Melanoma, EMPD, and a Prostate Drug Walk Into a Bar...

Welcome to season three of Derms on Drugs, a video podcast brought to you by scholars in medicine the best educational platform in dermatology and provided no cost medical providers. Derms on Drugs is where cutting edge dirt meets hit or miscommunity. A Matt Zyres of Dr. Dermatology in each week and join my residency buddies Dr. Laura Ferris from the University of North Carolina and Dr. Tim Patton from the University of Pittsburgh Medical Center. We use our 60 years of combined-derm experience to discuss debate and dissect the hottest topics in dermatology. It is everything you need to know to be on the cutting edge of dirt and you'll have some fun listening. New episodes drop every Friday on scholarship medicine, Apple Podcasts, modify another major podcast platforms and I want to tell you guys I highly recommend getting the scholars in medicine app. So you can send us questions in comments through the app and yes I will actually respond personally. You get the full show repository much less importantly you get the best Derm content in existence. So we're talking real content not far from a driven covering all of dermatology and supporting by a great ask Simon AI. If you go in there the first thing that you go to is the video banker is what it's called and in the core curriculum in dermatology has it's phenomenal and then there's all kinds of new cutting edge content coming out all the time. So let's go ahead and get into it for our episode. We've got a patented six pack episode coming at you today. We're going to start with Dr. Ferris but before we get into that first article actually did not watch the game. Dr. Ferris who won the Duke UNC game over the weekend. Did you guys pull it out? Oh you I know that you watched it and you're just trying to throw me off my game. You did not win unfortunately. And UNC got got crushed. Well they did not win. They did not win. But that's what we're like down our top two starters and you know who won with a full team a few weeks ago a month ago UNC. Okay. The PC tournament's going to be that's going to be good stuff. Yeah it is. I watch I watched the pregame but I had tickets to go see Kevin James you know from the King of Queens and Paul Blart and all that stuff. He was he was good. It was funny. I thought you were going to say another Abba cover band. All right let's get into that's enough. Let's get into it Ferris. Ferris what do you got? So I am going to start with kind of two papers but they were both in jab both by the same people both covering the same topic. So this is utility of the 31 gene expression profile for AJCC on cancer PT1A melanoma. So basically how does decision DX 31 GEP work on T1A melanomas then we'll move on to T1B melanomas. This is Joshy at all who are at Baylor. Okay. So our favorite. But we interrupt for a second first Ferris. I do want to tell you one of our listeners this week told me that literally their favorite thing is when I interrupt you and then you get you you put me in my place. They don't like me interrupting they like you putting me in my place but just I got to say I'm also going to be doing a gene expression profiling paper. I know we need Castle. We need Castle to start sponsoring that. Well it depends what we're going to say I guess. So let's see what we're going to say. All right I'll let you go. Okay. So basically there's these two. I you know it's nice to have these two brief reports. One is focused on T1A. One is focused on T1B. Okay. So let's start up with the T1A paper. So what they did was this was not like you know this was in a castle database. So this was a seer database. So seer has decision DX results linked in their database. So what they have is the class one A one B class two A to B result two seer. Now I will say that these authors are the first thing I was like pens going to be like everybody's you know works for and consoles for Castle blah blah blah. No conflicts of interest. Okay. So just putting that. Okay. Yeah. Okay. So yeah 33,513 T1A melanomas and then what they did. So the way that they kind of looked at the data there were some funny things to me, but we'll talk about that. So the first thing they did was they said are these low risk or high risk and so T1As. So low risk meant age over 42 not on the head neck. Brezlow 0.5 millimeters or less. My tautic rate under two per millimeter square high risk was sort of like the converse of these. So there were basically 1,060 low risks and 23 19 high risks. So it does look like you know certainly on average most of us would biopsy well more I would say more low risk T1As. So it does look like this wasn't like across the board equal use on every T1A. Okay. So what did they find 95% of low risk T1As and 90.6% of high risk T1As were class 1A overall or were class 1A. So that's 92% of all T1As. So if you're like you know this kind of fits with other data that we've seen in other groups which are like pretty much if you're going to send T1As their vast vast vast majority