Harvey I. Pass, MD: What is Mesothelioma?

Harvey I. Pass, MD provides an in depth explanation of mesothelioma.  He also discusses treatments, advocacy and what is up with all of those lawyer ads?

The Group Room at the 14th Annual World Conference on Lung Cancer (WCLC) was made possible, in part, by:

 

VIDEO TRANSCRIPT

Selma R. Schimmel, Founder & CEO, Vital Options International:

This is Selma Schimmel for The Group Room at the 14th World Conference on Lung Cancer, WCLC, organized by the IASLC, the International Association for the Study of Lung Cancer; we are in Amsterdam.  And now we’re going to talk about mesothelioma; and probably some of you are saying, ‘that’s cancer?’  Yes, and we’re going to learn more with Dr. Harvey Pass: Vice Chairman of Research, Professor of Cardiothoracic Surgery and Chief of the Division of Thoracic Surgery at NYU, School of Medicine, NYU; NYU is in New York City, United States.  Welcome to Amsterdam.

Harvey I. Pass, MD, Dir., NYU Division of Thoracic Surgery, NYU Medical Center:

Thanks, Selma.

Selma R. Schimmel:

So, thank you for making time because I think this is one of the cancers that the public really doesn’t understand.  Because, you hear mesothelioma and the first thing you think about is the law firm that just advertised on television that, ‘if you have mesothelioma, give us a call.’  I think, if you have mesothelioma, before you call the lawyer, you need to call the doctor.

Harvey I. Pass:

That’s pretty much correct.  Priorities, you must think about your family but at the same time you have to think about yourself if you have mesothelioma.  And because, as you mentioned, this is a rare disease; this is a disease of only 3,000 people in the United States.  And people really don’t know enough about the disease and it is as devastating as any the other malignancies that we deal with, including lung cancer and pancreatic cancer.

Selma R. Schimmel:

What exactly is mesothelioma?

Harvey I. Pass:

It’s a cancer that involves the linings.  The linings are made of cells called mesothelium, so when they’re disturbed by asbestos or other virus types they will transform into cells that get out of control and you will then develop a constricting, thickening, fluid-filled area around your lung or in your abdomen that is very rarely detected early.

Selma R. Schimmel:

We understand that the greatest risk for exposure comes from asbestos and when the general public hears about this disease they associate it mostly with shipyard workers, people who work with brake pads… can you give us some more background as to the whole history of how we came to understand the disease and what is unique about asbestos fibers?

Harvey I. Pass:

Well, it really started in South Africa with Chris Wagner who showed that in the asbestos mines the workers were developing this malignancy in the belly and the chest that really hadn’t been described before.  Finally it was figured out that it was the exposure to the asbestos that was causing this disease in the mesothelium, mesothelioma.  And then, through a series of studies in the United States, in New York, it was shown that insulating workers also developed this disease.

Selma R. Schimmel:

What year are we talking about?

Harvey I. Pass:

Talking about the 1960’s, and then in the 1970’s we have data that insulating workers are developing mesothelioma in the belly in the United States.  And they were working with a type of fiber, and we then saw that we were under-diagnosing this disease and that it is indeed people who were exposed to asbestos, boiler makers, people who were in the navy, people who work in the construction, electricians, that we commonly think about for that population.

Selma R. Schimmel:

Certainly prior to the 60’s there were some kind of fibers that had been around for a long time.  What was this sort of disease perceived as much earlier than that?

Harvey I. Pass:

It was really mixed up.  I mean, if you look in the literature and you look at the pathology literature about this, they really didn’t even classify it as some sort of tumor.  I mean, they didn’t even know how to classify it.  Many of these were unclassifiable and they really… and if you look at the records of the Massachusetts General Hospital you won’t find the term ‘mesothelioma’ used until much later.

Selma R. Schimmel:

Is asbestos a natural fiber or is it a manufactured fiber?

Harvey I. Pass:

It can natural, of course, and it can be worked on.  And it can also be fibers that are asbestos-like that are natural that can then be mined or contaminate other things unknowingly.

Selma R. Schimmel:

If it is natural, what is asbestos?  Where does it come from?

