BTK Clinical Challenges in Thoracic Surgery Mesothelioma

Hello, and welcome to another exciting behind the knife clinical challenge with your Swedish thoracic surgery team. I'm Kelly Dawes, a third year surgery resident, and I'm joined today by my fabulous attendings, Dr. Peter White and Dr. Brian Louie. Afternoon. Hi. Also new to our podcasting crew today, we have Dr.

Adam Bograd. Dr. Bograd is another one of our wonderful thoracic surgeons in our department here at Swedish. with a passion for all things thoracic oncology. We're very excited to have him here with us today to discuss these interesting cases. So today we are going to be talking about mesothelioma.

Let's dive right in with a case. You're asked to consult on a 50 year old female. She is previously healthy and presents with three months of cough and chest pain. She initially attributed this to a lingering cold, but then started to have some night sweats and get more short of breath, so she saw her PCP.

Her PCP got a chest

x ray, which showed this large right pleural effusion. So the patient was sent to the ER for a diagnostic thoracentesis. Her output's a little bloody and concerning for malignancy, so the ED provider gets a CT chest. And all of a sudden sees these pleural plaques, but there's no evidence of any pulmonary nodules.

All right, well let's pause here quickly. You know, obviously this is an episode about mesothelioma, and so everybody's thinking that. But but Kelly, what's the broad differential diagnosis for this patient? Absolutely, and I think for a lot of people, their mind might not jump right to mesothelioma in this case.

So Some things that might be considered, you could think about a chronic empyema, this can lead to some significant pleural thickening. You could also consider infectious etiologies like tuberculosis. For the infusion we also need to consider that heart failure and renal failure could be responsible.

So, a little bit less likely given the fact that the effusion is only on a single side and that there's pleural thickening present. In terms of other

malignant possibilities beyond just mesothelioma, you could think about a sarcoma, you could think about lymphoma, or even metastatic disease from a primary lung cancer or a cancer of non pulmonary origin.

Right, so Kelly, you look at the light's criteria and the fluid, you can sort out, is it transidative or exudative? You look at the cytology from the effusion and you may see some malignant cells. But Kelly, how likely are we to get a malignant diagnosis from a thoracentesis? And what's really going to be the most definitive way to make a diagnosis?

So, although a thoracentesis has better chances of diagnosing other malignancies than it does for diagnosing a malignant mesothelioma it's only about 15 to 30 percent sensitive in that case. This increases as you do multiple forced procedures as often times these patients get as they're trying to sort out the diagnosis, but it can still be difficult to differentiate between just reactive mesothelial cells and a true malignant mesothelioma.

So you really need tissue. The

definitive way you're going to make this diagnosis is taking the patient to the operating room and doing advanced pleural biopsy to send tissue to your pathologist. Right. Right. So. On a thoracentesis, if you get enough cells and they can make a good tissue block, there's actually very good reliability between cytology.

and tissue specimens for diagnosis. First, they've got to look at WT1 and calretinin. Those help differentiate mesothelia origin. And then once they know mesothelia origin, then they'll look at other tissue based biomarkers to understand, is this malignant mesothelioma? Or reactive mesothelioma. Some of those markers include BRCA one, associated protein one or BAP one, and they'll see a loss of that protein.

They can look at Mtap and then CDKN two A, which is P 16. And all of these can differentiate malignant from mesothelioma, some of which are immunohistochemistry, some of which are by

fish. And also we'll check for PD L1, although it's really not clear how PD L1 expression may predict immune checkpoint inhibitor response but it's still some valuable information to have.

Those are a lot of abbreviations, Peter. Now there are some very important considerations to make if you're concerned about mesothelioma when you do your VATs. So let's talk about that. Adam, can you take us through how you approach a VATs for this patient? I think that's a very important concern. You know, when you're planning out your vats incisions, you want to think in your mind, where is your extended posterior lateral thoracotomy incision going to be if it is a patient who winds up being resectable and is taken to the operation.

So typically for both extra pleural pneumonectomies or pleurectomy decortications, you're going to go through in the fifth inner space with removal of the six ribs. So what I. typically do standardly is I'll draw out the potential thoracotomy incision, and I'll

plan to place all of my VATS ports along lines of that thoracotomy incision.

