aproach to disease managment Flashcards

Question

Polytetrafluoroethylene as an intoxicant

Answer 1

AKA Teflon; used in non-stick coatings, especially on cookware. Primarily effects birds; humans can also be affected but symptoms tend to be self-resolving. Toxicology: Overheated PTFE releases fumes which, when inhaled, -> alveolar congestion and pulmonary oedema. Clinical effects: Respiratory distress, acute death. Treatment: Decontamination not possible Supportive care only – oxygen supplementation, NSAIDs and diuretics, fluid therapy, and supplemental heat Consider antibiosis Prognosis: Guarded to poor

Answer 2

Artificial sweetener, commonly found in chewing gum. Toxicology: Stimulates insulin release in dogs -> severe, rapid-onset hypoglycaemia; hepatotoxic. Clinical effects: vomiting, tachycardia, ataxia, depression, eventually coma, convulsions and collapse; signs of liver failure and coagulopathy less common. Treatment: Decontamination – emesis and activated charcoal IV dextrose CRI where hypoglycaemia is present Liver support (SAMe, silybin) Prognosis: Favourable if caught early, poor where liver failure has developed.

Answer 3

--> the uncontrolled, abnormal growth of cells Benign neoplastic masses do not spread (metastasize) - Examples include lipomas and sebaceous adenomas Malignant neoplasia frequently invade locally and metastasize "cancer" – Examples include lymphoma and carcinomas Both benign and malignant disease are commonly seen in practice Cancer is the cause of death in approximately 47% of dogs >10 years of age What type of neoplasia is it? - We cannot treat it effectively if we do not know what it is Is it benign or malignant? - Benign disease may not always need treatment If malignant, has it spread? "Staging" - Important for prognosis and treatment Are there any paraneoplastic effects? - High calcium with anal sac adenocarcinoma Does the patient have co-morbidities that could impact on treatment? Consider whole patient welfare and what is appropriate for the pet and owner

Answer 4

FINE NEEDLE ASPIRATE – For solid tumours or enlarged lymph nodes – External and internal via ultrasound guided FNA FLUID CYTOLOGY – Abdominal & thoracic effusions, prostatic wash etc. – Make a fresh smear and put some into EDTA (care some neoplastic effusions may not have detectable neoplastic cells on cytology) BONE MARROW ASPIRATE – Indications – Cytopenia - especially when multiple cell lines are affected (anaemia, thrombocytopaenia) Unexplained big increase in cell lines – lymphocytosis, neutrophilia etc. Hyperglobulinaemia (multiple myeloma) Slides are best sent to the lab in my opinion

Answer 5

Pros: Simple, quick and non-invasive Quick turnaround for results Lower cost than surgical biopsy and histopathology Performed awake in most cases unless: -Fractious -The mass in near a delicate structure -Abdominal mass Cons: Smaller sample so may not be representative Some masses such as sarcomas do not exfoliate well Masses cannot always be graded Contraindications: Bleeding disorders- If no gross bleeding disorders external FNA is fine. For internal FNA's check the PLT count first. (Clotting profile if unsure) Bladder tumours- Risk of seeding tumour cells Immobilise the mass/or lymph node with your non dominant hand Needle only: -Introduce a 21 or 23g needle into the mass and move the needle back and forth several times Suction: -Useful for masses that do not exfoliate well -Attach a syringe and apply suction whilst moving the needle back and forth. Release suction prior to needle removal Attach an air-filled syringe and spray onto the slide Make a smear Costs: £120 FNA plus consult fee £50 (local Staffordshire practice 11/23) Managing owner expectations - Important in all aspects of veterinary care: Make owners aware of the cost and the benefits of the procedure That samples may come back inconclusive or that further testing may be required That their pet may yelp or have minor bleeding from the procedure

Answer 6

Various methods - Incisional, excisional, pinch, Tru-Cut.... Pros: Larger sample so increased chance of diagnosis Architecture can be assessed, and masses graded Provides more prognostic info Cons: More invasive GA or deep sedation required Takes more time to get results Increased cost Risks: Bleeding, seeding, compromising future surgery Contraindications: Bleeding disorders, co-morbidities increasing the risk of GA In practice cytology and histopathology are complimentary: FNA's are often performed first to distinguish between inflammatory/hyperplastic and neoplastic lesions Biopsy and histopathology is used if the FNA is inconclusive Otherwise, histopathology is performed after full mass excision to confirm the diagnosis, allow full grading and to assess surgical margins INCISIONAL WEDGE BIOPSY- For solid tumours and LN Choose an appropriate location Avoid infected, haemorrhagic or necrotic regions Inclusion of a normal area of tissue can be useful, as long as the whole biopsy site can be fully removed at follow up surgery Be aware of local anatomy – avoid important structures! Surgery If subcutaneous incise overlying skin and blunt dissect down to the mass or LN Cut a wedge out of the mass – routine closure Place in formalin Do not include formalin histo samples in the same package as slides Excisional biopsy - removing the entire mass FNA advised first ideally. Excisional biopsy can potentially be used without FNA in: Mammary masses Haemorrhaging splenic masses – emergency Deep pulmonary tumours (FNA superficial ones – syringe on!) In some cases, for dog masses where funds are limited 60% skin masses benign in dogs vs only 20% in cats Not appropriate for: Masses of an unknown diagnosis Poorly defined masses Inflamed or oedematous masses (e.g. MCT) Rapidly growing masses (feature of malignancy) Ulcerated masses

Answer 7

Cancer cells have different thermal properties than normal tissue. Heat waves (visible blue light) are sent into the mass and are read by a thermal sensor. This is then assessed by AI and a numerical value is generated: 1 – 4 increased risk of malignancy, further testing recommended (FNA) 5 – 10 the mass appears to be benign (98% certainty) It cannot diagnose the mass, only give an indication of benign vs malignant Limitations: Deep s/c masses Large masses Some cysts False positives can occur in some of the above cases. Further testing would then be advised which would then identify that they are actually benign Interesting novel, non-invasive technique. Likely further research is required Cost: £80/mass local Staffordshire corporate 11/23

Answer 8

T – Tumour – What is the primary tumour? - Grade? N – Nodes – Has it spread to the local lymph node? – FNA, biopsy M – Mets – Has it spread to distant sites? – Imaging – Thoracic radiographs and abdominal ultrasound vs CT

Answer 9

Nodular interstitial pattern Always take 3 inflated views: R lateral L lateral VD or DV THORACIC RADIOGRAPHS: Pulmonary METS under 3 – 5mm are not visible CT Preferred to radiographs where possible Able to detect pulmonary masses as small as 1 – 2mm Even CT has limitations: Osteosarcoma - the chest CT may be normal, but around 95% of dogs have micrometastases at the time of presentation

Answer 10

Can be limited by patient size and equipment/operator - Even specialist diagnostic imagers often CT abdomens of large dogs >30kg before ultrasound Ultrasound cannot distinguish between benign and malignant nodules just on appearance- The exception are target nodules - 81% predictor of malignancy where there are multiple in one organ FNA's of nodules. Benign regenerative liver nodules are common in older dogs so a dog should not be suspected of having METS (and then euthanised) just off ultrasound A liver and spleen can also have MCT METS and look normal on scan!

Answer 11

KNOW WHAT IT IS BEFORE YOU ATTEMPT TO REMOVE IT!- With diagnosis and staging you can provide the owner with all the necessary information to make their decision You do not need to know all the median survival times and treatments off the top of your head, this can be researched once a diagnosis is achieved IS SURGERY EVEN APPROPRIATE?- What is the prognosis with or without surgery? What is the expected benefit? Will surgery be curative? What will the impact of surgery be? (to the patient and owner finances) SURGICAL PREP- Gentle surgical prep to reduce the risk of tumour seeding Strict asepsis due to the higher risk of post op infections in cancer patients SURGICAL MARGINS- The amount of normal tissue around the tumour that is resected Narrow surgical margins can be obtained in benign masses limiting morbidity If narrow margins are obtained in malignant disease, it is likely to result in treatment failure The aim is to fully remove the tumour with appropriate margins on the first surgery to get the best chance of a cure- Tumours are more active at their edges. Partial resection leaves the most aggressive cells behind There will be less tissue available for closure second time round. A wider resection is also needed second time round which can compound the problem.

