Good evening everybody. Welcome to the webinar vets on a lovely sunny Thursday night. Thank you ever so much for tuning in, and from my point of view, thank you to Webinar vets for asking me to speak.
It's always fun to do these sessions. My name's Owen Davis. I'm your speaker for this evening.
I'm an oncology specialist and I work in Bristol, at Highcroft Veterinary Referrals, soon to be Bristol vet specialists. And I've spent, I've been a vet for 18 years, I've spent roughly half of that in first opinion work and half of that in referral work. So this evening, in the background of the cost of living crisis, I'm going to give you some tips on, oncology without a CT scanner.
What can you do in-house? There's lots and lots of sexy, really exciting and very, very clever treatments that we can offer in oncology, like you have maxillectomies and right ricular mass resections, and surgical limb spare with endoprosthesis made through 3D printing. And we have CT scans and 3D reconstructions of CT scans and things like PET CT based on that as well and sentinel lymph node mapping and another CT based technology.
And then you can do treatments like chemo embolization, where under image guidance, you can cannulate an artery and deliver a high dose of chemo and block the artery off. And you have lots and lots of therapies like immunotherapies and small molecule inhibitors that we could employ. But probably the most important point I want to make this evening is that being a good oncologist is about none of these things.
The average referral I get is often quite a conceivably simple situation. For example, a canine mast cell tumour where some of the prognostic factors point in a good direction and some of the prognostic factors point in a bad direction. What do we do with this?
Do we worry about it, do we treat it with chemo? Well, we get the tumour, that's definitely a tumour, but the pathologist can't tell us which one. And after lots and lots of immunohistochemical staining, it's still a case where it could be tumour X, with a certain prognosis and a certain treatment, or tumour Y with a different prognosis and a different treatment.
And which one do we treat it for? Or you get the dog with lymphoma who for some reason, can't have one particular drug due to behaviour issues or comorbidities or costs, and you have to go off piste to kind of design a specially made treatment protocol for just that dog. So being a good oncologist is all about the details.
It's about putting together all the pieces of the jigsaw and ultimately making a judgement call. In a situation where very often there's little precedent or no recipe for dealing with this particular situation that you can find. Then after you've made that judgement call, you've got to take responsibility for it.
In front of the client and in front of yourself and your own oath as a veterinary surgeon. Now of course the clients are not going to comply with your recommendations if they can't understand you. So communicating is a really, really important part of the job.
You have to make clear to people who may not have a medical or biological background what exactly is going on and why exactly you are recommending what you are. And this spills into education. Because most people out there are not from a biological background, and they know that cancer is bad.
But they don't really know what it is. And I've heard about genes and cells and metastasis and stages and things like that, but they don't really know what they are. And let me tell you, if you can help people understand what's wrong with their pet.
That is half the way to making them feel a lot better about it. This is tremendously important and a very simple step we could do. So if we've made our judgement and we've taken responsibility for it, we've communicated our thoughts and educated our clients, we establish relationships based on trust and caring.
And I, I don't know if any of you have seen this study that was published last year about veterinary surgeons' perception of different specialities. In general, oncology did quite well. A lot of the other vets in our profession seem to have very positive views of oncologists, and I think myself and my colleagues are proud of this.
OK. It reflects the soft skills that we, that we work hard on. So the bottom line, ladies and gentlemen, is that fancy equipment and procedures are not necessary for being a good oncologist.
This evening, I'm gonna give you some tips on how we can deal with cases on a budget where we need to keep things in-house or referral isn't possible. We're going to concentrate a lot on staging because that's often the the step where you need specialist equipment to get the maximum level of information and how we can manage things like lymphoma, solid tumours, and mast cell tumours well, with less than the gold standard staging. Importantly, I'm not gonna leave the medical treatment alone, and I will talk about using injectable and oral chemotherapy in practise too.
So let's talk about a dog with lymphoma then, because a common referral request I get is this, I would like to refer this dog with lymphoma. Because we haven't got the facilities to stage him properly in-house. OK.
Let's explore the canine staging system. Stage one is just a single lymph node. Stage 2 is regional lymph nodes.
Stage 3 is generalised, or at least on both sides of the diaphragm. Stage 4 involves the liver and the spleen, and stage 5 importantly involves the bone marrow or the blood, or where there's extra nodal organ system involvement. Therefore, GI cases will be stage 5, skin cases will be stage 5, even without involvement of the blood or bone marrow.
And to stage a lymphoma case, you could do physical exam, haematology, biochemistry, urinalysis, image the thorax, image the abdomen, fine needle aspirates of the liver and the spleen and the other viscera if enlarged and take a bone marrow aspirate, and that's a very thorough staging. Because lymphoma will infiltrate organs insidiously, and you may see a little bit of alteration to their shape, as you see in these pictures, or you may see none at all, then you're going to need to take FNAs so things like liver and spleen, particularly, to see if they have lymphoma infiltration. And it's worth saying that there's a lot of vets out there in practise doing a great job with ultrasound, who could do this really, really well.
