Making Sense of Appendix Cancer Guidelines: What You Need to Know

0:00 good evening everyone and thanks for joining us. Let's go ahead and get started. My name is Alyssa Streckbein and I'm the operations manager for the appendix cancer PMP Research Foundation. I want to welcome you to the latest webinar in our 2026 educational series. We are very excited to have doctors Laura Lambert, Noah Cohen, and Zachary Brown here with us tonight. this esteemed panel of experts will review and discuss the recently released National Comprehensive Cancer Network guidelines for appendiceal cancer as well as the current peritoneal surface malignancy consortium guidelines.

0:38 And before I turn it over to them, just a quick refresher. the Appendix Cancer PMP Research Foundation's core mission is to fund and support research to discover new treatments for appendix cancer with a hope of one day finding a cure for all and to fund and support educational programs for healthcare professionals and patients, caregivers, and families to keep current with the evolving science and to increase awareness about this rare cancer. All this work is made possible only by the generosity of our donors and we are so grateful for your support.

1:15 A few quick housekeeping items. At the end of the review and discussion, the panel will address a selection of pre-submitted questions from registration and as many live questions that they are able to address as time allows. Please use the Q&A feature at the bottom of your screen to submit questions. We will not be using the chat feature. lines are muted to reduce background noise. The presentation is being recorded and will be available about an hour after the webinar is over via the Zoom event lobby and through an email.

1:49 It's also going to be made available on acpmp.org and on our YouTube channel later next week. If you have any questions or topic ideas for our webinar series, please reach out to our executive director Deborah Shelton at deborahs@acpmp.org. Alrighty. And now to the main event. one second. Oops.

2:24 Just trying to make sure we can see everybody. There we go. All right. Okay, and with that I'm going to introduce our speakers tonight starting with Dr. Laura Lambert. She's the professor of surgery, vice chair of academic affairs and surgical education, and the general surgery residency program director at NYU Grossman School of Medicine L and NYU Langone Health on Long Island. Dr. Lambert earned her medical degree from Harvard. Her general surgery residency was completed at the Dartmouth-Hitchcock Medical Center followed by a three-year fellowship in surgical oncology at MD Anderson.

3:15 >> >> She has held faculty positions at MD Anderson, the Department of Surgery at UMass Memorial Medical Center, the University of Utah where she was the director of the peritoneal malignancy program at the Huntsman Cancer Institute and the program director for general surgery at the University of Utah. Dr. Lambert's clinical practice focuses on the comprehensive management of peritoneal malignancies. Dr. Lambert is also board certified in hospice and palliative medicine and of course we are so grateful that she is the chair of ACPMP's Medical Advisory Board.

3:46 next up we have Dr. Noah Cohen. He is the section chief of complex GI surgical oncology and associate professor of surgery in the division of hepatobiliary and pancreatic surgery at NYU Grossman School of Medicine. Dr. Cohen earned his medical degree at SUNY Upstate Medical University and completed his general surgery residency at NYU Grossman School of Medicine as well as a post-doctoral research fellowship and a complex general surgical oncology fellowship at Memorial Sloan Kettering.

4:17 Dr. Cohen's clinical focus is gastric cancer, retroperitoneal sarcomas, and peritoneal surface malignancies. He also has expertise in robotic-assisted procedures and in performing CRS-HIPEC. and then last but not least we have Dr. Zachary Brown. He is assistant professor of surgery with a within the division of surgical oncology at NYU Langone Health. Dr. Brown has a special interest in treating patients with advanced or metastatic cancers originating from the appendix, colon, small intestine, stomach, and peritoneal surface. As a board-certified surgical oncologist, he is an expert in treating patients with CRS-HIPEC.

4:55 Prior to joining NYU, Dr. Brown completed his general surgery residency at Rutgers Robert Wood Johnson School as well as fellowships in tumor immunology and surgical oncology at the National Cancer Institute, National Institutes of Health, and a fellowship in complex general surgical oncology at the Ohio State University and the James Cancer Hospital where he received specialized training in treating patients with advanced and metastatic cancers. Thank you all again for being here. We are so grateful and excited to have you here and for this discussion and with that I will hand it over to Dr. Lambert.

5:27 Great. Thank you, Alyssa, and thank you so much to the ACPMP Research Foundation for hosting this event tonight and for allowing us to join you again with my colleagues Dr. Brown and Dr. Cohen. We're really excited to be here to talk about the recent guidelines, anything and everything about guidelines for cancer but specifically obviously about appendiceal cancer. I'll just let you know Dr. Cohen is actually going to have to jump off a little bit early so that's why we wanted to get it going as quickly as possible.

6:02 but it's great to see so many of you joining us tonight. I actually see a number of names on the list, people that I know so it's great to see you and glad that you could join us. So, we're going to we're going to kind of dive right in. I know this is a relevant and timely topic. Dr. Levine from Wake Forest recently published a editorial in the Annals of Surgical Oncology addressing the guidelines that now exist for appendiceal cancer which I have to tell you is truly remarkable because for a very long time there has until recently there really hasn't been anything like this.

6:39 So, we're excited to talk about it. I think it's a testimony to the amount of research that's being done in appendix cancer, the amount of attention that's being given to this rare cancer and the progress that we've made over a relatively short period of time. So, I'm actually going to start with a question for for Dr. Cohen. We're hoping this is going to become a little bit of a discussion and you guys can sort of listen in.

7:04 but I was going to ask Dr. Cohen if he could just speak briefly about just in general, what are what are cancer guidelines and and how do physicians use them in general? All right. So, you can hear me okay? Just want to make sure. So, cancer guidelines are evidence-based recommendations developed by expert groups that review the latest research on how to diagnose and treat specific cancers and they bring together data from clinical trials, real-world experience, sometimes even expert opinion to outline what is considered the safest and most effective care and you know, these recommendations can be based on high-quality data like randomized trials if they exist, if they're available.

7:46 Sometimes they're based on other data that may not reach quite such a high level like observational studies or as I said expert opinion. And physicians use these guidelines really as a road map when making treatment decisions for patients and they help ensure patients receive high-quality standardized care wherever you may seek care while still also allowing doctors to tailor recommendations based on an individual patient's condition, their preferences, and of course their overall health. So, sort of just gives us a little bit of a baseline standardized starting point where where doctors can at least begin a conversation with the patient. Yeah. And you know, as you guys know, both of you and everybody on this call knows appendix cancers and tumors are incredibly rare.

8:33 So, I'm sure a number of people on this call have been in a position where they've they've gone to see somebody and the person has said, "Wow, either I've never seen this or I saw one of these when I was a resident." And they're not really sure what to do, right? And so, so Dr. Brown, you know, in your experience, you know, how do you think these guidelines will help people in that situation? What what can we do to encourage the use of them so that so that people will will be able to get to the care that they need need to get to?

9:08 Yeah, that's a that's a great question. I think Noah used a a very important term that I like to use is that they're a road map. And they kind of gives a generalized guide on on what to do in different pathways that exist. If you open up many of the guidelines, you see a lot of branching points where you see if you in this situation, you can consider this. If you're in a different situation, you consider that.

9:32 it depends it's a little different when we look now at the former Chicago consensus, now known as the Yale consensus guidelines, and the NCCN guidelines. A lot of it is similar but there's a little bit of differences in there. And so, I think to just kind of use your best judgment in using these as a as a road map to approach patients with sometimes often difficult problems. But what I like to think is these are our guidelines and road maps, but before you treat the cancer, you have to first treat the patient. And you have to know the person you're dealing with and recommendations are are one thing, but can that person actually tolerate or should they get what what's actually recommended? And I think that's really where it comes in to be a a good clinician and be able to treat the patient and not just the disease. Mhm.

