Memorial Sloan Kettering - LAMN Clinic & Appendix Cancer

0:00 of 24. I've had to look over at him. Sometimes it feels like it's been longer, sometimes it's been shorter. But, shortly after he was diagnosed, I I started Appendicure, which is a Facebook group. and I did that because so many strangers were so amazing to us. We knew we didn't know what we were doing. Our doctors didn't know what we were dealing with. And so, so the the kindness of strangers is is what got us through. and I wanted to pay that back.

0:30 also my website is getting ready to launch. It has been very hard to do, but it's it's getting there and thanks to a survivor who volunteered to help me that I'll introduce at a later point. it's almost ready. so with that, I will turn it over to Chrissy. And Chrissy is the co-founder of Appendix Cancer, another amazing Facebook group that was super helpful to me in in my journey. our journey. so Chrissy, >> thank you so much Amanda. I'm so happy to be here with everybody tonight.

1:05 So I'm going to do a little intro about myself and my story and then I will introduce Dr. Caragonas. So my name is Chrissy Buddig. I am a 10-year appendix cancer survivor. I was diagnosed with stage 4 disease in 2015. At that time I did 10 rounds of fullfox and then I enrolled in memorial salone ketaring's Icarus trial which was comparing the effectiveness of highac to epic for appendix and colon cancer patients. During my surgery I was randomized to receive highac. So I did that and then unfortunately nine months later I was diagnosed with a recurrence.

1:41 at that time I did another CRS surgery and did three rounds of epic. So, I actually ended up with both H Highek and Epic. and it's been more than nine years since that final surgery. I was actually just looking at my Facebook memories before we started and saw that today was the last round of Epic for me. So, it's been nine years since that and I have no evidence of disease today. For those interested, Amanda and I hosted a webinar about the results of the Icarus trial with Memorial Sloan Kettering Dr. Nash back in August. That video is available on YouTube. remission has afforded me the opportunity to become a patient advocate. I have been on MSK's patient and family advisory council for quality for the past four years. Being a patient allows me to take part in hosting events like this like we are doing tonight with msk's Dr. Caragonis who is joining us to talk specifically about ln or lamine msk msk's clinic devoted specifically to that tumor type and what msk is learning from that clinic. So tonight I'm very happy to introduce Dr. Cara Gunonas who I have been hearing about from Dr. Nash for the past several years. Dr. Cara Gunis is a boardcertified surgical oncologist specializing in colctyl and appendix cancer with an emphasis on patients with peritineal metastases. His research focuses on how and why tumor spread within the abdominal cavity.

3:05 Something we all want to know, something so many of us are familiar with. Dr. Dr. Caragonus works with each individual patient to determine the best treatment options, including clinical trials to align treatment with the patients personal values. So with that, I will turn it over to Dr. Caragunes. >> Wonderful. Thank you both Amanda and Chrissy. A wonderful introduction and more importantly, a very very important job that you all do having these groups. I think that we were just talking about this before we started our presentation today. How the fact that this is can feel sometimes a very lonely diagnosis. It's not a very common thing and when something is not common, it's very easy to feel isolated. But it's a wonderful testament to the kind of dedication of a lot of patients, caregivers, forming these groups, learning how to kind of help each other through this that I don't know how our field would be if that there wasn't that. And it may be just the one of those we we love all of us to talk sometimes about how social media are a bad thing or maybe all these things that are happening nowadays. But this is a wonderful opportunity of people coming together around a common cause and it's wonderful to be part of this and thank you for the invitation. I will share my screen.

4:22 I think I need a a permission to share. There we go. And hopefully you can all see my slides. >> We see them. >> Wonderful. So as we talked about already for the introduction, I will talk to you about lowgrade appendicial mucinous neoplasms or what we call alamn or lamin. And for reasons that I will go through a little bit more in the discussion, this will take we'll touch on some other diagnosis that are adjacent. The focus we will try to keep it on specifically the the diagnosis of lowgrade appendicial mucin is neoplasms.

5:03 and of course after I go through everything I'm very happy to answer a lot of the questions. People have been coming up and sending us a lot of questions that we're happy to address and then anything that comes through during the presentation of course that's what we're here to discuss. So just as a disclaimer, broadly speaking, we will talk about a lot of generalized simplified algorithms and and paths and recommendations, but as you can imagine that may not apply to every single person with a lamin. And the reasons are sometimes people have specific circumstances other findings other medical issues or frankly sometimes they have a specific preference that we we strive to accommodate an outline of the talk that I will be giving you today. first we're going to talk a little bit or maybe a lot about what a lamin is and hopefully that will help keep things into perspective. I think that looking at the questions that came in, one of the biggest questions sometimes is how do we really define it? What is a lam and is it cancer and how do we think about it in the context of other diseases.

6:14 I will go over fairly briefly over a couple of general cases to illustrate the points the treatments and the way that we think about the treatment for this entity surveillance that is the scans and labs and follow-up that patients need after they had their initial treatment. I will briefly introduce the lamine clinic that we have set up over the last year or so at msk and why we think it's an important transition into streamlining care for something that for a long time has been happening more ad hoc rather than in an organized fashion that I think makes more sense and then very briefly touch upon some research and future directions that our group is taking and where I see the field taking us in the future.

7:04 So first what is a lamine? A lamine is a rare tumor of the appendix. there's about one to two per million people per year or if you want to think about it in the context of the United States somewhere between six and three and 600 cases every year of lamine. It's usually a a slow growing tumor that produces mucin which is a jellyike substance. Think about it similar to the idea that we have sometimes the the snot that comes from our nose right when we have a cold that's that mucus it's the same thing that is coming out of the appendix and that's why we call it mucinus and it often remains contained within the appendix for years and a question that I get very often is how long do you think this has been there or how long does it take for this to become a problem and the answer is probably much more than we think much longer than we think when sometimes we've had patients who come in with a CT scan scan with a new diagnosis of something that looks like a lamin or they just had it removed and then we go back and find a scan that they had maybe five or six or seven years earlier for a very different reason. We often see already there signs that there was something going on. So our current thought is that it takes several years to maybe more than a decade sometimes from the first signs that there's something there until somebody identifies it and most of the time it gets identified in an incidental way. However, it is important to know that if the appendix ruptures then the mucin can spread into the abdominal cavity and that can be a smaller or a bigger deal depending on how that mucin looks and I will get to that as well.

8:43 Now, why do we call it lowgrade? What does that mean? Well, lowgrade is the pathologist's way of saying that when they look under the microscope, it looks less aggressive. What that means is that the cells look more organized. They're structured. They're not growing haphazardly. They're growing slowly. They look very similar to normal cells. very few of them are actively dividing. And they're growing in a pushing pattern. That means instead of growing into tissues, they're pushing tissues away.

9:13 And if I can leave you all with one key message that I think everybody in the audience or everybody who is who knows somebody or is involved with this diagnosis should know is that most people more than nine out of 10 who have a lamine that when it was diagnosed it had not spread have been cured or will be have been cured by removal of their appendix alone. So a lot of what you may see or hear on or unfortunately may have experienced somebody who has spread from an appendicial tumor is only a subset of patients who do have a lamin unfortunately that is where most of our care has to go towards because that's where the needs are greater but for the vast majority of people who do come in with a new diagnosis and who at the time of the diagnosis and again I have to emphasize this did not have any evidence of spread then the appendectto is enough to keep them going without ever having to worry about this again.

