Conference Proceedings

• Cancer in cats – what is it, and can you treat it?
• Radioactive iodine – a glow-in-the-dark treatment for hyperthyroid cats?
• Use of external beam radiation therapy in the treatment of feline cancer patients
• Polo's pleural problem - a case of mediastinal lymphoma
• Caring for cats with cancer – the importance of good nursing
• Behavioural changes and support for sick cats

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Cancer in cats – what is it and can you treat it?

Dan Batchelor BVSc CertSAM MRCVS

Resident in Small Animal Internal Medicine/Oncology

Small Animal Hospital, University of Liverpool

Introduction

A tumour is an abnormal mass of tissue, the growth of which exceeds the body's requirement for new cells and is uncontrolled and progressive, and in which cell differentiation is often impaired.

Benign tumours usually grow slowly, and push normal tissue aside but do not invade it. Malignant tumours may grow by expansion and invasion into surrounding tissues. They can also spread to other, distant, parts of the body by the process of metastasis . The words “tumour”, “neoplasm” and “cancer” are often used interchangeably, but strictly speaking a cancer is a malignant tumour. The study of tumour biology and therapy is called oncology.

In the United Kingdom cat population, at least one in six cats will develop a malignant tumour during their lifetime.

Golden rules of cat (and dog!) oncology

1. Tumours don't go away, they grow and/or metastasise.

2. If you don't know what it is you can't treat it properly!

3. Early treatment is always more likely to be successful in curing the patient or providing a meaningful extension to life.

Approach to the feline patient with cancer

Questions that need to be addressed:

• “What is the cancer?” - Requires a histological diagnosis (from a biopsy) or cytological diagnosis (for example, from a fine needle aspirate sample) to determine accurately the tissue of origin and grade of the tumour. Tumour grade is an estimate of how malignant it is, based on the biopsy findings.

• “How far has it got?” - Determination of the extent of the disease locally and at distant sites. These diagnostic procedures are called staging .

• “Are there any tumour related complications?”- These are called paraneoplastic syndromes and are fairly uncommon in the cat.

• “Is there any concurrent disease which may alter prognosis or the cat's ability to tolerate treatment?” Concurrent problems are very common in older cats.

Having assessed these questions we then consider how we expect the cancer to behave in the future in this cat (this often means looking it up in an oncology book). Finally, we discuss options for treatment and likely outcomes with the owner. As in the treatment of any feline patient, the priority of treatment is to provide a good quality of life for the cat.

Tumours are classified in several ways, most commonly by their behaviour:

• Benign
• Malignant

Or by their tissue of origin:

•  Epithelial tumours- malignant ones are termed carcinomas

•  Mesenchymal (connective tissue) tumours- malignant ones are called sarcomas

•  Haematopoietic (blood cell) tumours – e.g. lymphoma, leukaemia, mast cell tumour

•  Others are recognized- a complete list would be very long!

There are three principal ways in which cancer is treated in cats:

1. Surgery  For cats that require surgery: remember that the first surgery a patient has is often the only chance for cure or long term control: the success rate for second surgeries is MUCH lower. This is why accurate diagnosis before definitive surgical treatment is vital!

2. Chemotherapy

3. Radiotherapy

Combinations of treatments can be employed.

Techniques for tumour diagnosis:

May be based on cytology (looking at individual or small groups of cells, for example from aspirates or effusions,) or biopsy (looking at a larger, fixed, sample of tissue). Cytology has advantages in that it is minimally invasive, probably doesn't require sedation or anaesthesia, offers rapid results, and is cheaper. However, as only small numbers of cells are examined, samples may be unrepresentative or misleading. In most situations in feline cancer, biopsy is required for accurate diagnosis: biopsy gives a larger, more likely representative sample, and allows assessment of tissue architecture.

Biopsy techniques include

• Needle core biopsy (e.g. “tru-cut” biopsy)
• Relatively non-invasive, and can biopsy relatively inaccessible lesions (such as liver or kidney lesions under ultrasound guidance)
• Not good for lymph nodes
• Incisional biopsy (commonest technique used)
• Some rules:
• Position the incision so that the biopsy tract can be easily and completely removed during any subsequent surgery
• Avoid excessive tissue manipulation.
• Minimize biopsy handling, especially by instruments. Avoid diathermy or cryosurgery (creates artifacts)
• Avoid necrotic or haemorrhagic areas.
• Grab biopsy
• Usually performed with endoscopy in inaccessible sites
• Take multiple samples as it's easy to miss the lesion with small forceps
• Nasal biopsies can be collected but avoid introducing the forceps beyond the level of the medial canthus of the eye (you don't want to perform a brain biopsy…)
• Punch biopsy
• For superficial lesions
• No good for lymph nodes
• Excisional biopsy
• Surgical removal of a lesion and submitting it for histopathology
• Only acceptable in situations where diagnosis would not affect the proposed treatment.

Selected cancers of cats

LYMPHOMA

Lymphoma (Malignant Lymphoma, Lymphosarcoma) is common in cats, and represents up to 25% of all feline tumours.

4 main anatomical forms of feline lymphoma are recognized:

•  Multicentric lymphoma - generalized enlarged lymph nodes, +/- liver and spleen involvement, +/- bone marrow involvement. While this is by far the commonest presentation in dogs, this form is relatively rare in the cat. Affected cats usually have non-specific clinical signs, and the abnormalities are evident on physical examination.

•  Mediastinal lymphoma - present as a mediastinal mass. Typically young cats, and usually present with difficulty breathing (because of the size of the mass and/or pleural effusion). Cats may be coughing or regurgitating (because of pressure on the trachea or oesophagus, respectively.) Physical examination may reveal caudal displacement of the apex beat and heart sounds, and a loss of the normal “compressibility” of the cranial thorax.

•  Alimentary lymphoma - solitary intestinal mass or multiple masses, or diffuse infiltration of the intestines, +/- enlargement of the mesenteric lymph nodes. Cats usually present with gastrointestinal signs, most frequently vomiting, diarrhoea, anorexia, and weight loss.