10:22 I agree. Yeah. And so you know, there are as you mentioned you alluded to, there are already a number of guidelines that include appendix cancer. Probably the most well known is the National Cancer Comprehensive Network or the NCCN as you talked about. And that's probably the most well known in the world. The next most well known and the earliest that appeared in the US would be what we're now calling the Peritoneal Surface Malignancy Consortium Guidelines or formerly known as the Chicago Guidelines and some informally known as the Yale Consensus Guidelines. And that was really driven a large by the efforts of Dr.

11:02 Turaga who was first at the University of Chicago and now is at Yale. And those are those are just fantastic. These were truly truly the first guidelines that came out specifically with guidelines for appendix cancer. The other group that is has been very much involved in this is the Peritoneal Surface Oncology International Group or PSOGI. And they have published guidelines for many years and probably the well most well known in peritoneal disease specific guidelines in Europe.

11:31 And also the American Society of Colon Rectal Surgeons actually have published guidelines on the management of appendiceal cancers. They started their first version came out in 2019 and they just recently updated them in 2025. And so Dr. Brown, can you again can you speak briefly about the different methods of how these guidelines are created? Yeah, and I I think Noah touched base on this before. It's it's to use the best data and the best evidence that you would have.

12:05 The NCCN goes through a pretty extensive process where NCCN designated centers then elect a representative from the institution who then for each individual disease site, whether it's appendix, it's colon gastric cancer, they have a representative who then goes to to meetings to discuss current literature updates, different standard of care that people are are now implementing, and then to really have committee meetings and to they're supposed to talk with the people at their institution who are truly disease site experts to get a consensus on what they should put in these guidelines. So that's how NCCN generally runs to do it. I know I've heard Dr. Turaga talk about the development of the Peritoneal Surface Malignancy Guidelines here in the United States and it really sounded like a truly Herculean effort to put these together where he had a used a big group of residents, medical students even, and then collaborated a lot with peritoneal experts across the United States and they went through different rounds of of testing, of asking questions, and and getting answers, and then going back to the data, and really doing what's called like a Delphi method, and going through and and looking through the best evidence in the literature to come up with standard guidelines for us to help use to treat patients. Yeah.

13:34 Yeah, and I think one of the really unique things about the the Peritoneal Surface Malignancy Consortium Guidelines or we'll call them the Yale Guidelines now, is that they also involved patients and patient advocates in that process. So I think that's something that is unique to that process. So I I know you guys are both familiar with both. Any thoughts or like different what what strikes you? Are there any major differences between the two guidelines NCCN versus the Yale Consensus Guidelines or are they pretty similar? What are your thoughts about that?

14:18 I I can I can at least start with this. I mean it they're they're pretty similar. There's actually a lot of overlap. There are a couple a couple areas where NCCN does a a much deeper dive into chemotherapy. Into systemic therapies and also for biomarker testing. So when we're talking about doing mutation testing like BRAF or KRAS if those are familiar or HER2. And NCCN is a is a little bit more comprehensive than the Yale Guidelines. These are not really even mentioned in Chicago because the Chicago Guidelines were were written well before a lot of the targeted drugs that we have now. And so they weren't even thought of as as important things to look at at that time. But that's one I'd say major difference is is not just talking about the surgery side, but really on the chemotherapy and biomarker side.

15:12 The other the other thing that's possibly a little bit different is that for for patients specifically with low grade appendiceal mucinous neoplasms or LAMNs that for localized disease actually surveillance of of localized disease is is an option for NCCN. It's a little bit different than than Yale and and Chicago where cytoreduction and HIPEC is is recommended across the board whether it's localized or sort of more diffuse acellular mucin.

15:46 Great. And and to to piggyback right off of that, I think one of the important differences is is if you look at the the authorship of who's heavily involved in in who made these guidelines, the NCCN guidelines are are very heavily weighted in medical oncology. Is that a a vast majority of the authors on those guidelines are medical oncologists? And so they really delve deep like like Dr. Cohen said into the into the medical treatment on the different chemotherapy regimens. I mean there's pages of them of different options you can use with targeted therapies. And then feel like the the Yale Consensus is is is surgeon led. So the one thing that I I really like and I refer to the patients in talking about them with their disease is especially if you look in in the metachronous disease. So people who've had their appendix out and then develop peritoneal disease at a at a later time, they really help stratify who's high risk. Who are these high risk people? When was your recurrence? What's your tumor markers showing? Where is the disease? What is the character of your primary tumor? Did you have lymph nodes or not? And so it really kind of helps break down the nitty-gritty of should you do this or should you not?

16:58 And I think that can be very helpful for for surgeons, but also for patients who are looking at it. Mhm. Yeah. I think the other thing about that I really like about the Yale Consensus Guidelines is then the comprehensive review that they do. They really did system they they identified two or three key questions about each disease and then they did a drill down really hard and did like a systematic review of the literature that was really well done. And so when you go and you read those Consensus Guidelines in addition to the road map that they provide there's also a really nice review of again a couple of specific questions related to that topic that they decided to go deeper in.

17:45 And they also the other thing that I like about those guidelines is that they include social determinants of health which I don't think is something that's in the NCCN guidelines. I will also add that you know, I think the NCCN guidelines are still a work in progress for appendix because before it was just lumped in with colon. And we all know that the appendix is not the colon, right? Like everybody knows that So Great. Well Sorry, I didn't mean to cut you off with that. Like just piggybacking off of that, if you pull up NCCN guidelines from other site for other disease sites, at the very end there's a a very long discussion. Generally the appendix right now it still says under development. It's still it's still a work in progress. It is, yeah, very much so. It's coming. And I agree with you like in looking at the authors on that, it is mostly very heavily medical oncology.

18:43 But as Dr. Brown said, the the idea or the concept is that there's somebody at these designated cancer institutes where there's a lead for that section and then they're supposed to talk to the content experts at their institution and get their input. So they may not show up on the author list, but hopefully that's where they're they're getting their their input from so that they're still using the collective wisdom of the of the community that takes care of these patients the most.

19:12 So Great. Dr. Dr. Cohen, I guess maybe just some logistical questions here. Can anybody access the NCCN guidelines? And if so, what what what guidance would you give to patients, their families, their primary care doctors about using them? Yeah, absolutely. So anybody can. The NCCN guidelines are available. It's nccn.org. You just have to make a profile, make like a username and and a password. So you do have to log in every time. And then each cancer for which there is a guideline, so not every cancer has a guideline, but but many many do and finally appendix does.

19:58 you can click on that and then you'll be able to see what the guide it's like PDF files that that show up. you know, I I think it's very helpful for patients to to certainly read. I mean not it's not written, you know, it's written for physicians, so it's it uses medical jargon. you know, but just for patients to understand sort of why a doctor they might be seeing is is giving a recommendation. Well, to go back to NCCN guidelines because they are so commonly cited and used in clinical practice by by most doctors. And again, most doctors don't see patients who have appendix cancer.

20:41 and so that's probably going to be a resource that if the physician that, you know, you might be seeing doesn't know that they exist it might be a good thing even for a patient to say, "Hey, can you look at the NCCN guidelines?" They may not even know that there's an appendix section now because it is so new. And and so that's very helpful. it's also helpful because possibly in the past and depending on where some patients seek care the idea of cytoreductive surgery, the idea of HIPEC is not even you know, in as part of the conversation because it's not it you know, it hadn't made it to a guideline, let's say. and here it sort of gives front and center, you know, in the guidelines there a very clear recommendation for when surgery should be considered and not just, you know, stay on chemotherapy and and and never see a surgeon. And so again, some doctors who may not see too many patients with appendix cancer in their career is very helpful for them as well as for the patients and their families to to review these NCCN guidelines to see actually what's in them. And so nccn.org, just create a username and password and you can log in and see the guidelines.