But do you want to do this? That's a different question. Because the information we have to hand from historical studies is that stage 1 and 2 cases do a bit better.
And the stage 5 cases do a bit worse. And the first thing to note is that stage 1 and 2 cases are pretty rare, and I'll develop this one in a minute. So if you think most dogs will be 34 or 5, well, it's only the stage 5s that seem to be different.
And here's a question for you. Just consider it, I don't need you to vote or anything. What would make you call a stage 5 case a stage 5 based on haematological involvement?
Do you need to see circulating cancerous lymphocytes? Or do you need to find cancerous lymphocytes in the bone marrow? Because please don't assume it's the same thing as this study here shows.
You had twice as many dogs had involvement to the bone marrow as had circulating malignant cells. And if we look at the data on which the studies are based. So sorry, the studies on which the data is based rather, you'll find that some of them call stage 5 circulating malignant cells, some of them have to have infiltration of the bone marrow.
So there's no standardisation. And if you have a dog with multicentric lymphoma, he's presented with one week of diarrhoea. Mildly thickened intestines, do you assume that you're stage 5 because of GI involvement, or do you assume that the GI issues are nothing to do with it?
Or do you go in and take gut biopsies to find out? So, stages were very difficult to actually pin down on a dog. And then in 2006, this study came along and it changed the way that I look at lymphoma staging, for one.
They, it's a very clever test. They were using PCR techniques to find lymphoma in the lymph node, and then they went to look for that PCR product in the blood. And they showed that 80% of stage 3, in inverted commas, lymphomas could actually be found in the blood as well.
And so the, it's the old adage, if you look harder for it, you're going to find it. The more you stage a dog, the more likely they are to be stage 5. And in this study, 80% of stage 3 cases came up as stage 5.
Let me tell you that this was using the PA test, a test that is limited by sensitivity. So it's likely that it's gonna be much more than 80% of lymphoma cases are actually stage 5. So the benefit to prognosis is minimal and the benefit to treatment decision is also minimal if you stage a dog, especially considering that they're almost all stage 5.
And you might be thinking, well, let's, let's just write off staging for lymphoma then, let's, let's not do it. And it's a little bit more complicated than that because I do recommend staging for lymphoma. And that's for reasons like this.
OK. This is a CT scan of a dog's liver. And you see the liver is very, very nodular where normally it would be smooth, and the liver's also very, very smooth.
This is nothing to do with lymphoma. This is the end stage of chronic hepatitis. This is a cirrhotic liver.
Now, the dog had hardly any elevation of liver enzymes and the dog was otherwise happy and healthy. But what if I was to give him drugs that are metabolised by the liver, for example, vincristine or doxorubicin. Do you think this liver's gonna handle them as well as a completely healthy liver?
I think I would have in effect have overdosed the dog had I used hepatically metabolised drugs. And this dog here, I'll play the the CT in a minute. You can see this is the spleen, OK, which should normally be on the left side of the body.
Keep looking at the spleen. See the spleen is a bit patchy and a bit swollen, and it stays underneath the dog all the way through. It's not kind of where it should be.
And when you look at the side view, you realise what's happened. Can you see that the spleen is lying on the, the ventrum of the dog really from cranial? The caudal And if you look at this picture on the right here, you can see the swirling where the mesasentry is twisted.
And the picture on the left with the red arrows, you can see the thrombus in the splenic vein. So this is a splenic torsion. And for whatever reason, this dog wasn't showing any clinical signs of it, but actually, it's a surgical emergency and needs to be addressed before any chemotherapy is started.
And then look at the lungs of this dog. Now, this dog had an indolent lymphoma, and it's one of the cases where you might not need to treat them. You tend to treat them if they have a high disease burden or they have clinical signs, and the dog was fine.
From the outside, I thought the dog had a very small disease burden because there were only 2 or 3 lymph nodes moderately enlarged, but then you look at the lungs and you see the amount of interstitial pattern there, there's actually most of the disease in the dog's lung, and that changed the treatment decision I made. So When you stage and you image a dog who's of middle age upwards. It's quite likely you're gonna find some comorbidities.
And as I've shown you, a lot of these comorbidities may change the way you treat your dog. So I think staging is very important for comorbidities. It's also very important for monitoring.
How will we know the cancer is remission in remission when treatment finishes if you didn't know exactly where it was to start? There's also a risk that if a dog has a very high burden of disease and if you start treatment or guns blazing, then the dog may get worse, before they get better because cancer cells are still the body's own cells, and they could create inflammation when they die. There's also a small risk of something that's quite rare in veterinary medicine, tumour lysis syndrome, which is characterised by electrolyte abnormalities, due to lots of cancer cells dying at once.
