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Pathologies that can be potentially treated with hadrontherapy

Primary tumours of the liver and the biliary tract

AGAINST RADIO-RESISTANT AND INOPERABLE TUMORS Pathologies that can be treated Primary tumours of the liver and the biliary tract

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Primary tumours of the liver and the biliary tract are hepatobiliary neoplasms that can be classified into:

  • Liver tumours
  • Biliary tract tumours

Primary liver tumours

The most common primary liver tumours, i.e. those originating from hepatocytes, can be subdivided into:

  • Benign tumours
    • Angioma
    • Focal nodular hyperplasia
    • Adenoma
  • Hepatocellular carcinoma
  • Angiosarcoma
  • Intrahepatic cholangiocarcinoma
  • Hepatoblastoma (in children and infants)

Among primary malignant liver tumours, the most common one is certainly the hepatocellular carcinoma.

Primary tumours are usually rarer than secondary tumours because the liver, given its function as a filter for the body, receives blood from most body regions, thus becoming the ideal location for the development of metastasis.

Primary liver tumours generally tend not to migrate to other organs, but they are more susceptible to spread within the liver itself, giving rise to multifocal tumours.

In most cases, primary liver tumours develop after the age of 50 years, mainly in male subjects.

Primary tumours of the biliary tract

Primary tumours of the biliary tract, on the other hand, can be divided into:

  • Extrahepatic cholangiocarcinomas
    • Klatskin Tumour
    • Distal bile duct tumours
  • Gallbladder tumour

Primary tumours of the biliary tract develop more frequently in women, with an average age of onset around 65 years.

Causes of primary tumours of the liver and the biliary tract

The causes of primary tumours of the liver and the biliary tract have not been yet fully elucidated, although there are some risk factors common to both of these pathological categories:

  • Cirrhosis
  • Chronic infection with hepatitis B virus
  • Chronic infection with hepatitis C virus
  • Haemochromatosis
  • Chronic liver or biliary tract diseases
  • Chronic inflammatory bowel diseases
  • Obesity
  • Smoking
  • Environmental agents including exposure to aflatoxins, dioxin, nitrosamines, radon and asbestos
  • Metabolism disorders such as diabetes, high blood pressure, hypercholesterolemia
  • Genetic susceptibility (KRAS, INK4a, p53 and EGFR mutations)
  • Autoimmune diseases such as primary or congenital sclerosing cholangitis, deficiency of enzymes such as alpha-1-antitrypsin or tyrosine

Symptoms of primary tumours of the liver and the biliary tract

Both liver and biliary tract tumours, especially at their early stages, are completely asymptomatic. Specific symptoms occur as the disease progresses, and may include:

  • Upper abdominal pain; it may irradiate up to the back and shoulders
  • Swelling of the belly
  • Tiredness
  • Fever
  • Weight loss
  • Loss of appetite
  • Nausea
  • Vomiting
  • Feeling of satiety
  • Jaundice
  • Dark urine
  • Light-coloured stools

Diagnosis of primary tumours of the liver and the biliary tract

In case of suspected primary tumour of the liver or the biliary tract, the doctor should perform a physical examination including palpation of the abdomen, check for ascites, observation of skin and eye colour. Then, the doctor should take the patient’s medical history.

Afterwards, the doctor can request blood tests to check transaminases and bilirubin. In addition, the doctor can perform an evaluation of alpha-fetoprotein (AFP), a protein whose detection in adults can, in most cases, indicate the presence of a hepatocellular carcinoma.

The doctor can then prescribe a series of imaging tests including:

  • Abdominal ultrasound scan
  • Computed tomography (CT)
  • Magnetic resonance imaging (MRI)
  • Positron-emission tomography (PET)
  • Hepatic angiography and/or cholangiography
  • Echo-endoscopy

Finally, a liver biopsy is required to analyse the tissue suspected to be affected and to provide a final diagnosis.

Once the presence of a primary tumour of the liver or the biliary tract has been established, the stage of the tumour has to be determined in order evaluate the most suitable therapy to treat it. In this case, there are two different staging systems: the TNM system, which is more effective for predicting the prognosis of patients undergoing resection, and the BCLC system, which is more significant in the prognosis of patients not undergoing surgery.

The TNM staging system is based on the following parameters:

  • T: size or extent of the tumour 
  • N: degree of spread to lymph nodes
  • M: presence of metastases

Numbers from 0 to 4 are added after these letters to indicate an increasing severity.

The BCLC staging system is based on the following stages:

  • A: early
  • B: intermediate
  • C: advanced

Treatment of primary tumours of the liver and the biliary tract

The treatment of primary tumours of the liver and the biliary tract varies depending on a number of factors such as the patient’s general medical condition, the stage of the disease, the number of tumour masses present, where they are located, their size and if there any metastases. Therefore, the therapeutic treatment has to be always assessed by a multidisciplinary team.

The therapy of choice is usually surgery, although this approach cannot be often adopted due if the disease is diagnosed when it too advanced.

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