21:55 And it's free like you said and you just have to set up an account. this is what it looks like. You'd click on appendiceal neoplasms and cancer. It is a PDF document basically and you can just scroll down. You can see all the people that contributed to creating the guidelines. these are the representatives at the different institutions. it tells you like what version it is. This is version one 2026, so really kind of hot off the press. And then as we were talking about earlier, you'll see this is kind of this a quick snapshot to depending on where the person's starting coming into these diagrams. You find out so example of the lower part of the of the sheet here, confirmed appendiceal neoplasm or cancer appropriate for resection or an incidental finding already resected. It tells you what workup you should do, tumor markers, imaging, blood test, colonoscopy, talking about fertility if it's a young patient. And then you kind of just keep following this down staying in your in your lane. The pathology was reviewed depending on what type of tumor you have from a low grade appendiceal mucinous neoplasm to an adenocarcinoma, goblet cell cancer, undifferentiated whether it's localized to the appendix only, whether it's in the peritoneum, the peritoneal cavity, whether it's extraperitoneal. And then you just kind of keep following the these lanes down.

23:32 Lamin and Hamman appendiceal adenocarcinoma, goblet cell adenocarcinoma localized, the surgery that you should have or the chemotherapy that, you know, what you should go on. And they do recommend certain lines of chemotherapy. So you just kind of keep following these down and then eventually you will get to like some guidelines about the principles of the imaging, the principles of pathology and the molecular review, what we're should be looking for under the microscope.

24:07 they'll talk about the principles of surgery and intraperitoneal chemotherapy, the principles of palliative systemic therapy or chemotherapy. And it'll go through So it has a lot of information for pretty much anybody and everybody. And then at the very bottom or after all of this, there's usually again as Dr. Brown was saying a discussion that reviews the literature. here it gives you the references, but that discussion hasn't been completed yet. So this is the discussion is under development. So that's that will be coming. The Yale consensus guidelines look very similar. They're a little bit more complete.

24:53 but they but they do it's a similar pathway for that. So again, this is available to anybody to go and look, to share them with your primary care doctor, with your medical oncologist if that's who you're seeing, whoever gynecologist gynecologist, gynecologic oncologist. the that's that they're they're there for you. The Yale consensus guidelines are a little bit they're published in journals, but they're still available to the public.

25:25 So if you just Google them, you will you will find them. Dr. Brown, anything that you'd like to see added to the guidelines going forward? Well, besides the discussion that they >> >> I think I think I think the one thing is is we we now really know appendix cancer is not colon cancer. And that and we used to treat appendix as just another extension of the colon, but we're learning more and more that it it's biologically distinct. And I think the one I'm sorry, there's a fire alarm going off right now. Okay, I can hear it.

26:00 I think the the one thing is is if you look at the guidelines or if you look at especially NCCN, there's a very distinct point saying that these are all two A recommendations, meaning they're really not based off of the highest level evidence and data that we can. And I think that's something that we really need to to work on if we can to to focus to try and get higher level evidence for appendix cancer. And so that's and it's not because they're not using that evidence, it's because that evidence doesn't exist at that level.

26:35 Again, because it's such a rare disease and it's hard to do the gold standard randomized control trial and that sort of thing. So yeah, I agree. Yeah. But that and that's exactly, you know, the purpose of ACPMP is to, you know, try to help support that research to develop that data, to gather the collective wisdom of the patients and their families. You know, they have their patient registry where patients can go and put their own information in and and just kind of get everybody working on this together so that we can come up with that evidence that that you said we need so so desperately. So yeah, yeah. Dr. Dr. Cohen, what do you think? So patients and their families, should they use these guidelines to advocate for themselves and if so, how?

27:27 Oh, I think you're muted. Sorry. I'm unmuted now? You are. Yes. >> Okay, great. Me and technology. Okay. So yeah, I mean I I I absolutely think that that patients and their families should be using these to advocate for themselves. As I said before, you know, depending on where patients are seeking care, you know, some patients may be going to see physicians who are not very familiar with appendix cancer, may not know about the NCCN guidelines because they're brand new.

28:04 you know, the the issue I think with the Chicago and the Yale consensus guidelines is is people who are deep into the field of appendix neoplasms and peritoneal surface neoplasms know these and read these and they were published in journals that we read, right? But they're not they were not published widely in journals necessarily, although in in some journals that medical oncologist who have a broad practice or surgeons who have a broad practice may may be reading. And so they may not be aware of these and they're not promoted in the same way and given the same recognition as the NCCN. So that's why it's such a big step forward actually that the NCCN has these guidelines. It's truly amazing. So I I do think that patients and their family should be advocating for themselves by reading the guidelines, by showing them to their treating physicians, by asking the question of saying, "Okay, if this is me, you know, where am I on on on this algorithm, so to speak?"

29:02 Clearly none of this is cookie-cutter medicine. I mean this is why this is what Dr. Brown was saying. It's not like just go down the pathway and you you forget who the patient is in front of you. I mean it's it's all about the patient in front of you. but but to be able to at least have a discussion, a very informed discussion with with your doctor about, "Okay, this is where I stand. Now that we have these guidelines, what do you think we should be doing?" And if, you know, and and that may may hopefully improve patients' access to additional treatments and and can also help their physicians guiding their treatment if they may not be so familiar with appendix neoplasms.

29:40 Yeah. Dr. Brown, any anything else to add to that? No, I I think I think Noah said it really well. It's just it it's to kind of guide and frame your disease course and to get a basic understanding of of what can be done, what pathways exist with the understanding that you might not fit into any particular pathway. Mhm. Yeah. But I I I agree with you both and I think you absolutely have to be looking at the person in front of you, their exact situation, not just the guideline. But for the patients and their families who are, you know, just getting started, it is a it is a way of getting you hopefully to someone who has seen a lot of people in that situation and knows the guidelines, knows sort of like what the if there was a standard way of treating like what that would be, but also knows when the situation is not standard, right, how to how to pivot, what should what's what the other alternatives are, what makes the most sense, really be able to translate those guidelines into really valid treatment options. And so, you know, I know that's also another huge part of the ACPMP's mission is to get help people advocate for themselves to get to the experts, right, to get to the high-volume institutions that do HIPEC.

31:09 Those are the places that are going to have the medical oncologist and the pathologist and the radiologist who know the know most about appendix cancers and tumors, know how to treat the whole the whole spectrum of the of the disease and really help take care of of the patient. So, and this is I think this is a great I think this is a place if you are working with a general surgeon who you know, says, "Well, I I saw one of these when I was a resident." You know, let them know, advocate for yourself. this is really important and say, "Well, hey, have you looked at the NCCN guidelines about like what to do? Do I really need to have my right colon taken out? Or, you know, should I be seen at a at a high-volume peritoneal surface malignancy center?"

31:53 Right, I think this is a real opportunity for that to to happen. you guys, any thoughts like how did does this help us or hurt us in regards to insurance companies? What do you think? I've seen both. Yeah. To be honest, I I I've seen I've seen both, especially when before the appendix cancer guidelines came out in light of the PRODIGE 7 trial, which was most focused on colorectal patients and they compared people with cytoreduction alone, so only getting their tumor removed to tumor removal plus HIPEC, I've had some insurance companies in in light of that study deny HIPEC for colon cancer. Even though we use a different drug, it's a different regimen, that study is ongoing of a lot of what we do now use now in the United States. So, I think it's still a work in progress to see what will happen with appendix cancer.

