and tag specific types 5:05 of molecules that are present in this one, it's almost always positive for a very specific type of molecule called chromogranin A. All right, chrommoanin A. Now, here's what I want you guys to think about. When we got this small cell, what do I want you to take away from it? Central mass. If I take and I biopsy that thing, what am I going to see? I'm going to see those neuroindocrine called Chitsky cells. If I stain them, what is going to come up? Chromogan. This is a really big thing to take away from this. All right. Now, you're probably going to start asking the question, Zach, I'm really kind of confused as to how these cells actually proliferate. Well, we'll talk about it. often times there's some type of carcinogen and then therefore that carcinogen causes damage to the DNA which leads to a mutation. That mutation then leads to a loss of function or gain of function of a particular type of gene and that will cause this proliferation. We'll talk about that in a little bit but before we do that let's move on to the next component here which is the non 6:05 small cell lung cancer. So with this one we have adno carcinoid squamus and large cell. So there's four different subtypes to this one. >> [sighs] >> How am I supposed to remember this? Bro, don't worry. I got you. Adnocarcinoma most common. It is the most common lung cancer in general. And actually, when you compare non small cell and small cell, non small cell significantly more common. All right, maybe 15. This accounts for maybe around the 80 85%. Now, adnocarcinoma location, this one loves the peripheral locations. So what happens with this puppy is it loves to really involve more of the broncoal alvolar tree and so you're going to get a tumor that's most likely going to form within the periphery. So this is going to give you more of your peripheral tumors or masses. All right. Now if I took that tissue zoomed in on it to take a look at it what would I see? All right. If I took that tissue and I zoomed in on it 7:05 what we're actually looking at is we're looking at this bronco alvular tree. So here you're going to have like a respiratory bronchiel and then here you're going to have the alvoli, right? These are my alvoli. When I take these and I zoom in on it, you guys remember what are the primary cells that make up an alvoli, right? It's your blue squamus ones, which is the type one. And what are these little black cuboidal ones? The type two. This is called my type two pumytes or my type two alvolar uh cells. Should we play a little game, my friends, and say, "Hey, what do these cells do? Do you guys remember?" They make what a what is it? They make surfactant. In this case, they're going to jack everything up because they're going to make something else. Now, type two alvolar cells in this disease, they get hit usually with a mutation. It's not often times smoking, which is interesting with this one. They have a spontaneous mutation that occurs that causes these cells to just rapidly 8:05 proliferate. Now when they do they kind of proliferate and then they kind of differentiate and what they do is it's very interesting they make somewhat because these are simple cubuidal they make somewhat of a glandular type of structure and then these cells they gain the capacity to actually produce a lot of mucin which can actually increase the risk for uh pneumonia in certain scenarios funny enough. But yeah, these guys are going to be alvolar cells that start to do what? They start to proliferate and they give off this glandular look. So this is going to give off this glandular appearance. And then the other thing is that these glandular cells, these cuboidal cells, they actually start to secrete what they secrete mucin. How should we represent mucin? Green. And it releases all this mucin. And sometimes the mucin you can actually stain it when you do imuninohistochemistry is actually could be in these cells too. 9:06 But it's going to have a lot of mucin. So it's going to have an increased amount of mucin. So you guys get the point here. We take these type 2 alvolola cells. They start making like a glandular type of appearance and then they can contain and secrete mucin. Now when I look at this hystopathology, I kind of already hit you with some of the introductions here that this is going to have a glandular type of appearance of those type two alvolar cells. So let's write down here that's going to be a glandular appearance. But let's add on to this. If I did aminohistochemistry and I stained mucin technically is a protein that I could tag for. So they'll have positive mucin staining. And you know what else is another protein or another kind of marker actually I should say for adnocarcinome which is actually kind of high yield. It's called TTF-1 TTF1. If a patient comes here and you get you see this you see the mucin or you see 10:06 the TTF-1 you think adno all right now I don't want to go crazy on this but there is a subtype of um adnocarcinoma called bronco alvolar carcinoma incitu meaning it kind of stays within this kind of like alvol area it doesn't invade the basement membrane and spread all right so that's one can have a kind of a decent prognosis but one of the problems is it produces tons and tons of mucin in the airways and can cause a lot of pneumonia. But that's something to just keep in mind is bronco alvolar carcinoma and site 2. It's kind of like a a little tweener where it's about to become adno but it's again it's not breaking through the basement membrane. All right. So next one is carcoid tumors. Now carcinoid tumors usually with these they're not super common. They're very I'd say relatively rare. But one of the things about these is they are also a central mass but they're usually kind of end bronchial. they don't usually get too big. So, it's going to be more of a central kind of endo bronchial mass. With these masses, 11:08 one of the things I want you guys to remember is again not super super common as compared to things like squamus and adno and large cell. But when we actually take this one, this is going to sound kind of familiar. If we take and we were to actually biopsy this tissue and if we did the biopsy, we would see again pseudoratified celita columnar. These ones are your basil cells, the progenitor ones. This is going to be the ones that are making a lot of our mucus production, right? So, goblet cells. And then this guy, neuroindocrine cells. So, it's funny because uh this is the tumor. This is the one that actually makes this mass. It under goes a malignant transformation and it makes this tumor right here that you see. And you're like, "Wait a second. Weren't these the cells for small cell?" Yeah. The difference here is that these become a little bit more well differentiated. They don't get super super aggressive. So this is actually going to be again our neuroindocrine cells. What are these cells called again? They're called the 12:09 kulchitsky the kulchitsky cells. With this if we took the hystopathology we would find these kchitsky cells are the neuroindocrine cells right? So you'd find these kulchitsky cells that'd be positive for them. The big difference between this one and this one is that this one is very well differentiated. Very well differentiated. And so well differentiated means it's not going to be as severe of a prognosis. Poorly differentiated means it's a little bit more aggressive. Now the other thing is immunohistochemistrywise this is going to come up similarly. What kind of stain would we find in neuroindocrine cells? Chromogan A. So we would actually stain this and we would see what's called chromo granin a positive staining. But again I need you guys to really remember something super important for the kulchitsky cells. What's the big difference with these? These ones I need you to remember are well differentiated. So let's actually remember a a important distinction. So when we say carcinoid 13:12 versus small cell lung cancer, the big thing here is that this is going to be what for carcinoid it is well differentiated cells. All right, that is a pretty high yield thing to take away from this. All right, now carcinoid tumors again you'll see this a little bit later. They have a very distinct presentation where sometimes they can present with this classic triad that we'll talk about a little bit later. All right. All right. That's carcoid tumors. So when I say okay location so far central hiler mass you say small cell. If I say peripheral tumor you're going to say adno. If I say central endob bronchial tumor you're going to say carcinoid. If I say which ones are neuroindocrine cells you'd say small cell and carcinoid. If I say which ones are really well differentiated you would say carcinoid. If I say they stain chromogan a positive, you would say carcinoid and small cell. If I say they stain positive for mucin or TTF-1, you would say adno. Now we come down to this son of a gun here, the good old squam 14:13 cell. Squamic cell is a nasty one, too. It's pretty bad. This one is a central mass. So, this is going to give you a central, but here's the big term that you want to see. So, central cavitary, it's a cavitary mass. So it likes to cavitate. And when we see this one again, it's actually kind of important to remember that this one is usually going to be again pretty nasty looking mass here in the central portion. So here we'll draw a decent central size mass. But what's the big difference? What do I have to have in the center of it? I'm going to have a little cavity. So I'm going to have a little bit of a cavitary mass. So that's a really really important thing to remember. Now I'm drawing these things colorcoordinated. Do you guys notice how adnocarcinoma was black and how neuroindocrine carcinoid cells were were pink? This one's red. So if I actually did a biopsy of this one and I took a look at this biopsy, I see pseudoratified celiac columnar. I see my basil cells or the progenitor cells. I see the cells that are making a lot of 15:14 my mucus, right? My gobble cells and I see the neuronocrine cells. Which cell out of this do you think is malignantly transformed? The basil cells. That's the one that gets affected here. is it's going to be our basil cells. These are the kind of like the progenitor cells. They kind of make some of these cells here a part of our epithelium. So it's the progenitor cell essentially. These ones undergo malignant transformation. And what they transform into is squamas cells like the tissue that's on our skin or in our esophagus. Can you imagine that? And you know what squamama cells, they're kind of unique in that they make a very significant amount of a protein that kind of makes our skin or maybe even parts of our esophagus really resistant to abrasion. It makes it tough. Do you remember what that protein's called? Keratin. Keratin. So this is going to transform, man. And what you're going to get is you're going to get a lot of squamas cells and they are going to be filled with keratin. All right? We call them keratin pearls sometimes. That's actually kind of interesting. So here I 16:14 would represent this. Let's do with like a little bit of orange. Maybe a little bit of contrast here. You're going to see all these like things here. There's going to be these like little keratin pearls. And this is just chunks of keratin that these cells are meant to actually secrete. But they should not be secretreting this in the lungs. You see why that's a problem? They also have something else here um called intercellular bridges. They're kind of like these little desmosomes that stick them together to hold them nice and tight. But here's the thing. If I were to look for a tag. So if I said TTF-1 mucin adno if I said uh the chromogan a you'd say carcoid and small cell for P40 P40 that's squamous cell. So this is going to come up with a P40 positive staining. I know this is a lot I know but we will recap this when we get into the diagnostic section. But again, really important thing to remember here is that when you look at these squamas cells and you look at them, they're going to be filled with what? Let's just remind ourselves here. What are they going to be filled with? What is this orange structure here? These are keratin 17:16 pearls. And then they're going to have like little connections between them. What are these little guys here? Are desmosomes. So when you look at these, the key thing to remember is these squamas cells are going to have lots of what's called keratin pearls and they're also going to have inter cellular bridges which are basically just these desmosomes. And that's some characteristic findings that you want to be aware of when they talk about this. Sometimes they'll bring step one questions into this, but you want to be aware of this on your step two exam, especially in the diagnostic section. All right, squam cell. Boom. Roasted. Let's come over here to the large cell. Large cell is a son of a gun because when we think about this one locationwise, it can occur really most often in the periphery. So, it's most often going to be in the periphery. Now, when we get this lesion, here's the 18:16 thing that's weird about this one. It don't look like nothing. It don't look like nothing. I don't know where the heck this thing came from. And so when you actually take a look at this again, it's going to be more of a peripheral tumor. A peripheral tumor or mass. But when you take and you biopsy this thing, you're like, "Dude, it doesn't look like anything I've seen so far." That's the key. Looks nothing like it. You're like, I don't know what in the Sam heck this tumor is. I really, really don't. It doesn't look like anything I've really ever seen. And it doesn't stain with any of the other things that I've seen. So, I'm not even kidding. Within the name, these are large, poorly differentiated cells. So, on his topology, you're going to see large poorly differentiated cells. And here's the key thing. When they tag this thing, it doesn't tag for shhat. All right, that means that you're 19:17 going to get negative P40 for so it's not going to come up with the squamus. You're going to get negative TTF-1, which means it's not going to show anything for adno. You're going to get negative for the mucin. You're going to get negative for what else? I can't fit it, so I'm going to bring it down here. You'll get negative for chromogranin A. That's the key big kind of takeaway for this son of a gun here is it's not going to have any kind of markers. It doesn't look like any of the cells. So, what I want you to take away from this is when I tell you central tumors, I want you to think of S squamus and and small cell. They like to be central like they want to be near the smoke. They want all the smoke, right? because usually there's smoking associated. Your peripheral is going to be adno and large. The one that's kind of a funky one that we kind of just find a way to fit in there is carcoid. Carsonoid technically likes to be an endo bronchio central tumor. All 20:17 right, we've hit the pathofizz, but we got to really kind of talk now what in the sam heck is causing these cells to just start replicating and proliferating undesirabably. All right, so causes of lung cancer. What's really making these cells again? you know the neuroindocrine cells, the type two alvolar cells, the basil cells, what's triggering per se them to go from being a normal cell to oh dang, I'm going to jack this lung tissue up kind of thing. So what's triggering this malignant transformation? That's what we need to really know. And often times what makes this neuroindocrine cell kind of become very poorly differentiated culty cells that grow or the type 2 alvolar cells or the basil cells to grow is going to be carcinogens. These are the real reasons and these basically are kind of coming here and triggering these cells to undergo mutations. The mutations cause loss of function of specific types of tumor suppressor genes and then these cancers grow. 21:18 >> [clears throat] >> Sometimes it can even be um protoonco genes too. But what are these carcinogens? So there's a couple of them, but I think there's three primary ones. So obviously smoking is going to be accounting for the the the bulk of it. All right? So if you're out there, you know, taking down three sigs at a time, you probably should stop, bro, because 80 to 90% of, you know, lung cancers is due to smoking. Now, the other one is radon. Right on will probably come in as a close second. So make sure that you're kind of monitoring those like Toby in the office. And then the other one is asbestous. All right. Now with this kind of thing, you'd see this more in like insulation and ship builders and things like that, but smoking radon and asbestous are going to be carcinogens. Meaning that what happens is these guys get exposed and they kind of damage the DNA in these cells. when they damage the DNA, they can cause a mutation. That mutation may potentially lead to these cells 22:19 proliferating. So when I say that mutations are are present, carcinogens can actually cause mutations. So that's what I want you to remember is carcinogens have the capability of triggering mutations. When I talk about mutations on its own though, it's really really crucial that you can remember that mutations don't always have to be triggered by a carcinogen. They can happen spontaneously and we have no control over that. When I talk about mutations in general, these things can also individually cause this. But these could be and I want to be a little bit more careful when I say mutations. It could be spontaneous. So let's say for example I take a patient who is a nonsmoker a non-smoker right so if I take a non-smoker or they don't have any type of true exposure from radon or asbesus but this is going to be the most common one this is oftent times associated with adno 23:20 adno carcinoma so usually small cell squamas cell large cell they're almost always inclusively associated with carcinogens like smoking Adnocarcinoma can be seen in non-smokers and the reason behind this is they may have specific acquired mutations in certain types of proliferative pathways and so there's a lot a lot of these man I don't want to go through all of them please for the love of goodness don't memorize these there's only a couple but there's things like the eGFR mutation that's really an important one because this probably accounts for most of the mutations that we see um another one could be the KRAZ. So there's a Kraz mutation. This one not as you know probably as high yield but something to consider. And there's also the al rearrangement that sometimes can be asked about. But I'd say again that EGFR is going to be the really really important one. I'd say that this is going to be the key one here. The EGFR mutation. This is 24:22 also a potential one. This is also potential one. But the question that you're probably going to start asking is, okay, carcinogens can cause mutations. What are the difference in the mutations from these as compared to the carcinogens causing these other spontaneous mutations? Well, here I'll quickly remind you guys that if it's smoking or carcinogen related, so this is non-smoker. If I bring this back up and I bring this to the smoker, if I bring this to the smoker, which is really almost all the other ones, this is associated with other distinct mutations. So, this is going to be ones like your p-53, your uh RB, your retinol blasto protein. Um, it also can be associated with um another one called CMYC. So, CMIC, this one's heavily associated with um small cell lung cancer. But really, any of these mutations where there is a loss of function here or a gain of function, these things can cause the cells to rapidly proliferate. So, if they're a non-smoker associated with these, if they're a smoker, associated with these. 