That's very rare, as I say, but it has been reported or suspected in a couple of cases. So that's all very good. Staging is what it is and it isn't what it isn't.
But coming back to our dog with lymphoma, if we want to maximise the return for our investment in the investigation of a dog with lymphoma, what tests do we need to do to find out whether he's one of the dogs who will live for a few months, or one of the dogs who'll live for a couple of years? Well, the first thing is make sure you're happy you're dealing with a peripheral nodal case. 85% of dogs with lymphoma have disease in their peripheral lymph nodes.
If you've got one of the 15% that hasn't, then you might find that their prognosis is relatively characterised and they're not gonna be so variable as having a few live some months and a few live some years. For example, the primary gastrointestinal cases or the dermal cases. So those tend to be quite well characterised and you may not need a lot of further investigation.
Now to the peripheral nodal ones, the first thing to consider is substage, OK? Whether the dog has clinical signs of disease at the outset. If you've not seen one of these Cavan Meyer survival graphs before, just talk you through it, have 100% of dogs alive up here, 0% alive down here against time.
So it follows that the dogs who have the best outlook will have a curve. Towards the right longer. And the dogs of the poorest outlook have a curve that gets down to 0 sooner.
So you can see two very different survivals of these two groups of dogs. Group A didn't have clinical signs of disease. Group B did.
Then you've got the immuno phenotype, whether they're B or T cell. And that I think is less important than the WHO subtype. The WHO subtype involves the immuno phenotype and also the histologic features of disease.
I'm gonna tell you a bit more about that in a minute. And you've got whether they're anaemic, hypercalcemic, or have a mediastinal mass, that will also affect prognosis. And then very importantly, something that we always forget.
The treatment we give, both the type and the amount, has a tremendously important effect on the prognosis. We don't think of treatment as a prognostic factor, but it really is, and it's something that we can control. So, how I approach canine lymphoma, I start by ascertaining the budget and planning.
And I'll discuss with the owner that compromises may be needed. I'll discuss the information which will change the prognosis and the treatment like substage, WHO subtype. And I'll discuss that if our dog's got splenic torsion or end-stage chronic hepatitis or an adrenal tumour that's eating into the vena cava, things like that, this is gonna be very, very useful information to know.
I'm gonna talk that we want to know if a dog's got a complete response to treatment, because then we might be able to stop treatment, or if they've got a partial response to treatment, in which case we're best to continue. So knowing where the disease is to start with is also important. And I discuss and illustrate with examples the benefits of staging these guys.
But I do tell the owners that ultimately we have to make a compromise. And it would be foolish to spend all the money on staging and not have enough left for treatment. So, I tend to make owners, I, I don't allow owners to feel bad if they can't afford the full staging.
Because often we have to compromise in all sorts of things in life, don't we? Have you not heard people, not least veterinary professionals say that they'd love to have more sleep, and they'd love to have a healthier diet and to spend time exercising more and stuff like that, and they have less stress. We are compromising with our own health sometimes when we work in very busy, stressful environments.
And eat food that's possibly not the healthiest and don't do enough exercise, etc. And if we deal with the, the health systems like the health system in the UK. That's also a compromise as well, and some of the best treatments may not be things that are actually funded.
So life is always about compromise and if people can't afford the staging or decide it's not for them. That's OK. As long as I've explained things OK and they fully understand the connotations of that.
Now just a side note here, I was telling you that the WHO classification of lymphoma is a pivotal importance. I'll just tell you a few more practical tips on that one. These are the types of lymphoma that are available, OK?
And it's based on histopathology. So if you diagnose lymphoma of the histopath, then just ask your pathologist to immuno phenotype with immuno histochemistry. And then apply the WHO classification and it's easy.
Now, a lot of dogs with lymphoma, I don't want to anaesthetize if it's just for a lymph node biopsy. So if I've made a cytologic diagnosis, you can play the odds to find what type of lymphoma is most likely. And in most cases, that's how I do it.
Playing the odds revolves around there being 6 most common types of lymphoma. These are gonna be well over 80% of peripheral nodeal lymphomas that you see. Three of them are aggressive, rapidly developing high grade diseases.
Three of them are indolent, slowly progressive, low grade diseases. 3 are B cell, 3 are T cell. So when you superimpose the grade and the immuno phenotype, you find that if a lymphoma is high grade and B cell, it's almost certainly diff fuselage B cell.
If it's low grade and T cell, it's probably T-zone. And the other categories have two types within them. You can often use clinical features of the case to separate these two.
And even if you can't, it doesn't make an awful lot of difference to the extent of these, these differences. So we need grade and we need immuno phenotype. Grade is principally something given to you by the histopathologist based on the mitotic count that they see down the microscope.