Harvey I. Pass:

It comes from rocks, so it gets mined, so then it gets processed.  And, these fibers, when they get processed: different lengths, different sizes, different characteristics of their lining…  Same as fibers in Turkey that are like asbestos but they’re called erionite.  And they have the same sort of characteristics and they cause the same sort of disease but…

Selma R. Schimmel:

Turkey, as in?

Harvey I. Pass:

As in the central part of Turkey, called Cappadocia; where, because people have lived for centuries in houses, that the houses are built out of blocks from the mountains that contained erionite and they live in those houses that, there was this strange interaction between genetics and the fibers that one, in one house a family, 50% of the patients would develop mesothelioma while in another house nobody would develop mesothelioma.  So, some genetic link with a fiber and families, maybe.  But certain fibers have certain characteristics that will cause a reaction in the mesothelium to make certain pathways get turned on.

Selma R. Schimmel:

What about fiberglass?

Harvey I. Pass:

Fiberglass is not.  And, in fact, silicon dust or fibers do not cause mesothelioma.  And, in fact, when we do experiments we use those as the controls.  So, we don’t develop, or look at non-fibers that don’t cause problems.

Selma R. Schimmel:

So, asbestos is used in insulation, it’s used in boiler rooms, it’s used in ship yards, it’s used in tires, brakes rather…

Harvey I. Pass:

You’d be surprised, there are fibers like asbestos where you’d never even think of- insulation, you mentioned.  Well, how about potted plants? What does that have to do with this?  Well, it turns out that vermiculite is a type of material, that little puff-ball stuff that you put in for potted plants, it has to be processed, and it’s mined, and then it gets processed into plants, and it gets popped.  And it turns out that from certain vermiculite mines that were contaminated with certain fibers that can cause mesothelioma.  Now, the problem is vermiculite is used a lot for insulation, so there are hot spots that can develop all over the world.

Selma R. Schimmel:

Now I live in Los Angeles, so in certain homes or public buildings, it’s not uncommon, we call them cottage cheese ceilings and other people have called them popcorn ceilings, we think it looks a lot more like cottage cheese, and in order to have that removed you have to call in a licensed specialist and they have to test the levels and the potential home owner, let’s say, is not allowed to move in until those levels are safe.  But if you do not touch your ceiling my understanding is that you’re fine; it’s when you start touching the ceiling and those fibers become loose…

Harvey I. Pass:

That is correct, when the fibers become airborne… and that’s why you have people, like the government will, come in and actually do testing of individual places to see what the fiber analysis is of the ambient air and, if it’s of a certain level then that’s not good.

Selma R. Schimmel:

So, let’s talk about the cycle of this disease.  And, how does the disease present?  What drives the patient to finally go see their, let’s say, their primary care physician?

Harvey I. Pass:

Well, usually the patients present with a sudden onset of shortness of breath and maybe it won’t be sudden but over the last 4 months dad or granddad started to get short of breath and they can’t figure it out, and they used to be climbing mountains and now they can’t.  So they present to the hospital and they get a chest x-ray and sure enough there is a bit of fluid in the lung, around the lung, known as a pleural effusion, and needs to be looked into.  Maybe somebody thinks congestive heart failure or some other problem, maybe had a little bit of pneumonia, we’ll treat it with antibiotics and tap it and we won’t even, ya… And the fluid goes away, the patient feels better, and unfortunately that’s not the end of the story.

Selma R. Schimmel:

So, unlike many of the other related lung cancers that we’re discussing at this meeting over these days, this does not have the genomic or the genetic mutation component, this is really related to environmental exposure?

Harvey I. Pass:

That’s a great question and a great segue, I mean, indeed there are many genomic things that happen to these cells that are abnormal but to find one specific mutation like we have found in adenocarcinomas in certain populations, and then we can use tarceva, we haven’t found that.  We just find so many changes- we look at how many chromosomes are affected by the lesions or translocations or mutations and it’s all a jumble.  So we haven’t found specific targets yet but there are multiple, multiple changes.  There are some that are common but we haven’t been able to exploit those for either treatment or for early detection yet.

Selma R. Schimmel:

How do you treat the disease?

