Appendiceal Masses - Edited

Welcome, BTK listeners. My name is Dan Sheese, and I am one of the Surgical Education Fellows. I'm excited to have Scott Steele join me, along with our guest, Dr. Michael Valente, to discuss the somewhat challenging topic of appendiceal masses. Dr. Michael Valente is the program director for colon and rectal surgery at the Cleveland Clinic.

He also leads the stage four metastatic colorectal cancer program and is a specialist in terms of how we deal with peritoneal carcinomatosis. So Dr. Valente, welcome to Behind the Knife. Thank you. Happy to be here. So super excited to have you here. And, you know, Mike, I just wanted to start off kind of very high level overview and talk a little bit about appendiceal masses, and maybe a little bit about the terminology, you know, throughout the time that I've been in practice, I've seen so many different changes in terms of what the terminology, you know, what's a, what's an appendix is.

Adenocarcinoma is pretty straightforward, but you know, a lamin versus, you know, you know, mucinous

neoplasm all over. Can you give us a little bit of an overview in terms of the terminology and then kind of how you think about things with that? Sure, absolutely. And you're absolutely correct that the terminology is very confusing for, you know, not just the patients who, who have to hear about these things, but multiple different surgeons and physicians and pathologists all have different years that they trained.

Some people you know, there's different terminology that comes out kind of, often. And that this is a good time to talk about, you know, the NCCN, which, which is one of my favorite resources for all things, cancer, of course, actually updated in March of this year has a little section on Appendiceal adenocarcinoma.

It's like one or two pages in like the 700 pages of colon cancer, but it does kind of break it down a little bit and how things are kind of broken down. Big, big picture appendiceal masses. You know, you think of the broadest categories are epithelial versus non epithelial, and I'll start with

some non epithelial, like that would be a neuroendocrine or carcinoid lymphoma, some other kind of exotic type things of that nature gist, but very rare there, so non epithelial.

And then epithelial, which is what we would consider adenocarcinoma, and some of these other. Things we'll talk about now, low grade and high grade mucinous carcinoma peritonitis. So, If you look at how the appendix can be classified now in terms of appendix cancer, so they could be considered an invasive adenocarcinoma.

This would be with or without signet ring cells. Signet ring cells are known to be a much worse histological subtype. So you have your standard adenocarcinoma with or without signet ring cells. Now there's also going to be a topic of mucinous adenocarcinoma. So the vast majority of adenocarcinoma of the appendix will have mucinous features for the production of mucin.

And then in that subcategory is what you would

consider goblet cell or goblet cell part neuroendocrine. So those are little goofy, weird ones. So it's not really a neuroendocrine tumor. It's not really an adenocarcinoma, but it's both. It predominantly has adenocarcinoma features, so we treat it like a adenocarcinoma.

And then another one that gets very awfully confused, And I may have confused the listeners already, is these low grade appendiceal mucinous neoplasms so LAMN, L A M N, this is the one that we get which traditionally has led to a term called pseudomyxoma peritoni. Now, Pseudomyxoma is a whole nother term that they're trying to get away from for certain reasons, but that's essentially the mucinous accumulation of whatever tumor it is, either low grade or cancer in the abdominal cavity.

So let me rephrase everything now. So we have this lamin, this low grade appendiceal mucinous neoplasm, which is the one that traditionally people would understand. This is what we got Hypec for, or CRS and Hypec, the sugar

baker procedure. This was the one with all the mucin, the jelly belly, they call it.

That's from a low grade appendiceal mucinous neoplasm, not actually a cancer, but that's very confusing for some folks, of course. And then there's also one called high grade mucinous neoplasm, which is also non cancer, which is treated with CRS and HyPIC as well. And then as I talked about first, there was the adenocarcinomas, which can be mucinous and they can have with or without signet ring cells.

These patients are treated like colon cancers. including systemic chemotherapy and they may either have just a right hemicolectomy, which is the standard, which we'll talk about and, or those patients that they do have peritoneal disease could potentially go for a CRS and HyPIC as well in conjunction with systemic chemotherapy.