10:10 So, a little bit more about what a lamin is. These are a couple of pictures from our pathologist. This is a normal appendix. If you focus on the screen on the picture on the right, for example, this more purple area in the middle, that's the inside lining of the normal appendix. You can see that it has a lot of it's a it's a thick layer. It's almost like a nice little carpet on the inside of the appendix and that's what it's supposed to look. This is again on higher magnification. You can see this purple area on top. That's the lining of the appendix when it's normal.

10:41 When it's not normal, you can see the pictures on the bottom. That layer becomes really, really flat. And the way we think about it, the reason it becomes really, really flat is you have mucus on the inside of the appendix pushing against the wall and slowly but surely over the course of years making it thinner and thinner and thinner. And the lamin diagnosis is based on what we see and what we don't see in the appendix when we look under the microscope. So what we see is that epithelium that lining that is really compressed and we see that the the edges of that epithelium are just pushing into the different parts of the of the wall of the appendix. But we don't actually see any tumor cells growing into that appendix wall as would for instance in say a colon cancer or another type of cancer or even sometimes of appendix cancers.

11:35 So that brings us to the first big question. I I get that from my patients very often and I know that several of you have submitted this in the questions before the webinar today. Is a laminina a cancer? And it's a very long answer. it's not a yes or no answer. So if we think about what is a cancer, how do we define cancer? Well, when pathologists define cancer, where clinicians define cancer, they usually define it based on two characteristics. A cancer grows into other structures. So as you can see on the left, the the roots of a tree, it's growing into the ground. And then it also has the capacity to spread. So it can go from one part of the body to a different part of the body. Those are the two hallmarks as we consider them of cancer growth into and spread.

12:23 The colon cancer for instance is a very clear type of cancer that has those characteristics. And we also beyond that we have a very clear line where once a cancer or a colon polip if you look at this is a polip for instance in your screen a colon polip once it grows past a certain layer on the bowel wall we call it cancer because now it has grown into so it has fulfilled the first parameter and then we know that once it grows past that line it goes from no chance of this ever spreading to now it has a chance of spreading. So then we can define very easily under the microscope this is a colon polyp benign this is a colon cancer the appendix is not like that unfortunately as I showed you before because of the way that this is growing by pushing we don't really see any invasion so a lamine by definition does not invade so it doesn't fulfill that first parameter of a cancer but it can spread so sometimes it can have that second characteristic of a of a cancer so whether it is a cancer or not is difficult to to determine ahead of time. So it's difficult to predict. That's why we use sometimes terms like uncertain malignant potential which is very convoluted way of saying we don't know ahead of time if this is malignant or a cancer or benign and by taking it out we are done. But what we do know is by going backwards and seeing when we see people who have this kind of appendix tumor, how many of them go on to be cured by having their appendix removed, how many of them go on to have something come back at a different part.

14:01 That's something that we do know and that helps us make those determinations even though it's a little bit like a crystal ball that we cannot see inside and know ahead of time if this is one that will eventually spread or not. different way of thinking about how lammens evolve. They start from the inner layer of the appendix and we use a staging system. You might have seen or heard about TIS or T insideu T3 T4 A or B and these are all different ways that the tumor grows inside the wall of the appendix through the wall of the appendix and outside of the appendix. So TIS is confined to the inner muscle layers, doesn't go through the muscle of the appendix. Whereas once it goes through the muscle of the of the appendix, it can be a T3 if it's going more into the fatty tissues around the appendix or a T4 if it goes through all that into the final layer top of the appendix.

14:58 And this really matters because it changes a lot of how we expect this tumor to behave. So the base the basic staging system that at least our institution follows for this is the American Joint Committee on Cancer or Ajac staging system which uses these thresholds to define different stages of the of the appendix tumor of the lamine and for instance we know that when we're talking about a TIS or one that is on the inside of that muscle layer the risk of that tumor coming back is about one in 100. So fairly low. And even in those cases, we tend to think that the reason this happened was not so much that this was a bad tumor that we didn't that didn't look as bad under the microscope, but rather as we take different and we look at different parts of the appendix, we cannot look at every slice of that appendix under the microscope. Between those slices that we check, there may be something that was worse than a TIS that was missed. So that one in a 100 is probably more a our inaccuracy of in identifying some area of concern rather than a true recurrence from from that type of tumor. But once it breaches through and it goes through that muscle layer, things start to change. risk starts to go up and the general way of or the general statistics that you will see vary a lot as you can see on the a picture or on the table here T3 T4 let's just say for for the purposes of this there are anywhere between 3% and 30 40 50% risk of having something come back by that point alone but this is something that here in our institution we feel that is not the most precise way to think about it and that's why we have broken the two groups down. So what we consider here to be a lamine at msk is when we have or a t3 or a t4 is when there is breach of that wall of the appendix but there's only mucus or the mucin going through it no tumor cells and when we see that when we see just the mucus going through the appendix without any of the tumor cells as you can see that we are much more precise in estimating the risk that something will come back and the risk is actually lower than most people think both patient s and providers. As when we've looked at our own data and when we've seen other people report their data, the risk of having a tumor come back in that scenario is probably somewhere close to 5% plus or minus.

17:40 Whereas on the other hand, when we have tumor cells outside of the appendix, which is only a minority of patients, thankfully, that's when we start seeing a higher risk. And for that reason we term those tumors appendix cancers or even though even if it's a lowgrade appendix cancer we would call that an appendix cancer as opposed to a lamine because the lamine implies that there is something more gentle something more potentially benign about it. Again that is in our terminology you might see these things and you might hear these things a little bit different depending on the center that you're consulting with. So, as I said, just to drive that point home, when some of the studies that we've looked over the years over with patients followed up for a decade or more, we see that having a little bit of mucus outside of the appendix is not a high risk factor for having the this type of tumor return in that area or anywhere else in the abdomen. It is one of those things that historically we used to be very concerned about anything being outside of the appendix being bad news. But more and more we're realizing that it's actually necessary to have tumor cells outside of the appendix to really be worried. And even in the ones in the cases like these that we see somebody who doesn't have tumor cells out of the out of the appendix have recurrences in the future. We again think that this is a matter of us not being able to look at every little drop of mucus and see if there is a tumor cells. If there is a tumor cell, sometimes there might be so few of them that it is hard to investigate every single one of them.

19:19 But again, in theory, if it's only mucus outside of the appendix, there is no reason why a tumor should come back. There wouldn't be any tumor cells to come back from. So putting all this information together, if we want to think about a risk stratification for for folks who are diagnosed with a lamine, most patients or a significant number are going to fall into the low risk where they have a tumor that is confined to the appendix. It has been removed completely and there is no mucin outside of the appendix. And those folks have about a 1% risk in our calculation of having something return in the future.

19:57 Then you have an intermediate risk. Another big group of patients who have either a perforation or a hole in the appendix, mucus without cells outside of the appendix that depending on the characteristics can have a higher risk of having something come back. And then you have the high risk group where we actually see tumor cells outside of the appendix. And that's where we truly worry because when we see tumor cells in one area, we know that our eyes are not perfect. We cannot see every little tumor cell. Our CT scans, our MRIs are not perfect. We cannot see every single cell. So even though we can remove very effectively what we can see, there is other areas that potentially can be there and can grow later. And that's why we see that.

