Appendiceal cancer is very rare. It is estimated that approximately 1 or 2 people per million in the United States are affected by primary appendix cancer each year. However, according to recent studies, appendix cancer as such is becoming more common. It occurs more often in adults aged 50 to 55 years, but it can arise at any age. There are various types of tumors that can start in the appendix, for example neuroendocrine tumors, appendiceal mucoceles, colonic-type adenocarcinoma, etc.
On the occasion of Appendix Cancer Awareness Month, which is observed in August, we spoke with Dr. Paul Sugarbaker, one of the leading appendix cancer/pseudomyxoma peritonei (PMP) specialists worldwide. He is the Secretary General of the Peritoneal Surface Oncology Group International (PSOGI) and a pioneer of the HIPEC (Hyperthermic Intraperitoneal Chemotherapy) therapy, or the Sugarbaker procedure.
Note: The statements and opinions contained in the video and the podcast episode are solely those of the speaker.
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Please tell us more about appendix cancer, its causes and symptoms.
Appendix cancer is very different from its first cousin, which is colon and rectal cancer. Remember, the appendix is a very small diverticulum that comes off the first part of the large bowel. But the disease is extremely different than colon cancer, and the reason is anatomic. The tumor in the appendix grows slowly over the course of time, the appendix makes a lot of mucus, and then you’ve got these cancer cells mixed with mucus. And what happens? You get a blowout. You get an appendicitis-type situation, but it’s not infection that causes the appendix to blow out. It’s a tumor. And it used to be, 30 years ago, when you had this rupture of an appendix with a mucinous tumor in it, it used to be that the survival was zero. Not zero, but double zero. Nobody survived. What we call peritoneal metastases are spread throughout the abdomen and pelvis.
Unknown to most people we have made huge progress in the management of appendiceal malignancy. So, as in the past zero patients survived, we’re now looking at about 75%. We’re looking at a very large number of patients with a new surgical technology; we call it cytoreductive surgery. And then there’s chemotherapy washing of the abdomen and pelvis after the surgery. We call that HIPEC or hyperthermic intraperitoneal chemotherapy. My data would show that about 75% of patients can be cured of this disease. So, there is a huge improvement in the treatment of appendiceal cancer. And I would contrast that to colon cancer, whereas the survival is now longer as a result of special treatments. In the end, the cure rate is just about the same. But we’re talking now about people who are alive 20, 25 and 30 years after the treatment of peritoneal metastases from their mucinous appendiceal malignancy.
So, the cause is different. It’s a blowout of a naturally occurring diverticulum, and its treatments have changed remarkably and the salvage is just incredibly different now than in the past. And why don’t we get more press about it? Well, because only one in a hundred colon cancers are in the appendix. So, we haven’t gotten, I think, the credit that the appendiceal malignancy patients or the appendiceal malignancy physicians should get in their new treatments for this disease.
How is it diagnosed and what are the risk factors for appendix cancer?
There are no special risk factors. No special risk factors except that everybody is at risk, just like everybody’s at risk for appendicitis. Why some people get these mucinous tumors in the appendix and then you have this blowout with mucinous tumor being spread throughout the abdomen and pelvis, I don’t know.
The first part of the question about diagnosis is pretty straightforward. For the most part, over half the people, they just get a big abdomen. They get distended. It’s often referred to as the „jelly belly“. And the jelly belly is just a buildup of this mucinous tumor within the abdomen and pelvis. Now, another rather substantial proportion of patients, about a quarter of the patients, they have an appendicitis. But, unfortunately, it’s not a routine appendicitis where you remove the infected organ and the patient gets better. It’s an appendicitis, but it is accompanied by this leakage of mucinous tumor into the peritoneal space. And so that’s the second important symptom. The third one is really very interesting, and that is a new-onset hernia. Many patients will develop a bulge at their belly button, at their umbilicus, or a bulge in the inguinal region often referred to as an inguinal hernia. And this is the mucinous tumor making its way into this small defect and expanding, and the patient goes to their physician saying, „Gee, I’ve got, I’ve got this bulge“. And the surgeon will say, „Oh, well, it’s a hernia“, and then he’ll operate. But then as soon as he begins to extract the sack, sometimes liters of this mucinous fluid will come out. And so those are the three major symptoms that are associated with appendiceal malignancy.
