OK, good evening, everyone, and welcome to tonight's, webinar. So I assume, those that have, are listening live, and you've managed to tear yourself away from the tennis and the football that's going on tonight, and that's the last I'm gonna mention of it. So my name's Sofia, I'm from the University of Edinburgh.

And before I, go ahead and introduce the speaker, for tonight's talk. If you have any questions, then please use the question and answer box that you have that you can see on your screens. And if you've got any questions for the speakers, just put them in there.

You can ask them anonymously if you want. Also, if you have any technical issues, and we've got Dawn on standby, and again, just put them in the Q&A box, and, Dawn will hopefully be able to help you, if you you are having any technical, problems. I'd also like to thank, Bailey's Horse Feeds for sponsoring, tonight's, equine webinar.

And, well, I'll just move on to introduce, Jamie Protton. So Jamie, during, his veterinary degree, at Liverpool, and also undertook a bachelor's in veterinary pathology at the Royal Veterinary College. He then, once he graduated, he then went on to work at a mixed large animal practise in Yorkshire.

Following a year and a half in that role, he started an internship at Rossdale Ek Hospital in Suffolk, and it was there that he became interested in equine internal medicine. Then after the internship, he moved to California to start, his internal medicine residency at the Veterinary Medical Teaching Hospital, at the University of California in Davis. So he's gained his diploma status from the American College, of Veterinary Internal Medicine, in July 2015, and he is currently working at the, Lip Hoek equine Hospital.

So, over to you, Jamie. Thank you very much, Sophia. Well, thank you for everyone for, for listening in this evening.

As we mentioned a moment ago, I got a little bit of interest in oncology whilst I was doing my pathology degree and what I've learned is that in the equine industry, we know very little about oncology at all. . So this evening I'm going to try and give a bit of an overview of some of the most common neoplasias that we see within the equine industry.

Also have a bit of a, a workup situation so that we all know how to go through each case. And then go into some of the treatment modalities that are available for each of these these main neoplasms, and what also has occurred recently within the research because there has been a fairly good progress with with a lot of the research. So why are we interested?

We don't see all that many cases of neoplasia in the equine side, as, as we're all aware, but there was a recent or a few years ago now, a study that looked at just shy of 1000 cases throughout the UK of which they found about 25% of them were sarcoids and then working through our squamous cell carcinomas, lymphomas, melanomas, and then a few other smaller ones. What was interesting was the melanomas ranked so low in the percentage chart, and I think that's because this study was pre performed at a referral centre where the vast majority of melanomas are not presented to the clinicians. They also found that there was an increased risk of squamous cell carcinomas in cobs, and I think that's often due to their colouring, and that mares were involved, at a higher risk of the squamous cell carcinomas as well.

And again, I think that's likely because we see a lot of volvo and, vaginal squamous cell carcinomas. Melanomas interestingly with ponies and obviously colour related whilst Marcel tumours fit into an Arabs and cobb session. I think unsurprisingly, it doesn't really make much of a shock that increasing age was associated with an increased risk.

And then another study following this one again in the UK showed that donkeys, 72% of all tumours that were presented to a referral centre were sarcoids. So it really, sarcoids really do present as a big problem. So the approach to the neoplasia cases, it's, it's multimodal and I think it's often very underutilised and actually most people just jump to a diagnosis.

So I think it's important to really go through how and why we need to take each step. So obviously you're going to be presented with a case that has a suspected mass. And the first thing is to get a good detailed history, and I, I know I'm teaching most people to pretty much everyone listens to this, how to suck eggs on this one, so I'm sorry.

But it is important because you need to know how quickly that mass has been growing. Are there any other masses that you may miss on your clinical examination because most owners have touched every single part of that horse before you get there. Are any of the horses affected on the yard, because it may well be actually some of those dermal nodules are something completely unrelated to neoplasia and more likely and is in a granuloma or similar.

Physical examination, obviously, we need to sort of look at our vital signs, our rectal examination and that side of, of things, and the reason why that is so important is with a lot of paraneoplastic syndromes, you're going to see quite a marked systemic change including cardiovascular abnormalities, be it tachycardia or, dysrhythmias. And also a recive examination is going to give you a good chance to assess the internal inguinal lymph nodes just over that pelvic rim. Recording of these cases again is hugely important because we need to map and record every single size of all the masses and assess all lymph nodes that this horse has.

And I think lymph nodes again are an undertested area, and we, we can look at the submandibular lymph nodes, the retropharyngeal, the pre-scapular, the prefemoral, the external inguinal, and the internal inguinal. They're all easily accessible by palpation alone. Further testing, and I'll go into these individually, obviously falls into your indirect such as haematology, biochemistry, and urinalysis, your further imaging, and also biopsies.