Answer 12

Narrow margins – up to 1cm – Suitable for benign masses Wide excision - 2cm+ depending on grade, plus a fascial plane- -Low – intermediate grade MCT - 2 cm and one fascial plane (1cm for low grade) -High grade MCT – 3 – 4 cm and one fascial plane Radical excision – The removal of the tumour with extensive margins (includes limb amputation) CAN YOU GET THE REQUIRED MARGINS? Tumour location may make it difficult or impossible to get appropriate margins (for example – distal limb) Advanced surgical skills may also be required to close deficits created by these surgeries (surgical flaps etc.) Referral may be required Even in referral hands margins may be impossible to achieve due to tumour size and location This is where adjunctive treatments play a role Chemotherapy to shrink a tumour pre surgery

Answer 13

Be careful with tumour manipulation during surgery as this could seed cells – use atraumatic forceps rather than rat-tooth's Ligate vascular supply to the tumour as early as possible If there are any adhesions to the tumour remove these with the mass as they could have tumour cell invasion Remove local LN if staging has shown them to be affected or if they appear grossly abnormal during surgery. Biopsy normal appearing local LN Lavage the op site post excision and change, drape, kit and gloves prior to closure Adhere to normal surgical principles of closing dead space and reducing tension Avoid chemotherapy 7 days prior to surgery and 7 days post-surgery – can affect wound healing Approximate first opinion costs of GA, surgery, histology £600 - 800 for an average size mass £1000+ for more involved surgery Cost could be reduced where needed, depending on the case, as long as the potential impacts are discussed: No pre-GA blood – save £65 No IVFT – save £110 No histology – save £165

Answer 14

The use of cytotoxic drugs to kill tumour cells Chemo drugs target rapidly dividing cells: Tumours with a high growth rate (high grade and mitotic index) GI tract and bone marrow- Diarrhoea and myelosuppression The dose and frequency used aims to balance effective tumour kill whilst minimising side effects by allowing time for normal tissue to recover Lower dosages are used in veterinary medicine compared to human oncology. We want to improve median survival times in our patients whilst limiting any negative side effects As the main treatment for conditions such as lymphoma/leukaemia and metastatic neoplasia After the surgery of tumours with a high risk of metastasis - Intermediate grade MCT with a high mitotic index, high grade MCT, osteosarcoma, haemangiosarcoma Neoadjuvant chemo to reduce a non-operable tumour into a smaller operable size For in-operable chemo-sensitive tumours There are published protocols for a variety of neoplastic conditions, but in an ever-evolving field it can be useful to contact an oncologist for advice Chemopet is an oncologist led business that provides expert advice and pre prepared chemotherapeutics to first opinion practices Cytotoxic drugs are carcinogenic, mutagenic, teratogenic, abortifacient and increase the risk of stillbirth. At risk people should avoid administering chemotherapy and being around patients post treatment At risk groups: Pregnant, lactating or people trying to conceive Young children and elderly people Immunocompromised people Safe handling is essential to reduce the risk to staff and owners Appropriate PPE: Thicker nitrile gloves Gown Face shield/eye protection Mask Use PPE when handling patient urine, faeces, saliva or vomit. Drug residues can be found in the urine and faeces for around 7 days Double bag faeces Pour water over the site of urination/defecation

Answer 15

Safe administration of injectable chemotherapeutics PPE Low risk staff Safe handling using a needle free closed system to reduce the risk of spillage Appropriate disposal of materials contaminated with cytotoxic residues miroclave extentsion set syringe with spyros attached

Answer 16

Chemotherapy drugs have a narrow therapeutic index so accurate dosing is essential:- Use mg/m^2 rather than mg/kg for most dosages (table in the back of the formulary) Save peripheral veins for chemotherapy – take bloods from the jugular "One-stick" technique when placing IV catheters- Avoids multiple punctures of the vein that could lead to chemo drugs leaking perivascular Draw back to demonstrate a "blood flash" Vincristine, vinblastine and doxo/epirubicin are vesicants – local tissue necrosis can occur if the chemo leaks outside the vein Early signs of extravasation: Pain, swelling and redness at the catheter site If extravasation is suspected: Stop the chemo Attach a new syringe and try to aspirate as much as possible Cold and warm compresses – contact an oncologist for specific treatments where available iv protocall- Pre-procedure checks – Appropriate neutrophil count - >1.5 × 10^9/L - if less, delay treatment (2 – 7 days) & reduce dosage (10 – 20%) Maropitant First stick catheter Attach extension set with the clave port Saline flush and demonstrate "blood flash" Put on PPE Attach the chemo syringe Spiros to the clave port Administer the chemo at an appropriate rate Monitor for signs of extravasation Flush 10 – 15ml saline through to clear drug residue from the catheter lock off and do not disconnect Remove the IV, extension set and syringe as one and put into cytotoxic bin Apply dressing – remove PPE and wash hands

Answer 17

GASTROINTESTINAL - Diarrhoea, nausea/loss of appetite Pre-treatment with maropitant – oral for home use Delayed ileus with vincristine – metoclopramide and supportive treatment MYELOSUPPRESSION - Takes time for max suppression – monitor the neutrophil nadir(peak of suppressiom) – around 7 days (5-10) Risk of sepsis if the neutrophil count drops <0.75 × 109/L- Prescribe prophylactic potentiated amoxicillin Febrile neutropaenia is an emergency – isolation, IV broad spectrum AB including a fluroquinolone STERILE HAEMORRHAGIC CYSTITIS- Cyclophosphamide RENAL TOXICITY- Carboplatin and cisplatin CARDIOTOXICITY- Doxo/epirubicin HEPATOTOXICITY- Lomustine

Answer 18

Electrical pulses are administered to a mass after an IV or local dose of chemotherapy The electrical pulses make the tumour cells more permeable to the chemotherapy drug allowing greater uptake and increased sensitivity to the drug- may decrease dose needed Side effects are generally low but can include local inflammation and myelosuppression Whilst general chemotherapy for conditions such as lymphoma can be performed in general practice ECT typically requires referral Treatment is administered under GA/sedation and often two treatments are used two weeks apart Indications: Tumours that are inoperable As part of palliative care in advanced disease Typical tumours treated: Carcinomas such as nasal squamous cell carcinomas in cats Mast cell tumours Melanomas, sarcomas

Answer 19

High energy x-rays from a linear accelerator can be used to kill cancer cells Indications: Tumours of the nasal cavity (carcinoma, lymphoma) Brain neoplasia – Meningioma Palliative pain relief of bone tumours such as osteosarcomas Palliative care of inoperable tumours e.g. oral malignant melanoma that is not amenable to surgery After the surgical removal of invasive tumours (mast cells tumours, soft tissue sarcomas) to reduce the risk of regrowth Acute: Inflamed skin, hair loss etc. Reversible Late: Damage to vascular and connective tissue Cataracts, retinal issues, skin & joints etc. Rarely neoplasia Irreversible

Answer 20

The control of pain is essential in all aspects of veterinary care to ensure patient welfare Sources of pain in oncology patients: The cancer itself – bone neoplasia is notoriously painful The treatment – surgery etc. Pre-empting pain and multi-modal analgesia is essential. Chronic pain is often underestimated Multi-modal analgesia- NSAIDs – Ensure no contraindications and do not give to patients having corticosteroids as part of their treatment Paracetamol – Dogs only Gabapentin – Good for neuropathic pain Monoclonal antibodies targeting nerve growth factor (Librela/solensia) Amantadine – Good for pain refractory to NSAIDs but could be restricted Ketamine – Low dose subcutaneously – monthly to weekly Antidepressants

Answer 21

One of the options to alleviate pain and suffering in our patients It must be approached with great care and empathy In our patients it could be due to welfare of the patient and/or cost concerns We need to be compassionate and ensure the process goes as smoothly as possible lead with open questions. "Have you thought about euthanasia" is too direct and can be jarring "How is Kevin getting on?" "How are you feeling about his treatment?" If open questions do not prompt the discussion and you are concerned about the patient's quality of life a delicate more direct approach can be considered: "We always have to be mindful of how happy our pets are. Are we having more bad days than good days?" "I'm worried Kevin is not doing as well on treatment anymore. What do you think?" Quiet private room and where possible ensure there is enough time Ensure consent and understanding "Put to sleep term" Options for their pets afterwards Signed consent form Discuss the procedure and whether owners would like to stay Most do but never assume

Answer 22

Benign Raised pink to pigmented lobulated masses – “wart like” – “brains” Common in middle aged to older dogs – terriers, poodles, cocker spaniels The appearance is fairly typical but ddx can include: Viral papilloma Dermal MCT Melanoma Basal cell tumour Squamous cell carcinoma Melanoma Diagnosis: High suspicion on gross appearance – definitive by FNA/histo Treatment: Not required if not causing a problem – just cosmetic Surgical excision if bothering the dog

Answer 23

SEBACEOUS ADENOMAS BENIGN CUTANEOUS CYSTS HISTIOCYTOMAS LIPOMAS CANINE MAST CELL TUMOURS (MCT)

Answer 24

Multiple types which can be considered under the umbrella term of cyst Follicular cysts – Dermal raised masses filled with a thick keratinaceous material (cheese/paste like on gross FNA) – dilated hair follicles Sebaceous cysts – look similar – develop in and around the sebaceous gland Both can rupture generating an inflammatory response and secondary infection Common in multiple breeds of dog including Shih Tzus, Hounds, Schnauzers and Boxers Ddx – dermal MCT, deep pyoderma – can look similar to a ruptured cyst Diagnosis: Suspicion on appearance and paste like gross FNA material Benign on heat imaging although false malignancies can occur Definitive on FNA/histo Treatment: Monitor vs surgical excision Excision recommended for cysts that are prone to rupture

