So thank you very much for following this webinar. Tonight I'd like to talk to you about electro chemotherapy and how that can be a very useful tool for anti-cancer treatment and a great option for patients that may not have many other options. First of all, I'd like to, display some conflict of interest.
I do work with the Veterinary centre Referral Service where many of the cases I will present, have been, have been treated. First of all, I'd really like to introduce to you all different types of cancer treatments so that you know where electro chemotherapy sits among these. The main type of cancer treatments involves local type of treatments where you treat a mass on a specific tumour, and these are surgery, radiotherapy, electro chemotherapy, and nowadays, we also have intralesional intralesional therapy.
A typical example would be something like elfonta. There is then systemic treatments, and we all are familiar with chemotherapy that involves the use of medication taken by mouth or injection, immunotherapy to stimulate the immune system. A typical example is the canine melanoma vaccine and also hormone therapy, although it's not as used in veterinary medicine as in humans.
Local treatments are generally used to treat a specific tumour like a mass, or they're used as well to. Tumours after surgery when complete histological margins have not been achieved, while systemic treatments are generally used for systemic tumours or tumours that are high grade or metastatic or specific isotypes like the ones that are listed in the slides like hemangiosarcomas, anosar carcinomas, melanomas, plastic sarcomas, and isocystic sarcomas. So today we'll focus on a local type of treatment that is electro chemotherapy.
What is electro chemotherapy? Electro chemotherapy is an anti-cancer treatment technique that combines the administration of chemotherapy with brief electrical pulses that are of course generated by a machine. Electrochemotherapy uses a principle of drug perfusion that is called electroporation.
So what electrochemotherapy does does uses brief electrical pulses that creates some transient pores in the cell membranes. In this whale, some medications that don't usually enter the cancer cell where They are supposed to exert their mechanism of action will be able to enter effectively any high concentration of the cancer cell, and this is usually molecules that are large, for example, larger drugs or even DNA or RNA medications that are generally lipophobic and therefore come across the membranes such as bleomycin, cisplatin, or carboplatin. And as you can see, this is an example of electroporation which is induced by electricity.
Electro chemotherapy uses two different types of electroperation. Strictly speaking, when we talk about electro chemotherapy, we look at reversible electropoation where this increasing permeability of the membrane is only transient, and after the electricity has assisted, the membrane reseals itself again. The cells will continue to live and therefore the chemotherapy has entered.
The cell will act and kill the cancer cell. There is a way you may hear in the future talk about irreversible electroporation. Well, we actually use the electricity to kill the cancer cells, so we call direct cell death by necrosis, and this is where we use higher energy pulses and could potentially help increase the efficacy in larger, more, more aggressive tumours.
Electro chemotherapy therefore increase the uptake of chemotherapy by the cancer cells through the use of electricity. So electricity is used mainly to deliver the chemotherapy, and the beauty of this technique is that the cancer cells appear to be to be more sensitive compared to normal tissues, and this. This is why the rate of complication to the treatment area is actually quite low and at the same time, because the action is primarily on the tumour, so it is not a systemic treatment, it is a local treatment.
Therefore, the systemic toxicity, gastrointestinal adverse effects, myelosuppression, and so forth are very, very low to basically none. And we use electro chemotherapy to increase the uptake of not only chemotherapy drugs, but also anti-cancer vaccines and also cytokines, what we have defined as immune, immune medication and immune immune therapy. But how is electro chemotherapy performed?
So this is an example. This is one machine, an example of one veterinary electro operator. As you can see, the machine uses different probes.
Some are plates and the tumour may go in between the plates. Some other probes use needles. This looks quite long needles, but obviously only a small part of the needles is inserted in the tumour or the skin, and there are also much smaller.
Probes than this and different types of probes. The needles of different lengths, different thickness, and not all electroperation machines are similar. And that's why, when we compare paper looking at results of efficacy from different electro chemotherapy treatment, we also need to consider what machine has been used because techniques are standardised, but also it's very operator dependent still and also machine machine dependent.
So briefly speaking. A patient that needs to be treated with electro chemotherapy would be sedated or anaesthetized, depending on the area that needs to be treated, how sensitive this area is. And what we would do, we would administer chemotherapy, the medication that we want to use for, for our treatment.
Generally we use the chemotherapy bleomycin. And this can be injected intravenously in most of the patients, although occasionally we can inject it inside the tumour intralesionally, and then cisplatin or even calcium. So cisplatin, as you know, cannot be administered safely intravenously to cats, but with electro chemotherapy we can administer it intralesionally.
Calcium as well can be used. Calcium is not a chemotherapy by itself, but it is very tightly regulated in the body, as you all know, and it is primarily an extracellular, an excellular electrolyte. So, when there is an increased permeability and the calcium increases within.
The cancer cells because it manages to get inside, then that as well can be highly toxic for for the cancer cells, and this is what we would call calcium electroporatio. So calcium can be used as well as a form, as part of the anti-cancer treatment in the electro chemotherapy. And as we said, the, the goal of electro chemotherapy is to increase the concentration of of.
Within the cancer cells. So in the case of bleomycin, if we give bromycin intravenously, we would achieve a certain concentration, let's say 1, within the cancer cells, but with the application of the electricity, the concentration is 500 to 7 times higher within the cancer cells. So it really corresponds to blasting the cancer cells with chemo, something that we would never be able to achieve if the medication was given only intravenously.