That's kind of the, The big picture, which is a lot of stuff, Scott, but a lot of stuff. But like I said, NCCN, the DCR has a wonderful, you know, the practice guidelines

which a new one's going to be coming out soon for Appendiceal. It's in revisions right now, I believe. Well, Mike, we appreciate that as an overview, and there's a ton to unpack there, and just for the listeners at home, CRS is Cytoreductive Surgery, something that we'll get into in just a little bit.

And so with that, we're going to go through three cases specifically to kind of highlight some of the learning points and your approach to these appendiceal masses. And with that, I'm going to turn over case one to Dan. All right. Thank you. And that was a wonderful introduction to get started into these cases.

Our first case involves a 45 year old female who is suspected to have acute appendicitis, based on her presentation with right lower quadrant pain. During laparoscopic surgery for suspected appendicitis, an atypical mass is noted at the tip of the appendix, for which histopathology confirms a carcinoid tumor.

And so really, to get the discussion started.

Let's just get started with what are the typical symptoms of appendiceal NETs and how are these tumors usually diagnosed? Yeah, thanks. So I guess maybe it's a little trick question. So most of these don't have any symptoms whatsoever. They're incidentally found either during a right hemicloid for other reasons say Crohn's disease or ileocecectomy or more commonly after a bout of acute appendicitis and a patient healthy otherwise, appendix looks just a little inflamed, comes out and oh my gosh, there's a, you know, five millimeter, maybe a one centimeter, neuroendocrine tumor that is, that is there.

So most of these are found incidentally of the appendix and most of the appendiceal I would say the vast majority really, they don't, aren't really biochemically active similar to like the rectum. It doesn't really usually secrete the chemicals, but so they really don't have symptoms. Usually the symptom is appendicitis.

And it's incidental. And I missed the second part of the question. I apologize. And

no you answered it pretty much. How are these diagnosed? Usually just on surgery since they really aren't presenting any other way than appendicitis. So moving on to the treatment options what are the current treatment strategies for appendiceal carcinoid based on a size and histological features and location in the appendix?

Yeah, so, I mean, we always talk about how these are classic quote unquote board type questions but, you know, sitting in any of our tumor boards, multidisciplinary sessions these come up quite a bit, and we still kind of go back and forth on what the best answer is. And once again, looking at NCCN and other You know, literature out there.

Some of the key numbers over the years and currently now is about two centimeters as a generalization. So say this patient had a, you know, 1. just in general. Let's go easy actually. Let's say it's one centimeter, okay? One centimeter or less than a centimeter. They did an appendectomy, clear margins you know, the, it's a low grade or grade one,

meaning it has a low, you know, mitotic index, it has a low KI 67 score, etc.

So those, all those features that's well, you know, it's a nice looking tumor. It's very small. You're done with an appendectomy. Most people would even say something at the tip or the base, or even the, even, you know, mid, excuse me, even at the base, upwards towards two centimeters really is the cutoff in NCCN guidelines.

If you have good features, two centimeters or less you know, clear margin, you're probably okay. However between 1 and 2 centimeters, 1. 5 to 2 centimeters, there is some controversy out there on what to do. I think it's individualized. That's a time when, you know, imaging would be of help as well. So, say she has a 1.

8 percent carcinoid on appendectomy. And then the question is, do I need to take a right colon out or not? And that's once again looking at the the differentiation of the tumor. You know, was there clear margins mitotic index, et cetera, KI67. And then this is a good time to get CAT scan imaging to take a look and see if there's

any question of lymphadenopathy.

If it looks suspicious like there are, you know, lymph nodes there potentially, you know, then you'd be more apt for that kind of borderline gray zone between one and two centimeters. Maybe I should take out the colon and get the lymph nodes. Because the whole point is looking for lymph and not, and just like colon cancer, et cetera, you want, you're looking to get lymph nodes out to make sure nothing has locally spread.

Okay, perfect. So then now that you've taken out the the carcinoid when is chemotherapy typically used for these cases? And maybe if you want to touch on what regimens are used? Yes. So for carcinoid for neuroendocrine tumors. If it was a simple one, like we said, we were happy with everything.