20:38 But it the good news is for any of those groups for the low risk, the intermediate risk, the high-risisk patients once they have been diagnosed with this and they are presumably following up and having their structured surveillance as we say kind of following up having the scans that they need to have watching their symptoms. It's extremely rare to come back with a new spread or new areas of of tumor that now cannot be taken out with surgery. The folks where surgery is not sometimes feasible are the ones who were not aware that they had this diagnosis. Years went by and things went beyond a certain point. But with consistent follow-up, we think that there is a very very high likelihood that even if that were to come back, we could do surgery to rescue that patient from from that situation.

21:34 I will just go very briefly through this just I know that a lot of people who might be joining today may not necessarily have a lamin type of appendix tumor. So that's why I think it's important to think a little bit about this and understand in in the most simplified way. I usually tell people there's two dimensions that we're looking at appendix tumors to simplify it. They can it can be how extensive it is and how aggressive it is. On the aggressive scale, you can have a lowrade tumor or you can have a high-grade tumor. Low grade means when we look under the microscope or in the CT scan or in the operating room, it just doesn't look that aggressive. And we know from from history of patients with that type of tumor that it typically doesn't behave in an aggressive way. And on the other hand, when it looks aggressive under the microscope or on the CT scan, those are the ones that we worry a little bit more about and may need additional treatments beyond just removing their appendix.

22:28 Similarly, we have less or more extent if the tumor is confined to the appendix, whether it's a lamine or if it whether it's an high-grade appendix cancer, but an early appendix cancer, very often surgery alone is enough. But when we're talking about spread away from the appendix, that's when we start thinking about different treatment options. And that's when things get a little bit more complicated. And then there is a term that I know is very widely used. It's in in a lot of the support groups. It's in a lot of the nomenclature that we use for this disease that I find sometimes to be a little bit confusing. And that's the idea of PMP or pseudomixoma paroni. You may have noticed I haven't mentioned it so far and this will be the only time I really mention it. And the reason I find this to be confusing is it describes the situation more than defines a medical problem. So a pseudomixoma peroni means that there is mucus inside the abdominal cavity. Essentially that's the the definition of it. But it can happen in the context of somebody who has a lamine with a little bit of mucus outside. It can happen in the context of somebody who has a an early appendix cancer with a little bit of mucus outside of the appendix. So it can happen in the context of a broad spectrum of people who have tumors that have spread within the abdominal cavity whether they are low grade or highrade or intermediate grade. So even though it is a very widely used term, I find that it can sometimes make things it can group together a lot of people who have very different treatment experiences and very different and can have very different expectations of what will happen in the future. So the short answer is yes.

24:14 Salamine could theoretically it does sometimes progress to the as a next step into a PMP state that is having mucus outside of the appendix that can spread but it's not necessarily a key factor in how we think about the next steps or how we think about the management or how we think about anything else because we primarily focus on what is present at any given time more on the side of tumor cells than on the side of the mucus.

24:47 So, a few illustrative cases again to ground our conversation and I'm sure folks will will have very specific questions as we go through that. first let's think about a 50-year-old man who had their appendix removed for appendicitis and then once the pathology came back it said that well there was appendicitis but there was also a laminis or a 30-year-old woman who had her appendix removed for what was called a mucous seal on a CT scan that is an appendix that looked unusually large and was found to have a laminant T4 and how that would be or wouldn't be different if there is a bit of mucin outside of the appendix in surgery or if there isn't any mucin outside of the appendix in surgery and then finally a different scenario where you have somebody who was found during a routine CT scan for another reason to have both a tumor in the appendix that was a lamin but then muin in many parts of the abdomen that is something that is beyond what we would discuss today as a as a typical lamin so what do we do in these cases how do we make decisions And some key questions that again come up often is who needs more surgery on the appendix? When should we remove part of the colon? What about cyto reduction high? And one other key message that I would like everybody today to have in their mind is so much of what we do today is based on consensus and expert opinion. It is not based on the gold standard in medicine which is randomized trials. So so much of our protocols, whether they're national guidelines, whether they're institutional guidelines, are driven by a lot of us putting our experiences together and trying to make sense of hundreds of patients who have been seen and treated with this and and what are the things that seem to work better than not. But it is not again the gold standard which would be we have a 100 people or a thousand people and then by flip of a coin half get treatment A half get treatment B and then we know which one is the actual better treatment. That also means that you can visit as I I like to joke you can visit 11 10 specialists with for this and you're going to get 11 different opinions.

27:04 there is not always a lot of consistency and that is a healthy part of a field that is not hasn't finalized their conclusions. Right? If we all had the same exact answer without having these fundamental trials, then it would be a sign that we're not being inquisitive enough and thinking about this enough. So surgery or surveillance after having the appendix removed. Well, we have to like everything else in medicine, we have to balance the risk of surgery to the risk of surveillance. The risk of surgery is what can go wrong if you have an operation. The risk of surveillance is what can go missing if you don't have another surgery.

27:43 So lammens typically show up when the appendix is removed from for some other reason. That's the more common scenario. Or a second scenario is somebody's having a CT scan for some other reason and then they identify an an appendix that to the radiologist just doesn't look normal. That can be that mucus seal that we talked about. That's a large appendix that has a lot of fluid in it. Sometimes they can see what we call neural calcification. So that's calcium on the wall of the appendix. If you want to think about it, it's almost like the the appendix is is growing a shell of that looks like an eggshell on the outside. That's calcium. And that's usually a sign wherever that is in the human body is usually a sign of something that has been there for a very long time because it's a very late change that our body creates around it.

28:35 Anything abnormal is forming that that calcified or that calcium deposit around it. And it's very important I have to emphasize this that because these are relatively rare tumors, it's very it's key to have an experienced pathologist who can identify the nuances review that to make sure that the correct diagnosis is assigned that this is indeed lamine and not sometimes as we often see a benign polip of the column that was just very close to the appendix or sometimes we see an invasive cancer in that area.

29:12 But going back to the treatment as we discussed or as I mentioned before in most cases having the appendix removed alone is enough. Removing the right side of the colon or a right hemicolectomy is very very rarely if ever needed. the few exceptions for that are when some somebody has a positive margin or there was tumor at the edge of the appendix when it was cut out. Sometimes that is a reason to consider additional surgery that may go up to a hemiclectomy or if there is concern that this was not truly a lam and something just doesn't look right and in those cases if we think that this is more of an invasive cancer we often recommend a right hemicolectomy. The reason that a hemiclectomy is not needed or removing part of the colon is not needed is we remove part of the colon primarily to get the lymph nodes that a tumor from the appendix would spread to. But lammens if they are true lammens and they grow by pushing rather than by growing into are extremely rare to go to the lymph nodes. So the chances of actually getting anything important by doing the colon removal are is very low and the risk of removing part of the colon is always still there. So there is no rationale for people who have a lamine to have part of their colon removed again unless there are certain circumstances like the ones that I mentioned and maybe a few others.

30:40 the role of cyto reductive surgery. Another point that often is brought up or intraparital chemotherapy which is advocated in in some centers in our again interpretation of the data and what we know the cyto reductive surgery or removing visible disease only has a role if there is visible disease. So if at the time the appendix was removed the surgeon and that's why it's so important to have a a clear well doumented surgical report at the time of the appendix removal. If the surgeon says everything else looked completely normal then it makes it very unlikely that by going back for another surgery we're going to add anything to it. If at that time on the other hand the surgeon says that there was a few spots here and there we only biopsid one or two we don't know what the rest represent it may make sense to approach this again and try to see if there is more disease to be removed.

