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Welcome, BTK listeners. My name is Dan Schies, and I'm 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 4 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.
Adenocarcinoma is pretty straightforward, but, you know, a lamin versus, you know, mucinous neoplasm. 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 not just the patients who have to hear about these things, but multiple different surgeons and physicians and pathologists all have different years that they trained. Some people, there's different terminology that comes out kind of. often. And this is a good time to talk about, you know, the NCCN, which is one of my favorite resources for all things cancer, of course, actually updated in March of this year, has a little section.
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 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. 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 peritonei. 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 adenocarcinomas. So the vast majority of adenocarcinomas 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. It's both. It predominantly has adenocarcinoma features, so we treat it like an 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 peritonei. Pseudomyxoma is a whole other term that they're trying to get away from for certain reasons, but that's essentially the accumulation of whatever tumor it is, either low-grade or cancer in the abdominal cavity. 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 HIPEC for, CRS and HIPEC, 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 HIPIC as well. And then as I talked about first, there was the adenocarcinomas. which can be mutinous and they can have with or without signaling 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, or those patients that they do have parateal disease could potentially go for a CRS and HIPIC as well. in conjunction with systemic chemotherapy. That's kind of 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. 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 in 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. Let's just get started with what are the typical symptoms of appendiceal and how are these tumors usually diagnosed? Yeah, thanks.
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 hemiclighting for other reasons, say Crohn's disease or ileocectomy, 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, they aren't really biochemically active, similar to 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 now 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...
on a size and histological features and look 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, 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 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, 1.8, 1.5, 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, it's a low grade or a grade one, meaning it has a low mitotic index. It has a low KI-67 score, et cetera. So 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 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 one and two centimeters, 1.5 to two 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 one-point carcinoid on appendectomy, and then the question is, do I need to take her right colon out or not? And that's, once again, looking at 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 questionable lymphadenopathy, if it looks suspicious like there are 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. Because the whole point is looking for lymph and not 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 carcinoid, when is chemotherapy typically used for these cases? And maybe if you want to touch on what regimens are used?
Yeah, 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 isn't really really secreting much but also uh dt scans or doted to take pet scans etc but for ones that you know you
took out so you had to do a right collectively due to its size or bad features or even those say there was no lymph nodes positive and you did a right collectively you're pretty much still looking at surveillance in those patients But the patients who have lymph node positivity or anything more advanced than that, of course, you do...
you would consult with our medical oncology and there's really no like chemotherapy like you think of like a full fox or 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 we don't treat, but going with tumor board, even the specialists, everyone's a little bit varied on their approach.
But if you have all the 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 octopreotide. 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.
But if you do a simple kind of right-click, I mean, not all 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 he'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. CT report says, yeah, maybe some invasion of local fat into the area and maybe even some possible involvement of ileocecal bile. So seeing you in clinic is otherwise kind of doing okay, not obstructive type feeling.
What is your diagnostic approach to this patient? How do you go about next steps? Yeah. I don't like some of the features on a CAT scan, like possible invasion, kind of going into the illusical valve, that area. So sometimes, you know, we get referred. or 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 paracetal disease, something I'm looking to see, you know, is this something that I need to potentially biopsy beforehand, but, but. I would think colonoscopy, if they had one, would be a next step as well to take a look inside. If it's a panaceal 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 time, 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 like a frozen section and it's adenocarcinoma.
Well, that'd be great. But otherwise, probably do a right collect me in this situation. If I didn't 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 colectomy or how much stock do you put into that? And that was kind of one of the biggest factors right there. Without having pathology, without having kind of diagnosis. That right there, I don't like. Low-grade mucous tubers don't do that in isolation usually. Carcinoids, I mean, they could, but if a carcinoid is that bad, you probably need to recollect them anyways.
So, Mike, let's just say that it comes back and you get what's called a T3 node positive and no cursor. 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, the appendix, if indeed they are needed? Sure. So in that situation, whether it's lymph node positivity, they absolutely would...
benefit from chemotherapy in the adjuvant setting. And the appendix overall is extremely rare. So they extrapolate pretty much all of their data from stage two and three colon data. Technically speaking, it is part of the colon. It does act differently. So they do the typical colonic stage 2, iris stage 2, and stage 3 lymph node positive type of treatments. And that's all 5F2-based. That would be most likely...
The first option would be something called Folfox, which is 5-FSU, Leucovorin, another drug called Oxyplatin. And that is usually a basis for a standard Leuco-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 are specific mutations as similar to colon cancers, especially like a KRAS. But none of those drugs per NCCN are approved for appendiceal. Really, it's just standard 5FU-based. treatment at this time uh 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? Genuinely. Technically 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 real role for radiotherapy as of 2024.