Answer 25

Benign small pink-red domed cutaneous mass, often found on the limbs, ears or head/neck Common in young dogs <2 years but can be seen in middle aged dogs too They can ulcerate -> self-trauma Ddx Dermal MCT, Ulcerated melanoma, Cutaneous lymphoma Non neoplastic lesion – inflammation, FB, insect bite Diagnosis: Suspicion on appearance in a young dog on the limbs Benign reading on heat imaging Definitive on FNA (ideal) Treatment: May regress spontaneously in a month or so If not and/or bothering the dog – surgical excision is curative

Answer 26

LIPOMAS Subcutaneous mass made up of fat cells, normally soft and mobile on palpation (occasionally can be found internally) Very common in middle aged to senior dogs Gross oily fat on slide after FNA Ddx: S/c MCT, soft tissue sarcoma, liposarcoma Diagnosis: “Targeted” FNA Cytology will come back as “lipid”, but this could be just subcutaneous fat, so the clinician needs to ensure the FNA was directly from the mass Treatment: None required unless growing in an areas that could cause a problem – axillae - surgical excision Is it appropriate to diagnose a lipoma based off the exam and demonstrating a fatty oil-like appearance on gross FNA? No – some neoplasia such as MCT can appear fatty Yes & no – Where funds are limited, or surgery would never be considered As long as the limitations are discussed with the owners and documented in the clinical notes

Answer 27

Mast cells have an important role in inflammatory, immune and allergic reactions They are present in most tissues in the body and malignant transformation leads to MCTs 7 – 21% of call canine skin tumours Majority are dermal but they can be subcutaneous Predisposition: Any breed but particularly Bulldogs, Staffordshire bull terriers, Boston terriers, Boxers, Pugs, Beagles, Lab/Golden Retrievers, Dachshunds, Shar-peis, Rhodesian Ridgebacks, Weimeraner Pugs are prone to getting multiple low grade MCT Shar-peis tend to get high grade metastatic disease Appearance - Variable – why FNA is so important Approx 2/3rds of masses may show benign behaviour and present as a slow growing cutaneous lesion Subcutaneous masses are often less aggressive and may appear like lipomas – FNA’s are very important Masses can be inflamed from histamine release and can wax and wane in size (vomiting, diarrhoea/melaena) Rapid growth and mass ulceration can be seen in high grade MCT MCT diagnosis FNA - fine basophilic cytoplasmic granules The Camus grading system and 2022 Paes adaptation were developed to try and give an indication of grade based off cytology The study showed a high correlation between cytological and histopath grade so it can give a good initial indication Cytology can overestimate the grade compared to histo MCT Grading from Histopathology: Currently only apply to cutaneous MCT's not s/c ones although dogs with s/c MCT's tend to have a longer survival time Various grading systems - Patnaik or Kuipel Grade correlates to prognosis OTHER PROGNOSTIC INDICATORS- Size and growth rate – High growth is a sign of malignancy, larger MCTs are harder to remove Appearance – Inflammation, ulceration and pruritus = poorer prognosis Systemic signs – vomiting and melaena = poorer prognosis Breed- pug low grade, sharpei high grade Location – In some but not all studies, preputial, muzzle, nail bed, perineal and those in mucocutaneous areas = a poorer prognosis Grade is the most important prognostic indicator The histology report will come back with the grade and the option of further testing - proliferation markers. These can provide more prognostic information Ki67 – identifies the growth fraction (actively dividing cells) AgNOR – identifies the generation time (speed of cell cycle progression They can cost an extra £300 odd to test SHOULD WE TAKE AN INCISIONAL BIOPSY AFTER FNA OF EVERY MCT TO ALLOW FULL GRADING? Historically yes – before the cytological grading system was developed this was the only way to establish the MCT grade to then know what surgical margins to take Today with a good cytological grading system we often decide on appropriate staging and treatment based off the FNA grade and other prognostic indicators

Answer 28

CANINE MCT - GRADING Grade 1 (low grade, well differentiated) – no mitotic figures Grade 2 (Intermediate) 0 – 2 mitotic figures per hpf, some pleomorphic cells- variation in size Areas of oedema and necrosis Infiltration of lower dermis/subcutaneous tissue Grade 3 (high grade, poorly differentiated)- multiple abnomal cells 3 – 6 mitotic figures per hpf, sheets of pleomorphic cells Odema/necrosis/haemorrhage and ulceration is common, Infiltration of lower dermis/subcutanous tissue

Answer 29

Low grade High grade- 7 or more mitotic figures Generally low mitotic index and well differentiated = lower grade and better prognosis High mitotic index (>5) and poorly differentiated = higher grade and worse prognosis

Answer 30

Ki67 from immunohistochemistry: A high Ki67 expression = increased rate of local recurrence, metastasis and mortality This can be useful for intermediate grade MCT as around 30% of these are found to be more aggressive when Ki67 tested (Van Erp, M et al) Higher AgNOR counts are also associated with an increased rate of local recurrence, metastasis and mortality

Answer 31

FNA the local LN LN positive for METs- Full staging Abdominal ultrasound FNA lesions FNA liver and spleen even if they look normal Lung METs are very rare --> LOW – INTERMEDIATE GRADE WITH METS 2cm margin, 1 facial plane excision Remove the metastatic LN Grade the mass and assess margins Chemotherapy OR LN negative- Surgical excision 2cm* margin & one facial plane Biopsy the local LN if the FNA was inconclusive Grade Assess margins --> LOW – INTERMEDIATE GRADE CLEAN MARGINS (no METS) No further treatment Consider proliferation markers for intermediate grade Monitor the site For low grade reoccurrence risk is low For intermediate grade this risk is slightly higher (up to 23%) consider the implications of histamine release during surgery Chlorphenamine is used pre-op alongside omeprazole which is continued post operatively

Answer 32

Referral where possible – they are very difficult to manage Wide excision + post op radiotherapy + chemotherapy (regardless of margins achieved) High grade MCT median survival time (MST) with surgery = 3.5 months Surgery + radiotherapy = 20 months Surgery + radiotherapy + chemotherapy = 65% of patients alive at 3 years

Answer 33

INDICATED POST SURGERY FOR DOGS WITH POOR PROGNOSTIC INDICATORS: High grade III MCT High mitotic index Intermediate grade with high prognostic indicators METs Other factors such as tumour location and malignant features Chemo is often started around 2 weeks post op to allow time for wound healing Typical first line protocol IV vinblastine – 8 doses – weekly for the 1st 4 then every 2 weeks Oral prednisolone In cases where gross disease is present this protocol may be continued weekly until full effect is seen then the frequency decreased. In some cases, lomustine is used Contacting an oncologist is advised! MCT location (such as on the distal limb) can make it impossible to achieve the desired surgical margins. Options for these cases: Referral Pre op (neo-adjuvant) chemo can shrink some non-operable masses down to an operable size 1 – 2mg/kg prednisolone for 7 – 10 days prior to surgery +/- vinblastine Pre op radiotherapy Tigilanol Tiglate (Stelfonta®) intra-tumour injection

Answer 34

(Stelfonta®) - A natural molecule extracted from the seed of an Australian plant. Injected intra-tumour It break down the tumour cell walls and blocks blood vessels to the mass --> inflammation, tumour necrosis & drop off --> wound healing For non-resectable, non-metastatic mast cell tumours of the following types in dogs: - Cutaneous mast cell tumours (located anywhere on the dog) - Subcutaneous mast cell tumours located at or distal to the elbow or the hock. Tumours must be less than or equal to 8 cm3 in volume and be intact/non ulcerated to avoid product leakage Local LN must be FNA'd or biopsied first Prednisolone and H1/H2 receptor blocking agents are needed both before and after treatment Sedation can be required along with a 2nd injection in 4 weeks Cost £400 per vial

Answer 35

CANINE MCT Anti-cancer and anti-angiogenic properties Toceranib is licensed for use in recurrent, non-resectable intermediate or high-grade MCTs Masitinib is licensed for use in non-resectable intermediate or high-grade MCTs with demonstrable c-KIT mutations. Not first line therapy - reserved for masses where clean surgical excision is not possible, or where surgical excision to microscopic disease followed by radiation is also not possible