25:23 That's the key difference here. Okay? Non-smoker here, smoker here. These are the ones that we can target. We can't really target these as well. That's the big difference. When I think about carcinogens causing malignant transformation or mutations causing malignant transformation or carcinogens causing mutations that lead to this malignant transformation, the big thing to remember here is when we talk about these mutations, what are they really affecting? Well, these guys here are causing abnormalities within the tyrroscen kynise pathway. So here I'm going to have what's called a tyrrosine kynise receptor. And you guys remember that this receptor, it can trigger so many different pathways. You can have some type of lian bind to this receptor and it can trigger multiple different intracellular pathways. I don't think it's worth mentioning all of them. There is the RAZ, there's the PI3K AKT pathway, there's the jack stat pathway. Either way, that's not really relevant here. They send signals to the nucleus and this will tell the cell to undergo 26:25 intense cell proliferation. So, it'll increase your cell proliferation. And so the abnormalities really exist in some point in this pathway, these guys here. So these mutations alter maybe a component of the receptor or some of the signal transducers. So it's at some point here of this receptor or along this pathway that these things are triggering this which is causing an increase in cell proliferation. It's causing the receptor to be constituently activated. So imagine this thing is just like oh baby I'm stimulated as can be and because of that it's going to cause a massive kind of increase in this pathway and that's where we see this. So these types of mutations here are associated with an abnormality in the tyrroscenus receptor. So again let's just quickly recap to make sure when you take these cells and transform them what's the reason why it's a carcinogen. Most of the time these carcinogens will cause the malignant transformation, but 27:25 just remember the way that they truly do that is they cause mutations. Usually if you're a smoker, it's in these genes. And when these genes get hit that causes this malignant transformation, you can also have mutations that occur nothing to do with smoking. It's these mutations which alter the tyrrosen kinase receptor. If that happens, this triggers cell proliferation and these cells will malignantly transform and you'll get this big tumor. That's the big thing to remember. So, what I want you to take away from it, smokers, they have these mutations. Non-smokers, they have mutations that they have no control over. Even if they didn't smoke one cigarette their entire life, they still have a risk of lung cancer. And that's an ADNA. That's the one I can't let you forget. All right, let's now move on and talk about I got a tumor. How would I present? And what are the complications? All right, so we're going to get into the part of complications. Now, you got to get this, you get this goober in your lungs, right, unfortunately, and this thing is compressing things or it's kind of obstructing airways. We got to think about how would this potentially 28:26 present. Often times, we probably don't really have the a truly symptomatic patient. So, they may come in with some classic findings of cough and wheezing and dysna, but there's a lot of diseases that can come in with cough, wheezing, and disna. That could be asthma, that could be COPD, that could be tuberculosis. How do you know? [sighs and gasps] In some ways, if they present on the exam, this is where I want you to listen. You listening? If they have cough, wheezing, dizzy, and an unintentional weight loss, it may have you have a stronger suspicion for malignancy than other kinds of conditions, especially if they're a heavy smoker. So yes, in a classic patient on the exam, they may come in been smoking 50 siggies, you know, pack of your year history, coming in now all of a sudden with cough, wheezing, dysnia, and maybe even some unintentional weight loss. That should make you have a suspicion of a malignancy. Um, but that's not always the case. Sometimes they come in with complications and then you find it incidentally on imaging. So what are some of those things? So one is if a 29:26 tumor is central it's going to obstruct bronchi and bronchi are really really important to air flow and mucus flow and getting bacteria out of the lungs etc. So one of the big things here is if let's say I have endob bronchial tumors let's say the first off I got a tumor and it's starting right here. Here's the tumor. It's kind of an indo bronchial tumor. It's somewhere within the central airway. Oo what's what's our central ones? Come on think about it. Squamasan small cell. You got it. Now if I take these puppies here and what happens is we have bronchial arteries which are high pressure arteries that are kind of supplying some of these cells. If this tumor invades this thing invades into those arteries it's game over. So that's what I want you to remember is does the tumor tumor invasion. So tumor invasion into bronchial arteries. If so watch out man because you could actually have these guys erode. So let's say here I kind of zoom in on it, right? And then this patient can get hemopsis. The reason why 30:26 is here's the tumor. Here's the bronchial artery. If this thing kind of starts invading out here to that bronchial artery, guess what can start happening? Blood can start leaking into the bronchus and then what can happen is that can be coughed up. So that's the big thing here is hemoptsis could be a presentation. Now, clinically, hmopysis is coughing up blood. So, it's different from hemoteis, which is vomiting up blood, but it's going to be coughing up blood. Now, it is rare for this to be massive, and that can help somewhat in the differential. If you have a little bit of streaking of blood on your hand or a Kleenex or a napkin or something like that when you cough into it, that's definitely going to be more likely a presentation. It's a very mild type of hemoptis because it's a slow gradual tumor invasion into the bronchial arteries that's causing this type of presentation because it erodess into the vessels and that's going to lead to this blood leaking into the 31:28 bronchial tree. If it was massive large amounts of ammopticis you think about tuberculosis, you think about bronchiactis, you think about an ankovasculitis, you don't think about malignancy. All right. Now, if a tumor is pretty big, man, and this I've actually seen this in the ICU um a lot, maybe not necessarily from tumors, but from mucus plugs. It can kind of act the same way. Here you have a tumor that maybe almost partially or completely obstructs that bronchial tree. Now, you know that if I do that, we naturally are supposed to move mucus through this to be spit out. Now in this scenario, what did we just do? This thing was bleeding. This one, it was bleeding because the tumor invaded into the bronchial arteries. So this patient is going to be coughing up some blood. But what if I had a patient who wasn't coughing up blood via hemoptsis, what if in this scenario, I have so much 32:32 bacteria and mucus that can't be mobilized here because this tumor is obstructing it. Then what happens is this this mucus and bacteria these things just stay man you know and and as they stay they really kind of colonize and eventually they start to cause infection and inflammation and then before you know it what just started off as just a tumor there blocked all this bacterial mucus and you end up with an infection of the lung tissue. If this tumor happens right here, it basically obstructs mucus flow. And that mucus flow, if I'm obstructing, so normally you have psyia, right? So let's say that I want to move this big mucous chunk right here. And you know, mucus and you know, come on, think about it. Bacteria is present in pretty much kind of any lining of the tissue. It's supposed to be a kind of a natural commensal relationship. So there's going to be some bacteria that are present here, which I'll represent in kind of this like maroon color. But if I can't move the bacteria this way because of why? Because I got this goober here 33:34 that's oluding it. This is going to start building up. Mucus bacteria going to build up just past this or post to where this obstruction is. And that you got a recipe for pneumonia, dude. And so postive pneumonia is a pretty scary one. Um, and funny enough, this actually tends to be one of the most common presentations, um, especially in your textbooks, but you want to look for this in a patient who comes in with like fever. You want to look for it in like cough or disna. Now, that cough, it's usually productive. So, most of the time in this scenario, I want you to think about this illustration as someone hacking up kind of a perilent type of material. All right? The other thing here is I only do a fever, cough, and dysnia. But here's the other thing. If you get a chest X-ray on this patient because they come in with features of pneumonia, they'll have pneumonia in the same lobe, right? So you're going to see often times 34:34 recurrent pneumonia and that recurrent pneumonia is going to be in the same location. So for example, let's say I had a patient I just I found I you know I diagnosed them with pneumonia and it's in their left lower lobe. They come back a couple months later they got an infection in that left lower lobe again and then an infection in that left lower lobe again. That should have a high degree of suspicion of malignancy. So when I say recurrent pneumonia in same location what should you start to have you know like little pings going off in your brain? location you think malignancy and then you start kind of investigating this. So recurrent pneumonia in the same location malignancy. You got to figure out what in the heck is obstructing this because often times what happens in ICU is we get patients who get mucus plugs and the mucus plug you can't get air flow in. So what do you think happens to this portion of the lung shrivels up right and that's called 35:35 adalcttois. So post-obstructive adalcttois is also something that you could see with these tumors. And then if you have the adalcttois guess what that also is a potential risk for infection occurring there. So post-obstructive adalcttoysis and post-obstructive pneumonia are very common presentations of patients coming in with these central end bronchial tumors. So now peripheral tumors you want to think about adnocarcinoma. You want to think about large cell carcinoma. As compared to central tumors you think about squamus and you think about small cell. Now if I got a peripheral tumor come on let's just think about this a little bit guys. We got a tumor hanging out here near the periphery. What is it next to? Come on. It's next to the plura. So, I can get some plural invasion. And if I invade the plura, then I'm going to start getting ausions. And that's often times a pretty scary one. So, if this tumor starts to invade the plura, that's when you can get these malignant plural uh eusions. So, again, we were worrying about plural invasion. So, that's a 36:36 concerning features. Now, let's say here we kind of zoom in a little bit on this area. So here's the blood vessel. Here's the alvolar kind of like me or the parankma of the lung. And then here is the visceral plura. Here is the parietal plura. And here's the plural cavity. You see how this tumor was supposed to be confined to the lung parankma but it invaded here into that visceral plura. At that point you cause injury. That's injury. And also these tumors they also are capable of producing small amounts of cytoines. And so what they'll do is whenever there's kind of injury it will release different things like interlucan one. It'll release things like tumor necrotic factor alpha. It can even release things like interlucan 6. And in just in general it's going to cause localized injury. But either way this tumor can gain the capacity to secrete these cytoines. These cytoines can go and act on the vessels and do what? Make them leaky as a son of a gun. If I make this thing leaky, so I increase the permeability, 37:36 I increase the permeability of these capillaries that are sitting near the plura, what do you think is going to happen? Things are going to start leaking out and I'm going to get things like proteins, which can actually fit through these big spaces. Now, I'm going to get things like LDH that can s fit within these spaces. And so you're going to get things like lots of LDH and lots of proteins that are going to really really accumulate out here. And it's going to be a recipe for making fluid build up in the plural cavity. And what's that called whenever you got lots and lots of fluid in the plural cavity? A plural eusion. And if it continues to keep happening over and over and over again, that's what we call a malignant plural eusion. Now believe plural fusions once this happens it's very important to remember that this point we have stage four lung cancer which regardless of which type it is this is stage four lung cancer all right so that's a really important thing to remember once we get to this point at stage four just like when I told you guys inflammatory 38:36 breast cancer inflammatory breast cancer usually when it presents it's often times stage three if you have a malign perusion this patient's already stage four so that's pretty sad now the other thing is that you can also have a lot of these malignant cells that flake off. So you see how these malignant cells are kind of like here. What if they flaked off, they could also be in here. And so sometimes they can even invade this vessel too and you can even get blood. So when I think about clinical presentation for these patients, often times think about how a plural eusion would present. It's not always super obvious, but you may have some dullness to percussion, right? What else? What else is another potential presentation? If I were to go and I would actually listen to that that side, what would I hear if I have a lot of fluid that's kind of between the plura and the lung, I would have decreased breath sounds. So there may also be some decreased breath sounds. So that's the other thing I would want you guys to remember is that they can present with this, but oftent times that's not very specific. There's a lot of things that could do this. So 39:37 then what you'd have to do is you'd have to get some type of chest X-ray. And this chest X-ray would likely reveal a large plural eusion and probably an associated lung mass. But either way, we're going to see a pretty decent plural eusion. When you get plural eusions, what do you have to do to determine the type of it? You have to do a thorosentesis. Do you guys remember that from the polar disease? I know you do. And then in terms of it's transudative or exudative. So in order for me to truly figure out what this is, I would need to do a thora centesis. And the thorosentesis, you use something. Come on, spit it out. The lights criteria. And the lights criteria in simplicity tells me what's the LDH. What's the protein? All right. And if I got a lot of LDH and a lot of protein in this plural fluid, it tells me a permeability problem, a leaky problem, not a pressure problem. So if I have 40:39 lots of LDH and lots of protein, usually LDH greater than.5, protein greater than 6 when you compare it to the serum, and there's 2/3 the upper limit of normal of the LDH in the plural fluid as compared to the serum. This is really really high yield for an exudative eusion. This is exudative man. This is exudative. That's where we use the lights criteria because if it was low LDH, low protein, that would say transitative. You think about CHF, cerosis, nefertic syndrome. But what's the key thing that I would need to do? I'd need to send the cytologology. If I sent and I actually looked for cells, what kind of cells would I find here? Would I find white cells and bacteria and stuff like that that would suggest paranommonic fusion? No. I would get cancer cells. So I would do cytology and the cytology would show malignant cells. So this is kind of a nice little recap here of when we talked about plural diseases. So when a patient comes in and they have a plural eusion, you 41:40 definitely can't always rule out that it could be malignancy related. If it's recurrent, if it's continually continuously happening, you should do a thorosentesis and figure out how it's actually going to be presenting. All right. Now, you'll see this with ADNO. You'll see this with large cell. For the central tumors, you're going to see squamus and small cell. All right. What if these tumors are near the apex? Because you know cancers, malignant tumors, they're usually more upper lobe, whereas more of like benign nodule kind of appearances are usually middle lower lobe. So, if you get tumors up here near the upper lobe, especially near the thoracic