of them are going to come back as low risk. So what does that really mean? So in terms of survival in the low risk T1A group there were five percent of patients who had that non class 1A result none of these died of melanoma probably not shockingly. So there is no survival analysis in the high risk group. The class 1B or higher group had a hazard of melanoma specific death. There hazard of melanospec death was higher. Their hazard ratio was 5.72 versus class 1A and that 95% confidence interval was like that was statistically significant. Now there were so few in there that when you look at you know the table in there their table one they just had to call it less than 20 because if you're a lot if you're great if you have less than 20 they can't actually give you for privacy reasons number. So this is not a huge number of patients. So the other thing that they you know is that they're like that they found which is not surprising was that well in the high risk T1A group age over 42 was associated with worse melanoma specific survival hazard ratio of 7.51 whereas breast load depth over.5 mitotic rate location on the head and neck were not statistically significant. Proceed predictors. So you know the thing is what I don't like about this is the age thing. So this is my big beef on you know looking at age and stratifying in Sentinel node and risk. Having being older makes you less likely to have a positive Sentinel node being older also makes you do heavy worse survival with your melanoma. So we know that like we're using like Sentinel node in and of itself is not an important outcome. It is important because it is a predictor of survival from melanar of basically bad melanoma outcomes positive node greater risk of having you know distant metastases death from melanoma etc etc but older age lower likelihood of having a Sentinel node that's positive. So if you're you know so they call it a high risk feature but it's high risk of a positive node low risk of death okay so that's my soap box about that. So you know they they also don't capture things they see you they can only see what see your capture. So lymphovascular invasion not going to be you know counted the transsected melanomas we're going to fall you know probably in that high risk group so maybe some of those were actually like 1.5 or 2 millimeter melanomas. So you know it's also retrospective registry base blah blah blah. So this kind of gets back to I think what you know I've always thought which is that this is not a super helpful test particularly for like your run of the mill T1A melanomas the vast majority of them are going to be low risk and you're really not going to get a lot of additional information okay. Great fairs can I can I or you go to first yeah can I answer okay okay so here's what so I did not know shockingly that older people were less likely to have a positive node and more likely to die. Yes. What what does that I feel like that's one of those things that I was surprised to hear it and therefore it is like telling us something interesting. Well you're very smart and so that is why so I always wondered that and then I have I heard somebody give a talk on this Jason Luke who was a medical oncologist well known melanoma oncologist who used to be a pit with us. So it turns out that the lymphatics get leakier the older that we get which means that Like they, and they have, you know, data where they've like looked at the Technician and you know, how much of the Technician makes it to the draining No of in younger or old people. You're lymphatics like everything else as you get older. Don't work as well. So the thought is like, you know, a few cells here and there, like you just don't have, it's like you got bad pipes getting you to the lymph node. And you basically the melanoma cells leak out. You know, probably like if you've got a big honking tumor, that's going to make it in. But if you've got a couple of cells, it's not going to that the integrity of the lymphatics is not as good. And that would make some sense in the sense that if the cells don't get to the lymph nodes, you are less likely to generate an immune response to them. And so therefore you're in theory more likely to die from your melanoma because your immune system never got to learn about it in the lymph nodes. Yeah. And just as you get older, your immunity is, it does it is, you know, kind of is impaired as well. So yeah, like everything else, it sucks. So, you know, so basically like this is, I think that this age thing is a really important consideration that we say they're younger, do a sentinel node because it's more likely to be positive. But that's a reflection of the integrity of their lymphatics. It's not a reflection of risk. In fact, you know, a 40 year old, you know, and then like, what, how do we come up with 42? It is in the NCC and NCCN guidelines. It is based on like one retrospective study out of one center that looked at T1A melanomas that it had sentinel node biopsy and they picked like the 25th percentile among like