We just did an appendectomy. You're done. Surveillance is even questionable in some of these. You're going to be looking at maybe you know, how about getting chromogram and A levels, which once again, the appendicitis doesn't really secrete much, but also a CT scanner. go to take PET scans, et

cetera. But for the ones that, you know, you took out you had to do a right colectomy due to its size or bad features or even those, say there was no lymph nodes positive and you did a right colectomy, you're pretty much still looking at surveillance in those patients.

But patients positivity or anything more advanced than that, of course you do. You would consult with our medical oncology and there's really no like, like chemotherapy like you think of like a full FOX version. Nothing, nothing like that for this. This is more giving medicines like octreotide in a kind of a maintenance type of fashion.

Now this is definitely something that we consult with our medical oncology team. It's something that, you know, that we don't treat, but, you know, going with tumor board, even, even the the specialist, you know, everyone's a little bit varied on their approach but if you have other disease out. You can either watch these folks with yearly surveillance scans or PET scans.

Some people, if they had really a lot of disease, very aggressive disease, you may consider going on Octocreatide. But that's usually meant

for more folks who have known disease that's not resectable, metastatic disease in the liver, peritoneal disease. That's more mostly for controlling symptomatology and potential growth of those lesions.

But if you do a simple kind of right colectomy and all the lymph nodes are negative, or you got maybe two lymph nodes out of 25 that came out, sometimes you could just, of course, watch those patients. So let's go on to the second case. So you have a 60 year old male who presents with vague abdominal pain and it's got a feeling of fullness.

There is really no significant history of cancer in the family. As a part of this workup, you get a CAT scan that demonstrated a two centimeter mass at the base of the appendix. And the CT report says, yeah, maybe some invasion of local fat into the area. And maybe even some possible involvement of the ileocecal valve.

So, see you in clinic. is otherwise kind of doing okay, non obstructed type feeling. So, Mike, what is your diagnostic approach to this patient? How do you go about next steps? Yeah I don't like, I don't like some of

the features on a CAT scan, like possible invasion, kind of going into the ilicical valve that area.

So, sometimes, you know, we get referred ones where it's more of a Just an appendiceal mass, but this seems like it's doing more, more maybe into local structures there. So obviously I want to see, you know, make sure there's nothing else going on in the abdominal cavity. Make sure there's no peritoneal disease or something.

I'm looking to see, you know, is this something that I need to potentially biopsy beforehand? I would think colonoscopy, if they haven't had one, would be a next step as well to take a look inside. If it's a appendiceal tumor, you know, Invading into the valve. Obviously, you want to get some biopsies of that if possible.

If that's successful, then we have an answer, hopefully, but say that doesn't come back and in real life, a lot of times, just like it would on the board exam does not come back with any conclusivity. So we have to figure out what to do. So if I can't get any kind of biopsy beforehand you know, the question is with this lesion, I would take him.

I would probably do a diagnostic laparoscopy in this situation to kind of look at the

area, see what's going on. And you know, non cancerous appendiceal tumors don't usually have that appearance on CAT scan where they're kind of invading into other structures or into the colon area. So, you know, I'd be more prone and more likely to obviously, if there's something, I think a frozen section and it's at no car snow, but that'd be great.

But otherwise, probably do a right collect me in the situation. If I did have any other data and I couldn't get any conclusivity that this is cancer I would do it to assume it would be a cancer. So that's great, Mike. So let's just break down a couple of points within this. So, you know, the fact that it showed local invasion or potential local invasion into the kind of the fatty mesentery right there.

Is that one of the strongest predictors of why you say that you would do a right collect me or how much stock do you put into that? And that, that was kind of like one of the biggest factors right there without having pathology without having kind of diagnosis back that cut that right there. I don't like, you know, low grade mucus tumors.

Don't do

that in isolation. Usually carcinoids. I mean, they could have a carcinoid that bad. You probably need to recollect him anyways. Yeah. So, Mike, let's just say that it comes back and you get what's called a T3 node positive adenocarcinoma. Can you talk a little bit about adjuvant therapy options for an adenocarcinoma of the appendix?

And if at all, does it differ from that of the colon? And what are the types of chemotherapy that are typically used for an adenocarcinoma of the appendix, if indeed they are needed? Sure. So in that situation, where there is lymph node positivity, they absolutely would, would.