Answer 36

In dogs – approximately 50% are benign, 50% are malignant Malignant transformation of benign mammary masses can occur with time Entire bitches and those neutered late are predisposed Can present as a single mass or multiple along the chain Smaller mobile masses <3cm are more likely to benign vs larger masses which can grow rapidly and ulcerate In cats' mammary masses are rarer but up to 95% are malignant MAMMARY MASS DIFFERENTIALS - Ductal and lobular hyperplasia – can be influenced by oestrus Mastitis Mammary enlargement related to oestrus Pregnancy or pseudopregnancy DIAGNOSIS- FNA- Not commonly performed as it normally cannot distinguish between benign vs malignant Benign mammary masses should be removed anyway to avoid malignant transformation Could be used to rule out other differentials such as ductal hyperplasia EXCISIONAL BIOPSY- Removing the entire mass and then sending for histo is performed most commonly Cases with small solitary mobile lesions <3cm are more likely to be benign These cases could be taken straight to surgery and the mass assessed on histo post excision If benign – no further staging or treatment if needed If it was malignant --> full staging This approach can save client funds and reduce the length of GA Full staging should be performed on all cases with larger or multiple mammary masses This helps with prognosis and decision making Is it fair to do two mammary strips in a dog with pulmonary METs? The surgical approach depends on the case Neutering has no effect on future malignant mammary tumour development, or on incidence of metastatic spread It can be considered in entire bitches however to eliminate the future risk of pyometra

Answer 37

Single or regional (more than one gland) mastectomy is generally indicated 2cm margin and one facial plane Mammary strips (radical mastectomy) +/- local LN are used when multiple masses are found along the mammary chain Surgery is normally staged in bilateral disease

Answer 38

Repeat surgery for dirty margins or for very narrow margins in high grade disease Chemotherapy is debatable but normally recommended for high grade tumours or if there is evidence of LN METs Various protocols: Single agent carboplatin Single agent doxi/epirubicin They are given once every 3 weeks for 4 – 6 treatment If chemo is declined for personal or cost reasons ongoing NSAIDs (meloxicam) could be considered as they have some anti-neoplastic properties with carcinomas Neutering before the first season drops the risk to 0.5% Note - this must be balanced against the behavioural impact of early neutering and the increased risk of joint disease and bone neoplasia seen with neutering before the first season in some larger breeds of dog For this reason, neutering is often advised to be performed around 3 months after the first season Neutering after the first season, prior to the second – 8% Neutering after the second season, prior to the third – 26%

Answer 39

Multicentric lymphoma Reactive Infectious- Severe generalised pyoderma Leishmania, Ehrlichia, Babesia (important in travelled dogs) Brucellosis Aspergillus Inflammatory Mineral associated lymphadenopathy Leukaemia Secondary to METs from other neoplasia

Answer 40

Neoplasia arising from lymphoid tissue 7 – 24% of all canine malignant neoplasia Various forms Cutaneous Alimentary Thymic Hepatic etc We will be focusing on the most common form Multicentric lymphoma (around 70% of all lymphoma cases) Any breed can be affected, higher incidences in: Golden Retrievers GSD Boxers Cocker spaniels Basset Hounds Scottish terriers Rottweilers Affected dogs are normally middle aged but younger patients can be affected too. Most dogs are well on presentation with no clinical signs other than the generalised peripheral lymphadenopathy, normally affecting all peripheral LN. Owners typically noticed the enlarged submandibular LN 20 – 40% of cases present with additional clinical signs: Lethargy Anorexia Weight loss Vomiting Dogs that present with these clinical signs typically have shorter survival times Diagnosis is normally straightforward and involves FNA of the enlarged LN – sample multiple nodes - The Once diagnosed we need to discuss with the owner the implications of this diagnosis Rapid progression to death without treatment 4 - 6 weeks Most patients however do well on treatment and whilst it cannot be cured, remission with a good quality of life can be achieved

Answer 41

We also need to discuss the costs and benefits of finding out the specific type of lymphoma (immunophenotyping) and disease staging The form of lymphoma (B vs T cell) and whether it is low or high grade, has a big impact on prognosis and treatment Most are intermediate to high grade and B-cell phenotype High grades can be identified on cytology, but low grades may need LN biopsy and histopathology to identify - They are often resistant to doxorubicin (commonly used in lymphoma) so a different protocol should be used B-cell lymphoma - the most common form (70% of cases) High grade T-cell lymphoma – Aggressive and have a poorer prognosis Low grade T-cell lymphoma (Indolent) Better prognosis of around 2 years Chemo does not affect prognosis and so may not be needed, only if the disease if progressing NK-cell lymphoma – Like high grade T cell is associated with a shorter remission and survival times PARR CLONALITY - You can ask the lab to run this PCR test on the FNA slide you already submitted It identifies whether the lymphoma is T-cell or B-cell Useful if the owner declines further sampling FLOW CYTOMETRY- Uses a liquid suspension of a fresh fine needle aspirate More accurate than PARR IMMUNOHISTOCHEMISTRY – On LN biopsy BLOODWORK - Haematology, Biochemistry &Urinalysis Needed to assess co-morbidities that could affect treatment, for screening of paraneoplastic disease (hypercalcaemia) and for staging Further staging (ideal for unwell patients) involves imaging the thorax and abdomen +/- sampling (aspirating liver and spleen for example) Always be mindful of costs and ensure this does not impact on treatment

Answer 42

As a systemic disease chemotherapy is the treatment of choice As a rough guide multidrug chemotherapy will induce remission (happy dog with no detectable disease) in 60 – 90% of patients 80% of patients live for a year, 20% of these up to 2 years This does depend however on grade and phenotype Treatment choices will be impacted by owner views, the individual dog (co-morbidities, bad at the vets etc.) and finances Oral prednisolone only- Remission achieved in 45 – 50% of cases Remission lasts 60 – 90 days Fairly common low-cost palliative option Note – cannot start treatment with prednisolone alone and then decide to use a full chemotherapy at a later date as the efficacy will then be reduced

Answer 43

CHOP PROTOCOL- The most effective protocol currently for B-cell lymphoma (8K) Vincristine (IV), Cyclophosphamide (PO), Epirubicin/doxorubicin (IV), Prednisolone (PO) Weekly induction protocol, moving to every 2 weeks. 25-week duration – then stops 90% of dogs (with uncomplicated B-cell lymphoma) go into remission with this protocol Duration of first remission is 10 – 12 months on average There is no maintenance phase after this protocol. When most patients come out of remission a rescue protocol can be considered COP PROTOCOL INDUCTION Shorter 8-week induction with Cyclophosphamide (PO), Vincristine (IV), Prednisolone (PO) Then ongoing maintenance protocol – IV & oral protocols vs less expensive oral only protocols 70% remission with B-cell lymphoma Average first remission time of 5 – 6 months

Answer 44

High grade T-cell lymphoma carries a worse prognosis Shorter remission times are seen with "standard" lymphoma protocols, so the LOPP protocol is favoured Includes alkylating agents such as lomustine and procarbazine alongside prednisolone and vincristine Use for 6 months and then followed by a maintenance protocol 6 – 11 months median survival time In cats and some dogs, sedation is used to facilitate the first stick catheter This does require a lot of sedations depending on the protocol so this may not be appropriate in every case Oral only palliative protocols could be used (which are also lower cost) such as prednisolone only or prednisolone in combination with other oral chemotherapy agents

Answer 45

Low grade T-cell lymphoma is the least aggressive form Median survival time of around 2 years Treatment is not always needed unless there are clinical signs in which case prednisolone and chlorambucil tablets are the treatment of choice Prednisolone every 48 hours and chlorambucil every 2 weeks

Answer 46

Lymphoma is the most common neoplasia in the cat Like the dog there are various types but, in the cat, alimentary lymphoma is the most common anatomical form The median age of affected cats is 10 – 13 years Cats may present with vomiting, diarrhoea, and weight loss Low grade lymphoma leads to diffuse thickening of the intestinal tract, and it can be tricky to distinguish from inflammatory IBD Intermediate to high grade lymphomas generally present with a palpable abdominal mass and often present more acutely and severely than the low-grade form Patients are more likely to present with GI obstruction with the intermediate-high grade as the mass can block the bowel

Answer 47

Cases present similarly to IBD with chronic gastrointestinal signs and weight loss. Appetite can be normal, reduced, or increased Intestinal thickening and enlarged mesenteric lymph nodes may be palpable differentails Routine bloodwork, urinalysis and TT4 In limited finance cases biochemistry plus T4 If super limited just biochemistry (ALT is up in most hyperthyroid cats and there is often other clinical signs)- Other hyperthyroid clin sig: Normal to PP appetite Palpable goitre Tachycardia/gallop/murmur Dry, unkempt coat Spicey FPLi for pancreatitis where appropriate, FeLV/FIV If all normal – imaging and cobalamin testing (B12) Then diet trials, faecal testing, intestinal biopsy etc. Rule out non-GI disease with bloodwork Cobalamin (B12) bloods Hypocobalaminemia can be present in up to 78% of cases Abdominal ultrasonography Could be normal! Often see intestinal thickening, especially of the muscularis layer +/- mesenteric lymphadenopathy You also see this in IBD! As the u/s appearance is not specific further testing is required Fine needle aspiration of enlarged mesenteric LN and PARR clonality can be used to try and achieve a diagnosis of LGAL over IBD but this is not always possible Gut biopsy FOR DIFFUSE ALIMENTARY NEOPLASIA - Such as feline alimentary small cell lymphoma Endoscopic pinch biopsy vs full thickness surgical Endoscopic: Less invasive – especially important in hypoproteinaemia – poor healing Further equipment and expertise required Smaller sample – less chance of diagnosis Surgical: Larger sample including all layers – increased chance of diagnosis Multiple areas of the GI tract can be sampled More accessible in first opinion practice Ideal for ileal biopsy in low B12 cases as upper GI endoscopy cannot get to the ileum Higher risk of complications which can be very serious – peritonitis Dehiscence risk of 1.9% (Swinbourne et al. 2017 vs older report of 12%