•  Extranodal lymphoma - can affect any organ or tissue. Clinical signs depend on the location of the lymphoma. Commonly seen examples:

•  Renal lymphoma causing kidney failure

•  Nasal lymphoma causing sneezing/nasal discharge

•  Central nervous system lymphoma causing neurological abnormalities

Diagnosis is based on cytology or biopsy of the affected tissue. In cats with lymph node involvement, cytology is less frequently diagnostic than in dogs. These cats often have low grade small cell or mixed lymphomas, which are difficult to differentiate from reactive lymph node hyperplasia on cytology. Therefore, biopsy is often required to diagnose multicentric lymphoma in cats. To perform lymph node biopsy, surgical excision of the whole node is recommended (or wedge biopsy, if the node is enormous). Extranodal lymphomas or mediastinal lymphomas are often higher grade, so are easier to diagnose on cytology. Wedge or trucut biopsies can be taken, depending on the situation. In alimentary lymphoma, endoscopic grab biopsies may not be diagnostic and full thickness biopsies may be required. In cats with CNS lymphoma, cerebrospinal fluid analysis may be diagnostic for lymphoma if malignant lymphoblasts are found (but normal CSF doesn't rule it out).

Staging usually involves radiography of chest and abdomen, and an abdominal ultrasound scan. Ideally, bone marrow aspirate and biopsy is performed.

The role of Feline Leukaemia Virus

Historical reports document that approximately 70% of cats with lymphoma were FeLV positive. Possibly because of more vaccination against FeLV, nowadays less than 10% of cats with lymphoma are positive for FeLV. However, FeLV viral elements have been found in tumour tissue from cats with lymphoma that are FeLV negative, i.e. not persistently viraemic. It is estimated that cats that have been exposed to FeLV (but have recovered) have a 5X increased risk of lymphoma. Persistently viraemic cats have a 50X increased risk. FeLV positive cats with lymphoma have a poorer prognosis, they may not respond as favourably to chemotherapy, and may have other diseases.

Treatment of lymphoma

Median survival without treatment is 4 weeks. Treatment options include:

• Corticosteroids alone (short increase in survival)
• COP chemotherapy protocols
• Multidrug chemotherapy regimes (e.g. Madison-Wisconsin, CHOP)

In cats the high-dose COP protocol is an excellent protocol, and is generally very well tolerated. One fairly recent retrospective study showed a 75% clinical remission rate, with one year survival rate of 49% and two year survival of 40% with this protocol. Comparison of different protocols is difficult because of the very varied nature of the feline lymphomas treated.

Prognostic indicators are not as well defined as in canine lymphoma. Whether or not the cat achieves clinical remission (i.e. no detectable tumour left) is the only proven positive prognostic indicator (it is not possible to know this before starting treatment!). Cats with small volume extranodal disease may have a better prognosis.

Negative prognostic indicators include failure to achieve clinical remission; FeLV positive status; and (unproven) prior treatment with steroids.

MAMMARY TUMOURS

These are common in cats, and sadly 80-90% of feline mammary tumours are malignant. They are generally seen in older female cats, although cats of only one year of age, and male cats, have been affected. At presentation firm masses in the mammary glands are found, and involvement of multiple glands is common. Metastasis to local lymph node and to the lungs is common.

Surgery is the treatment of choice for feline mammary tumours and an aggressive approach should be taken. In very aggressive cancers, or later on in less aggressive cancers, tumour adherence to the overlying skin or the underlying muscle can be a problem. Because of the unpredictable nature of lymph drainage in the feline mammary chain, removal of all the glands on the affected side is often recommended. When deciding on a surgical plan each case should be approached as an individual. Decision making should also take into account the presence of pulmonary metastasis.

Tumour size has a major impact on prognosis: median survival time after surgery for cats with a tumour > 3cm across was 4-6 months, whereas it was > 3 years for cats with a tumour < 2cm across.

The use of adjunctive chemotherapy in combination with surgery has not been assessed in controlled studies, although may be of benefit in prolonging survival time. 50% of cats receiving chemotherapy for inoperable mammary cancer did have short term palliation of their cancer, although survival was only marginally increased.

SQUAMOUS CELL CARCINOMA (SCC)

These are common skin tumours of cats. There is a recognized association with exposure to sunlight. SCC usually occurs in non-pigmented areas (so white cats are predisposed) and in areas with thin fur covering: the commonest sites are the nasal planum, pinnae, and eyelids. In some cats there are multiple lesions.

The lesions may be proliferative but are often ulcerative and erosive. Early lesions often present as small “scabs” that do not heal. Later on, this can progress to a deep, inflamed ulcer. The tumours are locally invasive, and although they can metastasise, this is quite rare and occurs late in the course of the disease.

Diagnosis is by biopsy, and staging involves checking for metastatic spread to the local lymph nodes and lungs.

Surgery is the treatment of choice. Lesions on the eartips are easier to manage, because more aggressive surgery can be performed. The cosmetic appearance of the cat after removal of the earflap is generally fine. Surgery is also the best treatment for SCC at other sites, but, as always, chance of a successful outcome is much higher for small lesions that are treated early.

Prevention involves avoidance of UV exposure. It is difficult to stop cats sunbathing. High factor sunblock cream should be tried but needs to be applied frequently, and cats are quite good at licking it off!

ORAL TUMOURS

Tumours of the oral cavity in cats include:

• Squamous cell carcinoma (commonest, 60-80% of tumours)
• Fibrosarcoma (10-20%)
• Osteosarcoma
• Lymphoma
• Melanoma

Benign tumours are rare (benign odontogenic tumours are occasionally seen in young cats). Cats do get a number of non-neoplastic conditions that affect the oral cavity, especially eosinophilic granuloma.

Diagnosis is on biopsy (fine needle aspirates are rarely diagnostic). Wedge biopsies must be deep to ensure a diagnostic sample. Radiography is useful and may show evidence of bone invasion. CT or MRI scans are more sensitive for detecting bone involvement and are useful to determine tumour extent in cats that may be candidates for surgical treatment. Staging involves aspiration of the submandibular lymph nodes, and thoracic radiography.