How can appendix cancer be treated?
The treatment for appendix cancer, this is the mucinous epithelial malignancies, is from its theoretical point of view extremely straightforward. In actuality, it’s quite complex. So, the treatment is complete removal of all visible evidence of the disease from the entire abdomen and pelvis. It sounds simple, but it’s not. Because the tumor has made its way into all of the peritoneal spaces. So, in order to do this complete cytoreductive surgery, that’s surgery to remove the tumor down to the cellular level, we have to strip the peritoneum from the undersurface of the right and left hemidiaphragm, from the paracolic sulcus, the areas on the side. We have to remove all of the peritoneum from the pelvis. So, we have these five different peritonectomy procedures.
Peritonectomy procedures were actually invented in order to treat the mucinous appendiceal malignancies and weren’t really described before that. The tumor doesn’t stick to parts of the abdomen and pelvis that are in motion like the small bowel. So, the small bowel is for the most part spared. We say it’s relatively spared. But then there’s portions of the small bowel that don’t move like the entrance of the stomach to the duodenum and the ileocecal valve region are where the small bowel connects into the large bowel and then way down in the pelvis where the colon and the rectum come together. So, very often you must combine these peritonectomy procedures with rather extensive visceral organ resections.
Not enough. You do a big surgery, it’s a big abdominal incision. Sometimes this surgery will take 12 hours. OK, you have to have a fairly strong surgeon and you have to have an even stronger patient to tolerate that. Following this complete removal, we lavage the peritoneal space, usually for 90 minutes. Now there’s a number of different HIPEC treatment regimens, but for the most part there’s a 90 minute lavage of the entire abdomen and pelvis, especially the bowel surfaces are what we call the visceral peritoneum, and we would basically wash the abdominal and pelvic spaces with chemotherapy. It’s a very diluted chemotherapy. Our goal is to get rid of any free cancer cells that have been left behind.
You know, it’s the old saying: „It’s what the surgeon doesn’t see that kills the patient.“ OK, so we’re going to try and not leave any of these mucinous tumor cells behind. So, we do the peritonectomy procedures, and that’s followed by the visceral resections, and then that’s followed by a HIPEC or hyperthermic intraperitoneal chemotherapy. Then we put everything back together and we hope against hope that we don’t have any complications. And usually we do not. We have about a 1% mortality now with this big 12-hour surgical procedure and about a 10% serious complication rate. So, we’ve learned a lot over the last 30 years. We can treat this disease very effectively.
What is the most frequent question asked by patients about to undergo treatment for appendix cancer?
Well, of course they want to know: Are they going to go through this big surgery and the chemotherapy and be in the hospital for ten days to three weeks and is it going to profit them? And so it’s extremely important that a very careful preoperative workup takes place. So, you can look the patient in the eye and you can say, based on a review of the pathology, is it a low grade, easy to remove or easier to remove, or is it a high grade, and probably these visceral peritoneal surfaces are going to be involved. You’ve got to carefully review the histopathology, and the patient should ask, and if they don’t, I’ll tell them, you have a low-grade tumor or a moderate-grade tumor. Or, you know, the appendix, a perforation can occur at any time. It can occur early in the course of the disease where you’ve got low-grade cancer, or the appendix perforation can occur later on. This is the Perforations and Mutations Hypothesis. You can have all different grades or all different invasive or noninvasive cancers.
Histopathology or what the pathologist sees on the slide is very important to us. Then, CT scan. We have learned a tremendous amount about the preoperative CT scan and which patients, based on this radiologic study, are likely to have a complete cytoreduction and have this 75% chance of being alive and well at 20 years. 75% chance of being alive and well at 20 years versus maybe only 25% if it’s a high-grade disease.
