Good evening, ladies and gentlemen. Welcome. Welcome.
Welcome. This is this evening's webinar vet presentation on oncology proba cases. My name is Mark Edberg.
I'm a veterinarian or a veterinary surgeon. Depending on which side of the Atlantic you work on. It is my great pleasure to welcome Owen Davies.
With us tonight, Owen is an R CV S, an American and European specialist in veterinary oncology. Before his residency, he spent almost 10 years in general practise undertaking large animal and small animal work both in the UK and in India. Owen currently works at High Croft.
Veterinary referrals in Bristol and a few housekeeping things before we go, huh? For those of you who have been with us before, I'm sure nothing's a surprise here. If you have any particular questions you'd like answered, please put that in the Q and a box.
If you just have general comments or or you have issues with, sound or anything like that, or video, let us know in the chat box. Right. And that's it for me for today.
Over to you, Owen. Welcome. Great.
Thank you. Thanks for that introduction, Mark and thank you. To dawn and the Webinar vet team for inviting me on once again.
Just one quick update. High Croft referrals doesn't exist anymore. It has now rebranded to become Bristol vet specialists, but it's still the same team of people, and it's still roughly the same place.
So my apologies. No, no problem at all. I.
I should have updated the, profile I had with Webinar vet anyway this evening, there's no specific topic. We're gonna discuss some challenging cases I've had to manage. And if there's anything that I talk about that's of particular interest to people, there's probably more detail on it to be found in some of the other webinar vet webinars that are recorded for you to listen to on the Webinar vet platform.
So let's start with Phase one. Who is Wesley, an 11 year old crossbreed, and Wesley's very well, but he's got a mass on the distal right falling just there, and the owner brings him to you, asking, What can we do about it? You take an FN A, which is just about lets you do conscious and you get mesenchymal cell proliferation.
And that's a bit vague, isn't it. So you then have him in for general anaesthesia. And you take a true cut biopsy and it comes back as a soft tissue sarcoma.
Likely low grade. While you're taking a biopsy, you take some rounds of his chest and they're unremarkable. So it suggests we've got an issue with just controlling the local tumour with these soft tissue sarcomas.
That's nearly always the case, isn't it? If it's a local disease issue, it's fewer than 15% of these low grade ones will actually metastasize. So in dealing with this mass on the poor, what options can you think of now?
Just to, make a note of the date. It's currently 11th of July for those of you listening again, and it's less than a week since we had a general election. So I think we've done enough voting for one week, and I'm not gonna ask you to vote tonight.
But to stimulate your interest, I am gonna give you some options. And I'd like you guys to just consider to yourself and not tell anyone anyone else what one you would do if Wesley was in front of you in your clinic. So my options for Wesley would be narrow surgical excision and primary closure surgical excision, and that the more generous surgical excision rather, and repair with the skin flap a similar excision with, proper margins and then just leaving it as an open wound amputation of the falling radiation therapy or metronomic chemotherapy.
What one do you think you would go for personally? There's no right or wrong answer here. Let's talk about the surgical options first, and I'll give you some some of my comments on these, but number one is a narrow surgical excision and a primary closure.
Now, if we do this with a soft tissue sarcoma, we're pretty much certain to get incomplete tumour excision. And so local recurrence of the tumour is a big risk. But perhaps that's not so crazy, because we know that not all in completely resected soft tissue sarcomas, will recur, particularly of the low grade ones.
There are studies out there to say it's only between about 10 and 30% of these things that will actually recur. So perhaps that's not so crazy after all but one word of warning here, the term incomplete excision is, a very varied category. It's not a discrete entity.
Incomplete excision could mean you've tried your best to get the tumour definitively excised, and you've left one or two cancer cells in situ. It could also mean you've just taken out a chunk of the whole mass, and there's a huge golf ball sized amount of tumour remaining at the surgical site, and it could mean everything in between. So it's a bit unreliable and very, very risky to rely on incomplete excision, meaning recurrence In the minority of cases, if you deliberately go for incomplete excision on the, quite naive assumption that it will mean only a few of these things recur, then you're almost guaranteeing that this will be one of the few that does recur.
So please don't abuse the statistics here. The incomplete excisions reported in those papers have been incomplete when you've been trying your best to do a definitive surgery and get those margins that you need. So option number two.
Could we do a surgical excision and then repair with a skin flat? I like that option even less OK if you put a skin flap on the site of a tumour, excision you are. You need to be very, very, very confident.
You've got complete excision. If you put a skin flap on the site of an incompletely excised tumour, you will be spreading the tumour all along the cut surface of the flap. So when the tumour recurs, it's not just one recurrent tumour.
You can get lots of recurrent tumours all along the suture line. So you've got to be very, very careful with this option Number three surgical excision and then manages an open win. Well, I think I like that idea a bit better.
You need the right candidate here, for example. You need a dog who's quite happy to let you examine the wound and dress the leg. You don't want a very, very nervous dog or an aggressive dog, for example, and you need an owner who's tolerant and will be able to bring the dog back for bandage changes, and is able to afford the number of bandage changes, which could add up to quite a considerable cost.
