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Secondary Liver Cancer or Liver Metastasis

What is secondary liver cancer or liver metastasis?

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When cancer starts on a different part of the body and spreads to the liver, it is then called liver metastasis (or metastases in pleural) or secondary liver cancer. Where the cancer starts is called primary cancer. At some point in the natural history of primary cancer, cells can separate from the tumour and enter the lymphatic system or blood stream. If they survive the immune system, these cells can create colonies in other organs and parts of the body, forming secondary cancers or metastases. These metastases are made of cells similar to the primary cancer. For example, a metastasis in the liver from a primary colon cancer, is made of colon cancer cells.

The liver is a very common destination of secondary deposits. Secondary liver cancer (liver metastases) is much more common than primary liver cancer (cancer that starts in the liver). Someone can have one metastasis in the liver or multiple and it/they can be in any part of the liver.

The most common cancers that spread to the liver are: colorectal, lung, breast, pancreatic, stomach, oesophagus, ovarian, melanoma and neuroendocrine.

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What are the symptoms of liver metastases?

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Liver metastatic disease may not cause any symptoms at first, because the liver is large and can retain its function even if there is cancer in it. Symptoms may depend on the number and location of liver metastases in the liver. These symptoms may also be caused by other conditions rather than liver metastasis as well. These include:

  • Loss of appetite

  • unintentional loss of weight

  • fatigue

  • feeling of being sick (nausea)

  • Yellow skin or eyes (jaundice) and itchy skin

  • Discomfort or pain in the abdomen

  • Swelling of the abdomen due to accumulation of fluid (ascites)

  • Swelling of the ankles

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How are liver metastases diagnosed?

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The initial approach to diagnosing liver metastases is a medical history and clinical examination. Then the doctors usually order a series of blood tests, including a full blood count, liver function tests, kidney function tests and certain tumour markers that can aid in the diagnosis. However, the most important and accurate investigations for the diagnosis of liver metastases are the radiological imaging investigations. These include Ultrasound scan, CT scan, MRI scan and PET CT scan. Sometimes a biopsy may also be required to correctly identify the origin of the liver metastases (which organ the primary cancer is originating from).

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What is the treatment of liver metastases?

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For some type of cancers that spread to the liver, a curative treatment may still be possible. For other types of cancer, controlling the symptoms and trying to slow down the progress of the cancer and the liver metastases may be the only treatment option.

All cases of liver metastatic disease should be discussed in a multidisciplinary meeting (MDT). which is a meeting of cancer specialist doctors of various specialties, including surgery, radiology and oncology, as well as other healthcare professionals, such as specialist nurses, dieticians etc. The MDT goes through each case and suggests an individualised plan. This plan should take into consideration:

  • where the cancer started

  • how many metastases are and their location in the liver

  • the size of the metastases

  • the presence of any metastases in other parts of the body

  • cancer treatments already administered

  • how well the liver is working

  • patient fitness and wishes

Treatments that can be offered include surgery, chemotherapy, ablation, radiotherapy, hormone therapy, targeted therapy and immunotherapy. In general, the various treatments can control and slow the growth of or even shrink the liver metastases, however, most metastases don’t go away completely unless removed by surgery.

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When is surgery possible for liver metastases?

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Surgery is the treatment option with the higher chance for a cure for liver metastases, if it is used in the appropriately selected cases.

Surgical resection may be possible depending on oncological, technical, liver-related and patient-related factors.

Oncological factors include the type of the primary cancer and any previous treatments received, as well as the presence of any metastases in other parts of the body. Systemic disease stability and control is crucial for a positive outcome. In general, there are types of primary cancers that their liver metastases are treated well with an aggressive surgical approach, such as colorectal or ovarian cancers. On the contrary, current evidence suggests that this is not the case for other types of cancers, such as lung or pancreatic.