And typically you can do most of your pleural biopsies through a single incision. If for whatever reason they have a fused pleural space or they've been talc before they've gotten to you you can actually just make a cut down on the interspace and excise out some pleura through a single incision.

I think one of the things that's most important is to make sure you sample deep enough. So, I was always taught that a good rule of thumb is you want to make sure your biopsies are deep enough to see either fat, blood, or muscle. Most likely all of the above. And then I typically send frozen sections, not necessarily because I want them to make a absolute diagnosis at the moment, but just to make sure they have adequate lesional tissue, to do whatever testing they need to later in order to ensure a diagnosis.

All right, so for our patient you do your VATS biopsy with either one or multiple incisions through the fifth inner space

and the pathology comes back as epithelioid malignant mesothelioma. Now real quick for our listeners, what are the different histologic subtypes of mesothelioma and why is this distinction important?

So there's two main subtypes for malignant pleural mesothelioma. There's epithelioid and sarcomatoid. But then there's also a third class that's biphasic or a mixed subtype of both of these types. This distinction is so important because management can greatly differ between the subtypes. For patients with sarcomatoid, or more advanced biphasic, surgery really is not part of their treatment algorithm, and it's not been shown to have any clinical benefit above and beyond chemotherapy alone.

And so these are generally managed with systemic therapies, with cytotoxics, as well as immunotherapy. Early biphasic, you could still consider them for surgery, although their long term prognosis is still worse than straight epithelioid subtyping.

Great, now our patient has the epithelioid subtype, which is good news to us as surgeons and the patient.

But Kelly, what additional workup needs to be done prior to even starting discussions about surgical options in this patient? Right, so every time I think about an oncology patient, after you get the diagnosis, your next step is staging. So our patient needs to be staged. The first step of the staging evaluation is going to be through imaging.

Our patient already has a CT chest but the next step would be to obtain a PET CT. Now a PET wouldn't have helped you with the diagnosis, but it will help you stage the patient once you have that diagnosis. So here with the PET you're assessing the mediastinal lymph nodes, you're looking at potential transmediastinal spread to the contralateral side, and always looking for evidence of distant metastasis.

You could also use an MRI as part of the staging process to try to ascertain if there's involvement in brachiocephalic vessels, the chest wall, any central mediastinal structures, or the diaphragm as well.

Perfect, so first step is always imaging, CT chest with IV contrast, PET CT, potentially an MRI.

But what's the second step when it comes to staging? Yeah, so if imaging suggests that you have resectable disease, you're now going to need to move forward with surgically staging your patient. Yeah, but let's pause real quick and let's kind of nail down a bit more on these imaging findings and which ones would actually preclude someone being a surgical candidate.

And then let's talk about what's actually considered technically unresectable. Adam, what are these things that you're looking for on imaging and how would you give your answers to these questions? I think you have to look at imaging in the context of what your goals of surgery are. I'm personally not somebody who believes in the concept of R0 resections in mesothelioma, so the goal of surgery is, should be an R1 resection, which is a macroscopic complete resection.

Order to achieve that you can't have any involvement of unresectable

structures nor even, nor any evidence of disseminated disease outside of the involved plural space. There are a series of very specific imaging and invasive staging procedures that I typically do before considering somebody for surgery.

Part of that involves looking really carefully at the diaphragm, both on imaging and then eventually at laparoscopy to make sure that there's no involvement of the undersurface or the peritoneal surface of the of the diaphragm. We're looking on this, on imaging to see if there's any mediastinal involvement of unresectable structures.

You always think about contralateral pleural involvement, I personally have never seen it. But it, but I'm sure somebody has you want to look also at the lung parenchyma to look for any signs of invasion that, that may, wouldn't really sway you, resectable or not, but may push you towards a certain resection procedure or not, namely a extra pleural pneumonectomy versus a

pleurectomy decortication.

I think one of the things that's the most common break point in figuring out if something is resectable or not is chest wall invasion, which is actually really difficult to identify. Some people it's obvious on their imaging that they have, you know, destruction of ribs or growth into and through the chest wall into some of the muscle, you know, a history of chest wall pain, which is really common with mesothelioma.