breaking them down into inter-core tile ranges. It was a sort of, it was not an, it was based on the data out of one center. That was a retrospective step. So 42 is not magical. You know, if you look at the castle data, they'll say, oh, you know, you, this is helpful in predicting risk of a positive sentinel node. And patients, I'm going to get the number. I think it's on age 55 and older and like an old, an older study that was published in like future oncology. So yes, and the reason is that if you look at people younger, they're just more likely to have a positive sentinel node. So I think that's important. No, okay. Okay. All right. Next paper. Two, the T1Bs. Okay. So, you know, little more anxiety provoking group, the T1Bs. So what they did was they looked at whether 31 GEP can help us decide who should actually get a sentinel node biopsy using the same C or decision DX. So what an NCCN guidelines say about T1B. They say discuss and consider. So that's the group where you'd say the probability of a positive sentinel nodes between five and 10% discuss and consider not slam dunk, you know, they're shared decision making. Think about the patient level of love. So, you know, it would be great if it were, if you could add in more data like, hey, this is a lower stumer. You don't need to, you know, do this. And there are decide data, which is more of a prospective study. This is retrospective that might suggest that that could be true. But in this analysis over 1200 T1Bs, these patients average age was about 60 years old. Just kind of thinking about that everything we just talked about. Mean, breast, low duct, 0.8613% were all serrated of these 57% of patients actually underwent sentinel lymph node biopsies. And among the group, the positivity rate was 11.5%. So 80 patients had a positive node. Now here's the thing you look at those 80 66 of them 82.5% of them actually had a class one low risk GEP result. So that kind of would suggest that, you know, these are the node positive people and 82% of them have a low risk result. Now, there's, you know, what about the people only about half of the people who would have been candidates a little more than half. So interestingly, a little more than half of the people who got the test still ended up, you know, getting a sentinel lymph node. And, you know, of those people, so 80 of them actually had a positive node. It's like how were people really following this result a whole lot. And, you know, but there's a group where people decided not to do it. Maybe they were all class one a the thing I didn't love about this paper is like there's no table in there. I want to see the table of like, you know, these are the numbers. This is the number who had a sentinel node. This is what the, you know, the breakdown. There's really not a lot of granular data to sort of hypothesize about what is going on. So they said among those who did not undergo sentinel node biopsy those with class one B or higher had similar melanoma specific survival to those with class one a. So the people, if you, you know, if you forgo the sentinel node biopsy and say I'll use the GEP result. They really had pretty similar outcomes. The hazard ratio was 2.1 confidence interval cross one though. So really the data did not say, oh, non class one a patients who skip a sentinel node are doing worse. So, you know, take that for what it's worth. So the authors concluded that their data do not support using 31 GEP to omit sentinel node and T1 B. They, they say that there's a male clinic paper that we actually talked about maybe a few months ago. That also did not find this. In fact, the male one found higher node metastases and the low risk GEP. So, you know, this paper was odd. I just really would have loved a table to break down everything to try to think about it. We also don't know like why the test was ordered was there like was this just people who order it and everybody or these patients and some reason for some reason considered to be higher risk, lower risk that surgical candidates. We just don't know. And then, you know, why did they get a sentinel node biopsy if the result was class one a anyway. You know, did they have that IG we know we don't know. And then we answered to those questions. The castle test thing is round down our throats that we need to do it on every melanoma that 0.3. And the reason that one a still got the sentinel node is because they were like, all right, I'm going to order the castle testing at the dermatology office before patient is even talk to an oncologist. You should have that discussion with an oncologist and a surgeon and the oncologist and the surgeon were like, we don't we're ignoring the castle data. We don't go by that and they got the sentinel node on top of it. And this is the problem with the castle testing it is done indiscriminately. And it's not helpful. And most oncologists and surgeons. Absolutely ignore castle stuff because they're like, look, I have seen bad melanomas that were 1a. It's not a reliable test in their