And the same thing is for cisplatin. We achieve a concentration which is 4 to 8 times higher compared to, to the extracellular, extracellular tissues. And as you know, cisplatin is a highly toxic chemotherapy, so increasing 48 times the concentration means a very big increase in, in toxicity if we did it intravenously, but as well of efficacy, of course, with, with elective chemotherapy.
The electrical pulses are very, very. We talk about milliseconds or microseconds. The treatment duration is very brief as well.
The patient is sedated or anaesthetized. The area is clipped because of course we can't apply electricity on top of her. We see some sparkles, some sparks, and then we wait 5 to 8 minutes so the chemotherapy achieves a certain concentration within the bloodstreams and also the area where the tumour.
And we treat the patient. The treatment lasts only a few minutes. It's a very, very quick treatment, and the electricity induces electroperation for a duration of about 20 to 40 minutes.
So we have that amount of time to complete the treatment. And as I said, it only takes a few minutes for a treatment, but in tumours that are more complex in areas they are very wide. Again, some time it could even take a good 10 to 15 minutes to treat the whole area.
We said it can be done under sedation in most patients, of course, with analgesia, sometimes with local blocks as well, but the, the voltage that we use, we're talking about anything between 800 to 1300 volts, so they are painful stimuli, and therefore patient is to be unconscious, during, during the treatment. Very importantly, these machines, allow a safe generation of pulses, because as you know, electricity can burn. And these machines are, are set so that they can control the amount of electricity that is delivered very tightly and also may allow, may block and may stop working if there is a potential of overheating or overcurrents.
So there are very important safety mechanisms that are within this, the software, the hardware of these machines. How many treatments do we need? So if we treat, if you use electro chemotherapy in the adjuvant treatment, so if you have a wound where, a tumour has been incompletely resected and you want to use electro chemotherapy to try and decrease the chance of local recurrence, usually we would do 1 to 2 treatments depending how extensive the wound is and how anatomically complex the.
Is to make sure that we cover with electricity the whole area because of course you could give the chemotherapy, but if then you don't cover with electricity everywhere, the chances are the treatment is not going to work. Similarly to radiotherapy, you could have geographical mass if you don't treat the area where, where you need. Treatments are administered anything from fortnightly to up to 6 weeks.
Generally, within a couple of weeks, most patients are fully recovered even earlier. Some patients may need a little bit longer, so I would say no, no more than 6 weeks. And we usually start as with chemotherapy as soon as the stitches are out, as soon as the wound, is well healed.
So I would say 2 to 3 weeks in areas where the skin is a little bit thinner or if there has been a complication or there is still inflammation going on, I prefer to wait an extra week or two, and that's because obviously the tissues may be more sensitive. The negative effect of electricity and pressure or potential of electric burns, which obviously shouldn't happen and would be considered a complication. We do use electro chemotherapy also intraoperatively.
Intraoperatively, it means that I go into theatre with the surgeon. The surgeons take it with the tumour, cut the tumour out, and before. Before suturing the wound, I can treat the tumour better to allow me to treat deeper into the tissues and avoid geographical waste and the wound is sutured, and if you're happy with that, there is no tension, that there is no specific, you know, fear that there could be some complications in the wound, I treat already also the wound itself, and then we do repeat another treatment after 2 to 3 weeks.
From externally. When we treat the gross disease, so when instead of treating a wound, where a tumour has already been removed, so when we treat gross disease, we usually would do one treatment and then assess the response. If the tumour is very small, one treatment is sufficient.
If the tumours are larger, it may be that we need to repeat a treatment maybe after generally 3 to 6 weeks. This is the first example. It's a cut, sorry, these are actually two different cuts, but this is to show you more or less the position of the tumour, where the tumour was.
This is a 9 year, 7 month old female spade domestic shorter that had a basal cell carcinoma, located in this area, had been removed by the vet with incomplete margin, had recurred. So what the surgeon did, he debrided the tissue with the skull. The blade down to the dermis and then treated with coagulation diathermmi for coagulation and we went on and treated the area with with electro chemotherapy.
There's some indication of, of the bases as well. This is one of the probes that we use and as you can see there's a couple of needles. The part that actually to conduct electricity is only this bit, the silver bait, which is about 0.5 centimetre deep inside the skin.
But what are the adverse effects we would expect from a treatment like this? Well, the functional impact, should be minimal, particularly in a case like this. We do have some swelling, in the 1st 2 to 4 hours, sometimes up to the 1st 24 hours, depending on the technique that we use, in that patient because it was a recurrence, we treated quite heavily and the owner was not going to allow us to do a second treatment, but.
Generally the swelling is quite minimum. I find that with muscle tumour the swelling may be a little bit more pronounced. This is the patient after 18 hours, it was quite a bit of swelling, but we'll see, the swelling does resolve very quickly.
The swelling is the consequence of the electricity, and so it does resolve very, very quickly. We should not see healing, to the area. We should not see, sorry, damage to the area, and to the normal.