Answer 48

Diet- Hydrolysed/hypoallergenic (Purina HA), or novel Pre and probiotics can play a role Supplement B12 Faecal sample/fenbendazole trial Prednisolone anti-inflammatory to immunosuppressive dosages Chlorambucil if signs persist

Answer 49

B12 Prednisolone 2mg/kg then taper based on response and chlorambucil 20mg/m^2 every 2 weeks Diet Pre and probiotics Supportive treatment Mirtazapine appetite stimulation etc. Prognosis – 70% chance of remission (95% partial response), 26 – 29-month median duration of remission

Answer 50

Clinical signs are normally more acute, and cats are often unwell Cats present with GI signs and a palpable abdominal mass in the majority of cases GI obstruction or intussusception can occur in some cases Ultrasound- Identify the mass FNA- May require PARR testing if inconclusive cases Treatment- Chemotherapy (e.g. COP) MST 1 – 3.5 months 7 – 10 months in 33% of cases that fully respond Palliative prednisolone B12 supplementation if needed IF THE CAT IS VOMITING AND HAS GI OBSTRUCTION: Stabilisation and surgery is required – end to end anastomosis

Answer 51

The most common primary bone cancer in dogs They are seen more often in larger breeds and cause significant pain, lameness and occasionally, pathological fractures Microscopic METs are present in around 95% of cases at the time of diagnosis Often larger breeds: Dobermans Greyhounds Rottweilers German Shepherd dogs Golden Retrievers Great Danes Irish Setters Irish Wolfhounds Deerhounds Saint Bernard It can occur in smaller breeds, but it is rarer. Progressive lameness- Can become non weight bearing Initially maybe partially analgesic responsive Limb swelling/mass - More obvious when the distal radius/tibia is affected Pathological fracture - Not as common a presentation but it is still seen Any large breed dog presenting with a fracture should have the radiographs scrutinised closely for any traces of possible bone neoplasia

Answer 52

Radiographs- Typical appearance on radiographs: Single, aggressive bone lesion Forelimb – Proximal humorous and distal radius Hindlimb – Distal femur, proximal and distal tibia (“away from the elbow and near to the knee”) Areas of lysis Periosteal reaction “sun-burst” Radiographs are typical but full diagnosis requires cytology or histopath FNA- It is relatively non-invasive, quick and can be performed under sedation A full osteosarcoma diagnosis is not always obtained but a diagnosis of a malignant mesenchymal neoplasia (that is most likely an osteosarcoma) is Jamshidi needle

Answer 53

Thoracic radiographs - 3 inflated views CT is the preferred modality for a MET check - Note - >40% of METS seen on CT are missed with radiographs 95% of cases have micro-METs at the time of diagnosis that will be missed by imaging FNA local lymph nodes

Answer 54

This depends on several factors including patient suitability, the presence of gross METS and owner opinion/finances. Euthanasia will be required in all cases at some point. Analgesia - Bone neoplasia’s are very painful Multi-modal analgesia is required Most cases are euthanised within the first few weeks - months due to uncontrolled pain or occasionally from pathological fracture Can be combined with bisphosphonates Osteoclast inhibitors Palliative radiotherapy- Four treatments (fractions) given once a week under GA Useful in patients that are not good surgical candidates 80 – 90% get a good analgesic response which can last up to 6 months Unfortunately, pathological fracture or metastatic disease can affect them sooner, leading to a 3 – 4-month MST AMPUTATION- Fastest way to a pain free patient, if appropriate Where gross METS are present the median survival time is 3- 4 months Surgery where there are gross METS can be considered as part of palliative analgesia but should be carefully discussed with the owner before pursuing Without gross METS the median survival time is: 6 months with limb amputation alone Approximately 1 year if combined with chemotherapy, with 20% of patients living for 2 years LIMB SPARING- Aim to remove the bone neoplasia and preserve the limb Higher risk of complications than limb amputation Survival times are similar to limb amputation As a highly aggressive malignant cancer chemotherapy following limb amputation is indicated Various protocols 4 – 6 treatments of intravenous carboplatin every 21 days is used most often Myelosuppression and GI side effects The drug also reduces the glomerular filtration rate – watch the kidneys

Answer 55

surgery not normally possible due to location-> urethral obstruction chemotherapy main treatment- treat secondary utis: check sediement, bloods not reliable

Answer 56

2/3 malignat 80% of cases presenting with haemoabdoent have mailgnant splenic tumour acutr bleeds- collapse, lethargy pale mm hypovolemia pu/pd gi dingd mass may not be palpable in large dogs enlarged abdomen histeopath post splenectomy non heamoabdomen cases- FNA and cytology staging- abdo ultrasound chest radiographs chech right atrium if possible individal factors effect treatment treat hypovolemic shock- fluid bolus postop chemo if hsa chemo- doxyrubicin

Answer 57

Interdigital dermatitis (scald) Footrot Contagious ovine digital dermatitis (CODD) Toe granuloma Toe abscess Shelly hoof (white line disease) – usually not lame

Answer 58

Shelly hoof (white line disease) Toe granulomas (‘strawberries’) Foreign body penetration – thorns, sharp stones Soil balling – mud stuck in the interdigital space causing inflamation Hoof cracks – exposed corium Overgrown, damaged or misshapen claws Injuries to the limb

Answer 59

primary pathoges for scald and footrot Primary aetiological agent of interdigital dermatitis (scald) and footrot Gram negative rod – terminal swellings giving ‘dumbbell’ appearance; anaerobes Can survive in a wet environment (soil) - reservoir for infection of other sheep – spreads in sheep in wetter conditions – esp. Spring and Autumn in UK Persists long time on disease interdigital skin and in lesions within the hoof – need to isolate clinical cases – but can eliminate if remove these sheep as environmental reservoir will die out if not seeded repeatedly Multiple strains – wide range of virulence – some extremely virulent, others benign Theory: moist, softened or traumatised interdigital skin > inflammation and necrosis facilitates subsequent infections with D. nodosus > footrot develops as scald and can progress to full-blown footrot if not treated Often also associated with presence of Fusobacterium necrophorum – regarded now to be a secondary pathogen in footrot (excreted in faeces by some sheep) The microbiome on diseased feet also appears to play some role – some kind of bacterial dysbiosis = footrot

Answer 60

Dichelobacter nodosus Often also associated with presence of Fusobacterium necrophorum – regarded now to be a secondary pathogen in footrot (excreted in faeces by some sheep)

Answer 61

The research evidence base shows that: Aiming to treat within 3 days of onset has the best outcome – inspect flock regularly and pick out anything lame Treat with antibiotic injection (oxytet. LA) and spray i/d space and foot – don’t trim. Analgesic for pain. Focus on individuals to reduce flock spread – aim to avoid whole flock treatment Flocks where feet are never trimmed have the lowest prevalence of lameness Sheep footrot vaccine – Footvax (MSD Animal Health)- Can be used for prevention or in the face of an outbreak

Answer 62

‘For the active immunisation of sheep as an aid to the prevention of footrot and reduction of lesions of footrot caused by serotypes of Dichelobacter nodosus.’ Can be used for prevention or in the face of an outbreak Thick, viscous vaccine (oil adjuvant) so hard to inject in cold weather, and can provoke skin reactions

Answer 63

10% zinc sulphate solution (or copper sulphate) (frowned upon for heavy metal environmental contamination) 3% formalin solution (carcinogenic chemical for humans, granulomas) Others: e.g. Digicur Advanced 2% - combination of glutaraldehyde, copper and zinc Others: e.g. Hoofsure Endurance - organic acids, tea-tree oil and wetting agents [Antibiotic footbath solutions] - (soluble antibiotics (e.g. lincomycin) licensed for chickens/pigs) - imprudent use and lacking evidence of efficacy! Lot of vets will support their use, esp. for scald outbreaks in lambs Evidence for the efficacy of footbaths? Limited actual scientific trial evidence, but very commonly used over the years results suggest 2% Digicur is ineffective at reducing the load of D. nodosus when applied as a one off or weekly footbath, however sheep may act as a reservoir for multi-drug resistant bacteria creating opportunities to spread antimicrobial resistance to other sheep and their environment.’