Can sometimes imply that there is chest wall invasion you know, vertebral body invasion is another one that you don't want to really be resecting. From a lymph node standpoint, it's also important to, you know, consider nodal involvement. The mesothelioma staging system is a little bit different than the lung cancer staging system in that mediastinal lymph nodes that are on the ipsilateral side are still considered N1 disease.

And so patients, if they're N0 or N1, meaning they have metastases to ipsilateral hilar nodes or mediastinal nodes those

wouldn't technically be unresectable, but progression to contralateral mediastinal nodes would. Would be. And so it's important to look at staging imaging in that context because it's nice to spare somebody a a morbid procedure if you can identify that they are either unresectable or wouldn't do well before you submit them to a big, big operation.

So we review our imaging for our 50 year old female, and lucky for her, there's nothing to suggest invasion of unreceptible structures, or a metastasis to contralateral, supraclavicular, or any distant nodes. So now the patient's sitting in your office, and she's ready to discuss with you what those next steps are going to be.

Well Kelly, the next step really is about surgical staging, and making sure she's also a good surgical candidate. Thank you. So, we want to make sure she has adequate functional status, we look at her ECOG performance status and is she capable of completing multi modality treatment. My in clinic assessment includes having them walk up several flights of

stairs usually with an oxygen oximeter on their finger.

We often, we always supplement those with pulmonary function tests and then we want to get a VQ scan to make sure that they have enough function. right left split or left right split. We want to get an echocardiogram to make sure their pulmonary pressures look okay, and if I have any concerns, I'll get a stress test.

After confirming all of this, I'm going to discuss whether a mediastinal lymph node staging with a mediastinoscopy or EVAS as well as a diagnostic laparoscopy. So while mediastinoscopy or EVAS stages the mediastinum, and it's always important to know if there's any one nodal station disease, what we're really looking for is are they a surgical candidate, and N2 nodal station disease meaning contralateral or supraclavicular nodal disease, would rule them out as a candidate.

When we talk about diagnostic laparoscopy, it's used to evaluate transperitoneal diaphragm involvement, and so we'll do visual inspection,

we'll take biopsies of anything that looks suspicious, and we'll also perform a peritoneal lavage, and if any of these are positive, than for mesothelioma, they're not a candidate for surgical management because it's just not going to provide them any additional benefit.

While you don't always need laparoscopy, especially on imaging, if there isn't any involvement of the diaphragm or deep into the sulci, I generally favor being more aggressive with staging these patients, and I would do media stenoscopy and laparoscopy on pretty much everyone. And that's because surgical treatment can be quite morbid.

So you really want to do the best possible job you can to identify who truly is a candidate and who may not be. Brian and Adam, so for which patients would you do diagnostic laparoscopy and do you generally get EBUS or do you also favor mediastinoscopy? You know, Peter I'm like you, I favor aggressive staging.

I think loading the boat in terms of data. To determine if they're a good

surgical candidate from a cancer perspective is critical. And so I favor laparoscopy for everybody, regardless of what their imaging looks like. And I think mediastinoscopy is a better option here than than EBUS, and so I tend to do those.

Personally for me in terms of pre resectional invasive staging, I tend to get laparoscopies on. pretty much every patient that I'm considering for surgery. It's a pretty low risk, low morbidity procedure that there is a definite upside if you can identify a transdiaphragmatic invasion and spare somebody a fairly morbid surgery if you can.

In terms of lymph node staging, mediastinoscopy and it's one of the few settings where I actually favor Proceeding forward with medicinoscopy rather than E bus I've spoken with a fair of, fair number of pathologists who have a somewhat difficult time sometimes identifying small mesothelioma deposits

within lymph nodes.

You know, it's also helpful to have the architecture of a lymph node itself. You know, one of the, one of the, One of my trouble points with mediastinal staging in mesothelioma patients is sometimes you're not actually sampling lymph nodes, you're actually sampling the tumor rind. And you can really definitively say that you have lymph node if in your mediastinoscopy biopsies you have a tumor that's surrounded by normal lymph node architecture.