Tissues, so the healing should occur with no damage, and that's another important thing in comparison, for example, to radiotherapy. The cancer cells are the ones that are affected if you perform electro chemotherapy and therefore, the part, the area should be healing normally without destruction or without much scarring. But of course if there is any overheating of the area or if you use irreversible electropo operation.
Energy is too high and of course there could be some damage to the interstitial space, not just to the cancer cells and some scarring may may occur. There may be occasional bleeding from the area where you said the needles, but, generally the bleeding is very minor to none really, and electro chemotherapy as well does cause vasoconstrictions and therefore could be used to treat tumours that bleed and to help to stop the bleeding as well. Can be used in tumours that are ulcerated and it does cause, because there is electricity, it does cause some transient, muscular contraction.
Obviously, one question is, is it suitable for patients with a pacemaker? Is it suitable for a patient who has epilepsy or, or cardiac disease? Yes, absolutely, because we are treating the surface, of the, of the body, and if you're treating the head or the chest, no complications have been .
Have been reported. Generally pain is very well manageable just by paracetamol or nonsteroidal medication, depending on what the patient can tolerate. Basterol is not generally used unless the patient keeps licking the area and scratching, but again, that may be just very transient, maybe for the 1st 24 to 40 hours if it is at all needed.
This is the same cut that we saw in the previous, . In the previous slide, and this is 2 weeks post treatment, you see there is a little bit of a scar in here, 3 weeks post-treatment, 5 weeks, and this is 6 weeks post elective chemotherapy, it's completely healed. And this is one year, the patient after one year, had a recurrence on the bridge of the nose.
We suspect it was probably a therapy miss. The primary tumour was located near to the side. We obviously considered some margins, but the owner noticed some other growth, and, and after a year there was some recurrence in the area, and this is still treatable.
We could still go back and treat with, with elective chemotherapy. Systemic adverse effects we said are very minimal. Cisplatin is safe intralesional in cats, although we have to consider that when we put cisplatin in the area, make some pains and more necrosis.
In the cat I've just presented, it was quite a marked reaction because we did put some cisplatin as well, in retrospect, possible maybe there wasn't even, even needed. It was one of the first few cats we, we had treated. Allergic reaction could occur to cisplatin, bromycin, although these are extremely rare in our patients.
Pulmonary fibrosis, nephrotoxicity again has been reported in humans, but very rare in pets. We haven't seen any instance of this. But of course, if you have a patient with, renal disease and you're also gonna use no steroidal medication and anaesthetic, you have to be extra careful with, with anything that you add on that could be potentially nephrotoxic.
We always perform a baseline general health assessment before treatment, which included full haematology, full biochemistry, and full urinalysis. Ideally we treat tumours that are not metastatic. That was the initial guidelines, but, nowadays we can treat tumours that are metastatic as well because this is a great treatment which is minimal invasive.
To, to help patient to palliate clinical signs from the primary tumour itself and I have treated some lymph nodes as well, where they were suspicious of metastasis, and so there are studies in humans as well where they do treat lymph nodes as well so there is still a lot to learn and there's a lot of potentials of this technique. Electrochemotherapy is not indicated in general as an alternative to surgery when surgery is possible with a good oncological and functional outcome. And this is because a lot of tumour can be cured by surgery, while with electro chemotherapy, the response is very high.
We'll see like 80, 90%, but it's a different concept. You leave the tumour in situ and if there isn't a complete response, the possibility. Of a recurrence is still there.
There are some tumours we'll see like carcinomas, the one that we've just described, or, well, chemo elective chemotherapy could really well as well be considered as an alternative because of the high efficacy. So we use electro chemotherapy in tumours that are inoperable, including highly vascular tumours, as an adjuvant to surgery. So you remove your.
Tumour you have achieved incomplete surgical margins, and then, your patient, you cannot go ahead and do a second surgery. There is no possibility to perform radiotherapy or the owner considered radiotherapy to be too intense as a treatment because it does require multiple anaesthetic, maybe travelling and maybe a high cost, and so, . And so electro chemotherapy is a very good alternative, and that is also in, in patients where the tumour is not immediately operable, but you can perform a cytoreductive surgery and then plan to go ahead with electro chemotherapy.
Electrochemotherapy could be used prior to surgery to decrease the size of the tumour, but this is not a very frequent, . Frequent indication, that, that we use it for. And the beauty of elective chemotherapy is that you can use it at first presentation where the tumour has recurred after surgery, radiotherapy, chemotherapy, after any type of treatment, and even if it recurs.
After elective chemotherapy, there is still a possibility to repeat the treatment, also because you may repeat the treatment with the same technique but also with different technique in terms of different drugs, and also different, different techniques like reversible versus irreversible electrooperation, . Interior, resistance is not a concern with the electro chemotherapy because as we saw in the previous slides, the con the, the medications achieved such a high concentration within the cancer cells. That really this should overcome resistance and I think obviously more studies needs to be done with this, but very often we have the feeling that if there is a recurrence, it's likely due to cells that were maybe not covered by electricity and therefore were not hit by the treatment as as strongly as, as, as needed.
So very, a very, very flexible, technique, a very, very effective technique in many instances. Any tumour type can be treated by electro chemotherapy, so there isn't a specific tumour type that is more sensitive, although, of course, because of because of how they sit, because of where they sit, like anatomical location or because of specific characteristic of the tumour environment. Some tumours may be more sensitive than others, but in general, all tumours could be treated with electro chemotherapy.
