OK, OK, thank you, Anthony. Thank you to Webinar vets for inviting me. Thank you ever so much for you guys coming along to listen tonight.
I'm gonna start by telling you a story. OK. This is Rocco.
Rocco's an eight year old male neutered domestic shorthair, and he presented to a good friend of mine who works in general practise where he is an advanced practitioner in the surgery, and he does a lot of surgery for their group of practises, OK. So Rocco has a painless subcutaneous lump developed in between the shoulders, and this occurred about 5 months after the last booster in that area. It was 2.5 centimetres in diameter and apparently mobile.
My friend biopsied it, says you should, and it came back as an intermediate grade soft tissue sarcoma. So let's think for a second what we'd do about that. Well, quite sensibly, my friend went to do some research and thought sarcoma in the sight of a vaccine.
I've heard a bit about that. He Googled some advice from the vaccine associated feline sarcoma task force, the catchy VAF STF group of people. And they published a document around 2005, which gives some very specific advice on treatment.
OK? They say remove these things with at least 2 centimetre margins and 1 fascial plane deep. So, Rocco was staged, negative.
No spread of the tumour. The mass was removed with 3 centimetre lateral margins and 1 fascial plane deep. Histology confirmed it was an intermediate grade soft tissue sarcoma.
They said it was completely excised, but they couldn't guarantee complete excision at the deep margin. And it recurred 4 months later. And it was looking really pretty ugly then as the CT shows.
Again, staging was negative. It hadn't metastasized, in other words. So Rocco had a second surgery.
And this time, the excision was frankly incomplete at all aspects. So he was given a course of doxorubicin chemotherapy, but it recurred whilst having the doxorubicin chemotherapy. And this is only about 8 weeks after the surgery.
Again, there was no metastasis. And clinical signs worryingly started to develop, OK, discomfort, primarily, but then other things. And if any of you haven't seen one of these before, and you're not sure how they could create clinical signs, then I'll explore that a little.
I haven't got any pictures of Rocco, I'm afraid, but this is a similar tumour in a cat. Look at how big it's got. And look at the CT scan.
Because the tumour you're looking at on the outside is just the tip of the iceberg. In fact, the tumour has eaten through all the muscles and through the ribs into the thoracic cavity where a lot of it lies. Now you can just imagine if you or I had one of these, it would be extremely debilitating.
The other thing we see on the CT is patches of darkness and patches of light area. And that's because we're given a contrast area, a contrast agent, sorry, and the contrast agent highlights the bits with a rich blood supply. The bits that are not highlighted are probably dead.
And these tumours can start growing really aggressively such that they outstrip their oxygen supply. Bits of them start to die off and become necrotic, and the dead tissue causes things like inflammation, making the cat feel poorly and putting him off the food, and a fever. OK?
And in the end stage, some of these tumours can even start to eat through the skin as it is happening to this poor cat here. OK. So very, very sadly, Rocco was euthanized 11 months after initial diagnosis.
And this ladies and gentlemen, is a fairly typical example. Of a terrible terrible disease. Now as coincidence would have it, if you think I've been showing you an extreme case, an outlier, I can show you a picture of a cat who presented to me this morning.
OK? This is a six year old female neutered cat. And you think that this is the mass creeping down the cat's flank?
Well, sadly that's only one lobule of it. The mass actually extends all the way round here. And you know what, the mass also extends all the way into the abdominal muscles and round the other side, and I apologise, this CT is a bit slow, .
But it is quite a big file. It's doing its best. Yeah.
It was a nice idea, but I was wanting to show how this mass here, if you can see, extends through the abdominal wall and goes right round onto the other side, but perhaps that's one for another time. Anyway, my point is this is an extremely unforgiving and terrible disease where you need to get things right as soon as you see the cat, OK? These diseases will never occur sufficiently frequently for us to get extremely proficient in dealing with them.
That's why they need to be on our radar. And in this talk this evening, I'm gonna give a brief introduction to soft tissue sarcomas. I'm gonna talk about what's different about the feline injection site sarcoma.
I'm gonna talk about steps in the diagnosis and investigation that I recommend. And finally talk about the management. Ultimately, what I'm driving at here is two really important questions.
How can I cure feline injection site sarcomas? And how can I prevent them? OK.
Sarcomas then are cancers of mesenchymal cells, and we're very familiar with soft tissue sarcomas in dogs like these guys. These are mesenchymal cells. They have a characteristic Christmas cracker-like morphology, a thin nucleus with a whisper cytoplasm on either side.
And in the aggressive tumours that develop from them, they tend to be much more pleomorphic and irregular like these cells down here. But at least you can see even those ugly cancer cells are trying to have the straight lines that you see up here in the normal soft tissue sarcomas. Lots and lots of different mesenchymal cancers are available.
And that's because mesenchymal cells form the parenchyma, the structure of the body. Now things like osteosarcoma and hemangiosarcoma may look similar under a microscope, but they have a different behaviour than a lot of soft tissue sarcomas. So they're often considered separately.
And the histiocytic sarcoma is, if you like, a bad term because it's really a cancer that's developed from the monocytes and macrophages. In other words, it's not a mesenchymal cancer. It's got more in common with lymphoma, actually.
It is to the macrophage what lymphoma is to the lymphocyte. But these tumours at the top here are the ones that are commonly referred to as soft tissue sarcomas. And in dogs, the most important common ones would be the fibrous sarcoma and the peripheral nerve sheath tumour.
No matter the histology of these common soft tissue sarcomas. It doesn't seem to matter so much as the grade. And I'm sorry about this, this is based on dogs, for all you cat enthusiasts out there.
But the key thing we need to know in dealing with your average soft tissue sarcoma in the dog is the tumor's grade, OK? The grade is very, very strongly prognostic and it's based on three simple but very important features of the tumour, these things here. If you've not seen any of these survival curves before, they're very easy.
