Knowledge is power ~ what I learned as a result of Tilly's cancer that could help other dog-owners to make more informed choices for their best friends.

On Saturday 10th February, I had to make the decision that every dedicated dog owner dreads. Although I'd had a couple of months to prepare myself for it, I wasn't ready, and to add insult to injury it didn't happen how I'd planned it; how I'd wanted it to happen. I know that it wasn't what Tilly wanted either, but within the realms of the limited choices laid out before us at the time, it was the only decision that wouldn't have involved prolonged or unnecessary suffering for her. However, the point of this post isn't to discuss the right time to say goodbye to a beloved canine companion, nor how to cope with the devastating loss. It's about imparting the knowledge that I gained throughout the last eight months or so of Tilly's life, which might just help other dog-owners to make better, more informed choices for their best friends.

Although Tilly was officially diagnosed with gastric adenocarcinoma on 3rd January 2018, her symptoms had preceded this by about seven months. In June 2017, she developed a slight, intermittent tremor whilst resting; mostly in her hind legs, but sometimes the rest of her body would tense up for a couple of seconds and then release, as though she was shivering from cold. I filmed a couple of these episodes and took the clips and her along to the vet who advised, despite my concern that it might be abdominal pain, that it was probably nerve degeneration due to her age. Then, during July and August, she started vomiting – infrequently at first, maybe once every two to three weeks, and only during the early hours of the morning on an empty stomach. Another trip to the vet in September brought another 'nothing to worry about', but by November, the early morning vomiting had increased to a couple of times a week. I was 100% certain that she didn't have a gastro-intestinal blockage, and dietary changes had brought no improvement. The vet we saw mid-November time didn't seem overly concerned that she was vomiting a couple of times a week, or that her tremor had worsened, but I knew that something was seriously wrong. She had never been a 'sicky' dog. In fact, throughout her entire life with us prior to summer 2017, she hadn't vomited once. The first few times that it happened, she seemed genuinely surprised.

I wasn't happy that her symptoms kept being dismissed as 'due to age' and 'nothing to worry about' and asked for blood tests. Although these returned a supposedly clear result, during the first week of December she vomitted four times. We returned to the surgery and saw a different vet, who had recently seen another, very similar case. The vet had performed exploratory surgery, removed a benign tumour from the pyloric area of the dog's stomach, and the dog had made a full recovery. However, I wasn't prepared to put Tilly under the knife on the off-chance that the outcome would be the same. Instead, I opted for an ultrasound scan referral, and a week or so later, my worst fears were confirmed – a highly suspicious mass, approximately 6cm by 2cm, situated within the lining of the inner curvature of the gastric fundus.

In the midst of that awful moment, I knew that I had made the right choice with the ultrasound referral, because had I opted for exploratory surgery at my veterinary practice, it would have undoubtedly ended with Tilly having to be put to sleep on the operating table. And despite the vomiting, she still seemed bright, happy, and interested in living. I asked the ultrasonographer whether blood tests could indicate a cancer diagnosis, but was told no. I later discovered, through my own online research, that there is a blood test indicator for cancer – the Neutrophil-to-Lymphocyte Ratio (NLR) – and if this had been common knowledge in general veterinary practice, maybe, just maybe, Tilly's cancer could have been diagnosed early enough for surgery to have been a viable option. The same could also be said about her 'shivering' episodes. However, at the time, we were where we were.

The ultrasonographer recommended referral to a veterinary hospital that could offer us a combined soft tissue surgery and oncology appointment, and a fortnight later, a squashed cell preparation and endoscopic biopies provided a definitive diagnosis: gastric adenocarcinoma – a highly aggressive cancer that is unresponsive to chemotherapy, and due to a combination of tumour location and size, removal and resection to prolong life with any degree of quality was no longer an option. Prognosis with palliative care was 1-2 months.

Between the ultrasound and soft tissue/oncology appointments, I was able to reduce the frequency of her vomiting with Ranitidine (an antacid) and Metoclopramide (an anti-emetic). She seemed brighter, and she was eating well. But the diagnosis also threw a spanner in the works in the form of Tramadol. In recent years, Tramadol has become the 'go to' pain relief drug for dogs suffering a variety of types of pain, from arthritis to cancer. For carcinoma cancers, it is recommended that Tramadol is given alongside meloxicam.Tilly had had meloxicam in the form of Loxicom some years previously and for an extended period of time, so I was fairly confident that this wouldn't cause her any issues. However, she didn't seem to be doing well on Tramadol. Her vomiting increased again, and she seemed to be in more pain, not less. It would have been easy to put this down to the cancer worsening her symptoms, but a small amount of online digging unearthed some interesting research-based facts about Tramadol and dogs; the main one being that dogs do not possess the necessary receptors for Tramadol to work as a painkiller. Furthermore, the drug still has to be metabolised by the liver, and dogs, as humans, may suffer nasty side effects including nausea, vomiting and abdominal cramps.
  