Technical factors include the size, number and location of the liver metastases in the liver and in relation to crucial liver structures, such as vessels and bile ducts. Assessment of each case by an experienced Liver Surgeon is very important for an appropriate surgical approach to be identified and planned. This may include a major liver resection or smaller resections or even combination of resection and ablation. In any case the primary goal is to treat all the liver tumours effectively by preserving as much liver as possible.

Liver-related factors refer to the size and function of the liver. In a liver with normal function and no previous problems, 70% or more of its volume can be removed with surgery without any problems. On the contrary, if a liver is not healthy or has been affected by lifestyle choices (diet, alcohol etc) or treatments, such as chemotherapy, the amount that can be removed may be much less. There are also cases that the liver is so much affected (example in cirrhosis), that a liver resection cannot be performed at all.

Finally, as liver resections are major operations, the patient’s fitness is very important. This should be assessed by a specialist anaesthetic and surgical team and various tests may be required, such as pulmonary function and cardiac function tests or an exercise stress test. Some patients may be deemed very high risk for an operation. In these cases, alternative treatments should be considered.

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What is the role of chemotherapy in treating liver metastases?

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Chemotherapy is the most common treatment offered for liver metastases. Chemotherapy can help slow the growth of cancer and relieve symptoms. Sometimes it can even shrink liver metastases and allow surgical removal. Chemotherapy may be also administered after surgery to reduce the risk of the cancer coming back (adjuvant chemotherapy).

There are 3 main ways to administer chemotherapy:

  1. systemic chemotherapy: the chemotherapy drugs are administered into the bloodstream via an intravenous infusion or orally as tablets. They circulate throughout the body and destroy cancer cells. The type of drugs and combinations depend on the primary cancer (where the cancer started).

  2. Hepatic arterial infusion (HAI): the chemotherapy is administered directly to the liver via a pump that is positioned surgically in the artery that brings blood supply to the liver (called the hepatic artery). HAI may be used to treat liver metastases when surgical resection is not possible and the cancer has not spread outside the liver. HAI is not used as often as systemic chemotherapy due to its complexity.

  3. Transarterial chemoembolisation (TACE): the chemotherapy is delivered directly to the liver metastases. This is achieved with interventional radiology. The doctors access a peripheral artery in the body with a catheter and a guidewire and find their way under x-ray guidance into the hepatic artery (the artery that brings blood supply to the liver). Then they advance the catheter into the small arteries that feed the tumours. They inject the chemotherapy drugs directly into them and use a special substance to block the tumour feeding vessels on their way out. With this way the chemotherapy is delivered directly into the tumour and additionally by blocking the small feeding arteries, the tumours are deprived of oxygen and nutrients that they need to grow. TACE can be used in cases when the primary cancer has only spread to the liver.

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What is the role of ablation in treating liver metastases?

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Ablation is the procedure that destroys liver metastases with heat, chemicals or electrical signals. It may be performed under sedation through the skin under ultrasound or x-ray guidance and then it is called percutaneous ablation. It can also be performed during an operation under general anaesthetic, either as an open or as a laparoscopic (keyhole) procedure. Ablation is usually used in small tumours (usually less than 3 cm in diameter) that cannot be removed with surgery or in patients that are not fit or willing to have an operation.  Sometimes, ablation can be combined with surgical resection in an effort to treat effectively as many liver metastases as possible.

The main type of ablation in the past was radiofrequency ablation (RFA). In RFA a probe is inserted in the liver metastasis under ultrasound or x-ray guidance and heat is used to destroy it. More recently, microwave ablation (which also delivers heat via a probe to the liver metastasis) has been shown to have superior results to RFA and this is now more commonly used. Irreversible electroporation (IRE) is another modern ablation method that utilises electrical impulses that create small holes in the cancer cells outline, resulting in their death. IRE is also delivered via a probe under imaging guidance and has the additional benefit of being less disruptive to normal tissues and structures that are located near the tumour.

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What is the role of radiotherapy in treating liver metastases?