You have 100% of animals alive at the top, 0% at the bottom, plotted against time. And it follows that the tumours with the best survival will have the curve nearest 100% for longer. Those with the worst survival will have the curve getting down to zero sooner.
So we've got the three grades with very, very distinct survival curves here, grade is very prognostic. And when we deal with these things in dogs, local control is the key. Most of these soft tissue sarcomas in dogs are very invasive and can be a challenge to deal with, but they don't metastasize.
So if adequate local surgery is available, Hinging on the margins. Then we can cure these things. And we can use that word with the clients, we can cure these things, OK?
If you don't remove a normal soft tissue sarcoma in a dog completely, well, there's a couple of studies here which show that actually, it's only the minority that recur. They're relatively forgiving if you have only a small degree of incomplete excision. In this study at the top, over 100 soft tissue sarcomas from first opinion practise.
Only the minority, fewer than 10% had 3 centimetre margins, but it was less than a third that recurred. OK. Here's another study of a large group of dogs.
75% of these tumours were incompletely excised, and your common low grade and intermediate grade ones, you know, at maximum of a third recurred. OK, and I promise you guys this will be the last slide on dogs. In 1991 though, in a letter to the editor of Jaffer, a couple of pathologists reported that they thought they were seeing some different sarcomas in cats.
Now cats have always got sarcomas at quite a low frequency, just like dogs get sarcomas. But these ones were a little bit different. OK.
For a start, these were more aggressive, but they also had two key differences. If you look at this histology picture here, you can see sarcoma tissue here. And it's borne out of a bed of inflammation.
What is more, you found multiple foci of sarcoma developing seemingly separately in all this inflammation, granulomatous inflammation. So that was weird. The granulomatous inflammation, if you think back to pathology, involves lots of lymphocytes and lots of macrophages.
And the second difference with these is that the macrophages had something in them. Some kind of bluey grey material. This was investigated further under electron microscopy.
Here on the left you can see macrophages with that bluey material. And up close, you can look at it on electron microscopy. And long story short, these macrophages were containing aluminium hydroxide.
So putting all these clues together, these sarcomas commonly occurred at vaccine sites. They had some foreign material, aluminium hydroxide within them. And it so happened that a few years before, it had become law in a couple of states in America and then a few more states in America.
That cats needed to be vaccinated against rabies. Now to make sure that the rabies vaccine worked, the manufacturers put aluminium hydroxide in as an adjuvant to make the immune system realise it's there to stimulate a good immune response. And around the same time, a new killed vaccine had been developed for FELV and that was being used as well.
So, the increasing prevalence, or sorry, the occurrence of this new type of super aggressive sarcoma was linked to the use of these vaccines in the preceding years. And of course, we all know about the, the fallout that that created, socially. Around the time vets were starting to specialise more in small animal work, offer a higher level of service, often for a higher cost, quite understandably.
And around the time, people were becoming more suspicious of science and medicine in general. And so it was almost like a perfect storm. But we're not gonna talk more about that today.
From this evidence then and the early work in the 90s by the pathologists, people started calling these tumours vaccine associated sarcomas. And you can quite understand why, can't you? But actually this isn't the full story, because if you wanna use the term vaccine associated sarcoma, I think you need to give me a very good explanation for this.
Because these tumours aren't really anything new. Cats have always had very, very aggressive sarcomas being borne out of a bed of inflammation in their eyes. Is it quite a rare occurrence?
You're not gonna see many of these at all. But often as a legacy of feline uveitis or a penetrating foreign body injury, cats can get extremely nasty, extremely invasive sarcomas in the eyes that look very histologically very similar to the injection site sarcoma. And also we know that tumours can occur in a number of species, not least cats, at the site of orthopaedic implants.
OK. So now the dust has settled, and people have looked at this objectively, it's an inflammation issue. Cats have funky immune systems, and some cats can develop very aggressive sarcomas as the legacy of chronic inflammation.
Now, these vaccines have been an important cause of that inflammation in the past, but they're not the only thing. Hence the term now injection site sarcomas. I'm gonna spend most of the talk talking clinically, but I'm just gonna have a brief digression now and explore how chronic inflammation may promote cancer, because we see a lot of cancers in a variety of species, especially in our own species, which develops from chronic inflammation, and I think that's quite interesting.
I'm gonna give you two alternative explanations, quite a simple one and a more involved one. The simple one is that the acute inflammatory response. Is stereotyped.
It's always the same, no matter what causes it. And a key thing that it involves is the production of reactive oxygen species. OK?
This is probably an evolutionary thing which is designed to kill or kill pathogens by damaging their macromolecules. The acute inflammatory response also involves promotion of cell division and angiogenesis as part of the healing process. So what are we doing with inflammation?
We're producing lots of reactive oxygen species that causes mutations, and we're encouraging cell division at the same time. Quite simple. That's often the way I think of it, to be fair.
For those of you who are doing certificates and higher qualifications, or those of you interested in oncology, I'm gonna give you a more correct explanation, but it is a little bit more complicated now. OK? These are the hallmarks of cancer.
As set out in this extremely elegant essay by Hannahan and Van Feinberg. So 0.1.
For a cell to become malignant. It must have a number of hallmark features, about 9 or 10, and they're set out here. 0.2 when we think of a tumour.
Imagine the bulk of a tumour. It's only the minority of that bulk of tumour that's actually cancer cells. We first start thinking of cancer like this, just a big lump of cancer cells, but actually it's more like this.
Cancers hijack benign normal parts of the body into supporting them. So a cancer will have blood vessels and nerves and fibroblasts to support it. It will also recruit immune cells to help defend it from the body's immune system.
It is extremely, extremely clever. So point to then Cancers actually contain a lot of benign cells recruited to support the malignant cells. And finally, OK.
Cancers are about much more than just mutations. The, we, we think of cancer as being caused by mutations, but a lot of these hallmarks of cancer that we have seen are actually driven by cell signalling, that is, molecules in the environment of the cancer binding to a receptor on the cell surface, which then promotes a change in gene expression in the nucleus. OK?