Squamous cell carcinomas generally affect older cats. A common site is the base of the tongue. They are very locally aggressive and are often not amenable to surgical treatment. Radiotherapy is generally associated with a poor outcome, and side effects can be a problem. These tumours respond poorly to chemotherapy.

Fibrosarcomas are also locally invasive, but fairly infrequently metastatic. Complete resection is the best treatment: early diagnosis is desirable as cats do not tolerate radical jaw resection well. Radiotherapy may be palliative in some inoperable cases.

VACCINE ASSOCIATED SARCOMA (VAS)/ INJECTION SITE SARCOMA

This is a complex disease, and despite much investigation the cause of VAS is still poorly understood. The incidence in the USA at the most recent estimate was 0.63 sarcomas/10,000 cats vaccinated. In the UK , incidence appears to be lower: 0.21 sarcomas/10,000 cats vaccinated were reported between 1995 and 1999. It is a rare problem and not a reason per se not to vaccinate a cat (considering the large health benefits afforded by vaccination!). The benefits of vaccination should be weighed against risk according to circumstance for each individual cat. VAS has been linked to both rabies and FeLV vaccines, although sarcomas have been seen in cats that have not received these vaccines.

Vaccine associated sarcomas are very aggressive locally, and some (around 20%) will metastasise. Although most cats receiving rabies or FeLV vaccines may develop a small lump at the injection site, these mostly resolve within 2-3 months on their own. (VAS rarely develops before 3 months after vaccination). Any post vaccination lump still present at 3 months should be biopsied (or sooner if it grows to around 2cm).

Management of VAS is difficult and even radical surgery may not be curative, with local recurrence being common. Adjunctive radiotherapy has been shown to be better than surgery alone, used either pre- or post-operatively. Alternatively, for cats that have surgery alone, adjunctive chemotherapy appears to prolong the time to recurrence.

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Radioactive iodine – a glow-in-the-dark treatment for hyperthyroid cats?

Sheila Wills

Feline Advisory Bureau Resident, Feline Centre, University of Bristol

What is hyperthyroidism?

The thyroid gland consists of two lobes with one located on each side of the trachea (windpipe). The thyroid gland produces thyroid hormone, a substance that is transported via the blood to every cell in the body. The primary function of thyroid hormone is to control the rate at which cells function and too much thyroid hormone makes the cells work very fast thus increasing the body's metabolic rate. This condition is termed hyperthyroidism.

Hyperthyroidism in most cases (95%) is the result of a benign change (hyperplasia) in one, or more commonly, both thyroid lobes (often one lobe is more severely affected than the other). The cause of this benign change is unknown. In approximately 5% of cases, the thyroid gland is affected by a malignant tumour called a carcinoma. These cases may show signs of hyperthyroidism (functional tumour) but some cats do not show any signs except for a swelling in the neck region (a non-functional tumour).

Thyroid carcinoma's will be discussed in this talk but the main focus will be on benign thyroid hyperplasia, the most common cause of hyperthyroidism in cats.

Clinical signs

Hyperthyroidism is one of the most common diseases diagnosed in cats 8 years of age and older and shows no sex or breed predisposition. Each cat may respond to hyperthyroidism a little differently but the most common observations by owners include weight loss, markedly increased appetite (polyphagia), increased thirst (polydipsia) and increased activity which may be manifest as irritability, hyperactivity, restlessness and sometimes nervousness. Many cats also develop an unkempt appearance to their coat due to failure to groom. Other signs include vomiting and diarrhoea and occasionally cats may develop marked breathing difficulties as a complication of hyperthyroidism (discussed later). More advanced cases may develop lethargy, generalised weakness and loss of appetite although this is rare.

Complications

The action of excessive thyroid hormone on all cells of the body results in extra “strain” on many organs. One organ that is commonly affected is the heart. Hypertrophic cardiomyopathy, a form of heart disease in which the heart muscle becomes abnormally thickened, is a common complication of long standing hyperthyroidism. Cats with this condition can suffer heart failure and cats typically will show signs of acute onset respiratory distress due to a build up of fluid either within the lungs or surrounding the lungs (thus preventing normal expansion of the lung lobes) together with anorexia, weakness and lethargy. This condition requires immediate treatment and once controlled, the underlying cardiomyopathy should be treated. Fortunately in many cases, the heart disease can be significantly improved or even resolve with treatment of the hyperthyroidism.

Hypertension (high blood pressure) is a possible complication of hyperthyroidism and can cause damage to the kidneys and the eyes and place extra work on the heart if left untreated. Specific treatment for hypertension should be implemented but usually the high blood pressure resolves with treatment of the underlying hyperthyroidism.

Kidney disease may also be apparent after treatment and correction of hyperthyroidism. This is thought to occur when pre-existing, mild kidney disease exists (quite common in the elderly cat). The diseased kidneys become dependant on the higher blood pressure that occurs as a result of hyperthyroidism and thus when this is corrected and blood pressure returns to normal, kidney function may deteriorate. This is a newly recognised complication of hyperthyroidism and is an important consideration in the management of all hyperthyroid cats with possible kidney disease.

Diagnosis

Hyperthyroidism is often suspected after obtaining a detailed history and physical examination of the patient. Findings during examination may include a cat in poor body condition with an unkempt hair coat, a markedly elevated heart rate and a palpable thyroid nodule in the neck region (either unilateral or bilateral). In some cases a thyroid nodule(s) cannot be palpated and this may be due to overactive thyroid tissue located in an unusual site (“ectopic”) such as the chest cavity or at the entrance to the chest cavity. Many hyperthyroid cats can be difficult to examine due to their nervous, hyperactive or irritable nature!

Definitive diagnosis of hyperthyroidism is usually confirmed on a blood test that measures the thyroid hormone levels. Other laboratory tests may be abnormal including liver enzyme elevations (as a result of the increased liver workload) and increased renal parameters together with abnormal urine test results indicating renal disease.

In cases of suspected cardiomyopathy as a result of hyperthyroidism, an ultrasound examination of the heart, together with chest x-rays and an ECG may also be performed to thoroughly assess cardiac function and to look for any evidence of heart failure.

