Good evening, everybody, and welcome to tonight's members webinar. Slightly earlier than we are used to, but, we are here nonetheless. For those of you that, haven't been with us before, just a quick little bit of housekeeping.

If you do have a question for our speaker, just move your mouse over the screen and you'll see the control bar pops up. It's normally at the bottom. Click on the Q&A box and type your question in there.

They will come through to me, and we will hold all of those over, until the end. And then we will get through as many as we can. So we are very pleased tonight to have with us Owen Davies.

Owen is an RCVS American and European specialist in veterinary oncology. Before his residency, he spent almost 10 years in general practise undertaking large animal as well as small animal work, both in the UK as well as in India. Owen currently works at Highcroft Veterinary Referrals in Bristol.

Owen, welcome to the webinar, vet, and it's over to you. Thank you, Bruce and thank you to Fiorella and Dawn and team at Webinar Vett for asking me to speak. This is my 3rd and last webinar of this year and I've really enjoyed them all.

So the theme for this evening is anal gland tumours, what's new? And this story starts, like many good stories. With a lump on the back end of a dog.

Perhaps I shouldn't have said like many good stories, but you know what I mean. So, there are more than one type of perianal masses in dogs, and just for a second before we go on, I'll briefly draw attention to this. And we have the perianal hepatoid adenoma or perianal hepatoid carcinoma, the malignant version, that that is a cancer of the scent glands, the hepatoid glands, you get around a dog's perineum and along the tail.

You also have tumours of the anal glands themselves, and telling the two apart is often extremely simple. Like in the case of the left here, you can see a cutaneous mass that's not affecting the anal glands. There's a long way from the anal glands.

This is much more likely to be the adenoma or the carcinoma of the perianal glands. You don't often see anything with a anal gland tumour because as I'm sure you know, they're often very small. But in the case on the right here, you can see an absolutely huge mass, one of the biggest ones that I've seen.

But sometimes in the case of these huge masses, or in the case of the perianal tumour that's on the left here with a blue arrow. There can be a bit of debate as to whether they're actually a perianal gland tumour or an anal gland tumour. And if you've got that quite unusual situation, but something that does happen, then there's two things that you can do.

The first is a very detailed rectal exam, because you should be able to palpate anal glands in all dogs, providing the anal glands haven't been removed. If you can't, and there's a large mass in the 4 o'clock or 8 o'clock position, you've got an anal gland tumour. The other thing you can do is that histopathology should very easily tell you the difference between the two tumours, so a biopsy would be indicated.

I think this is useful to make this distinction because as we know, the anal gland tumours have a much higher metastatic rate, and they're much more aggressive tumours altogether. So this webinar, we're gonna be talking about the proper anal gland tumours. I would take any mass in a dog's anal gland very seriously, or a cat's anal gland for that matter, because benign tumours of the anal sac are very rare.

The principal malignancy we deal with is the apocrine gland adenocara carcinoma of the anal sac. And for the purpose of this lecture, I will refer to it as an agasacker. But it's not the only type of cancer a dog can get in the anal gland.

Melanomas are possible and do occur on rare occasions, that's do squamous cell carcinomas. And I've seen a couple of melanomas and one squamous cell carcinoma in the last 10 years that I've been doing oncology referrals. The Agasaka, for want of a better term, is something that we'll usually see every couple of weeks or so.

So in order the prevalence then, it's the Agasaka that we're gonna be talking about today. And I'm going to start with a brief introduction. So this is a disease where the breed has shows an important predisposition.

The spaniels, especially the English cocker spaniel, are predisposed. German shepherds, malamutes, and dachshunds are also reported to be overrepresented. But in my clinic, I would consider this a disease you could see in pretty much any dog.

Spaniels, definitely cocker spaniels, as well as Labradors are some of the commonest breeds I see with this disease. The mean age is about 10 years old, 9 to 11, but cancer doesn't respect age, and these things can often be diagnosed from about the age of 4 or 5 years old, up to the age of 14 or 15. And the key thing to note about this cancer is that it's highly metastatic, and it's incredibly rare to cure them.

A diagnosis, you know, has a huge range of metastatic rates depending on when you pick them up on the disease timeline. And I'll talk about this a little bit later, but we consider that pretty much all of them have a very significant metastatic potential, and that's the bottom line. About 14% are reported to occur bilaterally.

And that may not be synchronous at the same time, it could be metacrenous, and that is separated by a period of time. We've got to remember that if we treat one anal gland tumour, the other anal gland will have the same genes and being exposed to the same environmental factors. So it's understandable that at a later date, the unaffected gland could show malignant transformation.

And also, this tumour is a common cause of hypercalcemia of malignancy. I think in a dog at least, it's probably the 2nd most common cause of hypercalcemia malignancy, second to lymphoma, and therefore a careful anal gland investigation is indicated in all hypercalcemic dogs. So I guess from what I've just told you, it sounds pretty gloomy, doesn't it?

Very metastatic disease, rarely cured, common cause of hypercalcemia, etc. Etc. But probably the most important thing I'd like to teach tonight is that the prognosis can be good.

It often is good And why can it be good? Because typically the course of disease is slow, and from reading a textbook that I find that the slow course of disease is not very often emphasised. It's quite possible that a dog who's diagnosed at, say, the age of 10 or 11, may die of other things before the anal gland tumour has the chance to become life limiting.

And I think that's a very, very useful point to pragmatically treat these guys. Let's look at some of the clinical signs that you may get in a dog with an anal gland carcinoma. Well, to start with, there may be none.

OK. A significant number are diagnosed incidentally. If we do get clinical signs, I've categorise them into 4 different categories, reflecting the variety of disease that can be caused.

The first is disease due to the primary tumour. This may present us discomfort. Or swelling around the back end, you may get perianal irritation or even fresh blood on the faeces.