outlet, what can I mash on? Oh, there's a bunch of nerves and vessels. Let's talk about that. compressive effects of these tumors are sometimes classic exam questions and things that'll tip you off to really think about a tumor that's a little bit more apical. So a lot of the times when we think about upper lobe tumors, especially if they're near the superior sulcus, we call those pancos tumors, right? And these tumors can mash on a lot of different nerves. And so let's think about some of these. The first way 42:40 that this can happen is if you compress what's called the sympathetic chain ganglia. So let's say here's an apical tumor. And again, we can call these apical tumors. We can call them apical or we can call them penost tumors. Now I ask you the question my friends which types of tumors would you associate an apical or pancose tumor with? I want you to write them down. Please pay attention. It's used to be squamus which was the primary one. Nowadays we're seeing an uptick in adno. Squamas adno squamis adno associated with apical pancos tumors. Now, this apical pancos tumor, look at this thing. Look at this son of a gun. It's just mashing on this thing right here. What the heck is this thing? This is our sympathetic chain ganglia. This is again, what is this called? This is called the sympathetic chain ganglia. Gang gang gang. So, we got this thing here. When these guys come up, you have some ganglia here that they'll synapse 43:41 on. But this one, this nerve, this is your sympathetic nerves. Now imagine if I have some nerves running up through this thing and it actually goes to your face. So just for now I promise I'll I'll make it a little bit more you know detailed but this is going to give sympathetic supply. So this is the sympathetic supply SNS supply to the face. And there's specific structures just hold on. If I mash on this puppy here I'm going to decrease the flow to the face. I'm going to decrease that sympathetic nervous system supply to the face. How is this going to present? Well, let's think about it here for a second. If I have this thing mashing in here, I'm going to have a nerve and this nerve actually runs through here and it goes and supplies the iris, the pupil. It's supposed to control the pupil. And then there's another one here that's going to go and supply a muscle. So, let's say here I have a muscle. This is for the levator 44:41 palpro superiors. And then here I'm going to have a muscle which is going to be for the iris for us to have pupilary constriction or dilation. Right? When I have damage or compression of this nerve and this nerve, what's going to happen if this is supposed to elevate my eyelid? I know it look freaky right now, but it doesn't do that anymore because the supply is damaged. What's going to happen? That thing's going to droop. And so because of this, this is actually going to cause injury to the or to the sympathetic nervous supplies, the levator palpabra superiors. What's going to happen? And this is going to causeto tossis. It's going to causeto tossis of the upper eyelid. All right. From this component here, this is also supplying sympathetic supply to the pupil. Now sympathetic dilates. Parasympathetic usually is going to constrict. But in this scenario, what happens if you lose the sympathetic supply? Will you be able to dilate now? No. So what will start happening is it'll start kind of constricting and getting smaller. So in this scenario what's going to happen if 45:41 I lose my sympathetic supply I'll get miosis which is pupilary constriction again not supplying the levator palp superior not causing dilation of the pupil leads tois and meiosis respectively you know what else the sympathetic nerves are also supposed to supply let's represent this in blue here you're supposed to be able to control the sweat glands so here is going to be some sweat sweating on this side. What are you going to have? No sweating. There will be no sweating that occurs here because the sympathetic supply that's supposed to go to the sweat glands is lost. So you get what's called anhydrosis. Anhydrosis. So if a patient comes in with pam pam pam pam, right? Tois meiosis and anhydrosis, you need to be thinking about her syndrome. Horner syndrome could be due to a lot of different things. There could be some kind of 46:41 compression of this nerve and there's a lot of things that could do that. Dissections can do that. But if I think about a tumor, a pancose tumor near the upper parts of the lobe that can definitely smash on that. So her syndrome, think about that and patients with apical lung tumors. Okay, we got this one done, right? So we mash on the sympathetic chain. What if we mash on the frenic nerve? What happens then? Well, let's think about this. I got a tumor. Again, this could be apical. It could even be central. So it doesn't have to just be apical. Again, the frenic nerve comes down through the thoracic outlet, but it also moves down through the medastinum. So if there's compression at any one of these points, you can get frenic nerve paralysis. It doesn't just have to be at the apex, but usually these tumors are going to be a little bit more within the central or again usually the apical portion where they're going to mash on the frenic nerve. Now frenic nerve comes from what roots? C3 to C5 nerve roots. comes down, moves through the thoracic outlet into what? Into the superior mediainum and then it goes into the middle mediainum 47:42 and goes down and supplies the diaphragm. So, what's it supposed to do? This is your right hemi diaphragm. Diaphragm is such an annoying word to spell, right guys? Come on. I have to spell it like fragum from uh in order for me to do this dang thing. So, right hemi diaphragm and over here is going to be the left hemi diaphragm. In this scenario, I have a tumor that's compressing on the right frenic nerve. If it's compressing on the right frenic nerve, I'm going to get decreased supply to the right hemi diaphragm. I want you to think about this for a second. What does the diaphragm do whenever it contracts? Come on, domes down. So that you can increase the cavity of your thoracic uh your increase the volume of your thoracic cavity. In this situation, will the right hemi diaphragm go down? No. Will this one go down? Yes. So, the common clinical presentation is when you get a chest X-ray, you'll see an elevated hemiaphragm on 48:46 the chest X-ray. So, you'll have a elevated hemidiaphragm. Now, you're probably like, okay, that's good to know, but there's a lot of things that can cause a elevated hemihapra. Is that can't adalacticist do that? Yeah. So, how do we really confirm this? We actually have to do something called a sniff test. So, they have what's called a positive sniff test. So, they have what's called a positive sniff test. You're probably like, "Okay, cool. What's this mean, bro? Come on, hit me." A positive sniff test is is kind of more of like a fluo study where you actually see things happening live. You literally take them, have them take a sniff. If you take a sniff, your diaphragm should contract enough to dome down and open up your volume for your thoracic cavity. If the right's paralyzed, the right frenic nerve is paralyzed, is that right diaphragm going to depress? No, it remains elevated during the sniff test. Other ways that these patients present is dysnia, especially when they're flat. So think about that as well. And the patient who presents with disna and a elevated hemi diaphragm on the affected 49:47 side, think about frenic nerve paralysis. All right, come down here. Brachio plexopathy. This one is apical. So remember apical. Apical. Apical. Apical 100%. This one could be apical or central. So here, let's right over here we got a apical or what else could we call it? Come on. Penost tumor. And this is near that superior sulcus, right? This thing is Oh my gosh. Look at this. You see this? These are nerve roots C8, T1, T2, usually that level. And so what you do is you these things are just, oh my gosh, look at this. They're just mashing on these nerve roots. So this is your brachio plexus, which is going to come down and supply the arm, right? If I compress some of the nerve roots, I can get a bunch of different symptoms. And so usually what happens here is you compress is there is compression I'd say often times more than not compression of C8 to T2. All right of the brachio plexus. Now when you compress this this 50:50 area is most often going to cause referred neuralgic pain to the shoulder. All right? So you're going to get some shoulder and arm pain. It's usually going to refer to the shoulder and the arm. Some pain there. But then remember what distribution often comes from this portion of the brachio plexus and it comes down the pinky side the olar distribution. So you can get some pausy effect here. So if I get some ular nerve pausy what could happen here? I could have some weakness. I could have some atrophy and I could even have some sensory deficits of that ular nerve distribution. So you could even get some olar nerve pausy. This is really important. So again, think about some weakness and atrophy potentially of the muscles here in the forearm or even within the hypoththenar eminence are some of the digits. And think about sensory distribution. You may get some like numbness, some tingling, some paristhesas that could also present. And patients who have pankose tumors often 51:52 times they can pres present with a combination of these two. It's called panko syndrome. Panko syndrome is oftentimes a combination of brachial plexopathy and Horner syndrome. All right, the last nerve is the recurrent lingial nerve. Now, this one is kind of an interesting one. You got the they're coming from the Vegas, right? So, here is your right vagus. Here is your left vagus. And um with these they come down. So the right vagus comes down and swoops right underneath the right subclavian artery and then comes back as the right and I'm going to abbreviate this because it's just I don't have enough space right recurrent luringial nerve right [snorts] this one here and that goes up to the crycoyroid of the larynx right and then this one left vagus and here let me actually do this so we can kind of really identify you see I swoop it swoop it there swoop it and then 52:53 we'll swoop this one here this is going to be which one comes down left swoops underneath the aortic arch and comes up. This is the left recurrent lingial nerve. Textbooks will say that you're often times going to get more likely compression of the left recurrent lingial nerve. It doesn't really matter too much. I just want you to know that usually these apical tumors, they're going to compress one of these recurrent lingial nerves. The recurrent langial nerves as they come back they supply the vocal cords really the crycoyroid that controls your vocal cords right to control your speech. What can happen here is if I have compression of these dang things. Look I'm I'm mashing this son of a gun here. Mashing it. Am I going to get good supply um to this actual what the voice box? No. So what can happen here is you can actually get what's called vocal cord paralysis. Now, it's usually since you're most often the tumor is in the right lung, it's going to be unilateral. So, it's 53:54 ipsyal vocal cord paralysis. The most often way or common way that these patients will present is one of two ways with V. So, let's actually do this with vocal cord paralysis. They may present with horarsseness of the voice and very rare scenarios. they can aspirate because see again your vocal cords are supposed to close close when you're swallowing. But if this one's paralyzed, can it actually close properly? No. So you have the risk of food and fluids getting down there and that's it's a nasty recipe for pneumonia. So it increases the risk of a horse voice, but also increases I don't know what the heck happened there. Aspiration. And aspiration breeds a ground for pneumonitis or pneumonia. So that's something you really want to be thinking about. So if a patient comes in, they're saying, "Man, cough, wheezing, dysnia. I got some unintentional weight loss." And then now they say, "Oh, I got I've noticed a change in my voice. It's really horse. I've been aspirating when I eat food or 54:55 drinking liquids. I've also noticed that I have some dysnia." And particularly when I got my chest X-ray last time, they said that my demi hemi diaphragm was elevated. They probably wouldn't say that, but you get what I'm saying. And they also endorse other potential features liketosis, mossis, and hydrosis. And then lastly, maybe they also endorse some pain running into the shoulder, the arm, and some weakness of the ulnar nerve distribution. Those are things to start thinking about as compressive symptoms. This is going to come up in the exam, I promise, one way or the other. So really commit this to memory. The four nerves that are going to be potentially pinched is going to be which ones again? the sympathetic chain, the frennic nerve, the brachial plexus, and the recurrent lurenial nerve. What else can be compressed? Let's talk about that next. And that's the superior vennea. All right, my friends, let's move on now to talk about the compressive effects, particularly the vascular compression. So, we talked a lot about the nerve compression. The vascular compression, this is a really, really scary one. So, SVC syndrome is basically when a patient has extrinsic 55:53 compression of the SVC. So, what is it again? They have extrinsic, so usually a tumor compressing on the SVC. Let's write that out. Now the question that arises here is what is actually doing it. So remember I talked to you a little bit about how usually apical tumors will compress things like the brachial plexus. They'll compress things like the sympathetic chain and then you [snorts] can get something like a panko syndrome with that. We also talked about frenic nerve compression, recurrent lingial nerve compression. So things like that. In this scenario again it's more of a central mass and usually these things have to grow pretty darn big. This is usually seen with small cell lung cancer and squamas cell carcinoma. So again, which types of tumors would be causing something like this? This is something that you would usually see with a central mass. And usually these central masses the most common are going to be which two small cell lung cancer which we'll abbreviate as SCC and squam cell carcinoma which we'll 56:54 abbreviate SEC. So with this, we got this big old honker here. And look at this puppy just straight mashing on the SVC. Can you get a drop of blood down through that puppy? No, Siri. And so what happens is blood wants to rush this way, but it's blocked. And what happens is it starts to move upwards and backflow via the internal jugular vein or it also starts to backflow via the subclavian vein. And what happens is you're going to start getting some symptoms. And so you're going to get a lot of edema or a backflow. So you're going to get back flow through the internal jugular vein and you're also going to get back flow via the subclavian vein. And we'll talk about what that looks like though. But you can get back flow through subclavian vein. Now if you get all of this backflow, what's this going to present as? Well, clinical presentation is if I get back flow via the internal jugular vein, it's 57:57 going to cause swelling and a lot of types of um distension particularly of the jugular vein. So, one way that this will actually present, let's say that this is via um backflow. So, let's abbreviate this as the internal jugular vein is the one that's being affected here. In that scenario, this patient will get what's called a JVD, jugular venus distension. All right, that jugular vein will be popping. All right. The other thing that will also happen is is they'll get a lot of face and neck swelling. So they'll get a lot of face and neck edema. The other thing that can really be scary with these and we'll talk about it is sometimes as blood starts to back up via the internal jugular vein, it can start to fill these like small venus collaterals near the larynx and that can get super ademinous and can cause lingial edema as well. That's a very scary complication. If it backs up via the subclavian vein, where will this one go? It'll go to the arms, the upper extremities. And so with this, the patient can start having arm and chest swelling. So this will cause arm 58:59 and upper chest swelling. And sometimes this can even produce more of like a bluish like hue to it. It actually looks a little bit like this. So, if you have a patient who looks like this, what is the biggest concern? Like, what could actually cause this patient to potentially die? Well, the emergent component because this is kind of like I'd say an urgency. The emergent component of this, the scary scary stuff, so scary complications is if this swelling occurs enough that I told you it backs up via the venus collaterals near the neck, it can cause lingial edema and that can cause a lot of respiratory distress. So, lingial edema is the thing that you got to be careful of. This is the scary one. The other thing here is the internal jugular vein. What else does it drain? Come on, think about this. You have your cerebral veins, right? So you have your sigmoid, your transverse sinuses, they all dump in and 1:00:02 they go via the internal jug of the vein. If you have a backflow in the internal jug of the vein, you can't drain those sinuses. What happens if you keep a lot of blood inside of the brain? The pressure goes up, of course, according to the Monro Kelly doctrine. So another thing that can happen is this can definitely increase people's intracranial pressure. One of the things that when I worked in the ICU is we never wanted to plug up or put a central venus catheter in the internal jug of the vein if they have high intraanial pressure because you're impeding that drainage. Same thing here. If you have a big big pressure dam because of this compression you're not able to drain that vein and because of that sounds really funny drain the vein but if you can't you can't release the pressure from the brain. That can really be disastrous in certain patients. All right, SVC syndrome. We got it. Compressing the SVC, blood backflows. That's where the issue exists is right here. You're compressing on this area and blood can't move through