But a good clinical pathologist and good smears will provide a strong indication. We only want two categories really, low versus intermediate or high. And as far as we're concerned as clinicians, intermediate and high grade lymphomas will behave similarly.
And how do we get the immuno phenotype? Well, you've got a few choices. You've got flow cytometry, you've got PA test, and you've got immunocytochemistry.
And as you can see in this study here, flow cytometry agrees very strongly with histopathology, 94%, par test much less. So I would use flow if at all possible. Now let's look at our feline friends with lymphoma, and I've got a question for you guys to consider.
You have diagnosed a cat with lymphoma, what further tests do you think it's sensible to do now? Giving you some options. We've got FELV FIV.
They're getting the WHO stage. The WHO histotype. The immuno phenotype or the grade.
Have a think what ones you think are most important. Well, let's look at FELV and FIV. If a cat is FELV positive, they have a 62 times greater risk of developing lymphoma.
If they're FIV positive, they have a 5.6 times greater risk of developing lymphoma. Does this have an effect on the prognosis though?
Probably not. So once they've developed lymphoma, I'm not sure it makes a lot of difference at all, and there are now studies to support that. The only exception is if you have things like end stage of either disease where, for example, in FELV you may have a very dysplastic bone marrow and numerous blood dysgrasia that are unrelated to the lymphoma just because of the FELV.
Those guys may be find it much harder to withstand the myelosuppressive effect of chemo. And again, if you have the FIV positive cats with say end-stage renal damage or lots of cutaneous infections, that could be difficult as well. But in most cases, there shouldn't be a significant difference.
Then you've got the T cell or B cell thing, well, that actually doesn't make any difference as far as we can tell in cat. And if we build that into the histologic subtype. Here's a study.
The effect is actually very mild. We see two types of lymphoma in this study. Had a significantly better prognosis than all the others.
But it is a small study. And I'm not sure it is the actual histotype that's driving the better prognosis in these cases, it's the grade. These are the low grade diseases.
So it's the grade rather than the histologic subtype, which is most important in prognosis. The other thing with cats is that you can use the information you get for free. The anatomic site in which you find lymphoma in a cat often correlates very strongly with the type of lymphoma that you find there.
In some cases, there's a principally one type of lymphoma. For example, renal lymphoma in the cats is always a high grade disease. But gastrointestinal lymphoma has low grade and high grade diseases and a subtype of the high grade called the larger granular lymphoma.
So you may want to take the, the GI cases further. Stage, however, is not prognostic and does not, or hardly ever affects the treatment decisions. So in feline lymphoma, I think you need the grade and the anatomic sites.
And after you've got that, The only other thing you need is the response to treatment. Now, in many studies, response to treatment outweighs any other prognostic factor considered, OK? You want a complete response where the disease disappears.
Rather than a partial response where the disease gets better, but you can actually find it through palpation or through scans, etc. And that's the most important determinant that a lot of us write off. A lot of us think, oh, the cat's getting better, he's much happier now.
The lymphoma burden has got a lot less. Happy with that. What we want is to go one step further and make sure that we're getting that complete response.
So really grade anatomic sites and response to treatment are the key things you need. There's a big difference versus dogs here, that the T cell versus B cell, the WHO histotype, the substage, and the treatment that you use. Have not been shown to have an effect on prognosis.
Now, just like dogs, the cats with lymphoma are very often middle-aged and over, and it's quite probable they could have important comorbidities. Just like dogs, we want to know if the cancer's in remission when the treatment is finished, so we need to know where the disease is. And for cats, which is much more important than in dogs.
You do have a subset that could benefit from a local therapy rather than chemotherapy, OK? And I'm thinking here of things like nasal lymphoma. 80% of feline nasal lymphomas is just in the nose and not in the rest of the cat.
So we could send these guys for radiation therapy and radiation is a superb treatment for these guys. Lymphoma is exquisitely sensitive to radiation, and cats are very resistant to the side effects of radiation, so that is a great combination. You want to stage these guys as an insurance policy to not make sure you're missing the lymphoma in the abdomen.
But if you've got one of the 80% that's just in the nose, you can treat them with radiation, and hopefully they'll be in remission for another 18 months, 2 years, you could then break out the chemo when the disease comes back. On very, very rare occasions, you can get situations like this in dogs, but therefore often rare indolent lymphomas that are not affecting the dogs systemically, they're just in one area. In cats, this is much more common situation to deal with.
Let's look at the solid tumours now. Now the solid tumours are the sarcomas, the carcinomas, and the melanomas. OK, just like these here.
And I've got a question for you to consider. What is the benefit of using CT to stage these guys over X-rays for solid tumours? It shows increased extent of tumour.