So we're not talking about mutations on their own causing a cancer, we're talking about mutations with a combination of certain genes being switched on and other genes being switched off. And this is a very, very important part in the development of cancers, and it's affected by all the molecules. In the cancer cell's environment.
So back to a feline injection site sarcoma. The more correct view on how it forms is that chronic inflammation can promote cell mutation. But because of the tumour microenvironment be enriched in fibroblast-like cells and inflammatory cells, these things will fan the flames of the fire that was ignited by the mutations.
OK? These cells in the micro environment will produce cytokines and growth factors which will promote the development of the tumour. A particularly important and well studied facet of this is that the lymphocytes in the injection site sarcoma, will produce platelet derived growth factor.
And the cancer cells have receptors to this. And we've shown that when the, this platelet derived growth factor is added to cultures of fibroblasts, they can adopt malignant features just by the adding of these growth factor. So a lot of the malignant features are from the environment, from the cells around the cancer cells, in other words.
OK. So, apologies if you prefer the more simple explanation, but that's a very, this is a very good example of how things like this can occur. But back to the clinical picture.
It's an inflammation problem. It's not just a vaccine problem. And here are some of the things where I've seen injection site or inflammatory sarcomas develop vaccination sites, injections of NSAIDS.
Antibiotics, especially the long acting ones that persist. Steroids, especially the long acting ones that persist. Insulin that's repeatedly given often in very similar places on the body.
Microchips that persist forever. Leuenuron implants that persist for six months or so. Bits of Penrose drain that have been left in situ after a surgery, spay wounds, surgical wounds, and cat bite abscesses, OK.
So these things, as I said, are at a kind of static level now. There was a spike of injection site sarcomas in the early 90s with adjuvanted vaccines and things. Now the vaccine manufacturers have got on the job and made much safer vaccines.
But they still occur If we look at some of the incidents of these, we'd see 1 to 4 per 10,000 vaccinated cats in America. That was over 20 years ago. In Poland, a more recent study says 16 out of 10,000 cats in general practise, or up to 85 per 10,000 cats in oncology specialty practise.
And I understand that it's routine to vaccinate cats for rabies in Poland. And in the UK possibly the prevalence is a bit less. But it's still high enough.
The FELV and rabies vaccines have been implicated as being worse than the other vaccines historically, but I'm not sure how true that is in the present day. Vaccines with adjuvants like the aluminium hydroxide are worse than the modified live vaccines. The number of injections given at the same site is proportional to the risk.
Cold vaccines. Increase the risk And . Irritation or persistence caused by medications, for example, if it's given traumatically as opposed to much more gently.
And there is some suggestion that there could be a familial link in the underlying genetics, that's I think one study has shown that siblings of affected cats are at greater risk and another study hasn't. How often do these things occur after injection? Well, it could be any time.
It's been linked between 1 month to 10 years. And as we said, these are incredibly aggressive, if you can see like this picture I showed you before, just how invasive these things are. Few of them metastasize.
25% at the most, typically to lungs or the regional lymph nodes. And a prognosis is based on the control of the local disease. OK.
That is, if you've got a case that's metastatic, the Mets are very unlikely to spell the end of the cat if you haven't dealt with a primary tumour appropriately. So, I'm gonna suggest now about how we can pick these up earlier. That's because some studies say that up to 100% of cats get some level of vaccine site reaction.
And 100% sounds quite hard to believe, but In my time in practise, I've never checked a cat's vaccine site in the weeks following an injection unless there was a specific problem. So I've never looked. How would I know?
Another study has shown around 12 vaccine site reactions per 10,000 vaccinated cats that were actually brought before a veterinary surgeon for an issue with the vaccine site. So it could be some number in between 100% and the 12 in 10,000 here. But either way.
It's thought to be 1 in 35 to 1 in 40 cc vaccine reactions develop into an injection site sarcoma. And given the difficulty dealing with these tumours, it is really imperative to pick them up at an early level. The vaccine associated fibrosarcoma taskforce or feline sarcoma taskforce in America, created the 321 rule, which I think is really, really useful.
If you've got a lump at a vaccine or injection site that persists beyond 3 months after a vaccine or injection, biopsy it. If there's a lump, that's greater than 2 centimetres, biopsy it. And if it's still increasing in size one month post vaccine or injection, biopsy it.
Now when we're doing a biopsy, please, please, please. Take an incisional biopsy. Please do not just whip it off excisionally.
And this is possibly the most important thing that I can say this evening. If you do an excisional biopsy. You will very often sign the cat's death certificate.
And I'll explain why shortly. When you're taking a biopsy though, incisional, as we say, always make sure to biopsy in the middle of the tumour and make sure that the biopsy tract can be removed later at surgery. That's because if you biopsy down the side of the tumour, you will create inflammation and allow the tumour to spread in that direction.
And this is such an unforgiving cancer that it will often start spreading in that direction by the time you're taking sutures out of the biopsy site. And it's for the same reason. That we don't want excisional biopsies to happen is we will create a ring of inflammation all around the tumour, and you will allow the tumour to suddenly get a lot bigger by this fanning of the flames that the extra inflammation will make.
So you need to get a representative sample. But you do need to make sure it's right in the middle of the tumour and where the biopsy tract will easily be removed at a later surgery. Now be careful when you take a biopsy that these tumours are very heterogeneous, and I said at the start, they contain bits of necrosis like that.
So if you took a biopsy like this, you'd probably get necrotic tissue and like this, you'd probably get necrotic tissue. If you took a biopsy there. You'd get viable tissue that would give you the diagnosis.
And that's why having a CT is very, very helpful for these. If you've got a suspect injection site sarcoma, a CT is useful to plan surgery in any case. Histology can be almost any type of sarcoma really, including osteosarcoma.
