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==Description==
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Primary hepatic tumours are rare, accounting for less than 1.5% of all canine tumours and 1.0-2.9% of all feline tumours. However, the liver is a common site for metastatic tumours due to its rich blood supply from the hepatic portal vein and hepatic artery and in dogs, hepatic neoplasia are 2.5 times more likely to be metastases than primary neoplasia.  By contrast, primary hepatobillary tumours are more frequent than metastatic tumours in cats.
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* Primary hepatic tumours are rare (less than 1.5% of all canine tumours and 1.0-2.9% of all feline tumours) * However, the liver is a common site of metastatic tumours due to the rich blood supply (hapatic portal vein and hepatic artery)
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Malignant tumours are more common in dogs but benign neoplasia is more common in cats.  Primary tumours found in the liver include:
* In dogs, metastasis to the liver is 2.5 times more likely than primary neoplasia
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* [[Carcinoma#Hepatocytic|Hepatocellular carcinoma]] or [[Adenoma#Hepatocytic|adenoma]] (hepatoma)
* In cats, primary hepatobillary tumours are more frequent than metastatic tumours
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* [[Carcinoma#Cholangiocellular|Cholangiocellular carcinoma]] or [[Adenoma #Cholangiocellular|cystadenoma]]
* Malignant tumours are more common in dogs
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* Gall bladder carcinoma or adenoma
* Benign tumours are more common in cats
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* [[Haemangiosarcoma|Haemangiosarcoma]]
* Malignant primary tumours include:
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* Mast cell tumour
** [[Carcinoma#Hepatocytic|Hepatocellular carcinoma]]  
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* Hepatic carcinoids (neuroendocrine)
** [[Carcinoma#Cholangiocellular|Cholangiocellular carcinoma]]
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** Gall bladder carcinoma
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** [[Haemangiosarcoma|Haemangiosarcoma]]
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** Mast cell tumour
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** Hepatic carcinoids (neuroendocrine)
   
* Benign tumours include:
 
* Benign tumours include:
** [[Adenoma#Hepatocytic|Hepatocellular adenoma]] (hepatoma)
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** [[Adenoma #Cholangiocellular|Cholangiocellular adenoma]]
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** Gall bladder adenoma
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Note: Distinction must be made between all hepatic tumours and [[Liver - Nodular Hyperplasia|benign nodular hyperplasia]] that is frequently observed in the older canine. The most significant primary tumours in the dog are hepatomas, [[Carcinoma #Hepatocytic|Hepatocellular]] and [[Carcinoma#Cholangiocellular|Cholangiocellular]] carcinomas and hepatic carcinoids. [[Carcinoma#Hepatocytic|Hepatocellular carcinoma]] and  [[Carcinoma#Cholangiocellular|Cholangiocellular carcinoma]] are the most significant in cats.
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Care must be taken to distinguish between all hepatic tumours and [[Liver - Nodular Hyperplasia|benign nodular hyperplasia]] which is frequently observed in older dogs. The most significant primary tumours in the dog are hepatomas, [[Carcinoma #Hepatocytic|hepatocellular]] and [[Carcinoma#Cholangiocellular|cholangiocellular]] carcinomas and hepatic carcinoids. [[Carcinoma#Hepatocytic|Hepatocellular carcinomas]] and  [[Carcinoma#Cholangiocellular|cholangiocellular carcinomas]] are the most significant in cats.
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==Diagnosis==
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==Signalment==
Symptomatic in approximately 75% of dogs and 50% of cats, particularly if malignant.
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===Clinical signs===
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* Usually non-specific:
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** Weight loss
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** Inappetance
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** Lethargy
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** Polyuria-Polydipsia
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** Vomiting
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** Ascites
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* Neurological Signs - seizures, ataxia and weakness occur less frequently. They may be due to metastasis to the central nervous system, [[Hepatic Encephalopathy|hepatic encephalopathy]] or hypoglycaemia which can occur as a paraneoplastic syndrome
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* Icterus - Particularly in dogs with extrahepatic cholangiocellular carcinomas and diffuse carcinoids
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===Physical Examination===
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* Cranial abdominal mass - palpable in up to 75% of cats and dogs
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===Haematology and Biochemistry===
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* Usually non-specific. The following are frequently observed in dogs:
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** Mild non-regenerative anaemia - cause idiopathic, however anaemia of chronic disease, inflammation, red blood cell sequestration and iron deficiency may play roles
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** Leukocytosis - resulting from the associated inflammation and necrosis that can occur with large liver masses
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** Thrombocytosis - potential causes include production of thrombopoietin as a parneoplastic syndrome, iron deficiency, inflammatory cytokines and anaemia
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* Elevated hepatic enzymes - likely due to hepatocellular damage or biliary stasis though the extent of enzyme increase is not proportional to severity of liver damage
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* Hypoalbuminaemia
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* Hyperglobulinaemia
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* Hypoglycaemia - can occur as a paraneoplastic syndrome where there is increased utilisation of glucose or increased production of hormones with insulin-like activity.
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* Elevated pre- and postprandial bile acids
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* The following have been observed in cats:
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** Azotaemia
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** Elevated hepatic enzymes
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** Elevated serum bilirubin - particularly in those with hepatocellular carcinoma
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===Plain Abdominal Radiography===
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Hepatomegaly and rounding of the margins of the liver may be observed. Alternatively a cranial abdominal mass may be visible with displacement of the stomach caudally and laterally with massive hepatic neoplasms. Occasionally mineralisation of the biliary tree is observed in dogs with cholangiocellular carcinoma. Three thoracic views should also be taken to assess lung metastasis although this is uncommon at the time of diagnosis.
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===Ultrasonography===
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Advised to evaluate the condition of surrounding structures. It also allows classification of the mass as massive, nodular or diffuse. Doppler techniques can also be utilised to assess the vascular structure of tumours. Guided fine-needle aspirates or core biopsies can also be taken at this time (a coagulation profile is highly recommended prior to performing a liver biopsy due to risk of haemorrhage). If the lesion is solitary and massive surgical resection without preoperative biopsy is usually undertaken as diagnosis and treatemnt are accomplished in one procedure.
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===Advanced Imaging===
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CT and MRI are more sensitive in detecting small lesions and confirming the relationship of the mass with surrounding tissues and vasculature.
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===Abdominocentesis===
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Cytological examination of the sediment may reveal neoplastic cells. Effusions are usually modified transudates and haemorrhage may indicate tumour rupture.
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==Signalment and Description==
   