But I don't think this is a bad idea. You can actually hybridise a couple of these. You could do a definitive surgical excision and leave the wound open and dressed until you get the And if his pa tells you quite confidently you've got complete excision, then you could speed up the healing process with the use of the skin flap.
At that point, for example, Option four amputation is something that I think we all understand, and we're all very capable of doing in practise. It is a quick fix to the problem, and from that point of view, it's probably the cheapest and easiest and most consistently effective thing. But since we all understand it, I'm not gonna go into it in a lot of detail.
It's also nice to leave that as a salvage procedure if other options have failed. So since this is an oncology talk, I'm gonna be asked talking more about the things people ask me questions on rather than the things we all understand. But I'll just say that.
So it's been said so those then are my thoughts on the surgical options. But I've not quite finished because we've got things like radiation therapy to consider as well. Now, just to bring everyone up to speed as I know, some people will be exposed to radiation therapy?
Quite a lot due to where they work near a radiation centre. Other people, much less so. So a few key points.
If you're unfamiliar with the use of radiation in treatment of cancer, and the first is that you can calculate the amount of radiation needed to sterilise a tumour, and you could potentially give that all in one go. If you were to do that, however, it would cause unacceptable side effects. So we rely on the fact that tumours have a reduced capacity to repair their cells than normal tissues.
We give a dose of radiation that will damage the healthy cells and the cancer cells equally. But we wait for just enough time for the healthy cells to have prepared, but not enough time for the cancer cells to repair. And then we give another dose, and then we wait for a bit of time until the healthy cells are repaired and the cancer cells haven't repaired.
Then we give another dose. So overall, over a treatment course, the net effect on the healthy cells should be minimal. But the effect on the cancer cells should be maximal.
So that's the idea and That's why the chopping up of a radiation dose into lots of little fractions is an incredibly powerful way of maximising tumour control, minimising adverse effects. But until you realise that the necessity of lots of doses of radiation is just a bit annoying, the other thing we need to know about radiation therapy is that the response isn't equal between tumours. The response depends on the intrinsic nature of the cancer you're dealing with.
Some cancers, like lymphoma, are very, very sensitive to radiation, and you don't need much to treat effectively. I'm afraid to say other cancers like sarcomas, are really quite resistant to radiation, and you need a lot to treat effectively. In fact, if you were to try to treat a cancer like this, the gross tumour that you can see and palpate is a few centimetres across.
Radiation therapy is gonna do very, very little for this sarcoma. OK, What we can do, however, is use another fact, radiobiology, and that the sensitivity of a cancer to radiation therapy depends on the proportion of cells that are in the cell cycle. More cells in the cell cycle more sensitive to radiation, and the proportion of cells in the cell cycle, is directly proportional to Oh, sorry.
Inversely proportional to the size of the mass. So if you surgically debulk a tumour, you will shift the cells from the resting phase into the, cycling phase of the cell cycle, and you will increase the sensitivity to radiation. And so that's a very good idea for dealing with a soft tissue sarcoma in the gross disease setting.
Radiation's gonna do almost nothing. But if you excise the tumour incomplete. So you've got microscopic traces of sarcoma you need to treat rather than macroscopic disease.
Then radiation should be very effective in controlling these microscopic traces of cancer. Got a little study to show you here. OK, post-operative radiation therapy for canine soft tissue sarcomas.
The majority didn't recur at all after radiation, and in this study, the ones that were occurring were almost always the very aggressive oral fibro sarcomas. And I think as many of us know, they're much harder to treat than a lot of these soft tissue sarcomas of the skin and subcutis that dogs get on their limbs. You can see this if you look at the survival of the dogs.
Those who had the oral S site sarcomas. They're much worse than those who had the non oral sight sarcomas. So if we started with surgery, did perhaps a conservative excision and then radiation therapy, that would be a good treatment.
And finally, let's talk about the other option. We have metronomic chemotherapy and just to bring people up to speed on this one. If you're not familiar with this treatment, metronomic chemo is talking about using conventional cytotoxic drugs at lower doses, typically like 1/20 of the normal dose.
But doing it every day with no, no large interval in between them, we often use oral drugs like cyclophosphamide and chlorambucil for this because they're easy to administer at home. And, they're relatively cheap. We combine this with an NSAID, because non steroidal drugs have a very modest anticancer effect in themselves, and it can be useful when they're combined with another anticancer agent.
So this type of treatment adjusts the environment of the cancer and to make it more hostile to cancer growth, it doesn't tend to kill cancer cells itself. It, stops. It makes it harder for the cancer to develop a blood supply and fine tunes the immune response such that you're more likely to have an anticancer immune response.
As I said, it's oral. It's at home, low cost, less frequent monitoring and a low prevalence of adverse effects. And this ticks a lot of boxes for us.
It's also very easy for the same reasons we can deal with this quite nicely in a practise environment, it's very unlikely to cause gastrointestinal upsets and very unlikely to do much at all, actually, apart from sterile hemorrhagic cystitis, which is, the biggest risk with using oral cyclophosphamide. If you're worried about the risk of sterile hemorrhagic cystitis, you could use Camil instead of cyclophosphamide, which doesn't carry this risk. But it is a bit more myelosuppressive.