Harvey I. Pass:

That’s one of the big controversies.  Some people think that you shouldn’t even treat the disease and maybe if somebody even presents with mesothelioma and it’s early, maybe it’s justified to wait a little bit because we don’t know what is going to happen to that patient, because there’s varying biology.  Some mesotheliomas can grow very fast and some mesotheliomas are a little indolent, slow.  But the bottom line is the medial survival of this disease, if you don’t treat, is nine months.  So I’m a very proactive treater, and if you can combine elements of treatment in a multi-modality way, surgery, chemotherapy and radiation therapy, depending upon the patient, and the patient’s function, and how much tumor burden the patient presents with, and what the patient can tolerate, then for an early mesothelioma it would be good to think of chemotherapy either before or after an operation to try and remove the disease so you can’t see it, and then maybe some radiation therapy.  But unfortunately, only 15% of patients will present with that modus that is good.

Selma R. Schimmel:

What is the chemotherapeutic agent that you use for this disease?

Harvey I. Pass:

ALIMTA, pemetrexed, is the drug that has been shown to have a 40% response rate, which compared to some of the older drugs that we used to use before the big randomized trial that showed that, we had response rates of 10-15%.

Selma R. Schimmel:

Is there a metastatic component to this disease?

Harvey I. Pass:

There is.  The biggest problem, though, is local control.  The disease, even if you try to eradicate it locally, comes back 95% of the time.  But it can come back locally or it can come back systemically.  And in the later stages of the disease it can absolutely metastasize to the opposite lung, to the opposite pleura, to the abdomen.

Selma R. Schimmel:

I think what I’m trying to understand is that, if the disease is initiated by exposure, let’s say to asbestos or these fibers, logically you would think of it as an obstructive disease.  How does it transform itself into a malignancy?

Harvey I. Pass:

If we have another two days we could really figure that out.  What I can tell you is that there are a series of steps that asbestos will probably make the cell make certain secreted products that are danger signals that recruit other cells in that are trying to take care of it, and then those other cells will secrete things like oxy radicals, or free radicals, and then you’re making the cells a little bit different, they’re a little bit different, they’re a little stronger, they’re fighting the…

Selma R. Schimmel:

It’s a domino effect.

Harvey I. Pass:

That’s correct.  A series of genetic or environmental events that make these cells that should die from the asbestos… Asbestos should kill these cells; some of them do not die, they become stronger and then they create an inflammatory reaction which feeds them.  They grow more and more, they get a blood supply, and before you know it you are implanting your whole chest.

Selma R. Schimmel:

Doctor Pass, this is really scary.

Harvey I. Pass:

Well, that’s why we have to find it earlier.

Selma R. Schimmel:

How do you screen? X-ray, is a spiral CT effective?

Harvey I. Pass:

I wish.  You have so many people who are exposed to asbestos, we don’t have… we can’t… it’s very difficult to ask somebody, ‘what was your asbestos exposure?’ unless somebody works in the industry.  And we’re seeing some people who don’t work in the industry are getting mesothelioma for some reason.

Selma R. Schimmel:

I understand also that children, as an example, whose parents may come home and it’s on their clothes… what is the frequency of that kind of spread, you know secondary exposure?

Harvey I. Pass:

Absolutely, it’s actually the wives of, first of all, the men who worked in the plant or worked in the navy and bring home the clothes and then they wash the clothes, or work in the brakes… you know, or an auto mechanic and they brought home the stuff… and the wife will develop mesothelioma and not the man- so why is that?  Why is she more susceptible?  So there may be an underlying element of, you can fight it to a certain extent because the certain genes that you’ve got… and she didn’t have the genes, he did, to fight it, so who, how do we figure that out?  So, how do we figure out the risk population?  And then how do we screen for it?

Selma R. Schimmel:

So, while we understand the lungs and the lining of all these tissues in the upper airway, upper chest… where is the esophagus in all this?  Will it relate to the esophagus or think of the esophagus as upper GI?