Increased osteolysis, detects metastases at a smaller size. All of the above or none of the above. What do you think?
It's actually all of the above. First, CT is the best way of identifying the extent of a tumour. I suppose MRI would be one step further, but, CT is what we commonly use as a gold standard.
So, in, as illustrated here with injection site sarcomas, you can see this. For example, the, the tumour here, is extending right through the ribs into the thorax. Isn't that horrible?
And look at the picture in the middle where this horrible swelling on the side of the cat's flank is actually extending all the way around, into the groyne on the other side. These really are the most invasive tumours you'll ever find, an extension, is up to 100% greater on the CT. And then with oral tumours, CT is very useful for demonstrating osteolysis.
60% more osteolysis is revealed by CT and by radiography, and that can be very, very important in deciding where you cut the tumour and where you don't. And when you're looking for metastasis, CT wins as well. Radiographs will show you mets above about 7 millimetres in diameter, but CT shows mets above approximately 2 millimetres in diameter.
So, radiographs will show you mets this size on the left, but it's not gonna show you these. On the right. So CT is the gold standard and the most commonly used staging tool.
And I think we'd recommend a CT to plan the surgery for any large, ugly, aggressive tumour. Feline injection site sarcomas is a good example, but high grade soft tissue sarcomas in a dog or a muscular or subcuumangiosarcomas. Oral tumours, nasal tumours, head and neck tumours, pulmonary tumours, and hepatic tumours.
This is useful for surgical or radiation planning because it shows the full extent. It outlines osteolysis and vascular involvement. But for other tumours, which are not gonna be so, not gonna depend so much on the planning for the treatment, consider the specific way in which the CT information is gonna change the way you manage, manage the case.
Give you an example first with osteosarcomas. If a dog with an osteosarcoma has limb amputation, and then chemotherapy will expect him or her to live for 10 to 14 months. That is assuming that they're non-metastatic at diagnosis.
If they are metastatic and given the same treatment, the average survival is about 3 months. This is very important information, isn't it? This will often change the way the owner wants to play the game.
So it might make sense to think that if you diagnose CT mets on a CT it would be very useful. But the information on the metastatic cases having a much poorer prognosis is based on radiographs, radiographically large meths. So you could have a weird situation where you have mats of 3 or 4 millimetres in diameter, they'll show up on a CT but they're not gonna show up on a radiograph.
And for those cases that are non-metastatic on a radiograph but metastatic on a CT. We seem to find that they'll have a much better prognosis in the 3 to 4 months, as you might expect. To get the most concrete evidence in terms of what you do with a dog then, radiographs, as long as they're inflated and carefully positioned, well exposed, that should be enough.
A similar situation is for splenic hemangiosarcomas, much of the prognostic information is evaluated using radiographically visible nets. You do have a staging system for hemangiosars as I've got here. Stage one is a non-ruptured splenic tumour that's non-metastatic.
Stage 2 is a ruptured spleen or a large splenic tumour or with a lymph node net, and stage 3 is distant metastasis. But this doesn't really matter so much, providing you treat them with a doxorubicin-based protocol. If you see this graph down here, the survival curves of the stage 3 dogs with distant nets pretty much overlap and intertwine around the survival curve for the stage 1 and 2 cases without the distant net.
If you treat a hemangiosarcoma with a doxorubicin-based chemotherapy protocol, in other words, you will correct for a high stage. And then we've got anal gland carcinomas. Now, the first sight of metastasis is nearly always the sublumbar lymph node chain, as you see here.
If we try to outline sublumbar lymph node mets on radiography, it's really hard. Can you see it? I'm not sure I can, even if you zoom in.
But this dog here is the same one that I've just shown you with this huge cluster of metastatic lymph nodes. And CT is great because it can outline the cluster and shape of the lymph nodes and it can also outline in involvement of the other structures. So it's good.
And if you're staging a case of anal gland carcinoma, then, you want to know how we got mets in the lymph node, because in theory, you could do a cordal laparotomy and remove those lymph nodes, and that's been shown to be very beneficial in the prognosis. It kind of turns back time, if you like, to a non-metastatic state. And we often do that at the same time as taking out the anal gland tumour.
So finding these lymph nodes and deciding whether they're metastatic matters. And CT again is great because it can find out all these lymph nodes. And no matter what their size really, whether they're normal size or whether they're enlarged.
I've shown you that radiography is not very good, but ultrasound can also be used to find these lymph nodes, and this is well described. How does that compare to CT? Well, in this study, ultrasound detected 31% of enlarged lymph nodes, which sounds a bit rubbish.
However, ultrasound correctly identified at least one enlarged lymph nodes in all the cases of affected dogs. And that ladies and gentlemen, is enough. Because that will dictate what you need to do.
