Liver metastases

Metastatic tumors in liver are approximately 20 times more common than primary tumors. The most important reason for this is that the liver, in contrast to the other organs, receives intense blood from two separate vessels (both the hepatic artery and the portal vein). Because of this intense blood supply, the organs of the digestive tract, especially the stomach, intestine and pancreas, often metastasize to the liver. These tumors account for about 50% of all liver metastases. Besides, breast, ovarian, lung and kidney cancers are among the types of cancer that frequently metastasize to the liver.

How are they diagnosed?

Liver metastases are usually detected when investigating the cause of symptoms such as abdominal pain, jaundice, fatigue, and impaired liver function tests, and sometimes just by coincidence, during an ultrasound, CT, MRI or PET-CT, performed for unrelated reasons. In some patients, a cancer has already been diagnosed and treated elsewhere in the body, and liver metastases may develop later (metachronous metastases). In some patients, metastases are also seen in the liver when the primary tumor is detected (synchronous metastases). Or rarely, there are metastases in the liver but the primary tumor can not be seen on imaging (liver metastases with unknown primary).

When the masses suggesting metastases are seen in the liver on imaging methods, a trucut needle biopsy should be made to diagnose both metastases and determine the origin (primary tumor). In most patients, the liver biopsy can make both diagnoses. However, in some cases, it may be necessary to perform a biopsy from the mass which is thought to be the primary tumor.

How are they treated?

The classical treatment of cancer with distant metastasis is chemotherapy. This also applies to liver metastases. In many patients, however, chemotherapy cannot control the metastases in the liver alone, and some additional treatment modalities should be used in these patients. In some liver metastases, the liver lobe can be removed by surgical operation (resection). With this method, survival has been shown to be prolonged, but surgical resection is possible in only 15% of patients with liver metastases. This may be because the general condition of the patient is not suitable for operation, the metastases are too many or extensive. Sometimes, the metastases are located in a single lobe but the other liver lobe will be insufficient (too small) for the patient after resection. In this case, the small lobe may be induced to grow by some treatments to the diseased lobe such as portal vein embolization or radioembolization (radiation lobectomy). In this way, some of the patients who cannot be operated may become eligible for surgical resection.

The liver is an ideal organ for the application of minimally invasive treatments in many respects. First of all, it is suitable for percutaneous ablation methods such as radiofrequency and microwave owing to its large size. In addition, since the vessels feeding the tumors and the vessels supplying normal liver tissue are different, arterial (transarterial) treatments such as chemoembolization and radioembolization can be performed more easily and safely. In general, percutaneous ablation is performed if the metastases are small (less than 3 cm) in diameter, few (less than 5 in number) and they can be seen on ultrasound or CT easily. If the metastases are large and numerous, transarterial therapies are preferred to ablation.

The classical ablation method is radiofrequency. Radiofrequency is a well-known ablation method that has proven to be safe and effective in liver metastases. In radiofrequency, ablation is slower but controlled and safe, with less chance of damage to non-tumor tissues. The efficacy in tumors close to large vessels is slightly less.

Microwave ablation is an ablation method that has been increasing in popularity all over the world and is frequently used in liver in recent years. In microwave, ablation is more rapid and more effective in tumors close to large vessels. However, it is necessary to be more careful about the complications because heat formation is rapid.

Cryoablation is a valuable ablation method commonly used in prostate, kidney, lung and soft tissue tumors. However, the efficiency in the liver is less and the cost is higher. Therefore, it is not routinely used in liver metastases. However, it is sometimes preferable in large tumors and in those located adjacent to critical structures such as bile ducts and liver capsule.

Nanoknife ablation is an ablation method which has been popular in recent years. The difference from other ablation methods is that it can kill the tumor without damaging the structures such as bile ducts, nerves and gastrointestinal organs. Therefore, it may be used in tumors adjacent to such organs and tissues, for example in pancreatic and prostate cancer. It may also be preferred in the liver, especially in hilar cholangiocarcinoma, and in metastases adjacent to the main bile ducts with main vessels. However, it is an expensive method to be performed under general anesthesia and there is not enough literature evidence supporting its widespread use.

Transarterial therapies are preferred if there are large or multiple liver metastases that are not suitable for percutaneous ablation. The simplest of these therapies is to give the chemotherapy drug directly into the arteries feeding the tumors, which is called intraarterial chemotherapy. In this method, the effect of chemotherapy on tumors is increased and the systemic side effects of the drug are reduced.

A transarterial treatment that is frequently used in liver metastases is chemoembolization (TACE). In chemoembolization, the chemotherapy drug is administered either by mixing with a substance called lipiodol, which is accumulated in the tumor tissue, or by pre-loading the chemotherapy drug into the specially produced small obstructive particles. In this method, the feeding vessels are obstructed and high-intensity chemotherapy drug is released from the lipiodol or occlusive particles for several days. This method, which was first applied in hepatocellular cancer in the 2000s, has been also used in cholangiocarcinoma and liver metastases of colon cancer since 2010 and successful results have been obtained. It has been shown that chemoembolization can increase survival by twice when it is applied together with classical chemotherapy in liver metastases of colon cancer.

Another minimally invasive treatment for liver metastases is radioembolization (TARE or Y90). In fact, radioembolization is a kind of radiotherapy "performed intraarterially". Because liver is a highly sensitive organ to radiotherapy, normal liver tissue may be damaged during classical external radiotherapy and as a result, liver failure may develop. Therefore, in classical radiotherapy, high radiation doses that are necessary to kill tumors in the liver cannot be reached. In radioembolization, a radioactive isotope called Yittrium 90 is loaded into very small glass or resin particles and these particles are injected directly into the hepatic artery branches which feed the tumors in the liver. As a result, a radiation dose that is 4-5 times higher than classical radiotherapy can be given to metastases. In this way, a very high dose of radiotherapy is applied to the tumors, and the intact liver areas are protected from radiation. Radioembolization is a useful treatment modality for liver metastases in both liver metastases and primary liver tumors such as hepatocellular carcinoma and cholangiocarcinoma. It is most commonly used in colon cancer metastases, but has been also used successfully in breast, ovarian, lung and gastric cancer metastases.

Another minimally invasive treatment that has been introduced in liver metastases in recent years is chemosaturation (isolated liver perfusion). In this method, the arteries and veins of the liver are isolated from the systemic blood circulation using various catheters and balloons during angiography. A chemotherapy drug called Melfalan is then administered at a very high dose into the liver artery and tumors are treated. The melfalan in the veins of the liver is then filtered through special filters and re-injected into the neck vein. In this way, the liver is exposed to a very high dose of Melfalan without any drug leakage into the systemic circulation. With this method, especially in the liver metastases of an eye cancer called "Uveal malign melanoma", significant success has been achieved and it is still considered to be the most effective treatment in these patients. The method is also tried in other types of metastases.