32:49 I still advocate I still do HIPEC for colon cancer, I do it for appendix cancer. And so, I do also carefully document what I do. Like I will cite the peritoneal surface consortium guidelines in my note that what the insurance company would look at to say this is recommended by this Mhm. And I really haven't had a whole heart of a whole lot of a hard time with appendix cancer, it's been more with colon cancer. Yeah.

33:20 Yeah. Yeah, I I I think it's it's my experience has also been quite mixed. I think that the PRODIGE 7 trial for some insurance companies made it very challenging to do a HIPEC for patients with colon cancer specifically and having to get into a lot of discussions with with the insurance carriers about about coverage. And I think that it's helpful. I mean, just because things are in the NCCN guidelines does not mandate insurance coverage or like center for like CMS coverage for for things.

33:54 Usually only the highest level of data you know, so level one evidence, that's when we have a randomized control trial where half the patients get one treatment, half the patients get another treatment, we have a you know, a very clear answer from that. Insurance companies will will always essentially or almost always cover that. Anything that's sort of less than that, it's a lot of it's based on the carrier, I think, and it's not like just because it ends up in a guideline, it has to be covered.

34:23 most of the time it does get covered and that's also one of the interesting things specifically about NCCN guidelines is that they're very aware that the things they put in the guidelines are typically covered by insurance most of the time. And so, they are careful with what they put in because they know that you know, carriers have to usually cover it. They're they're so new. I I I'm not sure what the effect is right now from NCCN.

34:51 Yeah. Yeah. Well, I I I agree with you. I've had a similar experience particularly in in colon, but you know, I and I've had less trouble with getting HIPEC for appendix ever approved. but I would just say that, you know, anybody who's listening, if you do run into that situation, I think we're in a position now where these guidelines, especially with NCCN, will actually help. So, you know, if you run into trouble with your insurance company saying usually they say it's experimental. I think we're well beyond that now. I hope nobody's still running into that problem. if it's just not covered by your insurance company, that can be another another battle like Dr. Cohen was alluding to. but the other thing, too, is if you're in an area where there aren't high-volume specialists within your network, there's a a way to get around that if you need to be seen by a high-volume specialist through what's called a gap exception and you just need to ask your you know, whoever you want to see to to request that for you and hopefully you can then get to see the provider that you want to see that's a you know, a specialist in the area and I think these guidelines will also support that, right? Like that this is a this is a rare disease, it is complicated to manage sometimes and it really needs to be taken care of by somebody who is an expert and specialist in in this area. So, so something else another way to kind of leverage the the guidelines.

36:25 great. Dr. Cohen, are you are you good or do you have to go? >> >> in in about a minute I do have to go. I'm sorry. All right. Well, any any parting thoughts and then we'll probably go to some of the questions. for me, you know, we I I think Dr. Lambert you mentioned before that there was a patient advocate who was part of the the Yale guidelines. There's actually also patient advocate in the NCCN guidelines. So, for for patients and their families or, you know, ACPMP or or whomever else, you know, there are ways that patients and and advocacy groups can be involved in in shaping guidelines and at least having a a seat at the table.

37:13 Yeah, great. Yeah, I absolutely. and I and I encourage people to seek out those opportunities. I'm sure through ACPMP they could help people who want to get involved and partake in in being a part of these guidelines and see how the branch or even just seeing the process. it really is quite quite something. I know Deborah Shelton was involved with the Yale consensus consortium guideline the the process of developing those. So, it's an eye-opening experience, but yeah, great.

37:45 Well, let's let's So, we have some pre-submitted questions. thank you, Dr. Cohen. Good luck. >> >> Thank you. Thanks, everybody. but Dr. Brown and I will we'll kind of pick away at some of these questions and then we'll open it up to the live questions that may be coming in. so, Dr. Brown, we received some questions about like surveillance and follow-up. so, somebody was asking what is the best surveillance protocol for a low-grade mucinous neoplasm a T4A and also how many people diagnosed with a low-grade mucinous neoplasm a T4A after laparoscopic appendix removal have a recurrence of the appendix cancer elsewhere in their body? Your your thoughts on that?

38:35 So, there are there are guidelines to follow. Now, in the NCCN they they lay out some guidelines. They talk about scans about every 6 months for 2 years and then yearly for a couple years afterwards and then scans every 2 years up to 10 years because even though it was removed, sometimes people can have this show up and it can show up again much later. there's some guidelines if you look at that say that if you don't have free mucin throughout the belly, you don't have any signs of extraperitoneal or spread throughout the abdominal cavity, you get a complete resection, you could actually forego surveillance. So, there it's it's really a a mixed bag on these. Dr. Lambert, I'd like to hear your thoughts on that, too.

39:17 Yeah. Yeah. so, you know, what I again like you know, that really depends on the histology. So, it obviously in this case it's a low-grade mucinous neoplasm. in that case and it's a PT4, so there's a perforation somewhere. The way I approach these is I when I'm doing the laparoscopy or if I get the report, I look to see if there's any mucin anywhere else in the in the abdomen, if there's any development of that yet. If there was some mucin reported time of surgery and the surgeon said they got it all out, but it was confined to the right lower quadrant and I just survey those patients. I don't recommend any additional surgery at that time and and just keep a close eye on them. If there's mucin that has gotten out of the right lower part of the abdomen, then I start talking about cytoreduction and HIPEC and suggest that at some point the person is probably going to need it, but depending on the actual circumstances, if it's just a very low volume, maybe a little bit up around the liver or something in the pelvis, you know, it and we that's something that you can watch, right? It's this tends to be a very indolent process.

40:35 If you're keeping a close eye on it, what I always tell people is you're not going to miss an opportunity to treat somebody for cure in that situation with that disease if you're surveilling for a while and as soon as you see that it's getting starting to change, then you can talk about going ahead with surgery at that time. So that's usually how I approach it. My surveillance is usually 6 months for the every 6 months for the first 2 years along with tumor markers, three tumor markers, CEA, CA 19-9 and CA 125 and then yearly after that out to 5 years and then every other year after that out to 10 years.

41:15 And at that point we're not really sure what to do. Like I've asked other people, I'm sure you've thought about this too, Dr. Brown, that you know, like at 10 years at the likelihood of it coming back is extremely low. It's not zero, but it's low enough that I think it's safe to to stop surveilling every you know, every other year. What are your thoughts on how do you your timing of of surveillance? I I follow follow basically the same thing that you do. I think that's a pretty a pretty good pathway. What do you what are your thoughts on CT versus MRI?

41:47 good great question. so >> >> so I think I think both are good studies and each one has its plusses and minuses, right? It's pros and cons. I think the obvious benefit of MRI is the lack of radiation, right? So if you have a young person who's going to be followed for a long period of time, a lot of scans, you know, and and is eager to avoid as much radiation as possible, I think MRI is a very good option. The caveat to that is you need a MRI radiologist, like a dedicated abdominal MRI radiologist who's interested in reading these these scans and is willing to do the specific protocol that you need, right?

42:35 With the rectal contrast, the oral contrast, timing it just right so that you're getting the bowel pacified and all that sort of stuff. And then the MRI takes time, right? So somebody has to be there for a while. And then the challenge, I don't know about for you, but I am not great at reading MRIs, right? Like I I do okay, but not for subtle findings. It's that's it really takes an extra lot of training to to read an MRI well, but but as a surgeon, you know, we get really good at reading CAT scans. And so for a surge you know, putting on the surgeon hat it's a lot I find it a lot easier to read a CAT scan. It gives me all the information that I need to make a decision about whether to go to the operating room or not. It's faster for the person that's getting it and and the and the radiologists are also very good at reading CAT scans too.