Or chondrosarcoma, etc. And what's going on here is that it probably is a fibrosarcoma to start with. It's just these cancer cells are so wild, they're expressing all kinds of genes that shouldn't be expressed, including that of producing osteoid or chondroid.
You'll find that around 60% are high grade on the dog grading system, 36 grade 2, intermediate, and 5% are grade 1, low. But actually, the grade doesn't really affect how we treat these. If I think it's an injection site sarcoma and it comes back as low grade.
I'll treat it as an injection site sarcoma and the grade won't really affect that. The grade has a couple of subtle effects, we'll talk about later. But it's not gonna change the initial approach to every case.
Now you don't have to do a biopsy to diagnose these. We don't want to take multiple biopsies because that creates more inflammation that will fan the flames. But one thing that could get around that is cytology, actually.
And you see some very, very pleomorphic mesesenchymal cells here in this huge multinucleate cell here. And I tend to use cytology when I'm approaching these things first line because I know it's gonna produce minimal inflammation to fan the flames. And by moving a needle through the tube mate, you can correct for getting it in necrotic or inflammatory bits.
When you do cytology in-house, always have a look at one of the slides first, just to make sure you're not sending this to a pathologist and charging the client 70 pounds for the privilege. And then see if you've got cells with nuclei. And what you want is a dominant population of cells that are not inflammatory cells.
Inflammatory cells look like this. And if you send this to a pathologist, they'll probably say inflammation. So you're allowed some inflammation, but you do want a dominant population of cells with nuclei and with cytoplasm all the way around.
And if you've got that, Then I think you'll have a diagnostic cytology sample. So my approach would be to aspirate the mass. You'd need to use a different technique to that you'd use to aspirate a lymph node or a lipoma.
I would use a wider needle, 2021 gauge. And I would use 3 to 5 mLs of negative pressure, moving the needle back and forth, releasing the pressure before you withdraw the needle. Check cytology in house as I mentioned.
Are there nucleated cells? Are they intact? Do they have cytoplasm all the way around?
Is there a dominant non-inflammatory population? And if yes, that's all you need. I could be confident in that.
If you find you're not so confident, fine, take a biopsy. Keep the slides in case you need them at a later date. Now, finally, to conclude the diagnostic section.
The question often arises, have we got an injection site sarcoma, or have we got a non-injection site sarcoma? Both do occur in cats. And this comparison may help.
An injection site sarcoma is usually large, rapidly growing, and subcutaneous. Non-injection site sarcomas are usually cutaneous. It can be helpful if the injection site sarcoma occurs at a site of known inflammation or injection.
Non-injection site sarcomas usually don't. And the injection site sarcomas are histologically more aggressive. They're much more pleomorphism, multinucleated cells, granulomatous inflammation around the edge, multiple foci of tumour within the inflammation.
Central necrosis, they're growing so fast, they outstrip the blood supply and bits die, and they have a transition zone between inflammation and the tumour. And this macrophages with the blue-gray material. The non-injection site sarcomas are histologically much less aggressive.
Usually they occur singularly without inflammation. And I suppose it's very rare for the non-injection site sarcomas in cats to metastasize. If you find you've got a metastatic tumour, then that already makes it likely to be the injection site sarcoma.
Now, as I alluded to just now, getting a CT of these cases is very, very useful. We all know that CT is more sensitive at picking up metastases than plain radiography. But in a tumour that is so invasive and so unforgiving as this, you want to do as aggressive surgery as you possibly can and so a CT is brilliant to find the extension of the tumour.
There are some studies that have shown that an injection site sarcoma will extend 100% greater distance in some aspects. On CT than it will on physical exam alone. 100% greater.
OK. So then, the diagnosis and the staging, I would often do in one. I'd look for CT imaging while the cat's sedated, I'd aspirate the mass.
If I'm not happy with the aspirate, I'll take a biopsy. And along with that and bloods or blood pressure or things that make you happy or unhappy to anaesthetize the cat at your discretion, that's the suggested workup that I'd do. So I'm gonna talk about treatment now.
Excuse me. So I think we said, the thing that kills these guys is the problems treating the local tumour. The way they keep recurring and they're very, very difficult to control.
If these tumours are marginally resected. They'll recur within 2 or 3 months. And they'll often be in a much more aggressive guise because of the perid tumoral inflammation that fans the flames we're talking about.
It's going to be nigh on impossible to cure these guys after the surgery's just marginally resected it. Now with a wide resection, I'm afraid they still recur. Most cases, not all, and when they recur, it's significantly longer, nearly a year.
If there's a non-specialist surgeon doing the surgery, these things will recur reliably within 2 months. If you have a board certified surgery specialist, recurrence doesn't always happen, but when it does, it's about 8 months later. So I hope you're getting the impression that surgery on these things is often as hard as soft tissue surgery can become.
Now the vaccine, the fibrosarcoma taskforce from 2005 made some recommendations. And this is the document that my friend was looking at in the first case I showed you. Excised with greater than 2 centimetre margins lateral and deep to the tumour, OK?
That results in 50% of tumours being incompletely excised. And recurrence usually happened around 4 months later. Out of those that were completely excised.
Recurrence still happened but at a later date. 35 to 59% of cases with clean margins will still recur if you use this technique. Ultimately, the ones that had the clean margins will be, you know, around 35% disease free at one year.
So 2/3 are gonna have tumour recurrence by 1 year and 10% will be disease free. 90% have recurred at 2 years. So this isn't very promising, is it?
Why do so many of the ones with clean margins recur? Well, let's consider how margins are assessed for a moment. So they, this is a tumour.
And this is the cut tissue with a healthy margin between the tumour and the cut, cut border. In a lot of cases, margins are assessed by drawing a cross through the tumour. And measuring the distance between the edge of the tumour and the cut tissue like this, this red area.