it. So, it backs up. Looks like this. Real quick, let's do a quick quick quick recap because I know we talk about a lot of 1:01:02 stuff and I know it can sometimes be really really stressful. When you're a student, you have to learn all this stuff and you got to take it for an exam. It stinks. I get it. Let's remind ourselves though. If we have compression and we compress the nerves. What were the nerves? Well, the first one we talked about was the what? We talked about the sympathetic chain, right? That was a big one. So, we'll say the sympathetic chain. What else did we compress? We compressed the recurrent lingial nerve. So, we compress the recurrent lingial. What else did we compress? The frenic nerve was another really, really important one. And then what was the last one? The brachio plexus. So, again, it's really important to remember that with these, you're compressing these. And usually what type of scenario the sympathetic chain and the brachoplexus are usually apical tumors. With [snorts] this these are usually central tumors or more hiler tumors. All right. With this one you get her syndrome. With this one you get voice paral or vocal par cord paralysis. With this one you get a asymmetric elevation of the hemi diaphragm. In this one you can get arm shoulder pain and then paristhesas in the ulnar 1:02:03 distribution. With the vessels, what are you compressing? The superior vennea. Where would this one be? More of a central hiler mass. Small cell lung cancer is the most common, but also consider squamasel. All right, we've compressed the vessels, we compressed the nerves. What's the last type of complications that we have to be worried about with a tumor besides them spreading? Another thing is that these tumors, some of them gain the capacity to make hormones. What? Yeah. And if they can make hormones, they can cause a lot of different paranoplastic syndromes. Let's talk about that. All right. So, paraneoplastic syndromes are basically whenever a tumor gains the capacity to produce hormones. That's where it's kind of nerve-wracking and this is really, really high yield. So, if you're taking your exams, there's at least 100% chance that one of these are going to come up. Most of the time, it's going to be focusing on small cell carcinoma or small cell lung cancer. So, really, really pay attention here. But again, paraneoplastic syndromes, very, very common board questions that are going to come up. Now, how will they look? Well, again, the patients will 1:03:00 come in and usually in the vignettes they're going to come in with some type of like non-specific symptoms, maybe a cough, maybe shortness of breath, maybe some wheezing due to the end bronchial kind of obstruction or they could come in with some other complications like pneumonia, right? So, post obstructive pneumonia, hemoptasis. They could come in with compressive symptoms, compressing specific nerves, compressing specific vessels. But another way that you want to look for them to present is potentially with a paraneoplastic syndrome. How will that look? All right, let's say I have small cell lung cancer. Now small cell lung cancer is the most aggressive lung cancer. When this is present, what this thing has the capability of doing is producing hormones. Now one of them and again it's because they're neuroindocrine cells. Remember the the the cell the kluchetsky cells the klchitki cells they are neuroindocrine cells. They have the ability to produce hormones and what they can gain the capacity to do is make a hormone. One of them is ADH. Now if they produce too much ADH this ectopic ADH is a problematic thing. The reason why is if you guys remember ADH will 1:03:58 then circulate through the bloodstream and what it'll do is it'll go over here and it'll bind onto this ADH receptor. You guys remember what kind of receptor this is, right? This is a vaso2 receptor. Vasopressin 2 receptor. This ADH will bind to the vasopressin 2 receptor and stimulate it. When it stimulates it, it sends signals that activate aquaporins. And aquaporins will open up. And when you open up this aquaporin, it's going to allow water that's moving through the collecting duct to start flowing through these puppies. So now water that's rushing through this area. Here's going to be the water, it's normally not supposed to be able to go through here. It's kind of impermeable or dependent upon hormones. If ADH is present, it's going to open up that aquaporin and it's going to flush that guy in. And when the water moves here, what's going to happen? We're going to end up getting a lot more water into the bloodstream. And so you get more water into the bloodstream and less of the water goes into the urine. So you're going to get more water in the 1:04:58 blood and you're going to less water that goes into the urine. Less of this is going to look we'll have a little bit of drippiness here, a little bit of drippiness here and you're going to have less water in the urine, more water in the bloodstream. What this does is this makes a super super concentrated urine. And way that we look at concentrated urines on um specific tests is we look at what's called urine osmolality which I'll talk about a little bit later because this is you know something that we just need to focus on the SADH. Another thing that happens is when water gets into the bloodstream that will actually do what to the bloodstream? Well if you get lots of water it actually kind of reduces the osmolality of the actual blood the serum. And so that's one thing but the other thing that happens here is there's two things. One is going to reduce the serum osmolality but the other thing is it's going to dilute down the amount of sodium that's present within the bloodstream and so it can drop the sodium but it can also decrease the serum osmolality. So it decreases the oz 1:05:59 molality and it also is going to decrease the serum sodium. So here's what I want you guys to remember. If a patient comes in and they have a history of lung cancer and all of a sudden they present with hyponetriia all right which is a sodium that is less than uh 1 35 mill equivalents per liter then you say okay they got hyponetriia how do I know if it's sadh I send off a serum osmolality what will my serum osmolality be it'll be low less than 300 usually so they're going to have a low and I'm going to abbreviate this serum osmolality Then what you're going to do is you're going to then say, "Okay, I have a hypotonic hyponetriia. The next thing I need to do is look at the urine. What's the urine tell me? It's very concentrated. And that tells me that the urine osmolality is going to be pretty really high. So I'm going to have a high urine osmolality. Usually greater than at least 100 to 300. It's definitely going to be high. If that's the case, 1:07:01 then I have right here a hypotonic hyponetriia which is ADH dependent. Then what do I do? I look at volume status. What's the volume status for this patient? Umic. Look at their history. They have lung cancer. That's how I would prove that this is SADH. All right. Next component here. It also can make other hormones. All right. What other hormones you say? All right. This can also make what's called act. Now this is kind of problematic because act is normally supposed to be produced by the anter pituitary. This is supposed to be produced by the what? The posterior pituitary. So when act is released in large amounts act will go to the adrenal glands the zona faciciculata it'll act on the zona faciciculata and tell the zonopiculata cells to make what? It'll tell it to make another hormone here called cortisol. and cortisol levels will go up. And when cortisol goes up, what does it do? I 1:08:02 don't want to focus too much because we talk about this in the Cushings uh disease and Cushing syndrome lecture. But what we know about cortisol is it has so many different multiffactorial effects. It's health causes what? It causes lipolysis and distribution. So they get the moon face, the buffalo hump, they get abdominal obesity with stria, right? They also get a lot of muscle wasting. It also causes hypoglycemia and what else? It can cause a lot of sympathetic activation. So it can cause patients to have a lot of hypertension. And so you're going to see a lot of these features with patients who have a Cushings type of picture. The key thing here is when you have Cushings, you always want to know is it coming from the adrenal gland or is it coming from the pituitary or somewhere else? And so what you'll do is is the patient will have a high cortisol [sighs] and then you'll also check their ACT. What would their ACT levels be? That'll be high. Problem is is you don't know if this is coming from the pituitary or if it's coming from a lung tumor. How do you determine this? You 1:09:04 have to do what's called a highdosese dexamethasone suppression test. And this will not suppress. So if you do what's called a highdosese dexamethasone suppression test, you'll still have cortisol that's elevated despite that. So cortisol will still be increased. Woo! Son of a gun will be increased despite high dose dexamethasone suppression. That's usually a telltale sign. All right. So if a patient comes in and they have cushion like features, check their cortisol, check their ACT, and then from there, you may have to do a dexamethasone suppression test, high dose to see if it suppresses. If it suppresses the pituitary, cool, then it's definitely from the cancer, the lung cancer. All right, what's one more? Another potential picture here is that this tumor, it doesn't make hormones or make it doesn't make an antibbody. What happens is your immune system on this, 1:10:07 you have what's called tumor antigens. So let's say here is a tumor antigen. And this tumor antigen is viewed as foreign. And when it's viewed as foreign, the problem with that is is that our immune system will produce antibodies against that tumor antigen. So here it's going to pump out a couple different antibodies. Here's one. This is an ugly blue. Let's get a different blue here. This is going to be a better blue. So here, woo, that's a that's a dark color there, my friends. We're going to have here some antibodies. When we produce these antibodies, these antibodies are going to be made and directed against these tumor antigens. So, they're going to like this. And what they're going to do is they're going to try to go and bind to this tumor antigen because, you know, you don't want this to be there. So, it'll activate your immune system cells. Your immune system cells will come and try to fight this off. Here's the problem. Sometimes these antibodies can look like other proteins. There's a protein that's present on our synaptic neurons that go to our muscles 1:11:07 at the neuromuscular junction. So here this is all a part of our neuromuscular part of our neuromuscular junction. This part here. All right. Now at the neuromuscular junction there is a channel here and this channel is called a voltage gated calcium channel. We actually give it a specific name. and we give it a PQ voltage gated calcium channel. The whole point of this is that opens up, brings calcium in and helps to trigger the release of acetyloline onto the muscle. These patients produce antibodies and unfortunately these are supposed to go here. They're supposed to go and interact, but sometimes they may go rogue and they say, "Oh, let me meander over here." And that's what it may do. and it may bind onto this PQ voltage gated calcium channel. If you do that, you block the channel. If you block this channel, it doesn't work. I can't get calcium in. If I don't 1:12:10 get calcium in here, then this fusion here where I take this vesicle and I fuse it to release the acetylcholine doesn't happen. If that doesn't happen, I don't make these neurotransmitters. If I don't make these neurotransmitters, this neurotransmitter will not bind on to the acetylcholine will not bind on to this protein here. If it doesn't bind onto the protein, so it's supposed to come here and bind. It's supposed to come right here and bind to this puppy. Guess what? It's not going to. I'm going to block it because I'm not going to allow the acetylene to get released. If it can't do that, it can't take this channel cuz you know what it's supposed to do? It's supposed to sit in here like a seesaw and whip it up. It's not going to. It's going to stay closed. And if it stays closed, can I bring sodium into the cell to deolarize it? No. And so the sodium won't be able to do that. And so because of that, I don't get any positive ions here. So there's going to be no there will be no depolarization. 1:13:13 Let's actually just do this. Let's do there's no deolarization. We'll do this symbol here. No depolarization. Now, if there is no depolarization of the muscle, is it going to be able to contract? No. And so, what happens with this is if I can't deolarize the muscle, you're not going to get muscle contraction. And if I don't get muscle contraction, what's going to happen to them? They're going to be super super weak. So, often times what this does is this causes weakness in these patients and it's called Lambert eaten mythenic syndrome. All right? It's very interesting. So for this one, they'll have proximal muscle weakness usually at the it's usually upper and lower extremities. Lower extremities is a little bit more predominant, but proximal muscle weakness. So it's going to affect more of the shoulder girdle and the pelvic girdle. Here's the big difference with Lambert eaten myic syndrome. The patient's weakness gets better with 1:14:14 exertion. Myastthenia gravis, it gets worse with exertion. So that's a really really important thing to remember here. So if it gets better, so if weakness improves with exertion that suggests more of the Lambert eaten mythenic syndrome rather than myastthenia gravis. Another thing is that both of these can also present with some of the bulbar stuff. So they can present with dipopia, right? They can also present with dysphasia and disarthria. So also remember that. But again the biggest thing is weakness at the proximal extremities that improves with exertion is Lambertinic syndrome whereas myia gravis is it gets worse with exertion. It usually gets worse throughout the day. You can also check for this type of channel antibbody. So this antibbody is being directed against this antibbody uh against this protein. You could actually check for that. You could check for the antibbody against the PQ voltage giddy calcium channels. But that is small cell lung cancer. Now we come to the next one. Now again, if you're going to get tested on one, it's 1:15:14 going to be these three. So I really wanted you to focus on these and think about it. Okay, adnocarcinoma doesn't come up as much. This one is actually not as high yield, but I want to quickly talk about it. Adnocarcinoma, this one does have the ability to produce different types of procoagulants. [sighs and gasps] These are usually tissue factor. So tissue factor is probably going to be one of the big ones, but there is other different types of procoagulants. Now when you make tissue factor what we know is the tissue factor is a part of the extrinsic pathway. It activates factor 7. Factor 7 helps to activate factor 10. Factor 10 in the combination with factor 5 helps to be able to convert what? Prothroin into thromen. Throman activates eventually fibbrin and fibbrin helps with forming a clot. So what's going to happen here? These patients will lead to the formation of clots. So this is going to cause more of a hypercoagulable state, right? And this can induce basically a higher risk of thrombosis. Now this thrombosis you would think oh it's going to cause 1:16:15 DVTs and pees. It can but it's actually more likely to cause superficial venus thrombus and it get causes the vessels to get pretty inflamed. So it can cause something called superficial superficial venus thrombbo flabitis. Okay. And it actually looks a little bit like this. So you can see there that the patient has these hard, tender, red kind of cords. That's where the clots occur in the superficial veins. They get really blocked and they can cause inflammation of that vein. Other things that yeah you definitely have to be considering is that any kind of patient with cancer or malignancy carries that risk of thrombosis of of a lower leg vein that can then spread and cause a PE. There's one other one that can sometimes be tested and you want to think about it. If a patient comes in, they have endocarditis and you have negative cultures and your echo is showing that you have some type 1:17:16 of small vegetation there, you want to think about what's called nonacterial thrombotic endocarditis. Sometimes they call this morantic endocarditis. So MBTE it's non-bacterial thrombotic endocarditis also known as a morantic endocarditis. Now this is one that I actually would take into consideration. Remember here another thing that can happen is this tumor can make something called transforming growth factor beta. So transforming growth factor beta is a um kind of like a a weird cytoine that can act on perryostial cells and different types of osteoclass. Right? So, it's going to come over here and it's going to act on different bone cells and different types of perryostial cells. And what it's going to do is it's going to cause these cells to start depositing calcium and collagen like matrix into the bone. So, what it'll do is it'll tell these cells to start depositing calcium and collagen into the bone. Now, when it starts to do that, right, so you're going to activate 1:18:17 different bone cells, and you're going to also activate different types of fibroblasts, and this is going to start producing lots of again collagen and lots of calcium. So, you're going to produce lots of calcium and lots of collagen, a lot of different types of extracellular matrix here. And what's going to happen is all of this stuff is going to start just depositing into the bone tissue. when it deposits into the bone tissue, what you're going to get is you're going to get a thickening of the bone tissue. That bone tissue is going to really, really thicken. And what happens is when you get thickened bone tissue, so thickened bone tissue, it tends to happen most often around the digits. And what it'll look like is it'll produce something called finger clubbing. So, it's called finger clubbing. And