And the appendix overall is extremely rare. So, they extrapolate pretty much all of their data from stage two and three colon data. And technically speaking, it is part of the colon. It does act differently. So, they do the typical colonic stage two, stage higher stage two and stage three lymph node positive type of treatments.

And that's pretty much it. Full

5 FU based, that would be most likely the first option would be something called Full Fox, which is 5 FU, Leucovorin, another drug called Oxalipatin, and that is usually a basis for standard lymph node positive appendiceal cancer. You know, as you get into more aggressive appendiceal types with peritoneal spread, there's a little bit more nuances there with different regimens and different agents, but more second and third line things, but standard chemotherapy.

Now people always ask about also immune therapy really hasn't been extrapolated into the appendiceal world yet, but I'm sure it will someday. There, there are specific mutations as similar to colon cancers, especially like a KRAS. So, but none of those drugs per NCCN are approved for appendiceal.

Really, it's just standard 5FU based. Treatment at this time, like I said, pretty rare overall, so they extrapolate from colon cancer. And then, just because we have multiple different ways to treat cancer, and in some ways it may be more common or less, can you talk

about, is there a role at all of radiotherapy here?

Generally, generally speaking no, but I would never say no for every case. There could be some isolated cases where radiotherapy could be in a palliative setting but as of right now similar to colon. No, no real role for radiotherapy as of 2024. And then finally, Mike, how would you follow this patient?

Yeah same as I would a colon cancer we're going to follow them aggressively. So say we did the right colectomy, lymph nodes are positive, they were going to get they would get at least four, but likely up to six months of adjuvant chemotherapy. And then at that point on CEA, CT test to have in pelvises would be done every three to six months moving forward.

And then, you know, annually, once you hit like that two year mark or so three year mark for, you know, for the usual five years. So aggressive aggressive screening or surveillance, excuse me. And CAT scans are quite important in this population because appendix cancer,

as opposed to colon or rectal cancer.

It does have a propensity to metastasize to the peritoneal cavity as well. So, some of these larger tumors can because of the nature of the anatomy of the appendix, do tend to go into the peritoneal cavity. So a lot of times we'll see large T3 or lymph node pods or a T4 because they perforate at the time of appendicitis turn out to be some peritoneal based disease as well.

So that's a whole nother spectrum of disease there. That's great. Okay, back over to Dan. All right, for our third and final case, we have a 55 year old female with increasing abdominal girth and discomfort over several months. She undergoes a routine pelvic ultrasound, which suggests a possible mass in the right lower quadrant.

This is further imaged with a CT scan, which reveals a large mucinous neoplasm, where mucin is seen in the peritoneal cavity. So to start Can you discuss the relationship between mucinous tumors of the appendix and what we are currently calling

pseudomyxoma peritoni? Excellent. So pseudomyxoma peritoni, as we discussed, is considered an umbrella term for, I don't You know, massive mucinous ascites accumulates in the abdominal cavity, and that could be from a multitude of different things, but usually the most famous one is from what you're describing in this case, it sounds like is low grade appendiceal mucinous neoplasm that has then taken over the abdominal cavity by appendiceal you know, perforating and then feeding the abdominal cavity with mucin.

Tumors are different than what we just discussed as invasive adenocarcinoma. They are completely different. May they originate from the same cell lines, etc., or same mutations potentially, but really, as I tell all the trainees or patients, it's not a cancer, but it can act like a cancer if it's allowed to be untreated and get to the point of

pseudomyxoma.

So this low grade appendiceal mucinous. Neoplasm is usually confined to the appendix, but if it perforates, then the mucin and the cells will then migrate to the abdominal cavity and cause the condition. Now, there's also a kind of another category called high grade appendiceal mucinous neoplasm.

It's kind of potentially borderline malignant, a little bit more aggressive. But yet for low grade and high grade chemotherapy as we just discussed is not an option in the intravenous or systemic treatment like we normally would for cancer, invasive cancer. So sometimes we'll have patients like this gal who maybe they did a biopsy and it showed some mucin cells.