So coming back to the mapping situation, I think this is just one of those diagrams that comes from a, passport, essentially, and the only area that's really terrible at diagramming is the external genitalia and the anus, which obviously is vitally important for your melanomas and your squamous cell carcinomas. So please do extend the diagrams as appropriate. And I think measuring the size, not only the location is vital.

I use a pair of callipers similar to the one in the diagram to get diameters, and that's a fairly crude method, and also ultrasound for certain masses within the horse. Coming back to this, and we, we move on to talking about biopsies, and I think this is something that's, often we don't really talk about enough, because lots of people have this preconceived idea that biopsies are bad. There's a lot of aspects that say, actually I'll come on to that in a second, so sorry, biopsy technique is the sample selection is vital to get what you need.

So just remember the centre of the tumour may well be necrotic and, actually just having a case today where somebody had aspirated the centre of it and got neutrophils, assuming it was an abscess, but it was a, a large lymphoma. So then the biopsy technique comes into question and obviously a true cut is absolutely great for your internal organs using something like a guini showed in the middle picture. Wedge biopsies are good if they are incisional biopsies as long as you're going all the way through the tumour ideally.

Complete decision obviously fantastic if you can manage it and punchbos is adequate as well. Now, final needle fine needle aspirates are not OK in the equine equine patients, they don't. Give us a good enough answer, which is frustrating and I, I would never recommend doing it.

The only case where it does fall into a useful category is with melanomas. Obviously correct handling of the sample is going to give the best answers you possibly can, so you need to put the sample into forming fairly rapidly. If it's a large sample, then cut it into sections and ideally label the margins.

This can be done as simply as with a needle on the dorsal aspect so that the pathologist can, tell you which side of that that sample it was, or using specific tissue markers which you can buy to paint on the sample. An appropriate history is is required for the pathologist. I've had plenty of samples come back with a very ambiguous answer.

I think the vast majority of time it falls into my fault rather than theirs because they really can't see that patient and know what's going on. I'll come back to the margins depending on the tumour. In most cases, a 5 millimetre margin histopathologically is adequate.

But in circles you need a 1 centimetre margin, and that means taking a much bigger circle than 1 centimetre to guarantee that. So come back to that question of whether to biopsy or not, and for me, it's absolutely essential for the diagnosis. You, if there is a treatment option, then you need to biopsy to give yourself the best possibility of success and also the best prognosis.

There are risks associated with it. One of the biggest is that you can see neoplastic cells both locally and systemically via the lymph and blood vessels. So that should be, the owner should be warned of that.

It doesn't cause malignancy per se, but it can cause the tumour to become more locally aggressive. And so it is only an option when treatment is available. So if it's not, don't do it.

It also will stop unnecessary treatment. So if you find out that actually it is a granulate some granulation tissue rather than a squamous cell carcinoma, that's going to really change what you do with that patient. So, moving on to coming back to our further testing now, looking at the indirect testing.

It's fairly simple slide, but looking at your haematology is going to give you a good indication as to whether there's some sort of lymphocytosis or leukocytosis, which may indicate something more like an abscess. A pancytopenia is going to tell you whether, including cytopenia, that is, it is going to tell you whether or not the bone marrow may be ablated by, whatever neoplastic event is going on. In some of the more uncommon forms of lymphoma, where you have a leukemic lymphoma, you may well get amorphic cell types where every single lymphoma looks like the picture, here, where there's absolutely nothing going on between each one, and there's no evidence of an inflammatory reaction, including sort of cytotoxic granules within the cytoplasm.

Biochemistry is obviously important if there is local infiltration of any individual organ, and your analysis is very important for any renal or bladder tumour that might well be suspected. So the final stage of our, our workup is going to be our further imaging. And for me, it's absolutely essential that further imaging is undertaken.

Now, the first stage will obviously be ultrasound, and that's going to include looking at the lungs and at each organ individually. Remembering that ultrasonography will only show superficial lung lesions and anything beyond that plural surface will be obscured by the air. Radiography has its limits in equine patients because obviously the size of the horse is very big.

And so any small. Metastases seen within the lung parenchyma will often not show up on on radiography. Only later stage tumours will.

CT is becoming an absolutely fantastic adjunct to our diagnostics. Again, limited by the equine patients, so we can look at most of the neck, any distal limbs, and if we've got a nice small patient we can stick the whole body through the CT. And this is a picture, the bottom one show.

Showing a melanoma sitting just within the paramastoid process of a horse with facial paralysis, which I'll show you later on. Gammaintigraphy has its place, if you really do suspect a a bone tumour, but they are very uncommon in horses, so I as of yet have never usedgacent for a case. So treatment overview is.

Why, what can we do and how should we do it best? So response to therapy is obviously going to be better when the lesion is small. And so for me, the wait and see approach is completely outdated now and, and not appropriate apart from in cases where the owner is not willing to treat.