A specialised scan may also be performed to assess for ectopic thyroid tissue in cases where the thyroid gland cannot be palpated but the cat is confirmed hyperthyroid on blood tests. This type of scanning is called scintigraphy and involves injecting a radioactive compound that is taken up by the overactive thyroid tissue. This is then detected by a special camera thus highlighting exactly where the overactive thyroid tissue is located (i.e. left or right thyroid gland, within the chest cavity or at the entrance to the chest cavity). This scan is very useful in helping to determine the best treatment options in hyperthyroidism.

In cases of hyperthyroidism with a very large palpable mass in the neck region or chest cavity, a biopsy may be performed before further treatment options are considered to assess for the presence of a possible thyroid carcinoma.

Treatment

There are three principle treatment options in cats confirmed with hyperthyroidism and each of these have specific advantages and disadvantages. A decision as to which treatment modality is used is based on all available information including concurrent problems (e.g. kidney or heart disease, hypertension) and after detailed discussion with the owner (e.g. the owner may not be able to administer medication).

•  Medical management

Anti-thyroid drugs reduce the production of thyroid hormone. They do not provide a cure but can provide long term control of the disease. Methimazole (Felimazole®) is the only licensed preparation for longterm hyperthyroid treatment and is administered orally twice daily initially until the thyroid hormone levels reduce to normal and the tablets are then continued either once or twice daily. Another treatment commonly in use is carbimazole (Neomarcazole®). Although this product is not licensed for use in cats, it has been used extensively with good results for many years before Felimazole® was marketed. The medical treatments have to be continued for the rest of the cat's life and regular monitoring of thyroid hormone levels is recommended.

In most cases, the above medications are a safe and effective treatment for hyperthyroidism. Side effects are rare but should be monitored for. They include milder signs such as vomiting, anorexia and lethargy or more severe signs such as marked itchiness resulting in excoriation of the face, liver disorders and reduced white blood cell counts. These signs usually develop within the first few weeks of treatment and thus regular blood tests are performed during the initial treatment period.

The advantages of medical management are that it is readily available, inexpensive and is easily (in most cases!) administered at home. The disadvantages are that the medication needs to be administered at least twice daily for the rest of the cat's life and it is not curative. In rare cases, some cats appear to be resistant to the treatment or may develop the above side effects necessitating cessation of the treatment.

A further advantage of medical management is that it is reversible and thus if any deterioration in kidney function occurs during initial management, the dose of medical treatment can be tapered to allow control of both the hyperthyroidism and the renal disease progression.

With medical management, control of hyperthyroidism usually occurs after two to three weeks treatment.

•  Surgical thyroidectomy

Surgical removal of the affected thyroid gland tissue (thyroidectomy) can provide a permanent cure and is not a particularly complicated procedure. The disadvantages are that it requires general anaesthesia and many cats are older with other problems that could complicate anaesthesia (including those discussed previously as a result of the hyperthyroidism). Accidental damage or removal of the parathyroid glands (small glands important in calcium metabolism attached to the thyroid glands) can occur during surgery and in some circumstances, the thyroid gland can regrow (depending on the surgical technique used) and become overactive again or previously unaffected thyroid tissue may become overactive. All patients should be pre-treated with anti-thyroid drugs for three to four weeks prior to surgery to control as many of the complications mentioned earlier as possible. Specific treatment for any heart disease may also be required.

Damage of the parathyroid glands results in a reduction in parathyroid hormone secretion, which is usually temporary, but can be life-threatening if it causes a significant fall in blood calcium levels (hypocalcaemia). This occurs more commonly when both thyroid glands are removed at the same time. To minimise this complication, surgery is often performed in two stages, removing the most severely affected gland first thus allowing four to eight weeks for recovery of any damage to the parathyroid gland before removing the remaining thyroid gland.

Ectopic thyroid tissue (i.e within the chest cavity) is notoriously difficult to remove from the chest cavity or the entrance to the chest cavity and thus will often require a different treatment modality.

Thyroid carcinomas can also be removed surgically if the tumour is in the neck region (and not in the chest cavity) and it is not too invasive in the surrounding tissue but again this can be a very difficult procedure and it is often difficult to remove all of the tissue (thus a high risk of regrowth of the tumour).

•  Radioactive iodine treatment

Radioactive iodine (I 131 ) can be used to provide a safe and effective cure for hyperthyroidism as a result of benign thyroid hyperplasia and also thyroid carcinomas. The radioactive iodine is taken up by active thyroid tissue, but not by any other organ or body system. The radiation therefore selectively destroys all affected thyroid tissue, including any thyroid tissue that is inaccessible to surgery (i.e. in the chest cavity), but spares the closely associated parathyroid glands.

A single subcutaneous injection of I 131 is curative in around 95% of cases. In the small percentage where hyperthyroidism persists, the treatment can be repeated. A higher dose of I 131 is required for carcinoma treatment but is often the only effective treatment for these cases.

The advantages of this treatment is that it is curative, has no serious side-effects, it does not require an anaesthetic (although mild sedation may be needed to ensure the patient remains still whilst being injected) and is effective at treating all affected thyroid tissue regardless of it's location. The disadvantages are that it involves the handling and injecting of a radioactive substance and all radioactive waste produced by the cat over the following few weeks. For this reason it has to be carried out in a specially licensed facility and the cat has to remain in the licensed hospital until the radiation level has fallen to within acceptable levels (often hospitalised for three to six weeks). This carries no significant risk to the patient. Once the patient is injected with I 131 , he/she can only be minimally handled initially and thus any possible complicating factors that may cause ill health whilst hospitalised must be carefully evaluated and considered prior to treatment.

Cats that receive the high dose I 131 for carcinoma treatment require a longer hospitalisation period (ten weeks) to allow radiation levels to fall to a safe level.

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Use of external beam radiation therapy in the treatment of feline cancer patients

Ellie Mardell

Feline Centre, University of Bristol

Types of external beam radiotherapy

External beam radiation treatment is where radiation treatment is delivered to the patient from an external source. This is in contrast to locally-administered radiation which has some specialised uses in feline patients (such as strontium-90 for squamous cell carcinoma) or systemic therapy (radioactive iodine for functional thyroid adenomas and carcinomas). External beam radiation can be generated and delivered by a number of different types of machine. The linear accelerator is the most versatile, and although purchase and maintenance costs are high, there are a number of specialist veterinary centres within the UK which have access to such units. Linear accelerators have the ability to produce ionising x-ray radiation of varying energy intensity, which allows a wide range of tumours to be treated.