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Radiotherapy works by destroying cancer cells. It can shrink a tumour and in some cases even completely destroy it. Radiotherapy can be used in combination with other treatments, such as surgery and chemotherapy. It may be used before surgery to shrink the tumour in order to facilitate resection or after surgery to destroy any remaining cancer cells and prevent the cancer from coming back. Radiotherapy can also be offered to tumours that are not possible to be removed with surgery as a palliative treatment to control their growth and symptoms and prolong life.

Radiotherapy can be delivered as:

  1. External radiotherapy or external beam radiotherapy: this is the most common type. A machine is used to produce a radiation beam which is then directed at the tumour. Stereotactic radiotherapy is a more modern way of delivering external radiotherapy. It involves delivering of the radiation beam from many different angles around the body. This means that a higher dose can be delivered to the tumour, with less effects to the normal tissues around it and therefore fewer side effects. Stereotactic body radiation therapy may be used when there are 1 to 3 small liver metastases.

  2. Radioembolisation or selective internal radiotherapy or brachytherapy:  with this method radioactive beads (that contain the radioactive Yttrium 90) are positioned directly into the tumour. This is achieved with interventional radiology. The doctors access a peripheral artery in the body with a catheter and a guidewire and find their way under x-ray guidance to the hepatic artery (the artery that brings blood supply to the liver). Then they advance the catheter into the small arteries that feed the tumours. They inject the radioactive beads directly to them and use a special substance to block the tumour feeding vessels on their way out. The beads deliver the radiation directly to the tumour with minimal effects to the healthy tissues around it. Additionally, by blocking the small feeding arteries, the tumours are deprived of oxygen and nutrients that they need to grow.

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What is the role of targeted therapy in treating liver metastases?

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Targeted therapy drugs identify and attach to specific cancer cell receptors. These are substances in the surface or inside the cancer cells, such as specific proteins. By attaching on these receptors the drugs disrupt the signals that promote cancer cell survival and growth. Targeted cancer therapy is used usually in combination with chemotherapy and options depend on the primary cancer (where the cancer started). Target therapy drugs include tyrosine kinase inhibitors (that block signalling required for cancer cells growth), apoptosis-inducing agents (that promote cancer cell death), angiogenesis inhibitors (that block formation of blood vessels needed for tumour growth) and others.

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What is the role of immunotherapy in treating liver metastases?

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Immunotherapy, also called biological therapy, biotherapy or biological response modifying therapy (BRM therapy), is a set of treatment techniques that boost the body’s natural defences to fight cancer. Some immunotherapy treatments boost the immune system overall, while others try to teach it to attack specific types of cells found in tumours. Treatments may include the administration of vaccines, tablets or monoclonal antibodies (these are a type of protein that can attach to cancer cells in the body).

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What is the role of hormone therapy in treating liver metastases?

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Hormones are produced by certain organs (glands) in the body, travel through the bloodstream and control how some cells and organs function and grow. Glands in the human body that produce hormones include the adrenals, pituitary, ovaries, testicles and pancreas.

Hormone therapy is the treatment that adds, blocks or removes certain hormones that are necessary for cancer cells to grow. This can be achieved by removing a gland with surgery or using high dose radiation to destroy it, so it will not produce hormones. It can also be achieved by the administration of certain drugs that interfere with the production of hormones or work against certain hormones or their effects.

Hormone therapy may be used in combination with other treatments, such as surgery, chemotherapy and radiotherapy.

 

Are there any clinical trials for liver metastases?

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Clinical trials are medical research studies that are trying to find better or new treatments for liver metastases. There are pros and cons to taking part in a trial. For example, a trial may be an opportunity to receive a new treatment, however, there is no guarantee that every patient will receive it. Interested patients should speak to their cancer specialist about the existing trials and whether any of these are an option. Useful information, including an online tool to identify potential clinical trials, can be found on the Pancreatic Cancer UK website.

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