So I really prefer mediastinoscopy and I do it on everybody. So my routine staging practice for patients. Pre resection in mesothelioma patients would be imaging, of course, invasive mediastinal staging with a mediastinoscopy and a diagnostic laparoscopy across the board. Well, that's very impressive.

All three of you actually agree on how you would manage that. Sounds like diagnostic laparoscopy almost across the board and definitely favoring the mediastinoscopy over EBUS.

So, our patient, she's our previously healthy 50 year old female, she's ECOG0, she has excellent physical fitness and would definitely be able to tolerate multi modality therapy.

She has an epithelioid malignant mesothelioma that's limited to one hemithorax covering all pleural surfaces and the diaphragm. And luckily, her PET CT doesn't have any evidence of distant disease. So, she ultimately undergoes a mediastinoscopy and a diagnostic lab. That demonstrate no evidence of nodal metastasis or peritoneal involvement.

So she ends up getting stages T2 and 0 or stage 1B. So we're ready finally to discuss with her, her surgical options. So what are the two procedures that we can offer her and which are you going to recommend she consider most strongly? So before we get into surgical options, we do need to mention that she could be a candidate for induction.

cytotoxic chemotherapy. Should get 3 or 4 cycles prior to surgery and that's also

included in the NCCN guidelines. But, regarding our surgical options, we'd be looking at either extra pleural pneumonectomy or pleurectomy decortication. But, Aside from surgery, even if she is surgically resectable and an appropriate surgical candidate, it's still appropriate to talk about systemic cytotoxic therapy with the addition of immunotherapy as a reasonable alternative.

We won't get into a lot of the details on this particular podcast, but the MARS 2 trial was recently presented. at ISLAC World Conference in September 2023 in Singapore, and we are expecting we'll likely see that publication later this year. And that will give us some additional information about whether surgery versus cytotoxic chemotherapy and the results of each of those for this type of patient.

So, let's very briefly describe. Or maybe not so briefly, describe each procedure and we'll talk a bit more in depth about which

option may be best for this patient and which we would choose. So to start, Brian, will you walk us through how you'd perform an extra pleural pneumonectomy? Sure, Peter. You know, I learned this operation from Dr.

Valliere who was our guest on our last edition of Behind the Knife. And so, extra pleural pneumonectomy, you know, is an on block resection of the entire parietal and visceral pleura. with the ipsilateral lung, resection of the pericardium, and diaphragm mostly. And so, I usually start this with a postilateral thoracotomy and I resect the 6th rib.

And when I resect the 6th rib opening of that 5th inner space, we try to keep the parietal pleural capsule intact. And then we begin finger dissection on the rib above and the rib below to create some space. One of the things that you will notice when you take off the parietal pleura, there's a, there will be a fair amount of raw surface bleeding from the chest wall, and packing is critical.

And so we'll always pack with

laparotomy pads. We, when we pack these, we use, we pack them with pads that are soaked in dilute betadine because Dr. Vallier had some belief about cytotoxics in the bet, in the betadine, but it helps us there. Yeah, I When I trained, we never really used betadine soaked pads, but definitely packed to help control for hemostasis.

And using the argon here is another excellent way to achieve hemostasis on those broad, raw surface bleeding. You know, once that hemostasis is achieved, key things to sort of also look out for, you need to look out for some of the head and neck vessels, the inominate artery, subclavian veins, all those are in play depending on what side of the chest you are on.

It's often helpful to put an NG tube in as you try to peel the pleura off of the esophagus without damaging the underlying musculature of the esophagus. Yeah, or the vagus nerve. And then, you know, the biggest challenge that

I find is the diaphragmatic recesses when you get down to those areas.

Sometimes you need a thoracoscope to have a look and so you can see better as you're trying to dissect the tumor away from the diaphragmatic recesses. And generally one of two things will happen at that level. Either you will end up bluntly evulsing the attachments of the diaphragm from the chest wall, or you may find in an area where, There is no tumor, if you're lucky, that sometimes we'll trim the edge sharply so that we'll have a di, a rim, a diaphragm to soak the the cortex too, as we can reconstruct the diaphragm.