Therapeutic action of radiotherapy

Radiation is absorbed by living tissue and causes cell damage at the molecular level. This leads to cell death, either through direct damage to DNA, or other molecules which are vital to the cells.

Although cellular damage occurs immediately, cell death may not occur for days to months after irradiation. This is because DNA is not necessarily vital to cell survival, but it is required for viable cell division, and in healthy tissue cell division may not be required for some time. Tissues consisting of rapidly dividing cells, such as the bone marrow (particularly which blood cell lines) are inherently more sensitive to radiation. Tumours, which consist of cells that are dividing more rapidly than in normal tissue, are more sensitive to radiation and cell death occurs soon after irradiation. Such cells also have a reduced ability to repair DNA damage compared to normal body cells. However, cells that have a poor oxygen and/or nutrient supply are more resistant to radiation, and this may be the case withlarge tumours which may have grown to a size that outstrips their own blood supply.

Fractionation of radiotherapy

Once cells have been killed by radiation, the body's tissues repair themselves by direct cellular repair and by cellular division of surviving undamaged cells. This happens in both healthy and neoplastic tissues. Rather than delivering treatment in one big dose, repeated small doses of radiotherapy are required to prevent tumour cells repairing themselves, while allowing normal tissue to recover. This also maximises the number of tumour cells killed, as cells are relatively resistant during some phases of division, and the normal repair mechanisms that the tumour attempts following the first dose of radiotherapy will “push” more cells into the radio-sensitive phase of their cycle. In addition, blood supply improves, so that relatively resistant hypoxic cells become vulnerable to the next radiation dose.

Side effects

All living tissues are sensitive to the effects of radiation. “Toxicity” occurs when the lethal effect occurs in healthy cells in addition to the target tumour cells. In veterinary patients in the UK , the vast majority of tumours treated with radiotherapy are superficial ones, rather than cancer affecting internal organs, and this means that serious side effects are usually avoided.

However, side effects can occur in normal skin and mucus membranes. Acute effects can be seen in these tissues, which can include red, sore skin, which may be itchy and flaky, or there may be some degree of discharge known as moist desquamation. Such lesions usually heal fairly rapidly as the cells of the normal tissue divide to repair the damage.

Later adverse effects on the skin include hair loss, whitening of the hair, fibrous thickening and scarring. Of more concern, non-healing wounds and deep ulceration can occur, although this is rare, particularly in the cat. Healing is impaired in tissues that have previously been irradiated, and this may impact on even very minor surgical procedures, and surgery should be avoided in these areas wherever possible unless specialist advice is sought.

If radiotherapy is required for tumours in or around the mouth, damage to the delicate mucus membranes may occur. Pain control must be provided, and nutritional support (via tube feeding), until healing is complete.

Practical aspects

In each individual case, radiation fields are carefully planned to ensure that they include the entire tumour, while sparing healthy tissue. Radiotherapy is then calculated to a total dose, and this is divided into 3-5 treatments (usually once a week). Anaesthesia is essential in veterinary patients to ensure that movement does not occur during treatment, and each treatment takes around 10 minutes to administer. After the diagnosis of cancer, initial patient assessment will need to include evaluation of general health status (especially heart, kidneys and liver) if radiotherapy is to be considered, to ensure that there is no increased anaesthetic risk. However, as anaesthesia is very brief for each radiotherapy session, with patients awake and ready to go home shortly after their procedure, very few problems are seen. Cats that dislike repeated blood samples and veterinary visits may still be suitable patients for radiotherapy, as in contrast to chemotherapy, bone marrow suppression does not occur so that there is no need for regular white blood cell counts. In addition as they are asleep during the procedure, there is very little associated stress, even for the most nervous felines.

Tumours treated with radiotherapy

For most tumours, the treatment of choice would be complete surgical removal. However, in many cases this is not possible due to factors such as tumour size, infiltrative behaviour and location. In these cases, chemotherapy and/or radiotherapy may be used as alternative or additional treatments. For many tumour types, there may be more than one form of treatment that may be suitable, and decisions are made on an individual case basis, so that the most appropriate treatment protocol for patient and owner is selected.

Radiation therapy is a localised treatment, unlike chemotherapy, and it is therefore unable to treat any metastases that may occur. As with all cancer patients, once the diagnosis of a primary tumour has been made, thorough “staging” must be performed. This may involve blood samples, radiographs, ultrasound scans, and other tests as appropriate to ensure that there is no detectable spread of the tumour beyond the intended radiation site. Radiation therapy does not always cure cancer but it can provide long term control of many tumours. In addition, in some cases it can be offered as a palliative treatment for painful tumours that are known to be aggressive and are likely to metastasise.

External beam radiation therapy is becoming increasingly used in feline patients as a primary treatment modality or as part of a treatment protocol. The following list gives some examples;

Localised lymphoma – eg nasal, skin, or mediastinal lymphoma, or solitary lesions within the brain. Chemotherapy is more commonly used for lymphoma but for some cats radiotherapy may be a preferred option for some forms of the disease in some patients, especially where the tumour has become resistant to chemotherapy, or in individuals where chemotherapy produces unacceptable side effects.

Squamous cell carcinoma (SCC) – palliative treatment of bulky, painful SCC affecting the oral cavity. Use of external beam radiation has also been described for pinnal and nasal SCC although other forms of treatment are now preferred.

Fibrosarcoma – these bulky, infiltrative cancers that are difficult or impossible to remove in their entirety can be treated with radiotherapy, often after de-bulking surgery. Eg interscapular, oral or limb fibrosarcomas.

Mast cell tumour – those affecting the skin which cannot be completely removed surgically.

Carcinoma – eg nasal, sinus, salivary gland.

Thymoma – may be effective where surgical excision is not possible.