So I stopped the Tramadol. After a couple of days she seemed much brighter, more coordinated, and noticeably more comfortable; and I felt mortified that I had been giving her something, albeit on veterinary advice, that had not only been making her ill and causing her pain, but had been giving her liver yet another set of chemicals to deal with. The Ranitidine also seemed to have begun to correlate with vomiting episodes, so I stopped this too. During December it had worked well to reduce her stomach acid production, but I felt that it had served its purpose for the time-being. I continued to give her Loxicom and Metoclopramide, and for a few weeks she seemed to be doing better. We also tried veterinary acupuncture to see if it would reduce the frequency of her vomiting, which it did seem to do on a short-term basis as she always had at least one vomit-free day post treatment. She continued to eat well – even regaining the weight that she had lost during December. Her vomiting was occuring only when her stomach was empty, and she was still enjoying fuss, walks, and barking at the postman.

It was on the 9th of February that she took a turn for the worse and her vomiting suddenly spiralled out of control. Although she still managed not to throw up any food, she refused to eat from lunchtime onwards, and despite continuing to drink, she was becoming dehydrated. That night, she slept in my arms for what I knew would be the last time. Come the morning, the whites of her eyes were showing the faintest yellow tinge, and her blood pressure had dropped. I made the call, but despite being assured previously that whenever the time came, day or night, a practice vet would be available to her put to sleep at home, I was told that a home visit was not possible until Tuesday, which was three days away. However, if I could get her to the surgery by close of business at 12.30pm, a vet would do it there. I felt angry and cheated, but I couldn't allow my girl to suffer. I told her what was going to happen and we got a taxi to the surgery so that I didn't have to drive. She literally clung to me for the entire journey – her claws gripping my legs as she lay across my lap. She never laid across my lap. I knew what to expect when we got there – I've had other dogs put to sleep – but what I didn't need to hear from the vet was that he had to use twice the anaesthetic for a dog of Tilly's size, and that she was a strong little dog; a fighter. Not only did this add to the pain of letting her go, it added doubt to my decision to put her to sleep. Over a month on, the 'what ifs' are still haunting me.

And so, to the point of this post – knowledge. Whilst I do not advocate going against veterinary advice, I do encourage dog-owners to question it – particularly if it could cause, or appears to be causing, a dog more harm than good. Veterinary professionals aren't always up-to-date with the latest research, and importantly, no vet will ever know your dog as well as you do. 

Hind-leg tremor and/or shivering, as though cold. I know now that Tilly's tremoring was not due to age-related nerve degeneration, and that my initial, gut feeling that it was abdominal discomfort, was correct. I know this because lowering her stomach acid production with Ranitidine eased it considerably. Gastric adenocarcinoma causes ulceration of the stomach lining. When the stomach is empty, stomach acid and/or bile reflux will cause irritation and burning. If your dog is shivering on and off as though cold but is clearly not cold – particularly if this occurs a few hours after eating or whilst resting – it could be an indictation of abdominal discomfort; not necessarily of cancer, but of some kind of upper gastro-intestinal tract irritiation such as heartburn, acid reflux, gastritis or pancreatitis, that warrants further investigation. The same goes for early morning vomiting, known as bilious vomiting syndrome. This occurs on an empty stomach as a result of bile refluxing into the stomach and causing irritation. Despite being suggested as a fairly common, benign affliction in older dogs, it could be an indication that something more sinister is going on, and shouldn't be dismissed as being due to age. 

Neutrophil-to-Lymphocyte Ratio (NLR) (Uribe-Querol and Rosales, 2015). It is true that there aren't any blood tests that will diagnose cancer in dogs; however, research suggests that the Neutrophil-to-Lymphocyte Ratio (NLR) may serve as a prognostic factor for cancer. Extrapolation of Tilly's blood results from November produces an NLR of 5:1 – this is the ratio that has been found to indicate cancer. 

The NLR cannot be used to specify cancer type, rather, it is a biomarker for various tumors including some lung cancers, hepatocellular carcinoma, nasopharyngeal carcinoma, colorectal cancer, melanoma, breast cancer and gastric cancer. My advice is to always ask for a copy of your dog's blood results, even if your vet tells you that everything is nomal. A full blood count will specify the levels of neutrophils (NEU) and lymphocytes (LYM) in your dog's blood. If NEU is five times higher than LYM, this may indicate that your dog has cancer, and in which case, depending on your dog's symptoms, the early use of non-invasive diagnostic techniques such as ultrasound, MRI and x-rays may be able to detect where this is, and perhaps buy your dog some valuable time in getting it diagnosed and treated.