Once, once we get to the pericardium, we'll incise it sharply. And then we'll resect around it. The phrenic nerve will come with the pericardium as part of that because you have no diaphragm to innervate anymore. And then once we have the entire tumor out, we've divided the bronchus and the vessels, then it's a question of reconstruction.

And so for me, the pericardium is reconstructed with the micromesh with some

additional fenestrations. Essentially tied somewhat loosely, but enough to prevent the heart from herniating. And then cortex for the reconstruction of the diaphragm, which sometimes can be sewn to the edges of the diaphragmatic rim if you have one, or it needs to be tacked to the the underlying ribs using a Carter Thompson or encircling the ribs depending on what your axis of preferences are.

It's interesting that you use Vicryl as the pericardial reconstruction too. where I trained we would use a thinner Gore Tex for a permanent reconstruction. Obviously either one is gonna be fine. Alright, thanks Brian for that great description of an extra pleural pneumonectomy. So our other potential surgical option is a pleurotomy decortication.

Adam, can you go through how this is a bit different from an extra pleural pneumonectomy and how would you perform that operation? So, pleurectomy and decortication I'm going to use the term PD going forward because it gets tiring saying pleurectomy and decortication

is different from an extra pleural pneumonectomy in that it is lung sparing.

I think there's been a lot of studies that have come out, it's a little bit beyond the scope of the discussion to go through them showing that they're equally good operations. I personally think that leaving people's lung intact allows them to potentially get through subsequent therapies easier.

And so I prefer to do them. In terms of the procedural differences itself, they start out fairly similarly. You know, the first step is really, you know, Making your incision, which we talked about before it tends to be a fairly large extended posterolateral thoracotomy incision. It spans usually the fifth inner space, and I was taught to make it curve down towards the diaphragm, towards the costal margin, so that you can do all of your work through a single incision.

Some people will use two different level thoracotomies in order to access the diaphragm easier, but I haven't found that to be necessary. So after you make your incision your, you know, your first step

is development of an extra pleural plane. You'll usually, well, I'll usually remove the sixth rib.

It's important to spare the intercostal muscles, because that's what you're going to be closing at the end. In order to have a nice closure, you have to really save the intercostal muscles. The sixth rib is removed. And this is really where you determine whether or not somebody is resectable or not.

So, you know, the difference between resectable or not is whether or not your hand slides or not. in the extrapolar plane or not. So once you've determined that, or once we've determined that the patient is resectable, I tend to extend the incision to its full, full extent. You know, as you're developing the extrapolar plane as was mentioned before, it can be fairly bloody.

And so, I tend to pack as I go and it really does help. There's all sorts of devices that you can use to help with hemostasis, argon beam coagulators and I think the Aquamanus or tissue link devices is particularly

good for that. And then as you. As you develop your plane, you know, I try to be systematic about it.

I was always taught to start anteriorly, and then move apically, and then go around posteriorly in terms of developing your extraplural plane. And, as mentioned before, there are certain structures depending on the laterality or side of where you're operating that you have to be cognizant of, you know, the esophagus on one side, versus the azagus on the other side, you know, so there are some considerations with that.

After your pleurectomy is essentially developed I then move to the mediastinal lymph node dissection once those areas are developed. exposed, and I do a pretty aggressive lymph node dissection with these. After that's done, I'll progress down to the diaphragm. The diaphragm is, can be tricky at times, but other times it actually is fairly straightforward.

There's some folks where you can actually get the disease off the diaphragm pretty

easily. You know, when you're developing the diaphragm plane, in my mind, the goal is to save as much native diaphragm as possible without leaving tumor behind. So, in some instances, you can really strip off most of the diaphragm.

It gets a little, it gets a little tricky as you get to the central tendon and typically you do have to resect a little bit of it, but if you, if you do something analogous to almost like a Coker maneuver, you can typically strip off some of the layers without going full thickness in the diaphragm, removing the tumor.

Other times there's really bulky disease down in the costophrenic angles posteriorly and laterally, and you actually have to do a fair. Fairly decent sized diaphragm resection. You know, there's ways to do it. You can either bluntly avulse the diaphragm off of the chest wall. Or you can intentionally enter it in a certain location, leaving a cuff that you can sew to later.