And does metronomic chemo work well in this study, they have dogs with soft tissue sarcoma a bit like Wesley's. They're treated with metronomic chemo, and it stabilised the disease it stopped. The tumours growing didn't make them shrink, but it stopped them growing.
And when you took biopsies, you showed that the tumours had much less of a blood vessel network, and the immune system cells within the cancer was significantly different. The study didn't have a large follow up period, and what I've seen clinically is that there's always a finite time for which metronomic chemo works. If, for example, you've got a nine or 10 year old dog, it's certainly not gonna work for the rest of their life.
Even if it did work for a long period. You've gotta keep buying the drugs, and you've gotta keep seeing the dog for blood tests and monitoring visits every month, every couple of months, and over time it can become quite expensive. Metronomic chemo is more effective, though.
Were you having a microscopic disease rather than macroscopic disease in the same principle as the radiation therapy? And in this study here, we showed, delay to tumour occurrence in dogs with incomplete resected soft tissue sarcomas. Now the follow up in this study was relatively short as well, and I have seen in completely excise soft tissue.
Sarcomas recur after some time, so 6, 12 months on metronomic chemo. That's not particularly unusual. So if you've got a incompletely excise soft tissue sarcoma and the dog's likely to live more than six or 12 months, I'd encourage you to think about a different treatment for this one.
OK, so we've discussed the options here. I don't think I'd like to go for a skin and flap. Radiation therapy and metronomic chemotherapy are not gonna do much for a gross un resected disease.
My choice out of these, I think, would be number one. I would go for narrow surgical excision and primary closure, and then either radiation or metronomic chemo. My second choice would be surgical excision manages an open wound, and you could possibly consider putting a flap on it if you definitely get complete excision on the So that's what we did with Wesley.
Did the narrow excision with the beta radiation came back with an intermediate grade soft tissue sarcoma? What was our biopsy? Our biopsy was low, wasn't it?
And this illustrates quite a common situation where the tumours will get upgraded from biopsy to excision. And that's not because of the tumour changing. It's just because the tumor's quite heterogeneous and you've got to apply the grading system on the nastiest looking bit of the tumour.
The chances are you could well have missed that by taking a true cut so that you'll experience this quite commonly. Also, in the hist pa, we got complete excision, which was great with three millimetre margins, laterally and 0. 0.8 millimetre margins deep.
So we could be quite pleased about that. But I would like you guys to think of how these margins have been assessed. When a pathologist assess margins, there's different methods available, and the most common one is using radial, sectioning or cruciate sections.
This is the tumour here represented by a blue dot and this is the cut tissue in the white area around and with the radial cruciate sections. You take the lines through the tumour like this, and you measure the red bits the distance between the tumour and the cap tissue. And that that gives you the measurements we've just seen.
But a tumour is very rarely a perfectly spherical object. Tumour might look a bit like this, and if we did radial sectioning just like I've described, this tumour here would come out as completely excise. But if you can see my cursor, there's a couple of places where it's crept across the cut margin, and this is how completely excised tumours can recur.
So where it matters where it's important, you can do a few other things. You could ask your pathologist to take other sections, and this would catch this area, for example, but it wouldn't catch the lower area in the bottom. So it's quite a useful technique.
If you've marked your tumour and the pathologist is able to orientate it and you say, Look, I'm particularly worried about the distal end or the deep end or this particular bit or I put a suture and then they can focus their efforts there, so that can be useful. But another technique that you may want to ask the pathologist about is tangential section, where you take shaved samples all around the cut edge. And then you ask the pathologist to examine each one of these for the presence of tumour cells, and this is going to be the most accurate way of assessing whether a tumour is completely excised or not.
You'll get both this area here, and you'll get both that area there as well. Now it can't replace the radial sectioning because it doesn't tell you how completely a mass is excised. It just gives you complete or incomplete, so ideally, you'd use both.
But in submitting tumours like this solid tumours, I'd suggest we in the margins, we mark the closer, difficult areas, send photos, send imaging and hopefully that will give you the best chance of knowing whether it's completely excised or not. Right going on to a different tumour type. Now, this is honey.
Honey is a delightful little Jack Russell with a mass on her muzzle just there. This has been present for at least 15 months. Otherwise, we've got a very well little dog, clinical exams completely normal.
And finally, last of the mass gives you a mast cell tumour diagnosis. What would you like to do now? Well, there's a few options here now.
I think the first one would be we could do surgery just like I've discussed. We could do a marginal excision and a primary closure. We could give stona intralesional tail Tate, or we could primarily use a tyros in KA a drug, for example, palaia tin or masts.
Maci. Finally, we could also stage the dog and take a biopsy of the tumour before making a decision. So please consider what you would like to do.
We've got surgery. With the two centimetre margins, we could do a marginal excision and primary closure and hope for the best. We could give steal ponter, intralesional, tigon or TIG Or we could use a TK I or we could say, Hey, we're not gonna make any treatment decisions before staging a biopsy.
What would you like to do? I can tell you what I would like to do. I'd like to do the staging and a biopsy before making a decision, and I hope my reasoning for this will become clear.