And that falls down to the very simple fact that benign does not mean fatal. So a benign melanoma on cytology or histopathology. Does not mean that it will not cause a fatality due to obstruction of the, the rectum or compression of a facial nerve.

So if treatment is available, it should be undertaken. And ideally treatment choice should be proven, effective, safe. And there has been a lot of research in the last 5 years, and I'm going to try and touch on as much of it as I possibly could, within those 4 cancers.

And as I said before, diagnosis by biopsy is essential to create a treatment plan. And that really falls into when you're reading these . These treatment, plans and research projects that a large number of them really don't actually look histopathological for diagnosis.

And that's why when we look at these topical treatments, I haven't included the AW 5 cream because for me there's, there's very limited research. Now I know anecdotally, having used it myself many times that it has a fantastic effect, on a lot of the superficial of the flat sarcoids. But also the human health risk is, it's huge.

It's platinum-based heavy metal-based product, and I think care should really be taken, and I know people are very, some people are very lackadaisical with its use and also where it's stored. So looking at this slightly more researched and proven efficacy treatments, 5 fluorouracil is a topical cream that inhibits DNA synthesis causing apoptosis within those cells. It has a very good proven efficacy for squamous cell.

Virus that is frequently associated, whether it's causative for sarcoids does not have the ability to phosphorylate the curing and therefore will not activate a cycle of it. I put mistletoe extract in here, not because I think it's an appropriate treatment, but because it is something that is out there on the forums. It's a complementary therapy, shown to have immunomodulatory effects in cell lines in humans, but it has no proven efficacy within, clinical trials.

There was one study undertaken, and I, I can't believe it got published because even in the placebo group. They have spontaneous remission of sarcoids and anyone who's treated a sarcoid knows sarcoids don't just go into remission. So more interesting is the current drive for immunotherapy.

And the idea behind immunotherapy is that we're going to activate and sensitise the host to the neoplastic cells themselves. There are two ways that this can be done, and one is through activating non-specific cytotoxic T cells, which is what BCG is most frequent or is doing when, when that's used. It's fairly, as I say, it's non-specific, but it can be very, very effective.

And the second is to try and expose antigen presenting cells to the tumour antigen and then try and get the immune system to react to that. And that's what we're looking at with the Immune FX vaccine, which I'll come on to a little bit later. Whilst the onset vaccine is specifically for melanomas, and again, I'm gonna touch a little bit more on that, when I get to the melanoma site.

So, looking at sarcoids, the dearth of information that's coming out at the moment is, is very interesting, and there's some very useful changes that can be implemented. I'm not going to go a lot into what sarcoids are. I think everyone knows what they look like, and how they occur.

There's a very brief overview. They're induced tumours of the fibroblasts. So often on histopathology, they can look like spindle cells as well.

And I'll come on to why that's important at the moment. They appear to be closely associated with bovine papillomavirus one or two, depending on your location within the world. And there does seem to be a slight breed predilection to thoroughbreds, quarter horses, Arabs and Appaloos.

What we can say is that 70% of sarcoids develop in over 4 year olds. So the younger they are, the less at risk they are, although 30% in under 4 year olds is still a pretty high percentage. A recent study showed that sammoxis calcitran, so just that boring old little fly, can carry the bovine papillomavirus on its feet, and therefore may well act as a vector and plays back into the, I think the very common advice that most of us give about fly control in these cases, especially when they're open and weeping.

Yeah so sarcoid classification, it's pretty simple, and these are just 4 pictures without stealing Derekno and Bell's absolutely fantastic, diagram of 6, which I'm not sure if you would have allowed me to. These are just a few of the examples. But we all know that they fall into your varicose mixed, fibroblastic, nodular, occult, and malignant.

And as such, each of those different types carries a different prognosis and also a different treatment protocol. So, how is the best way to approach a sarcoid? And being a medicine specialist, I wish I could say that surgery is not the best option, but sadly, it really is, although there are some additional things we can do to make treatment better.

And I know this picture is a melanoma, but it was the only laser one I could find. So these are two relatively big studies. Well, the top one's not that big at 15 horses, but the bottom one is for equine studies, and both showed a very similar outcome, of around, well, this top 1 73%, success rate, and by that they mean remission, I think it was at a year's time.

And The second one has a 40% reoccurrence, so actually a little bit worse than that top one, with 60% of other of horses developing sarcoids in further locations. So really not that great an outcome. So how can we improve on that?

Removal is obviously the ideal, but as I said earlier, you need to ensure that you get adequate, margins to ensure that there is no reoccurrence of the sarcoid in that primary location. If that is not possible because of the size, location, whatever it may be, then debulking can be done prior to any further treatment. Immunotherapy, as I said before, the BCG vaccine has got a relatively good rate of 7, 70% in fibroblastic sarcoid lesions, but it was very poor in your varicose or occult lesions.

