Appendiceal Cancer - Symptoms, Diagnosis, and Prognosis

MD Anderson Cancer Center
Date: 10-25-10


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Lisa Garvin: Welcome to Cancer Newsline, a weekly podcast series from the University of Texas M.D. Anderson Cancer Center. Cancer Newsline helps you stay current with the news on cancer research, diagnosis, treatment and prevention, providing the latest information on reducing your family's cancer risk. I am your host Lisa Garvin. Today our subject is appendix cancer. We have two guests in the studio today, Paul Mansfield, who is a professor of Surgical Oncology here at MD Anderson and Keith Fournier, who is an assistant professor of Surgical Oncology. Welcome to you both this morning.

Paul Mansfield, M.D: Good morning.

Keith Fournier, MD: Thanks.

Lisa Garvin: I know Dr. Mansfield, you have treated some appendix cancer patients in the past that we have featured on YouTube videos and so forth. How rare is appendix cancer or appendix tumors?

Paul Mansfield, M.D: I think it depends upon how you classify them as one of the things that people may start to find out when they start looking on the Internet is this is actually a huge spectrum of diseases. And what we are primarily talking about is non-carcinoid tumors of the appendix, things that come from the epithelium or the lining of the appendix and these can be anything from a very, very benign appearing and behaving tumor to one that is extremely aggressive. And so, it is sort of a broad spectrum and it oftentimes ends up into a sort of a collection of tumors that are really not the same. But somewhere estimated between around 500 and maybe 1,000 cases a year in the United States and Keith?

Keith Fournier, M.D: Yeah. Again, it just depends on how you classify these tumors and obviously, we are not going to be able to pick up all of them that are out there, but in general the range is somewhere between 500 and 1,000 new patients a year.

Lisa Garvin: So when you have--but we treat the lion share of them, don't we? Don't we see a fair amount of appendix tumor patients at MD Anderson?

Paul Mansfield, M.D: We, this year probably will see over 100.

Keith Fournier, MD: Yeah, I would say more than 100.

Paul Mansfield, M.D:  Yeah.

Keith Fournier, M.D:  But, you know, there are other institutions that are also involved with caring for these patients as well.

Lisa Garvin: How do people--what are the symptoms, are there any classic symptoms of this group of tumors?

Keith Fournier, M.D:  You know, often they are asymptomatic. Sometimes in women particularly, they are picked up after a gynecologic exam and they are found to have an ovarian mass or what is thought to be an ovarian mass. And then they undergo, you know, further work-up and, you know, they find out in the end that it turns out to be an appendix cancer and not actually ovarian at all. The other way that might present this is such as an appendicitis actually and the patient is brought to the operating room for a presumed appendicitis to go to take out the appendix, it looks abnormal or on final pathology comes back as one of these appendiceal tumors. So, there is a range of ways that people present the cancer.

Paul Mansfield, M.D:  We also have patients who are going to surgery for another reason and such as a gall bladder or hernia and when they operate on the patient they find what is the product of this tumor oftentimes which is a gelatinous, almost sort of looks like orange marmalade-type material that is very sticky. But that may be actually be found in the hernia sac or that the surgeon who is performing this other surgery finds this. And unfortunately, because of the rarity of this, most surgeons have not seen it or maybe have only ever seen one case in their career and so, when they encounter it, it is sort of starting all over again.

Lisa Garvin: Well, that must be startling to see that gelatinous mass and you know if you are opening somebody up for surgery for another you know condition.

Paul Mansfield, M.D: If you have never seen it before, it is quite striking and startling, and some of the descriptions are read in people's operative notes have reflected that.

Lisa Garvin: What is the morbidity and mortality on these tumors?

Keith Fournier, M.D: You know again, it ranges very much on the actual pathology of the tumors. So, as we said there is a broad spectrum of tumors within the appendix and some of them, the ones that are more benign and what we call low-grade tumors tend to behave in a very benign way and they have very long term survival and there are some—

Paul Mansfield, M.D: With appropriate therapy.

Keith Fournier, M.D: With appropriate therapy and then there are some with a very high grade tumor that behave in a much more aggressive way and they actually tend to be more like a colon cancer than one of these more benign appendix cancers. So, it is hard to give it an exact number. It depends on what exactly you are talking about.

Paul Mansfield, M.D: And it also depends upon the where the diseases is, some recent work fit Dr. Fournier has looked at in patients who have what we call tumors of uncertain malignant potential and factors that may influence the survival; that may be you could speak to that, Keith.