So with honey, we took a punch biopsy and we got a pic intermediate grade and we got a cup, a low grade, and we got a low mitotic count and no unusual morphology of the mast cells. So, in other words, we've got a very common picture on the biopsy of the tumour. For those of you less familiar with these terms, we've got no red flags over aggressive Marcel tumour behaviour on this biopsy, however, cytology of the right retropharyngeal lymph node was given mast cell tumour, metastasis, liver and spleen.
Cytology is negative from our cell tumour metastasis, but we've still got lymph node metastasis nonetheless. So I'm quite pleased we staged the dog first because yeah, it certainly changes the plan. And what do you think about, the metastasis here?
Well, actually, it's quite common in mar cell tumours of the muzzle. The muzzle is an area we do worry about with Mars cell tumours. Because the mast cell tumours there seem to have a much higher prevalence of metastasis about 58% of the metastasize.
And we often think this may not be anything to do with inherent properties of the tumour that occur on the muzzle we hypothesise. This is more likely to be due to the richer, lymphatic drainage that you have in the muzzle. You can imagine the mast cells getting sucked into the lymph nodes much easier.
So that's one point. Another point is that if you've got metastasis to one lymph node only in a mast cell tumour with nonconcerning histopathology, then you can probably cure it. And that's pretty cool, isn't it?
We don't often talk about curing metastatic cancer in veterinary medicine, but this is one example where it's quite possible the vast majority of cases will be cured, providing you're able to take the local disease out of the picture with surgery plus minus radiation or plus minus stealth hunter, and we give chemotherapy as well. I should also add that as well as taking a local disease out of the picture. We need to do something to take the lymph node out of the picture, typically surgery or radiation.
So we end up with one of three scenarios with a mast cell tumour. And that's how I'd like you to think of mast cell tumours, not just metastatic or nonmetastatic. Think of them as nonmetastatic, lymph node, metastatic or distantly metastatic.
So following the, recommendations in that paper, I showed you and other papers are available to recommend the similar things. We went for surgery first, took the lymph node out, and then we did the surgery. And Dan, my colleague in surgery, has given us some brilliant pictures here so you can see the mass on honey's muzzle just up here.
And now you can see that the mass has gone and Dan has very, very cleverly advanced the side of her muzzle to fill in the gap. So it's very, very cosmetic, procedure here. Then I gave a course of GLAST and Prednisolone, and that seemed to solve the issue.
So let's ponder for a moment if surgery is not possible. Because, you know, I was lucky to work with a very skilled surgeon who was able to do such a beautiful, flap like that to close the deficit and get us complete excision. Well, we've got a few options here.
We could use radiation therapy. We could use intralesional tickling or TL C funter. We'd need to give chemo afterwards because, Stona will just focus on the primary tumour.
It won't do anything for the metastatic mast cell tumour. The good thing about radiation is you could treat the tumour and then you could treat the lymph node met, in separate radiation fields only minutes apart. Well, finally, we could use a drug, and the options would be the tyrosine kinase inhibitors like snib palaia or Nitin mast or chemotherapy drugs like Vlast and Lomustine.
So I'll give you some comments on these radiation therapy from our cell. Tumours is best characterised in a post-operative minimum residual disease setting just like us telling you about soft tissue sarcomas radiation will be more effective where you have more cells in the cell cycle. That's, in other words, with a lower burden of cancer.
So you debulk a tumour. You make it smaller, you will increase the sensitivity to radiation. And that's where it's been traditionally used and is best evaluated for mast cell tumours.
But we find that it can be quite useful on gross disease as well. You see, one of the advantages is that mo more disease is much more sensitive to radiation than sarcomas are. In this study here, we gave only three or four fractions of radiation therapy, and the Sein Palaia started a week before.
I should say that all these tumours, were unreceptable so out of 17 dogs with these unreceptable tumours a medium diameter of 4.3 centimetres, some were high grade, others were just diagnosed on cytology. Eight of them were metastatic.
Two of them were multiple, 76.4 respond. Ex responded.
That is experienced tumour shrinkage, and in almost 60% the tumours completely went away in the remainder. It was just partial where the tumour remained visible and smaller, and this response was maintained for almost a year, and the average survival of these dogs, which included those with high grade tumours and metastatic tumours, was over a year. So this looks like quite a promising treatment, and it's a relatively, easy treatment to do.
If you're able to give radiation therapy, it's just three fractions of radiation and then a drug that can be given or lie at home. So it's worth considering. Secondly, with Mar cell disease, we have stona, and this is an intralesional injection, and it's a unique drug, kind of in a class of its own.
Just with one injection into the tumour, you get regression of three quarters of the mass of tumour, rising to up to 90% after two injections, and it causes necrosis of the tumour within hours of the injection. There's a couple of mechanisms here, but the thing to remember is that it seems to be very specific to tumour vasculature. It will affect all blood vessels, but it causes much more of a devastating effect on the tumour blood vessels, and that makes it reasonably specific to the tumour.