Pituitary adenomas – functional tumours causing endocrine abnormalities, and their sheer size may cause other adverse effects such as blindness or seizures. External beam radiation has recently come in to favour as one possible treatment in feline patients with uncontrolled endocrine disease, as surgical removal of these tumours is extremely difficult, and medical therapies are often ineffective.

Spinal and brain tumours – lymphoma of the spine may be sensitive to radiation therapy in many feline patients. Several different types of tumour can occur in the feline brain, meningiomas are the most common, and surgical removal is often possible and very successful. However, other tumours do occur (lymphoma, ependymoma, oligodendroglioma, astrocytoma) and surgical removal is usually inappropriate or impossible due to the position of the tumour. Radiation therapy can be a very effective treatment in such cases.

Case report

Tumours of the pituitary gland are becoming increasingly recognised as a cause of endocrine disease in cats. Two such diseases are hyperadrenocorticism (HAC, Cushing's disease) which results in an excess of steroid hormone production, and acromegaly, which results in excessive levels of growth hormone. Both conditions tend to cause diabetes mellitus which is very difficult to control with insulin. This case report describes the diagnosis and treatment of a cat with acromegaly.

Signalment

Prince, an 8 year old, neutered male tabby and white domestic short haired cat.

Acquired at 9 months of age from the RSPCA.

Regularly vaccinated for ‘flu, enteritis and FeLV.

No previous illnesses.

History

Polydipsia/polyuria/polyphagia, weight loss.

Blood samples indicated diabetes mellitus.

Insulin treatment commenced at standard doses.

Little response seen to the insulin. Gradual increase in dose over the next few weeks, and also tried with a longer-acting insulin preparation, but again little response, with persistently elevated blood glucose and fructosamine levels.

IGF-1 hormone levels measured, and found to be elevated, suggesting acromegaly.

Referred to specialist centre.

Physical examination

Looked like a normal cat! Grade II/VI heart murmur, but no associated symptoms. Slightly underweight.

Investigations

Haematology unremarkable, serum biochemistry showed slightly elevated protein levels but was otherwise within normal limits. Thyroid hormone levels normal.

Urine sample- glucose positive, ketones negative, bacterial culture negative.

Blood glucose curve- no response to insulin.

Similarly no response on alternative insulin.

MRI scan- pituitary gland mildly enlarged in all directions, suggestion of haemorrhage likely secondary to pituitary tumour.

Treatment

Insulin regime initially unaltered.

Course of radiotherapy- 5 weekly fractions under general anaesthesia.

Monitoring and follow-up

No side effects from radiotherapy

Blood glucose checked weekly, at expected nadir. Still little response, so dose gradually titrated upwards. Prince still well in self, but persistence of polydipsia/polyuria/polyphagia. Glucosuria but no ketonuria. However, recent reports show that response to radiotherapy can take several months. Further increases in insulin have therefore been avoided at present, as a sudden drop in insulin requirements may occur once growth hormone/IGF-1 levels drop, and this could lead to hypoglycaemia.

Feline acromegaly

Acromegaly in cats is caused by a growth-hormone secreting tumour in the pituitary gland. It is uncommon, but is still an important cause of insulin-resistant diabetes mellitus. Growth hormone (GH) exerts its effect through other hormones, particularly insulin-like growth factor-1 (IGF-1), and levels of this hormone, as well as GH are measurably increased in acromegaly. In addition to insulin resistance, which may initially be the most obvious outward sign, GH and IGF-1 excess has a number of other adverse effects. These include excessive growth of the soft tissues (including internal organs) and thickening of the bones. This gives some cats a characteristic appearance (with a big head!) but more seriously can lead to disease in other organs, most notably hypertrophy of the heart muscle. Sadly this may result in heart failure in time.

Diagnosis of the disease includes hormone measurements, and CT or MRI scanning to demonstrate the enlarged pituitary. Several treatment methods have been tried, including pituitary gland surgery, medical treatment to antagonise the effects of the hormones, and external beam radiation therapy. Treatment is often challenging and the response can be frustratingly poor. However radiation is showing much promise, as this avoids the side effects which frequently occur with medical treatment, as well as the risks involved with surgery. However even with radiation, the cat may take several months to respond and show a reduction in GH levels. The aim is to not only achieve better control of diabetes, but also to limit and hopefully reverse the soft tissue and cartilage growth, so that the risk of organ failure is reduced.

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Polo's pleural problem – a case of feline mediastinal lymphoma

Nicki Reed BVM&S, CertVR, CertSAM, MRCVS

Feline Advisory Bureau Senior Clinical Scholar

University of Edinburgh

Anatomy

The mediastinum is the central area in the chest between the right and left lung lobes. It is divided into two sections by the heart. The cranial mediastinum lies in front of the heart, and the caudal mediastinum lies behind the heart. The cranial mediastinum contains blood vessels, the trachea (main airway), the oesophagus (gullet), lymph nodes and the thymus. The thymus is a glandular structure present in young animals, which produces lymphocytes (white blood cells) involved in immune function. As an animal ages, it reduces in size, and it can usually only be detected in radiographs up to the age of 6 months.

Mediastinal Lymphoma

Lymphoma is a form of cancer affecting what is known as the lympho-reticular system. This system is involved in the body's immunity, and consists of lymph nodes, spleen, thymus, and bone marrow. Lymphoma of the cranial mediastinum may either affect the lymph nodes in this area, or the thymus. A number of textbooks or references may therefore refer to this condition as thymic lymphoma, however, as it can be difficult to ascertain clinically whether the thymus or lymph glands are affected, the author's preferred term is mediastinal lymphoma.

The age distribution appears to have a bimodal peak, with a group of young cats being affected at a mean age of 2 years, and a group of older cats being affected at a mean of 10 years 1 . Siamese cats tend to be over-represented, and some references sight a male pre-disposition 1,2 . It has been suggested that the susceptibility of Siamese cats to lymphoma is due to a recessive gene 3 . Mediastinal lymphoma previously accounted for 10-20% of cases of feline lymphoma in surveys conducted 20-25 years ago 4 . At that time, it was associated with a high incidence of feline leukaemia virus (FeLV) infection, with approximately 70-80% of cases being FeLV positive 4. It was generally associated with a poor prognosis. Nowadays, the incidence of FeLV has substantially reduced, and in a recent survey conducted at the author's establishment, only 4% of all cases of lymphoma tested positive for FeLV, and none of the cases of mediastinal lymphoma were positive for FeLV. 30% of the cases were Siamese cats, which only comprise approximately 5% of the general hospital population.

