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PRINCIPLES OF ONCOLOGIC SURGERYLaurent Findji DMV, MS, MRCVS, Diplomate ECVSVRCC Veterinary Referrals, Essex, United Kingdom

“Tumours belong in formalin jars” – William Stewart Halsted (1852-1922)

Surgery has been and remains the mainstay of treatment of solid cancers and most cancer cures in humans today still result from surgery alone. Historically, surgeons were first limited in the extension of surgical excisions by their own technical insufficiencies and shortcomings of supporting disciplines such as anaesthesia and intensive care medicine. As progress was made in these other fields came the era of large resections. Initially, it appeared that wider resections improved the prognosis. However, this was only true to a certain point and, although local disease control was more often achieved, metastatic disease remained an obstacle to cure. Surgery as sole treatment of cancer was obviously not the panacea. The most efficient treatment of cancer is today multimodal. It is now clear that surgeons should be members of a team including radiographers, anaesthetists, criticalists, pathologists, and medical and radiation oncologists. In addition to surgical skills, surgeons need to have a good knowledge of tumour biology to determine the role and contribution of surgery, for each case, to the whole treatment. They also need to understand how other therapies work, in order to adapt their surgical technique to previous or later treatments.

These are exciting perspectives for oncologic surgeons. Their role is constantly evolving as they are increasingly working in close cooperation with other specialists in fields such as chemotherapy, radiotherapy and immunotherapy. Whilst the times of extensive, technically challenging resections are not over, the oncologic surgeon has evolved from a technician to a more complete clinician, whose deep knowledge in cancer biology allows more concerted and tailored procedures.

Every surgeon treating cancer should not only be an oncologic surgeon but rather a surgical oncologist. Like in the other fields of surgery, thinking in terms of biology is the most important concept of oncologic surgery. It means that above all, the surgeon needs to know what type of tumour they are dealing with, and what its characteristics (expected behaviour, response to treatment, possible paraneoplastic syndromes, etc.) are.

Roles of surgery in oncology

Diagnostic surgeryBiopsies

Biopsies are crucial in the diagnosis process of tumours. They can be incisional or excisional. They are performed percutaneously (core-needle biopsies), or by minimally-invasive or conventional surgery.

L. Findji – Principles of oncologic surgery – AMVAC 2013 1/19

Staging surgerySurgery can be involved in tumour staging. Lymph node biopsies (incisional or excisional) provide helpful information on locoregional spreading of a tumour. Exploration of body cavities for signs of metastatic disease can also be performed, either when operating the main tumour (e.g. inspection of the abdomen when resecting an abdominal tumour) or separately. Minimally-invasive surgery (laparoscopy, thoracoscopy) is increasingly used in such indications.

Curative-intent surgerySurgery is most often performed with an intention to cure, whether it be through surgery alone or combined with other therapies. Depending on the “dose” of surgery administered, several types of tumour resections are possible: cytoreductive or intracapsular, marginal, wide and radical.Cytoreductive surgery consists of removing as much of the tumour as possible but leaving macroscopic disease behind. It is only considerable in a view of potentiating a planned adjuvant therapy is planned. However, adjuvant treatments are less effective in presence of macroscopic disease, which makes cytoreductive (debulking) surgery very rarely acceptable1.Marginal resections consist of excision of the tumour with minimal amounts of surrounding tissues. The likelihood of leaving microscopic residual disease is high and this type of resection should be avoided as much as possible. However, in certain cases, it is preferable to more extensive resections, either because of difficulties in wound reconstruction (e.g. tumours of extremities) or vicinity of non-expandable structures (e.g. brain tumours). In such cases, surgery should be followed by adjuvant therapy, radiotherapy especially.Wide resections consist of excision of the tumour with enough surrounding tissues to expect complete excision including microscopic disease. This is the type of resection to seek as often as possible. Its main limitation comes from the fact that precise guidelines as to what appropriate margins should be for each tumour type are lacking. Therefore, in some cases, microscopic disease remains, leading to recurrence. Good communication with the pathologist is essential to have as precise an assessment of the excision margins as possible.Radical resections consist in even wider resections. Often, it consists of the excision of body parts (amputations). A good definition is that after radical excision, there is no need to await the pathology results to know that the surgical margins are free of tumour.

Palliative surgeryPalliative surgery is performed to improve the patient’s quality of life, without extending its life expectancy. Amputation for an appendicular osteosarcoma and splenectomy on a haemangiosarcoma are two examples of palliative surgeries, as they do not improve survival times per se.

The difference between curative and palliative surgeries mainly lies in the intent2: whenever the surgeon is seeking a cure, the surgery is considered curative although in many cases a cure will not be obtained and the surgery will at best be providing palliation. The goal of palliative surgery is to improve the patient’s quality of life by relieving as much as possible the clinical signs resulting from its cancer. Palliative surgery may also increase life expectancy, as a result of this improvement of the quality of life, but also through its direct action against the tumour development when possible. Overall, the line between curative and palliative surgeries can be very fine: with many tumours,


the surgeon knows that the tumour is unlikely to ever be cured even though a curative-intent procedure will be performed. In every case, the surgeon aims at getting the longest disease-free interval and his means are similar, whether the procedure be performed with an intent to cure or merely to palliate.

When opting for a palliative surgical intervention, it is most important to balance the expected benefits and improvement of quality of life against the risks and morbidity associated with the procedure. The less likely a tumour is to be curable, the smaller the operative risk and the shorter the expected recovery from the procedure must be. In deciding the “dose” of surgery to apply to an animal with cancer, the discussion with its owners is critical: it is most important for them to be well informed of the prognosis and of the results which can be reasonably expected after surgery in terms of disease-free interval and potential postoperative complications.

Preventive surgerySome cancers, such as hormone-dependant cancers, can be prevented by surgical procedures: prepubertal ovariectomy in dogs dramatically reduces the risk of mammary tumour; castration of dogs prevents the occurrence of testicular tumours and perianal adenomas; etc.In human surgery, preventive or prophylactic surgery, defined as the pre-emptive operative of an organ prior to malignant transformation or while the cancer is in situ3, is used increasingly as the increasing knowledge of genetics increases the ability to determine the individual risk of patients to develop cancer of some organs in their lifetime. Common applications include preventive surgery for hereditary forms of ovarian, breast, colon or thyroid tumours.

Ancillary surgerySurgery for medical support

Placement of feeding tubes can be necessary to support nutrition of cancer patients. Cachexia is a major concern in some cancer patients. Nutritional support is known to decrease associated morbidity in humans.

Surgery for treatment device implantationSurgeons can play a part in non-surgical treatments by placing several types of implants such as vascular access ports, intracavitary catheters, brachytherapy catheters, etc.