Stoner then promises to be a kind of skin sparing treatment, compared to surgery, and it can be used to treat mar cell tumours on the nose. This is a dog here who is treated with steal hunter for a Mar cell tumour on the muzzle and it's actually healed. You can just see some fibrosis, this kind of pale area here, if you can see my cursor.
Unfortunately, I don't have any, pictures while he was going through treatment. So stona can be good to treat the primary tumour. But remember, it's off licence for the metastatic cases, and you're gonna need to combine it with chemotherapy to treat the lymph node or surgically excise the lymph node in this particular case here.
Now, when we think of drug therapy for gross mast cell tumours, I think we should order this last in the preference list. A proportion of dogs who respond to medical therapies are listed in this table, and hopefully that gives you the reason why Prednisolone only one in five dogs with a mast cell tumour will respond to it much, much less than lymphoma. Lomustine and Wim blast traditional chemotherapy again.
It's 40 to 50% of dogs will respond to it, and then these new sexy designer drugs, palaia and max again. 40 to 50% of the dogs will respond. If you look in the column on the right, you can see that the duration of response is finite with all of these.
So if you're looking for a treatment for the long term, then drugs on their own are not going to do it now. With the the new designer drugs PAF mast, the presence of the secret mutation will increase the likelihood of response so you could test for the secret mutation and see if it's present. But to be pragmatic, it's an expensive test, and it won't always tell you whether the tumour will respond or not.
You can see brilliant responses, sometimes in tumours that are negative for this mutation. So perhaps a more pragmatic way of finding out whether these drugs are appropriate is just to use them and see what happens. You see, in this picture here, this is a huge grapefruit size Marcel tumour on an 11 kg Shetland sheepdog, and after a few weeks, the tumour shrank away to that, so it can be very, very gratifying.
If you get a brilliant a response like this, you feel brilliant. You feel very clever, but you should realise that there's no defined stopping point when you use Pynchon ASE inhibitor drugs like mast or palaia. I'll illustrate that here.
OK, if we're gonna give a course of chemotherapy, we will gradually bash down the cancer burden to what we consider zero. And then we can stop the course. Chemotherapy kills cancer cells.
BLA or mast will change the behaviour of cancer cells. They don't kill them directly. So we'll still have the cancer cells.
Just, with handcuffs. I'm able to, proliferate the way they want to. Some of them may start to fizzle out after a period of time due to restoration of more benign behaviour.
Some of them not so because you're not killing cells and you maintain the cells in a different behaviour. There's not really any very clever point at which you can stop this treatment. The best advice is just to keep monitoring and making sure it's safe and making sure that the dog responds to it and keep going.
You're able to. So over a period of time, this can get very expensive. Here are some costs as well the use of these drugs, per month.
Just buying the drugs from the cheapest place I could find, you know, is 350 to 400 pounds for a 30 kg dog. And then you've got the cost of blood test, urine test, blood pressure, prescription costs, examinations, et cetera. And suddenly, if you're on this drug for six months, it's not such a cheap option overall.
So the question I get asked a lot is, when do I use the TK I drugs like palaia macit? Or when do I use the cytotoxic drugs like a blast or lous? And I tend to think in two scenarios.
If we've got microscopic disease after a surgery with traces of cancer left behind microscopically, or, say, a tumour that's completely excised with a strong risk of Mets. And I would choose in blaspheme or possibly the must team. But whatever I would use as a course, and then you can stop palaia are Ma are not very well evaluated in this setting.
There's nothing to measure their efficacy like you can't measure a tumour shrinking and they are expensive, and they don't have a very good stopping point. If you've got a gross disease setting that is a tumour. You can see an unresectable tumour with Mets or strong risk risk of nets.
Then I would choose these TK I drugs first line. That's because response can be measured. They're much better characterised in this setting, and the minority can do very, very well.
But where you've only got a local tumour, and the risk of Mets is low or it hasn't metastasized. Please explore surgery or radiation or steal ponter as the primary treatment, because these drugs will only do a certain amount in a gross disease setting. And they're much better played to treat the threat of metastasis or, at the very least, microscopic remnants of tumour to surgical site.
Let's move on to Gypsy. Now. Gypsy is a very nice 12 year old female domestic, short haired cat, and this is more of a a medical work up.
So gypsy, an indoor cat, regularly wormed. Normal diet has been intermittently vomiting for 18 months normally occurs at least twice weekly, but not at all. In the last month, she's been found to have a recent elevation in creatinine 100 and 59 micromoles per litre with poorly concentrated urine.
So this puts, just over the border into iris Stage two renal insufficiency. But she's still active. Still very happy.
Exam is pretty much normal On bloods. You see a borderline anaemia, mild elevation of a LT and a high normal T four. You do abdominal ultrasonography.
Find that most is normal intestinal width at the top of the normal range. Layerings present prominent muscularis layer in the small intestine. Several prominent lymph nodes, 6 to 9 millimetres in size.
But the normal structure, normal shape. And to be thorough, you get an FN A from those two lymph nodes. So it looks fairly boring, doesn't it?
We haven't found anything dreadful. And the cytology report says, Overall, we've got a heterogeneous population of lymphocytes and a lymph node, so it may be reactive. There is a expansion of a small to medium sized lymphocytes could be part of lymphoid hyperplasia, and emerging lymphoma is possible.