===Hepatocellular Tumours ([[Carcinoma#Hepatocytic|Hepatocellular carcinomas]] (HCC) and [[Adenoma#Hepatocytic|Hepatomas]])===
 
===Hepatocellular Tumours ([[Carcinoma#Hepatocytic|Hepatocellular carcinomas]] (HCC) and [[Adenoma#Hepatocytic|Hepatomas]])===
 
* HCC occurs more frequently in dogs and hepatomas more commonly in cats. They are the most common primary liver tumour in dogs and the second most common in cats.  
 
* HCC occurs more frequently in dogs and hepatomas more commonly in cats. They are the most common primary liver tumour in dogs and the second most common in cats.  
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* These tumours are aggressive and metastasis to the spleen and lungs is frequently observed.
 
* These tumours are aggressive and metastasis to the spleen and lungs is frequently observed.
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==Diagnosis==
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Tumours are symptomatic in approximately 75% of dogs and 50% of cats and this is more likely to be the case with malignant neoplasia.
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===Clinical signs===
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Signs are usually non-specific or they may indicate a disease of the liver:
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*'''Weight loss''', inappetance and lethargy.
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*'''Polyuria''' and '''polydipsia'''.
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*'''[[Vomiting]]'''
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*'''[[Modified Transudate|Ascites]]''' due to the development of portal hypertension.
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*'''Neurological signs''', including seizures, ataxia and weakness are not as common as the signs described above. They may be due to metastasis to the central nervous system, [[Hepatic Encephalopathy|hepatic encephalopathy]] or hypoglycaemia which can occur as a paraneoplastic syndrome.
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*'''[[Icterus]]''' occurs particularly in dogs with extrahepatic cholangiocellular carcinomas and diffuse carcinoids.
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*A '''cranial abdominal mass''' will be palpable in up to 75% of cats and dogs
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===Laboratory Tests===
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The results of blood samples are usually unremarkable but the following findings may be documented in affected animals:
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*Mild '''non-regenerative anaemia''' of unknown cause.  The anaemia may be caused by anaemia of chronic disease, inflammation, red blood cell sequestration and iron deficiency may play roles
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*'''Leucocytosis''' resulting from the associated inflammation and necrosis that can occur with large liver masses.
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*'''Thrombocytosis''', of which potential causes include production of thrombopoietin as a parneoplastic syndrome, iron deficiency, inflammatory cytokines and anaemia.
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*Elevation in the blood levels of '''hepatic enzymes''' probably occurs due to hepatocellular damage or biliary stasis.  The extent of the elevation is not proportional to severity of liver damage.
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*'''[[Hypoalbuminaemia]]''' due to reduced hepatic synthesis of albumin.
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*'''Hyperglobulinaemia''' due to a chronic inflammatory process.
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*'''Hypoglycaemia''' can occur as a paraneoplastic syndrome where there is increased utilisation of glucose or increased production of hormones with insulin-like activity (such as the somatomedins or insulin-like growth factors).
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*Elevated pre- and post-prandial '''[[Bile acids|bile acids]]'''
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*[[Bilirubin|'''Hyperbilirubinaemia]]''' which may be sufficiently severe to cause [[Icterus|icterus]].
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===Diagnostic Imaging===
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====Radiography====
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'''Plain radiographs of the abdomen''' may show hepatomegaly and rounding of the margins of the liver. With massive hepatic neoplasia, a cranial abdominal mass may be visible with displacement of the stomach caudally and laterally. Mineralisation of the biliary tree is occasionally observed in dogs with cholangiocellular carcinoma. Ideally, all three thoracic views should also be taken to assess for the presence of pulmonary metastases, although this finding is uncommon at the time of diagnosis.
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====Ultrasonography====
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An abdominal ultrasound scan is advised to evaluate the condition of structures surrounding the liver. It also allows classification of the mass as massive, nodular or diffuse. Doppler techniques can be utilised to assess the vascular structure of tumours and guided fine-needle aspirates or core biopsies can be taken at this time, although it is desirable to await the results of a coagulation profile before undertaking this procedure.
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====Advanced Imaging====
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CT and MRI are more sensitive in detecting small lesions and confirming the relationship of the mass with surrounding tissues and vasculature. They may also be used to detect early metastases.
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===Other Tests===
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Cytological examination of ascitic fluid may reveal the presence of neoplastic cells. Effusions are usually [[Modified Transudates|modified transudates]] but [[Haemorrhagic Effusion|haemorrhage]] may indicate the the tumour has ruptured.
    