We will know in these dogs taking the anal gland tumour out itself out is not going to be enough. They will ideally need a caudal laparotomy and removal of sublumbar lymph nodes. And during the surgical exploration, hopefully any other enlarged lymph nodes could be identified.
And now let's look at mast cell tubers on a budget. Now mast cell tumours are complicated and frustrating, OK? Remember I said we had solid tumours, the carcinoma, the sarcomas, and the melanomas.
When solid tumours metastasize, you get other solid tumours. And then you've got what I sometimes call liquid tumours. These are the lymphomas and the leukemias and histocytic sarcoma, the cancers of the blood or the immune system.
And when these things spread, or should I say, infiltrate other organs, there's often very little change to the shape of the organs. Often there's no change at all visibly. And to find out whether they're, they've got infiltration or not, you need to take FNAs.
So we have two distinct behaviours of tumour cells, then you've got the solid tumours or the vernacular term liquid tumours. And what do you think mast cell tumours are? Do you think they behave more like solid tumours or the liquid tumours?
Well, actually, they do a bit of both. It's in the primary mast cell tumour setting, they behave like solid tumours. And we talk about surgery and margins and complete excision.
When Mar cell tumours metastasize, however, they behave more like the liquid tumours. That is, they will infiltrate organs insidiously, and the organ may not change invisible appearance. What is useful though is that mast cell tumours metastasize quite reliably by the lymphatics, to a draining lymph nodes and ultimately to the liver and spleen.
So I can give you quite a simple and effective approach to stage them. Assess the draining lymph node, assess the liver and spleen. That is the first stop in the lymphatic chain and then the last stop.
And this can be effectively done in practise, if you're competent with ultrasound and taking fine needle aspirates. Remember that these organs will look normal and can be effaced with mast cell disease. Some comments on doing this practically.
First, with a regional lymph node, remember that this lymph node may not be enlarged. Also, the draining lymph node is not necessarily the one that's anatomically closest, and that happens in 40% of cases, which is very, very annoying. So ideally if you're FNA lymph nodes, you could FNA more than one if feasible and safe to do so, and use ultrasound to help you do that.
Things like sentinel lymph node mapping exist to solve the problem and find a draining lymph node, but if we're doing it without a CT scan and on a budget, that's not gonna be possible. Now who X-rays chest for mast cell tumour staging? I certainly do at times, but please don't look for this.
If a mast cell tumour metastasizes to the chest, you'll almost never see other pulmonary nodules. However, Radiogram graph in the chest is justified to look for things like this, an enlarged mediastinal lymph node. So if the tumor's on the back half of the dog, I don't tend to image the chest.
If the tumor's on the front half of the dog, I will image the chest, but I'm looking for enlarged lymph nodes. I'm not looking for nodules in the pulmonary parenchyma. Now when you look for distant nets in the liver and spleen, I've got another challenge for you here.
This is a normal liver, which is a bit darker than the spleen. This is a liver that's brighter. And this is a liver that's darker and you can see it's darker because you can, the texture is actually darker than the billy tree here with the red arrows.
So which one of these three? Has metastatic mast cell tumour in it. Think to yourself.
Actually, it's all of them. And it's a spleen. And the spleen that's got this almost like mottled cottage cheese-like appearance here.
Which spleen has got Marcel tumour in it? Well, that's both of them as well. There's more than one study now showing that the sensitivity of ultrasound for detective ma cell infiltration was 43% for the spleen and 0% for the liver.
In other words, it missed 100% of cases in the liver. Therefore, you need to take cytology of these. It's not just the nicety.
In my final section this evening, we'll talk about using chemotherapy in-house. And this is another comment I often see on referral requests. I would like to refer this cat for treatment because we haven't got the facilities to treat him or her in-house.
Now if that sounds like something you, you might say, there's no shame in that, don't worry. What would stop you from giving chemotherapy in-house though? Is it that you haven't got a fume cupboard?
Haven't got the train star, haven't got special PPE personal protective equipment and a special room. Haven't got facilities, or it's just no one else is really interested. Which one of those?
Oh, There's plenty more to learn, but it's actually very easy. You can give chemotherapy very safely if you have 3 things in place. Use of personal protective equipment like chemo-tested gowns, chemo-tested gloves.
Use of a laminar flow hood, a fume cupboard. Or use a closed system transfer devices, OK? Now how many of you guys have got a few fume hood, laminar flow hood in your practise?
No, well, I certainly didn't in practise either. And you don't need one. The drugs should be drawn up in a laminar flow hood, but it doesn't have to be your lamina flow hoods and it doesn't have to be on your site.
You could buy syringes preloaded with chemotherapy drug and have them carry courier it to you like we've done here. So if you buy the preloaded syringes, you avoid the need for laminar flow hood, you just need the PPE which you can order in, and the closed system transfer devices which you can order in. Many companies will often supply these things along with the chemo in the same shipping package.