Of course, in order to be able to be treated, we need. To be able to access the tumours with electricity because as we said, if we don't cover the tumour with electricity, if the cancer cells are not hit by the electricity, then we won't be able the, the, the chemotherapy won't be delivered within the cancer cells and it won't be as effective. So it comes with it that certainly all cutaneous and subcutaneous tumours could be treated.
Carcinomas are particularly sensitive, but we'll see muscle tumours, sarcomas, melanomas as well, and particular interest feeling carcinomas. And of course we talk, we think straight away about head and neck tumours which are often very difficult to address surgically. So we have oral, ocular, auricular tumours, parotid tumours, phelum squamous cell carcinomas.
We discussed metastatic lymph nodes. We discussed bleeding tumours and. In Humans, they already perform percutaneous or laparoscopic treatment of tumours like thymomas, prostatic tumours, allopathic masses, and this has been reported in veterinary medicine as well and can be done in veterinary medicine as well, included bladder tumours.
Of course, you need to have specific machines for treatment, as I said, all, not all electro operators. Not all veterinary electro operators are the same, and not all of them are suitable to perform advanced electro chemotherapy treatments and in humans there is of course research looking into tumours such as pancreatic tumours, bone tumours, the treatment of bone metastasis, lymphatic tumours. So it's a, it's a very, very interesting, interesting technique, and we'll hear more in the future.
Is there any contraindication? Well, I mentioned already that no, epilepsy is not a contraindication unless of course it is a very high risk in terms of sedation or anaesthetic. If there is significant arrhythmias, pacemaker, again, that those are not contraindications as long as the patient can be sedated or anaesthetized.
Obviously they would require. Certain precaution in regard to selecting the appropriate sedative and anaesthetic protocol, and monitoring as well, having a surgical implant, diabetes, or other comorbidities is not a contraindication as long, of course, you don't put the electricity straight on metal, which obviously won't be a very good idea. Each patient, of course, needs to be, assessed for, .
I need to have a general health assessment, as we said, making sure that there isn't any specific contraindication to the administration of chemotherapies, but bleomycin, that is the one that we, we use generally, it's, it's a very safe medication. It's very mildly myelosuppressive, and, and really we do don't, we do not tend to see gastrointestinal signs. I do administer an anti-nausea medication on the days such as metoclopramide.
Or well Maropetent, that's the first sign, but I've stopped sending these patients home with Maropetent because, they do, as long as they recover well and there isn't any adverse effects from the sedation and anaesthetic itself, they generally do recover very quickly and there's no systemic signs to, to see. But I do find that if there is any gas in sizes, most of the time it's attributable to a sensitivity of that patient regardless sedation or anaesthetic. So let's look at some specific cases and we'll look through examples of different types of tumours where electro chemotherapy can be used.
Overall, the rate of complete tumour aggression following electro chemotherapy is reported to be high, although these passengers may vary among the tumour type, and as I have explained, unfortunately, it's very difficult to compare, different studies as well because it is different electropoation, different electroporation machines, and they could be tumours that have different characteristics and Also different experience of the operator and even in cases of partial response, electro chemotherapy can result in an improvement of the clinical signs such as pain, bleeding, reduction, and also the amount of need of medical care that these patients may require. With electro chemotherapy, it's a very frequent tumour that we see in both in general practise and referral practise are muscle tumours, and typical, as you know, muscle tumours, they don't choose where they occur. They can occur everywhere on the surface of the body.
They can be very difficult to remove even if small because of where they are, and they require quite wide margins. We know that very often and very frustratingly, you may achieve. Complete histological margins which obviously carries the fear that the tumours may recur, and in these cases you could consider further surgery, radiotherapy, or as well electro chemotherapy.
Of course you could perform and administer systemic chemotherapy to these patients, but this is more intense. It's generally not needed, and the most effective way would be to select a local type of treatment amongst surgery, radiotherapy, and electro chemotherapy. So, there is, at least one study, but there is more than one, but this is just an example.
This is a study published in 2006 by Enrico Spgnini, who, is, one of the most experienced, one of the most researchers in this field. He showed an overall response rate of 85% and Also aid an estimated time to recurrence in patients that had the muscle tumour removed with incomplete margins of 552 months. So it is quite, quite a big effect and with a range of 40 to 60 months.
So this compares very well, as you can see with the data on the right of the use of Adivan. Therapy we have high tumour control at 2 years with the use of chemotherapy as well where there is 50% relapse at 1 or 2 years and and obviously as an alternative we could use adjuvan previsceral antihistamine, but there's no specific studies to compare, to compare with electro chemotherapy. These are some examples of patients with tumours that underwent elective chemotherapy.
You see, this is a patient that had the tumour removed in a quite a difficult area. Obviously the second surgery here would not be very possible. Well, it would be possible for lateral margin possibly, but there's not much delay that you could remove in here.
This is another patient that. The tumour removed from the palmar aspect and again, second surgery here will be very difficult once you get diagnosed with incomplete margin and as well as having a tumour recur in this area would be very problematic for these patients. This is a cat, as you can see with the tumour removed from the lateral aspect.