31:40 Traditional chemotherapy, intravenous chemotherapy, oral pill chemotherapy is rarely recommended for this and again the exceptions are extremely few and the reason for that is these are tumor cells that as we talked before are very slow growing and that makes them really resistant to chemotherapy. So chemotherapy usually works by finding cells in our body that are growing really fast and slowing them down and causing them harm in a way that kills them. If the tumor cells like these ones are growing so slowly, the chemotherapy won't do much to help. In addition, lammens do not spread through the bloodstream. So they don't go to the same areas that you that a chemotherapy that we would take through the IV or by mouth would go to. And then as I showed at the beginning or earlier in the talk, the risk of having something coming back after the appendix is removed is fairly low. So even if there were a potential benefit from chemotherapy, it would be very hard to justify the negative aspects of chemotherapy when the risk of a tumor coming back is so low because chemotherapy as many of you are well familiar with is in itself not an easy course of treatment.

32:55 Finally, surveillance after treatment is done. Surveillance is very important to detect the few cases when the tumor returns after the initial treatment. Most of these recurrences, most of the time that the tumor will return will happen in the first 3 to 5 years. And that's what makes this the most important window for us to keep watching and making sure nothing is showing up. Most, as I mentioned before, of the folks who will have something come back can be rescued with surgery as long as there is followup established and it doesn't take too too long from the time that something changes to to be identified with medical workup.

33:36 And even though it's it can be intimidating, especially for those who are newly diagnosed, to plan for a very long-term surveillance, which in our institution is usually 10 years, it's important to remember that while the anxiety never completely goes away, it does decrease over time. So the second year is probably going to be better than the first and the 10th year is probably going to be better than the ninth. What we usually recommend for surveillance depends a lot on that staging that we talked about. For TIS tumors with the risk being so low about 1%. We feel that the risks of radiation the other side effects from the radiation of the of the CT scans I mean the anxiety that is caused by having to come for scans every year all those disruptions are not justified by a risk that is that low. So we usually recommend symptoms-based surveillance. That means if anything changes in your health. We want to know and then we can investigate this further. I will say this is personalized. Sometimes I've had patients who even though I had this very frank conversation with them about the low risk of something coming back.

34:48 They're not zero risk of of being exposed to CT scans for for a long period of time. they still wanted to have an in between arrangement where we still did some some scans at periodic intervals. However, for T3 and T4 tumors, our practice is to have imaging either a CT or an MRI every four every year for four years and then every other year until year 10. And here a key thing to remember is that change is more important than finding something. So you might get a CT scan, they see a little spot somewhere. Sometimes that creates a lot of anxiety, but in in isolation sometimes this can be a finding that somebody has for a different reason.

35:32 It's more the evolution that we find to be key in understanding who needs something more and and what that may be. And of course beyond just the imaging we need to have a history to obtain the history of the patient through the last year. Examine them and test some serum tumor markers. That's the blood work that we test to see if there is any reason to suspect something is going on. So, some symptoms to report if this is a diagnosis that you've been diagnosed with and you're in surveillance is progressive bloating or abdominal distension, new persistent abdominal pain. Again, usually these are things that tend to last a long period of time.

36:13 It's extremely unlikely that you will have a 10-minute symptom or a five minute symptom that will be related to this in any way. But if it is weeks of dull pain or dull discomfort, that can be something to be concerned about. The presence of a new mass, early satiety, that is feeling full quickly after a meal, unintended weight loss, a new persistent fatigue. These are all things that many times have nothing to do with this may have a completely different explanation but in the context of somebody who has this diagnosis it's important to keep in mind. So going back to the patients that we talked about the cases we discussed that first patient who had incidentally found TIS lamin doesn't need in our opinion anything beyond symptomatic surveillance just looking to see if there is anything from that develops from symptoms but scans may have less value the patient who had the T4 and in this case I will say whether they did have some mucin outside of the appendix or whether they didn't have as long as the mucin didn't contain tumor cells we would recommend having a scan every year and blood work for those 10 years as we discussed. And then when we what do we do when we have somebody who has more spread from a lamin where we have spots in different parts of the abdomen and that depends a lot. It depends on of course the the nature of those. We need to biopsy them and analyze them thoroughly to make sure that is there a tumor, is there no tumor cells, are there no tumor cells there? And then it also depends on whether there are other medical problems, what else looks, how it looks under the microscope and what the priorities of the patient are in that time. But often those are the cases where additional surgery is necessary to clear up anything else that is in the abdomen.

37:59 With that, I wanted to transition a little bit into the multiddisciplinary team that we alluded to at the beginning of this where this is an initiative we've had over the last two years and we fully implemented it approximately a year ago as we try to streamline the diagnosis and work up patients with lamin at our institution. We want to make sure that the care is consistent, the follow-up is consistent and of course to have an ability to keep track of the patients and understand this disease better. have opportunities for future research that is focused on this entity that is so understated. So how does that this work in practice is when a patient requests a consultation at our institution for this diagnosis before anything else happens before we even see them we try in the background to have the specimens and the imaging the scans reviewed here and while this consultation is again being scheduled we have a multi-disiplinary discussion we have a specialized tumor board that meets once a week that is focused only on low gradede appendicial mucinis neoplasm neoplasm and where we discuss these things in a little bit more detail than we would have the opportunity otherwise. Do we see anything in that mucus outside of the appendix? Is there some particular characteristic that departs from what we would classify easily as TIS or T3 or T4? Sometimes the pathologist when we have a chance to talk to them directly can be a little bit more detailed in their description than what they can put down on a report. And then the patient consultation happens. And the beauty of this system is by the time we have the patient consultation, we've done all this leg work. So we can now discuss a recommendation that is specific to what this particular patient had and then move on to surveillance. And for the surveillance, we have enrolled one of our nurse practitioners who remains the the key person to continue the chain of surveillance across the years and maintain that consistency. So the team as I alluded to involves the three of us from surgery Dr. Nash, myself and and Rachel who is our nurse practitioner a medical oncologist Mike Foot who is also another person in our group who like myself has made it a mission to figure out appendix tumors, appendix cancers. What can we do better and different? But we wouldn't be able to do any of this without our radiologists and our pathologists. And the reason is no matter how much we think that we have some answers or we don't have some answers about lamins without the expertise of our pathologists to tell us exactly what they see the nuances we would not we would be driving blind essentially. So it's extremely important and that's the most important part in our multi-disiplinary clinic is having that direct input from their pathologist from the pathologist the day before the consultation.