I prefer the latter it tends to give you a little bit of diaphragm to sew rather than

avulsing it off the chest wall. Inevitably some of those sutures are going to have to get passed around the chest wall. A Carter Thompson suture passer device is really helpful for getting around ribs that may or may not be easy to pass needles around.

It's particularly good at helping prevent you from stabbing yourself while you're doing that. Next, I tend to move to the pericardium. You know, the pericardium, sometimes it's not involved at all. Sometimes it is involved. I selectively remove pericardium. As of late, most of the people I've seen have had fairly bulky pericardial disease, so I have been doing pericardial resections.

And you, you take, What's involved. I tend to place stay sutures as I go because the pericardium has a habit to pull away And then it disappears away from you, kind of deep into the chest, and then you're kind of fumbling, looking for the edges of it. So I tend to place stay sutures as I go, I leave the needles on those sutures, and those are some of the sutures that I use to pass through the mesh during the reconstruction.

And I do reconstruct

every pericardium, I know that people probably argue about that, whether or not you have to do that if the lung remains in place, as opposed to with an EPP. But I do resect the the pericardium universally the mesh that you can use, you can use a vicryl mesh if you want there's thin Gore Tex mesh that if you pie crust it, it works really well to prevent fluid from building up and preventing people from getting tamponade.

And I think a point that's important in this is not making the mesh too tight where you can induce a, almost a restrictive physiology around the heart. You know, once that and once that's done, you move on to the part of the operation that most people who are opponents of the operation site, which is the visceral decortication.

This is tends to be the most tedious part of the procedure. This is where you're, you're peeling the visceral pleura off of the lung analogous to removing an orange skin off of an orange. And it's really tedious. It can take hours. In particular, it's difficult when

there's a lot of visual based disease.

But it's It's something that it just takes time and you have to do a good job at it if you want the person to do well afterwards. I think one of the things that can be helpful with that is, keep the patient breathing, have the ventilator keep using the lung on the side that you're operating on.

It tends, I find it easier to enter into the correct plane with the lung inflated. So sometimes I'll have the lung up while I'm doing this. I'll initially start getting into that under that tumor rind with a knife. I'll get under it sharply and then using a combination of some blunt dissection with, you know, sponges and kitteners I sometimes will use cob dissectors.

It's an orthopedic instrument. It's a nice blunt tipped instrument that allows you to, to dissect really nicely in that space. And then electrocautery with a needle tipped cautery can be helpful also to really finely focus where you're dissecting. That's probably the hardest part. It's tedious, for sure.

Everybody gets air leaks afterwards. They can be really problematic to deal with. They tend to be a bit more bloody than extra pleural pneumonectomies, but I do think there is a benefit to leaving people's lung in place in terms of allowing them to tolerate future treatment modalities.

Alright, so now that we have gone into great detail about both of these two surgical options I think our listeners have a great understanding of the nuances of these two procedures. So for our patient that we've been chatting about throughout this clinical challenge, which surgery would you offer her and why?

So for this particular patient with what imaging suggests is really, Not a lot of interparenchymal lung disease. I would offer her a pleurectomy decortication. Whether it's EPP or PD, the ultimate goal remains macroscopic complete resection. And as long as I believe that can be performed successfully with PD, I would go ahead with that.

Yeah, I agree with Brian. For this patient, I would do a pleurectomy decortication. Not to say that EPP is wrong, but it has been shown that EPP has higher morbidity and, and mortality associated with the pneumonectomy even though that there are some other benefits. And in certain cases, really the only way to get a good macroscopic resection would be an EPP.

It's just for this case with her a bit more limited disease, I think a PD is going to give us the resection that we need. Okay. So. So, for you, what cases would you perform an extracleral pneumonectomy, if not for this patient? Well, you know, I think their pulmonary function, their cardiac function on echo, are going to be critical factors in determining whether anybody is a candidate for EPP.

I think as we mentioned already, you know, when there's significant parenchymal invasion, Concern I dislike trying

to strip the visceral pleur off on those patients, so I think EPP is a better option when you have that, that significant parenchymal invasion. But there's not been any significant difference in long term survival between pleurectomy decortication and EPP, but there is a higher mortality and morbidity.