43:26 Like you don't need a specific dedicated MRI person. So but the downside is the is the radiation. So yeah. Yeah. There's some interesting data presented at the peritoneal surface oncology international meeting about MRI and then what they were finding is MRI properly timed MRIs can be more sensitive. So they can find disease earlier. So what I typically do if it's I feel like if it's a higher risk patient, if I if they're younger and I want to avoid the radiation, try and get that MRI for them. Then in going to surgical planning, I'm much more comfortable looking at CTs and I think it really gives you good anatomic definition if you get thinner cuts. So I then I would advocate for a CT scan.

44:09 Yeah, good. let me see. There looks like there's some question. This is there's somebody posted a a very interesting question about and I know you've come across this too, you know, in women who you know, present with a pelvic mass, a bilateral ovarian masses and and obviously the you know, the first thought is this is a GYN malignancy or an ovarian cancer cuz that is a lot more common than appendix cancer. But then they get taken to the operating room and and obviously and then people find out that it's it's actually an appendix cancer.

44:45 So the the the person that posted the question is asking you know, once we get the diagnosis, the real diagnosis of an appendix cancer versus an ovarian cancer, does that then get counted as an appendix cancer in terms of the statistics and are we are we is appendix cancer way more common than we think it is, but we've just been misdiagnosing it all along. What are your what are your thoughts on that? I I I I believe recently it it should all be classified as appendix cancer because it's it's really the the histological finding that that's being classified.

45:23 we see this all the time. It's a very common thing across the United States because they somebody sees a pelvic mass or you have ovaries that have tumor or mucin in them and you get sent to a GYN doctor. They think when they you're footsteps, they think horses and not zebras. So they think common things are common and that's kind of what they're going into this for. We get called to the operating room quite a bit to go in there when when this situation occurs and I I it's kind of just to tell them get tissue, understand what you're dealing with and stop cuz you want to be able to to treat the disease appropriate from there and and not do something that could potentially steer you down the wrong >> >> So I believe it's it's we're we're not misrepresenting the the incidence of appendix cancer with this situation.

46:18 But what are your what are your thoughts, Yeah, I mean I think I I think this is an interesting question. There's a lot of different aspects to it, right? Like so I I do I do think appendix cancers are still category they're they're still considered a rare cancer. But there is no question that we are there's more than I think what is is being reported, right? That the I think the statistics are behind what the truth is and we you know, we had the a report that came out last year showing an increasing incidence in younger people.

46:49 But there's definitely literature to show that the true incidence of appendix cancers and tumors is increasing and I do think that once somebody is correctly diagnosed and that gets counted in the appendix bucket like you were saying, right? But you know, the other other side of this question I think is is really important is you know, helping educate people to recognize an ovarian an appendix cancer instead of an ovarian cancer, right? And there you know, there are some things that I think are kind of low hanging fruit, if you will, that can help. So in in most women that get ovarian cancer, it's usually just one ovary that's enlarged when they have ovarian cancer. That's that's one thing.

47:40 They often do present with fluid in the abdomen or ascites, but that can look very different than mucin on a CT scan. So you got to get a sense of that. The appendix like if there's preoperative imaging, the appendix should look be looked at very carefully cuz you can often pick up that the appendix doesn't look normal before you go in to do an ovarian surgery or cancer surgery. The other thing is tumor markers. And if the tumor markers suggest that this may be coming from the intestine or the appendix, the tumor marker that's going to show that the most is the CEA.

48:18 The CA 125 is what we classically associate with ovarian cancer and it is a very good marker for that, but it can also be elevated in any other cancer that's growing in the abdominal cavity. But when you have a combination of a high CA 125 and a high CEA and or CA 19-9, now you need to be thinking could this be coming from some place other than the ovary? And I I know you've had this experience before where you meet a patient who's been taken to the OR, had a hysterectomy, oophorectomy, omentectomy, like all these the surgery even though the CEA was elevated way elevated before the surgery only to find out at the time of surgery that the appendix was abnormal.

49:06 and and that's and that's the other part of the education that I would love to to be able to get out there is that if you get into the surgery and you notice that the appendix is abnormal, to not do all the other things that you would do for ovarian cancer, right? Like stop and this is what we try to teach as you know, teach our residents, teach other surgeons is just if you if it looks like the appendix is abnormal, take the appendix out if it's easy or do what you have to do to get the right diagnosis and get the person to the place that they need to be to get the best care right from the start.

49:43 That you know that we I don't think we can say that enough. >> >> And I know we say it all the time in our webinars and with the ACPMP Research Foundation and everything that they do. So for those of you who are listening, we're trying. We're trying to get the word out and we hope that you know through like ACPMP will will advocate so that we can avoid this in you know in in as many people as possible so they just get the diagnosis right up front, get to the best care as quickly as possible. So Let's see, couple more questions coming in.

50:17 Let's see. So here's a question, would you recommend cytoreduction and HIPEC surgery if appendix cancer has gone into the liver flow liver or lymph nodes outside the peritoneal cavity? What are your thoughts about like how do you think about that? I think one what what is the the disease biology that you're really treating with? Like what does the tumor look like under the microscope? Is it presenting at the same time? Are they presenting at different times? What's the how long has the disease course been going on? Have they have you gotten chemotherapy? Have you not gotten chemotherapy and what was your response to that? So I think all those factors going to play to to making that some that sort of a decision. And kind of my thoughts, how I was trained, the people that I grew up with is you can do it but be careful.

51:14 And so it's all about selecting the right person that could benefit from it. Is what what I see as a as a failure on on my end is to take someone through a a very large operation, get a scan couple months later and the tumor is somewhere else. Yeah. So I think you really need to to prove the biology of the tumor that it's behaving, it's responding to chemo and that you can get a complete resection. Yeah.

51:45 >> be very hesitant to do a a very major liver operation that on its own is is risky and dangerous and combine that with a a bunch of other operations to clear tumor out. So I think a lot goes into play. Have I done it? Yes. Has have people done well afterwards? Yes, but it's really timing it out and being very very thoughtful about it. Very selective, exactly. You know, I think one thing you know that we hear from people is I mean I I think anybody who's got cancer, right? I mean the first thing you want is you want it removed, right?

52:20 Like that seems to be the most obvious thing, just get it out. This is going to be the most helpful. But like you said, you know, as much as we love to operate and that's you know what we want to do more than anything, we also don't want to put somebody through a huge operation that ultimately is not going to be helpful. And so I know it can seem like we're you know we're we're delaying or stalling or whatever, but when we're recommending that somebody get systemic therapy chemotherapy before a surgery, it's exactly what Dr.

52:54 Brown was was alluding to is that we want to make sure that when we do this big surgery that it's going to be helpful. And you know as as probably everybody in the on this call knows, the cytoreduction and HIPEC just treats the abdominal cavity. So if there's cancer outside of the abdominal cavity or inside the liver, we really need to make sure that we have treatment that's going to control that disease and hopefully get us to a point where we can remove it surgically as well. But this is so this is where it really comes down to why you need to be at a high volume center with surgeons who have done a lot of this and are thoughtful and they have partners that can help each other think about these things and look at it from all these different perspectives and you have medical oncologists who are familiar with disease and radiologists who can read the the films really well and pathologists who can really nail the pathology. I mean there's a number of questions in here about like HAM and LAM and and and we don't have even gotten into the pathology of appendix cancers and tumors, but that's a whole another you know kettle of fish and and very challenging. So you really need you want experts on on every every front when dealing with these these kinds of tumors. So and and so speaking of histology, right?