So it's, you should be curtailed to the fibroblastic sarcoid form. Now there are two problems. One is that it can cause Nephhylactic reactions and so whenever being given epinephrine should be carried with you as well as some steroids.

And also at the moment it's essentially impossible to get hold of, so we haven't used it at all in the last 3 years. So what else can we do? We can use, try using a micro mod, the Eldarra, and this was on 15 horses which had been histopathologically diagnosed with sarcoids.

Sadly, 4 were withdrawn, so you're looking at only 11 horses, which is a pretty small number. Three times weekly applications for 32 weeks. And as I said, at least through us, that's about 1500 quids worth of drug.

And I only had a 60% complete resolution, and 80% with 75% reduction. So unless there's a really difficult location, surgery definitely would be falling into your first line category there. 55 fluorouracil or Eedic, twice daily application, it may work for a cult, but really, the, again, the research is sketchy on that one.

And tasarine is another one, but 60% is just not good enough and a very small study. So more interesting again is coming to an autologous vaccine. I've, I've never done it myself in a horse, but they had a, a pretty good success rate with these ones, and out of 18 cases, 75% had a decrease in the number of lesions.

With nearly 94 having decrease in the size of the lesions as well. The problem is that 44% had complications both locally at the site of injection and also systemically with quality time so. It's you should really, you should worry about it from that point of view.

I've added the blood route here because I just love the pitch, and this is them selling Xterra. With somebody putting it on without any gloves on, really brings into question their, their ethics or their sensibilities, sorry. The one study on it is terrible.

It's a questionnaire based, from the owners, and they said 49 southwards out of 74 responded completely in 15 partially, but I would never touch the stuff based on that, study. So more interestingly and more consistently researched is cisplatin. Now, I know lots of places aren't using it due to the health and safety risks of it, within the, the, owners and also the vets and nurses.

But there was a big study in 2007 by Ala Alain Tion over in at UC Davis, sorry, who looked at 573 cases with a lot of tumours, and they had a 93.3% success rate of 4 years which isbain alone. A one year reassessment, they have 96% for sarcoids and the same for lymphama sort of working their way down for the other neoplasms.

So really, that offers us some of the best responses we can ask for. Electric chemotherapy, which I know some practises are offering as a way to increase the response rate, I can't get on board with it, because its success rate per the studies is less than just a plain alone. And using electro chemotherapy guarantees that you have to use a general anaesthesia because these horses do not tolerate it whatsoever.

So for me, I can't see an advantage in it. So look, it's flat and I'm sure if you doing. You you know how to do it.

If you don't, what we do is we mix it in sesame oil, and the reason for that is that it leads to an extended duration of release, and you're going to do 4 intra-tumor administrations at 2 week intervals. The lines must be no more than 1 centimetre apart, and that's because the yat will diffuse 1 centimetre but sorry, 0.5 centimetre but no further.

And then only a meg of cisplatin per cubic centimetre. If you are undertaking this, I think you have to be very honest with the owners that there will be tissue necrosis, which is what you're trying to achieve within the sarcoid itself. But also you're going to get hair loss and deep pigmentation in a lot of cases.

And as I mentioned, the health and safety concern really shouldn't be addressed. There have been a couple of recent studies looking at bleomycin. It's a dere job here and out of 118 cases, all sarcoids, as I've put in inverted because they were diagnosed on photography, they had a 77 to 78% resolution at one year, and I'll bring the table up in just one second to explain it further.

And then come to the acyclovir, so as I said, they don't have the kinase activity to activate acyclovir. So what it actually did was it increased the PCR that was recovered of bovine papillomavirus DNA, sorry, not DNA, and therefore actually increases the risk of spreading. The BPV virus vaccine, sorry, DNA to other horses.

So this was the study that Derek did and Bliomycin itself is a soluble glycopeptide antibiotic and it has anti neoplastic activity, with very little effect on normal cells, so that sounds fantastic. And previous studies that have been done have shown very little effect of with intralesional injections and actually initially it had no penetration of the skin until they have this encapsulated liomycin liposomes. And now that penetrates the epidermis, it should have a much better effect.

It does look numerically very good, so the 5 FU and bleomycin and the tazarine and bleomycin together combined had a much higher success rate of 77 and 78. The one thing to say is those cases were treated for 40 days, rather than the top two sarin and 5 if you alone, where they only had 10 days treatment. So whether you would see a much better response would be up for debate.

Periocular sarcoids are some of the most difficult to treat without question, and I think just to say these photos have been borrowed, ones from Researchgate and one's from the Animal Health Trust, and that's because I, I've never been involved in either of these treatment modalities. So low dose interstitial brachytherapy, which is our iridium wires or seeds to the top picture, that has a very good success case in these periocular neoplasms with 74 to 100%, success, which you can't ask for more in around an eye. The problem is that they have a hugely high risk to human health.