So, I think that the most important question that the patient needs to ask is: „What are my chances? What are my chances if?“ And then we also have to realize that in a disease like this, where a lot of experience and a lot of technical skill are required, maybe the patient wants to ask their surgeon and their oncologist: „What is your track record with this? How many have you done?“ And: „Have you published your results so that, you know, you have undergone a peer review of your treatments?“ And not so many groups have had the discipline to do that. So, if I were a patient, I would certainly want to ask my surgeon and the oncologist who’s cooperating in these treatments: „What’s your track record?“
What is pseudomyxoma peritonei and which role does it play in the context of appendix cancer?
Pseudomyxoma peritonei: It’s a complicated term, isn’t it? It’s stuck around because it tells us a lot. It’s pseudo, it’s kind of a pseudo-tumor. Is it like other cancers? No, it’s a pseudo-tumor. Pseudomyxoma. It’s myxomatous. It’s like the mucus that comes out of your nose, but unfortunately the mucus is contaminated by these low-grade cancer cells. Pseudomyxoma peritonei: Where is it? It’s spread all over the spaces within the abdomen and pelvis. So, it basically is involving sometimes all of the peritoneal surfaces, and we’d like it to be all those peritoneal surfaces except the ones that are in motion. The small bowel, the stomach, the colon surfaces which keep themselves relatively clean and allow us to do a huge surgical procedure, which in three months to six months afterwards the patient is back to normal because we have not had to remove large amounts of what keeps us going on this earth. And that’s the gastrointestinal tract.
You have to talk about pseudomyxoma peritonei when you’re talking about appendiceal malignancy. Remember, we said that the appendix is anatomically unique. It’s different from all of the rest of the large bowel. So, the tumor, as it mutates, and the molecular biologist, they tell us that it’s over 80 mutations in order to go from a benign tumor to an invasive tumor that can go into the lymph nodes and to the liver and then all over the body. So, what is pseudomyxoma? Well, pseudomyxoma is a blowout of an appendiceal tumor that’s just getting started. I don’t know how many mutations the pseudomyxoma will have. Probably only a few hostile mutations. Whereas an appendiceal adenocarcinoma will have over 80 hostile mutations.
Pseudomyxoma peritonei is an appendiceal tumor that has a blowout. The wall of the appendix has been breached by this appendiceal tumor. A very, very low-grade, minimally invasive and usually not invasive at all tumor. It’s just gotten itself spread around the abdomen and pelvis because it grew and it burst and it breached the wall of this very thin diverticulum that we call the appendix. Pseudomyxoma peritonei can have a huge volume of tumor, and yet with peritonectomy and visceral resections and HIPEC, we can cure about 85% of the patients with pseudomyxoma peritonei. Now, there’s one precautionary note. What really hurts us is patients who’ve had a lot of surgery but it was not completely removed, and then the pseudomyxoma gets caught in all the little nooks and crannies and scar tissue and the like. So, what’s happened prior to a definitive cytoreduction will have an impact on the long-term outcome.
Is an appendectomy recommended as a preventive measure to avoid appendix cancer? If so, do you expect that it will be possible to remove the appendix routinely during a colonoscopy in the future?
The answer to both of the questions is no. A prophylactic appendectomy just doesn’t make sense, with one exception. If you have an identical twin who has had an appendiceal malignancy, then you should have a prophylactic appendectomy. Because the likelihood that you, as an identical twin, will have that same tumor is extremely high. But the incidence of appendiceal malignancy is so low that you would have to remove literally thousands of normal appendix in order to help one person escape an appendiceal malignancy.
And then what about trying to remove the appendix colonoscopically? Well, I don’t know. I’ve done a lot of colonoscopies in my day. I don’t think I would like to try that maneuver. You can, of course, remove the appendix laparoscopically and very effectively. And a lot of surgeons will do a prophylactic appendectomy if they are in the abdomen for some other reason. Especially if you’re in the abdomen because there is ovarian cancer, because a lot of the ovarian tumors that we see actually come from the perforated appendix, and they settle out in the ovary. So, it’s a good idea for the gynecologic oncologist always to remove the appendix when they go in to deal with an ovarian malignancy.
Many thanks for your time and for the interview.