Usually that's what happens. They do a biopsy or they try to do a paracentesis and then they can't do it. So they try to get some other tissue and it shows, you know, a bunion. Acellular mucin or something of the such. And then they, well, we can't get a biopsy. We can't do anything. So they put them on chemotherapy for three months,

six months, nine months, and nothing changes.

They get a little bit worse even, or their ovaries are getting bigger, etc. So they don't, they don't respond to chemotherapy. They're not that kind of disease. They don't spread to lymph nodes. They don't do that. They don't do that kind of thing. So in this particular situation, this is a tricky one because she's having symptoms of this GIR, which is the accumulation of the ascites.

I mean, we need to get the importance I want to say about all the appendix tumors is the importance of getting histology and then getting that histology getting that pathology read by an experienced pathologist, you know, looking at tissue and really knowing that's the key to all these things is getting the right definition down because you can take a path, a patient on a very wrong pathway, both medically and surgically, if you get the wrong diagnosis, and that I've seen that happen.

So in this particular patient, you know, you try to get pathology in the earlier settings, if there's not too much mucinous accumulation, or we see what we, the quote unquote, you go seal the appendix, which, you know, really you know, if we see something like that, that's someone I would hopefully take for a

diagnostic laparoscopy and I see a dilated appendix, or I see mucin and some other implants.

That's the one I would get. do an appendectomy and get tissue so I could define it, make sure it's not an invasive adenocarcinoma. And that's what this patient sounds like I would do. I would try to take a prolaparoscopy if possible. Sometimes that's impossible. Percutaneous biopsy of something solid like the omentum, but really getting an appendix out is the best pathology you can get if possible.

And sometimes that requires doing like an X lab to get To get the answer, we try not to, but we try to do a laparoscopic if we can, so. Does your treatment strategy change if the mucinous neoplasm is confined to the appendix without any mucin in the abdomen? Yeah, so those are the ones we love to find where a lot of times they were getting a CAT scan for something else you know, kidney stones or whatever problem they have, and they see, they find like a six, seven, eight centimeter dilated appendix.

And there's nothing else going on. So that one I would take, you know,

pretty not urgently, but I would take them soon for a diagnostic laparoscopy. And that's when I'd be extremely careful doing a good survey of abdominal cavity. And if this thing's confined to the appendix. I carefully immobilized the secum, et cetera, put in a nice wound protector, put in a bag, take this, take this out.

If the base is clear, even better, I just staple at the base. If the mucinous lesion is, You know, kind of at the base, I'll do, I'll mobilize the whole right colon, pull up into the wound and the wound protector and do a partial cecectomy with it, just to get pathology. This is different than the last case where there was invasion into the local structures, it was, it looked and acted like a cancer.

These are, these look like little little fluid filled balloon sacs coming off the cecum, you know, and that's when I would get the pathology on those. Those then, if you get that, you're done. Patients in great shape. They don't need to have anything else done. You may want to do a CAT scan a year later just to make sure nothing's going on.

Grab some tumor markers, which are elevated mucinous neoplasm, but if you have a clean laparoscopy and the appendix is

completely out, you're done. They also get diagnosed very often during acute appendicitis, and it's like, you know, a T1 quote unquote L. A. low grade appendixial mucinous neoplasm.

Everything's confined. Those folks are also done. So that's nice. Those are the great ones. Those are the ones we try to find before they, before they rupture. And there's quite a few out there, actually. So in the intro we kind of talked about the treatment for rupture. But can you further go into kind of what your surgical strategy is for these ruptured mucinous neoplasms?

Yeah, so, so the low grade appendiceal mucinous neoplasms, the pseudamyxomas we were just talking about, like, that this lady has That is the treatment of choice because they can't get systemic chemotherapy, but they can get cytoreductive surgery and hyperthermic intraperitoneal chemotherapy or HIPEC.

So this is if you had there's been a lot of papers and discussion about CRS and HIPEC over the last few years, that's mostly been for

colonic adenocarcinoma. But in terms of This disease process, the low grade appendiceal mucus, this is the, this is what it was meant for. This is the one that has the best success rates.

This is a disease process that if you can achieve essentially what we consider an R0 even if you leave some microscopic disease behind and you do a good surgery for these patients, their N year to 15 year survival is over in the 90%. So this is a process that is actually very curable. But it involves a pretty expensive operation and called a psychiatric surgery in high tech.