Part test could be considered. To investigate this further, I've got some more options for what you want to do. Now, do you want to get a biopsy of the lymph node?
Do you want to get endoscopic biopsies of the gut. Do you want to do a laparotomy and take surgical biopsies or lots of different things? Do you want to do the palm the sample?
Or do you want to do a dietary trial? Have a think what you'll do now? I wasn't involved in Gypsy's care until this point, and the vet referred Gypsy to me as an oncologist after requesting a PA test and finding a B lymphocyte clonal rearrangement.
So this then, is supportive of a diagnosis of lymphoma, so it's a bit of a smack in the face for everyone. The vets, the owners and I was surprised as well. So consider then how you want to treat Gypsy?
Would you do a chop protocol? A cock protocol? Would you put her on Coram bil cred?
Or would you give no treatments? What do you think? I can tell you what I'll do at this point, I'd give no treatment, OK, because we should take a step back and ask, Does this diagnosis fit the clinical information?
Let me explain. You've not been vomiting in the last month. You're still active and happy.
This is not a typical history of a cat you diagnosed with lymphoma. Furthermore, think about two distinct phenotypes of lymphoma. You've got the intermediate or high grade lymphoma, sometimes a subset of the large granular lymphoma.
And then you've got the low grade gastrointestinal lymphoma. OK, the intermediate high grade lymphoma is usually a very unwell cat, with acute onset severe signs as well as gastrointestinal issues. They're often depressed, anorexic, weak.
You may have obstruction or perforation of the G. I tract a very commonly or palpate large masses in the abdomen and on ultrasound. You'll see, markedly deformed areas of guts or lymph nodes that have got huge.
And they have no normal, architecture within them. You can also get blood involvement, distant organ involvement, lymph node involvement. And I think that doesn't really sound like Gypsy does it, and then we've got the low grade gastrointestinal lymphoma.
This is sometimes called small cell lymphoma, and this sounds a bit more like Gypsy. Doesn't it kind of subtle, insidious onset, worsening clinical signs usually more than a month, often for several several months? And typically these guys have had IVD for a period of years.
Importantly, on physical exam, you may get thickened intestines. But you may be normal, and in my experience, most of them are normal. On ultrasound, you might find a third have enlarged mesenteric lymph nodes.
But, it's very rare for this to present with intestinal masses or organs in the abdomen with altered architecture. So gypsy, then if anything, is gonna be a low grade lymphoma. But low grade elementary lymphoma is almost always a T cell disease.
The high grade elementary lymphomas is most likely to be B cell. So despite Gypsy's clinical signs possibly fitting, but not very well with the low grade lymphoma, The PA Clonal arrangement is for a B cell disease, and she's very unlikely to have a high grade lymphoma from our clinical assessment. Let me show you this study here.
This was a 20 completely healthy cats, OK? And, these guys biopsy the gastrointestinal tract of these completely healthy cats and performed lots of tests on the biopsies, and they found that 40% had par clonal rearrangements. None of these cats had G I signs at all, but 40% had a P test saying supportive of lymphoma on histopathology.
All these cats had some degree of lymphoplasmacytic enteritis, but there was no correlation between this and the part test. And overall, there is no correlation between the lab findings the histo and the parts. So what?
I think this is telling us here is an important comment on, how we should use diagnostic tests. When you do a diagnostic test, you should always start with some suspicion of the disease. And we call that the pre-test probability and the power of the test is expressed as a likelihood ratio.
That is how much the test will change your Susic, your suspicion of the disease from pret test or posttest probability. You've got a positive likelihood ratio for increase your suspicion and a negative likelihood ratio for decreasing your suspicion here. If you've got a more specific test, it will increase the probability more if you get a positive result.
If you've got a more sensitive test, it will decrease the post test probability more with a negative result and so on. And the crux of it is there's no test powerful enough to take a pre-test probability of zero and end up with a posttest probability of 100. If you're testing where there's a very low clinical suspicion of the disease, say, for the sake of argument, 5%.
You may take a pre-test probability of 5% and a positive result will take you to a post test probability of, for sake of argument, 30%. It's still more than likely not to be what you're testing for. So I looked at Gypsy and the fact that the signs are very, very mild and they've gone away in the last month.
They're not worsening. And I tried symptomatic management, and I said, We've got a not enough evidence to call lymphoma here because my clinical picture doesn't fit even with the low grade lymphoma. If you've seen that, it's still a case where cats lose weight and the signs are worsening, and they've often been on pre for the IBD for ages, and it's not doing anything.
This cat isn't really gonna be one of these or at least is a very early case. So we manage symptomatically an ultrasound every three months. For the next year, we found that imaging was static, weight was static, clinical signs improved with a hydrolysed diet, and everything was fine until sadly, 17 months later, the cat developed an aortic thrombo embolism and was put to sleep.
Now let's look at Ted here. All these patients so far are lovely patients, by the way. So Ted's a basset hem six years old, very well, but has sat suma like sized peripheral lymph nodes.