I'm not even kidding. They're walking around with spoons for fingers, right? They can they can dip into their pesto or all their different stuff with their fingernails. And and I'm not even kidding. If you take a look at this, it's actually pretty sad. They have significant finger clubbing. And 1:19:17 it's usually due to a lot of this process here where they're producing lots of transforming growth factor beta that's causing different types of perryostial bone cells and fiberblast to produce lots of calcium and collagen that gets deposited into the bone. Really thickens the bone up usually around the digits. So that covers adnocarcinoma. Now let's move on to the next component which is squamasel. All right my friends. So now we move on to the next one which is squamasel. This one is a nasty cancer and I think the biggest thing that you could be tested on is actually this one too. So small cell lung cancer. There's almost always a question on something like you know Cushings or SADH or potentially even that Lambertioinic syndrome. But another one that's really high yield for the paraneoplastic syndromes is definitely the squam cell carcinoma. It can cause hypercalcemia malignancy. Now the reason why this happens is this tumor it actually gains the capacity to produce something called PTHrP. So this is called parathyroid hormone related peptide. Now this son of a gun right here it's kind of like parathyroid hormone. It's just it 1:20:19 doesn't really act too much on the kidneys to hydroxilate um increase the activity of the one alpha hydroxilase enzyme. But this one right here, what it's going to do is is it's going to go to the bones and it's going to act on these osteoclass, right? And so when you activate these osteoclass, what do uh osteoclass do? Come on, you know this, right? Scream it out. You're just at home, you're like, I know it breaks down the bone. So osteoclast, they're going to release things, different types of um, you know, acid phosphotases and things like that that are going to start breaking and eating away at the bone. And so as I start kind of chewing away at the bone, what's going to happen? Well, if I cause bone resorption, right, I'm going to start kind of liberating calcium and phosphates and stuff like that from the bone. So this is going to lead to a lot of like bone kind of resorption. And when you increase your bone absorption, the whole point of that bone absorption is to liberate calcium from the bone. 1:21:21 Now that calcium once it's kind of absorbed and removed, it's going to start getting into the bloodstream. And if we mobilize this into the bloodstream, what's going to happen to the amount of calcium inside of the blood? It's going to go up. And that's one of the ways that we can get hypercalcemia, right? So osteoclass definitely going to start kind of triggering this bone destruction. The other thing here is PTHrP also can act here on the kidneys really at the distal convoluted tubule. There's receptors that act like you know just like PTH they can act on this and they can increase calcium reabsorption. So what they'll do is is they'll stimulate calcium reabsorption in the distal convoluted tubule. And if I increase calcium reabsorption that's where we kind of get a problem here because now we got a two-fold problem here. We're reabsorbing calcium across the kidneys and then we're removing calcium from the bone. By doing that, I bring calcium into the bloodstream. And I really, really pump this dude up. Now, when calcium is high, obviously 1:22:22 there's a lot of different ways this could present. Could be completely asymptomatic, but it could also present potentially with the stones, bones, groans, thrown, psychiatric overtone presentation, right? We talked about that in the calcium disorder lecture. But the other thing that you have to remember is when you have high PTHRP that's liberating this calcium, high calcium does what to your PTH levels? Well, you have to remember that high calcium is going to inhibit your parathyroid gland from producing PTH. And so what will happen is this will shut down the parathyroid gland and tell the parathyroid glands to not make parathyroid hormone because the calcium is high. And that's really really important. So, one of the things that we'll see here is we'll have a patient who comes in, they may have symptoms, they may not. They may get a workup and on their um their chemistry, we find that they have a high calcium level, right? Then we check the PTH cuz we always want to make sure, oh, is their calcium really high because of PTH. And what we'll do is is we'll check the PTH 1:23:22 and we'll find that their PTH is low. And you should also check other things. you should check their vitamin D levels as well because their vitamin D would have no contribution in this whatsoever because remember PTHP doesn't hydroxilate that it doesn't increase the expression of one hydroxilate so it doesn't actually increase the vitamin D so their vitamin D will also probably be like low or normal that won't be the issue that's not the one that's high right so it could either be low or it could be normal but the whole point is that it's not going to be high and this one's not going to be high what you would have to check is the PTHrP And so if you see that this patient has a very high PTHRP that is going to suggest that this is a hypercalcemia malignancy due to likely a squam cell carcinoma. You'd also have to check to see if they have any metastasis as well. So check for any kind of litic lesions of the bone. That could also be something to consider. But this is kind of a really really big one to remember. All right. Boom. Shaka laka. Let's move on to the next one. Large cell carcinoma. Marshall carcinoma isn't really known too well for causing a lot 1:24:24 of these different types of problems like paranoplastic syndromes. But what it has been shown is that it actually may release things like beta hCG. And beta [snorts] HCG potentially can cause a couple different issues. One is it may increase the patient's estrogen levels. Um and so what that may do is this elevated beta hCG may cause potential, you know, sexual dysfunction, right? And so what happens is this may cause things like gynecomastia, right? And gynecomastia usually what we'd see here is you would see that these patients if you check you may check and say okay what could be other reasons of why they would have this. Now when we check large cell carcinoma one of the things that you would do is you would say okay they have gynecomastia let me check the prolactin and the prolactin shouldn't be the problem. This one should be kind of like normal right that's not going to be the issue. The other thing that you would do is you would check their FSH and LH to make sure that there's nothing kind of going on weird there. And this should be appropriately like normal or it should 1:25:24 be kind of like low or you know should be normal or suppressed appropriately. The thing that you would check is you would say, "Oh, let's check the beta hcg." The beta hcg is the one that's going to be potentially high and that's also going to be associated with an increase in estrogen. So these patients will have increased beta hcg and this beta hcg is going to increase their estrogen production. That's going to cause things like gynecomastia in males, right? So, they're going to have this enlarged breast tissue. The other thing is it also can cause certain changes potentially within the testes. So, it may cause potentially like infertility as well. But here, another thing we would want to remember is the beta hCG. Again, it's also going to go here and it's going to cause changes within the test. So, it may cause certain types of infertility issues or uh difficulty in being able to get a woman pregnant, right? So, they may it may cause the patient to become more sterile. and reduction in libido. All right, so it may cause sterility and it may also reduce again their testosterone production because you're increasing their estrogen production. This may also cause a reduction in 1:26:27 libido. All right, sweet. So large cell carcinoma again remember it's a pump up in the beta hCG that's going to cause their gynecomast when a patient presents with large breast tissue you should always check to see if their prolactin is high, their FSH and LH is high or if the beta hCG is high. If their echin's high, okay, cool. Figure out if it's from FSH and LH. If that's normal, cool. Check the beta HCG. The other thing is watch for other types of secondary sex effects such as are there problems with fertility or libido changes. All right. The last paranaloplastic syndrome is carcinoid tumors. Now, carcinoid tumors are interesting in the sense that they have the capability of producing a hormone called five hydroxyryptamine. And five hydroxyryptamine can actually be converted into serotonin pretty easily actually. And so these things can pump out a decent amount of serotonin. Now again it's important to remember carsonic tumors can occur in the lungs and they can occur in the git. Which one's more common? GIT lung less common. But five hydroxyryptamine it actually gets metabolized. And one of the things 1:27:29 that can happen is with five hydroxyamine is this can act in a a bunch of different ways because it can actually increase your serotonin. Right? So it's going to actually get converted eventually into what's called serotonin. And so serotonin is really where the problem exists because um increased serotonin can produce specific effects on the body, right? One of the things that can happen is serotonin can produce some changes. So it can act on a couple different tissues. One is it could act in the lungs. It could act in the git. It could also act on the skin. And it's going to produce a very classic triad. Let's remember this triad. The triad if it acts on the lungs is it's going to precipitate wheezing. All right? So it'll precipitate a wheezing effect. If it acts in the git it's going to produce diarrhea, right? It'll produce more of a secrettory diarrhea. It's going to cause a lot of secretion. And the last thing is it can actually act on the skin and this may be the the nascin reaction. It can also cause flushing. So this is a very common triad-like picture. Now 1:28:31 carcinoid syndrome with this also is really important that you pick up something else. Serotonin gets metabolized via the liver. And when it gets metabolized via the liver, it gets metabolized via what's called monoamine oxidases. And the monoamine oxidases convert this serotonin. So here we'll put like a little u let's put a cute little enzyme. This is called a monoamine oxidase. Monoamine [snorts] oxidase enzyme. It's going to catalyze this conversion. When it does that, it converts this into what's called five hydroxy indole acetic acid. And this puppy is going to go right to the kidneys where it gets urinated out. All right? So, it goes into the urine. So, you'll have high what's called five hydroxy indole acetic acid in the urine. In the urine, that's actually really helpful because this should not normally be that high. So when a patient comes in with wheezing, diarrhea, flushing, endob bronchial obstruction, 1:29:33 you think they have a carcinary tumor. What could you check? Check this level. And if they have a increased five hydroxy endo acetic acid, you can do further testing. There's a bunch of different other tests. We'll talk about that more in another lecture, particularly when we get into the gastrointestinal uh stuff like cancers, but this one is a really really important thing to remember. So check this and if it's elevated in the urine that can kind of be like a little initial test to see what's the likelihood of them having carcoid syndrome. All right, cool. That's our paraneoplastics. The last thing that I want to talk about here with complications of lung cancer is the ability of this cancer to have those little cells, those little cancer cells break off, get into the bloodstream or to the lymphatic system and cause tumors to settle in other organs of the body. Let's talk about that last. All right. So now metastasis. This is really really important that you have to remember this. So when a patient has lung cancer and they come in and you potentially see that they have features of lung cancer, you get potential imaging. So you start off maybe with a 1:30:32 chest X-ray. You say, "Oh, there's a weird opacity there." Then you get a CT scan of the chest and you get a very better characterization. You say, "Oh, wow. There's a big honken mass there. Maybe even see some lympadinopathy." The next concern is is do I start ordering tests for other potential areas that spread? You can. However, a lot of the guidelines say that you should order that test based upon potential, you know, symptomatology. Um, a lot of times we're going to do a PET CT scan to look and see the degree of metastasis anyway. Um, but again, it kind of just depends on the degree of what their chest CT shows us. Um, and the and the nodes really have a lot to do with a lot of that. So, when a patient has cancer of the lung, it can definitely spread. And so, the things that we worry about is if these cancer cells, you have so many lymphatic so many lymph nodes nearby, right? Right? So you have so many different lymph nodes and if these things just happen to spread enough that they get into a lymph node, this can spread via the lymphatic vessels, right? And so this can cause these lymph nodes to get really really enlarged because they can get contained with tumor cells. 1:31:30 And so let's just say for example that these cancers, they spread via the lymph nodes. Where could they go? Well, you have a lot of lymph nodes that are kind of located along these per bronchial tree, right? So a lot of these are near the hilum that we have a lot of these lymph nodes. They're near the hilum. And so if you see a lot of these, these are definitely the ones that are going to get hit the first, right? So when a patient has a lot of hiler lymph nodes that are involved, that's what we define as what's called N1 stage. So N1 stage is when you have a lot of hiler nodes that are positive. So you have positive hiler nodes and these things are pretty pretty filled with cancerous material. Now if this spreads so let's say it starts off here let's say you have a tumor right here um and that tumor again it's spread to these hiler lymph nodes right so this spread to the hiler lymph nodes that's going to be N1 now if it then spread from the hiler lymph nodes into the mediainum so now it's 1:32:32 still on the same side so we'll kind of cut this in half so let's say that I cut this right here in half here's the tumor spread to the ipssilateral hiler nodes if it then spread into the nodes here that sit in the mediainum. All right. Then it goes here spreads to this one. That's N2. All right. So N2 is you're involving the mediainal. So the mediainal nodes, but it's still ipsyal. So it's on the same side as the tumor. What happens is when we start moving, so here we have N1. Here we have N2 the point where it spreads to the lymph nodes on the other side. So it's contrateral. So it moves over here spreads to this mediainal node or spreads here to these paritracular hiler nodes. Then we have N3. Another thing that could happen is it could spread up above the clavicle. 1:33:32 And so if it spreads up above the clavicle then we have something called supraclavicular nodes. And so the way that we define the last one is N3 and N3 is it's supraclavicular nodes are positive or you have contraateral doesn't matter which one but the contraateral nodes are positive. So if you have superclavicular nodes that are filled with cancerous material or your contraateral nodes mediastinal hiler are positive then you're N3. All right. So that's really really important to remember because it helps us to determine the stage of the patient's lung cancer. All right. So it can spread via lymphatics via the lymphatics and if it does it can cause a lot of lympadinopathy. Now if it spreads via the bloodstream hematogenous right so then it's hematogenous. This is where we get a lot of other scary things. So let's say that this thing goes and it spreads over here to 1:34:33 the brain or it spreads to the liver or it spreads to the adrenal glands or it potentially goes and spreads to the bone. This is the most common organs or sites of metastasis. You remember this via the pneummonic blab. So blab is for the brain, the liver, the adrenals and the bone. Now how would this potentially look? Brain mets. If these cancerous tumors get here, they typically like to involve the gray white junction. They can kind of be scattered. They can be all over the place. And so this can present a bunch of different ways. This could actually hit an area and cause focal deficits. This could also potentially cause like just generalized symptoms like headache or in some scenarios which I've seen in the neuro ICU, it can cause seizures like a new onset. So you really want to be careful of this as a patient's coming in with focal deficits and headache and seizures. they may have metastasis to the brain and you'd probably have to go and get a brain MRI with and without contrast to really see those ring 1:35:33 enhancing lesions. The liver, it can deposit here and if it does deposit here, often times it doesn't really cause a lot of symptoms. You may get a light increase in the LFTs. So, you may have a slight LFT bump, you know, that you want to take into consideration just like in breast cancer, you'd have to check for them. Especially alkos that may be a little bit bumped, but often times it's pretty much asymptomatic. the adrenal glands. This is another one though. When these go, usually it involves bilateral. So, it can cause bilateral METS, right? Bilateral metastasis. And usually this doesn't cause any symptoms. But if it's enough that enough of the METs have incorporated into about 90% of the adrenal cortex, it can happen. It's relatively rare, but you do have to watch out for what's called adrenal insufficiency, right? also known as Addison's disease. That's rare, but you want to watch out for that. So, the patient can start having a drop in their cortisol, a drop in their eldoststerone, right? They can have hyponetriia, hypercalemia, they can have 1:36:33 hypoglycemia, they can have hypotension, hypoalmia. It's a really, really nasty