Keith Fournier, M.D: Yeah, so these are tumors that are a little bit hard to classify as whether or not they are completely benign in nature and that is to say that they are not likely to cause a problem down the road. And it is based on what we see under the microscope, our pathologist will make this diagnosis because they are not sure if it is, if and in fact it is going to become a problem or not and so, that is the reason for the uncertain malignant potential. And what we have found is that the location of the mucin that is associated with these kinds of tumors and also, whether or not some of the markers, tumor markers such as CEA, CA 19-9 are commonly looked at in colon cancer and also appendix cancer, if those are elevated and we found that, you know, these behave in a way that is not so benign. But you know, with the new data that we have, we are trying to make some headway into how these tumors really behave and who to treat with surgery and who to watch and those are all very complicated questions that we are trying to get the answers to now.

Lisa Garvin: And I know, we had a patient that I had interviewed a couple of years ago, she and her husband and she had pseudomyxoma peritonei and the surgical approach is quite, it is quite a laborious and intensive surgery, can you describe that?

Paul Mansfield, M.D:  Sure, the and actually, that is--before we talk about the surgery, the use of the phrase pseudomyxoma peritonei is sort of a catch all phrase for this huge spectrum. And most of the physicians around the world who see and treat a significant number of patients with these tumors of the appendix are trying to shy away from using that phrase because it was originally described to reflect this massive amount of gelatinous material. But that doesn't really describe, is it a poorly differentiated tumor, is it a signet ring cell tumor, is the tumor of uncertain malignant potential, all of which people and patients and oftentimes physicians will lump into the same category, but are in fact very, very different. The operation which is on average here, it takes about 10 hours. The range I believe is somewhere between five and I think 19 hours and it is a very challenging procedure, both for the patients, as well as for the surgeons, as well as the families. And I know that a patient you interviewed a few years ago, her husband was intimately involved in her care and can speak to the recovery. After about three to six months, most patients are back to normal activity, sometimes quicker, sometimes it takes a little bit longer. But despite that attendant morbidity, mortality rates at high volume centers such as ours is low and it's only lower about 1 percent.

Lisa Garvin:  Because it is apparently, this gelatinous mass doesn't just come out like as an encapsulated tumor, do you have, does it have to be scraped or I mean, explain the procedure. I know there is the rocking in the chemotherapy, but what goes on before that?

Keith Fournier, M.D:  Well, you are right about that. In general, there is not one large gelatinous mass, and although sometimes there is. But often what it is, is it is kind of sticky, almost as if you were to throw mud on the wall and it kind of it stuck there. It doesn't just peel right off and what you have to do is strip the linings that this is sticking to, so we call that the peritoneum. The peritoneum is what lines the abdominal cavity and these tumors tend to just stick on those and there is actually a way to remove that lining that takes the tumor with it. And in that way we are able to remove, you know, many times all the disease that is in there and that is the goal is to remove all of the disease that is in there. Also, sometimes there are some organs that are involved that we can't really strip the linings. It is just such that the anatomy is such that we can't do that. And in those situations we have to remove organs, sometimes a part, you know, a piece of the small intestine or the colon or the spleen. It all depends on what is involved at the time of the surgery. And as you say, after we remove all of the tumor, then we go to this chemotherapy in the belly and the chemotherapy is heated and then we place it into the abdomen for 90 minutes and we vigorously shake the abdomen to make sure that the chemotherapy can cover all of the organs and all of those areas that we removed in an attempt to really try to kill any cells that are left behind that we can't see with our eyes. And that is the premise behind that and then when we are done we put things back together again and often patients will have some tubes that will help them after surgery to prevent them from having nausea and to give them nutrition that they need.

Lisa Garvin: Do they often need to be tube fed after the surgery, is that common or—

Paul Mansfield, M.D: It is fairly common, but it is not because there is a loss of the continuity, if you will or the connections from the--how we eat and process food, but that the stomach itself actually goes to sleep in probably close to half the patients and that may last sometimes for six weeks. And that is what I call the doldrums of the recovery because patients oftentimes see their neighbors come and their neighbors go as far as in the hospital rooms next to them and that starts to wear on them. But I have yet to see a patient whose stomach hasn't woken up and it is usually fairly precipitous when it does occur and it is welcomed by all. If I could just comment one thing about the operation, as Dr. Fournier indicated, our goal is to remove all of the disease, but there are times when we can't. And in those settings, we may not do the heated chemotherapy because the patient may not benefit from it and still suffer the toxic side effects. And so, those are things that while we have a pretty good idea going into surgery, there are times when we find things that we don't expect to find and that can alter the surgery.