Now we all know that tumours aren't perfectly spherical, particularly aggressive sarcomas aren't. So if you use that technique here for a tumour like this. It'll come back as completely excised and actually there could be bits of tumour sticking over the cupboard.
You could make this more sensitive by doing more sections, and a lot of pathologists will do that. And you do pick up incomplete excision in one place. But you'll often miss it in another place.
So a more sensitive way of assessing for completeness of resection is asking the pathologist to take shaved, tangential sections all the way around the cut tissue, and that should be able to find both areas, in which case this tumour is incompletely excised. When you submit a tumour to the pathologist, remember to ink the margins so they can orientate it and you mark the areas you're most concerned about. Send them photos of the tumour so they can orientate it even better.
Send a CT scan, OK? And so we don't want to know whether it's just completely excised or not. Ideally, we want a combination of these things.
We want the shave tangential sections to say, is it completely excised or not? And if it is completely excised, then we want the original technique I showed you to know. What length of excision we've we can enjoy, is it 1 millimetre?
Is it 10 millimetres? OK. So that's one reason why 35 to 59% of tumours with complete excision recurred.
Can you think of another reason? Let's just let you ponder that one a second. Well, the scary reason is because with the best will in the world you're cutting tissue with a sharp object and you are creating inflammation.
When you remove one of these tumours. So when we're talking about recurrent tumours in an injection site sarcoma, we may, we may not be talking about recurrent tumours. We may be talking about new tumours.
The cat's already proved that he or she can form an injection site sarcoma. So we've provided more inflammation and around a suture or something that persists a bit longer, we may have a new one forming. It's a very, very scary thought.
But there's no easy way round that. If you have a, if you have to do a second surgery, if you've got an incompletely excised tumour. As I said earlier, a secondary section will never be as successful or never as, never have the potential rather to achieve complete excision.
And that's for these reasons here. The surgical site will be larger. The original anatomy will be altered.
That is, there'll be lots of scar tissue. And a lot of the fascial planes that protect spread of the tumour as best as they can have been broken down at surgery and so you can get a much more infiltrative tumour that will spread in all kinds of directions you're not expecting. Also, in surgery, even the best surgery in the world, you will leave traces of cancer cells at all corners of the surgical site, so you will contaminate and spread the cancer as you're going, even with the best surgical technique in the world.
OK? And as we've said, the more inflammation you have, it creates, increases the risk of de novo tumour occurrence. So the bottom line is you have one chance to remove these tumours, just one, ladies and gentlemen.
Obviously, with the results I showed you from the vaccine associated feline sarcoma taskforce earlier, we don't get the results we want. And, you know, it's only 9% of cats that are with us at 2 years. The survival, again, when you, when that's reported is around 1 to 2 years for this technique.
So we need to do something better to improve it. The first thing we know about sarcomas in dogs is radiation therapy. Is that any better?
Well, if you look at this tumour here on a cat's back, and excised sarcoma. The surgeons have put surgical staples in to mark the extent of the surgical dissection. And because of what we just said, the surgical field is all contaminated.
Then we Need to radiate the whole field if we're going to radiate it. So I'll put the surgical site there, you can see. If we're gonna radiate this cat, we'd need to radiate the whole field just like this.
And because you've got to radiate such a large area of cats, if you do this. You can cause a lot of collateral damage in the cat's healthy tissues, and it may not even be compatible with life if you gave a tumour killing dose of radiation to everywhere in this field. So the dose of radiation that you can give is watered down.
It's compromised if you like, because you need such a large field. So radiation can improve surgery. And it does, but not by the things we want, by the times we want.
The disease-free interval is in the order of 1 to 3 years with radiation. Survival times 1.5 to 3.5 years and still.
You know, around 1/3 of cases will recur. I think this study is quite interesting because it says the disease-free interval, the time before the tumour occurred, was 1.5 years overall.
But actually for complete excision, it's much longer, 2 and 2.5 years. Incomplete excision, much shorter.
So radiation then doesn't correct for an inadequate surgery. It helps a bit. But if the tumor's incompletely excised, you're still on an uphill struggle.
To cut to the chase then. The current excision recommendations are much more aggressive than the document produced by the feline sarcoma taskforce 15 years ago. We're now recommending 5 centimetre lateral margins, two fascial planes deep, OK, based on physical exam.
If you do this, most, almost every case will be completely excised and have a very low recurrence rate. If you have a CT because we can pick up tumour extension much better on CT, you can just do 3 centimetre lateral margins around where it extends to on CT and one fascial plane deep. I'm gonna show you now an example of a surgery for these, OK?
That's how the tumour started. And that is the level of excision you need to do. So put yourself in the gloves to the surgeon, ladies and gentlemen, who is not thinking how on earth am I gonna get this closed.
That is why you need an awful lot of experience and surgical expertise when you do this. It's not something you wanna do for the first time on your own. You want to do one alongside someone who's done 20 of them before and had really good results.
You do get a, with this, wound deistance can occur in 11 to 17% of cases, but generally, even a surgery this radical is well tolerated. Have you seen that in order to get the two fascial planes, you need to snip off the dorsal spinous processes for an injection site sarcoma in this interscapular area? So you need to remove an awful lot of tissue.
You need to think what is the tissue I need to remove to get rid of the tumour before considering reconstruction. Often that'll involve taking out dorsal spinous processes, maybe part of the scapula. If you have a tumour or something you can amputate, then often it's easier, you can just amputate that.
So, because the prognosis has been shown to depend heavily on the experience of the surgeon doing the surgery, we recommend referral to a specialist or equivalent surgeon who's very experienced, very interested in oncological surgery, and done a lot of these before. And if you want to learn how to do that, then that's great. I'm all for people in practise getting good at things and offering a great service in practise.
But it's a case where you need to go along to the surgery specialist too and scrub in with the procedure rather than having a go on your own. Finally, curative excision does require a small enough tumour because sadly, sometimes we get to tumours like the case I showed you from today, and they're just far too big to be able to do anything meaningful with. I put this paper in, which is some of the evidence on which the current recommendations are based, but I'm not sure I've got much time to go through this with you.