You palpate cranial organomegaly. You take an FN a of lymph nodes and you get a diagnosis of lymphoma. You do flow cytometry to immunophenotype of lymphoma, and it comes back with a high grade B cell lymphoma.
In other words, this is the most common type of peripheral nodal lymphoma that you're gonna see in practise Haematology shows a mild depression of platelets. Otherwise, fine biochemistry is boring. Decide not to do any imaging due to finances and instead invest money in the treatment rather than the staging.
Quick question. Then, if the owner asks you, what's the average survival for this type of lymphoma? What would you say?
They're giving you four options here? My answer would be number three. I think 12 to 18 months is fairly average.
It's heavily dependent on how much treatment these guys get, though, and a quarter of them go on over two years and some of them longer, sadly, not the case for all of them. But most cases of high grade B cell lymphomas can live 1218 months at least. And after the treatments, you know, lots of different treatments are possible for lymphoma.
Choc protocol at number one is by far, the most well established treatment and the treatment that has been never bettered by any other treatment. It may seem a bit complicated, but it's not really. The Madison Wisconsin version is very simple.
It's just a drug a week, starting with vincristine cyclophosphamide, vincristine Doctor E in and off. And then you repeat three more times in the first cycle. You give a tapering course of prednisolone, and in the last two cycles, you can drag out the intervals to every two weeks if you need to.
And that's been shown not to undermine the prognosis. So, Ted. Then we gave, Been Christine and Premise la Week one and the lymph nodes reduced in size, and that's great.
However, he developed acute hyperoxia vomiting two days after doing. Christine, this is presumed chemo related nausea, and how do you wanna treat that? Do you wanna just leave it?
You wanna reduce the dose? 10% reduce dose. 25%.
Do you wanna provide antiemetic drugs or do you wanna swap treatments? Well, many people, when I speak to them in practise would jump to reducing the dose of chemotherapy next time. And let me just discuss that now, This, red curve on the graph is the risk of adverse effects occurring.
And because it's so steep, you can see that a small change in the dose on the X axis is gonna have a big effect on the adverse effects, which you can see on the Y axis. So you don't need to go down the dose much to control adverse effects. But remember that the curve reverse effects is a shadow of the curve for cancer control.
So if say, you're here, having good cancer control, low adverse effects and you reduce the dose a little, So you've got even less adverse effects. You've got a markedly less, control of the cancer there. Do you see that?
So we've got to reduce doses if we need to. For animal welfare, that's fine. But if we can avoid to, we'd quite like to.
So my choice would be only to give a dose rate dose reduction if you feel it's absolutely needed for animal welfare. I would prefer to provide antiemetic drugs, increase the antiemetic treatment for this dog and give the same dose again if I can. And another issue with Ted here Week four de Doxorubicin.
You find lymph nodes have reduced in size, but they're not normal yet and he's otherwise quite well in himself. You check his haematology and you find everything's OK. Neutrophils are healthy, but the platelets are 12.
That's really low. And you think Oh, no, they plumped. You look at a blood smear, but they haven't clumped.
This is a true finding. You've got quite a marked thrombocytopenia here, the level where you may get spontaneous bleeding. So what do you wanna do now?
Do you wanna delay treatment three days, delay treatment, seven days, delay treatment, then start a new protocol or just continue the treatment regardless, what's your choice? My choice would be just to continue with Doctor Russon as planned. Please don't presume that the cause of thrombocytopenia is due or any adverse effect is due to the chemo, it could equally be due to the disease.
OK, if you listed the possible causes of thrombocytopenia, you've got failure for production increase destruction. Failure of production could be due to myelosuppression from chemo or myelosis due to disease in the marrow, increased disruption could be due to consumption of platelets, a new mediated disruption, sequestration in the spleen. Out of these, the possible causes due to chemo kind of one possible causes due to lymphoma, many others.
Let me remind you what the platelets were. When we first saw Ted, he had a thrombocytopenia. But less marked the diagnosis.
The lymph nodes are smaller, but they're not in complete remission. So this is one dog who you you will see at times just needs doxorubicin to get into a complete remission. And while the disease has been in completely controlled in the first few weeks of the chocy branch, we found that this has progressed while the lymph nodes have shrunk.
So we gave Doctor Weber in assuming this was an IMTP or some other lymphoma related thrombocytopenia and the thrombocytopenia result one week post doub in the lymph nodes are now normal in size that you have Ted in to look at because it's a week since the first time do was used and you wanna check him over and he found he's OK, but it's a bit off colour and a bit hyper today. It wasn't like it yesterday. Temperatures a bit high.
Otherwise, exam is normal. These neutrophils of 0.5 platelets, I'm happy to say, are normal so we can assume them with a fever and a neutropenia.
We've got a febrile neutropenia. The timing, seven days after doctor reusing suggests this is heavily related to Doctor Rusin use. There may be other causes, but regardless of those we've got to treat in the same way.
So how would you want to treat a dog with febrile neutropenia? Just like Ted, we hospitalise, give an IV antibiotics. Do we perform a blood culture before antibiotics and hospitalise and give fluids?