40:59 A few future directions before I conclude this and we can talk a little bit more about the questions that you all have. The first we are now in the process hopefully within the next few weeks we will have established a an appendix specific tumor registry at MSK where we want to include both patients who are newly diagnosed but also patients who have been diagnosed at any time at any time and with any type of appendix tumor. Remember in the a few slides ago where I showed you the early and more advanced tumors, the less aggressive and more aggressive tumors, all of them would be part of this registry. And what we're trying to do is obtain a very detailed personal, family and social history. we are all perplexed. Why are we seeing sometimes clustering of cases in certain parts or in certain families? Why is it that the newer generations and there's been a lot of not right in the news the last few months. Why are we seeing that the younger people are more often diagnosed with appendix tumor than they used to be? And we're trying to collect as much information having the the privilege of caring for a large number of patients with appendix tumors. consolidate all that information and try to answer some questions about what may be the ultimately the cause or the factors that contribute to it. It will also allow us to have everybody under one roof and offer tumor and patient genetic testing to both understand if there is a hereditary component but also if there are specific tumor alterations that change how patients do. Maybe we find out that certain profiles don't need to have any scans or others need to have more often CT scans. And ultimately what we're trying to do is understand lowgrade appendicial mucinis neoplasms better in in summary a few things that I wanted to kind of drive home. One is the importance of staging and driving treatment decisions by staging and extent of disease. the importance of having specialist consultation especially as I said not just the practitioner the surgeon the medical oncologist but rather a group of people and is particularly supported by a pathologist who can understand sometimes these nuances. It's important for those who need active surveillance who need to keep having imaging to commit to that because that's the way that we can prevent anything from happening or advancing too far where we cannot rescue it with surgery. It's important to recognize what could be unnecessary surgery.

43:40 Sometimes having a partial removal of the colon is not necessary. Most of the time it's not necessary. And finally, it's important to remember that wherever one may be in that whole spectrum, our modern treatments have led us to offer more and better quality of life to patients who even a few decades ago we would have had very few treatment options. In conclusion, if you're going to remember a couple of things from today's talk, one is the prognosis is favorable, probably more favorable than most people think when they're diagnosed with this. Additional treatment at the time of diagnosis is rarely needed.

44:18 And it's wonderful and very inspiring to see the excellent patient advocacy and support groups that are available. And I encourage all of you to to take advantage of all these resources. And then of course to be generous if you can with your time and help the next person in line who might have the same struggles and might be in that same tough situation in the future. And if you can stay optimistic, I think that this is probably a lesson in life in general that we know none of us know what the future holds. And I say until you have real reason to be pessimistic about it, stay optimistic.

44:57 It's a lot it's a lot nicer and it's a lot easier. So with all that, thank you and I'm happy to take any questions. Chris, I think you're muted. >> I got it. Thank you. Thank you so much, Dr. Caragunes. So we have a couple of questions in our Q&A for participants who are here with us live. If you look down on the bottom, you move your mouse around a little bit, there's a Q&A section where you can dump questions in for Dr. Caragonas. We're gonna start with a couple of presubmitted ones from the from the presubmitted questions when people registered. I actually did have one question about your presentation before we get to those, which is you said in part that whether or not surveillance is appropriate or different treatments depends on whether or not there was spread when the appendix was removed. How do you think about what's found during that appendecttomy by often surgeons who are not appendix cancer specialists? Right? Like when I had my appendix taken out, it was by a general surgeon up here in Albany, New York, certainly not a specialist. So, how do you approach it when patients come to you and they've seen another surgeon for that initial surgery? Do you take the reports? Do you do some sort of evaluation? How do you evaluate that?

46:08 >> That's an excellent question and you're absolutely right. the vast majority of times folks had their appendix removed in the context outside of of the care of a specialist in appendix tumors. Right? There is statistically it's it's very unlikely that it would happen otherwise. And that's why we that's where we have to infair a few things. We have to try to put the pieces together and figure out if that makes sense. And I will say it's possible that the reason we are seeing these tumors come back in that 3% 4% 5% could be more related to something not being properly looked at or documented or evaluated at the time of that initial surgery than anything else. It's hard to say and even harder to prove but that's possible. So that's why we take all the different pieces of the puzzle. For me that means reading their operative report that sometimes can be very revealing and unfortunately today in today's age a lot of people use kind of almost like cookie cutter verbiage in their operative reports and that can make it less informative. I also find it very helpful to ask patients directly because a lot of times their surgeon might have told them something that is not in the operative report. So often they will say oh my surgeon told me they looked everywhere and it looked very clean. It means different than sometimes when people say well my surgeon told me I need to see another surgeon which makes it more concerning. Then then we look at what the scans look like both before the appendix was removed and after. Then we look at what the blood work looks like after the appendix was removed. If all those pieces look reassuring then people can go on as we said to the surveillance getting their scans every year. If something doesn't look right, then we have a kind of almost like a escalation ladder where we move on to well maybe we need to get a scan a little bit sooner, maybe we need to check labs a little bit sooner all the way to having a laparoscopy that is putting a camera inside the abdomen to take a look again with now the benefit of hindsight which again the first surgeon didn't have at the time to be able to look at that. So depending on the scenario all those things are options.

48:16 >> Okay, thank you for that. So getting to a couple of sort of the themes that we saw in the questions that we got presubmitted, can you talk about what the value is of blood work in surveillance? >> Yeah, that that is another interesting topic and it's actually one that we were I just mentioned Dr. Foot on on my presentation toward the end. He and I were at a meeting two hours ago as we're trying to put our experience together and see how that enhances the value of of surveillance and identifying these lesions from when they're coming back. And what we've seen across the all the appendix tumors is that it probably gives you a sense sometimes 6 months, 9 months, 12 months before the time that the CT scan can show something when there is an increase in those tumor markers. So again, I caution people from looking at the numbers in isolation.

49:04 Some people are born with slightly higher numbers in the same way that some of us are born a little bit shorter or a little bit taller. But if their numbers are changing as the time goes by, that can be a sign that there is something there that that we need to be concerned about. And that's where what we found is that by pairing the CT scan or the MRI with the tumor markers, we get a little bit more information and that can help us say, well, this person probably should not get another wait another year for the next scan. Maybe we should do it in six months because something might be brewing.

49:36 And can you so we have a question in the chat actually about how can three blood tests CA125 CA19-9 be normal if an MRI is showing new growth. I can speak from my patient perspective. I have driven Dr. Nash insane about blood work over the years because my blood work has never been abnormal even when I had recurrence and active disease. So can you talk a little bit about like how I think if unless I'm wrong some for some people it does show and for some people it's just not really that great of a tool. So I I think that you're absolutely right. There is three different scenarios that that can cause that. The the most benign scenario is sometimes people will have mucus in their MRIs or the CT scans. The mucus doesn't may not have any tumor cells.

50:17 It's just leftover mucus from when the appendix was there and burst and maybe seated some of that mucus out. And if there are no tumor cells, there there's nobody to make those tumor markers. And they those are the folks who can have something on their CT and MRI that may stay stable for years. And sometimes we've had patients we've been watching for more than a decade. Nothing changes. There is no reason to go after it. The second reason and third are kind of related is some people make some tumors make a lot of it. Some pe tumors make very little and some tumors don't make any of it at all. So some people might have a tumor that doesn't make any of those proteins and then if they don't make it then the bloodstream is not going to pick it up or if they make so little it has to reach a certain threshold before it starts becoming abnormal in the bloodstream. We do think that some of the levels the way that they're defined by the the you know typical lab test you say less than five is normal more than five is abnormal might be a little bit too strict. in fact, in the in this research project that we're working on, we found that sometimes an increase of say 50% over what it was before may be significant.

51:23 Even though the new number might still be normal, that if it went from normal two to normal four, it may mean something, but I've also seen a lot of people or not a lot, but some people that go from two to four and then back to two, which means that there was something else that made that number change. So, I would not lose sleep too much over that number alone, especially if it's in the low range.