What I will say though, Is that the survival after an appropriate first surgery can be very good and a lot of cats can be cured. OK, 86% disease free at 3 years, and if they've got to 3 years without recurrence, often they have long term without recurrence. So finally then, I'm gonna look at those cases that are suboptimal.
You get them and they're just too big. And when that happens, you need to think about multimodality treatment. You need surgery, radiation therapy.
And chemotherapy to get the best results. So when you get these in to start with, please talk to whoever you're gonna send it to for radiation therapy first. That's because a lot of radiation oncologists prefer to radiate these things before surgery.
OK. And the reason is radiation after surgery involves a very, very large radiation field. And if you radiate them before surgery, you've got all the cancer cells you want to radiate in one place.
You can have a smaller radiation field and give a much higher dose of radiation, sparing the rest of the body. That's the idea. Cats also tolerate radiation really, really nicely.
You can see these cats have radiation, may have scarred skin, may have discoloured fur. But otherwise, this species tolerates radiation, remarkably well. So if you have a large tumour that has radiation and surgery and is incompletely excised, but it's given chemotherapy afterwards, doxorubicin or carboplatin, the average survival is about 2.5 years.
If you do a surgery, curative intent, complete excision, and radiation therapy, well, chemo has no benefit there. So the role of chemo is in certain cases. It's not a pivotal treatment on its own, but it's an important supportive treatment.
So I would consider chemo in the incomplete excisions with radiation and with surgery, as I said. In the cases that are metastatic, or the cases that are high grade, because the higher grade ones are more likely to metastasize. And the third place is to palliate gross disease.
If you've got a client who's not able or not wanting to pursue radiation or surgery. You can give chemotherapy to these guys like doxorubicin, typical. And around half of them, quarter to 50, will experience tumour shrinkage.
For on average 3 to 4 months. So those who respond to treatment will survive on average 8 months. Those who don't respond survive average 2 to 3 months.
It's, it's not very much, I know, but it's something. And a lot of people, if you honestly discuss this with them, will be very grateful for that small amount of time. You can buy the cat.
The typical protocol I use is the doxorubicin-based protocol, like the AC protocol there, but carboplatin is also used as well. There's some interesting information with regard to electro chemotherapy. Which is not consistently available in the UK, but there are, it has been offered certain centres do have it available.
And in this study, which is published in a human cancer journal, I might say. We The administration of these electrical pulses along with chemotherapy, with bleomycin. Showed a dramatically reduced recurrence rate of these sarcomas than surgery without this treatment.
So this paper doesn't tell you what kind of surgery these cats had, but you had a 100% recurrence in the surgery only group. So I'm guessing it's a more conventional sarcoma excision rather than the 5 centimetres to fascial planes. When the electro chemotherapy was given intraoperatively.
Much less re recurrence and post-operative administration where you just had a scar and only microscopic remnants of tumour to treat, it was half the recurrence of the sur surgery only group. OK. Some of the tumour recurrences were retreated and responded for a good period of time.
So electro chemotherapy. It does have some effect. It's not curative.
I wouldn't think of it in place of a definitive intent surgery, but it's better than nothing and it's something I might consider if available in the face of an incomplete recurrence. There's another paper here also supporting the use of electro chemotherapy. If you're wondering how electro chemotherapy works, actually, it's quite a clever technique, it's because all cells have a cell membrane that has a potential difference across it.
And if you use a probe like this one up here. To apply a potential difference locally across the tumour, you'll disrupt this potential difference across the cell membrane, you'll turn the membrane inside out, and that will make it much more porous. So a lot of antigens inside the cell that are normally protected from the immune system will be exposed to the immune system and it will promote the formation of an immune response.
And a lot of drugs that happen to be in the serum outside the cell can then get into the cell. At a much higher concentration. So electro chemotherapy is a clever technique.
It's been used a bit in veterinary oncology and it's fully utility is yet to be elucidated. The other thing we can consider that may help a bit is surgery with an intralesional interleukin 2 injection. OK?
So, in this study following surgery and radiation, again, the surgery was probably an inadequate surgery because a high, a high percentage of the control group recurred. But in those that had the same treatment as controls, but with local injection of the interleukin around the surgery site, the recurrence rate was much lower. OK?
So then again, I might consider this in an incomplete excision. It's well worth knowing about this because it's actually licenced and fully available to buy. It's the Muriel OnSE IL2 product.
A lot of interest exists in using TKI's for the treatment of these injection site sarcomas. Actually, the clinical experience we have with it is a very, very modest effect and a very temporary effect. This study down here is actually the best that I could find.
You know, most 3 tumours shrank a little bit, and 2 remain similar size for a period. Very small number of cats. I happen to know a lot more cats have had serin or or mesitinib used in injection site sarcomas with no obvious response to me.
So I wouldn't encourage people to use TKIs at the moment. And finally, you might hear about neoadjuvant chemo at sometimes, giving chemo before the surgery, and sometimes after the surgery as well. One study has shown it produced a good outcome.
However, there was no control group in that study, and one control study showed no benefit. So I don't talk about giving chemo before surgery in these cases. So, to bring this together, if I have a small enough tumour for curative intent surgery, I'd go for aggressive surgical excision, as I said, 5 centimetre lateral margins, 2 fascial planes deep with a specialist level surgeon.
I would go for adjuvant radiation and chemo if it's incompletely or narrowly resected. If it's high grade, metastatic, but completely resected, I'd go for adjuvant chemo only. Where you've got a huge tumour, you don't think you're gonna do much about it, I'd go for radiation, surgery and chemo together.
But I might consider electro chemotherapy or the IL2 vaccine product if the gold standard isn't available. And if you've got a case you want to palliate that's not having surgery, I'd go for chemo only, possibly electro chemotherapy, if available. When formulating a prognosis for these guys, we need to look at the size as a very key thing.