hands. Yeah, that's my. That's my theory. I can tell everybody, like it's like any other test. Don't order the test unless it's going to guide your decision making, right? If you're going to say here it is now I'm going to send you to oncology and or sort of oncology. And then you're going to get sentinel node anyway. Like was that guiding you yes or no? So there have been times that I have used this when I've had the discussion with the, you know, the whole team, right? So we've all agreed there's a reason why we want this information. If this if we get this result, we're going to make this decision of what this one will make a different decision. But that's. Yeah, it's the problem is we do it with everybody. Then we send them over to the oncology group is not a good strategy. And I think it's totally reasonable if you had a T1B and you're like, man, that sentinel node. I really don't like the sound of that. Is there any test I could do that maybe would discriminate? Is this really going to be pot? Like I think at that point when you've had the discussion with the surgeon and the oncologist and you say, you know what? I think I am going to go based on what my castle score is. Can we order that test? Totally totally reasonable. Yeah, that's just not the way that it's used. Not the way castle wants us to you. They want us to indiscriminately order it on everybody because that's how they're going to make money, which again, totally you got to make money. Pat but you did not bring out I know Pat and is particularly worked up when he brings out the term steak dinner. That's the like when he's I want to order to steak dinner again. I'm going to say something. So this was an interesting number. They said, you know, they said, you know, what's the different maybe there's cost savings, but they said using Medicare reimbursement data. $7,193 for the GEP test versus the cost of sentinel node. They said if it's done in an ambulatory surgical center, it's 3,470 or if it's done in a hospital as a hospital outpatient, it's $6,220. So it's kind of interesting both of their. Their sentinel node numbers are less expensive than the GEP test now everybody doesn't pay for the GEP insurance companies market down blah blah blah. There's all kinds of stuff. and stuff. So, all right, Ferris, I would say castle testing has gotten too complicated for me so that I actually no longer have a strong opinion on this. So how should people use this? Like what's the, when should somebody order a castle or is it like never, like according to patent, like the oncologist can order if they want it, I don't want it. Ferris, what's your, what's your ideal use scenario for castle testing? For me, it is when it is going to change what I am going to do. So if it is, I'm on the fence about a Sentinel node biopsy oncology is on the, you know, as a team we're on the fence about, is that needed? A little more data would be helpful. That's it. That's a help. That is a problem. Who's that patient? Who, like what is, because, you know, nobody. It is 90 years old. You've got a big, like, lentigo malignamalinoma. You've got, like, I don't know. Maybe it's a millimeter thick. It's going to be a bear to clear this, your bat surgical candidate. That's the person. Like, I'm not going to do it on a 35 year old because I know that, like, it's more likely to come back that they are likely to have a positive node, right? So, the younger, when you put in the, like, the IGEP where they are integrating a bunch of factors like the tumor thickness, the tumor location, the patient age. If I, if you have the same, you know, tumor factors and the patient's 35 versus 80, one of them, the 35 year olds, probably going to have a risk, let's say it's a point five millimeter malignamalinoma. The probability that the 35 year old is going to have a positive node is way higher than the probability than the 80 year old is. So you're going to get an IGEP risk of positive Sentinel node for the 35 year old. That's going to say, like, 8%. And you're going to be like, well, we should do it. And then you're going to get it for the 80 year old that's going to say 3%, and you're going to say, oh, I guess we don't do it. I think what it's doing is actually, like, reminding us that old people don't, like, that they don't do as well with malignamal, but they're not that likely to have a positive Sentinel node, right? Right? But maybe we could do that in a different way. Now, what do we need? We need prospective trials. So we talked about the Merlin trial where they actually prospectively, you know, it's a different GEP test. They got the test on everybody. They blinded everybody to the result. Then everybody got a Sentinel node. And then they went back at the end and said, what percentage of people had a positive node who were low risk or high risk? Now that number was like 7%, it was between 5% and 10%. So it did not come out to a number that you're like, great, that's what I wanted. I can find the less than 5% risk group, even for T1, it didn't. But we need a