disease. The last one is bone mets. If the cancer actually does have the ability to get into the bones, the problem with this is that this metastasis, it can activate. They release things like osteoclastic activating factor and a bunch of other things that cause the activation of our bone cells. And what's going to happen is the bone cells, your osteoclass are going to get activated and they're going to start chewing through the bone and you're going to get all these nasty litic lesions, right? And these litic lesions are going to start chewing through the bone. When they chew through the bone, this is going to cause a couple different types of symptoms. One is it can cause pain. The other thing is it can cause fractures, right? pathological fractures where they have undesirable fractures that occur and it doesn't usually make sense. And the last one is that sometimes with these litic lesions they can chew enough of the bone up that they can liberate calcium from the bone. Especially if you chew enough of this bone up, you can definitely liberate calcium from the bone. So you also want 1:37:34 to watch out for elevated calcium or hypercalcemia. So these are the things that you definitely would want to consider and I would even consider checking like an alkaline phosphatase as well. So when a patient has metastasis from the lung to other different areas, what are you looking for? Lymphodenopathy is one. Often times this is not something that's usually going to be easily found like we would in breast cancer where we can palpate a node. This is something that you'd probably pick up on a chest CT and if it was missed on a chest CT, you could pick up on a PET CT scan. Right? The other thing is the other organs. This is usually symptom driven. Now with these, you may not have a lot of symptoms, but with these you may have a lot of symptoms. So often times what we look for because some of them can be completely asymptomatic is doing PET CTS to see if the tumor lights up in the liver, lights up in the adrenals or lights up in the bone. The brain is a little bit more specific. This is the one where unless the patient presents with symptoms, we may not go getting a brain MRI unless we have good reason, meaning they're presenting with neurode deficits, neurological symptoms, or they 1:38:36 were diagnosed with small cell lung cancer, which can easily spread to the brain. All right, my friends, that covers the complications. I know it's a lot, but hang in with me because now what I want to do is I want to take you down through the most proper diagnostic framework to think about how would a patient who comes in with what I think may have some symptomatology of lung cancer, how do I diagnose it? But also, it is crucial for us to as clinicians to know how to screen those patients who are at high risk and to know what are the different modalities that we use to screen for pulmonary nodules or lung cancer and catch it before it's too late. Let's talk about that now. >> All right. So, let's now move into the diagnostic approach. So, we want to first start off with the concept of pulmonary nodules. So, whenever a patient comes in and they have a smoking history, obviously we determine that smoking history based upon the, you know, packs per year and and and it really also considers their age too. When we think about that, we can put 1:39:36 these patients into a higher risk category, saying that these patients who smoke, who are older, they have a higher risk of lung cancer. And I may identify a beginning stages of it, like a nodule, or maybe it's a little bit more of a identifier of a mass. And so, we have to always consider this as a way of being able to catch lung cancer before it's too late, not picking it up when it's stage three, stage four. So this is where we're going to talk a little bit about the approach to pulmonary nodules and then considering what happens if these nodules are low risk, intermediate risk, high risk. What do we do? So the first thing is you have to know which patients you actually screen to look for these dang coin lesions or nodules that are in their lungs. So what would that be? So this is a 50 to 80 year old patient with a 20 plus packyear smoking history. That is the way that I want you guys to consider that if they got a 20 plus year pack smoke uh uh packy year smoking history 50 to 80 years of age you need to start considering doing lowd dose CT scans annually. 1:40:37 Now the other thing that's going to be important to remember is you do this even if they're a current smoker or they quit [snorts] within the past 15 years. So that's also really important. So this could be a current or if they quit within the past 15 years, you still need to consider p pushing these patients to get a annual lowd dose CT scan of the chest because this is going to help me. It's going to be lower dose. You're not exposing them to as much radiation which is also beneficial and it's going to help us to see if we see any masses or lung nodules. Now if I do this and I find a mass, usually we kind of define that as the irregularity of the mass, the size of the mass, the kind of the overall look of the mass, the contents of it, that would actually help me to be very very considerate. So if I had a greater than 3 cm appearing mass, maybe it appeared irregular, maybe it was speculated or scalloped, maybe it had some heterogeneous kind of component or it was very very high density kind of opacity, then I'm going to be concerned with a lung mass, right? An example of that is if we look here, this is going to be a CT scan. I'm taking an axial 1:41:35 kind of section. You can see here in the right lung, look at this. This is this thing is like speculated and it's a very very homogeneous kind of like appearing tissue. And so this is definitely very very considerate of a I'd say a malignant kind of like presentation. This is definitely definitely high risk and I would say that this is a patient who likely has a right lung cancer. All right. Now, in the other hand, if I see a mass that appears like it's less than or equal to 3 cm, that could be considerate of a pulmonary nodule. And so, here you can see the same kind of situation here. Here's the left lung. Here's the right lung. You can appreciate right there. There is this well circumscribed kind of round opacity in the right lung. And that really would suggest more of pulmonary nodule where this one that's really kind of like large speculated. This would definitely be concerning of like a carcinoma especially something like you know adnocarcinoma or you depending upon overall I don't have a complete look at the location but this would definitely be a little bit more peripheral um so I would definitely be concerned with something like adnocarcinoma. 1:42:35 The next thing is we want to know is this a new or known pulmonary nodule. The reason why is if it's new this is something that we have to start kind of maybe tracking a little bit sooner being a little bit more careful with. Um, if it's a known nodule, then we just want to know, has it gotten any bigger or has it stayed the same? Because if it's gotten bigger, we need to be a little bit more aggressive. If it hasn't gotten any bigger, it hasn't changed, then we can probably just continue to go with their normal annual lowd do CT scans. And so, it's important to know, is it new or is it gotten bigger? If we have a prior chest X-ray or CT scan to compare it to, so that's the first thing is knowing is there any prior imaging available. If it's not, then we have to treat this as though this is a new pulmonary nodule. If there is prior imaging, again, I just want to know, has it gotten any bigger within the past 2 years? If there's been no growth, that's okay. That's a little bit more of a benign appearing nodule and I can just kind of go back to doing my annual lowd do CT scans. If there is growth and it's gotten bigger over the past two years, 1:43:35 well, then I need to start being a little bit more aggressive. This is a suspicious nodule that's getting a little bit bigger. So with these two we kind of treat them somewhat the same which is then from there we got to let's get a standard dose CT scan of the chest get really really thin slices get a good look at this and also consider their malignancy risk because now these patients I have to fit into are they low risk are they intermediate risk are they high risk because if it's low risk I can I can continue the lowd dose CT scans but if it's more intermediate or high risk I may have to go to the route of a PET CT I may have to go the route of a biopsy And so that's what we want to do next. So let's say that we get the standard dose CT scan of the chest and we start looking at the actual nodule that's gotten bigger or it's a new one. We can then use that as a way of looking at the size of it, the overall kind of like appearance of it, the location of it and combine that with their history. So we have three categories, low risk, intermediate risk and high risk. The patient history is obviously key. We 1:44:35 want to know age, we want to know smoking. Those are really going to be the big things. So age, we want to know if they're less than 40. That puts them at a lower risk. The older you get towards that 50 to 80 year old range, you get more of that higher risk kind of category. Smoking is we're looking at have they ever smoked? If they haven't, that puts them at a lower risk. You can still get adnocarcinoma um even when you don't smoke. But again, it is really important to know that smoking is a very very strong risk factor. So for those who are current or former uh meaning within the past 15 years and they have a 20 packear smoking history, it puts them at a pretty decent risk intermediate and high risk. Now the last thing is now we're going to use that CT scan of the chest and we're going to start looking at the overall size because size plays a big role. I always say size don't matter. In this case it actually does because it helps us to stratify them. So we would say if I saw a nodule and here I have this one and it's let's say that it's smaller. It's like less than 8 millimeters. that would make me think it's more of a lower risk pulmonary nodule. If I got one 1:45:33 that's a little bit bigger, you compare this one to this one. They definitely look different. Um, and also size-wise, it's a little bit bigger. And then this one's a pretty nasty looking appearing one, and it's a big goober here. This is definitely going to be a high-risisk nodule. Now, it's not just size, it's also just the general kind of location as well. So, we've found that usually in the lower loes, those are going to be more of the lower risk. They're more likely to be potentially benign. and even if it involves like the middle lobes as well. But if you look here, these are going to be involving the upper lobes. And so the upper lobes tend to be more of a potential for malignancy. So if you see small and lower middle lobes, you're thinking more benign appearing, lower risk. If you think more upper lobes and bigger, you're going to be thinking potentially more of the intermediate and high risk. Now, the last thing is also just kind of the overall appearance of that kind of like mass or nodule, I should say. Uh so what does the margins look like? Meaning the edge of the tumor. So this one's pretty round and rounded always is a good thing. If it looks more scalloped 1:46:31 like a scalloped potato here, this would be more consistent with an intermediate risk. And if you see this one which has all these like little divots and kind of looks like a little amieba, this speculated appearance, that's always pretty concerning for a high-risisk kind of nodule. So these are the ways that we like to stratify and put these patients into categories. If I said, "Hey, I have a patient. They are 40 to 60 years of age. They're a current smoker. Um 25 pack year history. We have that they also have a decent size nodule. U maybe it's 15 millimeters. It's in the upper lobe and it appears scalp. Then that would fit them into that intermediate risk category. And so that's kind of how we would do that kind of determining what would we do next. So now that we've categorized them, we can then figure out what we want to do with them. So if it's usually the less than 8 millimeter, they're in that low to intermediate risk kind of category, we can just do a lowd do CT scan. You can still do it in a year or you can do it a little bit earlier, maybe 6 months and then again at 12 months. All right? So that's something that we could do just to make 1:47:28 sure that we get a just a quick little interval in between and then we can go back to just our lowd dose annual CT scans if everything's normal. Um and so again, that's what we're going to try to do here, right? The next thing is that we have it's a little bit bigger. So maybe it's 8 millimeters or greater in their load to intermediate risk. So that size is a little bit bigger. In this scenario, what I would say is this patient should probably be getting a PET CT scan. The PET CT is always going to be great because it's going to help us to really really look for any kind of like look of that lesion and particularly look to see if there's a lot of uptake um of that FDG. And the FDG uptake is really concerning. If it's a pretty decent sized one and they really have all the high-risisk features, they're greater than 60. It's speculated, it's uh greater than eight, so maybe it's like greater than 20 millimeters, it's in the lower um it's in the upper lobes, they have a current 20 packear smoking history or greater. These are all things that really put them at risk of a high, you know, having a malignant kind of disease. And so for them, we should just go straight to a 1:48:27 biopsy. Now, what I want to say is that sometimes you can get a PET CT. And if you get that PET CT and it shows, look, oh my gosh, here's these like nodules that I have and they're really taking up all of that tracer, that's really concerning. That means it's a super hyper metabolic type of tissue and that usually screams cancer. And so for them, I would go straight to a biopsy if I had something like that. So that's really, really important to remember. You get a positive PET CT that shows this kind of like presentation, a very significant uptake in these nodules, you should probably just get a biopsy because there's a high chance it's it's malignancy. All right. So, that's kind of how I want you guys to think about this. So, the biggest thing to take away out of this is that you need to know when [clears throat] you screen. If it's 50 to 80, 20 pack year history or greater current or they quit within the past 15 years, you need to do annual lowd do CT scans. Look at prior imaging if they have it. If it's new or it's gotten bigger, you get a standard CT and then look at the risk stratification. If it's low risk and it's a small one, you just keep doing your SK CT scans. maybe 1:49:27 just a little bit sooner, 6 months. If it's a little bit bigger, low intermediate, you should get a PET CT scan. If that comes back positive, you get a biopsy. If it's high risk and greater than or equal to 8 millime, then you should be going straight to a biopsy. If you have the pictures and they don't look like they're any different, they haven't grown, just continue with your normal annual lowd do CT scans. It's all a way of being able to make sure that we determine which ones we should go and really be aggressive with and which ones we should just hold back and keep monitoring so that we don't catch this when it's too late. All right. Now, let's say that we have a patient that we unfortunately we caught this too late. We don't have a patient who's asymptomatic and we're trying to screen. They unfortunately come in with some symptoms. And [clears throat] a lot of the times with lung cancer it can be relatively non-specific. They can come in with things like cough, right? because of an endob bronchial kind of obstruction, wheezing and disna. And these are sometimes that when a patient has something like this, you think that they have something else going on. Maybe 1:50:25 they have pneumonia, right? That's that's something you could definitely think about. Maybe they have COPD because they're a smoker. And so oftent times what ends up happening is with these non-specific symptoms, you're looking for something going on with the lungs. And so you end up getting a chest X-ray. And it's a common initial test. It is not a diagnostic in the sense it's first line. You may pick up something. Oftentimes what happens this something that's really really important to remember is patients can get recurrent kind of like post-obstructive pneumonia and that's really really important whenever a patient has recurrent pneumonia in the same lobe something we talked about on the whiteboard recurrent pneumonia in the same lobe especially upper lobes and maybe they have some type of like hazy opacity so you can appreciate here on this chest x-ray you can see that there's kind of like this opacity here and it may be obstructing a part of the bronchus which is supposed to be getting secretions and bacteria moving and spit it out. If it's not, it's obstructing that leading to fluid leading to bacteria becoming static, colonizing. Eventually, that can really 1:51:19 lead to an infection. And so, you can get recurrent pneumonia in the same lobe that really screams some type of like endobial tumor like adnocarcinoma or like a broncogenic carcinoma. So, that's something I would definitely definitely consider here. So, we can definitely appreciate that. [clears throat] Now, if you see a suspicious lesion, it's always important to consider, do they fit the bill? In other words, you can have a patient who has, you know, maybe something else that looks like that could be a mass. Um, but you have to consider their history. And so for these patients, you want to look know, do they have a heavy smoking history? Are they 50 to 80 years of age? These are going to be patients who are more in that high-risisk category. So you always want to look at their history. We want to know, are they a heavy smoker? Do they have some of these classic findings that we talked about? And then also be a really good investigator. The things that we talked about on the whiteboard are like the complications. Are they presenting with post-obstructive pneumonia in the same