The whole time they're in there, they're going to irradiate anyone who comes near them, and also they do fall out and then you have to hunt for them. So I don't really know of many places doing that anymore. Whereas the high dose rate, high dose rate brachytherapy has been pioneered by the Animal Health Trust and Anna Hollis over there and it, it is a very, very interesting, protocol.

It's completely safe for the veterinary surgeons, so the high dose iridium disappears into a machine whenever it's turned off and then just sits around the wires. They only do it 2 treatments, so 2 fractions 7 days apart, and they've had 93% success rate in 54 cases. I can't remember the exact reason of the failures, but when Anna presented that to us, it, it was clearly evident that someone might be too severe even for the high dose.

And just as a down on cisplatin because I, I've been bigging it up for a little while, it has such a poor success rate in periocular tumours that I, I would really recommend it. So radiotherapy, it's not something we recommend regularly. And that's because it can only be done at Cambridge or if you go to America, although this is the radiation teletherapy unit at David.

Which we use a lot for horses until they updated it and then we the human table so that stopped any further teletherapy on horses. What it does is it causes a direct damage to cells by DNA damage or an indirect by free radicals, and it allows the, the normal cells to repair because they have a normal function. It can also rupture the cells by damage to the proteins and lipids within cell wall.

And what's interesting is that the rupture of these cells seems to expose the body to the antigens that are there within, and that increases the response to other tumours of that type within the body, so it does have both a primary and a secondary effect. There are various number of. Radiotherapy is available.

I know at the Health Trust other than the high dose brachytherapy, they are also doing therapy, which is actually fantastic for some of your squamous cell carcinomas, particularly in limbal regions. And the high dose brachytherapy, as I've mentioned, is a very good success. So, we should mention the side effects of radiotherapy, of which the main ones are in the acute stage with the skin erythema, discrimination of the skin, depigmentation in the vast majority of cases, as well as permanent epilation.

In some Chronic cases you do see effects, particularly if you're anywhere near the eye, and that's very true for even your strontium therapy with a very small penetration. In some really bad cases you'll get bone. Necrosis, but because we don't use it too often, we don't see too many cases.

Interestingly, in humans, there is this radio genomics which shows some people respond very, very differently to the radiotherapy than than others. So a bit of a sobering study. Gone through a lot of different treatment modalities there and 230 cases 6 and 14 start between them all.

They only had a rate of 75% and electrical electrical. Electro cells, sorry, in the highest success rate of around 87%. What they found was Compare other stuff Or whether that it has some surgery which you know, I think we all know isn't the best.

Effect as it is. Interestingly they did have an increased success rate with immuno treatment. What's the take home message of the sarcoids really, I think and that.

With cisplatin does seem to the highest success rate, but that we have to be. The Watch and wait is just going to grow. They're going to probably come back or be around.

I was with multiple locations. So the earlier the treatment, the easier it is. Get going hospital we we now see a lot of these.

Sarcoid they these guys have very low risk of malignancy. They can be distinguished from, sarcoids by chemistry. And they just range from some more.

S Sarcoid on the skin and also if they do so actually be somewhat difficult to remove permanently. So prognosis is guarded or is very high, the risk to the horse is relatively low as long as you keep on top of it. So, squamous cell carcinomas, .

They obviously they're gonna present most frequently. As She They It's the penis or vagina. When early in the course, they can also just be very small lesions, you know, you see them on the penis very frequently, very little small ulcer ulcerative lesions.

As we progress through the disease, they can metastasize. So that top picture shows marked lymph node, they're not testicles, they're marked lymph node involvement of a penile squamous cell carcinoma. And then, also, they can get a huge amount of bacterial infection which can cause a lot of secondary problems.

Interestingly There was a case study of about 5 horses that showed out of them 3 had. Distant metastases of squamous cell carcinoma. So I think with these cases, they really should be checked for metastasis check with all the imaging that I talked about earlier.

So there is a predilection to squamous cell carcinomas in Haflingers, particularly the limbles squamous cell carcinoma. What was interesting was this was in 15 horses all had one common stallion ancestor, which through the genetics, which are far beyond my comprehending, they were suggested as an autosomal recessive, disease. So whether that can be bred out of these fingers, seeing as I've never seen a case of it in the UK would be very interesting.

In those cases of limbals squamous cell carcinomas, they remove them surgically with strontium, following strontium and mitomycin treatment. There also is a breed predilection to Clydesdales, Belgian Shires and Appaloosas, so we will see a good few of those in the UK, although there does seem to be some evidence that, you know, you need some sun, which over the last 4 weeks or so, we, we definitely have had a little bit of that. There's been some research trying to work out which of these squamous cell carcinomas is going to actually be malignant and cause a lot of problems because.

It really does seem, having seen a fair few now that there's a complete split. In the, the patients with those with absolutely no problems on going after you and those that have marked internal problems. They showed that the expression of P53, which is one of the main genes involved in apoptosis and the like, correlates with metastasis.