Answer 64

First recorded in UK in 1997 Not quite as common as footrot, but still common in the UK (up to 58% flocks in UK) Severe lameness and significant welfare issue on affected farms Lesion at the coronary band and then extending under the horn down the toe – end up with avulsion of horn – exposes hoof laminae and affects pedal bone Staton et al. (2021) found in an experimental study that 84% of lesions arose from existing scald/footrot lesions Multiple bacteria present in CODD lesions – Treponema spp., D. nodosus, F. necrophorum The treponemes: Treponema medium, Treponema phagedenis and Treponema pedis found Can respond clinically to treatment with injectable LA amoxicillin (Betamox LA, Norbrook) or LA oxytetracycline; analgesics Oxytetracycline injectables: licensed in sheep- Zoetis, Norbrook, MSD, Bimeda Other antibiotic injectables: licensed in sheep- Norbrook (amoxicillin (not authorised for use in sheep producing milk for human consumption) ), Zoetis (– tulathromycin (macrolide)) , Boehringer Ingelheim (gamithromycin (macrolide))

Answer 65

No licensed analgesics in sheep in UK Use of NSAIDs under the cascade Some farmers are seeing the benefits of analgesic use – persuaded by vets Meloxicam most purchased NSAID in this sample of 52 N. Irish farms More work for vets to do with sheep farmers to educate regarding the benefits for sheep welfare

Answer 66

Detachment of hoof horn wall from the underlying epidermis (often the abaxial wall) The separation itself does not usually cause lameness, unless horn breaks off to expose sensitive laminae – very painful Separation leaves a cavity – space for dirt to become impacted Foreign body penetration easier into sensitive tissues - abscess formation and then severe lameness risk facotors- Reeves et al. (2019) found more likely in flocks that were footbathed in formalin compared with not footbathing (OR = 1.65; 95% CI 1.19–2.30) It was less common in flocks that stocked ewes at higher stocking densities more than eight vs. four per acre (OR = 0.34; 95% CI 0.17–0.68) – why? Found weak associations between shelly hoof and foot trimming Reeves et al. (2019) proposed that flocks with shelly hoof would decrease incidence if farmers stopped footbathing (esp. with formalin), and avoided foot trimming whether as a therapeutic or routine practice

Answer 67

Granulation tissue in response to injury/untreated footrot Usually caused by excessive trimming Bleed profusely and painful hard to fix- Regrow if removed Nursing care, analgesia, cull Footbathing in formalin appears to predispose

Answer 68

Occurs when infection gets into the white line – e.g. stone or thorn penetration – abscess develops under the wall or sole horn Pus from the coronary band once bursts Smelly Hoof likely to be hot to the touch and painful before pus becomes visible Very painful = acutely lame Can often see the penetration on white line on sole – gentle paring may reveal

Answer 69

Caused by Erysipelothrix rhusiopathiae (also causes dimond marks in pigs) Typically, in sheep that have been dipped in a dip that was used the day before and allowed to stand overnight E. rhusiopathiae contamination from soil the previous day multiplies overnight and enters small skin abrasions – bacterial soup! Dull, lame and pyrexic within next few days Can have sizeable proportions of the flock affected, esp. lambs Treat with injectable penicillin; avoid keeping dip too long

Answer 70

Mainly Streptococcus dysgalactiae subsp. dysgalactiae Lambs usually < 4 weeks old – clinical signs often at 10-14 days Swollen, hot joints – lameness, recumbency – outbreaks possible Thought to be acquired in first few hours of life – ewes, unsanitary conditions, lack of colostrum, untreated navel – umbilical entry, ear tag, tail dock, mouth Procaine penicillin drug of choice, NSAIDs for pain Joint pathology can be permanent if does not respond to treatment

Answer 71

Culling policy – breeding for genetic resilience (less susceptible ewes) Biosecurity - closed flock (rams), quarantine and examine all incomers, prevent straying, transport vehicles, recognize contaminated pastures, move feed troughs, isolate infected sheep if possible Vaccination – only one vaccine on the market – Footvax (MSD) Treat individuals promptly and effectively for the benefit of the whole flock The five-point plaN- - Treat, quarantine and avoid contaminated pastures to reduce challenge - Cull to build resilience - Vaccinate to establish protection Lameness treatment drives most of the antibiotic use in sheep Emphasis must also be placed on the importance of long-term commitment to lameness control strategies, as there is no one, short-term panacea for controlling lameness

Answer 72

Known as well as Canine Cognitive dysfunction (CCD) in dogs, also affects cats (limited data). Progressive neurodegenerative, linked to aging in dogs and cats and characterised by decline in cognitive performance and behaviour changes. Risk factors identified in dogs – further research needed (MacQuiddy et al., 2022, Dewey et al., 2019) Age Anecdotally mentioned : Female, neutered, Low BCS, Diet? One study - high quality, controlled diet are 2.8 times less likely compared to uncontrolled low-quality diet. Concomitant disease? One study on IE, more likely to develop at young age. 28% for dogs between 11–12 years old and 68% in dogs 15–16 years old. (Neilson et al., 2001) 8.1% in ages 8 to <11 years, 18.8% in ages 11 to <13 years, 45.3% in ages 13 to <15 years, 67.3% in ages 15 to <17 years, and 80% in ages >17 years (MacQuiddy et al., 2022) 14.2% for dogs between 8-19 years old, only 1.9% were diagnosed by a vet. (Salvin et al., 2010) Cats: 36% 11-21y, 50% at 15+ and 28% 11-14y. (Moffat et al., 2003) Pathophysiology - Pathologic features: Perivascular and parenchymal neurotoxic amyloid beta (Aβ) protein accumulation into plaques that affect exchange at level of BBB. Cerebrovascular diseases: decreased oxygenation to affected part of the brain. Oxidative brain damage, due to decrease in endogenous antioxidants, leading to neuronal death and increase in free radicals. Reminder: brain tissues has high level of polyunsaturated FA, very sensitive to oxidative damage from free radicals. Neuronal mitochondrial dysfunction Decreased neuronal glucose metabolism Glutamate-mediated excitotoxic neuronal damage Decrease in catecholamine (Norepinephrine, dopamine), serotonin and GABA neurotransmitters and cholinergic system dysfunction, increase in monoamine oxidase B activity (MAOB) Structural features: Cerebrovascular disease: hemorrhages or infarcts Meningeal calcification, Reduction of overall brain mass (frontal and temporal lobes, hippocampus) with degeneration of white matter, demyelination,. Increased in ventricular size Generalised gliosis: Microglial dysfunction: pro-inflammatory Astrocyte dysfunction: increased neuroaxonal degeneration, decreased glutamate uptake, increase in free radicals.

Answer 73

Often unreported and missed by owners as thought to be part of the normal aging process, especially with mild signs (socialization and sleep changes in dogs, vocalization and house soiling in cats). No apparent early clinical signs to owners, but cerebral changes will already be occurring. Dogs (> 8yo), Cats (>10y approximately) DISHAA (L)- Disorientation Alterations in social Interactions Changes in Sleep-wake cycle House soiling (part of it linked to memory) Alterations in activity levels Anxiety level changes Learning and memory Diagnostic approach: Based on history, signalment and exclusion of other pathologies Identification of stress factors (acute or chronic) that may impact wellbeing Examination: general, neurological, orthopedic, pain assessment. Use of scale / scoring tools: Canine Cognitive Dysfunction Rating scale (CCDR) (Salvin et al., 2011) CAnine DEmentia Scale (CADES) (Madari et al., 2015) - better at differentiating stages of CCD, identify earlier stages and follow progression

Answer 74

Delay onset and progression – Uncurable currently Early recognition and intervention is likely to lead to positive outcome. Client education is paramount. Preventative approach even in subclinical cases as patients no behavioral changes may still have pathological changes Consistency at home is important to prevent increasing stress levels diet and nurtritional suppiments pharmcologic intervention cognative and enviromental enrichmet adjunctive therapies CARE - Lack of clinical evidence in cats and many drugs are off licence. cognative dysfuntion- Increase and provide varied training, play and exercise time Introduce new stimuli: toys, smells, sounds and touch. Introduce hand or voice cues to palliate for sensory changes Ensure positive and varied interactions (people and pets). Ensure opportunities to explore new areas. Cats: provide 3D environment and favours hunt-and-chase game. soiling- Increase frequency and safe proof access to outdoors Add an indoor toilet area Cats: provide low sides litter tray and add-in ramps mobility- Ramps Ramps Physical support devices: slings, cart, pram. Facilitate access to ALL resources (outdoor, toileting area, sleep area, feeding area, toys) sleep- Provide a consistent day-night cycle: reduce exposure to artificial light during nighttime, increasing outdoor time Reduce night disturbances Provide a safe space for rest Allow a final interactive and physical session before sleep nutrition an ideat supliments-- Combination with behavioural enrichment would lead to a better cognitive performance compared to without (Milgram et al, 2004). Provide antioxidants (AO, including vit B, C, E ), mitochondrial co-factors, phosphatidylserine and Omega-3 Fatty-acids to reduce the effects of free radicals and reduce Aβ deposits. MCT (medium-chain Triglycerides, C8 and C10) - Provide alternative source of energy to palliate for deficient glucose metabolism. Phosphatidylserine - neuronal membrane component and participating in synaptic processes. Hill’s Prescription Diet b/d Canine - AO, omega-3 Purina One Vibrant Maturity 7+ Senior Formula (US) - MCT Purina ProPlan Veterinary Diet NC NeuroCare - MCT No current specific diets for Cats but Hill’s Prescription Diet Feline j/d – AO and omega-3 Coconut oil Senilife®, Ceva - dogs/cat. Phosphatidylserine and AO Aktivait®, Vet Plus – dogs/cats. Phosphatidylserine, AO and co-factors. SAMe – increase AO production, improve catecholamine system performance. Care when use alongside serotonergic drugs. Silymarin (milk thistle) – AO and anti-inflammatory properties.