Or do we want to do oral antibiotics as an outpatient? Or do we wanna do a blood culture and no antibiotics as an outpatient? My choice would be three.
I think we'd give him oral antibiotics, and we can keep him as an outpatient that's because he's otherwise well. He's hemodynamically stable. He has good pulses, good circulation, good blood pressure.
He's not in septic shock. If I was worried we had a dog in septic shock, I would go with number one. You buy the antibiotics and keep them in.
Hi. I wouldn't do a blood culture, and I wouldn't withhold antibiotics if the neutrophils are this slow. I know it's good practise to make sure we have a culture before dispensing antibiotics, but to be frank, when the neutrophils are this low dogs can go south very, very quickly and die before you've had the chance to even submit the culture to the lab.
So it is quite important we go on antibiotics and we go on antibiotics, ASAP and in most hospitals, the responsible use of antibiotics Policy has a dispensation for neutropenic animals just to make sure we don't lose them. But when I'm talking about antibiotics, have a think what antibiotic you like to use? Do we use amoxiclav and metrano as well?
Do we give and reflux and me as well Do we get called the pen in or do we give trimethoprim sulfonamides? What would you like to use. Well, my choice here would be number four trimethoprim sulfonamides.
Is there a good broad spectrum ca category of antibiotics that will treat the four quadrants? You know, the gramme positives, the gramme negatives, anaerobes and some of the, betalin resistant organisms as well. Trimethoprim sulfonamide is a very old drug, and we don't worry about T MP S, resistance in human medicine.
I think number one is quite a good option if you need to give IV antibiotics in an animal who's very, very sick. You don't have quite all the gramme negative coverage there. But what we're trying to treat here is not super bugs.
We're trying to treat the normal comsal organisms, in an animal's gut or an animal's throat at the very worst would be trying to treat organisms in their ear, as well. So I don't think we need to assume we're treating a super bug. And I would withhold things like flac in, because fluoroquinolone resistance is a big concern in human medicine.
I also wouldn't use flac in metronidazole simply because it's not broad enough in its spectrum. You've got very little gramme positive coverage there. And I certainly wouldn't be using the advanced, drugs like carnine, which I think would be best reserved for where you have, demonstrated need for treatment of this in a very serious and very resistant infection.
So in summary then and in no particular order of what I presented, remember that pathology tests can be unrepresentative. And ultimately, the clinician has to make the judgement on the final diagnosis. Don't rely on the pathologist.
Your job is not done by a computer for a good reason. Think of the years of training that you've had. You are the one who assembles the pieces of the jigsaw from all the different areas.
You get clinical information. You ultimately have to sign off on a diagnosis, particularly be careful of running a very good test where there's very little clinical suspicion of a disease that can run you into an awful lot of trouble. When you've got a solid tumour, consider local treatments where local control is most important and systemic treatments where metastasis is likely what has occurred after removal of a solid tumour.
Consider asking for tangential sectioning on solid tumours to make sure you can assess the completeness of excision correctly. It'll be a lot more work for the pathologist, and quite rightly, they should charge more for that. But I think it's well worth paying when we're talking about mast cell tumours.
Remember that regional metastasis just to the lymph node from a mast cell tumour with nonconcerning histology like pic intermediate grade. This is potentially curable. You just need to treat the local disease, treat the regional disease with something like surgery or radiation, and then give chemotherapy, to treat potential, spread other places.
And remember that an animal who is on chemotherapy unwell doesn't automatically have adverse effects of the chemo. We need to remain open minded about these. It could also be progression of the disease.
It could also be something completely unrelated. Finally, I've mentioned radiation a few times in this talk. I'll point out where that's available in our area now.
I work at Bristol Vet Specialists in Bristol, so I'll give a quick plug to us. We've got a new linear accelerator there. It's very sophisticated, and we're enjoying, helping a lot of pets with this treatment.
But radiation therapy is also available. In these locations in the UK, Cambridge, Liverpool, Glasgow and Edinburgh universities and Southfield Referrals in Essex. So nearby, we've also got radiation available in Lille, in France and at all four vet school in Paris.
That's me. That's where I work at Bristol vet specialists. We've got a lovely new hospital in Avon there, and we'd love to help you if you've got any interesting cases.
That's able to come to see us like to acknowledge my team. We've got Julie and Jerome, other specialists. We've got our residents and interns.
Kate. Beth Holly. And we've got our nurses, Inger and Sam.
Sam won't give me a picture, I'm afraid. And the therapeutic radiographers Meg and Simone big shout out to Inger who's passed her BT S exams in oncology just last week. I'd like to end by thanking, everyone at Webinar Vets and Mark and Dawn for the assistance and introduction this evening.
And thank you to you guys for listening. Right. Well, thank you very much.
Owen immensely enjoyed that. And for me my if I have for myself one take home thought it is how many options we have compared to even 20 years ago when it was amputation, euthanasia, or pres. And now it's What can the wholesaler bring?
It's amazing. Thank you so very much for your time. On behalf of Don and his team of webinar be I'd like to thank all our attendees watching via Zoom or the website.
And, we hope to see you in future on some of our evening Webinars. Thank you very much. Thank you, guys.