And a giveaway here is that if you do get bleeding from an anal gland issue, it's usually present on the last bit of faeces, because that's when the anal glands should be squeezed. If you get a stripe of blood along all the faeces, it speaks more of a rectal polyp. But if you get just a spot or a kind of splatter blood on the last segment of defecation, it's talking more about an anal gland issue.

Oh, it should in theory anyway. You can also get disease due to the regional lymph nodes. I don't know why.

But this tumour often gets to quite a small size. When in the presence of very large metastatic burden. For example, you might find a 12, 2.5, 3 centimetre anal gland mass.

And a cluster of regional lymph nodes that are effaced by metastatic disease and say 10 or 15 centimetres in diameter. So in the case of a small anal gland mass and a region, large regional lymph nodes, you could get things like tensmus or constipation or obstipation or flat faeces is sometimes reported. Thirdly, you may get clinical signs due to hypercalcemia.

And the prevalence of hypercalcemia seems to differ between the different studies, but I think of it as around 25% to 3% of dogs. Certainly the ones I see will be hypercalcemic. Now with hypercalcemia, You can get polyuria and polydipsia.

That's because high calcium will inhibit ADH in the kidneys, therefore wasting an awful lot of water, and you'll get a compensatory polydipsia. High calcium will also cause the the renal arterioles to go into spasm. And so you'll have less delivery of blood to the kidneys, less glomerular filtration, and the dog could become aotemic.

Typically, these renal signs are reversible because in a hypercalcemia of malignancy, it has come on quite acutely. And there's not any time for the long term permanent effects of the high calcium to be manifest. And what I'm talking about there is that high calcium can, if left for some period of time, cause precipitation of calcium salts within the tissues, often the kidneys, causing irreversible damage.

But one protective effect here is that the mechanism of hypercalcemia involves elevated PTHRP that mimics the action of normal parathyroid hormone. And of course, parathyroid hormone tends to raise calcium while lowering the phosphate and having, and the risk of precipitation of calcium salts within the tissues. Is often proportional to the product of the calcium and the phosphate together.

So I guess you can get PUPD and usually that's a reversible thing. Calcium also affects the neuromuscular conduction. It can affect the potential difference across the excitable membranes of nerve and muscle.

And from that we get a variety of signs, for example, gastrointestinal signs, muscle twitching, or cardiac dysrhythmias. And finally, you can get clinical signs due to the distant mets. And for this one, to list what that could potentially cause is almost as long as long as a piece of string.

But lameness, pain, orthopaedic discomfort have been described on occasions due to the bone involvement. You can also get abdominal masses, say, in the liver or the spleen, but many other signs are possible. So I guess there's no classic clinical signs for this disease.

If there were, I suppose it would be those reflective of the anal gland mass or the regional lymph node cluster. But bear in mind that almost 50% of these are incidental. So it's something we should keep on our, on our radar, in a dog presenting almost with nothing.

And just to mention some of the other histologies that we see rarely with the anal sac melanoma or the squamous cell carcinoma. Usually the clinical signs are due to the primary tumour only. Typically bleeding, ulceration.

Perineal irritation. It would be very unusual for these tumours to present incidentally, and the ones I've seen, the dogs have been very, very irritated by a fast growing ulcerating mass that's often eaten through the perineum. Again, it's unusual for these tumours to present due to metastatic disease in the regional lymph nodes.

It's typically a primary tumour problem. And let's not forget our feline friends, because cats can get these tumours too. And they typically the anal gland carcinoma, the apocrine gland adenocarcinoma of the anal sac.

Usually older cats, but again, it has been reported in very young cats. And like all, like all cats with cancer, the Siamese cat seems to be predisposed. Presentation is usually perineal ulceration and discharge, and actually a lot of these guys present as abscessed.

So a cat who's suddenly got an anal gland abscess in middle age or late age without a history of anal gland issues or perhaps skin issues should be a red flag here. You can see cats presenting with lethargy, hyperexia, tensmus, and constipation, too. But I think the most common presentation I've seen is that of an anal gland abscess.

You treat with antibiotics and you find there's actually a mass remaining afterwards. In the cats, the principal source of disease again is the local infiltration. It's very difficult to remove adequately and there's a very high recurrence rate.

The metastatic rate in cats is less well defined than in dogs, but metastasis certainly occurs. And for the steps I'll take to diagnose and stage a cat would be similar to a dog. And I'm gonna talk about that just now.

So if I have a dog with an anal sac mass. I will make sure the following steps are conducted. I'll do a thorough physical examination, paying attention to all the lymph nodes in particular.

And then I'll do a very detailed rectal examination. So I will empty both anal sacks. I'll empty them completely and I'll take time.

I'll palpate the anal glands on one side and then the other. And then I'll extend my finger forward to palpate the sub lumbar lymph nodes. I will then .

Look to see how the rectum moves relative to the mass, and that's a very important step in assessing how easy to excise the tumour will be. Some of these tumours will eat into the rectal wall, other tumours will be totally separate from the rectal wall. Finally, I'll take measurements of the mass with callipers.

Typically that's done by holding the callipers in one hand and doing a rectal exam with the other hand, pushing the lymph node up to the perineal skin so you can feel it on the other side. And finally, I'll take a fine needle aspirant. Now, if you've got a dog who's very, very shy of doing a rectal exam, I think you're well justified to sedate him or her to make sure you can do the rectal exam properly.

If you found an anal sac mass, I think you're well justified in doing this. And especially to take an FNA I'd make sure that the patient is sedated. I would then clip and aseptically prepare the perineum over the mass.

Insert a glove finger into the rectum and like I was just saying, push the anal gland tumour as far from the anal sphincter as possible up against the perineal skin, and gently take an FNA using a 23 gauge needle and no syringe, either spinning the needle round on its long axis, or very gently realigning a few times. And then before the dog's woken up, I'll check the cytology in-house to make sure you get the lesion. You can see here, if I sent this sample to a lab, the pathologist would say, I'm sorry, this isn't diagnostic.