So I think you have to balance all of these things off. And an EPP on the right side with less tissue coverage has a risk of a bronchopleural fistula, which is a devastating complication. And as, as you know, EPP also comes with SVT, PE, pulmonary failure, Kyle leak, cardiac failure, these are all issues compared to pleurectomy decort where you leave the lung in, but there's such a higher rate of prolonged narrowing.

And I think it definitely, we don't dive into it a ton just for time's sake, but there's a lot of complications these patients can face and really having to counsel your patient ahead of time of what could happen post operatively. Our patient in great hands did

well didn't have any complications and she actually discharged home on post op day six.

She eventually sees you back in the clinic to discuss her, her next steps in her therapy. So what adjuvant treatment is indicated for this patient? So I think adjuvant treatments for mesothelioma that have been resected optimally is probably a podcast in and of itself so we'll just go through things briefly.

The, you know, local failures tend to be the, the lion's share of of the recurrent disease initially in patients with mesothelioma. So everyone's tried to figure out ways to reduce local recurrences. You know, an obvious first step for that would be radiation. I think that's an easier discussion in people who have had an extra pleural pneumonectomy because the lung's not there.

So you can do pretty hardcore hemithoracic radiation after EPP, and I think that's currently standard of care. In terms of patients without a pleurectomy decortication, the lung is still there so you

really can't give somebody large doses of radiation throughout their lung field because that lung will be rendered non functional.

And so there have been some studies using intensity modulated techniques, you know, IMRT or imprint which is a radiation modality that maps the pleural surfaces with hopes of sparing underlying lung and other structures. It's not standard of care yet. There's been a few trials one of which we were lucky enough to participate in that does have a promising signal in terms of benefit but I think it remains to be seen if that is going to be standard of care going forward.

You know, a lot of these patients are also at high risk for systemic metastases even when their initial Versexian pathology is no negative that again is a very complex subject as to whether or not you proceed forward with regular cytotoxics, which many of them had gotten before their operation versus pushing

forward with immunotherapy.

And so I'm going to not comment on something that I'm not entirely sure of at the moment. So this has been a really awesome discussion on the surgical management of malignant pleural mesothelioma. I know I have learned a ton and I hope all of our listeners out there have too. So now it's time to close out our podcast with some quick hits.

Alright, so first quick hit, Kelly, what are the histological subtypes of malignant pleural mesothelioma? So you have epithelioid, sarcomatoid, and then the third, biphasic or mixed subtype. Dr. Louie, which histological subtype is a candidate for surgical management? Epithelioid. Peter, what are the main characteristics required for a patient to be considered a surgical candidate?

So there's a couple factors, some of which are the disease related, others are patient related. So for the disease, well it's got to be limited to one hemithorax. They have to have no evidence of N2

disease or any peritoneal involvement and they have to have an ability to have a macroscopic complete resection, meaning they can't have invasion into the heart or any other unresectable structures.

In addition to that, the patient itself has to be able to tolerate the operation and tolerate multi multi modality treatment, so they've got to have appropriate functional status. So Kelly, what are the two main surgical options for treating malignant pleural mesothelioma? Well, I hope everyone knows the answer to this one by the end of the podcast.

Our two options are extra pleural pneumonectomy or pleurectomy decortication. And Dr. White, what are the deciding factors when choosing which surgery to offer a patient? Well, of course, this is a more complex answer than what we can give in these quick hits, but really for me it comes down to which can achieve a complete macroscopic resection.

If I can do it with a pleuroctomy decortication, then that's what I favor, but an

EPP is also a great option if that's the way to get our good resection, but you also have to consider functional status and comorbidities because some patients could just not physically tolerate an EPP because of the increased mortality and morbidity.

related to it. But if you look at local regional recurrence rates and APP is better because they can also get hemithoracic radiation treatment versus IMRT with a PD. And so it does tend to be a bit more of a complex scenario. Fantastic. Thank you all for listening to another Swedish thoracic surgery podcast with behind the knife and as always dominate the day.