lobe? That recurring pneumonia in the same lobe really screams lung cancer, especially 1:52:17 adno. Do they have any hypothesis? This can sometimes present if you have a pretty nasty tumor. Usually, it's got to be broncogenic. So, it's got to be somewhere within that lumen. Um, so you can definitely see this in things like squam cell or small cell, maybe an adno. Compressive symptoms is another really important one. Do they have compression of the recurrent lingial nerve causing horarsseness of the voice? Do they have compression of the brachio plexus causing brachio plexopathy? Do they have compression of the frenic nerve leading to a asymmetric you know movement of the diaphragm? Right? That uh kind of problem where you can see it on chest X-ray where they have an elevated hemiaphragm and maybe some shortness of breath when laying flat. Um do they have compression of the sympathetic chain ganglia causing her syndrome? So they have miosis and tossis and anhydrosis. Do they have compression of the superior vennea causing SVC syndrome causing uh you know distension of the jugular vein causing swelling of the face, the neck and the arms with that bluish hue to it? These are all things that you want to 1:53:19 think about that could be consistent with compressive symptoms from a large tumor. Uh usually things that are going to be in this scenario you think about they're going to be a little bit more centrally and more apically located which you can see with squamas cell with small cell with adnocarcinoma. Now recurrent plural eusions are something that you can definitely also see with peripheral lesions. Things like large cell carcinoma, adnocarcinoma can also cause peripheral um kind of involvement of the lung tissue and that can lead to again a lot of exudative kind of properties, fluid leaking out, proteins leaking out, LDH leaking out into the exodative fluid or the uh plural cavity that's leading to these recurrent plural eusions. Often times you'll tap these, you'll get maybe a bloody aspirate, you'll send it off for cytology and you'll send it off for the lights criteria will suggest exudative and your cytology will come back and you'll show some evidence of some malignant cells. And lastly is paranoplastic syndrome. This is a classic one you have to remember. Again, it's talking about that patient with small so comes in with SIADH, right? That's a really really big one. You 1:54:18 can't forget that. The Lambert eaten syndrome is another one that they can present with as well. uh which is the kind of the weird presentation of the myastthenia gravis. Um you can even present with like a Cushings type of appearance because they can present with a lot of high act levels. So those are definitely things to think about whereas you know the squamic cell they present with the hypercalcemia and so these are definitely things I would kind of try to put together if you have a patient who comes in they're a heavy heavy smoker they have some of these non-specific symptoms they've had recurrent pneumonia in the same lobe they have now also you see on their BMP a low sodium um and you also notice they have Cushing like features um and then on top of that they also have maybe some compressive symptoms like recurrent luren ial nerve or maybe some frennic nerve that would make me start thinking about a tumor that's in the lungs that's causing a lot of these problems. And then from there I got to get one of the best tests to really determine that. A chest X-ray is not going to be the one. Chest X-ray may show me an abnormal like 1:55:18 opacity, but the CT scan is going to be the best. And what it's going to really do is it's going to help me to elucidate the overall look of it. Look at this nasty looking mass here in the right upper lobe. So, this is a really really nasty looking mass and it's definitely a decent sized one. It definitely has an irregular type of appearance. It's super decent sized and it's likely causing some obstruction here which can definitely lead to pneumonia in a lot of these patients as well. But this is pretty pretty concerning. That's a pretty scary looking one right there. So, that's definitely a lung mass. Another thing that you can sometimes see on the CT scan is you may be able to see if there's any lymph nodes involved like any higher lymph nodes involved or other associated lymph nodes because that can help you to determine if there's a significant amount of beginning of of kind of some local spread or metastasis. Now once I see this it's it's it's straight to a biopsy. You got to get a biopsy. But the biopsy the way that we do a biopsy on a viscera like this kind of depends upon where the lesion is. So, if it's centrally located like like this one is, I'd probably just do a 1:56:17 broncoscopy, uh, and then you can go down there and you can do a biopsy of that tumor, especially if it's in the lumen. And so, you're basically taking a broncoscope, you're going to run that thing down into these bronchi, and you can't get super far. You can probably maybe get to like the secondary uh, maybe tertiary bronchi, but that's pretty far down. You're going to get down there and you're going to see if you can find that tumor indoluminally, and you're going to help to take a piece of it out, and then send that off to pathology, right? So that's what I would say is the best thing to do for a centrallylo lesion is a broncoscopy with a biopsy. Now if it's more periphally, so it's towards like the wall towards the chest wall, then running that bronoscope, you're not going to be able to get that thing far enough down to like the level of where you want it. You need to go from the outside. And so we can do CTg guided uh fine needle aspirations where we use things like CT scans to locate and pinpoint that and then use real time we can stick a needle down through the chest wall and then help to pull that actual sample out with the biopsy needle. So that's something 1:57:16 that we can try to do there. Another one that's pretty aggressive, we don't really do this unless it's truly something that you can't do with a CT guided FNA, but you'll do a VATS, a video assisted thoroscopic surgery, and you'll go in literally and you'll try to utilize um a different source where you can visualize the mass and you'll take forceps and take a piece of that actual tissue out. This one's pretty aggressive, but you can do this for decent sized, you know, I'd say a little bit more complicated cases. It should be a CT guided FNA first. This would probably be a little bit more of the latter one in a complicated patient. All right. Now, for the plural eusion, which is still kind of peripheral, but they don't have maybe a obvious peripheral lesion, or maybe they do, but you have maybe a peripheral leion with a malignant associated plural eusion, you can tap that and you can pull it off. And if it comes back positive with a bloody aspirate um which show a little bit of more of that malignant cells, that's immediately that's that's stage four lung cancer. So, you definitely can do that with a thorosentesis. And so, again, let's say that they had a tumor 1:58:13 here. here they had associated plural eusion that was kind of accumulating some bloody cells. You could take your needle, pop right in, take some of that sample off, and then send it. And if it comes back positive with any kind of malignant cells, you have right there, you have you have cancer. And so from there, we then say, okay, let's take all of these different samples, whether it's the broncoscopy or biopsy from the central leion, the CT geted FNA or the VATS from the peripheral lesion, the cytology from the thorosentthesis from the plural. Let's send it off to the pathologist, have them take a look at it, figure out what type of cancer it is. Is it large cell? Is it small cell? Is it squamas cell? Is it um adno? Is it carcinoid? All of those things. And sometimes we even throw in aminoistochemistry. This is a little bit more for your step one. I wouldn't say that you're going to get as heavily tested in this in the step two, but I'm going to briefly kind of recap it in the sense that when we think about carcinoid tumors, they're really well differentiated. It's a neuroindocrine type of tumor. Neuroendocrine tumors usually present with a on a stain, they 1:59:10 have a chromogran a that comes up positive. And there's another tumor that's kind of similar to carsonic tumors called small cell. They're also neuroindocrine tumors, but they're very very poorly differentiated as compared to the carcinoid tumors. But if you look, it'll still have that chromogan a stain. Then we have squam cell carcinoma. Squamic cell carcinoma is going to be squamas cells. They're going to have these keratinals, these bright pink kind of appearing uh kind of like lesions that you'll see on the actual hisytologology. Again, that's going to be more step one. What I do want you to know is that if you test the imohisty chemistry, it'll come back positive for a specific molecule called P40. That'll be positive there. Now with adnocarcinoma, this is going to be glandular cells. They're going to have tons and tons of mucin staining. And when you check the immune chemistry, it should be for the TTF-1. And lastly, there's large cell carcinoma. These will have these poorly differentiated large cells. And you shouldn't have any chromogan A. You shouldn't have any P40 that comes positive on this one or even any TTF-1. So from there, we've said, okay, we took 2:00:07 the the actual sample, we send it off to the pathologist. They'll give me the diagnosis of the type of lung cancer. And then from there, I just need to determine, has this lung cancer? And you should sometimes be able to pick it up from your CT scan. Is it involved other areas? Sometimes you can see it, sometimes you can't. And you got to start extending your CT scan parameters to get a little bit more of the chest, maybe get more of the abdomen, the pelvis, get other imaging if needed to see if this thing is spread. So, a CT abdomen and pelvis is pretty good. The literature is actually starting to suggest that the PET CT is even better because you can still do the CT chest ab and pelvis and then if it really doesn't give you anything sometimes PET CT is good for picking up some things that you couldn't see. It's a little bit more occult. It's a little bit harder to see. So the PET CT scan would probably have the better sensitivity but often times we just go with a CT abdomen and pelvis first. Now, if you did that um CT abdomen and pelvis and you don't find any distant Mets or you, you know, you want to then go the next step, you can do a PET CT after that if you still have 2:01:07 a high degree of suspicion for METS. But if there's no distant METS, then we say that that's usually stage one to stage three non small cell lung cancer. So that really only includes the ones that we talked about, which is going to be again in this case, it's going to be your adnocarcinoma, your large cell, and then your um uh your large cell and squam cell. Those are going to be the primary ones I want you to remember for your non small cell lung cancer. Um the limited small cell lung cancer that's going to be small cell and that means that it probably hasn't spread very much beyond one side of the lung and we we'll we'll define this right but at this point if they don't have distant meds it could be anywhere from stage one to stage three non small cell or limited small cell to give you a little bit more on that. So let's say that a patient has non small cell lung cancer. We want to determine if it is stage one to stage three. Well we know it's not based off distant mets. How do we determine it then? Well, then it's dep based upon the tumor size and if there's multiple different types of lymph nodes involved. So, for example, if I have a tumor here 2:02:05 and there is some nodes but none of the nodes are involved, it's just a tumor itself. That's more likely to be stage one. All right? Now, if the tumor is maybe a little bit bigger, right? And it's starting to involve other nodes that are in the same side. So, like these per bronchial nodes, that's going to be stage two. If it's stage 3A, you're getting a decentsized tumor. But now what's starting to happen is is we're starting to go from per bronchial and we're starting to venture our way outwards here into the mediainum. So then what I would probably start seeing is more of the mediaininal lymph nodes being involved on the epsilateral side. Right? Stage 3B is you have now the problem is that some of these nodes can start spreading over to the contraateral lung. So now if you had a tumor in the left lung with all the nodes in the left lung that are getting involved because this tumor is spreading into these lymph nodes. Right? Now if it starts to spread to the other side or it goes upwards into the clavvicular nodes now you have stage 3B. All right. So that covers your stages one to stage 2:03:06 three. We don't determine it based upon if it spread to the other areas of the body like the brain, the bones, the liver, things like that. We determine it based upon the size of the tumor and more particularly the nodes that are being involved. All right. With small cell lung cancer, it's actually very simple because there's only two stages. It's limited and extensive. And limited is simple. It just it that tumor and the nodes, it's only in one side of the lung. So you could have a tumor that's gargantuous and you could have nodes that are involved in that entire lung. But as long as it hasn't tumor hasn't gone to the other lung, the nodes haven't spread to the other lung, it hasn't distantly metastasized, you have limited stage small cell lung cancer. All right? Now, when we have distant mets, now we're talking about a potential problem here. So that means that this tumor has gotten into the bloodstream and it's spread to other organs. A very common one is the bilateral adrenal glands. Look at these. Look at these. [laughter] They're gargantuous. So your adrenal glands are like just cantalopes down there. This is very very consistent with a metastasis, especially if it's 2:04:06 bilateral. If you got adrenal megaly and it's bilateral, you should always be concerned about this kind of presentation about a metastasis, right? Um, another one is hpatic metastasis. You can see all these like hypo dense kind of lesions here on CT scan. They're super scattered. This is pretty consistent with hpatic metastasis as well. And then here we got a bone scan u because it it loves hits the bone. So it loves the liver, loves the adrenal glands, loves the bones. So you're going to see here there is a primary tumor. Look at all these areas that this this dang thing has spread to. So it's involved a lot of different types of bones. Some of the pelvis, some of the vertebrae. So they're probably going to have some bone pain, some increased alkos. Those are definitely things that I would say this is distant metastasis. So when you got distant mets, now it's stage four or it's extensive. It's that's pretty much how we kind of get to this point. So we got stage four or we got extensive small cell lung cancer. All right. Well, let's say how do we determine stage four? It's usually if it's distant meds. There is other ways. And so I I just need you to know that we 2:04:59 don't always just base it on distant mets. Sometimes the exam will say distant Mets is the biggest reason. But it also could be due to uh let's say here um I consider that I have a tumor, right? And it started to spread to other nodes. But I'd say the biggest one here is it started to distantly metastasize. But what if this tumor broke off, went through these nodes and went to the other side? Oh, tumor in the contraateral lobe that also is stage four. So if you have a tumor in one side and it then it spread to the other side that's stage four lung cancer. The other one is if it broke through if it broke through and got into the plural cavity. So you got plural invasion dude that is stage four non small cell lung cancer. All right. So we got an idea of the stage four now that it's distant mets but it's also if the tumor went to the other lobe or if it went to the plura. for extensive. We had a tumor that was here and it was a big honker and if it distantly metastasized that was one reason we said it could be stage four 2:06:00 but it's the same concept if these nodes go beyond or you get a tumor in the contrlateral lobe. Now this one usually small cell doesn't get close enough to the plura to ever cause plural eusions but it is going to be one that it can spread to the contrlateral lobe or involve nodes of the contrlateral lung. So if you got a contrlateral tumor or you have nodes in the other lung, it's beyond the hemithorax, we now have extensive small cell lung cancer. All right? So those are the ways I want you to think about it. So it's not just it mets, it's if the tumors in the other lobe or if the plura got invaded. That's the big thing to remember. For extensive, we just say, did the nodes go also to the other side as well. All right, cool. Now that we've hit that, my friends, we've covered a decent chunk here of staging. The next thing it's also important to remember when it comes to staging is we determine how we're going to kind of treat these and we're going to get into it a little bit, but we say how likely these patients are to get surgery depends upon their stage. Stage 1 to 3A, we can say pretty decently that with stage 1, stage two, you could go straight to surgery 2:07:01 for these patients. With stage 3A, we may have to shrink the tumor down a little bit, give them some neoagivant chemotherapy, and then do surgery. But there's always a chance of resecting those, especially if they do well to the uh the chemo and the radiation. With these, it's not often likely that they're going to respond well to chemo and radiation. They're probably going to need chemo, radiation, amunotherapies, different types of targeted therapy as well. So, these are not usually reectable. All right. Now, one other thing that's really important to remember is the brain is a very common area for the lung to spread to. So, if they have small cell lung cancer, you should always have a high degree of suspicion of it spreading to the brain. That's probably the biggest one. Um, so small cell lung cancer, you should probably consider checking these patients for a brain MRI. If