This is also not diagnostic and it's a pity because I've got lots and lots of cells. It's just I've been far too rough, probably in the smearing technique, and I've smashed them all up. So the principal reason for checking cytology in-house is to make sure you've got nucleated cells with cytoplasm all around.

And that's what we've got here in beautiful aspirate of an anal sac mass given to me by a colleague, Doctor Nick Il Ilation of Dick White Diagnostics. Now for an anal, anal gland adenocarcinoma, it shows what we call the neuroendocrine pattern. And that typically involves lots and lots of cells where the nuclei are intact, but the cytoplasm's ruptured.

So rather than the nuclear streaming that I just showed you here, you may get lots and lots of free nuclei that are not broken, but the cytoplasm is. So lots of raw nuclei. The second thing you may get is actually very few outstanding features of malignancy.

The, the features of malignancy can be very, very mild. We zoom in a bit here, this is actually really neatly prepared and you can see up towards the top, see if my cursor will work. There we go, up towards the top, you've got a few badly prepared sort of badly preserved cells and you've got some more nuclei there, but a lot of them do have cytoplasm.

And what we're seeing here down here is a rosette formation. That's like a secretoryacinous and that can give you a clue that you're in secretory tissue. So after a rectal exam and an FNA, or just before, it doesn't matter.

I'd make sure the following tests are done, that we've got haematology, serum biochemistry. And ionised calcium and electrolytes. Then I would go to imaging of the thorax and the abdomen to stage the patient.

And as we know, there's different imaging modalities that are available. I think it's very important to image these guys thoroughly because metastasis can be present even when the primary tumour is extremely small. So what's the best imaging modality for these guys?

The radiograph is the common one. It's what most of us have in practise at least. And how good is that?

Well, What do you think? This is a lateral abdominal radiograph of a dog who may or may not have enlarged sublumbar lymph nodes. What do you think?

I'm not asking you to vote, just consider that. I'll zoom in for you. What do you think?

Is there sublumbar mass there? I'll show you the answer, this is the CT. There is a huge sublumber mass here.

And a huge anal gland tumour as well. So on a CT then. It's very easy and on radiographs, it's very difficult.

Of course, the sub lumbar cluster of lymph nodes is soft tissue density. And the rest of the viscera in the abdomen is soft tissue density, so there's very little distinction there, and you can hardly tell the difference. But CT will show you beautifully.

CT will also show you if these medial iliac lymph nodes in this case are normal size, and they're really quite small. You see? CT can help plan.

If surgery and show you how invasive a large cluster of lymph nodes is too. So CT I think of as the gold standard in detecting small metastatic lesions. And also planning surgery, showing the extent of different things.

But I think if I was to poll you guys and ask who's got CT in your practise, it's probably the minority. And I certainly didn't have CT in practise when I was in practise. So what about ultrasound, how good's that?

The answer is it's quite good. These, these are the lymph nodes that we're concerned about, the media iliac lymph nodes either side of the aorta just before the bifurcation. And you've got the hypogastric lymph nodes, a bit further into the pelvis, and finally the sacral lymph nodes.

And it's this lymph nodes, these group of lymph nodes that tends to be the ones to which an anal gland carcinoma is metastatic. You can see them all on ultrasound, they're all described. Here are some normal media iliac lymph nodes.

And here's an enlarged lymph blade. So the ultrasound is quite useful. How does it compare with CT?

Well, in this study, he had 2 dogs with an Agasaka. CT showed 13 out of the 20 to have enlarged ileosacral lymph nodes. Ultrasound only detected about 4 or 5 of them, 31%.

But ultrasound detected at least 1 enlarged lymph node in all 13 dogs. Look at another study, OK, 12 dogs with an Agasaka. And we found that, again, CT is detecting far more than ultrasound ever could, you know, 61 versus 30, 33 versus 1915 versus 0.

But out of the lymph nodes that were in abnormal, either in ecoexture or in size. Oh, there was no significant difference between ultrasound and CT. So what do we take home from this?

That's where, when it matters. Ultrasound is almost as good. Where you have the enlarged lymph nodes, the abnormal lymph nodes, ultrasound is.

Pretty similar to CT in in terms of its results. Where you've got normal size lymph nodes, which are tiny, ultrasound will often miss them, but then we don't care about those so much because if we can't see them, we're not gonna think about surgical removal. So to make the decision, have I got enlarged lymph nodes that we need to surgically remove, I think ultrasound can be a really good second best.

So, leads me on to the shoestring budget workup. And in this time of financial insecurity for many, I think it's pertinent to put slides like this in. If you want to do as best as you can, and there's very little funding.

Do a detailed physical exam, paying attention to lymph nodes, and a detailed rectal exam and FNA of the mass. Do as many blood tests, urine tests, blood pressure, etc. That you feel is indicated to have a safe general anaesthesia.

Do an ultrasound of the sublumbar lymph nodes. If you can look further on ultrasound, if you can radiograph the chest, but if we look at the sublumbar lymph nodes, that will be the most important site of metastasis screened. We just have to prepare the client that there's a small chance there could have been disease that has missed the sublumbar lymph node cluster and gone distantly, and you, you may miss that.

And ultimately at the end of your workup you want to have a clinical stage, OK? This is very, very important. This will have huge prognostic ramifications.

So I'll show you the stage here. Stage one is where you have a non-metastatic anal gland tumour up to 2.5 centimetres maximum diameter.

Stage 2, non-metastatic anal gland tumour greater than 2.5 centimetres. Stage 3A is where you have any size of anal gland tumour, but a cluster of metastatic lymph nodes up to 4.5 centimetres in maximum diameter, 3B over 4.5 centimetres in maximum diameter, and stage 4 is the stage given to any animal with distant nets.

We'll come back to this later. But now I think I've done all the work up I'd want to do, and now I'm gonna talk about treatment. Treatment can be difficult because these tumours tend to present in a huge range of stages and a huge level of clinical and clinical signs.

So I've broken this down into different scenarios. And scenario one will be a non-metastatic anal gland carcinoma. And surgery is the mainstay of treatment, end of.