And the less differentiated tumour is the increased risk of death to the patient. So it really Be another reason why when anything's removed surgically, it should be sent for histopathology. Another study looked at whether there might well be a viral component to this, and they found that Eus cannulu papillomavirus was seen in 6 out of 13 horses, and not in any solar damage cases.

They're the early stages of, of, or can be early stages of scram cell carcinomas. So whether that, that will become more interesting, who knows. Treatment wise, as I said before, with all, pretty much all neoplasms, surgical excision is by far and away the best way to go forward.

Radiation therapy plays its role. Intralesional systemic chemotherapy definitely has its place. And I'm not, I haven't really talked about systemic chemotherapy in this, lecture at all, because most people don't want to go for it.

And there's a number of reasons. Doxorubicin, the most useful and study of chemotherapeutics, is about 1000 pounds per injection to the clinic, let alone to the owner, along with everything else. Vincristin is quite useful, not for squamous cell carcinomas, but is financially viable.

Cispain can be used as an adjunctive to surgery as well. There's an interesting group who looked at photodynamic therapy, which is something that's regularly used in humans and in, dogs. And what they had was 24 cases of periocular squamous cell carcinoma.

And following excision, and regrowth, they had one group of horses that had, A regrowth within 1111 out of 14 had regrowth. Whereas in the group with the photodynamic therapy, they had 100% remission at 25 months. Normally the photosynthesizer, the vertiorphin, is injected systemically and then the light is put onto the lesion itself.

The problem is that that is not financially viable in in equine patients. So what they did was they injected it locally into the tumour and then activated it with the light. So, I think that would be a, a fantastic adjunctive therapy as well.

Meloxicam, end of one study, so no harm in putting a horse on it, but I definitely wouldn't use it as a primary care. By fluorouracil is by far and away the most common product I use for squamous cell carcinomas. It's, it's very important to note that it won't penetrate very far into the squamous cell carcinoma.

It'll only penetrate a few millimetres. Therefore, it should be used only in those cases where surgery has been performed or where there is only superficial or superficial squamous cell carcinoma. And it's also very useful for those cases with early solar elastosis, those changes that are likely going to become squamous cell carcinomas because it will kill those cells without affecting any normal cells around them.

Intralesional was not very effective, so we can sort of skip past that. And in those topical ones, this was only 11 horses, but it was applied every 2 weeks, every day, sorry, for 2 weeks in the mares, and then rechecked, whereas males are applied every 14 days for approximately 5 treatments because of the requirement to sedate to have the penis out. 10 out of those patients were in remission from 7 months to 52 months, and that was dependent on when in the study they were enrolled.

So a couple of random ones, the Metronomic is a long term ongoing use of meloxicam and cyclophosphamide, and again, it's end of one, so I really wouldn't spend too much time considering it. And immunotherapy is the same. This was an autologous vaccination that it essentially magic happened somewhere else and then they injected it into this one horse and they had 6.5 months of regression, before the horse succumbed to it.

Mitomycin for your ocular cases is absolutely vital, I think, in my opinion for treatment, and I think if you're doing surgery on these cases, they really should have adjunctive mitomycin without question, even if you think you've removed every single aspect of that squamous cell carcinoma. Couple of options. One is that you just apply it at the time of surgery, and you can apply it for 1 to 5 minutes and that had a fantastic success rate, with 90% of those patients having complete remission at 11 months post treatment.

And the one case that did fail, so that's only 10 horses, was inucilated at the owner's request because they didn't want to undertake further therapy. The second study looked at doing 0.2 mLs every 6 hours and through a subalppilava system for 7 days and then 7 days rest.

And they found that after 4 treatments they had resolution in 6 out of 8 cases, and when it was used without surgery, and when it was we used with surgery, they had about the same amount of response. So just remember, some of the insane people out there doing these jobs. Look at this study by Moulin 2018, there's references for it at the end of the presentation and.

These guys had a severe squamous cell carcinoma of the foot, on the Shetland pony, and they decided that amputation of the distal limb was the most appropriate therapy because there was nothing else to do. So they completely amputated it at, I think it was the distal, aspect of the carpus that broke down and so they did it at the middle carpal joint. After a number of months, it now has a prosthesis and it's basically running around in the field, so these things are possible as long as you have some insanity in your clinic.

So melanocytic neoplasias, I'm going to focus on your grey horses rather than the abnormal melanomas that do occur in other horses. It is most frequently obviously associated with coat colour, with 80% of grey horses, over the age of 15 having melanomas either externally or internally. They present unsurprisingly, as black rounded raised nodules, normally around the base of the tail, perineal gentle regions, but also the lips, salivary glands and internally.

It is obviously benign, or frequently, sorry, benign, but can metastasis. And what's more concerning is the growth of them around the anus or wherever they may well be. Unlike in humans, there's no apparent link with sun exposure.