51:46 >> Okay, thank you for that. U we had several questions about what you think is a better diagnostic tool, CT or MRI. >> that's a that's a very very good question. I I both are wonderful tools for this kind of diagnosis. I think it's important to go with the one that each institution has accumulate has the accumulated expertise with. for instance in our institution we use more CT than MRI for this which means that I trust a little bit more our radiologists ourselves frankly as surgeons in interpreting the fine nuances when it comes to CT scans rather than MRIs in this particular scenario but other places might have more of an MRI first approach there is pros and cons to each one many people are probably familiar MRI doesn't have radiation which is wonderful on the other hand takes a lot more time it's in a slightly claustrophobic tube and it it can be much more expensive as well. So there are pros and cons. At the end we don't think that one is a better surveillance strategy than another. So we like to have this more of as a collaborative discussion with our patients and sometimes we go one direction or another but a CT scan seems to be a little bit more straightforward for everyone involved. And we had a participant asked, do you know of any new imaging technology being developed to better detect specifically the mucin which in patient forum seems like a sticking point that sometimes it's hard to see.

53:12 >> Yeah. So there are a lot of things that are in the pipeline now. We're testing even here for instance special tagged scans that pick up different changes in in tumors and try to make this into a signal that then we can look. There's nothing that is ready for prime time that I would say, well, tomorrow we're going to start doing this on everyone. So, I think we're not there yet. The mucin itself, interestingly, is not always the problem. The problem is what's happening inside the mucin or underneath the mucin. We really cannot tell if the mucin has tumor cells in it.

53:43 There's so few of them. Sometimes, even when we take it out, the pathologist says they're struggling to look through it because it's a whole sea of mucin and then one or two little islands. it gets even more interesting and sometimes concerning in the more aggressive types of appendix tumors which we're not touching much today on which tend to grow a little bit more I like to describe it in two dimensions rather than three dimensions and they're not very easily picked up by scans but the majority of the more mucin making tumors the fact that they make all that mucin makes them a little bit easier to see sometimes.

54:18 >> Got it. Okay. one of the questions we saw repeatedly in our presubmitted questions was are there any emerging treatments? >> Yeah. So for for the the folks who come in with again trying to kind of go back to the the topic of today is the the lowrade appendicial mucus neoplasms that that start kind of in the appendix. They are in the appendix precisely because they tend to do so well. We don't have a huge need to try to improve our our treatment at that level. Where we really are focusing our attention is what happens when either that person had a lamin for a long time and then at some point it started spreading through the abdominal cavity or that same person who had their lamine removed now comes back years later with other areas of involvement in the abdominal cavity. And that's where we have a number of different treatments from the more now established cytoroductive surgery, chemotherapy for the ones who need it to more targeted therapies. We're starting a clinical trial in the coming days that Dr. Foot and I are are leading together where we're trying to see if imunotherapy can be helpful for certain types. This may be more tailored towards the more aggressive types of appendix tumor rather than the the well- differentiated lowgrade tumors. we have other things a little bit further back in the pipeline of targeted therapies where we're trying to find specific proteins molecules on the surface of of these tumor cells that are making them look particularly different from the ones that are healthy t healthy cells in the somebody's body to then be able to target them and and treat them with either radiotherapy or chemotherapy.

55:57 And I know it's not an emerging treatment, but one person asked, "What are your thoughts about genetic sequencing and signaturing technology?" >> Oh, I mean both both of these have a a role. So for the to answer the first question first the the sequencing we think is very important because that helps us know much more about these tumors and we also have evidence that depending on the type of mutations somebody has their prognosis can be somewhat different. Now that's a little bit more applicable to people who have spread from a appendix tumor rather than people who come in with a confined appendix tumor but it does help us get that information. the signatur which is a type of CTDNA or circulating tumor DNA that that's a kind of test that tries to find out fragments of tumor DNA that may be in the bloodstream and it has worked well in some types of tumors in in appendix tumors and specifically in low-grade appendix tumors it may be a little bit less useful for two reasons one for reasons we don't quite understand tumors that spread on the inside of the abdominal cavity don't yet to spill their DNA inside the bloodstream as much as tumors that grow into say the lungs or the liver or some other part of the body. So it's a little bit less likely that we are going to be able to see it. And the second thing is for these tumors because they're so slow growing and because they don't look that much abnormal. Sometimes it's harder to detect them or pick them up with circulating tumor DNA technologies. So, it's I would say it's under investigation, but I'm not sure how close we actually are to being able to use it.

57:39 >> Okay, good to know. a couple of the theme of the presubmitted questions had the theme of comparing outcomes for patients with and without H highac. so some patients get it, some patients don't. Do you have any data behind supporting one or the other? Yeah, that's that's an excellent question and that's one that I would say is if you want to create a little bit of I I like to joke if you want to create a little bit of drama in one of the conferences where all of us come together that's a good topic to start because there's always a lot of lively discussions about what one group thinks what another group thinks and as I prefaced before there is very few things that we know with absolute certainty in this field it's a rare tumor a lot of it comes down to institutional experience and expertise One of the trials that our institution ran for the for about a decade from 2013 to 2023 actually compared two different types of chemotherapy inside the abdomen. One was HIPPEC with mitoc which is what's most commonly used in this country. The other one was epic with fluxuridine which is a different type of drug that works with GI tumors. And it was very interesting and in some ways disheartening to note that even though people did actually better than we were expecting in general there was no difference between the two groups.

58:58 the and that was 212 patients. we had enough people there that we should be able we should have been able to see a substantial difference if there was one and our interpretation and again one can interpret this as meaning that both of those treatments are just as good or both of those treatments are not doing anything beyond the regular surgery and and I would say and this is not I'm for those that know me know that I'm a very optimistic person but I think it would be really optimistic to think that we don't have just one good treatment to give inside the abdominal cavity we have two of them that work just as well. I think it's more plausible that two treatments that are so different given in a different way at different times, different temperatures, different way that the drugs go about having the exact same effect doesn't seem very likely. So with all that together and without having any definitive proof in any study that high in appendix cancer or in lamin decreases the risk of the tumor coming back. Our institutional approach has been not to offer it in the sense that it is a toxic treatment and the burden of proof lays on proving that it works so that we can justify subjecting somebody to the potential risks that come from it.

60:14 >> Okay. Thank you. we had another presubmitted question that I wanted to ask. This person asked, "Can lamine grow outside of the abdomen?" You know, we hear some stories in the general appendix cancer community about some people have metastasis to the lungs and other and other areas. Can lamine specifically spread in that way? >> Yeah. So, it's thankfully very uncommon. it can happen. The number one place that they would go if they try to get outside of the abdominal cavity is typically the chest cavity. and that happens the way we think about it because these tumors are almost by the way that we define them. They're unable to get into blood vessels or channels and travel through the body. We think there has to be some physical connection between the abdomen and the chest. So what sometimes will happen is people are born with little tiny holes in their diaphragms that connect their chest cavity to their abdominal cavity and sometimes tumors can take advantage of that. or sometimes they had some sort of procedure that brought the two into communication but it's quite uncommon and beyond that having something go beyond the chest cavity somewhere else is is really anecdotal I cannot remember in many many years having seen somebody who had something beyond either the abdomen or the chest.