Anal succulectomy, a primary treatment of choice. And in cases where the diameter of the tumour is less than 3.2 centimetres, and there's no mets, the average survival is talking about 3.5 years, sometimes more.

Now it before surgery, of course, you need to go through the risks of the procedure with the owners, and actually 5 to 24% have minor complications like wound dehiscant or infection. Rectocutaneous fistula formation. Or transient for faecal incontinence.

I sometimes think that this risk is related to the intimacy with the rectum. That is how easy is it to move the rectum over the tumour? That is, if you can move the rectum over the tumour quite nicely, then hopefully, you can remove the tumour with minimal bothering of the anal sphincter, and you're very unlikely to get some of these effects.

But certainly this risk has been shown to be related to tumour size, and I think size can sometimes be a proxy for the intimacy with the rectum. What I will say though is that transient faecal incontinence will resolve and rectocutaneous fistulas will often get better, well, they nearly always get better over about 6 or 8 weeks. It's just a bit disgusting.

You have to put the dog in the bath and hose out the horrible perineal wound a couple of times a day after they've defecated, etc. But still there's a bit of a stigma with this surgery. And a lot of clients that you discuss this with may go online or talk to other people and may come back to you with, I'm not happy with this risk of incontinence, OK?

And so I've got a few points here that could help address that. First one is that the risk of incontinence is often overstated. In early studies, when vets started to treat anal gland tumours, they were doing very, very aggressive surgeries, often removing huge chunks of the anal sphincter.

And so the prevalence of incontinence is really high, and many of these cases are permanently incontinent, but we do things better now. We do a more refined, less aggressive surgery. Also, if you manage to damage the innovation of the anal sphincter permanently on one side.

It's still usually a temporary incontinence because the body's really clever and the innovation from the other side will grow round and compensate in about 4 to 8 weeks. So I very rarely see any significant problems with the anal sacculectomies that happened at my practise or at the previous place where I worked. Got some pictures here that my colleague Doctor Dan Ogden gave to me.

You can see an incision being made there, removing quite a hefty anal gland mass. And this is a very neat suture line at some distance from the anal sphincter. Oops, sorry, this is a case that we had a year or so ago, where the wound dehisted partially.

It was a very large tumour that was removed, to be fair, and you've got the bit in the middle healing by second intention. But still healed perfectly, and the dog went on to do really well. Moving on then, scenario two.

A regionally metastatic lymph node, OK? That's where you've got an anal gland tumour to remove and you've got a cluster of enlarged regional lymph nodes. Well, it's the same thing as far as I'm concerned.

Surgery is unequivocally the best treatment for both these lesions, and surgery can often be it can be performed at the same time. It's kind of like two surgeries in one, you'll have the surgical incision I just showed you, alongside the anal sphincter. And you'll also have a caudal laparotomy to remove these lymph nodes, but as dogs tolerate that really, really well.

And if you do that with surgery alone, no adjunctive treatment to the primary and the and the lymph nodes. A survival of 20 months in one study, sometimes longer actually. And I think it's very important to do this because this tumour has a carcinoma, is something that is not going to be so sensitive to radiation or so sensitive to chemotherapy unless it is debunked to microscopic disease.

The surgery should always be the most effective treatment in dealing with this, and it's been shown to be. Categorically, the best were even with the regional lymph nodes that are metastatic. And for this procedure, the client again might be a little bit unnerved.

Isn't that dangerous trying to remove lymph nodes? After all, if you look at the diagram on the right, you can see these lymph nodes are very intimately associated with the great vessels. Well, actually, the complication rate is really low.

Between 0 and 12%. It's certainly possible due to the anatomy of the area. That you could cause bleeding.

It's also possible that the nodes have invaded the vertebrate or the abdominal wall. And to be fair, if you've done a CT scan beforehand, you should be forewarned about that one. But the worst that tends to be is that the nodes are unresectable, or you may need abdominal wall reconstruction afterwards.

Sometimes those sacral nodes which are deep in the pelvis can be difficult to reach, and pelvic osteotomy has been described to help you reach these and expose them. But in my practise, a lot of the surgeons say I'm happy to remove sacral lymph nodes just by palpation only. So really it is quite well tolerated.

Now, After surgery then, either removal of the anal gland tumour on its own, or the anal gland tumour and the metastatic lymph nodes, we consider that the tumour is downstaged, OK, rendered to microscopic disease. We don't tend to talk about cure. That's because all carcinomas are cancers, they are invasive.

They will have a microscopic network of roots extending much further than you could possibly imagine. And we are operating in very anatomically limiting areas. We would like to remove these with 2 or 3 centimetre margins, but we just don't, you just can't.

You know, life wouldn't be worth living if we were to take, you know, take out the dog's anal sphincter, for example, and damage all the nerves at the back end or if we were to take a chunk of vertebrae, you know, the, the body of the vertebrae out, it's just not possible. So we'll have to accept that all these excisions will be narrow at best, marginal. And in a lot of cases, they'll be frankly incomplete.

So when we look at the histo afterwards, we're not looking for a certain excision margin. We need to say that the tumour is contained fully within the capsule to say it's been completely excised and frankly, that's quite uncommon. The, whether the tumour is incompletely excised or officially completely excised, it still doesn't affect the risk of recurrence.

And that's caused a few people to consider the pathology report, . But I think what's probably happening is that in these tumours that are completely excised and recur, it's just microscopic traces of cancer that hasn't been found by routine margin evaluation. If you want to explore this further with the pathologist, you might request a different way of assessing margins.

We consider this as a tumour. And this is the area that's been excised. In a lot of cases, margins are assessed by drawing a cruise ship through the tumour and the Undercut tissue.

And looking for the level of the, the number of millimetres by which the tumour is excised in these four locations. And that's very good for telling you what length of margin you've got. But tumours are rarely perfect geometric shapes.