prospective study like that. They are doing the same. Which is prospective, but it's not quite the same level of prospective as it didn't Merlin just get added to the NCC and guidelines. Which I mean, I guess that you can put somebody into the discuss and consider. So if you were like, oh, look, you should get this, you know, oh, you know, it helps to put people in discuss and consider. I'm a little surprised that they got put into NCC and guidelines. But I think it's because there's actually prospective data in a trial done the way that, you know, they would want a trial to be done that made them put it in there. It only, it only classifies them as discussing, consider. All right. And so for anybody who's not heard us talk about it before, the Derms on Drugs are big supporters of the NCC and guidelines. You can go if you just go online and Google NCC and it's in for national comprehensive cancer network. And they have these amazing like flow charts that are for, you know, what you're talking about Merkel sell or melanoma or I said like whatever, they basically tell you what, you know, based on these characters, here's what you did. They're very, very good and it's very data driven. You can be very certain that whatever recommendation. Yeah. I would want to second that. I always tell our, like every time I give like the melanoma lecture of the residency chair, I'm like go on to NCC and make an account. It's free. NCC and guidelines get updated, not infrequently, right? Like a few times a year often. So everything will be in there, whether it's a new immunotherapy option, a new study that shows, you know, when to use adjuvant therapy, they really incorporate these all into the guidelines. You might not always agree with it, but that is like your, you know, gold, your North Star. They are, you know, updated. There's a huge panel of experts that do it. So yes, and like, do I keep up with what to do with every stage of Merkel sell? Absolutely not. So NCC and guidelines, it's free. It's your best friend. Yep. All right. Let's move on. Have any any other insight into these papers? No, I mean, I think these tests are overused and I literally never order them. I think they have utility, but it is in that multidisciplinary decision making. Hey, do we need to do this? And working with a multidisciplinary team in like a weekly Qtani's oncology, the oncologist and the surgeons never, ever, ever use castle. So what's it a while? I will say that they do here at UNC. There is oncology, oncology will occasionally say, you know, this would be helpful to have more information. So they do actually use it here. I think it's mid, I remember in Pittsburgh it being minimally to never used and some people hating it. So I think it varies by center, but know what you're, I think that's part of it. Know what your surgical oncologist and medical oncologist will say or do before ordering it. Okay. All right. And what's the melanoma pattern? What do you got? All right. My first six pack, which actually it is more than a six pack, right? It's like what we tell the doctor, we would drink a six pack of beer, but it's actually like a 12 pack. That's, that's where our program is growing into. So my first not six pack papers from the February edition of postgraduate medical journal titled a retrospective study on mose micrographic surgery combined with adjuvant radio therapy and the treatment of extra mammary paget disease analysis of 87 patients. So extra mammary pagets, that's new, new topic. It was by Zang at all. I did do a little bit of reviewing with EMPD. It's been a while since I've actually seen a case, maybe saw one a couple of years ago. Jamma oncology actually has a nice review published in 2022, MIRAD, Alon was the senior author on that. So EMPD epithelial malignant meoplasm occurs in apocrine rich skin, including the vulva penis and scrotum. It can be epidermal or invasive, invasive EMPD should not be confused with secondary EMPD, which is EMPD that occurs with an underlying adenocarcinoma. EMPD is CK7 positive, CEA positive, and is negative for P63, which differentiates it from SEC and SOX10. It is negative SOX10 differentiating it from melanoma. It can be CK20 positive or negative with CK20 positivity, potentially suggesting secondary disease, but that's not 100%. I actually emailed you guys really late, but there was this new algorithm published in December 2025. I'm just going to cover it really, really quickly at the end of my deep dive paper, because that CK20 was like, okay, CK20 positive, they have an underlying adenocarcinoma, right? That's secondary, but only like 50% of secondary stain for CK20 positive, and like 22% of primary EMPD are CK20 positive. So it doesn't really help you really discriminate, do they have an underlying malignant seer or not? So, all patients should be screened from malignant seer, age appropriate, and location specific screening is recommended. Routine use of sentinel lymph node was not recommended, at least based on the review paper that I read. Surgery is