Cases of mediastinal lymphoma typically present as either dyspnoea due to pleural effusion, as in this case, or regurgitation, due to the mass pressing on the oesophagus, and preventing passage of food 5.

Assessment of pleural effusions

The type of fluid obtained from the chest by thoracocentesis may be assessed for things such as cellular and protein content. This then helps to classify the nature of the fluid, from which a list of potential differential diagnoses can be considered.

PMN = polymorphoneutrophils; RBC = red blood cell; WBC = white blood cell; Lymph = lymphocytes

In addition, the fluid should be submitted for culture to ascertain whether or not infection is present (a septic effusion).

Differential diagnosis of pleural effusion

Treatment

A number of treatment protocols for feline lymphoma exist. The COP protocol 6 is the most commonly used, as the drugs involved are reasonably accessible to practitioners, and the side effects associated with these drugs tend to be familiar to them. Cytosine arabinoside was included in this protocol as it affects the cell division at a different stage of the cycle from the other drugs. L-Asparaginase could also have been used, but is less readily available.

Newer chemotherapy protocols, such as the Madison-Wisconsin protocol, are being used by veterinary oncologists and at referral centres. These protocols are more intensive, using greater numbers of drugs with which practitioners may not be familiar, are more expensive, and may require more frequent visits to the veterinary centre. However, they should be associated with a greater chance of inducing remission. There are a number of difficulties in comparing the efficacies of different protocols, due to the fact that protocols may have to be adapted slightly to the individual animal. In addition, some studies look at lymphoma in general, whereas other studies look at a specific form of lymphoma such as intestinal lymphoma. The numbers of cases studied are also much smaller than would be involved in, for example, human medical studies. We therefore still do not necessarily know what is the ‘best' protocol for treatment of lymphoma in cats. Decisions are therefore based on:

• Owner commitment (e.g. how easy it is for them to attend the practice)
• Patient tolerance (can tablets be given; do they tolerate intravenous lines being placed; can they tolerate the side effects from the drugs)
• Financial implications; repeat blood tests, hospitalisation fees, chemotherapy drugs can amount to £1000 - £2000 over a 6 month period

The only conclusive prognostic indicator that appears to have been identified in cats is the presence of FeLV being associated with a poor outcome. Immunophenotyping of lymphoma cells in B type and T type appears less useful than in dogs, in which T Cell lymphoma is generally associated with a poorer prognosis than B cell. Most mediastinal lymphomas in cats are T cell in origin, yet this appears, especially in young cats, to be associated with a reasonably good prognosis, as Polo will testify to!

References

1. Gabor, Malik & Cranfield (1998): Clinical and anatomical features of lymphosarcoma in 118 cats. Australian Veterinary Journal 76 (11) 725-732

2. Court, Watson & Peaston (1997): Retrospective study of 60 cases of feline lymphosarcoma. Australian Veterinary Journal 75 (6) 424-427

3. Louwerens, London , Pedersen & Lyons (2005): Feline lymphoma in the post-feline leukaemia virus era. Journal of Veterinary Internal Medicine 19 329-335

4. Hardy (1981): Haematopoietic tumours of cats. Journal of the American Animal Hospital Association 17 921-940

5. Day (1997): Review of thymic pathology in 30 cats and 36 dogs. Journal of Small Animal Practice 38 393-403

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Caring for cats with cancer – the importance of good nursing

Suzanne Rudd DipAVN(medical)VN

Fortekor/FAB Nurse

University of Bristol

A Veterinary Nurse has many roles when nursing a cat with cancer. This lecture will discuss these roles along with a case study to demonstrate this. The main roles of the nurse are: -

•  Client support and communication

•  Assisting in the treatment of the patient

•  Caring for the hospitalised patient

•  Advice when discharging the patient

The nurse's role in client support and communication

When an owner is told that their pet has cancer, it can be very distressing. Most people will have been affected by cancer in some way, be it through family, friends or a personal experience at some point in their life. Although many cancers are now being treated successfully, the word “cancer” is associated with morbidity and mortality. Even if you have not been affected by cancer, we are all exposed to the media where pictures of people having unpleasant side effects as a result of cancer treatments are shown. It is therefore no surprise that people are extremely distressed when they are told that their pet has cancer and are very anxious about the prospect of treating this disease.

However treating cats with cancer is very different compared to treating humans. In particular chemotherapy is used far less aggressively as it would be unacceptable to subject and animal to severe side effects. The aim of treating cats with cancer is more to improve quality of life rather than quantity, and although a cure would be desirable, this is not our main priority. Remission however, can often be achieved, therefore extending quantity of life, depending on the disease.

The main role of the nurse at this time is to provide support to the client(s). When the word “cancer” is used an owner will understandably “switch off” through anxiety and distress. It is a good idea for the nurse to have a good knowledge of the type of cancer and to be present in the consultation with the owners. After the vet has discussed the disease and treatment options with the owner, the client will often have questions that the vet can answer. However, there are sometimes questions that they may feel uncomfortable asking the vet or more commonly only come to mind after the vet has finished the consultation. Information that was “lost” in the consultation, through anxiety or sheer volume, can be reiterated to the client(s) by the nurse. The nurse can be of great help and support to the client, owners will find the time spent with them invaluable.

Personalisation is of great importance to clients and their pets. The nurse will often have as much contact, if not more contact with the animal and the owner, than will the vet and so seeing a familiar face when repeatedly visiting the surgery is ideal for the animal as well as reassuring for their owner(s). Staff consistency will certainly help in the smooth running of the pet's treatment as well as helping to provide optimal care if the patient needs to be hospitalised at the practice.