They might be something like this. And so if you use the same technique with this tumour, you can see it's been incompletely cut in a couple of cases, but that just hasn't come before the pathologist. And they might say that the capsule is intact in these four areas.

You could do more sections through the tumour and you might get it in some places, but you won't in others. So probably the most holistic way of assessing for complete margins is taking shaved sections all the way around the submitted tissue and the pathologist examining each and every one. This won't tell you the number of millimetres by which the mass has been excised, but it will tell you complete, yes or no, as best as we can.

It's gonna be a lot more work for the pathologist, I think it's right that you pay more, for that procedure, and I'm very happy to pay more for that procedure at times. However, I don't think it changes what I do, so I don't routinely ask for that with anal gland tumours. I know they're all marginal excisions, the bigger ones are more likely to be marginally excised.

They've also got a very high metastatic rate. The metastatic rates or the rate of mets being recognised after surgery has taken place, you know, some months in the future, you know there's up to 70% in the regional lymph nodes and a good 15, 20% for distant sites. So when you consider a very significant metastatic risk and the fact that in reality, most excisions are as good as incomplete.

I think this should be managed as a chronic disease. And this is very important to discuss before the owner spends out on surgery. We don't want the owner to be thinking surgery is all that's needed to fix their dog.

Because that's not the case. You'll need to manage this as a chronic disease ongoing. I think in a lot of anal gland tumours, particularly the lower stages, we can comfortably tell the owners that if we treat the dog properly, we can hope for a good outcome.

We can hope for years of survival. But I think it would be unfair to think that one procedure will just fix the dog and you can forget about this. So that's the second most important point I'd like to impress on you this evening, that yes, we can do a lot for this, but it's not in one procedure, it's in constant management of a chronic disease.

So hopefully the owner is prepared for an incomplete narrow excision and a high risk of nets post surgery. And when you meet them for the post-op check, you can talk about adjunctive therapy. And the first adjunctive therapy that I would talk about is radiation therapy.

Excuse me. Now, radiation therapy focuses on the tumour and the lymph node bed, and those are the two sites which tend to cause clinical signs most commonly. So chemotherapy, for example, is diluted in the rest of the dog and it's gonna be less effective in one particular place.

So that's why I talk about radiation therapy first. Now, with radiation, The response to radiation depends first on the intrinsic nature of the tissues in question. And we can't do anything about those really.

We know this is an apocrine gland adenocarcinoma of the anal sac. We can't change that histology. But secondly, the response to radiation depends on the disease burden, and we can do something about that.

If we have a large gross tumour. It will have a higher proportion of cells in the resting phase than it will the cell cycle. It's the resting phase here, this is the cell cycle.

Now, If you debulk the tumour surgically, you will increase the proportion of cells that are cycling versus the resting phase. And that's important because it is the cycling cells that are most susceptible to the effects of radiation. So that's why radiation works best in microscopic disease rather than gross.

When the the client will understandably want to know what the radiation therapy involve? Well, the first thing is a number of fractions. If we were to calculate the dose of radiation needed to sterilise those microscopic traces of tumour at the surgical site, then you'd cause unacceptable side effects.

So the fractionation of radiation relies on the fact that tumours have a reduced capacity to repair themselves than normal cells. So what you do is give a dose of radiation that will damage the cancer and the normal cells equally. Hopefully give enough time for the normal cells to repopulate and mend themselves, but not enough time for the cancer cells to do that, and then you give a second dose.

So theoretically, in very simple terms, you should have little overall damage to the healthy tissue, but progressive damage to the cancer tissue with each fraction. But doing this, it requires many trips to the radiation centre, many doses, you know, sometimes 15 or 16 for an anal gland tumour. So therefore it can be costly.

It costs a lot of money to set up a radiation centre anyway, so it may not be available locally. These are the principal adverse effects that have been described after treating a anal gland tumour, with radiation after surgery. Acute colitis, desquamation of the skin over the perianal area, let me see here, rectal stricture, rectal perforation, and chronic colitis.

Now these two in green are acute effects, and these will happen to some degree, with the treatment. Typically they start occurring around the 3/4 of the way through the treatment course, and they can be managed with supportive care in most cases and resolve a week or two after the treatment course stops. I might also say they resolve without any legacy.

The acute effects then are due to the death of the rapidly populating epithelial cells. And the likelihood is related to the total dose of radiation as well as the size of the fraction given. The other three effects here are the late adverse effects, typically occurring a year later, or often more than that.

The very earliest would be about 6 months after treatment. And these are due to death of stem cells, OK, in the tissue. And as we can see, they're much more serious.

They can be catastrophic and dreadful. For example, rectal perforation might result in need for euthanasia. So we want to avoid these late side effects.

And the reason why we can do that is because the likelihood of late side effects is related to one thing, the amount of radiation you're giving in each fraction. Therefore, We have two types of radiation treatment, hyperfractionated treatments, or definitive, curative intent treatments involve lots of small fractions, typically 5 a week for several weeks on the trot. As I say, we'll do about 14 to 16 for an anal gland tumour.

And the risk of late side effects is extremely low because the fraction size is extremely low. You can get to quite a high dose of radiation here and you should to kill the cancer, and therefore the acute reversible side effects are most important. You can also get hypofractionated radiation.

Now this is often called palliative radiation, or I tend to use the term hospice care with the owners. But typically you'd give like one fraction a week for a few weeks. And you wouldn't get to a very high dose doing this.

You're unlikely to have a significant effect on the cancer, but it can be a really good means of numbing the nerve fibres and causing improvement in pain control. It can be a good means of controlling inflammation. Because we're using a .

Because in a hyperfractionated protocol, we know it's a palliative treatment. Then We're using high high high doses per fraction. The patient is likely to have died or been put to sleep long before the late side effects of radiation are likely to occur.