Here are closed system transfer devices, face seal at the top, on the left, and EuShield are two common manufacturers, other good manufacturers exist too. We tend to use face seal in my clinic. The idea with these though is it will stop drugs being aerosolized or spilled, and they're very, very protective.
They're great. I certainly wouldn't give chemo without these. And they're also very easy to use.
I'm gonna show you just how easy it is, in this two couple of slides here. First, you've got the vial of chemo that you're handling wearing chemo tested drugs, and you apply this special adapter on top. You have an adapter which fits onto a lure luringe as well.
And on the top of the adapter you have prongs a bit like a light bulb. You just push that into the top of the receiver. On the bottle, that's this bit here.
And you push in and twist like you would apply a light bulb. And then this blue stem here . Means that the contents of the syringe are separated from the contents of the vial.
If you push the push the syringe bit in so that the blue stem disappears, the contents of the syringe are connected to the contents of the vial and then you can draw the drug up. You have a special adapter that you attach to a dog's catheter. And then you have the flush.
With the lu lock, just connecting on the, the straight piece here. And you have the special chemo syringe with the adapter on the side connector, and it's like the reverse of what you've done. You, when the dog's settled and you're happy that the vein is, has been cannulated cleanly and there's lots of blood coming back and everyone's OK to proceed, you will just push the collar of the chemo syringe in so the blue stone disappears.
Like that, and now the chemo is connected to the dog. What you do is you push the, you empty the chemo syringe in. Then you'll flush.
Then you can flush some saline into the syringe and flush it out again into the dog. And there's lots of training videos made by the companies online showing you how to use these. Their reps are often very good at talking you through these as well.
So it's a very, very easy technique to master. The key bit is getting a first stick IV and making sure you have a relaxed and happy patient and a relaxed and happy person to assist you. Oral options for chemotherapy or cancer treatment exist as well.
OK. Metronomic chemotherapy is an interesting thing which is very, very accessible from all types of veterinary practise. This is using conventional chemo drugs, but at lower doses, often a 15th or a 20th of the dose, and those that would be used injectably.
And giving them every day at home. With this treatment, you're, the much lower doses will mean you're very much less likely to get gastrointestinal upsets or cause significant myelosuppression. This treatment doesn't directly target the cancer cells, it just makes the environment of the cancer hostile for them to live in.
So, as such, it's quite a broad spectrum treatment and is often used in a lot of solid tumour settings like sarcomas, carcinoma, melanomas. It's actually treating the angio angiogenesis, stopping the tumour, hijacking a blood supply of the host, and making the immune response more likely, or making the immune system rather more likely to make an anti-cancer immune response. So metronomic theory, metronomic therapy can be a very powerful treatment, very accessible.
And easier to use. But please don't think it's safer. It rather than injectable treatment, on the grounds of safety, it's not really in, not really valid.
Using drugs can cause sterile hemorrhagic cystitis, and actually it's more likely to cause sterile hemorrhagic cystitis, given like this than it would be if it was given as a pulse dose in a COP protocol. Things like lowmustine can cause hepatotoxicity as well, which can be very, very serious. The non-steroidals given as part of the metronomic chemotherapy treatment can also cause gastrointestinal upsets and renal damage, as we all know.
Metronomic chemo is also not safer for you and me giving it. In this study here are 20 veterinary specialist hospitals in the state, they did some environmental swabbing for commonly used anti-cancer drugs. They found no contamination.
With the injectable ones. But they found 4 out of 20 hospitals were contaminated with cyclophosphamide. And that's probably because cyclophosphamide is oral.
You can't contain it with a closed system transfer devices, and people are intrinsically less scared of oral drugs. And you get some people, you know who you are, who will never be beaten by a difficult cat. And if a cat spits a pill out, it's a case rights where you're making sure you get this pill, Sonny Jim, and you pick up the pill and you try to have another go at getting it in the cats, and the cat spits it out again.
And each time it gets spat out, it's a bit more soggy and a bit more flimsy and prone to breaking. And so we really shouldn't be doing this with, with cytotoxic drugs. Ideally, it goes down in one, or we wait, we let the cat chill and then we try a new pill afterwards.
But as I say, Metronomic chemotherapy can be very useful if used appropriately, and there studies supporting it using canine splenic hemangiosarcoma after splenectomy. Incomplete resected and gross soft tissue sarcomas. TCCs of the bladder, mammary tumours, thyroid tumours, lung tumours, and others.
In cats, it's less well established, but it has been used and I have found it effective in a few things in cats. Along a similar line, you have repurpose drugs like thalidomide. Which is a very, very strong antiangiogenic agent, and it's in dogs with splenic hemangiosarcoma, that weren't metastatic at diagnosis.