Where it is anatomically, in terms of how difficult the surgery would be. Has it had previous surgeries? How has it been biopsied?
What surgical technique was used and the surgical expertise, and the availability of adjuvant treatments where needed. Grade has a modest effect. The high grade ones are more likely to spread, more likely to recur, but actually the low grade ones are still bad enough, and that should not change your treatment.
So how do you cure an injection site sarcoma? It starts with the follow up from something that causes inflammation. Often an injection, surgical wound, cat bite, etc.
Monitor these things. Intervene according to the 321 rule. Staged them thoroughly.
Do the most radical surgery possible with the greatest expertise possible. Interrogate the pathology report to make sure that we know as thoroughly as possible, have these margins of excision been checked all the way around by shaved tangential margins? Do the margins exceed at least 10 millimetres in all areas?
And if that's all done, you monitor very, very regularly for metastatic disease. And how do we prevent these things? Well, avoid injections of irritating things if possible.
Easier said than done. Bring your injection to room temperature before injecting. Avoid repeated use of the same injection site.
I think you should vaccinate as often as necessary because vaccination has saved far more cats than have died of injection site sarcomas, but still we need to vaccinate as infrequently as possible. We offer those of you involved in health and safety planning will be familiar with graphs like this, looking at severity of occurrence against the probability of the occurrence. And actually, the probability of these things occurring is very low, it's just the severity that's high.
So I think we shouldn't avoid vaccination in these guys. We may want to risk assess the cats though, if they're not going out, do they need the same vaccine schedule as as every other cat who's going out and fighting and meeting lots of others. Choose a modified live or recombinant vaccine if possible.
And again, monitor those injection sites. Finally, let's choose a vaccine site that can be easily amputated if possible. And people have come up with diagrams like this, right hind rabies, left hind leukaemia, front leg for the routine vaccines and things, interscapular area avoided.
This is a great idea. What I find though is that a lot of vaccines tend to creep up above the hock or towards and above the elbow in a cats. And if you're doing that and then the injection site sarcoma forms, it may be so invasive that amputation is not gonna get rid of all the disease.
So it really needs to be very distal in these limbs or the tail if possible. And that can be a difficult thing to organise. So, some considerations people may have within their practise is which of our injections will pose the most risk.
Can we avoid or mitigate the frequency of injecting these? How can we lessen the risk when these injections are given? And how can we monitor for these reactions afterwards in team with a client?
So in summary, we need to get these tumours early and sample them appropriately following the 321 rule proposed by the vaccine associated feline sarcoma taskforce. Where I don't recommend following the guidelines of this taskforce is in the surgery. That's the guidelines they gave are now largely inadequate for surgery.
You need 5 centimetre lateral margins, 2 fascial planes deep, OK? You need a very, very skilled surgeon. Consider radiation and chemo to consolidate surgery if incomplete or narrow resection.
Chemotherapy after surgery were high grade metastatic or for short term palliation. Think of electro chemotherapy or immunotherapy if available, when you've got a non-curative surgery. And consider a practise plan to prevent or monitor these things.
If you'd like to read some more, I think this review here, a very recent review from the European Advisory Board on Cat Diseases is packed with lots of information, very well written and very up to date. And if you're interested in some of the biology behind these things and you're doing a postgraduate qualification, I'd encourage you to read these essays here. Finally, if you're interested in cytology and oncology, there's some great Facebook groups I've put here and everyone's welcome to join.
I'd like to thank these guys who tolerate me working with me every day. And at this time, I have to say a huge thank you to all these key workers, critical workers out there. People giving vaccines, people making vaccines, those caring for family members with COVID and everyone apply, you know, abiding by these lockdown restrictions.
Very, very much appreciated. Thank you everyone for listening. I'm really sorry I've gone on a bit too long.
Thank you ever, ever so much for Anthony and Dawn's invitation to speak tonight. If you've got any questions, I'll do my best to answer them. Great, thank you so much, Owen.
Can you hear me OK? Yes, I can, yeah. I'll put the headset on anyway because it sometimes cuts down.
I think Sandra's has been answered, what is your opinion on vaccinating cats in the leg or the tail? Obviously you mentioned that towards the end, . Do, do you think people sort of shy away from it because it just feels a bit more awkward and difficult, and you might upset the cat or, or do you think actually quite a lot of people are vaccinating cats in the leg when they're, when they're vaccinating now?
Is there enough of a recognition of the problem that people do that? I think from a lot of cats I've seen, a lot of vets I've worked with, they continue to be vaccinated in the interscapular area. I'm not saying that's necessarily a wrong thing, and what I don't want to do is preach to people on how to vaccinate these guys.
I just think it's sensible for a practise team to to risk assess this, because the, these tumours have a very low prevalence overall in an average practise, you're unlikely to see many of these in a period of 10 or 20 years. But I think you just need a defensible stance on it. You may think, actually, this vaccine is adjuvanted, it's a bit higher risk.
So what I'll do, I'll try to give it in a different anatomical area, or I'll give the clients some facts and ask them to monitor this and to come and see me again if there's any worries with it. The, as I say, the problem is, I think a lot of cats will would possibly tolerate a subcutaneous injection where there's a lot of subcutaneous space. In a distal limb or tail, that may be more painful and the cat may be more resentful.
So I can understand why it not be doing done routinely in the distal limb, because it can often involve a nurse holding the cat or even sedation for some cases, and it can be quite uncomfortable, but From a tumour point of view, it's a much better thing to do. Do you think that there are regional differences in, you know, how often this is seen in In, you know, American places are the more adjuvanted, adjuvanted vaccines used because, you know, it's certainly from a dermatology perspective, I saw very few of these when I was practising derm. I, I don't know if it's as big a problem as when I was going to lectures and hearing what the Americans were seeing.