the treatment of choice, and that can either be wide local oxygen or mose. Mose has lower rates of recurrence. For non-surgical candidates, which is not unusual, sometimes these are older patients, and they're just not going to tolerate surgery, and it's going to be an extensive surgery why the excision would be required. So you can consider a Miquel Mod CO2 laser, photodynamic therapy, or radiation treatment, most often, electron beam. All right, so that's my review. Listen to that five times, you'll ace any EMPD board questions. >> Wait, I got one. I guess what's the question? So what did you come across? Like, what percent of EMPD has an underlying tumor? Is that like a, like your, you're good? >> 18%. >> In the review, 18% of EMPD patients had an underlying malignancy. I am almost positive. Don't quote me. >> So like a GI malignancy, whatever kind of thing. >> Polorectal being the most common. It was really weird. The review paper, the second most common cancer associated with EMPD was breast, which that isn't that just pageants? >> That seems like it just be pageants. >> All right. >> So you're going to see that. >> Yeah. >> And then you also think about bladder and urothelial and prostate. >> Okay. And this is, and this is fortunate to something you're going to see so rare that the once in a while when you do see it, like you can go look it up and figure it out. >> Yeah. >> Pull up that 2022. and pull up this 2025 paper that takes you through a staining algorithm. It's pretty sweet. It's probably too good to be true, but the numbers are pretty nice. All right, so the six-packed article authors wanted to evaluate the effectiveness of combining mose with adjuvant radiation. It was a retrospective review 87 patients at Pay King University first hospital. From 2012 to 2021, they still call it Pay King University. I'm not in that position. I call it Bayesian. That one stayed. Patients underwent mose and then once, what's that? King, not just for ducks. It's correct. Patients underwent mose and once patients were healed, they went underwent radiation therapy. Prior to 2015, they received electron beam and 3D conformational therapy. After 2015, they underwent intensity modulated radiation therapy. I've no idea what the difference is between those two and so I didn't bother to learn. No patient underwent gentle cure, so don't even think of trying that people. Pable one list patient and tumor characteristics. I don't want to get bogged down details. Most patients were men. Most tumors were in the perinium. Most tumors were dermal compared to epidermal. So invasive EMPD versus just epidermal EMPD. Three lesions were in the axilla. Clearly, that's an area where apocrine glands exist, but before I read this paper, I had no idea EMPD could be in the armpit. Did you guys know that? I've never seen a main. I've never seen fast. What if yeah, you did it with apocrine rich, so on a test, I would have gotten that right. That's what matters. As long as you got it right on a test, we won't have to worry. Yeah, patient care. Let me tell you what I'm not going to test. As patients are failing all sorts of therapies. All right, median follow-up 71 months, five-year local recurrence rate was 3%. So that's pretty good. Previous recurrence rates for EMPD were reported in 2023, 26.7 for wide local exige, 7.3 for mose, so just mose alone. So this went all the way down to 3%. So better, fair number of patients had acute skin toxicities, but only six patients out of 87 discontinued therapy secondary to those toxicities. At the University of Pittsburgh, we talked about this just a little bit ago. We have a multi-disciplinary tumor board for cutaneous malignancies, and it's just awesome. It's an awesome tool for patients, and just you learned so much about skin cancers. In my experience, when you asked the radiation oncologist, would you radiate this? 99% of the time. They're like, yeah, we can. So my sense is with EMPD, not unreasonable to strongly consider adjuvant radiation therapy. And like everyone, if the patient's consolidated, radiation therapy is not easy. 25 treatments, I think, if they separated it with if it was got close margin versus there was a like margins were greater than a centimeter. They actually changed the dosing and the fractionation. So it's it's a lot. But if you took it from 7.3 down to three, not unreasonable to consider. So get your radiation oncologist involved in the carrier epin EMPD patients, I think. What do you guys think? Yeah, no, I think so too. I thought that was interesting. Those good to see their topic. How many radiations did they give them? Like ballparkie. 