Harvey I. Pass:

Why don’t we get mesothelioma in the esophagus?  I mean, you know it’s funny, you inhale, it comes in, you swallow… what happens to the esophagus?  It’s obvious it doesn’t get affected mainly because that’s not mesothelium.  So this is a targeted bombshell to a certain type of cell that seems to be more susceptible to these fibers than others.  And that’s where we have to figure out what makes this so susceptible and how do we take care of that?  But, maybe you swallow the fibers, the fibers go into the stomach and then they translocate out into the abdomen and maybe you get an abdominal mesothelioma.  So, and certainly it’s 90% pleural, 85-95 pleural, now 10% abdominal and then the rest found other places.  So, the pathogenesis of the disease is asbestos; how it gets to its place is extraordinarily interesting by migration and lymphatic channeling, but the bottom line is we can spend all day on that.  We got to figure out how we got to treat this disease.

Selma R. Schimmel:

What is in the pipeline?  Where is research taking us?

Harvey I. Pass:

Something like this- I mean, you have to start at the beginning.  First of all, how do you define how you’re going to find this disease early?  Because, certainly to operate, the chemotherapy people who deliver see that patients who are treated early seem to have an afferent effect and live longer.  So you need to find some non-evasive way.  So we’re looking at blood biomarkers, like many people at this conference have presented terrific work with looking at markers in the plasma or the serum, to try and find something that becomes elevated that should not be elevated, that says something is brewing, you need to move on to the next step and maybe get a CT scan to see if you’re got something going on; so, that’s for the early,  For the already diagnosed patient, obviously if a patient is not a candidate for treatment you must palliate that patient.  There’s a real, you have to make the patient comfortable- take care of the effusion, take care of the pain, but for the patients who can be treated, then you make the decision as to whether they’re going to get only chemotherapy or whether they’re going to participate in a clinical trial or whether they’re going to get a combination of therapy.  We’ve heard, mainly at this meeting, of combination therapies, and the idea of giving therapy before and then operating and then therapy after.

Selma R. Schimmel:

I want to mention an organization because I think it’s just about the only organization that’s out there to support patients with mesothelioma and their families- it is the Mesothelioma Applied Research Foundation, based in the Alexandria, Virginia area.  Research, education, support, advocacy- pretty important, isn’t it?

Harvey I. Pass:

MARF- is really the organization for advocacy as well as for research grants, has been and continues to be, has now elevated itself to be involved with all the major medical centers and provides an incredible service.

Selma R. Schimmel:

What is the story with the law firms, because as a general consumer or as someone who watches television or hears the radio, I’m very concerned that what it’s become a mercenary opportunity rather than the urgent need to treat?

Harvey I. Pass:

Here are my feelings about that; I think you’re absolutely correct.  I think that there are degrees of PR that is seen. On the other side, I think that there is some effort though.  These are elderly individuals, these are people that have worked hard and saved their money, what little they had, and now their families are going to be left behind and they’re going to need to have some way of surviving in the future.  So in reality, to a certain extent, as we see the corollary in the tobacco industry sometimes, that there needs to be advocacy for those patients that are truly injured so that their families will not be left with a tremendous health bill and will be able to be taken care of.  And in fact, there are foundations that have been set up by these law firms that try to support research and try to unite investigators; and so, as with anything, there are all degrees, but I agree with you that a little less commercialism may go a long way.

Selma R. Schimmel:

I’m wondering if there would be the chance to think about renaming the disease, rebranding this as a cancer in the minds of the public because, again, people have heard of mesothelioma; I don’t think the average person understands that it is actually an oncologic condition.

Harvey I. Pass:

I have to agree with you because the majority of patients who will present when they get the diagnosis of mesothelioma, do not know what that is and maybe that’s the part of MARF and us as investigators to educate, not only them, but the public about that this disease exists and this disease is more common than you think.

Selma R. Schimmel:

I’m really happy that The Group Room could help raise awareness for the general public of this disease that needs a whole lot more attention.

Harvey I. Pass:

You’re right.

Selma R. Schimmel:

Thank you, Dr. Harvey Pass: Vice Chairman, Research Professor of Cardiothoracic Surgery and Chief of the Division of Thoracic Surgery at NYU, New York University, School of Medicine.

Harvey I. Pass:

Thank you.

Selma R. Schimmel:

Thank you.

END OF VIDEO

 

 


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