54:08 So there's a a relatively new entity called HAM and and I see that coming up in the in the list here. Dr. Brown, your your thoughts on where HAM and fits in into the schema of things. It's again, it's a relatively new diagnosis or histology I should say and it's been challenging. What are what are your thoughts? Yeah, I think it it's extraordinarily challenging for the pathologists. The persons that's actually looking at the slides. So to call something a a true cancer or an adenocarcinoma, what they need to see is invasion. They need to see those tumor cells invading through certain invading through kind of like the the sub layers of the walls of the organ and or the appendix in this case. When we talk about a a HAM, HAM's very similar to what I think of as LAM. It's not invading through the layers, it's more pushing the layers.

55:07 And it can be very very challenging for the the pathologist to differentiate between a HAM or a high grade tumor and an adenocarcinoma. And to really call it an adenocarcinoma for say HAM, they really need to determine is it pushing or is it invading? And the difference really between a HAM and a LAM or low grade and high grade is really what it looks like under the microscope. Does it look more well behaving, more normal or does it more look more abnormal and and more high grade. So I I think that's a it's a very challenging entity. There there is a big discussion about that at the SOGI meeting about HAM and they're talking about how challenging it is is it and and there was a big talk on should we call HAMs actually just cancer? Are they actually just adenocarcinoma?

56:03 Are we are we really capturing the full full picture of what's going on there? But I think it's a it's a it's a big challenge on the pathologist's part to help really do that. And I think that's where it goes into really having a pathologist you know and trust who sees more than one of these a year to be able to make that determination. And and I would you know strongly encourage somebody if if you're getting a diagnosis at your institution and you're and it's a HAM and not a LAM and your surgeon's kind of like I don't think it's a if there's any sort of discussion, request a second opinion on the pathology. Your institution should be able to send your pathology your slides to an expert in appendiceal pathology if you don't have one at your institution and get that read. That it can have a huge impact you know, because if you look at the literature like Dr. Brown said, these HAMs are really in this gray zone.

57:05 They're they technically don't reach the definition of an a cancer, a true invasive adenocarcinoma, but they definitely are more aggressive. That's the word we use than LAM. So they're more likely to come back and if they come back, they're they're less likely to be treated for cure as well as a LAM. So it really makes a difference in how you're going to approach treating somebody afterwards if it's LAM versus HAM and the prognosis and what to expect. So it's worth getting a second opinion if your if you're at an institution where your pathologist is not like a high volume expert in appendiceal cancer.

57:44 The there's another question here on on genetic connections in appendiceal cancer. What are your thoughts on that, Dr. Brown? I think we have a lot of work to do. I would agree with that. I would agree with that. And I think that that's kind of the the biggest takeaway that I get from from doing this. We have a lot of work to do. You you mentioned that study that came out very recently that looks at the uptick of appendix cancer especially in younger generations. So younger generations are seeing a higher incidence of appendix cancer.

58:20 And I think the one thing is is we really don't know why that's happening. Mhm. Is it environmental factors? Is it genetic factors? We we're really not sure. Is it a combination of both? I'm often asked by people should I get my appendix taken out? You know, should I just prophylactically get an appendectomy? We really don't have evidence or or data to do that. There's really no such thing as a as a minor operation. So to go and and prophylactically take out the appendix so this doesn't happen, we don't really have that that data yet to do that.

58:54 And so I think appendix cancer still is rare. It's still rare tumor and and I wouldn't recommend people just getting their appendix taken out. Yeah. Yeah. Yeah, a lot of people ask me that. Why don't we just take out people's appendixes, right? And you know, we'd have to take out a lot of appendixes to avoid one one appendiceal cancer which obviously would be worth it but for that person. But you know, the at the end of the day, insurance companies aren't going to approve just having your appendix taken out to avoid cancer that is considered very rare.

59:30 But to but for the research part, so there actually is a study at Vanderbilt that is looking for people who get diagnosed with appendix cancer to join and to just submit their data and there's you know, answer questions on a survey. It's the GAP study. Dr. Hollowaty is the primary investigator on it. I'm sure you can find information on it through ACPMP. but you know, it feel free to you can Google it, find out more information and basically it's a patients putting in their their data into the to the survey and they're looking at all these different connections to try to figure out if there's something like Dr. Brown said in the environment and our diets genetically that's driving appendiceal cancer. I I personally have only had two patients that I know of who had like a first-degree relative who also had appendiceal cancer. which is which is actually, you know, kind of a lot for a rare cancer, but it's it's still not enough for us to say you know, if you have appendix cancer, then your children should have their appendix taken out. their risk of getting appendix cancer is is about the same as what yours was and still quite very low obviously.

60:52 So, let's see. And >> There's there's there's a question here I'd like to get your Yeah. have you speak about about the role of diagnostic laparoscopy. Oh, great. I think that's a a really interesting question and you want to you want to kind of address that like why why would somebody recommend a diagnostic laparoscopy? Absolutely, yeah. So, it kind of comes back to what we were talking about before wanting to avoid a big surgery in in in someone if we can. And so, we use it for a couple of in a couple of ways particularly I or I should I use it for in a couple of ways particularly with people who have the high-grade tumors. so one of the things that can be very challenging about those tumors that specifically like the signet ring cell or a poorly differentiated adenocarcinoma is that they tend to grow like a coat of paint on the sides of the abdominal cavity or on the bowel.

61:48 So, they're not making these discrete tumor nodules that show up really nicely on a CT scan or MRI and you actually can't see them on imaging at all. And so, the CT scan or the MRI will most often really underestimate the amount of cancer that's present in the abdominal cavity. So, by doing a diagnostic laparoscopy, we can put a camera in look around really assess the entire abdominal cavity specifically though, the small intestine and the sheet of fat that contains its blood supply called the mesentery. Because if those are heavily involved with cancer, then it's unlikely that a surgeon is going to be able to get a complete enough tumor removal where the heated chemotherapy would be helpful. So, by doing this you've now avoided making a big incision, you know, on the abdomen to get in and then find out this is this is unfortunate, but we're not going to be able to do what we hope to do today.

62:48 you know, you start out the the nice thing about the laparoscopy is you can do it with just a couple of tiny incisions. a person doesn't have to stop their chemotherapy to get it. You go home the same day. It takes about an hour. You can get pictures so that the patient and their families can see what's going on in the abdominal cavity and then they have a better sense of what the cancer looks like and what we're talking about when we talk to them about this and we can figure out if it's it makes sense to proceed with cytoreduction and HIPEC at that time or if somebody should continue with intravenous chemotherapy and or if that chemotherapy should be changed, right?

63:28 Because we can tell if the tumor's responding or not especially when we can't see it very well on on scans. So, yeah. How about you? Yeah, I I use it the same way. So, the one thing that I have is is can we do the operation that that you would need? And I don't like people to be surprised is that I like to be able to have an informed discussion with somebody of of this is the extent of what's going to have to happen in order for you to have an an optimal cancer surgery. So, I think it it allows me to assess can it be done, should it be done and then have a person know what needs to be done to them and not have a more of a surprise when they wake up because like you said a lot of these tumors can form sheets instead of discrete balls and so you your scans can underestimate it.

64:18 I also think it's helpful if there's a question of a diagnosis. So, you're getting your surveillance done your tumor markers are going up, you're getting the scans and nothing is seen. I think that's a a good role of a diagnostic laparoscopy is to to help try and make a diagnosis. Is something actually there that we just can't see? Mhm. there's a couple questions on signet ring cells. Yeah. Yeah, I I see that. It seems to be a thread. Yeah, yeah. I mean, I you know, signet ring cells are are tough as you know for the one for the reason that I just mentioned before, you know, that they tend to be hard to see on imaging.

