Sam is joined by Dr Meera Patel to talk about her research into the spread of bowel cancer to the peritoneum. Meera is an Academic Clinical Lecturer at The University of Manchester and a trainee bowel surgeon, splitting her time equally between her academic medical research work and her clinical practice treating patients in the Northwest of England. Sam and Meera discuss what the peritoneum is, how cancer can spread there and how it’s treated. Meera explains her research into the connection between this spread, bacteria, and the microbiome.
Peritoneal Metastases – Manchester Cancer Research Centre
Transcript
Sam
Welcome to Can I Butt In, the Bowel Research UK podcast where we welcome bowel cancer and bowel disease, patients, researchers, healthcare professionals and carers to butt in and share their experiences. We’re picking a topic every episode and getting to the bottom of it. I’m your host, Sam Alexandra Rose. I’m the Patient and Public Involvement Manager at Bowel Research UK, and as a patient myself, I’m excited to bring more patient and researcher voices into the spotlight.
Welcome, everybody, to another episode of Can I Butt In! This time, we’re talking all about research into the spread of bowel cancer to the peritoneum. With me today is Dr Meera Patel. She’s an academic clinical lecturer at the University of Manchester, working within its colorectal and peritoneal oncology research group at the Manchester Cancer Research Centre. She’s also a trainee bowel surgeon, splitting her time equally between her academic medical research work and her clinical practise treating patients in the North West of England. So hi, Meera. Welcome to the podcast!
Meera
Thanks very much. Good to talk to you.
Sam
Today we’re talking about the spread of cancer to the peritoneum. The first question that people are going to have is: “What is the peritoneum and what does it do?” So please, fill us in.
Meera
OK, so I like to think of the peritoneum as a lining. So, it’s like a continuous, almost a clingfilm-like lining that lines the abdominal and pelvic spaces and it covers most of the organs as well. Its function primarily is to support and protect the internal organs, things like the abdomen and pelvis. We refer to it as a barrier, so physiological barrier in response to inflammation, infection, and trauma. So, for example, in appendicitis, the peritoneum would generate an immune response. So as well as being a physical barrier to bugs, the peritoneum can respond to bacteria and start an immune response so it can produce immune signalling proteins to fight infection. It also produces a fluid, so it’s called, this is called peritoneal fluid and that circulates around the abdominal and pelvic spaces. This fluid contains immune cells as well as supporting the immune function of the peritoneum. It also acts as a lubricant, allowing the internal organs to move and function. So, it is a complex structure. The peritoneum is more complex than we appreciate, and it has a lot of other functions like tissue healing and scarring. It will certainly have a role in the detection of cancer cells or threat of cancer cells in the peritoneum.
Sam
Right. Thanks. That’s all really interesting to hear about how it has its own immune system and has, like a really important function in the body, but lots of people might not have heard about it before. Bowel cancer then can spread to the peritoneum, which is what you’re researching and what we’re talking about today. Does other cancer also spread to the peritoneum and does cancer start in the peritoneum as well?
Meera
Yeah. So, I’ll do your first question first. So, other cancers can spread to the peritoneum. The most common are ovarian and stomach cancer and then bowel cancer. So other cancers that are sort of from the gastrointestinal tract, that can spread to the peritoneum are also, cancers of the appendix, the pancreas, the bile duct, and also the kidney. Cancers from outside of the abdomen can also spread to the peritoneum such as breast cancer and also melanoma. You can get primary cancers of the peritoneum. They are quite rare. And then, you know, if we look at the incidence of those cancers of peritoneal metastases, it’s difficult to quantify it really, they’re not accurately recorded as such.
Sam
Oh, ok.
Meera
So, in terms of estimating the true incidence of peritoneum metastases, it’s difficult because it’s not captured by national cancer registries. Though we know from published cohort studies in bowel cancer that about 5 to 10% of patients will have peritoneal metastases, diagnosis of bowel cancer. And up to 20 to 25% with recurrent bowel cancer. So, patients who have already been treated for bowel cancer will develop peritoneal metastases. And those percentages are unfortunately much higher in people who die from bowel cancer. In ovarian cancer, the percentages are somewhere over 60% and in stomach cancer, the literature suggests anywhere between 15 to 25% and that depends on the type of stomach cancer it is.