Before surgery

Before surgery, the patient’s general health status must be evaluated as it may have consequences of the treatments to pursue, in type and extent. In addition, the findings of the general health profile may indicate further tests which may reveal extension of the malignancy in distant systems (metastatic disease). In addition, the tumour type and extension (staging) must be determined. The local staging of the tumour, obtained through imaging, will allow the precise planning of surgery.


Evaluation of the patientThe cancer patient is often an older animal. As such, it can be affected by concurrent diseases. However, age is not a disease in itself, and it should not be considered a negative prognostic factor4-6 as tumour biology and response to treatment are not influenced by advanced age. In fact, malignant tumours in young animals tend to have a more aggressive behaviour than in older animals. For instance, dogs of less than 2 years of age with osteosarcoma are reported to do worse than older dogs when treated with amputation alone7. The concomitancy of systemic diseases may nonetheless influence treatment options. It is therefore essential to obtain a general health profile in all cancer patients.In addition to diseases associated with age, a proportion of cancer patients will suffer from one or several paraneoplastic syndromes (PNS), which are diseases caused by substances, produced by the tumour, having a systemic effect. The PNS of greatest relevance for the surgeon in veterinary medicine are hypercalcaemia, hypoglycaemia, anaemia, thrombocytopaenia / coagulopathies, hypo / hypertension, and cancer cachexia / anorexia (Table 1).

Hypercalcaemia as a paraneoplastic syndrome is referred to as hypercalcaemia of malignancy (HM). Hypercalcaemia has pathophysiological effects on renal, cardiovascular, neuromuscular and gastrointestinal functions, but its primary clinical manifestations are usually due to impairment of renal function. Severe HM (i.e. calcium > 180 mg/L) should be considered a medical emergency: treatment is initiated in proportion with the severity of HM and associated clinical signs, and the cause of HM is investigated. Management of HM is beyond the scope of this text and is widely detailed elsewhere8-10. Briefly, it is treated with a combination of fluid therapy (0.9% NaCl), loop-diuretics (furosemide) once dehydration is corrected, steroids when the cause of HM has been diagnosed and, for extreme or refractory cases, calcitonin and bisphosphonates. Concurrently, the tumour responsible for HM is searched. Lymphoma is the most common cause and its presence must be investigated. A careful rectal examination is also important to detect an anal sac carcinoma, for which the primary tumour can be of very small size. Beyond these, a thorough physical examination, imaging and tests are used to localise the malignancy. With some tumours, such as anal sac carcinomas or parathyroid tumours, after an initial period of medical support and patient optimisation, surgery is rapidly necessary to treat HM.

Hypoglycaemia as a PNS most commonly results from beta-islet cell pancreatic tumours (insulinomas)8, 10. However, extra-pancreatic tumours can also be responsible for paraneoplastic hypoglycaemia. Such tumours include lymphoma, hepatocellular carcinoma, leiomyoma and leiomyosarcoma, haemangiosarcoma, salivary gland carcinoma and oral melanoma. Clinical signs depend on the severity, rate of onset, duration and cause of the hypoglycaemia. Similarly to HM, paraneoplastic hypoglycaemia is treated symptomatically as its origin is investigated. When a tumour is found which could explain it, the best treatment is excision of the tumour whenever possible. When surgery is not an option, a medical treatment (prednisolone, diazoxide, etc.) can help control the paraneoplastic hypoglycaemia with more or less lasting effects. When no tumour can be found by diagnostic imaging but insulin levels are high in the face of hypoglycaemia, an exploratory coeliotomy may be indicated as some insulinomas are too small to be detected by imaging techniques.

Anaemia is a common finding in animals with cancer. Numerous mechanisms can lead to anaemia as a PNS: the lack of red blood cells results either from loss (i.e. haemorrhage), destruction (e.g. haemolysis) or decreased production (e.g. anaemia of chronic disease,


myelophthisis). Most frequently, the paraneoplastic anaemia results from chronic disease, immune-mediated haemolysis, blood loss or microangiopathic haemolysis. For all these mechanisms of paraneoplastic anaemia, excision of the tumour responsible is the treatment of choice. However, in some cases, both specific (e.g. immunosuppressive drugs) and non-specific (e.g. blood product administration) treatments for the anaemia, can be necessary. Non-specifically, before embarking on surgery, the patient must be optimised and have sufficient oxygen-carrying capacity. Blood products or haemoglobin-based oxygen-carrying solutions (Oxyglobin®) must therefore be administered whenever haemoglobin levels are inadequate. As a rough guide, the oxygen-carrying capacity should be considered insufficient for surgery when packed-cell volume (PCV) is below 25% and the PCV should at least be maintained above 20% during and after surgery. However, the need for blood product administration depends on the clinical condition of the animal rather than on absolute values of its PCV. Ideally, when fresh blood products are to be transfused from one animal to another, the donor and recipient should be blood typed prior to administration. If blood typing is unavailable, a crossmatch should be performed. If time is lacking, using a donor negative for dog erythrocyte antigens (DEA) 1.1 and 1.2 greatly limits the risks of hazardous reaction. Furthermore, transfusion reactions are limited in dogs which have never received blood products previously because of the absence of native alloantibodies. To the contrary, in cats, donors and recipients should be typed, given the presence of natural alloantibodies and severity of blood transfusions in this species.The amount of blood to be administered depends on the PCV of the recipient, on the PCV of the donor and on the desired PCV of the recipient after transfusion. It can be calculated as follows:

Volume of blood to transfuse = V x (recipient desired PCV – recipient current PCV) / donor PCV,

where V=90 in dogs and V=70 in cats.

Alternatively, it can be considered that whole fresh blood administered at a rate of 2.2 ml/kg will raise the recipient’s PCV by approximately 1%.

Thrombocytopaenia is another PNS of great relevance for the surgeon. Like for anaemia, the lack of platelets can result from their excessive consumption (e.g. haemorrhage, disseminated intravascular coagulation), destruction (e.g. immune-mediated) or decreased production (e.g. myelophthisis). Thrombocytopaenia as a PNS is most frequently associated with vascular tumours or tumours infiltrating the bone marrow. Similar tumours and mast cell tumours can in addition cause coagulopathies. Any tumour can cause acute or chronic disseminated intravascular coagulation (DIC), which in turn can lead to thrombocytopaenia by excessive consumption of platelets. However, DIC is most frequently clinically relevant in cases of haemangiosarcoma. Excessive bleeding can also be observed in patients with mast cell tumours. It is likely the consequence of the release of heparin as mast cells degranulate.Most coagulopathies will be best treated by excision of the tumour. However, as sufficient haemostasis is required for surgery, symptomatic treatments may be necessary before surgery. To bring coagulation factors to the patient, plasma (fresh, fresh-frozen, cryoprecipitate) can be administered. To bring functional platelets, fresh whole blood should be administered as platelets are rapidly destroyed when blood is stored (within 2 to 4 hours). When thrombocytopaenia results from haemorrhage (e.g. bleeding splenic haemangiosarcoma) and the patient is stable enough to undergo surgery without transfusion, the administration of blood products is sometimes withheld until the bleeding is controlled.