Answer 75

Selegiline- Selective inhibitor of monoamine oxidase B (MAOI). Enhance brain catecholamine activity and decrease free-radicals production and increase clearance. Dogs– 0.5-1mg/kg SID in the morning. Improvement > 2 weeks. Cats (off licence, anecdotal) - 0.5-1mg/kg SID Should not be use alongside other serotonergic drugs (MAOIs, TCA and SSRIs - clomipramine, trazadone, fluoxetine and sertraline - tramadol) Propentofylline- Phosphodiesterase inhibitor. Increase blood flow to CNS, muscle and heart. Inhibition of platelet aggregation and thrombus formation. Decreases free radical production. Dogs – 2.5-5mg/kg PO BID 30min before food. Cats (off licence, anecdotal) – 12.5mg SID Bronchodilator, positive inotropic and chronotropic effects. Care in patient with cardiac disease and contraindicated in pregnant animals Anxiolytic and behaviour modification drugs- Memantine (POM off licence) – block activity of glutamate. Used in compulsive disorders in dogs – 0.3-1.0 mg/kg BID Sertraline (POM) – SSRI. Used in compulsive disorders in dogs – 3mg/kg SID. Fluoxetine (POM-V) – SSRI. Used in separation anxiety ad compulsive disorders. Dogs 1-2mg/kg SID, Cats 0.5-mg/kg SID Clomipramine (POM-V) – TCA. Used in separation anxiety and inappropriate elimination, compulsive disorders. Dogs 1-2mg/kg BID, Cats (of Licences) 0.25-1mg/kg SID Trazodone (POM) – antidepressant, sedative. Chronic anxiety. Dogs 2-5mg/kg up to TID Gabapentin (POM) – GABA analogue. 10-30mg/kg TID to BID and Cats 5-10mg/kg TID to BID Adjunctive therapies- Sleep and stress - Melatonin Alpha-casozepine (Zylkene®, Vetoquinol) – dog and cat Pheromones (Adaptil®,Feliway®, Ceva)- dog and cat Anti-anxiety/compressive gear (Thundershirt®) Situational use of sedative: inducer – phenobarbital, trazodone, benzodiazepine (clonazepam, lorazepam)) mobility- Physiotherapy, hydrotherapy Osteoarthritis treatment and management: NSAIDs, Paracetamol, Solensia®, Librella®, Tramadol, joint supplements

Answer 76

used for cognative dysdfunyion syndrome Selective inhibitor of monoamine oxidase B (MAOI). Dogs– 0.5-1mg/kg SID in the morning. Improvement > 2 weeks. Cats (off licence, anecdotal) - 0.5-1mg/kg SID Should not be use alongside other serotonergic drugs (MAOIs, TCA and SSRIs - clomipramine, trazadone, fluoxetine and sertraline - tramadol)

Answer 77

used for cognative dysdfunyion syndrom Phosphodiesterase inhibitor Increase blood flow to CNS, muscle and heart. Inhibition of platelet aggregation and thrombus formation. Decreases free radical production. Dogs – 2.5-5mg/kg PO BID 30min before food. Cats (off licence, anecdotal) – 12.5mg SID Bronchodilator, positive inotropic and chronotropic effects. Care in patient with cardiac disease and contraindicated in pregnant animals.

Answer 78

Structural abnormalities - Urethral length Urethral diameter Storage capacity- Innervation Detrusor atony Urethral tone- Bladder neck positioning Neutering Innervation transitional cell carcinoma in th etrigone

Answer 79

Patient factors: Age, breed, sex, reproductive status (neutered or entire, age of neutering) Description of the leaking: is it continuous or intermittent? Normal micturition in between episode? Episode information- time of day, progression over time & onset (acute, chronic, progressive, improving), association with stress, conscious or unconscious. Other useful information: defecation patterns, back pain/history of neurological problems, PU/PD, abnormalities in normal urination (eg: stranguria, pollakiuria, haamaturia) clinical exam- Physical exam- full clinical examination. Specific areas of focus on: Bladder size- normal/small or distended- obstruction? faulty innervation? Neuro exam- proprioception, sensation and movement of the tail, perineal reflex, lumbar-sacral pain. Genital exam- exteriorise penis, check for vulval dermatitis Rectal examination- palpate urethra (stones or masses), check prostate in males, lymph nodes Other indicators of conditions that maybe be associated with PU/PD for example: muscle wastage, alopecia in patient with hyperadrenocorticism

Answer 80

Hematology, biochemistry and urinalysis Radiographs – plain or contrast Plain- abdominal radiograph without any contrast medium. Retrograde urethrocystogram- contrast is administered via a urinary catheter and a series of radiographs are taken. Aids identification of structural abnormalities in the bladder or urethral. IV urethrography- contrast medium is administered IV and filtered out by the kidneys. Series or radiographs are taken. Helpful to identify pathologies associated with the ureters and kidneys. Cystoscopy – endoscopic examination of the urethra and bladder. Ultrasound CT

Answer 81

Reduction in the tone of the smooth and striated muscle comprising the internal and external sphincter respectively resulting involuntary urine leakage. Why does it occur? Anatomical abnormalities eg: short urethra and intra pelvic bladder position. Hormonal changes associated with neutering eg: reduced circulating oestrogen. Degenerative processes eg: loss of collagen Other risk factors include breed and obesity- larger breeds

Answer 82

Focus of treatment is to increase urethral sphincter tone. Phenylpropanolamine (Propalin) Mechanism of action: Adrenergic agonist that increases the contractility of the smooth muscle therefore resulting in a stronger close of the urethral sphincter. 1st line medical treatment in female and male dogs. Estriol (Incurin) Oestrogen replacement Mechanism of action: increases the number of receptors responding to phenylpropanolamine. 2nd line medical treatment to be used in conjunction with phenylpropanolamine. Contraindicated in male dogs as it is a oestrogen derivative.

Answer 83

You do not need to know how to perform each of the procedures just the principles of how they reduce incontinence by alternating urethral tone. Reduce urethral diameter by injection agents such as collagen, vet foam into the urethra. Minimally invasive procedure performed by endoscopy- will need to be repeated every 6 to 18 minths Increase urethral tone through surgical placement of a urethral cuff resulting in permanent narrowing of the proximal urethra- complex abdominal surgery, more invasive In patients with anatomical abnormalities eg: short urethra and intra pelvic bladder position a surgical procedure to move the bladder neck and urethra cranially. This will reduce incontinence as the urethra will be subject to intra abdominal pressures. Procedure name: colposuspension. no garentied fix, may be used in combo with medical managemnt

Answer 84

may present with- tetraparesis cervial ventroflexion bilateral misdriasis adrenal mass present on ultrasound the zona glumerolosa in the cortex of the ad=lrenal gland produces aldosterone- mainains systemic blood pressure- RAAS in this condition too much aldosterone is produced- more than 5 times normal range, ususlally due to functional mass assosited with low circulating rnin concentration- RAAS neg feedback causes hypocalemia which results in neuromuscular junction adn possible organ damage retinal detachmet ot intraocular haemorages can also be present can mimic other geriatric diorders- CKD, DM palpable abdominal mass systemic hypertension- coiuld presipitate renal disease can mimic renal signs- azotemia, isosethenuria

Answer 85

urinary aldosterone to creatanie ratio often used dynamic testing with flufrocortisone- has no effect in cats with htis disease so diagnostic abdominal ultrasound- not as specific, adrenals can be enlarged for other reasons

Answer 86

unilateral adrenaectomy treatment of choice- contraindications?- bilateral presentation, other diseases medical options- ARB- spirolactone potassium suplimentation calcium blocker for hypertension-Amlodipine

Answer 87

causes acromegally hepatomegally uncontrolled diabetes- high dose of insulin >1.5, plantigrade stance from diabetic neuropathy arythmia broad facial fetures Imaging- functional adenoma imaging not diagnostic overproduction og groth hormone- organomegally males more effected than females- domestic short hair polyphagia may be increased respiritory stridor - hyperglosia mild cardiomegally neuro signs form mass in later disease diagnosed by testing for inusline like growth factor- can get false neg repeat 6-8 weeks short term fasting can lead to false neg can test for growth hormone in a lab setting