And there have been some more interesting recent reports with corneal malignant melanomas. What I have to say is that it's often ignored by many vets, in these cases when in fact it's one of the most untreatable of equine neoplasias. Be benign neglect is often cited as an option as they grow so slowly.

And for me this can be done as long as a very strict protocol is in place for measuring them, so I recommend measuring them every month with a ruler and a photographer, and then removing them as soon as they start to grow. So this is the patient I was talking about earlier. Now this one was never going to be a surgically approachable case, even if we had picked up the neoplasia early on in the horse's life.

So when it's not an option, what, what else can you do? Local chemotherapeutics might be an option. Have the Cox has an end of one study that showed some improvement in the melanomas, so I did put this horse on it, didn't really help.

But this is where a lot of the immunotherapy is really coming into play, so the. ImmuneFX vet direct immunotherapy, which is by a company called Morphogenesis in Tampa in Florida. Now I have to admit I tried to contact them to find out if they would ship it to the UK and they're not contacting me back at the moment.

What they've done is they've inserted a single bacterial plasmidgen into the tumour cells taken from these sources, to produce antigens. They then inject the tumour with this streptococcus pyogen gene expressing EM55 over a number of weeks, and then months. And Looking at it, it's this, sorry, the second group of bullet points, the plasma DNA vaccination, expressing strep, .

Those tumours that were injected intralesionally had a regression of approximately 40% in size, and distant tumours reduced by 47%. You get all excited and then you realise it's one. So again, could show some real promise, and I, I think actually it is one of the most interesting because they are using this a lot in the human field and therefore I think it will rapidly become transferable to us.

There was another group that looked at IL 12 and IL 18 and even glycoprotein or tyroase or wasase. And they had a tumour volume decrease of 80% in 120 days, and this was in 27 horses. Sadly, that's not really gone.

Anywhere and actually nobody's even doing it at all. So onset vaccine is something that is very easily accessible, having used it a few times myself, it, it is quite useful. It is obviously licenced for dogs with melanomas, and what it's going to do is cause an immune reaction against tyrozinase within the cells.

And the equine melanoma cells that are abnormal overpresenteryrozinase. So it's 4 injections at 2 weekly intervals, and then every 6 months thereafter. There is limited research, a lot of anecdotal people saying that it's fantastic and made a huge amount of difference, .

Some horse, some dogs though say there's very limited response. They show show others, sorry, others show a very good response. In the one study of horses, there was 30% tumour reduction size, which could make, could well be very beneficial in some of the very difficult cases.

So at this moment in time for melanomas, I generally recommend surgical debridement or surgical removal as early as possible when they're nice and small. And then to consider the onset of vaccination, one problem with the onset vaccination is that you can only give it if you are an RCVS specialist. List, so it does require referral practises in the area.

So finally, for the last sort of 5 minutes or so, I'm just gonna talk about lymphoma or hemolytic routes. Eneaplasants and lymphoma being the most common of of those ones. So there's a a good classification system based on WHO organisation for human ones.

And multicentric generally has a variable involvement of any organ, but most often it will be seen in the spleen, liver, and kidneys. In some cases it can spread to the bone marrow, and that will lead to anaemia, pos possibly pancytopenia, and in very rare cases, a leukemic lymphoma. Alimentary is often very difficult because it's virtually impossible to distinguish from an inflammatory bowel disease, which we do see, well, I assume we see inflammatory bowel disease rather than lymphoma on a very common basis.

And they're both gonna present with thick and small intestine, normally, or large intestine, both diffusely and localised, and, often with weight loss, lethargy, nondescript signs. Duodenal biopsies can be rewarding in some cases, but more often than not they have a very limited use because they have crush artefacts and also very small. In the medias style, I think that's fairly explanatory, self-explanatory there in the mediastinium and can cause some problems with drainage of fluid, so you can get pleural effusion.

And finally, the cutaneous lymphoma is characterised by these dermal or subdermal nodules, and this picture on the right hand side sort of presents what often they, they come as and lots of people don't realise that these small nodules under the skin are actually lymphoma. There does seem to be a breed predilection towards thoroughbreds, and the vast majority will have an age range of 5 to 10 years, although in one study they found that over half of us presented for less than 5 years old, so don't believe just because it's young, it's not lymphoma. Pyrexia is often a common complaint in them, and it's thought that this is most likely due to tumour necrosis and infection if they're big enough or may well be mediated by a tumour produced lymphocytes, or even a reactive microphages releasings, causing a.

Based yorrexia. Pyoplastic syndrome, although rare, can cause alopecia or even hypertrochosis and generalised problems, and it's thought to be due to release of soluble polypeptide hormones, secreted by the tumour causing aberrant, biochemical results. So for me, coming back to diagnosis, I can't say it enough, biopsy is essential to rule out that this lesion is lymphoma or is not, and it isn't just an is an illic granuloma.