Of the, the feet again, very thin skin, no other layers, not much, not much poss other possibilities for surgery other than obviously radiotherapy. This is another dog that had some tumour removed at the base of the tail. This is again interdigital tumour.
This is a well master that had a big tumour, a couple of tumours removed from these areas, so we treated the whole side of the dog. This is again another patient. We had a tumour removed in this area, dorsal aspect of the foot, and this is as we treat it, and this is obviously treating.
We do have to gown because obviously we do use electric chemotherapy, administered electro chemotherapy as protective equipment and we do wear gloves to handle, handle these tissues. So these are quite good examples. Well, I guess all of you have been in, you removed this tumour again complete margin.
This is what we do. Cannot do more surgery. We can't just defend amputation, of course, here, my clients cannot go for radiotherapy because of costs and travelling issues and quite intense treatment.
I think in this case electro chemotherapy should be considered. And some wounds like this one, for example, they're quite nice, small wounds, this and this one treatment, one electro chemotherapy treatment may be sufficient. This is instead a slide showing the potential efficacy of electro chemotherapy in patients with gross disease, with massive tumour and gross disease, so where surgery has not been performed yet, and they compared it in the study.
In 2009 to surgery and they saw that there was quite high, high efficacy. There was 62.5% complete response rates within 4 to 5 weeks with 70% complete response at 30 months and that compared well with surgery.
Well, there was 50% complete response at 30, 30 months. However, please note that the response was good only for smaller tumours. So, this technique is possibly not suitable for tumours that are very large, and that's why we always prefer to debulk if possible.
This is the comparison with. Other, other techniques and possibilities that you may have. So when a tumour is emittedly resectable, you could use your adjuvant prednisolone or chemotherapy to shrink down the size of your muscle tumours followed up by surgery or radiotherapy, depending what clinical situation you find yourself in.
You could use a thyroxine kinase inhibitors such as mesitinib or tosatinib to shrink down the tumour. You could use vilastin or prednisolone, and as you know nowadays, you may have tigilano tagle as well, which is an intralesional type of treatment. Please remember that digilano tiglet is not an alternative to surgery.
It cannot be used in all paths with muscle tumours. There are very strict indication for for these medications and elective chemotherapy and the geno target could as well be applied in different patients. For example, you should be extra careful in using tillano taglet in tumours are ulcerated because of the irritant, because of the backflow when injecting medication into the tumour, and it can be irritant, and at the same time you're using it near the mucosa, and also because of, because of the tech the mechanism of action.
Could potentially cause loss of tissue, loss of function. So if you're treating, for example, eyelids or mucosis, you know, you have to be extra careful. The prodigilli piglet is not the best treatment.
In that case, you may have to take something different, such as electro chemotherapy or some debulking surgery, neoadjuvant treatment followed by, by surgery. This is an example, which has been kindly offered by BOPulse. You see there is a drug with a basal tumour which is interdigital, and in this case is after elective chemotherapy, this is after, after one year where there is.
Complete remissions. Other possibilities in treating these patients could be a debulking surgery or it could be some new audible treatment, for example, with palladian steroids or mestiiba steroids, before going ahead with surgery or before going ahead with elective chemotherapy only. Another big group of tumours that can be treated with elective chemotherapies are sarcomas and similarly to muscle tumours.
Very often they are tricky to achieve a complete wide histological margins, and the higher the grade, of course, more likely it is to recur. And this is where again part of the surgery, the therapy like chemotherapy can come and the. As you know, metronomic chemotherapy can be used in this distance as well, but as discussed with muscle tumours, if there is a complete histological margin, local treatment, one type of local therapy is, is always preferred.
And there are some tumours like low grade sarcomas that occur on the distal limbs. Some of these may never recur even if you remove them with the complete histological margins, but if they do, they're quite tricky to. To remove it could could be a life shortening and that's why we sometimes do offer, what we generally do offer the option to perform elective chemotherapy because it's not it's a non-invasive treatment, very well tolerated, I could really make a difference in terms, terms of efficacy rather than just watching and monitoring for a possible recurrence.
And these are some studies supporting the use of electro chemotherapy in the treatment of sarcomas. Again, the main medication used are bleomycin, but you can use intralesional cisplatin, and as you can see, the electro chemotherapy has been used both as in the adjuvant treatment, so after surgery, but also in. Comparatively, which is something that we do quite often with sarcomas as well because particularly in the limbs, where they can be located quite, quite deeply.
And this is a comparison, with, treatment of sarcomas, by adjuvant radiotherapy or metronomic chemotherapy. So you see with electro chemotherapy, we get a median inflammatory recurrence of about 730 days, which is really good and this compared quite well with radiotherapy where we've got 78% 5 years, 5 years . You may consider that many patients that actually come up with sarcomas as well, opposite to muscle tumours are actually quite old patients, and for some, obviously having extensive surgeries or intense treatments such as radiotherapy may not necessarily be an option of what the owners do want.
So this is a typical example. This was a senior Labrador, 10 years old, had a grade 2 sub tissue sarcoma, which, as you see, got to a certain point where really surgically speaking, the options were very limited. Getting a complete margin would have meant amputating the limb, and as you can see, it was kind of wrapped around the, the carpus.