Hypertension and cardiac arrhythmias can be life-threatening consequences of the presence of certain tumours such as pheochromocytomas. These tumours can produce catecholamines which can be massively released in the blood stream when they are manipulated. On the contrary, perioperative hypotension, secondary to the release of histamine and other vasoactive substances, can be encountered when mast cell tumours are manipulated and degranulate. In both cases, these possibilities need to be anticipated. When operating on pheochromocytomas, premedication favouring hypertension and arrhythmias are avoided and emergency treatments (phentolamine, lidocaine, propranolol, etc.) are kept at hand. If hypotension is feared when operating on a mast cell tumour, anti-histamine drugs (e.g. diphenylhydramine) and steroids are administered preoperatively.

Cancer cachexia consists of weight loss in the face of adequate nutritional intake. Cancer anorexia consists of weight loss associated with insufficient nutritional intake. Their cumulative incidence in veterinary oncology is unknown. In humans, it clearly is a negative prognostic factor for a variety of malignancies. Severe malnutrition may have deleterious effects on wound healing and postoperative infection rates. The effects of cancer cachexia and anorexia often last for some time after the tumour has been excised. For this reason, the surgeon must anticipate the need for forced enteral feeding postoperatively and be ready to place feeding tubes at the time of surgery.

Hypercalcaemia LymphomaAnal sac carcinomaMultiple myelomaThymomaParathyroid tumours, …

Hypoglycaemia InsulinomaHepatocellular carcinomaSmooth muscle tumours (leiomyoma, leiomyosarcoma)

Anaemia HaemangiosarcomaDigestive tumoursMast cell tumour, …

Bleeding disorders HaemangiosarcomaMast cell tumourThyroid carcinoma, …

Hypertension PheochromocytomaAdrenocortical adenoma / adenocarcinoma

Hypotension Mast cell tumourTable 1: Common paraneoplastic syndromes and associated tumours

Ideally, the work-up of any cancer patient undergoing surgery should at least include a complete blood count, a biochemistry panel, electrolytes and urinalysis. When the tumour to operate may be associated with coagulopathies or when the procedure carries a risk of significant blood loss (e.g. maxillectomy, liver lobectomy, thyroidectomy), a coagulation profile should also be run.

Tumour diagnosisKnowledge of the tumour type is essential to determine the best course of treatment. No mass should ever be excised without knowing its nature. This diagnosis is generally made on the basis of cytological (fine-needle aspirates) or histopathological (biopsies) examination of the primary tumour.Fine-needle aspirates are an extremely useful tool for the surgical oncologist, who should


have a good knowledge of basic cytology. They can be performed directly or under imaging (ultrasound or CT) guidance for deeper lesions. It is however important to acknowledge the limitations of cytology and not base decisions involving major surgeries (e.g. large resections, amputations) only on it. Cytology appears to be most reliable for diagnosis of cutaneous and subcutaneous masses (70%-91% of agreement between cytology and histopathology)11-13. It appears much less reliable for examination of hepatic and splenic masses12, 13. Diagnostic cytology is also more sensitive round cell and epithelial tumours then mesenchymal tumours, whose cells tend to exfoliate less12, 14. A more detailed review of the data of literature regarding the accuracy of diagnostic cytology system by system is available elsewhere15. Some tumour types can be fairly easily determined by cytology (e.g. lymphoma, mast cell tumour, melanoma), but cytology does not provide much information on the grade of the tumour (i.e. aggressiveness, invasion, etc.). Whenever knowing the precise nature and grade of a tumour will affect the treatment (type and extent) to pursue, a biopsy is indicated (Figure1). The principles of surgical biopsy techniques are discussed below in this text.In addition to cases for which a properly performed excisional biopsy is appropriate, there are a few situations in which a biopsy is not necessary before definitive treatment. When the precise knowledge of the tumour type and grade will not change the treatment options and when the risk associated with the biopsy is not worth the potential information it may yield. For instance, percutaneous splenic biopsies are often unrewarding, as a result of blood contamination, and carry a significant risk of haemorrhage and seeding of neoplastic cell in the abdominal cavity. Furthermore, should it lead to a diagnosis, it is unlikely that the appropriate treatment (splenectomy) will differ significantly depending on it. The same is true for primary lung tumours, whose treatment is lung lobectomy, regardless of their type and grade. In addition, percutaneous lung biopsies carry a risk of haemorrhage, iatrogenic pneumothorax or pyothorax, and tumour cell seeding in the pleural space. Another example is thyroid tumours. Percutaneous biopsies of thyroid tumours carry a significant risk of severe haemorrhage, which can prove difficult to control. In this case, the risk associated with preoperative biopsy is a great as the intraoperative risk. For thyroid tumours, the invasive versus non-invasive (adherent versus non-adherent) nature of the mass is a more important criterion to choose between treatment options.A particular case is bone tumours. If signalment, history, and clinical and imaging findings support the hypothesis of primary bone tumour, many experienced surgeons will be confident enough to amputate (or perform limb-sparing surgery on) the patient without performing a biopsy beforehand. The rationale for this attitude is that the degree of suspicion is often very strong and other differential diagnoses rather few, and that the biopsy carries a risk of pathological fracture and misdiagnosis if only reactive bone is sampled, and will delay definitive treatment. However, the risk is then to amputate a patient and find out that the lesion was not a tumour.


Figure 1: Surgical decisions facing a surgically resectable solid mass

Tumour stagingWhen the general health profile has been obtained and the nature of the tumour is known or suspected on the basis of its cytological examination, the tumour is staged. Staging follows the TNM classification: a score is given to 3 categories describing the presence and extension of the primary tumour (T), locoregional lymph nodes (N) and distant metastasis (M). Schemes adapted to various tumour types have been developed which correlate more accurately with prognosis, but the principle remains the same (Table 2).