So that's why hyperfractionated radiation can be useful to palliate end stage disease, and we're not so bothered about the late side effects because the animal doesn't really have a long term, to be frank. So in radiation for an anal gland tumour, we'd like a hyperfractionated protocol, which maximises the tumour control, minimises risk of late effects. And the reason why I've stressed this is because a lot of radiation treatments to date have kind of conflated the hyperfractionated and hyperfractionated idea.

It's getting a lot better now. We've got specialists in radiation oncology, who are able to do the most sophisticated treatments, and that they would tend towards hyperfractionating all of these guys. But the easier, cheaper, hyperfractionated protocols are certainly not gonna get you as strong a tumour control as the hyperfractionated ones.

I think that's all I'll say about radiation other than it's quite sophisticated now and we'd be looking at computer planning. In this case, we're looking at creating a lymph node in a cat. And we have special collimators which will shape the beam of radiation to the tumour that's trying to minimise the radiation that is applied to the healthy, healthy tissues.

But you can still get collateral damage in a healthy tissue where there's more of it in the primary beam. And so some new techniques which are now available at a few centres in the UK are things like intensity modulated radiation, where you can vary the intensity of the beam, just like pixels on the TV screen, you can divide the beam into little voxels, they're called, 3 dimensional pictures, some of them more intense than others, and that can also help to protect the surrounding tissues. So Radiation would be my first choice, if that's not possible, chemotherapy would be the second choice.

The same principle applies with with radiation as does chemotherapy. A microscopic disease should respond better because you've got a greater proportion of cells in the cell cycle, and that's where, where they're more susceptible to radiation. So disease, so drugs like moxantrone.

A milla have been evaluated in the injunctive setting after a surgery. And drugs like carboplatin or actinomycin D have been evaluated in the gross tumour setting for a cancer has been removed. But you could still consider using them in the microscopic disease setting too.

And there's been no clear winner out of these drugs, you know, all of them have benefits and drawbacks, none have been shown to be superior. And this brings me on to the elephant in the room. No clear benefit of radiation.

All chemotherapy post-surgery has been demonstrated. So you might think, why have I just been talking about it for the last 5 or 10 minutes? And I guess the reason is, well, it's complicated.

You're certainly right, no clear benefit of radiation or chemo per surgery has been demonstrated, but this certainly doesn't mean that they're not efficacious. It just means they haven't been trialled in the correct way. The first problem here is that the disease course of an anal gland tumour is typically slow, and dogs will have good, most dogs will have a good long-term survival, no matter what you do.

So it's not like you're comparing a survival of 2 weeks versus 6 months in the case of a hemangiosarcoma, for example. You're, you're trying to compare different shades of grey. And to do that, you need an awful, awful lot of, a lot more dogs than if you had a very short survival versus a long survival.

So at the size of a lot of veterinary studies, the statistics just aren't strong enough to show any benefit. The other thing is that the literature is a mess. It includes different stages of disease, often all in one paper.

If you look at survival times for different stages of disease here, you can see they're massively different from not reached stage 1 to 82 days and stage 4. They often include dogs with different levels of clinical signs, from the incidental ones to the ones that are at death stored due to hypercalcemia. They often poorly describe the comorbidities or even the reasons why the dogs are put to sleep.

Some dogs may be put to sleep for financial reasons. Some dogs may be put to sleep because they're howling all night and going senile. Some dogs are put to sleep because of being run over, for example.

Often the cause of death isn't recorded very well. So taking this all together, and from the first principles that an anal gland tumour is nearly always incompletely excised and has a strong metastatic risk, I would be giving adjunctive treatment to my dog, if he developed an anal gland carcinoma. And you can get studies like this, where they had some very advanced disease here, actually.

Half of them were stage 34 of them were hypercalcemic. And they treated with surgery and radiation therapy and then chemo with myoxantrone, and the average survival was over 2.5 years.

So as I say, I would use an adjunctive therapy in my dog. There he is, up there in the top right. But whatever path you choose, remember that this is a chronic disease.

We need to think of the regular rectal exams. We need to think of repeat CT scans every 6 to 9 months. If you're on a shoestring budget, you could consider the cheapest chemotherapy option available at the time, and that will probably depend on your geographic location as to what the cheapest is.

But still, if you're on a budget, do these detailed rectal exams every few months looking at the lymph node cluster and both anal sacs. You might miss distant disease, but it's more likely that these things will recur locally or metastasize to lymph nodes. Scenario 3 then.

You've removed the tumour. You've talked about adjunctive therapy, you may have done adjunctive therapy, and at a later date, you get a metastatic lymph node. What do you do?

Well, I'm gonna sound like a broken record here. Surgery, if you can. I'd stage thoroughly because if you've got a large burden of disease in other sites, it may affect your decision as to whether you do the surgery.

That's something to discuss with the owners. But with a recurrent anal gland tumour. And with metastatic lymph nodes, it's been shown that surgically removing them as and when they come up, will have a positive impact on the dog's survival and quality of life.

So effectively I'd go back to the beginning. I'll talk about surgery, then I'll talk about adjunctive therapy. And scenario 4 with distant metastasis.

I guess I would consider what the biggest problem is and how long this is going to remain the biggest problem. So what do I mean by that? So if you've got a few small lung nodules that wouldn't be seen on a radiograph but are readily seen on a CT.

It will be some time before these cause enough clinical signs to weigh down the dog's quality of life. So you might think, in the face of a grapefruit sized cluster of regional lymph nodes or an apple sized anal gland tumour, it would be a benefit to operate on these and then perhaps talk about a chemotherapy treatment to try to keep the distant disease under control. If you had cannonballs in the chest and the dog was dysmic, then obviously that's where your priority is, those are the signs you're trying to palliate.

So I wouldn't necessarily rule anything in or rule anything out with this treatment because you've just got to treat each case individually. And work out what the, the biggest burden to them is and whether that's going to change in the near future. And in this situation, say if you're not able to give a definitive treatment.

Or you and the owner have decided against it because there's a large disseminated disease burden. This might be somewhere where you could consider one of those hypo fractionated palliative radiation therapy protocols. They're cheaper, should be readily available at sites that offer radiation.