And then finally, Mike, how would you follow this patient? Yeah. Same as I would have colon cancer. We're going to be following 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's CPT test had been palpitative.
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. CAT scans are quite important in this population because appendix cancer, as opposed to colon or rectal, 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 lipinopods 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 other 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 image 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 paritonei. Yeah, excellent. So pseudomyxoma paritonei, as we discussed, is considered an umbrella term for... I don't want to call it the end stage, but the condition where massive mucinous ascites accumulates in the abdominal cavity. 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 mucin. This neoplatin has then taken over the abdominal cavity, appendiceal perforating and then feeding the abdominal cavity with mucin. These tumors are different than what we just discussed as invasive adenocarcinoma. They are completely different. May they originate from the same cell lines, et cetera, 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. Theoplasm 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 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 they can't do it. So they try to get some other tissue and it shows, you know, abundant 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, et cetera. So 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 kind of thing. So in this particular situation, this is a tricky one because she's having symptoms of this girth, 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, getting the right definition down. Because you can take a patient on a very wrong pathway. both medically and surgically, if you get the wrong diagnosis. And 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 the quote unquote mucosal, the appendix, which, you know, really, you know, if we see something like that, that's something I would hopefully take for a diagnostic laparoscopy.
And I see a dilated appendix or I see mucin and some other implants. That's someone I would 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.
Try to take it for laparoscopy if possible, but 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. Sometimes that requires doing like an X-lap to get... to get the answer. We try not to, but we try to do a laparoscopic if we can. 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 or kidney stones or whatever problem they have. And then they find like a six, seven, eight centimeter dilated appendix.
And there's nothing else going on. So that one I would take 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 immobilize the cecum, etc. I put a nice wound protector, put it in a bag, take this out. If the base is clear, even better, I just staple it at the base. If the mucinous lesion is...
you know, kind of at the base, I'll mobilize the whole right colon pulled up into the wound and the wound protector and do a partial seekectomy with it just to get pathology. This is different than the last case where there was invasion into the local structures. It looked and acted like a cancer. These are...
They used to 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 gone on. You could grab some tumor markers, which are elevated, museness, neoplasm. But if you have a clean laparoscopy and your appendix completely out, you're done.
They also get diagnosed very often during acute appendicitis. And it's like, you know, a T1 quote unquote LA low-grade dependency of mucous neoplasm. Everything's confined. Those folks are also done. So that's nice. Those are the great ones. Those are the ones that we try to find before they rupture. And there are 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 the low... grade of penicillomusis neoplasms, the pseudomyxomalins we were just talking about 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, at the end, 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 amuses, 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, they're, you know. end-year to 15-year survivals in the 90%. So this is a process that is actually very curable. but it involves a pretty expensive operation and called a center of surgery. So that's the one where we would take them. It can take anywhere from five to 10 hours on average.
depending on how much disease they have, depending on how long it's going to take. But that is something where we can, these low-grade tumors that are not invasive cancer, that are not metastasizing 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.
parotene over the liver, glistens capsule, bilateral salpingal oophorectomies are very commonly performed because the mucinus, the tumors tend to go to the ovaries. Sometimes right colectomy or ilustiquectomies, sometimes a small bar resection, splinectomy, you name it.
It's a very aggressive operation. Things, 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. It could 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.
bowel obstruction you know you're the oncologist at some hospital somewhere you're like what's going on this is something that we can't fix this so they usually end up dying for a bowel obstruction so this operation kind of hopefully can And we've seen that many times and done it many times where it quote unquote cares them, you know. 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 peritone carcinomatosis index between zero and 39. That kind of breaks up the abdominal cavity and the bowel and 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 And then pelvis and chest. And then actually these tumors, all of the traditional tumor markers, CEA, CA-1990, and CA-125 are all, can all be elevated in this disease process, even though it's not invasive cancers.
So we follow those yearly as well. And I have patients that are now 10 years out, 12 years out, a lot of five, six, seven years out from other surgeons as well, including my own from the last five years. And there are people who do recur. And some of the recurrences are...
But once again, they're having a good quality of life and it's not causing any major problems and this is not invasive cancer. So 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 that 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 ostomizer, but some of these folks are on TPN. 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 could 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 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 peritoneal disease? Do I need to take some biopsies? Maybe just get out of here, you know. if you do encounter something that involves the mucin thing be as careful as you can when you remove it try to do the right thing sometimes doing
Maybe just taking pictures and boxes and getting out to a wise thing if you're not prepared to take care of these things, but also there's changing techniques are changing and sec, et cetera. So try to keep up the date as much as possible. Look at the national guidelines. And, you know, call a 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.
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