Primary TumourT0T1T2T3

No evidence of neoplasiaTumour <1 cm diameter, not invasiveTumour 1–3 cm diameter, locally invasiveTumour >3 cm diameter or evidence of ulceration or local invasion

NodeN0N1N2N3

No evidence of nodal involvementNode firm, enlargedNode firm, enlarged, and fixed to surrounding tissuesNodal involvement beyond the first station

MetastasisM0M1M2

No evidence of metastasisMetastasis to one organ system (e.g., pulmonary metastasis)Metastasis to more than one organ system (e.g., pulmonary and hepatic metastases)

Table 2: TNM Classification scheme for tumours in animals16

The primary tumour (T) is staged by means of palpation and diagnostic imaging. Conventional x-rays are useful to detect bone involvement or reaction, but is somewhat


insensitive: loss of 30 to 40% of bone mineral density is required to induce radiographic changes17. Conventional radiography therefore tends to underestimate the extent on bone involvement. Ultrasound is most valuable for the evaluation of abdominal tumours and lymph nodes. It is also superior to conventional radiography in presence of cavitary effusions. It is sensitive but not very specific: it cannot accurately differentiate benign from malignant lesions18, but can guide the performance of fine-needle aspirates or core-needle biopsies. It may also help determine the nature and invasion of tumours within soft tissues (e.g. in the neck and limbs). In addition, Doppler techniques can provide information on the tumour vascularity. The amount and accuracy of the information provided by ultrasound are, however, very dependent on the skills of the operator.Advanced imaging techniques, such as computed tomography (CT) or magnetic resonance imaging (MRI), are much more reliable for determination of tumour extension and relationships. CT and MRI allow precise assessment of tumour extension within soft tissues. They are extremely valuable for planning surgical resection as they provide 3D images, either after reconstruction (CT) or direct acquisition (MRI). CT is generally better for evaluation of the thorax and it is indispensable for proper radiotherapy planning. On the other hand, MRI offers better tissue differentiation and is the imaging modality of choice of the nervous system.

Locoregional lymph nodes (N) are evaluated through palpation, fine-needle aspiration and biopsy. Lymph node enlargement is screened by palpation and imaging (ultrasound, CT, MRI). Fine-needle aspiration and cytological examination of the locoregional lymph nodes should however ideally be performed regardless of their size: a study evaluating 100 dogs with oral malignant melanoma showed that lymph node palpation and size are not reliable indicators of lymph node metastasis and that cytology or histology was required for accurate staging19. In another study involving 37 dogs and 7 cats, clinical examination of the lymph node also appeared poorly correlated with their metastatic status20. In that same study, cytological examination of lymph nodes for tumour invasion appeared 100% sensitive and 96% specific, showing that fine-needle aspiration is an accurate diagnostic tool for lymph node metastasis evaluation. However, tumours do not necessarily drain to the closest lymph node and may even drain controlaterally. Limiting fine-needle aspirations to the mandibular lymph nodes because they are superficial thus decreases staging accuracy. Ideally, individual mapping of the tumour drainage should be obtained to determine the position of the sentinel lymph nodes, which are the first to which the tumour drains and whose aspiration therefore is the most sensitive for detection of metastasis21. This is seldom performed in a clinical setting. In the absence of sentinel lymph node mapping, it can only be recommended to sample as many regional lymph nodes as possible, regardless of their size, in order to increase staging sensitivity. However, there is considerable variation in the number and consistency of lymph nodes, and some are not normally palpable. Staging accuracy is therefore limited by the impossibility of targeted or exhaustive lymph node sampling.

The presence and extension of metastatic disease (M) is evaluated by ultrasound, radiography and advanced imaging (CT, MRI). The pulmonary parenchyma is the most common site of metastasis of tumours, especially sarcomas. Thoracic x-rays are therefore most often indicated when screening for metastases. Two incidences, preferably 3, are required to increase the sensitivity of chest x-rays. As a result of the difference in the perfusion / ventilation ratio between the dependent and nondependent lungs, lesions of soft tissue density will appear more clearly when the lung they sit in is nondependent. Radiographs are not very sensitive (65% to 97%22) for detection of pulmonary metastases and lesions need to be at least 4 to 8 mm in diameter to be visible on conventional x-rays4, 22, 23. On the anaesthetised animal, manual lung inflation can be applied to improve


contrast. However, CT is more sensitive than conventional radiographs for detection of thoracic metastatic disease24.Scintigraphy is another means of detecting metastatic disease. It can be used to evaluate the bones, kidneys, thyroids, lungs and liver, using different radionuclides. It is very sensitive but poorly specific: benign (e.g. inflammatory) and malignant lesions have a similar aspect. It is therefore useful to signal distant lesions which must subsequently be investigated by other means (i.e. imaging, cytology, histopathology). The availability of appropriate facilities and equipment greatly limits the use of scintigraphy in a clinical setting. The choice of the imaging modality depends on the nature of the tumour to stage. For tumours preferentially spreading by lymphatic route (e.g. mast cell tumours), imaging is targeted at locoregional lymph nodes (e.g. abdominal ultrasound rather than chest x-rays) and fine-needle aspirates of these locoregional lymph nodes are more systematically obtained. Conversely, when staging sarcomas, imaging of the lymph nodes is of lesser interest, whereas chest x-rays are essential for evaluation of the pulmonary parenchyma. Similarly, the extent of the staging is dictated by the expected malignancy of the primary tumour to some degree: it may be decided not to stage a small mast cell tumour appearing well differentiated on cytology or histopathology before receiving the definitive histopathology results. Should the mass appear more aggressive (higher grade) than expected, more exhaustive staging may be pursued.

Planning surgeryOnce the tumour type and stage are known, treatment can be considered. This is where the surgeon needs to have a good knowledge of non-surgical therapies, to determine whether surgery is the best course of action and, if so, if it will be the sole treatment or merely part of a multimodal treatment. When in doubt, the surgeon must consult medical and radiation oncologists to discuss what treatment modality, if any, will be optimal for the patient. Similarly, if surgery is required, it needs to account for the treatments administered before (neoadjuvant treatments) and those administered after (adjuvant).

In every case, surgery must be planned. No masses should ever be excised without any knowledge of their nature, expected behaviour and recommended margins of excision. Unplanned marginal resections are associated with a higher risk of incomplete resection compared to well-planned excisions, and can significantly impair the chances of local disease control after revision surgery1.The most important point, when planning surgery for tumour resection, is to balance the consequences of surgery and potential complications against the expected benefits. In other words, the treatment should never be worse than the disease! It is easy for surgeons to be tempted to perform technically challenging procedures, which turn out to be of no significant benefit for the patient. Inversely, surgeons should not deter owners to proceed with some apparently extensive, but well tolerated, surgeries (amputations, extensive mandibulectomies / maxillectomies, etc.) because they personally feel uncomfortable with them. Referral should then be offered. It is crucial that surgeons place the patient’s welfare first, before owners’ wishes. In-depth discussion with the owners will allow understanding what their expectations are and whether they can be met by possible treatments. This will avoid misunderstandings and later issues.