It wasn't myself to treat this at that time. I did refer to a very experienced colleague, who is not retired but he's been one of the lumina of, of elective chemotherapy in the UK and what he did, he did a debulking surgery with intraoperative elective chemotherapy, did use some calcium as well. So 1st, 1st time they treated with calcium electro operation.
This is the patient after one week walking with a bus collar, no specific big scar or scar or swelling. This is 1 month after, we did decide to start metronomic chemotherapy as well. We were quite worried about the grade of the disease and the fact that although the bulky surgery was done, some macroscopic disease was left in situ as well, so not just microscopic.
After 6 months, there remained some swelling. And the patient unfortunately died. This is, this is the patient after a year, which was still free from local progressions, and also 2 years later again it was, it was doing very well, but in May 2020, he was, she was put to sleep unfortunately, and they're referring back due to anaemia to an abdominal mass.
We don't actually know if this abdominal. Mass, what organ it was, could it have been related to this tumour? Could it have been a metastasis, or was it something unrelated, you know, like in a month of sarcoma, which is also very frequent.
But nevertheless, let's consider how big the tumour was to start from, what the potential longevity of the dog would have been at that time, and this dog gained over 2 years of life with a good quality of life, and this was a pet with significant osteoarthritic, . Osteoarthritic disease, so really not a candidate for for any amputation for an amputation which would have been the only option for her. And you can see here she was very happy, you can see her tail wagging in, in the picture as well.
Electro chemotherapy is really super useful for, fe and cutaneous carcinomas. You know, white cats get these UV induced types of carcinomas that come on the ear tips and the ear, they can recur as well after you do a auricularinectomy. They occur on the eyelid, particular medial lateral countus.
They occur on the lips. They occur on the nasal planum. This is obviously an example of a very aggressive type of carcinoma.
If they're not addressed, carefully, we can get, they can get very invasive. They can progress. So, and this is a typical indication of electro chemotherapy where electro chemotherapy can really make a difference.
Filaneoplama carcinomas, these are some examples to use. So this is a pet that had already nosectomy, as you can see, for a carcinoma, but the tumour did recur, and so, the tumour was treated with elective chemotherapy, and this is the results. And this is a pet that would have not been able to be cured by surgery or would have required radiotherapy.
This is again another PET where the tumour is localised to the nasal planum, and again there was a complete response. There was a complete response. So that's the presentation, and this is 1 month after 3, after 3 treatments, and again, probably we could have even treated with fear.
We were still learning at that, that time. File cutinous carcinoma, this is a PET again. They came with carcinoma on the ear, on both ears.
There were some changes at one on the eyelids and one on the middle of the eye, one on the nasal lining, and we treated all of them at the same time. Particularly, I wanted to show you how in the auricular pinna, some necrosis was induced with some loss of tissue, but there was a complete, complete response, without, with any recurrence after quite some time. We do perform interoperative treatment as discussed.
Surgery allows the access of the tumours. They are deeply seated, either they are incavitary or either they are, in deep tissues, because with the needles you can only achieve a certain depth, of tissues. So and as we discussed, if you don't cover all the cancer cells with electricity, you are unable to, .
To get, to get a response that you have what we would call geographical miss. So this is an example of a peripheral nerve tumour that we treated, on these patients. We've done some of the brachopraxis as far as going up to, to the spinal cord, at the same time, you know, this is.
Near the stifle, for example, the surgeon has removed them. We treated the interparter and sutured it up, and this could as well be an a possibility for tumours that are high grade or very quickly growing, so that we don't give time to time, we don't have to wait for, for the wound to, to heal before, before starting the treatment. So it's a very versatile, treatment and it does not increase the risk of complications generally.
So, canine nasoplanum squamous cell carcinomas is another typical example where we could use electro chemotherapy and, And you may read in literature that opposite to cats, electro chemotherapy may not be as effective in dogs. That's not entirely true. The reason for that is because when we talk about electro chemotherapy, we use different techniques, and we have actually treated quite a few of them with quite good, good, good results.
And I think the main reason why in literature they report that cannona and plano squamous cell carcinomas do not respond as well is because opposite to cats, in dogs, squamous cell carcinoma tends to originate from inside the nostrils rather than on the surface and therefore they're less accessible to be covered by electricity. Less accessible to be reached by the probes. And we realise we're using a technique where we do perform a lateral rhinotomy.
I'll show you more picture later on, and where we can open basically the nostril and we can get access internally and therefore treat more effectively. This is quite an extreme case. This is a dog, quite a senior Labrador that was.
Had quite an advanced squamous cell carcinoma. We had recommended the bulking surgery, but the owner was not very keen for that. So we did the first interoperative treatment so that we could treat not only the outside of the tumour, but also internally.
You can see here there is a lateral knots. Formed and we are treating inoperatively with electro chemotherapy. You'll see in this video, you can hear the beeps, which are the pulses being delivered, and you'll see also the movement of the pheltrum, which is basically the muscle contractions that occur because of course the nerve is stimulated as well.
We had, of course, to be extra careful not to put the probe near obviously any metal, because that would have been dangerous. This is the pads of discharge, as you can see, had, quite, quite a swollen nose, but again, the swelling was mainly cranually. Everything else looked OK, of course it looks very different because it's been clipped as well.