So that's the one where we would take them. It could take anywhere from five to 10 hours on average. And depending on how much disease they have depends on how long it's going to take. And, but that is something where we can run these low grade tumors that are not invasive cancer, that are not metastasizing to the nose, to the liver, to the lungs, to the brain, that these are curable.

If we catch them at the right amount of time and we do aggressive surgery and we have to

sometimes do multivisceral resection, sometimes stripping of parts or all of the peritoneal cavity, including the diaphragmatic peritoneum, peritoneum over the liver, glycine capsule, you know, bilateral salpingo oophorectomies are very commonly performed because the mucinous tumors tend to go to the ovaries sometimes right colectomy or iliostekectomies.

Okay. Sometimes a small bowel resection, splenectomy, you name it. It's a very aggressive operation. Seems, you know, overkill, like, oh my gosh, this is an invasive cancer. But like I said, if you ever see one of these, it surely acts like an invasive cancer because it's everywhere and it can cause the biggest cause of death in these patients, even though it's not invasive cancer will be bowel obstructions or like TPN related issues or aspiration for bowel obstruction.

And then, you know, if these patients get into trouble, you know, You know, you're the on call surgeon at some hospital somewhere, like what's going on. This is something that we can't fix this. So they usually end up dying from a bowel obstruction. So this operation kind of

hopefully can And we've seen it many times and done it many times where it quote unquote cures them, you know.

So, so to wrap up this case how are you going to follow this patient long term? Yeah, so this lady, that seems like she has a lot. Like I said you know, I didn't get into it, but we quantify this with the peritoneal carcinomatosis index between 0 to 39. That kind of breaks up the abdominal cavity and the bowel into different quadrants.

And you get a score for how much there is. So the people that have a much. Lower score have a much easier operation and the recurrence rates are much, much less people who have a lot, maybe like this lady would, so, you know, you're always looking for recurrences even, even for everyone you're looking for recurrences, so that usually means imaging, CAT scans adenopalavis and chest, and then actually these tumors, all of the traditional tumor markers, CEA, are all, can all be elevated in this disease process, even though it's not invasive cancers.

Okay. So we follow those yearly as well and I have

patients that are now, you know, 10 years out 12 years out, you know, a lot of 5, 6, 7 years out from other surgeons as well, including my own from the last 5 years and there are people who do recur. And some of the recurrences are small, but once again they're having a good quality of life and they're, it's not causing any major problems.

And this is not invasive cancer. So we may, we may go back in if they grow or cause problems, or we may just leave it alone, but there is no other medicines or chemotherapeutic agents you could use. You know, then I have some patients who are on the other end of the spectrum that have had a tremendous disease when they were first encountered.

Never got it all out. And now they, you know, two, three, four years, every year or two, they may go for a quote unquote palliative type of bulking or procedure where we're just kind of clearing out as much disease as possible, maybe giving some different kind of ostomies or, but some of these folks are on TPN.

And then but you know, it becomes into a longer chronic disease, but if you could catch it, a lot of it's luck, of course, if you could catch it early and if you do find it early and you're the surgeon out there and you could treat it. You

can save these folks a lot of problems down the road if we could catch it early.

Well, Mike, thanks so much for taking this. Do you have any kind of last overview, if you will, or final thoughts about this entire concept of appendiceal masses? Yeah. So I think, you know, as a surgeon if you get into an operation that you weren't expecting something, maybe take a step back and say, Whoa, what's going on here?

You know, is there a pair of tail disease? Don't even take some biopsies. Maybe just get out of here. You know, if you do encounter something that involves the mucinous things, be as careful as you can when you remove it, try to do the right thing. Sometimes doing maybe just taking pictures and biopsies and getting out to a wise thing.

If you're not prepared to take care of these things, but also just changing techniques are changing and et cetera. So trying to keep up to date as much as possible. Look at the national guidelines and you know, Call call if you have any questions.

Well, we appreciate the opportunity for you to join us here, going over this complex topic and somewhat a little bit more difficult in terms of the terminology itself.

So for all of you BTK fans, thanks for joining us until then dominate the day.