They were seeming to see a lot more cases. Yeah, I think it's in, in America with the, or any country with the rabies vaccine, I think you'll have a higher risk of these things there. And in from the early mid-nineties, there was almost a kind of epidemic in the states that had made rabies vaccine a mandatory thing.
I think now it's, it's calming down partly because of all the good work of people and A lot of vets in America do tend to routinely vaccinate in the limbs for that reason. Yeah. No, it's interesting, .
Elizabeth is saying if you do not have CT can ultrasound help in biopsy planning? Yeah, I think it could. Yeah.
I think in ultrasound, you'll see different textures of the mass. You might not be able to tell which is the most vascular quite as easily, but, but you could do, you could get an an indication of that. With a, with a larger mass, of course you can true cut it.
And you've got more mass to play with and more more leeway if you like. It's the smaller masses where you can easily get it offside. Yeah.
And somebody is saying, that thank you so much. That was really informative and easy to understand. This is one of the problems of, of webinars.
You can't hear the tumultuous applause at the end, which is always a shame, isn't it? But, you know, that person seems to be very appreciative. Arthur's saying, it sounds like an old, old git, except then I realised I've been, qualified for 30 or 30 years.
So Arthur saying having practised for 35 years, so. Just a little joke because I'm nearly as old as you are. I've only come across 3 cases of injection site sarcoma, all had awful outcomes, but compared to the number of cats I've vaccinated in the neck, vaccines do seem quite safe, which I think is, you know, a fair comment, isn't it?
Yeah, exactly. It's the severity is high, but the probability of occurrence is low. Yeah.
Yeah. And how often have you seen it just with, you know, simple injections as you've said, I think you mentioned Leen you're on, you know, antibiotic injections. Is that something that you've You know, you see, reasonably commonly given that it's, you know, a rare condition, is it a mixture of injections.
Yeah, I think a lot of the cats that will come and see us in referral practise have had medical care when they needed it. So they've had routine healthcare like vaccines. They've also had injections of antibiotics and meloxicam and things.
And so it's hard to say what the culprit was. They will have had a lot of injections in the area. But I have seen several cases now of these things developing at flank bay wounds.
No history of any injection being given at the site, and very up to date suture materials that absorb used. I've also seen cases of non-vaccinated cats develop this at the site of a microchip. Hm.
They just have very, very sensitive skin, don't they? They, they seem to react and that also, I think pathologists often say it's difficult, obviously not as much with this, but sometimes telling the difference between inflammation and Something that is moving over into our In a neoplastic problem, you know, can also be sometimes difficult to, to recognise, can't it. Elizabeth is listening in from Southern California, so I guess quite a bit warmer where you are in Letitia in Malawi, so I guess it's much warmer in Malawi being in the southern hemisphere.
Do, and Anna's in Houston in Texas, so do please sign up for the virtual congress. We'd love to have as many of you as possible, coming to the conference, be it for the 6 hours free or hopefully coming for the whole conference because, . I think it's going to be a really excellent conference.
So do sign up those of you that are, are listening and obviously if you are a member, you, you do get a free ticket, so don't buy a ticket if you are paying a monthly or an annual fee for access to webinar vets and obviously we'd really appreciate you sharing it on. Social media and telling friends and so on. I think we've got another question.
Yeah, Suzanne is saying any evidence of harm from spot on preparations, i.e. Fipronil products, which have been used long term for some time now.
Thank you very much for an excellent webinar. So that's from Suzanne. Yeah.
Thank you, thank you. I'm not aware of any evidence like that. These these tumours are believed to develop from a fibroblast.
Which is in the subcutaneous space, not the skin. So I think long term use of fipronil or equivalent should be OK. And perhaps Anthony or other dermatologists might comment if they've seen issues with that, but I, I'm not aware of any.
I think you can get some reactions, but they're often, you know, focal reactions, maybe some hair loss like we see with flea collars often cause that sort of loss of hair around the neck. And some of the products. I think it was, I can't remember the name of the product now, but there have been some cases of pemphigus foliacious developing from spot-ons.
So there certainly are some diseases that can happen, but I, you know, I agree with Owen. I've never heard of. Tumour developing at the site, as he said it, it, it seems to need to go deeper to start the tumour off, doesn't it, Owen?
Yes, yeah. I think that's all of our questions. I've, I've really enjoyed the presentation.
How are you coping yourself at Highcroft with the, the pandemic because that's presumably changed the whole way that practise is being done with people left outside in the, in the cars, telephone conversations to get a history. It's, it's definitely changed the way that we've worked, hasn't it? How, how has it been different for you at Highcroft?
The, yeah, we . We do, the curbside drop offs and conversations over the phone. We are trying to minimise people in the prep room, so we were doing, workups at unusual times of day to try to cope with that.
So you, so you've never got a crowd in there at one point. Yeah. In terms of the case referrals, that seems to be fairly constant actually.
That that bit hasn't changed much. We've still got the same. Cases needing to be seen.
Yeah. We have had several members of staff get ill. Fortunately, touch wood, they're, they're fine at the moment, but we have had them, and a number of others self-isolating at times.
So, so it's been tough. And I think this is a difficult area in the NHS. Obviously there will be a lot of routine operations that aren't able to take place because There just isn't space is there.
So we are we're in difficult. Sort of future with the diseases that perhaps haven't been picked up and so on that You know, that, that we've not been able to treat because of the problems. So it's great to hear that you're able to carry on, you know, treating cases at the moment.
Yeah, for the time being, yeah. Owen, I've really enjoyed it. It is an area that I'm very interested in, and I think you've made it really clear to all of us, and, and, you know, many people have, have commented there.
So I really appreciate you coming on and, you know, keep safe and best wishes to all of the team at Highcroft. Yeah, no, thanks. It's an absolute pleasure.
Hope it was useful. Thank you guys. Yeah, no, really good.
Thanks again, Owen. Take care, bye bye. Cheers, bye.