61:30 >> Okay. we have one participant asking does caking on the spleen stomach qualify when you talk about spread is caking part of spread. >> Correct. So caking is is a a very very descriptive term. I I know that somehow pathologists and radiologists are always happy to make analogies to food or or food material whenever they describe something. Caking describes an that has tumor implants or mucus implants on it. So the is a piece of fat we all carry in the front of our abdominal cavity that for whatever reason really seems to attract tumors to it or any sort of spread to it. So yes having caking or having that change in the or the spleen would be a sign of a tumor that left the appendix and now is somewhere else.

62:20 >> Okay. I know you did some you know worrisome symptoms that if you're having these you should flag your team. One participant is asking, "Could bladder symptoms like incontinence be a concern for recurrence?" >> Good question. A lot of it depends on where what kind of scenario we're talking. So to go from having the appendix removed and having a lam in there and everything being perfect and then having incontinence I would say is a little bit there's a couple of steps in there that are missing to really tie this together. But what can happen sometimes is one of two scenarios. Some one would be if at the time of the original surgery somebody needed to have a lot of work in their pelvis because there was a tumor there and now it's growing back in that area that would make sense or if there is no not only that incontinence or urinary changes but it's coming in the context of bloating and lower abdominal pain that can be another reason for something like this to happen.

63:20 We had one participant ask, "Can colon cancer come in the form of lamine as well?" >> Yeah. So, I' I've seen and I've heard of a couple of people over the years that had lowgrade colon cancers or lowgrade colon tumors that tended to spread in a similar way. U if we are going to be technical about it by the A in lamin is is appendix. So, by definition we have to start from the appendix. But there are similar sometimes types of of spread from colon cancers that might give that same appearance of gelatinous materials, mucus outside of the of the colon, but it's much less common. Sometimes what will happen is the appendix is is itself attached to the colon for many years. In fact, I think pathologists and surgeons were a little bit blaming everything on colon cancer until we realized that no actually an appendix tumor is a distinct entity and we need to think about it as such. So it may often be that the colon is blamed by association rather than actually having caused it.

64:24 >> Is there any significance to the size of the tumor at diagnosis with lamine specifically? >> Not as much. I think that there is the as long as we're talking apples to apples and you have two people who have a TIS or a T4, it's it's not particularly important. Now the bigger the tumor almost naturally it's a little bit more likely that something might crack whether physically crack or the tumor kind of finally overwhelms the appendix and and bursts through. But if we are talking about two tumors that have the same exact stage and just different sizes, it doesn't seem to be as important.

65:02 >> Okay. we have one person asking, "Have you ever had patients in the same family who are diagnosed with lamin?" It reads to me like she and her sister have both been diagnosed. >> You know, I that that I I don't kind of remember of having two patients from the same family, but we do see sometimes people have one member of the family might have a lamin for example and somebody else might have an unusual type of tumor. That was one of the ideas behind us trying to create this registry to try to capture so much more of that information. We don't think that there is a hereditary component as best as we can tell, but it might just be that there's an environmental component, something in the in the diet, in the environment, in the pollution, in something else that may predispose some people. So, I don't know that we have a real really good answer, but that's something that we're very interested in looking. And I would say if there are two siblings that that have this in the audience, I think it would be really important to reach out to their providers to see if they can do some genetic testing because sometimes that's the the first best way we have to identify a new gene that is causing something is find two related individuals who have the same diagnosis and then go backwards to see what exactly is that they're sharing.

66:17 >> Okay. Can you talk about how often does lamine progress to hammen or other types of appendicial cancer or does that happen? >> Yeah, that's difficult question to answer because the reality is we don't quite know. the reason we don't quite know is that we only capture these things at one point in time, right? We don't have the chance to say, well, we took a biopsy in 2010, it was lamine and then in 2016 it was it was Hammond. We think that there is a progression from from a lamine some tumors become hammonds or some tumors might become invasive cancers. we do in fact see the other way around. Sometimes people come in with a cancer and in that same appendix there are some areas that look more benign, more laminike if you will.

67:02 but it's hard to give exact numbers because so much of this happens under the radar until things have kind of progressed more visibly and then it becomes more difficult to trace back. >> And I will also say one more thing as a diagnosis is a little bit more recent in a way. I think 1015 years ago we didn't appreciate it as much. So there is also a little bit incomplete data moving back about how many people really had ham 20 years ago.

67:30 This is basically the definition of how science evolves and we learn things, right? >> Yeah. >> can So one person is asking how can mucent be dormant for two years and then appear again? Like it's not new growth or new mucin but now it's active again. Does that mean it's cancer? >> Yeah. The way we think about this well it's one of two things and it's hard to tell which one it is in any specific individual but we think both play a role. One is these things grow so slowly that just to make a picture, imagine that you know you have one tumor cell sitting inside the abdomen to get to the point where we're going to be able to see it with a CT scan or make enough CA to be detectable. It may take two years.

68:15 So for two years that thing is slowly growing but it hasn't reached the threshold of of being visible. And that gives you the sense that wait a second, a whole year and a half it wasn't there and now it's there. Why is that happening? Sometimes it just might be moving that slowly. The second thing that happens to tumors in general and and appendix tumors are no different for reasons we don't understand. Sometimes they switch on and off and they can go into almost like a deep sleep state and then they start coming back up again.

68:44 These are things we're trying to understand how sometimes stress both stress to the tumor itself or stress to the individual who has the tumor can throw that balance off and and make things go back into a different direction. >> in the presubmitted questions, we got a couple of people looking for any recommendations you have on once they're diagnosed, what can they do in their daily activities to either help fight their cancer or prevent a recurrence? Is there anything that a patient can do?

69:14 >> Yeah. So, in particular for this type of tumor, we the short answer is we don't know. But we do know I always used to tell patients even if we don't know that this helps with your cancer, your tumor. We know that it helps in general to eat good food and to exercise and to be active and do all those things. Now, we can go one step further. There was a recent study in colon cancer which is probably the closest relative to these appendix tumors that we have in terms of biology that showed beyond I think reasonable doubt that for people who had a removal of their colon for colon cancer if they had if they went on a path of exercise a few times a week they had almost as much of a benefit in terms of reducing their chances of having the cancer come back as having chemotherapy. It was a very profound benefit from that. So while it is very I realize it's very easy for me to say tell people you know sit up here and tell people exercise three times a week. I know I'm not always doing that either but it's important to incorporate this because we know and we find more and more that a healthy body can can actually do more than we give it credit and that may be keeping things at bay that would otherwise try to come back.

70:26 >> Okay. one of our participants asked, "Is there any concern about taking GLP-1 drugs, particularly because the side effects could mask symptoms of a recurrence?" >> Yeah, that that is that's an interesting question. A lot of it can affect the the way that the stomach empties and can give people that satiety or early kind of feeling full. in some ways it's actually a good thing for the purposes that these drugs are used because it can decrease the appetite. The problem is you want to know if your appetite is decreased regardless and the weight loss. You cannot tell which where you should attribute this. We don't have any reason to think that it is making things worse from a biological perspective. But it is important that it can mask some of the symptoms. So, I think that anything that we we have to use our almost like a we have to just monitor the symptoms as they're going and figure out if it does correlate. If somebody just started a new medication and something is coming up, it's very easy to say, well, probably that's what it is. But if somebody has been on this medication for four months without any problems and all of a sudden something changes, that's a bit more concerning. but I think that symptoms again that's only part of the equation. We talked about the blood work, we talked about the scans. I think we have to look at everything together.