Sam
Right. And I guess things are quite close together, aren’t they? In the abdomen, organs are all quite close together. Is that why the spread happens?
Meera
Yeah, I mean, most certainly that is one of the theories between behind why; it develops through the proximity of the peritoneum and the shedding of cancer cells from the primary tumour, shedding of cancer cells into the peritoneum and the attachment of the cancer cells to the peritoneum and then the development of the metastases. And one of the other theories is the spread of tumour cells when we’re actually removing a primary tumour. So, when we cut through blood channels and lymphatic channels, that can result in spillage of the tumour cells as well. That can then implant into the peritoneum. But I don’t think we have an accurate, a truly accurate understanding of how peritoneal metastases develop and how they spread. And I guess this is where our research, this is something that our research tries to answer.
Sam
When cancer does spread, or when cancer is in the peritoneum, how do you get rid of those? Can you do surgery on that area or is it more sort of chemo, radiation?
Meera
Yes, so in the context of bowel cancer, it’s certainly a multidisciplinary challenge. And it depends on the extent of the peritoneal disease and what the aim of the treatment is. And in most patients, in many patients, it will involve some type of chemotherapy as you’ve said. And in some patients with peritoneal metastases from bowel cancer, they would be offered cytoreductive surgery and HIPEC surgery. This type of surgery aims to remove visible tumour with involving the peritoneum combined with the delivery of HIPEC, which stands for hypodermic intraperitoneal chemotherapy.
And it should be mentioned that not all people with peritoneal metastases will be suitable for this type of treatment, and it will be a select few that are where it is appropriate. I think it’s important to appreciate that patients and people with peritoneal metastasis often have a lot of symptoms, and I’d say, you know, from my experience, more so than people who may have spread to other sites, such as the lung or liver, and it’s not uncommon for people to experience abdominal pain and nausea, develop bowel obstruction, inability to eat enough, and a lot of those symptoms are difficult to control. And there is obviously often a huge psychological impact. Same thing with this. In people who have, to come back to your question about treatments, in patients who have more advanced peritoneal metastases, or in those where standard treatment has not been effective, the focus of their care will often be on trying to control these difficult symptoms.
Sam
You mentioned the sort of mental impact there. Does that also tap into having this multidisciplinary team looking after these people? Is there that psychological support available for people with this condition?
Meera
Yeah. So, I mean there will be care; these people will be cared for in a wider multidisciplinary team and there will be, they’ll be very closely supported by cancer specialists, oncology nurse specialists, you know, palliative care teams and nurses, consultants, and existing clinical pharmacology as well.
Sam
And then, are there people who-obviously you have a particular interest in the peritoneum-are there people on the team who specifically specialise in the peritoneum?
Meera
The research that I’m doing is closely linked with patients who have cytoreductive surgery and HIPEC at Christie. And the team there is led by – it’s a multidisciplinary team. From the surgical side, you have consulted colorectal surgeons with a specialist interest in treating cancers that affect the peritoneum as well as oncologists and specialist peritoneal – there’s a specialist peritoneal tumour service that’s supported by specialist nurses as well who are really experienced in caring for patients who have peritoneal metastasis.
Sam
Do you think that there’s barriers or difficulties in treating a patient or treating the cancer in the peritoneum that might not be present in other cancers?
Meera
Yes. So, we know certainly in bowel cancer that treating peritoneal metastases is challenging. We know, and this is really supported by clinical trials that have looked at the effectiveness of chemotherapy. And when you compare peritoneum processes to say lung or liver, there’s certainly a difference. This may be due to penetration of chemotherapy into the peritoneum or as I mentioned, people often have symptoms which could lead to interruption of their treatment plans or intolerance or malnutrition, and being able to complete a treatment. And I think some of the challenges are identifying the best combinations of the different chemotherapies that are available, whether we’re talking about standard chemotherapy or in combination with surgery. And I think those challenges are closely tied in with the research needs in the field. I think if we can expand the understanding that we have of how peritoneal metastases develop and how they spread and the processes leading up to them, I think it’d open up more avenues, particularly in how we approach the treatment and in the combinations of treatment.
Sam
Well, that leads me nicely into my next question then, which is just to tell me about your research. What is it that you’re looking at specifically?