25 if it was like, if they met certain criteria on the margins. And if it was like close margins or the margins were positive, I think they took it up to 30. So 25 to 30. Okay. Fair amount, but not like you're something like you're going for a year. Uh, okay. Well, I mean, the EMPD, thank you. Yeah, we have something we haven't talked about. And something, of course, now we're going to see like one case in the next 10 years combined between the three of us. But hey, we will be ready. There was that 2022 article in JAMA oncology. Right. And the AI. All right. So this algorithm cancers, the journal cancers, 2025, December. The, the, the stain that I had never heard of was this TRPS1 stain. So basically, you get your EMPD patient. And your first round of staining is CK7, CK20, TRPS1. If you are TRPS1 positive, that is primary EMPD. Like that's it. You're done. You don't have to go looking for cancer. No. Wow. In this cohort of stuff. Like I couldn't believe it. That's, that's really never going to answer like that. We're like, hey, we got a new test and it's useful. All right. If you are CK7 negative, which I didn't think was possible, but like 7% of EMPDs are actually negative for CK7. If you're CK7 negative CK20 positive TRPS1 negative, colon, that's what you work them up for. If you're CK7 positive, 20 positive TRPS1, then you do additional staining, CDX2. If you're positive, you do another stain, SATB2. If that's positive, colon. The diagram makes it much easier. And we'll put this in the slides. Yeah. And then if that CDX2 is negative, then you do P63, GATA3, Europlacen, and KX31. And that'll tell you the difference if it's Eurothelial, if it's prosthetic, or if it's primary perianal. So that TRPS1 negative, you can still be primary, but it's more specific to the perianal skin. I want to, I'm going to isolate that clip. And I, it was basically a foreign language. Like I was, I had no idea what you were. It was, but it's still pretty cool though. We will put, I will, I'll send you this little graph. And when you combine that with my babbling, it'll be, it'll be, it'll be slightly less coherent. It'll still be pretty clear into here. Yeah. All right. So move it also for our listeners. I'm going to move on to it to a much lighter topic, much easier study to understand. So first one that I've got is Sparona Lactone versus Bicolutamide in female pattern hair loss, a randomized double blind control trial. So this was done in China. And essentially they basically took 208, 204 women, 188 completed it, randomized them to either 100 milligrams a day of Sparona Lactone, plus whatever else versus 50 milligrams of Bicolutamide, plus whatever, I think they were monotherapy, but Brunel Lactone versus Bicolutamide and followed them for 24 weeks using Tracoscopy and the Bicolutamide kicks Sparona Lactones butt. So Hair Density, the Fronto Hair Density was almost twice as good. The improvement was almost twice as much. The Hair Shaft diameter, the Fronto Hair Shaft diameter almost twice as much improvement. Vertex, hair density more than twice as much improvement, Hair Shaft diameter and the Vertex, about twice as much improvement. So the Bicolutamide was a lot better. Now they did do clinical photography at baseline, it's six months in a clinical photography, you couldn't tell the difference, but that's probably just that they didn't give it long enough. So Tracoscopy shows differences a lot faster than clinical. So my bet is that if they gave it like a four year and then took pictures again, you'd see a big difference. So now obviously I'm guessing the most people are like me and have not ever thought about the possibility of prescribing Bicolutamide. Turns out Bicolutamide is a very cheap, very safe drug. It is what's pretty safe. So it's a selective androgen receptor antagonist with minimal cross reactivity and the only real concern with it, about 10% of people will get mild transamene salivations, much smaller number like in the 1% range will get meaningful liver, function LFT abnormalities. And so if you do decide to use, so the first the overall rate of adverse events was lower in the Bicolutamide group compared to Spurnal Actone. So Spurnal Actone had more hypotension, edema, stuff like that, the Bicolutamide, some mental changes, some rash, but overall the Bicolutamide had a lower rate of adverse events. So as I did some digging into this, if you were going to prescribe this to someone instead of Spurnal Actone, you would want to prescribe 50 milligrams once a day and you would want to check LFTs at baseline and then monthly for four months, then every three months for a couple more times. And if they get, if they get through a year, you know, and their liver was fine, they're going to be like you then can just check it once a year. But the risk of like clinically meaningful hepatic toxicity super low, like super duper low, like 20 reported cases. So, but that's in the setting of your monitoring it. So you're not just like, here's your drug go on your way, and that this was very timely because like, last week, last week we talked about this Bernalak tone in older women. - In the older women, yeah. I mean, up older women, women over 40, but yeah, over 40. - They're older. - Women that are under 40. - They're alive. - Yeah. So, yes. So that was, I thought this was really interesting. So, by Calludamide, like that, so obviously this is also a drug like finasteride. You would not