Tramadol. It doesn't work as a painkiller in dogs (Budsberg et al, 2018). Tramadol is an opioid-like drug, but unlike true opioid drugs that act as mu-opioid receptor agonists, the analgesic effect of Tramadol is due to the drug's metabolites blocking M1 opioid receptors only (Minami et al, 2015). Whilst humans and cats have M1 receptors, dogs do not. Dogs are still subject to the serotonin and norepinephrine effects of Tramadol, which cause mild sedation; however, sedation is not pain relief. Effective painkillers for dogs, particularly when opiate-based pain relief is required, include morphine patches if a dog cannot take oral medication or is already suffering with abdominal discomfort or liver disease, and Pardale-V – a non-prescription analgesic that contains codeine, which has been specifically formulated for dogs. I wasn't aware that morphine patches existed for dogs until the end of Tilly's life, by which time it was too late. Given the terminal nature and symptoms of her illness, I feel that we should have been offered this option much sooner. Tilly had a reasonable-to-good quality of life right up until the end, but if we had been able to use morphine patches instead of oral pain relief, I believe that her quality of life would have been further improved. 

Meloxicam – Metacam vs Loxicom. Meloxicam is a NSAID medication – a non-steroidal anti-inflammatory drug. More specifically, it is a COX-2 inhibitor, which has been shown to slow the growth of adenocarcinoma tumours. Meloxicam is the active ingredient in both Metacam and Loxicom, but the two medications are not the same in other respects. The difference is in the excipients – substances that are formulated alongside the active ingredient of a medication, and are included for the purposes of long-term stabilization and other factors, such as palatability. I'm sure that most dog owners are aware that a substance called xylitol, a sweetener often used in chewing gum, is highly toxic to dogs. What I'm also certain of is that most dog owners are unaware that Metacam – the brand of meloxicam favoured by the majority of vets and prescribed for a wide range of inflammatory conditions – contains xylitol. Loxicom on the other hand, does not. I realise that the amount of xylitol in Metacam is probably small, but why include it in a medication formulated for use in dogs when there are plenty of other, dog-safe sweeteners available? I don't know whether the xylitol content of Metacam poses a health-risk to dogs who take it on a longterm basis, but what I do know is that based on ingredients, Loxicom appears to be the safer option. 

Euthanasia – advice for vets for dealing with clients. Please don't say that a dog needed more anaesthetic than would normally be required to end its life. It is a totally unnecessary thing to tell someone. It's also unprofessional. It provides zero comfort to the newly bereaved and worse, it may cause a client to further question what has certainly been an impossibly difficult decision to make. What a client needs to hear is that their dog seems ready to go, and if you have to use more anaesthetic than normal, keep that information to yourself. And unless you truly offer an unconditional, any time 'at home' euthanasia service, please don't mislead clients into thinking that this is an option.

If this blogpost has given the impression that I'm unhappy with the treatment that we received from the veterinary professionals involved in Tilly's care, this was not my intention. Everyone that we came into contact with was kind and caring, and I truly believe that they all had Tilly's best interests at heart. However, it was a lack of knowledge about the presentation of abdominal discomfort and gastric adenocarcinoma, NLR as a progostic factor for cancer, and the (in)effectiveness of Tramadol as a painkiller, that steered the course of Tilly's treatment along a particular path. This path could have been different. The possibility exists that had her symptoms been viewed differently and taken more seriously, and had the cancer been detected early enough, she may still be with us ... and so, if any of the knowledge that I have gained during the course of Tilly's illness enables just one dog and owner to have more time together, then something good will have come out of our experience. 

In loving memory of my beautiful, brave Tillybean.

References 

Budsberg, S., Torres, B., Kleine, S., Sandberg, G. and Berjeski, A. (2018) Lack of effectiveness of tramadol hydrochloride for the treatment of pain and joint dysfunction in dogs with chronic osteoarthritis. Journal of the American Veterinary Medical Association, 252: 427-432.

Minami, K., Sudo, Y., Miyano, K., Murphy, R. and Uezono, Y. (2015) µ-Opioid receptor activation by tramadol and O-desmethyltramadol (M1). Journal of Anaethesia, 29 (3): 475-479.

Uribe-Querol, E. and Rosales, C. (2015) Neutrophils in Cancer: Two Sides of the Same Coin. Journal of Immunology Research. 

Bibliography 

European Drugs Encyclopedia