they got stage four, that's also a risk, but definitely not as high as small cell lung cancer. But the biggest one is if they present with neurological symptoms, you should definitely get a brain MRI. If you see something like this where they got all these different lesions 2:07:53 everywhere, that's definitely metastatic disease. And so this thing has spread to the brain as well. And that would consider them to be an extensive case, right? So you can have a patient come in, you don't know that they have distats, but they have lung cancer. All of a sudden they come in with neurological symptoms, you get a brain MRI, boom, oh you got dists, they're now stage four, right? But if they have small cell, they have stage four, you should consider getting a brain MRI to see if it is present there. U because this is a very very high-risisk one. All right. [clears throat] Now last thing is if a patient has stage four non small salt lung cancer, it's also really important at this point because they're not reectable. we need to know what's the best kind of targeted therapy or amunotherapy that I can use for this patient because that's really when we talked about the eGFR the alk rearrangement um and there's another one that we'll discuss a little bit called the PDL1 which is the program death lian which is really really important in determining how te- cells are either going to be you know not to be weird but like turned on or turned off and that 2:08:50 determines if they're going to kill the tumor cell or not these are really really really important things to remember so we should always get these like molecular genetic testing to see which one should we actually treat these patients with. So for example, if they have the EGFR mutation or the alry arrangement, those are going to respond well to targeted therapies like the receptor tyrroscene kynise inhibitors. Um those are going to be really really good ones that we'll talk about. Oscar mittenib, electibib going to be best for those scenarios. if they have the PDL1 um kind of like involvement and it's a a little bit higher, these are patients where I should target um I should target their PD1 on the te- cells and that's something where pimberlymab is really really good and they're going to respond to amunotherapy. So depending upon these determine which type of drugs we'll give we're going to target the receptor tyroscen kinise or we're going to target the PD1 um uh protein that's on the actual tea cells. So these are definitely really really important things to remember. That was a lot, right? All right. So that's really taking into consideration a patient who 2:09:47 presents with symptoms and maybe it's non-specific, but you find a mass you get to that point. You say, "What do I do? How do I biopsy it?" Okay, I've biopsy. I found the type of tumor. How do I stage it? Okay, I found that they have no distance. Well, how do I know if it's stage 1, 2, 3, A, 3, B, or limited? Okay, I've done that based upon the lymph node involvement. And if you know that's the primary thing and then okay they have distant mets that tells me if it's stage four if it's extensive but there's also other things like plural invasion and contrlateral lobe tumors and nodes in the other one that could make me think that it could also be uh stage 4 extensive and then from there I got to say if it is non small cell lung cancer how do I know if it's going to respond to targeted therapy or amunotherapy lots of stuff right let's move into the treatment of lung cancer so we're going to dig into non small cell lung cancer first with non small cellar lung cancer there's obviously different stages stage 1 2 3 A 3B and four we need to have an idea of what is the goal in treating these dependent upon that stage so stage one again 2:10:50 you're talking about you're having a tumor usually no kind of like nodes are involved what is the primary way that we treat this is surgery and there's different ways that we can surgically remove this tumor we can do like a wedge resection we could do a segmental resection we could do a loopctomy where you remove the right upper lobe in this case or you could remove the entire lung. So that's pretty aggressive to do in stage one. Oftent times just a wedge or segmental resection may be just the way to go with a stage one uh non small cell lung cancer. Now, another thing that's also really important is you can consider in patients who maybe aren't surgically fit because what you have to do is you always have to see if these patients are medically able to survive, I'd say, or do well with a surgical resection. And oftentimes that depends upon what their pulmonary reserve is. You're removing lung tissue, so you can take away some of their pulmonary reserve. So oftent times we'll do pre surgical PFTs to see where they're at and based upon those PFTs their multiple kind of like if they have multiple coorbidities and how well they'll do we'll determine if we do a surgery or if 2:11:52 it's really not a good idea and they they're not really about doing a surgery. Maybe they want to go the non-surgical option. You can do a stereotactic of blade of radiation therapy where you literally target on that tumor and you hit it with radiation to try to be able to shrink and kill some of those tumor cells. So that definitely is an um an ideal way. If you don't want to go the operating route um you don't have maybe that PFT reserve then they won't do that. They'll usually go to an an SABR. All right. Now stage two is you got the tumor, you got some per bronchial kind of nodes that are involved now. And so this one again surgery is going to be the best way to go. Um and I would say that's going to be preferable. The other thing is that afterwards you can hit them with some adgiant chemotherapy. Now the chemotherapy agents of choice in this scenario is usually going to be um cyplatin and a topoide and again you can use it adgivantly mean meaning that you use it after they get the surgical procedure. So after you get like a wedge resection a segmental resection a lectomy depending upon the severity of the tumor how invasive it is you will then follow it up with a couple 2:12:54 different cycles of cyplatin and a topoy. All right. Now, stage 3A is we got a tumor. It's a decent size. It's starting to involve medastininal lymph nodes on the same side, some per bronchial nodes. It's getting a little bit more aggressive at this point. You can still do um surgery, but at this point, we want to start shrinking that tumor. And so, we hit them with neoagivant chemotherapy and often times radiation therapy as well. You're going to goal is to get the tumor to shrink down, get a little bit better, get them to the point where we can do surgery, see if it's reectable. So you're going to see do your best, shrink the tumor down, see if you can get them to be a rectable candidate, then send them to get the surgery. After the surgery, follow up with a couple different cycles of the same chemotherapeutic agent. So you'll hit them with chemo, radiation, cyplatintopicide radiation therapy, shrink the tumor, cut it if able, and then follow up with adgivant chemotherapy. If they're stage 3B, these are patients that are not going to be really be medically operable. It's just they're going to have a huge tumor. It's 2:13:55 going to be involving nodes on the same side and the opposite side. So, it's going to be pretty extensive at this point. So, surgery really isn't going to be the way to go for them. You're going to do the same thing that you would do with stage 3A except it's not neoagivant chemotherapy. It's just definitive chemiation therapy. And then afterwards, you're going to see if you can do some consolidation with amunotherapy to kind of really reduce the growth and the development of that tumor. And so, often times we'll do that with dervalamab. Now stage four on the other hand surgery is not really an option. You got either distant metats, you got a tumor in the contraateral lobe, you got plural invasion and you got multiple nodes involved. It's just trying to go and resect that's going to be a nightmare. It's not going to be very very helpful. Sometimes it can be for palative reasons. If there's very very specific reasons like significant pain or recurrent pneumonia, things like that, you can go after some of them, but usually surgery is not an option. And so with these patients, we oftent times just do targeted therapy. Um, and so we tried that's when that kind of the 2:14:49 discussion of knowing if they have the EGFR, the aly arrangement, the PDL1 is really the key thing. So again, if they have the EGFR mutation, oscermitib is going to be the way to go. All right, that's going to be the way to go where you're going to be targeting this type of pathway and kind of this is really really important on this one. All right, so oerittib is going to be helping with that. Electib is going to be for the alarrangement mutations. And so these are both receptor tyrroscen kinas is just knowing which one of these they have that can help. But overall the targeted kum like the targeted therapy agents is going to be receptor tyrroscen kinus inhibitors. So you can think about like this here you have some cancer cells you're going to have um you know different types of growth factors binding on to these receptor tyroscen kinases. They're going to be activating this pathway the pi3k thet mtor pathway that's going to help to stimulate genes to increase your cellular proliferation survival increase blood flow to that tumor and helping it to be able to unfortunately metastasize. So all of these things are what's happening when you have the receptor tyroscen kynise 2:15:45 firing in that cancer cell. If I target this receptor to reduce its autophosphillation, reduce this pathway, then I'm going to then inhibit all of these processes. I'm going to shut down cell proliferation, cell survival, increase blood flow to the tumor, and it being able to metastasize. So this goal is preventing the progression of the disease, not necessarily curing it or removing it. It's just trying to reduce the progression. All right. This is a pathway that's really really heavily involved in EGFR because what happens is an EGFR mutations or alyer arrangement. This pathway is firing like crazy because you have some type of receptor abnormality where it's kind of autoactivating or an alyer arrangements. So you maybe have an abnormality in that kind of receptor where again it's just autoactivating. If you can try to shut that pathway down that will definitely be helpful. All right. Now, amunotherapy is really good if the PDL1 uh percentage is greater than equal to 50%. That means that you have like a really really strong chance to target the PD1 because if that percentage is 2:16:47 pretty high, I can give anti-PD1 antibodies and they're going to like pimbrlymab and that's going to nail that PD1 and it's not going to allow it to interact with the PDL1. So, let me let me show you what I mean. Here we have a tumor cell when they express lots of the PDL1, right? Because your T- cell expresses PD1 pro, you know, this is a programmed death receptor. You have a T- cell receptor on the tumor cell. It's going to have an MHC2 complex which connects with an antigen. But here, the PD1 is supposed to interact with the PDL1. And this is a way of the tumor cell increases expression to shut down the T- cell, turns it off so it can't kill it. If I give a drug that binds the PD1, it can't bind to the PDL1. If it can't bind to the PDL1, you lose that ability to turn the T- cell off. this thing's active. It's ramping up. It's like, "All right, baby." And it starts ripping the tea cells. That's when we would do this is when you have a high degree of PDL1 expression. If your PDL1 expression is on the lower end, you're unfortunately going to need to kickstart it and give it some more help. You can still do the pebrismap, but you're 2:17:49 probably going to have to add on some chemotherapy like the cy platin and the attopicide to really help with that process. All right, that's a crap ton of information, and I get it. I'd be overloaded, too. Let's put this together. If you got a reectable tumor, we're thinking stage 1, stage two, could even be stage three as well, right? Especially stage 3A, but in stage 1 to two, you want to first determine what's their PFTS. Are they a good surgical candidate? If they aren't, they don't have good PFTs, they just don't want to get the surgery, DSABR is the best way to go. If they're stage two, you're going to have to follow up with adgiant chemotherapy. If they're medically operable, they're a good candidate, good PFTS, they want the surgery, you'll then go the surgical route, whether it's the segmental, the wedge resection, the lbectomy, the pneumanctomy. That's pretty aggressive, but we would do those and then follow it up with agent chemotherapy if they're stage two. Now, again, if a patient's stage two, often times they're going to get surgery more 2:18:50 likely than the SABR, but you still can get this in stage two. All right? It's just it's going to be more common to get the surgical procedure. Now, if they're theoretically unresectable initially, that doesn't mean that stage three, stage 3A can be reectable, but you have to see if it is. So, let's say that it's theoretically unresectable. Well, then all we want to know is is it metastatic or not? Because if it's metastatic, I I can't do any kind of surgery whatsoever. If it's not, okay, there is a chance this could be stage three, but I don't know if it's stage 3 A, stage 3B. If there's mediainal nodes, that's the stage 3A. If it's starting to really get to the point where it's getting to the contrlateral, the clavvicular nodes, we're getting into stage 3B. Stage 3 A, you can hit them with neoagivant chemotherapy, cis platintopicide, radiation therapy. Shrink that [snorts] puppy down. And if it gets to the point where they are a surgical candidate and you get a good response, you can do surgery. All right? And then you can 2:19:50 follow up with some adgiant chemo as well. All right? for stage 3B though, that's the problem. No, I'm sorry. Now, if you don't get a good response, we're not going to be going the route of surgery. That's why theoretically stage 3A is reectable. But if you don't get a good response here, you're not going to be going to a surgical procedure. If you didn't shrink it, if you didn't actually get that thing down and they still are into So, you didn't get rid of any of the nodes. Unfortunately, at this point, you really just got to say we're just going to stick with the amunotherapy, the the consolidative immunotherapy like deer map. All right. Now, stage 3B is you got contraateral nodes, you got the superclavicular nodes you're hitting. That's stage 3B, right? At this point, we don't have any option of surgery. It's just you're hitting them with definitive chemo radiation therapy. And then you're going to follow up with some cons consolidative therapy. Now, here we got metastasis, right? We got it spreading. This puppy has spread to the bones. Maybe maybe it's spread to the adrenal glands. Maybe it's spread to the liver. Maybe it's spread to the brain. 2:20:51 At this point, you're stage four. With [snorts] stage four, we don't do surgery. We don't do like definitive in the sense of chemotherapy and radiation. It really comes down to what type of like targeted therapy would we go for? If they got the EGFR, the aly arrangement, it's the receptor tyrrosine kynases. Ocermitib for the EGFR, elective for the alk. If they got the PDL1 with the heavy expression, brother, the peberlymab is the way to go. But if the PDL1 expression isn't high, it's going to need a little bit of help. That's where you're going to get the pimberlyab and the chemotherapy as an added effect. This is a way of kind of taking and looking at everything we talked about in the table, the images, and just giving you more of a straightforward hopefully a systematic way of thinking about it. I really hope this helped. All right, small cell lung cancer, thank goodness, is so much simpler. When we think about this, when it comes down to if it's limited or extensive, there's not stage one, two, three, four, all these different things. So, it's limited. It's it's it's in the one hemthorax. And so, this one's chemo 2:21:52 and radiation. It's really the only way that we go about this one. There is a big goal here. All right? Where with small cell lung cancer, you can try to prevent the brain metastasis. So that's why you try to get if you have the diagnosis of small cell you should get a brain MRI as a baseline because if they get neurological symptoms oh shoot they got they got metastasis it's extensive you couldn't you can't do this anymore so if you check it and they don't have any brain metastasis you can do proylactic cranial radiation you literally are radiating the brain to prevent some of the micro metastasis from the lungs to the brain and so this is a very very very high yield to remember that for limited stage always try to consider prophylactic cran radiation with the goal of trying to mitigate and prevent to a degree brain metastasis. Now extensive is chemo radiation therapy isn't really going to help at this point. What can be considered as amunotherapy? Um so amunotherapy a tesalismab is very 2:22:52 interesting. It's a PDL1 antiPDL1 antibbody. So remember the PDL1 is the one where it's on the tumor cell right? So you got your T- cell expressing the PD1, the T- cell receptor. You got the tumor cell expressing the MHC with the antigen and you got it also expressing the PDL1. From here, if I give a drug now that blocks the PDL1 on the tumor cell, now the PD1 can't interact. That still activates the T- cell starts getting ready. It's getting cooking and it kills that tumor cell. Boom, baby. that can help that can help to reduce the growth of the tumor, reduce the kind of extensive growth and nastiness of that small cell lung cancer. My friends, this was a monster lecture and I really hope that it helped. I really mean that. I really hope that you guys enjoyed these videos. I hope it made sense. I hope that when you guys get an exam and you see anything on lung cancer, you feel confident that whenever there's any question, nothing can stand in your way. Man, I love you guys. Thank you guys for being so supportive and just love you as always. Until next time, my friends.