And typically we're talking weekly visits. With the hyperfractionated radiation, in one study, it did show that there was a significant shrinkage of the tumours in 40% of dogs. It would be nice if that percentage was higher, but it's still something we don't want to dismiss.

And 63% of those with clinical signs had improvement. A third of the hypercalcemia resolved. And overall, it was 10 months before the disease started to progress on average.

So it's not bad considering you're talking very kind of end stage disease. This study as well is very interesting. He had dogs with very, very large clusters of sublumbar lymph nodes.

15 had surgery. And the average survival of 6 months. 13 had radiation, again a hypofractionated palliative protocol.

And the average survival and the progression free intervals are more than double that of surgery. So in these ends stage palliative cases, The cheaper palliative radiation protocols, really something to think of. The second thing for these end-stage cases might be palladia.

It's a serrey. Now it's off licence. So the mechanism of action and the efficacy may vary from case to case.

But Pella has been evaluated best in the gross disease setting. OK. That is where you've got a tumour that you can physically measure.

And in studies like this and others, it was quite, quite interesting really. Over 2/3 of them, almost 70%, showed clinical benefit. But if you drill down into the details, perhaps you want more than just clinical benefit in general.

But if you break down the part the the responses, those that had a partial response, where the tumour shrunk by more than 30%. Compared to those with stable disease, where the tumour neither grew nor shrunk, you'd find it's actually the minority where the tumour shrank 1 in 5. Now, if the dog has no clinical signs and you're just happy to keep a lid on the disease, then this drug will probably be very beneficial.

But the chance is only 20, 21%. For a for a tumour that needs to be shrunk because it's causing clinical signs like tesmus, constipation, etc. And the chances for me are a bit slim.

The other thing with this drug is that everything is finite. It doesn't go on lasting forever. And before the disease progressed, you know, you're talking about 70, 76 days, 469 days in those with stable disease, or 347 days where they actually shrank.

Furthermore, And I'm saying this because there's often a lot of interest in using palladia for treating anal gland carcinomas. A lot of people find it easy and simple and a neat little treatment, and, but it is, to be fair. But there's a few things I'd like you to consider.

The way this drug works. Is by interrupting signalling through a mutated receptor. It's it's licenced for KI receptor in my cell tumours, and we're not quite sure what it's doing in the anal gland tumours.

It may be inhibiting the receptor for vascular endothelial growth factor, among others. But basically it's where the cancer is driven by a mutated receptor which it keeps on telling the nucleus of the cell to get the vision underway, even when there's no ligand or hormone bound to the receptor. So with Taserinib, for example, you'd abrogate this overactive signal into the receptor, you'll stop the uncontrolled cell division and you'll return the cancerous cell to behaving like a normal cell.

That's the idea. So it doesn't really kill cells. And consider this.

If we're giving cytotoxic chemotherapy like carboplatin, it's a bit like radiation, you're killing the cancer cells. With each dose, you should have a net decrease in the cancer burden. Something like to Serena.

Well, you're kind of maintaining stable disease. The cancer cells remain alive. And I've seen cases where I've taken the dog off the drug for some reason, perhaps a side effect, and you start to see the cancer growing back.

So there's no defined stopping point. Therefore, it can become expensive and the longer they're on it, the more likely they are to have some of the chronic side effects. These are the principal adverse effects.

Weight gastrointestinal like diarrhoea, vomiting, anorexia is very common, as well as weight weight loss in some cases. But then you've seen things like hypertension, protein losing nephropathy, myelosuppression, anaemia, hepatotoxicity, muscle cramping, lameness, epistaxis, immune-mediated hemolytic anaemia in some cases, as well as thromboembolism. So, I think some of them are acute like the GI ones, you know if you're gonna get them quite soon after you've started the drug.

Others of them have seen develop at a much later date. So, yeah, can certainly consider using the serenib to treat an anal gland tumour, but. I wouldn't consider it a safer, or more dangerous than a chemotherapy drug.

I'd consider them kind of equal. They can also be expensive. The response rate in those that are actually shrinking is quite low.

And if you do get a response, the time is finite. The other interest I find in the use of the serinib. Is as an adjunct to surgery.

That is, some people like to use the serinib in the microscopic disease set. And it's a sensible thing to think of. In this study here, they used to erinib as an adjuvant treatment, against adenocarcinoma in dogs in general.

And if you look at the figure on the right, you can see a very small benefit was shown. The average survival was 2 months greater in the surgery plus the serennib group versus the surgery alone group. But no, this is about adenocarcinoma in general.

And when we drill down to the the apocrine gland anal sac adenocarcinoma. Well, actually, there's no significant difference between the two groups. So for me, because the fact that the treatment's ongoing.

It can get expensive, etc. Etc. Risk of side effects.

And it's there's no evidence to show that it'll work in the adjunctive setting. I choose only to use it in the gross disease setting, personally. Finally, let's talk about the prognosis.

The overall survival in books is reported as between about 1 and 3 years-ish. But look at this, it's only 41 to 81% of dogs actually die due to the anal sac tumour. That's not much.

Really. So a key factor here is the stage of disease. Again, you know, stage one disease, it's very difficult to calculate survival time because most dogs are alive or have died of other things at the end of the study period.

And in this particular study, only 9% of dogs died of the tumour related causes. So, if we were to list the important prognostic factors, then I think stage and going into that is the size of the anal gland tumour, the level of regional metastasis, the presence of distant metastasis. Those with clinical signs will have a lower tolerance of disease than those without clinical signs.

And in that we'd have things like hypercalcemia, which I think we all know can make dogs very acutely unwell. And the treatment. If you don't treat a disease, you will have given the dog a very poor prognosis.

But if you treat with surgery and you look at adjunctive therapy, you're maximising the dog's chances. And lastly, treatment when progressive disease occurs. Please don't read the, you know, write these dogs off with removal of lymph metastatic lymph nodes that turn up a year or so later.