Meera
My research is focused on peritoneal metastases from bowel cancer, and we are interested in looking at what we call intertumoral microbiota. Or specifically, the bacteria that are found within tumour samples of peritoneal metastases samples. So, these bacteria may inside the cancer cell, outside your immune cells, within the tumour itself. And what we’re interested in is how these bacteria may contribute to the development and spread of peritoneal metastases. And specifically, we want to understand: how, what changes do the bacteria produce within the tumour to encourage spread of the cancer cells?
So, we know there are studies already that have looked at the presence of bacteria within other tumour types. So, for example, breast cancer. And we know that majority of tumours, you will have some kind of bacteria within them. And so what we want to know is, and what we’ve seen from our earlier results is that there are bacteria within peritoneal metastases. How do they contribute to the spread of tumour cells and what are the specific changes that occur within the tumour caused by the bacteria?
Sam
That’s really interesting. So, does that mean that tumours that can be found anywhere in the body, do they all have their own microbiome?
Meera
Yeah. So, I’m not going to say all because I can’t say that with certainty, but there are many types of cancer that have their own intertumoral microbiome, or the number of bacteria that are present within the tumour. And just off the top of my head, for example pancreatic cancer, breast cancer, lung cancer, these are just some of the other cancers that have been shown to have a microbiome within the tumour.
Sam
So if there’s this bacteria in the tumour then, and I’m guessing that there’s still so much to learn and to research in this area. But that makes me wonder, could that bacteria that’s in the tumour, could that be something that is then targeted with treatment in the future? Is that a way for you to target it specifically and to get rid of it?
Meera
Yeah, I mean that’s a really good question. And you know, if you think about it very simply, yes, there’s no reason why you couldn’t attempt to target the bacteria if you’ve found – if you have enough evidence to show that targeting it will help the process, or slow down a process or prevent a process. Probably not at that stage yet but certainly, it seems really sensible to think along those lines and to think “Well, if we were able to identify one, two, or maybe more bacteria that were clearly causing changes within the tumour, negative changes, things that were causing that tumour to spread or change”, then targeting the bacteria stain with an antibiotic, for example, seems a very sensible thing to do. But yeah, that’s certainly further down the line. That’s, you know, that is what we’re thinking.
Sam
Yeah. So the bacteria that’s in the tumour, is that a bacteria that you would also find in the gut microbiome? And what’s the relationship? Again, it might be too early for this, but if you can, what’s the relationship between the gut microbiome and the bacteria that might be found in the tumour? Can you see those changes happening in the gut microbiome? Therefore it could potentially cause cancer down the line. I know very, very big questions.
Meera
It’s a big question and I can’t accurately, scientifically answer that. But intuitively, yes, the two things should be linked. You know, what you have in your gut microbiome, which obviously refers to what is in the stool and the lining of the gut should reflect what is happening within the tumour as well. It should be an extension of what’s happening, but what we’d hope we’d be able to extract from the information in the tumour is: Which organisms in particular are contributing to the cancer development process or are important in the process of developing metastases? So yes, the two things might well be very intimately linked. Can I tell you definitely, that hopefully down the line, I’ll be able to tell you, “Yes, it is a reflection of your gut microbiome.” But yes, almost certainly, the two things will be linked.
Sam
Yeah, that’s such an interesting topic. And yeah, it’ll be really interesting to see as time goes on, what we learn about the gut microbiome because it does sound like a really important area that could potentially unlock a lot of answers.
Meera
Yeah, absolutely. I find the two things quite difficult to separate actually, and when you think about the bowels and the trillions of bacteria and then you think about bowel cancer and the mechanism and how it develops and how it spreads, I find it now very difficult to not think about well, “What is the role of bacteria in those processes, you know, we know there’s a lot of data about bowel cancer and the microbiome. Was it a healthy microbiome? But do we really understand how big bacteria contribute to metastasis? The development of an advanced cancer? I don’t think we really do and I think it’s really exciting time in this in this field.
Sam
Absolutely. So how’s your research going so far then do you feel?
Meera
It’s challenging, but things are progressing really well. We’re now at the stage where we’ve got pilot data, which we’re analysing, and the aim really is to expand. The Bowel Research UK grant has obviously helped us generate this pilot data. And once we’ve scrutinised it and really understood the important messages in that data, it will be fixed on this project. Make it bigger and get more funding, get more people involved.