71:46 But it is an evolving field with a GLP-1 agonist. The medications that have become popular now and they can change a lot of how our GI system works. >> Okay. we have about maybe 10 minutes left. we had a question. Does your PCI score have any correlation with recurrence rate? >> Yeah. So a PCI score just to give a a bit of context to for those who are not familiar is is when we evaluate somebody who's having surgery for for spread of any type of tumor we split the abdomen the abdominal cavity into 13 different fields and we assign a score about how much tumor or how much disease is anywhere. So PCI score is a way to quantify how many areas of the abdomen are involved. And we know that if we are looking at people who have tumors of the same type, then having more of it is more likely to signal somebody who is going to have that tumor come back than having less of it at the beginning. But of course, it's very different depending on the type. So having more of something low grade is better than having a little bit of something high grade and vice versa. So it's important to keep that it's a little bit outside of the of the lamin by itself but there is some degree of correlation between how much is going on and what the likelihood is. That being said a much stronger predictor of what will happen in the future is the ability at the time of site reduction to clear out everything that is there. So having a high PCI but still being able to clear everything is better news than having a low PCI but not being able to clear everything up.

73:25 >> Okay. what would you consider to be the normal range for CA and does that vary from facility lab? >> Yeah that varies slightly between labs. I think our lab defines it as less than five is normal. Five or more we call it abnormal. Every different lab has slightly different numbers when it comes to this. It can change for smokers in particular, people who smoke tend to have a little bit higher numbers than people who don't smoke. When we looked back at at the numbers though, as I mentioned, we found that and that I think makes sense instinctively. We all have a our own thermostat, right, where we we live at. So if all of us were to test our blood at a time where we don't have anything growing, it should have a specific number. And it's the change compared to that number that may be more informative, but that's still at an early moment. So I would say to me anything that is more than five always raises some concern that there might be something and on the other hand anything any increase that is more than say 50% or so over a period of time also raises some alarm but there are a lot of false positives so I wouldn't use that as the end all be all to make any determination.

74:35 >> Yeah. >> One of our participants is interested in the registry that you mentioned in your presentation. How do you anticipate patients will be able to sign up especially if they're not MSK patients? >> Yeah, that that's a good question. I for now I mean like first of all we haven't even opened it formally yet. It's going to be a few more weeks I suspect but the first step is going to be trying to include any person who we see in our clinics whether again currently receiving treatment or just following up or newly diagnosed. Eventually we hope to be able to expand beyond our institution but that would take a lot of additional kind of infrastructure that we have to make sure we have in place so that we can do that in in a proper way. So as of right now it it is in the near future I would expect it would be primarily limited to people who at least at one point or another cross paths with our clinic.

75:33 be sending my tumor right over there. okay. So, we have one question from someone who says they had CRS high recently and their surgeon noted that their mucin was very sticky and do you encounter this and do you find that recurrence rate is higher in these individuals who have sticky mucin? Sometimes we see descriptions like this. >> Yeah. So, again the it's all in the the devil is in the details. It all depends on what is in that mucin. So sometimes we see patients who have a lot of that mucin on the surface of their small intestine, sometimes throughout the surface of their small intestine. And unfortunately to to clean that up and remove it completely, we would have to remove the entire small intestine which is a not not a survivable procedure by itself. So we have to compromise. But what we've also found is many times when we send a little part of that to the pathologist to to look under the microscope, they say, "Well, it all looks like the mucus and reaction from the tissue underneath, but we don't see any tumor cells." So, people can have a lot of that sticky mucus, which we do see sometimes in the operating room, but as long as there are no tumor cells inside of it, it's still a favorable scenario. On the flip side, if they do have tumor cells, that becomes a much bigger problem because then it's harder to both clean it up or definitively address those tumor cells that are there.

76:59 >> Okay, great. we have one person who says they recently had surgery, appendix was removed, intact, but at a six-month CT followup, there was an ovarian cyst and kidney and liver hypodensity. So what is the point at which a surgeon like yourself looks at something like that and and worries versus says we should just wait and see how these things develop? >> Yeah. So is this in the context of having had a side reduction recently or just their appendix out? I'm sorry.

77:29 >> It says appendix Lamn surgery did not rupture G1 PTI. >> Yeah. So there sometimes we have to use some of that information to to help us guide ourselves, right? Our frame of mind. So knowing we're talking about G1, TIS, didn't rupture, that's about as good of a prognosis as you can have with this kind of tumor. So then that shifts how we interpret everything because it's way more likely for something to be a false alarm than a true alarm. Right? So that's why, as I said before, it comes into if we start with such an optimistic point of view, even if we see something potentially concerning, it makes more sense to follow it again and get another scan and maybe we don't wait a whole year to get the next scan or maybe we follow it a little bit sooner. On the flip side, if you have somebody who, let's just say, has a much less favorable looking appendix, you have a it was T4, it was perforated, there was mucus outside, that same finding might trigger a different or the labs are abnormal, that may trigger a different kind of reaction because now you're worried more about this is something that could be is more likely to be real.

78:37 >> Okay, thank you for that. and I think the last one we're going to get to is my sister had pancreatic cancer, my brother had seeum cancer, and I have appendix cancer. Could there be a genetic connection? No, >> absolutely. it's it would be hard to know without having all the pieces of the puzzle or the details, but it absolutely there could be. When we looked at folks at msk who came in with any sort of appendix tumor in a little bit less than one in 10 we found that there was some gene into their that they had inherited that was not normal.

79:10 It's hard to necessarily connect the two. A lot of us are walking around. We have some genes that we have inherited that were not exactly the normal copies. So it's not always easy to say that's why they developed that tumor. But there there is a connection there. There may be a connection there. And especially when there is a heavy family history, we have to be even more sensitive to it. Now sometimes that it comes the other way around, right? Like people we find a lot somebody gets diagnosed in your family with colon cancer and then the rest of the family I think understandably goes and has a colonoscopy and then they find a couple more polyp and then they that creates the impression that wow what is happening to us? Well, what is happening is you're now more engaged into this, right? and you're looking into this and you find things that especially slow growing indolent tumors like a lamin that could have been there for a while but now was discovered but I absolutely think that anybody who has a family history of a first-degree relative or multiple second degree relatives should be tested and in fact our practice here has been that anybody with appendix tumors we try both for for the sake of the individual and for our understanding of this to have the genetic testing done both for the tumor and the patient to see if there's something we can learn from that.

80:25 >> Yeah, I I definitely did it when I was diagnosed. It was a blood draw, so no big deal in the scheme of all the things that can happen when you have appendix cancer. okay. Well, I think that's it for tonight. So, I want to thank you, Dr. Caragonas, for your time tonight. This has been so insightful and I think so helpful for so many of us in understanding where things are going here and what what a diagnosis of lamin looks like for people. I will remind everyone that Amanda will edit the video a little bit and we will post it and share it with everyone who was registered and we will share it in the appendix cancer and all of the Facebook groups that we have been posting information about about this one. So, you will have that for use long term. And with that, Amanda, unless you jump on here and say you have anything else, I think we're gonna I don't see her coming. So, I'm going to say good night and thank you so much everyone for joining us.

81:13 >> That was great. Thank you so much, Chrissy. Thank you everyone for joining. A pleasure. Thank you. Have a good night.