This was on the. 5, there was still quite a bit of swelling and and here we did inject some calcium so that would increase the amount of swelling and necrosis. This is 6 months later.
Pat was doing very well, although there was some. Some stenosis of the nostril, and this is the PT 8 months later with a recurrence which again was, was treated by by electro chemotherapy. We don't usually perform all of this number of electro chemotherapy, but this was quite a complex case and the goal was to palliate the clinical signs.
The dog did tolerate this very well. The owners were, were very grateful. This is another typical example where these tumours do originate from.
They're generally inside the nostril. In this case, obviously there wasn't much, there was quite a, much of an option because it was very infiltrative, but you could have an option as well to remove just the tumour and treat with electro chemotherapy. But in this case, what it was decided to do in this 12 year old laborator, a quite senior patient, was to perform a nosectomy.
And of course, we did know that there was, because the tumour was extending quite casually in the philtrum, we did know there was going to be some residual disease. And this patient underwent electro chemotherapy postoperatively. Nowadays we do tend to perform this intraoperatively already to try and avoid the second procedure.
This is the histopathology, for these patients, and you can see that, the diagnosis was obviously, of a squamous cell carcinoma. It was very aggressive, 25 metres per 10. Our field and unfortunately there were no plastic tissue present within the submicular unilaterally.
So if we didn't go ahead and do electro chemotherapy again there would have been a recurrence and this patient tolerated this very well and recovery from this type of treatment is a very minor minor recovery. This is the technique I was discussing to you. We, we, we do perform a lateral anatomy.
We don't go into the bone, we just in the soft tissue part, as you can see, just the cuts, flip over the nose, get access to, to this area, remove the tumour, treat with, elective chemotherapy, and then, suture that up. So not a very invasive treatment, and this is if you want to read a little bit more, it's the paper of reference. Electro chemotherapy is a beauty as well for treatment of oral tumours, as all of you know, oral tumours, they cause discomfort, they cause malfunction, pets cannot eat, and also they're very difficult to remove when they're quite advanced, particular, and even when they're not, they do require a mandulectomy or a maxillectomy to, to be removed with a complete margin.
And although we've got a very good surgeon, very good analgesia, and our pets, particularly dogs. Tolerate maxillectomy, mandulectomy very well. Not all owners want to put a pet through that, and in not all pets that may be necessary.
In many tumours, you know, you could still have the options to remove the tumour without removing any bone and still performing electro chemotherapy as an adjuvant or to treat the tumour itself, with, with electro chemotherapy. This is an example of the treatment of a canine oral melanoma. This is a paper.
Published in 2020, and as you can see, the smaller the tumour is, the higher the response was, 100% in clinical stage one, clinical stage 2, 89%, and obviously the response decreases with bigger tumours and metastatic tumours as well. Melanoma is highly metastatic. We always recommend to use the canine melanoma vaccine as an adjuvant after surgery to try and decrease the risk of distant metastasis to delay the presentation.
And electro chemotherapy are shown as well to cause immune stimulations in humans, tumours that are distant from the primary may, go into remission as well. So we know for sure that with melanomas there is a systemic stimulation as well of the immune system. System which is a further advantage of, of elective chemotherapy.
But other examples are phin and canine oral squamous cell carcinomas, oral plasma cell tumours, oral sarcomas, and oralz ameloblastomas as well. And the more you have, the more you can, you can treat. This is one of our big successes.
This is both a senior, Labrador again, which came with a huge melanoma. You can see effect in the cranial mandible and arriving to the midline. This is the frelo that you are seeing.
What we did, we did debulk the tumour and treat it with electro chemotherapy. This is one week post interperative electro chemotherapy. You can see the surface of the tumour has become necrotic as it's diagnosed.
And yeah, so you can see here the the original size. And this is him as well. We're looking at the progression.
Some of the bone became necrotic as well, and then there was complete healing, from this. This is the clean wound in itself. And Bo did very well.
One year after treatment, there was no gross disease, and we are now over 3 years from, from treatment. Bo obviously had the melanoma vaccine as well. When I'd written on this slide again, I had because I had the last pictures from him.
Well, when he was having his 2nd melanoma vaccine booster, so a year and a half, this is him enjoying his, his holidays. I've got in touch with you on a recent little boy is still doing very well. He's not off the melanoma vaccine and, and has recently celebrated his, 13 to 14 years, .
1 14th birthday, what you can see here, these little red bits of tissue are not actually recurrence, where the bone had necrotized left like a little spike which was breaching through, breaching through the gum, but, as I said, there's. No signs of recurrence and after over 2 years we can consider this patient cured. So this is a real miracle story and we're all very, very pleased for these patients.
Consider the patients, if surgery was not performed or radiotherapy was not performed and he wasn't a surgical candidate, the prognosis for that patient would have been in the region of weeks. So great and well done both. Ameloblossom is another typical one where we can, treat, and, these tumours, were already responsive to intralesional treatment with bromycin and now if we had the electricity, we get even more response.
You can just treat with elective chemotherapy and you can do surgery. And adjuvant electro chemotherapy. This is again quite, quite a senior labordor as well.