Knowledge of the tumour type and biology is paramount in appropriate surgical planning. The surgical “dose” depends on it. The first surgery is the best chance to cure, it should not be wasted.


Surgery is planned on the basis of physical examination and diagnostic imaging (cf. local tumour staging). The recommended margins are determined around the tumour in 3 dimensions and anatomic structures included in this volume are considered. Structures which can be resected without significant morbidity usually are included in the resection plan and those which are not expendable (e.g. spinal cord, heart, brain) are preserved. Decisions have to be made regarding structures which can be resected at the cost of significant functional consequences. The benefit of their resection en-bloc with the tumour has to be weighed against the functional consequences and this must be well discussed with the owners.

When surgery has been planned, pain management must be anticipated. Some cancer patients are presented with pre-existing pain associated with their disease. It has been estimated that at least 30% of tumours of dogs and cats are associated with significant pain at the time of diagnosis25. Tumours themselves are not painful as they are not innervated. However, when tumours grow at the expense of surrounding structures, either compressive or invading them, pain is to be expected. Metastatic cancers are almost always painful.In addition, oncologic surgery is often aggressive and destructive. It is therefore expected to be associated with moderate to severe pain, depending on the procedures. The description of techniques and protocols of analgesia is beyond the scope of this text, but for optimal efficacy, systemic analgesia is often combined with local analgesia (e.g. epidural injections, nerve blocks, wound diffusion catheters, etc.).

Techniques in oncologic surgery

BiopsiesPerforming a biopsy consists of obtaining tissues for analysis (often histopathological) in view of getting of a better understanding of their nature. Properly performed, biopsies do not seem to negatively affect the course of the disease: there is no evidence of increases in the frequency of metastatic disease after biopsies, but seeding of cancer cells and subsequent tumour local spreading along the biopsy tract is possible26. It is therefore extremely important to plan biopsies keeping in mind that, should surgical excision of the tumour be later contemplated, the entire biopsy tract or surgical approach will need to be excised en-bloc with the tumour.

Many biopsy techniques exist and the choice of one of them depends on the organ involved, on the patient’s condition, on the clinician’s preference, on the tests to be performed, as well as on the most expected diagnosis. When histopathology is contemplated, the larger the samples obtained the better, as the accuracy of the histopathological diagnosis is largely proportional to the size of the sample(s)27. However, the larger the sample, the more traumatic the procedure. Therefore, the choice of a biopsy technique is a compromise between obtaining a sample which is large enough whilst remaining as little traumatic as possible. In addition, the procedure must be as safe as possible and the patient’s general condition and concurrent diseases are to be considered when making this choice.

In uncommon selected cases, lesions thought to be tumours can be excised without obtaining a pre-treatment biopsy. Primary lung tumours, bleeding splenic tumours and bone tumours classically serve as examples of such tumours as regardless of their precise nature, their treatment will invariably consist of lung lobectomy, splenectomy and


amputation / limb-sparing procedure respectively. In such cases, tumours are only examined by the anatomopathologist after their excision, which is referred to as a post-treatment biopsy.

In most cases, however, a biopsy should be performed prior to treatment (pre-treatment biopsy) as the knowledge of the nature of a lesion has often significant implications on its treatment. It also allows defining the prognosis more precisely, which is important to inform owners and help them make decision. From the surgeon’s point of view, a biopsy is useful for determining whether there is an indication for surgery and, if so, how aggressive it should be. For lesions which can easily be excised widely due to their size and location, fine-needle aspirates may be sufficient obtain a crude diagnosis prior to excision. However, whenever the surgical treatment is challenging or questionable, obtaining a precise diagnosis before embarking on it is essential.

Biopsy types Fine-needle aspirates

Fine-needle aspirates (FNAs) are not universally considered as biopsies as they do not preserve the structure of tissues but only provide information on their cell population. Therefore, a precise tumour grading cannot be obtained from FNAs, as grading partly relies on the examination of the structural relationship of the tumour and surrounding structures. However, for several types of tumour, determination of the cellular type and changes can provide enough information to guide treatment. Cytology is most useful in making the difference between a non-neoplastic lesion and a tumour, as well as in classifying a tumour as round-cell, epithelial or mesenchymal. A crude estimation of the tumour’s likely aggressiveness may also be possible.

Fine-needle aspirates can be used for deep and superficial lesions. For deep and intracavitary lesions, ultrasonographic guidance is useful to ascertain proper sampling of the relevant area.

The sensitivity of FNAs is better for round-cell (70%-100%) and epithelial (67%-98%) than for mesenchymal (50%-61%) tumours, which do not easily exfoliate. For cutaneous and subcutaneous lesions, the cytological and histopathological diagnoses were found to be in agreement in 91% of cases11.

Needle-core biopsiesNeedle-core biopsies are obtained with special needles (e.g. TruCut, Jamshidi) which can be manually or automatically operated. Here again, the larger the diameter of the needle, the larger the biopsy sample and the more accurate the histopathological diagnosis. The choice of the needle gauge therefore depends on the characteristics of the mass to sample (organ involved, cavitary or not, etc.) as well as on the estimated risk for inducing complications (haemorrhage, pneumothorax for pulmonary lesions for instance).

Needle-core biopsies can be taken percutaneously, either blindly for large, superficial and rather homogeneous masses, or under ultrasonographic or laparoscopic guidance in all other cases. They can also be a rapid means of obtaining a biopsy at surgery (e.g. kidney biopsies). When used percutaneously, these biopsy techniques give little control on potential complications, especially haemorrhage.

Samples obtained with this technique are fragile and should be collected with care not to compromise their diagnostic value. Gentle removal of the obtained tissues with the tip of a needle or small scalpel blade, or by directly dipping the open biopsy needle in the


formalin are two ways to collect tissue samples from the core-needle. If dipped in formalin, the core-needle is flushed with sterile saline prior to be used again for another biopsy on the same patient.

Surgical biopsiesSurgical biopsies can be incisional or excisional. Incisional biopsies consist of sampling a portion of the tumour to allow histopathological determination of its nature. Excisional (or post-treatment) biopsies consist of the complete excision of the tumour prior to any histopathological diagnosis.Excisional biopsies should only be chosen when knowledge of the tumour type or grade would not alter the surgical dose required for resection, or when wide excision of the biopsy tract will easily be possible if insufficient margins were to be obtained (Figure 1). Excessive and inappropriate use of marginal excisional biopsies is a major cause for cancer treatment failure. If in doubt, perform fine-needle aspirates or an incisional biopsy to ascertain that the subsequent resection plan is appropriate.