65:00 they grow like a plaque. they are considered a more aggressive type of cancer. They are more likely to spread to the lymph nodes you know, that that guard the appendix. I think on the on the the if there's a if there is any silver lining for signet ring cell, they tend to respond to chemotherapy at least initially, right? So, the way chemotherapy works in general is rapidly dividing cells take up the chemotherapy into their DNA and it's like throwing a monkey wrench into the works there. And so, because the signet ring cells tend to divide more rapidly, they are more responsive to the intravenous chemotherapy than say a lamin or a or a low-grade appendix adenocarcinoma where the cells are just kind of poking along dividing very slowly. So, there's less opportunity for them to take up the chemotherapy into their DNA.

65:59 so so and then you know, a lot of there are a lot of people who you know, probably don't think that there's a role for cytoreduction and HIPEC with signet ring cell but that has not been my experience or my practice. I will but I but I will approach this with recommending that we start with the intravenous chemotherapy first for the reasons that Dr. Brown talked about testing the biology of the tumor, making sure it's responding to chemotherapy.

66:31 And if it is, the benefits of that are one, we know that it responds to chemotherapy. Two, it's going to do some of the cytoreduction for us so that when we get in there to do the surgery, we have less surgery to do and it's likely to be more successful. so that you know, those are the reasons for for starting somebody on intravenous chemotherapy first and then assessing for the if if you can get a complete tumor removal and do the HIPEC, I will definitely offer that. And now we're starting to have another option for in a situation where if we're not quite able to do and not get the tumor out completely to do the HIPEC, we can offer something called PIPAC and I'm going to I'm going to let Dr. Brown talk about that a little bit. So, Dr. Brown, where does PIPAC fit into your your treatment recommendations? Yeah, so so PIPAC for people don't know is is laparoscopic administration of chemotherapy as an aerosol. So, it typically in the in the majority of cases, HIPEC is delivered at the the time of tumor removal. So, people get a cytoreductive surgery with or without the HIPEC. So, the liquid chemo.

67:45 PIPAC has been being done in in Europe for about the last 10 to 15 years has has really come to the United States within the last five years or so and it's an alternative method to deliver chemotherapy in the abdomen. Really good benefits from PIPAC is people can stay on their systemic chemotherapy. They can keep getting IV chemo and you can drop one of the IV chemo rounds and and instead of that you can do a PIPAC operation.

68:14 PIPAC I I really see it fitting into people that are either anatomically or biologically unresectable. Meaning, if you can't take all the tumor out, if you're progressing on chemotherapy if you've been through multiple lines of of trying to use this really as a as a salvage operation. We still have a a ways to go to to see where this could or would fit in our in our guidelines and whichever ones you're talking about NCCN, Yale to to really find out where this goes. So, it's still an ongoing project and and something that peritoneal surface surgeons across the the world are really working on is to try and figure out where this fits. But but right now what I what I see this is is a potential alternative to try and help salvage a situation. And and with that PIPAC does not replace systemic chemotherapy because the the PIPAC really only treats that disease in the peritoneum.

69:15 It doesn't treat disease elsewhere. So, if there's disease in the liver, the lungs, PIPAC will will not treat that. It's really only localized disease. So, I think there's there's still some work to go, but I I see it as kind of a an alternative method to deliver chemotherapy into the abdomen. Mhm. Yeah. All right. Yeah, exactly. And you know, as Dr. Brown mentioned, it's it's something that's evolving. I think there's a lot of data now that it is safe. We actually started doing it here at NYU just recently thanks to Dr.

69:48 Brown's efforts to to bring it here and we are offering it in very selected situations like like he said. And we're hoping to join clinical trial that's at hopefully will be opening up soon at the City of Hope to be able to offer that in the in the New York area. To have that as another option, but we are we are offering it now and again in very selected situations. We want to be very thoughtful about it as well. So, couple of questions are coming up about like repeat HIPEC and cytoreduction and and additional surgeries. What are your what are your thoughts on that, Dr.

70:32 Brown? I think number one is what what disease are you treating? Is it a a lamin sort of a situation? It's appendix cancer situation. For the lamins, I've I've done a bunch of repeat HIPECs on them. I think it's just when are you going to pull the trigger to to do it and to be thoughtful about it. It's safe to do repeat HIPECs on people. As a surgeon, it can be a little bit more challenging the more scar tissue you get, the more adhesions. It can take a little bit longer of a time. So, when it when are you going to go in to to do that, I think is the big question.

71:11 For appendix cancer, so the invasive cancers, I think it's again being thoughtful about doing it. What was the time frame between first surgery, second surgery, is there disease elsewhere? Have you gotten chemotherapy? If so, what has been your response to chemotherapy? So, I think what we know there's studies looking at this is that it it's safe to do, it can be effective to do and to really be thoughtful about doing it. Yeah. I think I you know, I hope like you sort of as as we're kind of thinking out loud like how we would think you know, how we would think about these situations in in real time, right? Is that it's it's you have to look at the whole picture, right? Like just like you said. What starting with what type of histology is the tumor? What treatments has the person had up till this point? What how did they respond to chemo? How did the cancer respond to chemotherapy if they got chemotherapy?

72:12 What does the surgery look like that that you would have to do to get a complete cytoreduction? you know, it's just taking it it's all it's the whole package and it takes a lot of thought and and personalization, right? There's just no we have guidelines, but there's no sort of textbook way to to treat this like there is every single person is unique and every situation is unique still at this point. So, so again, just really advocating for people to get to you know, to the place where they need to be to get the care that they that they need.

72:52 Yeah. So, let's see what else I think we still have a few more minutes. Go ahead. Yeah. There's a few questions about appendicitis. Yeah, yeah, yeah. I thought that was a great question, too. Those are interesting questions. What are your what are your thoughts? Antibiotics, surgical removal? >> Yeah, yeah. So, >> >> you know, obviously I think there I think there's definitely data to show that older people and by older I mean over 40. People over 40 who present with what we call complex appendicitis, meaning there's the the appendix is already ruptured or there's a lot of swelling and inflammation around it in the area around it and where it would be very challenging to try to get it out with surgery at that moment.

73:38 There you know, there's there's data that the typical practice is to put somebody on antibiotics, let the appendix cool down and for a while there was a move to actually not remove the appendix at all. And the reason for that was because the risk of getting recurrent appendicitis was only about 16%. And so, rather than going back on everybody and taking out their appendix to avoid you know, appendicitis recurrent appendicitis in 16 out of 100 out of 100 people when you could just take out the appendix if they had appendicitis again.

74:16 So, there was a a move towards that. But more recently, there's been a number of studies that have really in my opinion demonstrated that people over 40 who have complex appendicitis have a significant risk of having a tumor in their appendix that's related to what's going on. And they should have their appendix removed whether it's at that moment or as an interval appendectomy, it should be removed. As a matter of fact, there was a randomized controlled trial looking at following people with complex appendicitis with MRIs and there was such a high incidence of tumors found on the MRI that they actually ended the study early because I mean it was that significant and the recommendation was made to just do an interval appendectomy.

75:08 So, so that and so that's the way I think about it and then again, this has been confirmed in in a number of trials, small trials retrospective, but also larger trials as well, prospective trials. So, I I to that that's those are my thoughts on that. And yours? I think the the one thing too is part of the thought process was also like oh, people can get a colonoscopy. Mhm. You can get a colonoscopy to take a look. But the one thing is a colonoscopy doesn't look inside the appendix. It sees the opening or the orifice of where the appendix connects to the colon, but you actually don't look inside. So, you really don't know what's going on.