==Treatment==
 
==Treatment==
 
===Surgery===
 
===Surgery===
Surgical excision is advised for hepatic adenomas, bile duct adenomas and massive [[Carcinoma#Hepatocytic|hepatocellular carcinomas]]. Nodulectomy or lobectomy can be used for focal tumours of one or more lobes. Diffuse tumours and widespread nodular disease carry a worse prognosis.
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Surgical excision is advised for hepatic adenomas, bile duct adenomas and massive [[Carcinoma#Hepatocytic|hepatocellular carcinomas]]. Nodulectomy or lobectomy can be used for focal tumours involving only one or a small number of lobes. Diffuse tumours and widespread nodular disease carry a poorer prognosis.
    
===Chemotherapy===
 
===Chemotherapy===
Not currently recommended for primary hepatic neoplasia. Some metastatic sarcomas, for example [[Haemangiosarcoma|haemangiosarcomas]], may show some response.
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This treatment modality is not recommended for primary hepatic neoplasia. Some metastatic sarcomas, such as [[Haemangiosarcoma|haemangiosarcomas]], may show some response.
    
===Radiotherapy===
 
===Radiotherapy===
Not reported. Surrounding abdominal organs may show poor tolerance.
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This procedure is not undertaken as it involves irradiating the entire abdomen and some surrounding organs may show poor tolerance.
 
      
==Prognosis==
 
==Prognosis==
The mean survival time for massive [[Carcinoma#Hepatocytic|hepatocellular carcinomas]] following surgery is approximately 1 year. Otherwise the prognosis is poor for other malignant and metastatic tumours. If successfully excised the prognosis for benign tumours is good.
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The median survival time for massive [[Carcinoma#Hepatocytic|hepatocellular carcinomas]] following surgery is approximately 1 year. Otherwise the prognosis is poor for other types of malignant and metastatic tumours. If successfully excised the prognosis for benign tumours is good.
 
      
==References==
 
==References==
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* Morris J, Dobson J (2001) Gastrointestinal Tract, in Small Animal Oncology, Blackwell Science, pp 137-140
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* Morris J, Dobson J (2001) Gastrointestinal Tract, in Small Animal Oncology, Blackwell Science, pp 137-140
   
* Liptak J. M, Withrow S.J, (2007), Cancer of the Gastrointestinal Tract, in Withrow and MacEwen's Small Animal Clinical Oncology, fourth edition, Eds Withrow S.J, Vail D.M, Missouri, Saunders Elsevier, pp 483-489
 
* Liptak J. M, Withrow S.J, (2007), Cancer of the Gastrointestinal Tract, in Withrow and MacEwen's Small Animal Clinical Oncology, fourth edition, Eds Withrow S.J, Vail D.M, Missouri, Saunders Elsevier, pp 483-489
 
[[Category:Liver_-_Proliferative_Pathology]]
 
[[Category:Liver_-_Proliferative_Pathology]]
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[[Category:Neoplasia]]
 
[[Category:Neoplasia]]
 
[[Category:To_Do_-_James]]
 
[[Category:To_Do_-_James]]
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[[Category:Dog]][[Category:Cat]]
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