Sam
So you mentioned before about having multidisciplinary teams and then also doing this research as well. How are you and your colleagues across different disciplines working together on this problem?
Meera
So as you said in the intro, I’m based as part of the colorectal peritoneal oncology research group that’s in the Manchester Cancer Research Centre. So, we are a group focused on peritoneal metastasis research, and we’re very fortunate to have expertise from different backgrounds working together. So we’ve got surgeons and scientists, oncologists, pathologists. And this project would not be possible without their input and support. This project specifically though is supported by Professor Andrew McBain, who’s a professor of microbiology at the University of Manchester. And he has over two decades of Michael Bryan research experience so it really, the project really benefits from his expertise. So, it’s just really to emphasize that the research itself is very much supported by a lot of different people, and it wouldn’t be possible without them. I think importantly, the relationship that we have with the Christie hospital and the colorectal and Parity Oncology Centre at the Christie is very important for this research. Obviously without patient samples from patients who’ve undergone surgery for peritoneal metastasis, this research would not be possible. And there really are very few places where this research can be done because of access to those samples.
Sam
Do patients need to go to a specific hospital when they have cancer in the peritoneum? Are there only a few centres that can deal with that?
Meera
Yes, so there are, like you said, only a few centres that can deal with it. There are two nationally commissioned peritoneal tumour services that deal with cancers to the peritoneum and appendix cancers but there are other centres throughout the country that do deal with peritoneal metastases from bowel cancer. So it’s not specific; the bowel cancer metastasis is not specific to the Christie, but we do deal with them there.
Sam
What research do you think should be completed in the future on this? Again, I think it’s a very big question cause this sounds like so much that there is still to do.
Meera
Yeah, a big question and I think this field of microbiology in cancer is going will grow and I think that bridge in cancer research, sort of between the host, the person and the microbiome, I think that is only going to grow and we’ll understand more and more what specific effects bacteria have on the development of cancer and the spread of cancer.
I think also, you know, we know from other cancers that bacteria, all the research that’s been done, that they may have an effect on treatments and on things like chemotherapy and how effective they are. And I think we need to start understanding in bowel cancer now whether there are certain bacteria within the tumour that can predict treatment responsiveness or a lack of response. I think that’s the direction I see things moving in; it’s certainly something that I’m interested in.
Sam
So more sort of personalised care then for individuals.
Meera
Yeah, yeah, exactly. And really seeing if there is a, what we call a microbial signature within the tumour that will predict how effective certain types of chemotherapy will be.
Sam
I also wanted to ask what it’s like being a trainee bowel surgeon and a lecturer because it sounds like a very busy life. So how is your time divided? I’m just interested in how those two things interact and help each other.
Meera
Well, you’re right. It’s very busy. It is challenging and it is like having two jobs. It requires an awful lot of organisation and time management and as much as you try to separate the two, you never truly can. You’re often dealing with issues from both sides on days when you should be doing the other thing, so it’s really, you know, it’s really enjoyable because as stressful as it can be, it’s a real privilege to be able to be in this position because I’m able to develop a really acute understanding of the issues that patients face and the problems and the deficiencies that we have in treatments that are available and then use the time that I’m spending in research to think about them and think about, “How can we look at this in a different way? What have we not looked at? Is this something that that we can look at in our group?” It’s a really exciting position to be in.
Sam
Yeah, it sounds like it’d give you a real advantage in both places. Yeah, to get those different perspectives.
Meera
Yeah, definitely.
Sam
Great. Well, the last question that I ask all of my guests is what final words would you like our listeners to take away from everything we’ve spoken about today?
Meera
I guess the most important thing is that this research wouldn’t have been possible without the funding that it’s received. So, obviously the support that the listeners and the public and providers for Bowel Research UK is pivotal to this kind of research. And particularly for me as a early career researcher, this has given me a platform to be able to share it and to be able to promote the research and to grow it, and that really is something that I’m really grateful for. So, I guess just a thank you for all of the support and the support from Bowel Research UK.
Sam
Wonderful. It’s been really interesting chatting to you today, Meera. Thanks so much for coming on the podcast.
Meera
Thanks for having me, Sam.
Sam
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