75:50 And so, I'm I'm a big advocate if there's suspicion, you should do an interval appendectomy and take it out. Yeah. I yeah, I agree. Yeah. let's see. Did I ask this already or Let's see. I guess there's a number of questions also related to goblet cell cancer, right? So, what are your what are your kind of general thoughts on that? Where does it fall in the spectrum of these cancers? Do you treat it like as a higher grade tumor, a lower grade tumor? Do you do cytoreduction and HIPEC for them? What are your thoughts on that?

76:45 Again, it depends. So, I think the the the thing is I think of a goblet cell cancer is almost like a collision between two separate type of tumors. It's kind of a mix of an adenocarcinoma that you can get from the appendix and a a neuroendocrine tumor also known as like a carcinoid tumor. So, it's it can be a similar to a mix of those. And so, there are classification systems that we use. The older one is the Tang classification and it's Tang A, B, or C. A being a more well-differentiated, so a better acting tumor. A Tang C is a more poorly differentiated tumor. And a Tang B where it kind of hangs out in the middle. And so, when I think of a Tang A, it's more of the the neuroendocrine type tumor, more indolent, more slow-growing.

77:34 And and a Tang C is a more aggressive tumor. They've kind of started reclassify this. There's also the WHO or the WHO classification of this, the World Health Organization where it's one, two, and three. And it kind of follows the same pattern where A is one, B is two, C is three. And how I look at it is people with more Tang A or WHO one, those people I'm I'm a little bit more aggressive to take those people to the operating room and do cytoreductive surgery with or without with with HIPEC if they have peritoneal disease.

78:10 Now, I also do a I do do a right colon on these people as well. Where a Tang C, I'm I'm a little more cautious. Mhm. Is that these these tumors can spread elsewhere outside the peritoneum. And so, I generally advocate especially for the Tang C is those patients start with chemo. Mhm. because I think the the one thing to keep in mind is the one of the number one reasons why people don't respond to chemotherapy is they don't get it.

78:38 Is that it never actually goes into your veins. Yeah. So, you're going to go through a potentially could be a a very major operation with two months of recovery, that's going to delay the the start of your chemotherapy. So, it's really again being being thoughtful of the actual histology and the disease that you're you're dealing with. Mhm. Yeah. Yeah, I agree. And I I I manage them very similar to you. I kind of I talk about them as a rare subset of a rare cancer.

79:12 And I see them kind of somewhere in the middle between like a moderately differentiated adenocarcinoma and a poorly differentiated adenocarcinoma. And like you mentioned, it's almost like there's two different tumor types, the neuroendocrine and then the adenocarcinoma, and the treatment is really dictated by the histology of the adenocarcinoma. So, like you, I usually do recommend a right hemicolectomy if especially if the adenocarcinoma part is moderately differentiated or higher, grade two or higher, cuz the incidence of lymph nodes metastases is is higher with that. And then again, like you, just thoughtfully use cytoreduction and HIPEC as part of a multimodal treatment plan including systemic chemotherapy for for most people as well. So, yeah, great.

80:05 Let's see. So, you know, I know in other times people have asked about Bromac, and so we proud to say that we we actually had an opportunity to to use some Bromac here, and again, this is something that we're doing in a very very very selected way, but people have been asking about it for a long time. Dr. Brown, you want to share your thoughts on on Bromac and its role in managing pseudomyxoma.

80:44 Yeah, so Bromac is it's really a compound of two different drugs, bromelain, which is well known for being derived from a pineapple, so pineapple stems, and then acetylcysteine. Acetylcysteine is a is a drug that we've been using for a long time. A lot of times as a mucolytic in the lungs to break up a lot of times in kids with cystic fibrosis, they get these big mucin plugs in the lungs that can help break those up. So, it's a compound of these two different drugs to act as a as a mucolytic cuz one of the issues especially with PMP or pseudomyxoma peritonei where you have this really thick mucin in the abdomen is that sometimes it's not resectable surgically, and you can't take it out.

81:29 So, this is a a way to help treat those tumors, and and the way you do it is you you place a catheter or the interventional radiologists are able to put it a tube into that mucin, and then you can inject this drug, and the thought is that this will help almost dissolve and make a very thick liquid into something that can be pulled out of a tube. And so, I think it's a it's a palliative option that's out there. We're still looking to bring this to clinical trial in the United States, so it's done under compassionate use. So, you have to go through the FDA or we we go through the FDA to get specific and special permission to to do it, but I think it it has a role, and I'm I'm really hoping and trying to advocate that we can get get the company the kind of the support they need to to really help bring this to clinical trial in the United States cuz I I think a lot of patients could benefit from it.

82:26 Absolutely. Yeah, exactly. I'm hopefully we're hoping we can get there, too. I know we've been hearing about it for a number of years, and and a lot of people have have asked about it, and I think it will bring hope to a lot of a lot of people. So, I so, I just want to acknowledge that, you know, there are a lot of questions in the chat that are kind of very specific to individual circumstances, and I I hope you can appreciate from just the conversation that that Dr.

82:55 Brown and I have been having that it can be very difficult to answer specific questions to an individual circumstance without having the time to look over the imaging and and review the history and and and more importantly have a chance to talk to you directly and get you know, hear the story from you and get a sense of of where you where you are on the on this journey with with appendix cancer or pseudomyxoma. So, we apologize if it seems like we're kind of avoiding answering those very specific questions.

83:26 We would be happy to to see anybody in consultation. We are you know, we are in in New York, we're in Long Island. Dr. Brown also sees patients in Manhattan, so we are accessible. We can do virtual visits if somebody is is in a state where where we have where we're licensed to to see you virtually, but so please feel free to reach out to us. We would we would be happy to definitely see anybody in consultation to give you to give you an opinion, but and again, I apologize that we that we can't get more specific in this forum, you know, without having a chance to really meet you and and review all of the the data and the images and and go over everything with you.

84:08 The the last question here is why isn't Bromac used in in the US? Do you want to answer that? Dr. Brown, we're trying. We're trying. We're trying. It's currently not FDA approved, and I think one of the issues behind that is how the the drug is is formulated and and made, and it's it's a big effort by pharmacy cuz they have to compound and and mix the two drugs separately and then combine it together, and what the FDA really wants is it to be in almost one jar, and you just pull it out. And so, there I know they're actively working on that, and so I think once that's done, they can get it through the FDA to to bring it to clinical trial.

84:49 This is where support groups are really helpful, and then people advocating that there's there's folks around the country who could really benefit from this, and to to use great organizations such as this to really to push and advocate to to help get this through so it can get done. Yeah. Great. Well, I think that I I think this is I hope this has been helpful. I know that Dr. Brown and I have have enjoyed this.

85:21 We could talk about this all night. >> >> I could talk about this for hours. And we'd love we wish we could have answered everybody's questions like I said or have a chance to meet all of you in person and and and offer you our our opinions and and thoughts, and and obviously our hope that that everybody gets the absolute best care that they that they need and deserve, and you know, keep working we'll keep working with the ACPMP Research Foundation to to just, you know, get the word out there. Educate somebody put in the chat about Dr. Radio as a platform to spread the word. You know, again, ACPMP is doing that through radio programs programs like this, the symposium that they put on. So, we keep supporting them, and we keep supporting you, and please, you know, support each other and and support ACPMP to to to get a help us get a handle on this on this disease.

86:16 Thank you, Dr. Lambert. Well well said, and thank you, Dr. Brown, Dr. Lambert, and Dr. Cohen even though he had to leave early. This was so informative. I think I was amazing that you got to get to so many questions about this. And thank you everyone who attended tonight. I think everyone pretty stayed throughout the whole webinar. Fantastic. And yes, please stay up today on acpmp.org for future webinars, and if you have any questions, feel free to reach out. Thank you, guys so much. You're welcome. Thank you. And thank you for having us. We really appreciate it. Welcome. Have a great night, everyone. Good night.