Answer 88

durgical- transsphenoidal hypohyectomy medical- somatostatin analougs- pasireotide radiation therapy- widley used conservative options- high doses of insulin to control diabetes

Answer 89

slow bolus of Ca gluconate- 1ml/kg calium gluconate over 15-20 mins administer IV through IV catheter ECG attached submit blood to regional laboratory for a PTH

Answer 90

decreased ionised calcium and parathyroid hormone and absense of any other markers

Answer 91

results in electorlite imabalence low ca high p hyperexitability of cns and pns idiopathic

Answer 92

acute- iv calcium chronic- vitamin d- needs to be activated calcitrol- activated vit d 3 gold standard downside is short time to max effect no vet formulations cant split human capsuals alfacidol- one alpha best current option- not much literature check tCa/iCa daily and adjust dose incramentally

Answer 93

99% of body calcium resides in the skeleton and is stored as hydroxyapatite Most skeletal calcium is poorly exchangeable, and less than 1% is readily available 0.1% of total body calcium is in the extracellular fluid The rest of the calcium is in the cells and its organelles 50% ionised calcium (diffusible) E.g. Ca carbonate, Ca phosphate Physiologically active 40% protein-bound (non-diffusable) 10% chelated calcium Calcium pool- Gains from: GI absorption – 35% of ingested calcium is absorbed Bone resorption Loses to: Endogenous faecal excretion ~ 90% Urinary excretion ~ 10% Milk Bone formation

Answer 94

3 key components Parathyroid hormone (PTH) Calcitonin Vitamin D (Calcitriol) (also PTHrP) important for- Nerve Conduction Neuromuscular transmission Muscle contraction Smooth muscle tone Membrane stability Membrane transport Enzymatic reactions Hormone secretion Blood coagulation Bone formation Control of hepatic glycogen metabolism Cell growth and division

Answer 95

Total Calcium >3mmol/L or iCa >1.5 mmol/L Reference ranges vary between machines Mild increases may not be relevant in juvenile dogs High total calcium should prompt ionised calcium evaluation before further investigation Clinical signs proportionate to: Rate of increase Magnitude of increase Cause of hypercalcaemia Increased calcium ions is toxic to cells: affects membrane function and metabolism ultimately ends in cell death HARD IONS H – Hyperparathyroidism (primary vs secondary) A – Addison's R – Renal disease (acute and chronic) D – Vitamin D Toxicosis I – Idiopathic (cats) O – Osteolytic N – Neoplastic (e.g., lymphoma, multiple myeloma, anal sac adenocarcinoma) S – Spurious G – Granulomatous disease (infectious) Common Signs- PU/PD Anorexia Dehydration Lethargy Weakness Vomiting Chronic renal failure Uncommon Signs- Constipation Cardiac arrhythmia Seizures Twitching Acute intrinsic renal failure Calcium urolithiasis Death

Answer 96

Increased PTH increases calcium absorption- Increased osteoclast activity --> increased calcium concentration in ECF Increased calcium reabsorption from the renal tubules (less excretion) Increased absorption of calcium from the GIT Primary Hyperparathyroidism- Parathyroid tumour – usually single parathyroid adenoma Loss of normal negative feedback control Uncommon in dogs, rare in cats High calcium, low phosphate

Answer 97

30% of Addisonian dogs are hypercalcaemic Rare in cats Middle-aged dogs with Standard Poodles and Portugese Water dogs being over-represented Unknown mechanism

Answer 98

Relatively uncommon Common examples: Psoriasis cream (licking cream off the owner) Vitamin D tablets Nutraceuticals Rodenticide Plant ingestion e.g., nightshade, oatgrass, jasmine

Answer 99

CKD- Azotaemia, hyperphosphataemia, normocalcaemia/hypocalcaemia, isosthenuria Occasionally hypercalcaemia 31% of azotaemic cats, 10% of azotaemic dogs Feeding early CKD cats severely-phosphate-restricted diets can cause them to develop hypercalcaemia Renal disease due to other causes can also lead to hypercalcaemia

Answer 100

Cats not dogs Most common cause of hyperCa in cats Diagnosis of exclusion 50% don't have clinical signs at time of diagnosis 10-15% have calcium oxalate uroliths

Answer 101

Rare cause of hypercalcaemia Usually secondary to other disease e.g., multiple myeloma, primary bone tumours

Answer 102

Hypercalcaemia of malignancy Typically driven by tumour PTHrP production- Total calcium and ionised calcium increased Phosphate normal/low Low PTH, high PTHrP Also, with tumour metastasis to the bone Most common- Lymphoma – especially T-cell lymphoma AGASACA – rare in cats Multiple myeloma Less common- Osteosarcoma Metastatic bone tumours Mammary carcinoma Also reported in- Thymoma, pulmonary carcinoma, nasal carcinoma, malignant melanoma

Answer 103

Acidosis Lipaemia Haemolysis Young animal! (not spurious but also may be normal for them if mild)

Answer 104

Increased macrophages Macrophages can synthesise calcitriol from calcidiol without negative feedback regulation Macrophages may also synthesis PTH-rP which may activate PTH receptors Granulomatous diseases- Fungal (uncommon in the UK) Schistosomiasis Angiostrongylos vasorum Nocardia Mycobacteria FIP in cats

Answer 105

HARD IONS Cat versus dog Age of dog – is physiological likely? Breed- Large breed dogs <1 years old may have a mild hypercalcaemia Keeshonds over-represented for primary hyperparathyroidism Clinical signs- Anorexia Polydipsia/polyuria Vomiting Muscle weakness or twitching Diet- Raw diet Toxin ingestion e.g., Vitamin D tablets, creams, rodenticide exposure Supplements Travel? Palpate lymph nodes- Submandibular, prescapular, axillae, inguinal, popliteal FNA – can often reach diagnosis if lymphoma Rectal Examination- AGASACA – can be diagnostic with FNA Sublumbar lymph node enlargement or urethral stones may be palpable If not amenable, ensure do when asleep Orthopaedic examination- Bony swellings, pain

Answer 106

initial blood tests- Ionised calcium measurement- Is hypercalcaemia true, repeatable especially if no clinical signs associated with this CBC- Lymphocyte count Biochemistry- Renal disease Addison's (Hyperkalaemia, hyponatraemia) Phosphate Basal Cortisol in dogs PTH and PTHrP- When to perform? Is hypercalcaemia parathyroid dependent or independent? Dependent – PTH is high normal or increased Independent – PTH production is suppressed in response to the hypercalcaemia Vitamin D analogues Basal cortisol +/- ACTH stimulation if suspect Addison's FIV/FeLV in cats Angiodetect urinalysis- Increased excretion of calcium in the urine of cats that are hypercalcaemic can predispose them to calcium oxalate urolith formation Uroliths identified in 15% of hypercalcaemic cats – 73% calcium oxalate Evaluation for underlying renal disease- Protein imaging- Thoracic and abdominal radiographs- Include bones! Look at the spine Abdominal ultrasound- Kidneys Lymph nodes Neoplasia Ultrasound of parathyroid glands Soft tissue calcification- Kidneys and gastric mucosa are the predominant organs to be affected Uroliths, nephroliths, ureteroliths Other- Bone biopsy FNA/biopsy masses

Answer 107

Increased concentrations of fibre, sodium, water Fibre binds to intestinal calcium thus reducing reabsorption Decreased concentrations of calcium, vitamin D3, vitamin A (or a combination) Diet options: Hills Prescription diet w/d, or gastrointestinal biome Psyllium husk Chia seeds (controversial, but harmless?)

Answer 108

Underlying disease dependent! Treatment of underlying disease often can resolve hypercalcaemia Depends on the aim- Anaesthesia safety Supportive treatment? e.g., seizures, arrhythmias, urolithiasis Timing- Will it influence diagnostics? Steroids very effective but risks How acute is the hypercalcaemia? How unwell is the pet? Saline 0.9%- Increase calciuria Na competes with Ca reabsorption so more Ca is excreted Furosemide- Increases diuresis because of increased lumen electronegativity NaK2Cl transporter in the thick ascending loop of Henle aims to maintain electroneutrality Ensure patient well hydrated before therapy Glucocorticoid- Reduce bone turnover and GI absorption Also possibly increased renal excretion Cytotoxic to lymphocytes so reduced PTHrP Avoid use until definitive diagnosis reached Bisphosphonates- Inhibit osteoclast-mediated calcium mobilisation from bone Risks include oesophagitis and mandibular necrosis (especially in cats) e.g., Alendronate (give after fasting)

Answer 109

Intravenous fluid therapy (0.9% NaCl) - for fluid deficits and promoting diuresis Furosemide when well hydrated – promotes diuresis and rapid onset of action Calcitonin – may be helpful in short-term Oral bisphosphonates and oral glucocorticoid therapy have a slower onset of action (1-2 days after administration) so are often not helpful in the acute setting

aproach to disease managment Flashcards

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