use in a woman of childbearing potential. Right? - I mean, if they were, yes. Okay, yes. You said woman of childbearing potential. So, yes, you would not it be, but if somebody, I would say somebody had an IUD in. I'd probably be willing to prescribe this. - Okay. So, like, acutane. We'll think about it like, acutane. - Yes, at least like acutane. - Okay. - And then this was developed to treat like BPH, benign prostatic hypereplasia men, or what was, what's the original use of bicholudamide? - Metastatic prostate cancer. Okay. - That's the tricky cell right there. - Normally. - Yeah. - Usually. But for you, it's going to grow some hair. - For every hair will look better under a microscope to people who are experts. But the average person walking down the street won't be able to. - Well, at least not for six months. - It will be. - It will be fine. - And I can promise you won't get prostate cancer. - Yes. Or if you do, and it metastasizes, you'll do much better. - Yeah. I mean, I think you need like the true clinical outcome data, right? - They need something that is like, because none of us are treating our trichoscopic findings. We're treating, does my hair look thinner or not? - Yes. But it's strongly, the timing, like six months was too early for pictures. - And just, there's no such thing as topical bicholudamide? - Not to my knowledge, but there probably will be after this. - After this. - For sure, some compounding pharmacy is mixing it up right now. - Yes. And then you can also rub it on your metastatic prostate cancer. - Yeah. All right. I like that. - Article number two. The effective medication use on chronic paritis and patients with type two diabetes, malitis, and multi-center cross-sectional studies. So basically, this was a study where they looked at this registry of people with chronic renal failure. I think they were actually dialysis patients, and they looked at all the different drugs that they were on. And so, if there was anything that correlated with being with chronic paritis, and there definitely was. So, the drugs that really mattered here. So, number one, alpha glucositis inhibitors, which nobody's going to be using any of those. You can forget about that. Number two, dipeptidial peptidase four inhibitors had a relative risk of 1.29, so about 30% more likely. And then statins had a relative risk of 1.41, and they were additive. So, if you were on two out of these three, your risk of itch went up even further. So, this, now, on the other hand, this was not a prospective study where they then like stopped the drugs to see, did your itching get better? Like, maybe this was an association, not a thing. But, right, we know dipeptidial peptidase inhibitors cause pempagoid, so it kind of made some sense to me. And then statins, I know for sure, make old people itchy. We've had that data for a long time, because your skin has cholesterol in it. And your skin literally makes cholesterol in the skin. And a statin stops that. So, statins do cause drier skin. So, just a useful reminder, particularly those two drugs, dipeptidial peptidase inhibitors. And statins. And it also was my reminder that I bring up again, I am a firm believer that we weigh over diagnosed drugrashes. That if there's, if spongiosis is the primary clinical pattern, I think it's incredibly unlikely that something is a drug rash. There was a study on this couple of years ago, and basically it was common for people to get like temporarily better. Oh, we stopped the drug. Oh, month later, it went a lot better. And then a month after that, they were, it came back again. The drug had nothing to do with it. But so, spongiosis really takes me away from really thinking about a drug rash. Any like annoyed or interfacy, then like all over, it's like, interface or like annoyed plus eos. Like, that's a drug rash until proven otherwise. More bill of form drug rash is dressed, that kind of stuff, for obvious. But for the non specific itchy old person with a rash, I think we overdo drug rash is in general. Morally, or we say, oh, that's a drug rash. You're statin and they stopped their statin and they're better. But it's because it was really the paritic component or right. That's not really an allergic reaction. It is an adverse effect. Right. I think that's maybe the way to think about it. That's a very good way to put right. Right. They basically made their skin so dry that they got itchy. And then they could have gotten a rash and whatever from the scratching and the, you know, or the barrier impairment of that kind of stuff. All right. We want to thank everybody for joining us this week. We went through a lot, right. Got some deep stuff with melanoma and gene expression profiling. We got into some stuff with extra memory, pageus disease and a couple of little fun things. But, you know, we hope you really learned a lot. And we hope to laugh once or twice. But mostly we're hoping your plan to join us next week. Until then, I'm Matt Zyrus. I'm Tim Patton. And I'm Laura Ferris and we are Derms on drugs.