So quite a friendly treatment for owners and for, for older patients as well where, the owners are not so keen to go to radiotherapy and potentially more effective as well in some cases. Again, we treated these patients with bleomycin and this is us. We added some calcium in as well and because we treated the gross disease, I was very worried about the fact that the bone was affected as well.
I did, I think some irreversible electroation. This is the same patients. This is after the 2nd ECT, was letting us see.
You see how the healing is happening, healing, healing very well, and this is the patient as well enjoying his life, of course. Heart pellets are common, you know, heart pallets very difficult to, to operate on. In this case, we did the debulking surgery.
Thankfully the tumour had not broken through the bone into the nasal cavity, so I had some treatment. A thistle occurred, but there was no recurrence of, of the tumour. Another example is this cat, again, another case of sarcoma in this case rather than carcinoma, and we had a complete response.
Unfortunately, the sarcoma had invaded the foramen as well, and this cat relapsed after 9 months due to retro bulbar recurrence, but there was no recurrence within, within his mouth in the heart palate. This is an example of a dog with an oral squamous cell carcinoma already operated twice before coming to see us. This is sublingual.
There was a very large sausage, let's say, so they located between the space between the tongue and the mandible, and as you can see at the time of the 2nd galactic chemo. There was minimal tissue residual on the tongue. This is a recurrence from a previous squamous cell carcinoma that this dog had a few years earlier, so we treated both the surface of the tongue and this new recurrence on the on the side of the tongue.
This is a little, little senior Jack Russell. This is to show you again, the response. A little bit of fibrosis on the tongue, and this is again under the tongue, the complete, complete response.
We have. It's a little, little amount of tissue left. This is another more extreme case, the squamous cell carcinoma.
The whole surface of the tongue eventually was affected and this was all treated with electro chemotherapy. With tongues, you need to be extra careful, not treating full thickness for the full weight because there is no terminal vascularization. In this case, we did it, and this dog lost a little bit of the tip of the tongue, but overall did, did very well.
Plan oral squamous cell carcinoma, here is another one. So like a small sublingual that we treated with electro chemotherapy and this one I did also, calcium electroperation, and then, and just for the first time we did do some irreversible as well. You have to be extra careful we treat the tongue irregard of the extent to try and decrease and minimise the adverse effect, of course.
This is again, the same patients that we treated. This is another case, again, a different cut, again, a complete response after only 11 ECT. So you can see just some scarring tissue under the tongue.
Ernie is another cat with the sarcoma. We don't see sarcomas in cats' mouths very much, but as you can see, very large sarcoma affecting the mandible. I don't have the CT scan images, but the bone was affected.
And again you can see it was very obvious from outside. This patient had one treatment, and is still doing very well. Again, we're well beyond the 3 years of treatment now, so fantastic response to cat that wasn't able to eat and was probably going to be alternate very soon after diagnosis.
Ano cell carcinoma is another possibility. We are considering treating it interoperatively. We're looking into that, but if there is an enlarged perineal mass that again can be treated with electro chemotherapy, this is not actually one or more pictures, but it's again from the colleagues Enrico Spignini.
Other examples are perianal carcinomas as well, third eyelid carcinomas, cutaneous lymphomas. If you've got any large lesion that is not responding to treatment, you could ameliorate the clinical signs with electro chemotherapy. This is an epitheliotrophic lymphoma in the Scottish West Island, Scottish, area, sorry, and this is, cutaneous non-epitheotrophic.
Lymphoma on a patient that have specifically difficult lesions on the eyelid, and on the bridge of the nose they were not responding to systemic treatment, so we treated with electro chemotherapy. This patient was of course on chemotherapy as well, and this is a pet that had a treatment for the parotid gland carcinoma, although it would be preferable to treat this one intraperatively rather than postoperatively. So concluding, very exciting technique, you can treat also deep-seated tumours.
We're looking into trying prostate. There are papers already looking into bladders, metastatic lymph nodes. Electroimmunotherapy is possible as well, where you don't just administer chemotherapy, but also, cytokines such as interleukin 2, interleukin 12, and there are already studies in veterinary medicine, gene vaccine.
As well. We are combining electro chemotherapy safely with conventional chemotherapies. For example, dogs with muscle tumours that require ve blasting to have it given at the same time as electro chemotherapy or pets that require carboplatin.
That is another medication that can be used for, for electro chemotherapy. And of course, we're looking into combining that as well with radiotherapy as two complementary techniques. In summary, it is a reliable versatile technique.
It can be used in any patient depending on performance status unless it's really contraindicated to sedate them or to anaesthetize them. It is safe with reduction hospitalisation because it's only one treatment or just a couple. It is done on an outpatient basis.
It is rapid. It is efficient. It does reduce frequent signs such as pain.
And bleeding and improves quality of life with limited adverse effects and it is also cost effective because the cost, it must reduced compared to surgery for the smaller tumours, but of course something more intense and also more high tech compared to, for example, radiotherapy. This is, we had a change of team in the years, all wonderful nurses and looking after our cancer patients, and I'd just like to thank. Again for, for joining us today and if you need any advice, please do not hesitate to contact us, as I selective chemotherapy is very often still not a standardised procedure.
It's very operator dependent, so work may not be done in the hands of one clinician, maybe possibly the end of the other one. I will be always very happy to give you any advice. Thank you again, and I look forward to meeting you in other webinars.