In general, it is best to biopsy at the junction between healthy and tumoral tissues, so that the pathologist can study the characteristics of the tumour invasion in surrounding tissues. Also, many tumours are necrotic, inflammatory or infected in their centre, which may lead to misdiagnosis. However, some tumours, such as osteosarcoma, should be biopsied in their centre as they induce a strong reaction within surrounding tissues, which may lead to misdiagnosis is biopsied in periphery. In addition, if the surrounding tissues are essential for later reconstruction, they should not be included in the biopsy. Overall, it is crucial not to jeopardise later treatments by performing biopsies in a way that the biopsy tract can be later excised en-bloc with the tumour. Therefore, when sufficient margins may be difficult to achieve, it is best to limit the incisional biopsies to the tumour itself and not extend it to normal tissues, so that the required subsequent surgical resection is not made larger.

When performing biopsies, incisions should not be made with electrocautery as it can create polarisation artefacts which can hinder pathological evaluation of the tissues. This is especially important when the biopsies taken are small. If cautery is needed for haemostasis, it should only be used once the biopsies have been collected. Similarly, biopsies of friable tissues must be handled carefully and not crushed with the surgical instruments, as it creates a crushing artefact with can also complicate or prevent pathological interpretation.

Once samples have been collected, they must be handled appropriately. If they are large, they must be incised prior to be fixated, as formalin only penetrates the tissues 1 cm deep. The mass should therefore be sliced as required, but only partially so that it remains cohesive and the pathologist can still have a clear understanding of the orientation of the slices28 (Figure 2).


Figure 2: Large biopsy prepared for formalin fixation (d’après Henry28).

Tumour resectionAs often as possible, tumours should be resected widely. Fear of not being able to close the resulting defect should not limit the resection extension. It is better to leave a wound partially open but free of cancer than be able to close it over residual tumour as a result of a more timid resection6. Depending on the tumour type and size, 1 to 3-cm lateral margins are generally recommended. Tumour type and grade are probably the most important factors for determination of the required surgical margins. Benign and little aggressive malignant tumours can be resected with narrower margins than aggressive malignant tumours. For instance, some surgeons advocate very wide (5-cm) lateral margins for excision of feline soft tissue sarcomas29, which are extremely infiltrative tumours. In depth, depending on tumour type and size, one or two fascial planes should be excised en-bloc with the tumour.However, it seems that tumour size also influences the width of required margins: for a same tumour type, larger tumours are associated with greater microscopic extension in surrounding tissues and therefore require wider surgical margins than smaller tumours1.

If an adjuvant treatment is planned (radiotherapy especially), the surgical excision can be sometimes be more conservative. Taking intraoperative pictures and leaving metallic vascular clips at the margins of excision can then help the radiation oncologist plan subsequent treatments.

Tumours should be manipulated as little and as gently as possible to prevent seeding of tumour cells. Ideally, the tumour should not be approached or visualised and only healthy surrounding tissues be manipulated. Similarly, the pseudocapsule of tumours must not be approached, as it is not only reactive tissue but mostly composed of compressed tumour cells6, 30. Previous biopsy and drain tracts are excised en-bloc with the tumour. Whenever possible, major arteriovenous pedicles should be ligated as early as possible in the procedure and veins be ligated before arteries to limit the risk of macroscopic embolisation of tumour cells when the tumour is manipulated.Tumours located in body cavities can usually not be excised en-bloc with surrounding tissues. They are therefore directly exposed during surgery and should be wrapped in laparotomy swabs to limit the risk of coelomic seeding as a result of capsule rupture of the affected organ during its manipulation31. Such tumours may be found to be adherent to other organs or to the omentum for abdominal tumours. The portions of other organs


being adherent to the tumour should be excised en-bloc with it (e.g. omentum with splenic or digestive tumours, lung with rib tumours, etc.).

Tumour should be considered and treated as infected tissues would: any instruments, gloves and drapes which may have been contaminated by tumour cells should be changed. Likewise, any tissues having been in contact with the tumour are treated as if they were part of the tumour itself: they should be resected with similar margins whenever possible. The same instruments should not be used to excise, or biopsy, two separate masses. Similarly, when closing the surgical wound, it is important to remember that any distant tissues used (skin flaps for instance) will be considered contaminated if any subsequent treatment is required. For reconstruction, the use of multifilament sutures is not recommended as it has been associated with higher tumour recurrence rates1. Using large skin flaps after tumour excision should also be avoided if the tumour margins are not known to be clear. It could lead to tumour seeding and recurrence away from the initial site and prevent adjuvant radiotherapy as the irradiation field would become too large. An option allowing skin flaps to be used in the face of uncertain margins is to harvest the flap before starting the tumour resection. I regularly use this approach, which requires careful surgical planning.Similarly, drains should be used a rarely as possible as they provide a route for tumour seeding, should any residual disease be left in the wound. All tissues along the draining tract would later need to be considered as contaminated, which will increase the size of any revision surgery or radiotherapy field, should these be necessary. If the use of drains are absolutely necessary, they should be placed wisely, keeping in mind the potential future treatments, and as closely as possible from the surgical field. If a postoperative complication requiring placement of a drain occurs once the margins are known to be free of tumour, drains can then be used.

Postoperative care should be anticipated. Enteral feeding tubes should be placed as appropriate. Similarly, wound catheters can be left in surgical wounds, allowing regular instillation of local anaesthetics in the wound.

Even if the tumour has previously been biopsied, the entire piece of excision is fixed in 10 volumes of 10% formalin for each volume of tissue5, 27, 28, 32 and submitted for pathology. Prior to fixation, margins can be marked with India ink and the piece of excision be oriented using sutures, with appropriate explanations provided to the pathologist. It is important to remember that the formalin will not penetrate tissues on more than 1 cm in depth. Therefore, thicker samples must be sliced in 1-cm, similarly to a loaf of bread, leaving the deep (inked) margin intact so that the sample remains in one piece and can still be orientated by the pathologist1, 27, 28 (Figure 2).

After surgery

Postoperative careNon-specifically, postoperative care of cancer patients include wound care, analgesia, nutritional support, and medical care as appropriate. Depending on the tumour type, specific treatments of paraneoplastic treatments can be required (e.g. blood levels monitoring and management of calcium in patients with hyperparathyroidism or of glucose in patients with insulinomas, etc.). Depending on the procedure performed, specific management may be required (chest drain for thoracic tumours, nursing on animals with spinal tumours, rehabilitation for amputees, etc.).


Adjuvant therapies: should the surgeon care?Basic understanding of the principles of adjuvant therapies is essential for the surgeon working in cooperation with medical and radiation oncologists. Non-surgical therapies of cancer are an extremely wide and deep field of medicine, which can obviously not be covered here. Only a very brief presentation of the principles of radiotherapy and chemotherapy, orientated towards their relevance for the surgeon, will be attempted.