Average survival one year. Without average survival, barely 2 months. With a lot of cancers, we're used to the histology being very prognostic, .

And actually, the histology has not been of very much use to date in apocrine gland adenocarcinomas of the anal sac. OK. In this study here, which, to my knowledge, is the biggest one published.

We did find three factors, the presence of necrosis, the predominant histological pattern as in forming a solid mass or versus non-solid, or the presence of vascular invasion. These things had a significant effect on survival. Of note though, the mitotic count and the Chi 67, I mean histochemical score were not prognostic.

And that's a big difference to other tumours, for example, in mast cell tumours, soft tissue sarcomas, melanomas, lymphoma, and many others, and mitotic count particularly is very strongly prognostic. You can also do immunohistochemical staining for adhering as well, that has been shown to be prognostic. But I think if I was asked what the strongest prognostic factors are, as far as I'm concerned, I would go with the clinical ones like the stage, the treatment given, the clinical signs.

These things would be more of interest sake, or to try to refine any prognosis if I had to. Just a few words on some other diseases. In the melanoma of the anal gland.

Well, this is a very aggressive disease, and the cases I've seen have had survival similar to this, average 3 to 4 months. Often treated with a combination of surgery, radiation, chemotherapy, or vaccine, and you find most dogs die of local disease, sometimes distant disease. But in one particular study, there was one dog who lived for almost 5 years.

The, the key to this was that it was a small tumour and it was treated with appropriate surgery and chemo. And in the squamous cell carcinoma of the anal gland. And 9 dogs in this study.

6 out of 9 lived to about 0 to 7 months and 2 were lost to follow up. And after the 5 dogs were surgically managed, 4 out of 5 had recurrence within 1 to 5 months. Again, there was a long-term survivor in this group as well, but from the anal gland squams I've seen, there have been aggressive diseases that are just very difficult to keep under control, even for a short period.

I mean cats. Well, perhaps we shouldn't, but currently we don't have any other information to go on. The treatments are usually extrapolated from dogs.

Complete surgical excision is key. And the role of adjunctive therapy is not evaluated, but is often used in incomplete excisions from the first principles basis. I've never heard of many decent long, long-term outcomes in cats.

You often get disease progression quite soon, no matter what you do. So in this study then are 30 cats with surgery and chemo, the average survival was about 78 months. You do get some living longer than 1 year and some living living longer than 2 years.

Perhaps 1 in 5 might go to 3 years. But you can might be able to suggest those that have a poorer prognosis by looking at local tumour recurrence, 8 times more likely to have a short survival. Versus the as well as the increased nuclear pleomorphism score, where they're 10 times more likely than a short survival.

Right. So I think then that's just about all I had to discuss tonight. But I'll end on one thought.

Is there a better way to treat anal gland tumours? Well, I'll show you this. Again, I've shown this slide twice already, and I apologise for that.

But look at these stage 1 cases. Survival can't be calculated, or average survival can't rather, because they die of other things or they're all still alive. Only 9% of these stage 1 dogs die to tumour related causes.

So if you can pick them up early, you can get a really good outcome for these guys. And I would encourage you, particularly in the predisposed breeds like the cocker spaniels and things, to consider regular anal gland exams, perhaps at the time of yearly boosters to screen for these small masses before they become a really big problem. The second thing I think we can do is start to refine different treatments to different stages that perhaps that's a job more for the oncology community rather than the general practise community.

But we're let down in having poor evidence to base our treatments on because, as I said, you have studies with a potpourri of different stages and clinical signs, and causes of death, all one together, and it's hard to work out what's done what. In summary then, Any anal gland mass is likely to be a cancer. Of those, the apocrine gland adenocarcinoma of the anal sac is the most common.

The clinical signs are variable depending on the metastatic distribution or the perineoplastic disease. This is a very treatable disease though. We just need to manage it as a chronic disease and make sure the client understands that from the start.

Surgery should be the mainstay of removing these tumours. Radiation or possibly chemo are often used adjunctively to consolidate control. If you have progressive disease, please don't write these guys off.

Please take surgery and starting at the beginning again. And for the palliative therapy, where you've got a heavy burden of disseminated disease, consider radiation or to serinib therapy. Remember that the prognosis is heavily dependent on the stage and on the treatment that you give.

Melanoma and squamous cell carcinoma also occur in the anal sac, and the prognosis is dependent on local control principle. And finally, our feline friends get apocrine grandadnocarcinoma of the anal sac too. It's a very important differential for a perianal abscess.

The mainstay of treatment is surgery, just like dogs. Now, I, Bruce said that I work at Highcroft Referrals, which is true, but as of 23rd of October, we're rebranding and moving to a new hospital, and that will be Bristol Vet Specialists, and we're going to offer radiation therapy there. You can see our linear accelerator in the top right.

I'd like to acknowledge my colleagues from left to right, you have Kate, Beth, Andrea, Shannon Lottie, and at the top you have Jerome and Inga. These guys, too many to name, support us in surgery and imaging and anaesthesia. Thank you ever so much to Arbet for asking me to speak and thank you to you guys for tuning in.

If you've got any questions, I'll do my very best to take them now. As I have overrun a bit, you're very welcome to email me with questions too. Thank you.

Owen, thank you very much. That was unbelievable, presentation and very decisive and insightful. So thank you so much for putting that together.

The learning level was very, very high. I must say, I am incredibly jealous looking at those pictures of your new practise. I think you guys are gonna have loads and loads of fun playing with your new toys, and I wish you all the very best going forward.

Thank you. Thanks. And that's it, folks.

Thank you for your time, and, I hope you enjoyed this as much as I did. And, once again, to Owen for not only this presentation, but for the series that he's done for us. It really has been fantastic.

And as always, the recordings are all available on the website. This one will be up in the next couple of days if you want to go back and look at things again. So, Owen, once again, thank you very much.

Theo in the background, thank you to you too and from myself, Bruce Stevenson, it's good night.