Thalidomide was given to them after splenectomy, and the dogs actually had a very similar survival time to that of a doxorubicin-based protocol. That's very interesting. And again, this is a drug that can be ordered in and dispensed very easily in practise.
And of course we now have the small molecule inhibitors. These have stemmed from knowledge of how the cells work and how the cell communicates and receives signals and brings these signals into action in terms of cell division and growth and maturation, etc. And these are all the pathways that have been linked to cancers in people.
We know what these molecules are, we know what they look like, and we can design other molecules to inhibit them. That's the idea behind things like palladia to serinib, and massive maitinib. We've got to erinib and meitinib are licence, but lots of other small molecule inhibitors have been used off licence at times.
And again it's an accessible treatment to be used in practise. If you're using them for things other than mast cell tumours, or you're using TKI's other than Taserinib and meitinib, but you're, you're off licence, so the owner needs to know about that as well. You also need to bear in mind that the mechanism of action is unknown and it's likely to be different, from case to case.
Objective responses have been reported in a growth setting in some tumours, not others, like thyroid, anal glands, some squamous cell carcinomas, etc. But there's been very, very disappointing results in things like hemangiosarcoma and osteosarcoma. They're also not a panacea.
The benefits are nearly always transient. Cancer cells have a lot of redundancy. They have a lot of molecular pathways that achieve the same goal.
So if you inhibit one of those, it won't be long before one of the other ones will just be up regulated. So in human medicine, they're often combined with other things, not least injectable cytotoxic chemotherapy, just to maximise the benefit they have. And the other thing, they, they don't kill cancer cells, they just change the behaviour of cancer cells so they can't be used as the cause, and they have no stopping point.
Furthermore, they've only been assessed really in the gross setting before a tumour has been removed. And biologically things will be very different after a tumour has been removed. So if you've done surgery and you're looking for an adjunct to that surgery, then we haven't, we've got even less evidence to support the use of these things.
Again, thyrosine kinase inhibitors and these small molecule inhibitors are not any safer than injectable chemotherapy. They can have some quite severe adverse effects and certainly lots of them have been described. So if we try these on the grounds of safety, then perhaps we're a bit mistaken, but there can be times to use them very appropriately.
And finally, in terms of these oral treatments I've described both the metronomic treatments, the thalidomide and the thyrosyinnase inhibitors or the small molecule inhibitors. Bear in mind the changes they'll make to their cancer cells. If we look at the cytotoxic chemo, for example, of course have been blastine or carboplatin.
The cytotoxic chemo will slowly reduce the cancer burden down to what we hope to be zero, OK? After each dose, the number it'll kill cancer cells. The cancer will start to repopulate in the interval between doses, but hopefully not get back to it's starting level.
And then you give another dose and the and the cancer cells reduce again and another dose and cancer reduces again, etc. With the TKI's or the metronomic chemotherapy or the thalidomide, the cancer cells aren't directly killed. So the cancer burden stays the same, just the cancer cells become less active and cause less of a problem.
So on the one hand, there's no clear point as to when these things could be stopped, and really they should be carried on. I've had some dogs with mast cell tumours on TKIs for over a year, and the TKI has to be stopped for reason of another disease and the tumour grows back. Start the TKI again and the tumour goes away.
So, ideally they should be continued and that can get very expensive. The other thing is if you have a very large, painful, inflamed and debilitating tumour, these things are very unlikely to cause a significant reduction in the tumour bulk. They're more likely to maintain stable disease.
So it's OK if you've got a few metastatic lesions in the lungs and the dog's absolutely fine. Hopefully this kind of treatment can keep a lid on them. But if you've got a very ill dog, then these treatments that maintain stability of that ill dog are not really going to do what's needed.
In summary then, I would suggest for the lymphoma cases budget hard and have a very frank discussion about costs. Staging is useful, but it rarely changes the prognosis or the treatment. CT is unequivocally more sensitive to staging solid tumours, but consider when this information will change your plan or not.
Mast cell tumours and other round cell tumours infiltrate organs insidiously when they metastasize, so ultrasound guided FNA rather than CT is often the most important method of staging. By ordering pre-loaded syringes, chemotherapy can be safely given in any practise where there's willingness to do so. And many oral treatments for cancers are available and can produce clinical benefit, although they may not represent the gold standard.
If you're interested in being a keen oncologist in practise, these are some of the books that I will use and especially PubMed. And very finally, I'd like to acknowledge my colleagues at Highcroft Veterinary Referrals, which in the next month or two is going to become Bristol Vet specialists. We've got a team of whom I'm very proud.
We've got Kate, Beth, Andrea, Shannon, Lottie, Inga, and Jerome. They're all great people. It's a privilege to work with them.
And it's been a privilege talking to you guys tonight. Thank you ever so much for tuning in. I hope you found it useful.