RadiotherapyRadiotherapy consists of using ionizing radiation to kill neoplastic cells. Different sources of radiation are currently used: orthovoltage units, cobalt 60 units, linear accelerators, brachytherapy (implantation of a radioactive source) and systemic radiation therapy (radioisotope injections). The SI unit for absorbed dose of radiation is expressed is the gray (Gy). Radiotherapy is mostly a local (or loco-regional) treatment. As such it is used to help in controlling local disease.When the tumour and normal tissues are exposed to radiation, both free radical production and damage to the cell DNA ensues. A third of the radiotherapy effect is mediated by damage to DNA, the rest being a result of free radical production33. The majority of the DNA damage is mediated by oxygen free radicals, the production of which is dependent on the oxygenation of tissues. Therefore, hypoxic tumours will tend to be less radiosensitive than well-oxygenated tumours.Cells with damaged DNA do not die immediately, but when attempting division. Some may even be able to divide a few times before dying. Therefore, the effect of radiotherapy is not immediate and depends to a certain extent on the division rate of tumour cells and growth rate of the tumour. Slow-growing tumours may take months to show clinical response. This is also true for normal tissues: rapidly proliferating tissues rapidly show a response to radiotherapy (acutely-, or early-, responding tissues), whereas slow-proliferating tissues show more delayed reactions (late-responding tissues)34. The goal of radiotherapy is to destroy the reproductive capacity of a tumour without excessive damage to surrounding normal tissues34. Most adverse side-effects from radiotherapy are caused by exposition of normal tissues to radiotherapy, which is currently unavoidable. These adverse side-effects are however minimised by fractionating the dose of radiotherapy to administer into several smaller doses. This is called fractionation. As a rule, potential complications of radiotherapy are more likely as the total radiation dose, the dose per fraction and the size of the radiation field increase6.

Different protocols, in terms of total dose and fractionation, can be used for administration of radiotherapy. Briefly, the choice depends on the type and location of the tumour and on the aim of radiotherapy (palliative versus definitive, i.e. with intent to cure). Hypofractionated and hyperfractionated protocols have different indications and side-effects.

For the surgeon, radiotherapy is a powerful ally. Radiotherapy and surgery can be synergistic35, 36. Surgery is most efficacious are eliminating the bulk of a tumour, but most often fails at detecting and removing microscopic or small satellite nests of tumour cells around the tumour. On the contrary, radiotherapy is most efficient on microscopic or small size disease, as the centre of bulky tumours is often hypoxic, and therefore radioresistant. The combination of both treatments is therefore logical.

Radiotherapy can be administered either before surgery (neoadjuvant radiotherapy) or after surgery (adjuvant radiotherapy). Each option has advantages and disadvantages1, 33.A surgical scar is relatively hypoxic because of the vascular damage induced by surgery.


As such, it is relatively radioresistant. When radiotherapy is administered before surgery, no surgical scar is present and tissue hypoxia is kept to a minimum, making tissues more radiosensitive. Also, the irradiated volume may be smaller for preoperative radiotherapy than when surgery has been performed, as it may have required manipulation of more distant tissues for reconstruction. Preoperative radiotherapy also potentially decreases viable tumour cell seeding at surgery and it can in some instances reduce the size of the tumour which will facilitate surgical excision.However, preoperative surgery can make tissues more fibrotic and more difficult to dissect. It can also make intraoperative differentiation between tissues more difficult. Lastly, radiotherapy is detrimental to wound healing, which it delays, and complications such as wound dehiscence are more likely when surgery is performed on irradiated tissues. However, all these detrimental effects are mostly significant when hypofractionated protocols are used. When neoadjuvant radiotherapy is properly and carefully planned in view of being followed by surgery, the effects on tissues are hardly perceptible at surgery and wound complication rates are not significantly increased. The only potential exception may be oral tumours, which seems to be associated with a higher rate of wound complications when surgery is performed after radiotherapy.Conversely, postoperative radiotherapy decreases the risk of wound complication, but may have to be administered to a larger field and to more hypoxic, and therefore more radioresistant tissues. In addition, radiotherapy needs to be delayed by several weeks after surgery and potential residual tumour may have time to proliferate.

ChemotherapyIn oncology, chemotherapy refers to the use of antineoplastic drugs. Unlike radiotherapy, chemotherapy is mostly a systemic treatment. When chemotherapy is used in combination with surgery, it can be administered before (neoadjuvant, or primary, chemotherapy) or after (adjuvant chemotherapy) surgery.In veterinary oncology, a common indication for neoadjuvant chemotherapy is feline injection-site sarcomas. The rationale for neoadjuvant chemotherapy is that, like radiotherapy, chemotherapy is most efficacious against microscopic or small-size neoplastic disease. When administering neoadjuvant chemotherapy, it is hoped that satellite nests of tumour will be killed, resulting in sterilisation of the main tumour margins. In addition, the main bulk of tumour may shrink as a result of chemotherapy, which can facilitate its surgical excision.Nonetheless, chemotherapy is most often used in veterinary oncology as an adjuvant treatment to control the possible spreading of tumours with significant metastatic potential after the primary tumour has been addressed by other treatments such as surgery and radiotherapy. Usually, in this indication, chemotherapy is started early after surgery (most often 7 to 10 days postoperatively).

Although most chemotherapeutic agents experimentally impair wound healing6, 37, it is of little, if any, clinical relevance and should not be a concern for the surgeon.The main implication of chemotherapy for the surgeon is that patients on chemotherapy have an increased risk of developing infections. Therefore, any procedure increasing the risk of postoperative infection in patients destined to have chemotherapy must be performed cautiously. For instance, the use of massive implants, such as large prosthetic meshes for extensive wound reconstruction, should only be resorted to when no other option is available.