Building a good relationship with the client is vital and never more so than leading to and at the time of death or euthanasia. Euthanasia of an animal is an agonising decision and the grief requires deep compassion and understanding. Nurses can play a crucial role in this delicate situation minimising distress by helping to explain the procedure and ensuring thorough organisation, as well helping to make arrangements for the body after death and providing grievance support. Nurses will often take on the role of a “mini counsellor” and by all means the nurse should help as much as reasonably possible. However the nurse should never be afraid of recommending professional counselling.

Role of the nurse in the treatment of the patient

The role of the nurse will depend widely on the type of treatment the patient will undergo.

If the patient is to undergo surgery then often the nurse's role is that of an assistant in preparing theatre, preparing the surgical site and providing postoperative care for the animal. The nurse will often assist in the induction of anaesthesia and monitor the animal's anaesthesia during surgery and recovery. Nurses will often be responsible for labeling samples taken and ensuring that they are packaged correctly and posted to the laboratory for analysis. Postoperative checks to assess the wound and remove sutures may also be carried out by the nurse.

If a hyperthyroid cat is to be treated with radioactive iodine the nurse's role may be minimal if she/he is unauthorised to help with the care of the patient but may extend to daily management and care of the patients housing and feeding. Unfortunately minimal contact is allowed and certainly pregnant women should not be involved in the treatment or care of these patients. Nurses can be involved however in ensuring that the husbandry provides plenty of room for exercise and stimulation for the patient for the duration of their stay.

Nurses will generally take an anaesthetists role in patients being treated with radiotherapy as well as helping the Veterinary Surgeon with pre and post therapy assessment. Again pregnant women should not be involved with this treatment.

The role of the chemotherapy nurse will be discussed in detail through a presented case study.

The following protocol for the administration of a chemotherapy agent is the one used at the University of Bristol and implemented by Mark Goodfellow MA VetMB CertVR CertSAM MRCVS

PROTOCOL FOR PREPARATION AND ADMINISTRATION OF CYTOTOXIC DRUGS

a) ORAL MEDICATIONS – latex gloves should be worn and restraint must be adequate. Tablets must not be crushed or split under any circumstances. The technique of administration must not allow the cat to crush the tablets between their teeth if at all possible.

b) INTRAVENOUS ADMINISTRATION

AIMS

    Prevent extravasation of drugs with good catheter technique

    Minimise human exposure to cytotoxic drugs – protective clothing and preventing aerosol formation

• Calculate the dose
• Confirm recent haematology – adequate PLTs and PMN
• Confirm the concentration of the drug and weight of the patient.
• Calculate dose on a surface area basis
• Nurse present to calculate independently and verify dose 

• Place a catheter under normal aseptic conditions –
• Do not use an existing catheter
• Do not “cut down”
• Use a 20G catheter even in big dogs
• Use each cephalic and saphenous vein in turn
• Securely tape with T port if an infusion is to be given (flushed with 0.9% Saline NOT heparinised.)
• Bandage

The clinician or nurse should always place the catheter – good technique is vital to prevent extravasation of vincristine and doxorubicin! Catheter must be placed on first attempt

• Prepare the cytotoxic tray
• Ensure the following are present
• Incontinence pad lining
• 2 x 0.9% Saline filled syringes for flushing (23G Needle)
• Spirit soaked gauze swabs
• Swab/Tape/Bandage for leg on removal of catheter

• Prepare the Fume Cabinet
• Ensure the following are present

• Incontinence pad lining floor of the cabin.
• Sprit soaked gauge swab
• Syringes + 23G needles
• Diluent for cytotoxic drug if required.
• Plastic Ziplock bag for waste

2) Switch on fume cupboard.

• Gowning
• Clinician, nurse and students should gown
• Gloves are pulled OVER cuffs of gown
• Goggles/Mask should be worn for administration but if put on now, prevents need to place potentially contaminated hands near face later

• Preparation of Cytotoxic drug.

• Collect the drug from the cytotoxic cupboard/fridge
• In the fume cabinet draw up calculated dose via 23G needle.
• Do not inject air into vials
• Wrap the vial top with the spirit soaked swab whilst withdrawing the needle – thus mopping up any “spilt drug”
• Recap the needle with extreme caution

• Administration of cytotoxic drug

• Nurse to restrain the patient
• Unbandage catheter so vein can be directly observed during injection.
• Flush with copious amounts of 0.9% Saline via 23G needle – consistency in use of size of syringe and needle allows clinician to have a feel for resistance to injection, another method of confirming catheter patency and correct placement.
• Slowly inject cytotoxic drug, holding the limb and barrel of the syringe in the left hand and injecting with the right – thus if the patient   moves there is less risk of self injection or drug spillage. NB Hypersensitivity, and cardiotoxicity in the case of doxorubicin, is associated with increased rapidity of injection.
• Draw blood back into syringe and reinject – thus ensuring all drug administered and diluting residual drug in case of self injection.    
• Place syringe in cytotoxic tray, do not recap.
• Flush with copious amounts of 0.9% Saline.
• Untape catheter
• Place gauze over catheter tip to enclose as it is removed.
• Place catheter in cytotoxic tray, the tip lying on the spirit soaked swab.
• Tape gauze in place as a dressing.

• Decontamination

• All clinical waste to be placed in a Ziplock bag
• Sharps in cytotoxic sharps bin
• Cytotoxic glassware in DOOP
• Deglove taking care not to touch the outside of the gloves- into Ziplock
• Seal ziplock bag and place in yellow clinical waste bag
• Wash hands thoroughly + turn of fume cabinet.

In case of drug extravasation – stop infusion immediately, use catheter to withdraw   as much of the extravasated drug as possible. For VINCRISTINE or   VINBLASTINE inject hyaluronidae (150IU/ml) at the site subcutaneously.   DOXORUBICIN – ice compresses for 72 hours, do not infiltrate the area or   dilute the drug, buster collar to prevent self trauma.

VINCRISTINE » VINBLASTINE < DOXORUBICIN are vesicants and WILL cause skin sloughing if injected extravasualarly or even if dropped on the skin. Sloughing maybe so severe as to require amputation!

Hypersensitivity – L-asparaginase & doxorubicin can cause ACUTE hypersensitivity   reactions, i.e. during