Lisa Garvin: Now with women, are the chances that they lose their reproductive organs pretty high or I guess it depends?

Paul Mansfield, M.D: Well, part of it depends I think where you go. There are some centers that are a little bit more aggressive, shall we say with removing organs. Our philosophy tends to be one of conservation, if it doesn't really need to come out, if you don't have to take it out to remove the disease, then you are better off not. There is--and one of the things that Dr. Fournier mentioned about how the disease is, sort of like paint splattered, one of the examples I use for patients is it is like glue. And you can take your fingers and you could put rubber cement on your fingers and you can get that off, or Elmer's Glue, but if the tumor is more like super glue, that is when you run into trouble and that is where we can't necessarily get all the disease out and that can change the operation.

Lisa Garvin: Are there any new interesting areas of research or any ways of like improving the treatment or you know, making it--I mean, because I have this vision of, you know, the surgical nurses rocking the patient back and forth with chemo for like 90 minutes or whatever and are there any new exciting innovations down the line that you are looking at?

Keith Fournier, M.D: Well, one of the things that we are actually looking at here is there is a multi-institutional trial that is about to open here at MD Anderson. It involves two other institutions and we are going to be looking at different types of chemotherapeutic agents in the belly. That is to say we use a standard, what we call mitomycin C here at this institution. There are some other institutions that use other agents, and this would be the first time in a head to head way that we are going to compare these chemotherapeutic agents looking at, you know, the toxicities and also long term outcomes to see which drug is better overall. I think that this will be one of the first randomized trials performed in appendix cancer.

Paul Mansfield, M.D: [Inaudible].

Lisa Garvin: Are these new agents--oh, I'm sorry, are these new agents or just agents that we--the familiar chemotherapeutic agents?

Paul Mansfield, M.D: They are familiar agents or approved and commonly used agents, but I think the most essential point of this is as Dr. Fournier pointed out is in this country, this is the first randomized trial for surgery in this disease. The other thing, one of the other things that we are working on is using a prospective database which we currently have that has over 350 patients in it and allowing us, we think to over time better define who actually should have such an aggressive operation and maybe who doesn't need it. And we are also in the process of writing a Phase I study for an alternative therapy which I would rather wait to discuss until after we had that opened.

Lisa Garvin: Absolutely, but it seems like though given the rarity of this disease, accrual might be kind of slow. Are you worried about that?

Keith Fournier, M.D: Actually you might think that, but particularly the multi-institutional nature of this and the volume that we see being a tertiary center actually don't think we are going to have a problem with accruing the patients.

Paul Mansfield, M.D: Yeah, I think it depends upon the type of study that one tries to do and the--what I oftentimes use as an analogy when talking with patients is most patients come to a center because they want to be treated and an option of not being treated is not something they are interested in. And so a randomized trial that would include that is as you point out something very, very difficult to accrue to and if for example someone had colon cancer and they have lymph node involvement, we know based on randomized trials that patients should get chemotherapy and it will improve the survival on average of those patients receiving it. But it took 15 years to do those studies and that is a disease where there is 170,000 patients every year with the disease. So, if you do the mathematics for something that is 500 to 1,000 per year, I think our grandchildren's grandchildren will be gone before the study could ever be done.

Lisa Garvin:  Well, that is exciting news, though. People can go to the website and find out when this clinical trial is open, so that is good news.

Paul Mansfield, M.D: Yes. It is as Dr. Fournier also pointed out, it is a very motivated and increasingly educated population of patients.

Lisa Garvin: And in closing, it sounds like pathology is key here. It really sounds like you really have to get an accurate diagnosis for the best treatment.

Keith Fournier, M.D: That is absolutely correct. The pathology will determine how the patients are going to do and it is vitally important and it has been reviewed at the institution or with the pathologist who has a lot of experience with these tumors because it is crucial.

Paul Mansfield, M.D:  And that is one of the things that we are fortunate with. We have a planning conference weekly and that is attended by a pathologist who is dedicated to this disease.

Lisa Garvin: So, it sounds like multi-disciplinary care is probably the best route for this rare cancer.

Paul Mansfield, M.D: Absolutely.

Keith Fournier, M.D: Absolutely.

Lisa Garvin: Great. Thank you both for being with us today. If you have questions about anything you have heard today on Cancer Newsline, contact askMDAnderson at 1-877-MDA-6789 or online at Thank you for listening to this episode of Cancer Newsline. Tune in next week for the next podcast in our series.

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