References

1. Liptak J. The Principles of Surgical Oncology: Surgery and Multimodality Therapy. Compendium Continuing Education for Veterinarians. 2009;31: 14 p.2. Gilson SD. Principles of surgery for cancer palliation and treatment of metastases. Clinical Techniques in Small Animal Practice. 1998;13: 65-69.3. You YN, Lakhani V, Wells S, Jr. The Role of Prophylactic Surgery in Cancer Prevention. World J Surg. 2007;31: 450-464.4. Dernell WS, Withrow SJ. Preoperative patient planning and margin evaluation. Clinical Techniques in Small Animal Practice. 1998;13: 17-21.5. Liptak J. The Principles of Surgical Oncology: Diagnosis and Staging. Compendium Continuing Education for Veterinarians. 2009;31: 14 p.6. Withrow SJ. Surgical oncology. In: Withrow SJ, Vail DM (eds): Small animal clinical oncology. St Louis: Saunders Elsevier, 2007;157-162.7. Spodnick GJ, Berg J, Rand WM, Schelling SH, Couto G, Harvey HJ, et al. Prognosis for dogs with appendicular osteosarcoma treated by amputation alone: 162 cases (1978-1988). Journal of the American Veterinary Medical Association. 1992;200: 995-999.8. Ruthanne C. Paraneoplastic syndromes. In: Henry CJ, Higginbotham ML (eds): Cancer management in small animal practice. Maryland Heights, MO: Saunders Elsevier, 2010;94-100.9. Vail DM. Paraneoplastic hypercalcemia. In: Bonagura JD, Kirk RW (eds): Kirk's current veterinary therapy XIV. Philadelphia, Pa. ; London: Elsevier Saunders, 2008;343-347.10. Bergman PJ. Paraneoplastic syndromes. In: Withrow SJ, Vail DM (eds): Small animal clinical oncology. St Louis: Saunders Elsevier, 2007;77-94.11. Ghisleni G, Roccabianca P, Ceruti R, Stefanello D, Bertazzolo W, Bonfanti U, et al. Correlation between fine-needle aspiration cytology and histopathology in the evaluation of cutaneous and subcutaneous masses from dogs and cats. Veterinary Clinical Pathology. 2006;35: 24-30.12. Cohen M, Bohling MW, Wright JC, Welles EA, Spano JS. Evaluation of sensitivity and specificity of cytologic examination: 269 cases (1999-2000). Journal of the American Veterinary Medical Association. 2003;222: 964-967.13. Eich CS, Whitehair JG, Moroff SD, Heeb LA. The accuracy of intraoperative cytopathological diagnosis compared with conventional histopathological diagnosis. Journal of the American Animal Hospital Association. 2000;36: 16-18.14. Bonfanti U, Bussadori C, Zatelli A, Lorenzi Dd, Masserdotti C, Bertazzolo W, et al. Percutaneous fine-needle biopsy of deep thoracic and abdominal masses in dogs and cats. Journal of Small Animal Practice. 2004;45: 191-198.15. Sharkey LC, Dial SM, Matz ME. Maximizing the diagnostic value of cytology in small animal practice. Veterinary Clinics of North America, Small Animal Practice. 2007;37: 351-372.16. Cullen JM, Page R, Misdorp W. An Overview of Cancer Pathogenesis, Diagnosis, and Management. In: Meuten DJ (ed): Tumors in domestic animals. Ames, Iowa: Iowa State University Press ; [Oxford : Blackwell] [distributor], 2002;3-44.17. Séguin B. Tumors of the mandible, maxilla and calvarium. In: Slatter D (ed): Textbook of small animal surgery. Philadelphia: saunders, 2003;2488-2502.18. Forrest LJ. Diagnostic imaging in oncology. In: Withrow SJ, Vail DM (eds): Small animal clinical oncology. St Louis: Saunders Elsevier, 2007;97-111.19. Williams LE, Packer RA. Association between lymph node size and metastasis in dogs with oral malignant melanoma: 100 cases (1987-2001). Journal of the American Veterinary Medical Association. 2003;222: 1234-1236.20. Langenbach A, McManus PM, Hendrick MJ, Shofer FS, Sorenmo KU. Sensitivity and specificity of methods of assessing the regional lymph nodes for evidence of metastasis in dogs and cats with solid tumors. Journal of the American Veterinary Medical Association. 2001;218: 1424-1428.21. Tuohy JL, Milgram J, Worley DR, Dernell WS. A review of sentinel lymph node evaluation and the need for its incorporation into veterinary oncology. Veterinary and Comparative Oncology. 2009;7: 81-91.


22. Lamb CR. The canine and feline lung. In: Thrall DE (ed): Textbook of veterinary diagnostic radiology. Philadelphia ; London: W.B. Saunders, 2002;431-449.23. Dernell WS, Ehrhart NP, Straw RC, Vail DM. Tumours of the skeletal system. In: Withrow SJ, Vail DM (eds): Small animal clinical oncology. St Louis: Saunders Elsevier, 2007;540-582.24. Yoon J, Feeney DA, Cronk DE, Anderson KL, Ziegler LE. Computed tomographic evaluation of canine and feline mediastinal masses in 14 patients. Veterinary Radiology & Ultrasound. 2004;45: 542-546.25. Lascelles BDX. Management of chronic cancer pain. In: Withrow SJ, Vail DM (eds): Small animal clinical oncology. St Louis: Saunders Elsevier, 2007;291-306.26. Klopfleisch R, Sperling C, Kershaw O, Gruber AD. Does the taking of biopsies affect the metastatic potential of tumours? A systematic review of reports on veterinary and human cases and animal models. The Veterinary Journal. 2011;190: e31-e42.27. Ehrhart NP, Withrow SJ. Biopsy principles. In: Withrow SJ, Vail DM (eds): Small animal clinical oncology. St Louis: Saunders Elsevier, 2007;147-153.28. Henry CJ, Pope ER. Methods of tumour diagnosis: fine-needle aspiration and biopsy techniques. In: Henry CJ, Higginbotham ML (eds): Cancer management in small animal practice. Maryland Heights, MO: Saunders Elsevier, 2010;41-46.29. Kuntz CA. Modified wide local excision for vaccine associated soft tissue sarcomas in cats (abstract). Veterinary Surgery. 2000;29.30. Berg J. Surgical therapy. In: Slatter D (ed): Textbook of small animal surgery. Philadelphia: saunders, 2003;2324-2328.31. O'Brien MG. Principles of oncologic abdominal surgery. Clinical Techniques in Small Animal Practice. 1998;13: 42-46.32. Farese JP. Surgical oncology principles. In: Bonagura JD, Twedt DC (eds): Kirk's current veterinary therapy XIV. Philadelphia, Pa. ; London: Elsevier Saunders, 2009;320-324.33. Ruslander D. Radiation therapy. In: Slatter D (ed): Textbook of small animal surgery. Philadelphia: saunders, 2003;2329-2345.34. LaRue SM, Gillette EL. Radiation therapy. In: Withrow SJ, Vail DM (eds): Small animal clinical oncology. St Louis: Saunders Elsevier, 2007;193-210.35. North SM, Banks TA. Principles of radiation oncology. In: North SM, Banks TA (eds): Small animal oncology: an introduction. Edinburgh: Saunders Elsevier, 2009;45-53.36. McNiel EA, LaRue SM. Principles of adjunctive radiation therapy. Clinical Techniques in Small Animal Practice. 1998;13: 33-37.37. Hosgood G. Wound repair and specific tissue response to injury. In: Slatter D (ed): Textbook of small animal surgery. Philadelphia: saunders, 2003;66-86.


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