Peritoneal fluid is rarely useful, in most cases because that fusion just horses don't seem to shed neoplastic cells into fusions like they do in smaller. You can perform immunohistochemistry though looking at your activated BMT cells and therefore there is another sort of. On to that diagnostics.

Ultrasound is obviously essential, particularly looking at any intestinal wall thickness, with 3 millimetres being normal thickness. So in humans, aetiology does often seem to be associated with the viral challenge, HIV, Epstein-Barr virus, although there doesn't seem to be a correlation with this in horses. Immuno phenotyping is very important in the cases where you have managed to get a biopsy and T cell-rich T cell cutaneous lymphoma is the most common.

But one thing to remember is that B cell is bad, T cell is terrible, and so it does cause a poorer prognosis when you get T cells. Now the prognosis in all the studies is generally grave, I think because it often reoccurs and we never get complete remission. But you can, especially with the cutaneous form, have quite a long life on palliative treatment.

And that can include surgical excision and radiotherapy or more likely. Chemotherapy, I have used it a couple of times we've been Kristen being your main systemic, chemotherapeutic available, as mentioned earlier. But that picture in the bottom is a perineoplastic syndrome, .

And possible pristine side effects. Corticosteroids are going to be though your mainstay of treatment in all of these cases, and prednisolone, is the most appropriate, for two reasons. One is the cascade.

With the licenced prednisolone product, we have to generally reach that. And also the dexamethasone does generally have a higher risk of, complications, particularly in humans with In induced apoptosis, sorry, with, it changes in appetite and induced appetite optosis in lymphoid cells than normal. That said, if you're not getting a response with prednisolone, I think moving to oral dexamethasone or inject dexamethasone is a very good choice.

Teletherapy has been used but again hasn't been particularly very well. So I think to sum up the lymphoma. It's a very difficult disease to advise the owners on what to do, because, prognosis is great theoretically.

My feeling is to start treating the corticosteroids, possibly azathioprine. I didn't include that in the written stuff because there's no proof of that, but I do use it a lot myself. And even, you know, you can move to some of the more weird and wonderful chemotherapeutics if the owners want.

So in summary, for me, a thorough, well-documented workup is absolutely essential and pivotal. OK In my mind, assumptive diagnosis diagnoses are not appropriate appropriate if treatment is the option. And therefore biopsy should be performed in all cases where the owner is willing to move forward with a treatment option.

And therefore, wait and see, in my mind is generally not an appropriate response or treatment protocol unless the owners are given very strict guidelines, as I said before about measuring the size of the tumours. And also being fully aware that this course may well progress rapidly and could become inoperable at some point. And then there are multiple therapeutic options available.

Yeah. So if you have any questions, please go for it, but I'm guessing there aren't too many of you with questions because of. Brilliant, thanks very much, Jamie for a really good talk.

Definitely take home message. I think there's a little bit more research required, do you think, because a lot of studies with just N equals 1. Yeah, it's, it's infuriating when you think you've hit on something good and then you actually read the materials and methods and you realise it's another terrible study is as the vast majority are having done so myself.

So, is that limitation, do you think that you just don't see enough of the cases or absolutely, yeah, we just don't see enough cases. Sorry, I think I'm just losing you a little bit there. 00, can you hear me better now?

Yeah, I can hear you now, yeah. Yeah, I think it is that most aren't presented to referral practises, they are generally treated out in the practise. There are some good groups over in America who really are trying to get into some of the chemotherapeutics and long-term outcome of lymphoma and various other ones, so I hope they, they promise the research in the next year or two.

Yeah, yeah. So we've got a question regarding squamous cell carcinomas, and the question is, is there evidence of local recurrence following surgical removal of squamous cell carcinomas, which might indicate evidence of a field of pre-cancerous cells, as is seen in human head and neck squamous cell carcinoma. Yeah, really good question.

The answer on the human side is I, I wouldn't like to comment because I don't know enough about the human. I know their survival rate is much short term, much, much lower than ours. Now, yes, there is definitely, Tim Mayer did show some reoccurrence locally in one of his studies, so.

My general treatment with the 5FU is to use that following it, and it's amazing, following surgery, that is, sorry, and it's amazing how much of an area surrounding it will become resident or ulcerated where the 5FU is affecting those cells that have solar elastosis. So I think surgery alone should not be your complete treatment protocol. OK, cool.

Thank you. Yep. Yep, yep, I think it does.

So, that's all the questions for tonight. I think everybody's dying to find out what's happening with the tennis and the football. So, yeah, thanks again, Jamie, a really, really good talk, and, again, thanks to Bailey's, for sponsoring, and also, thank you to everybody who, has listened to this, and we'll hopefully see you at the next webinar.

OK, bye for now. Bye.