Interventional oncology in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC)

Hepatocellular carcinoma is the most frequent primary liver tumor. It originates from hepatocytes, the liver's own cells. It is one of the most common types of cancer in the world. The most important cause is chronic liver disease (cirrhosis) due to hepatitis B and C infections. This is especially true for the Middle East, Africa and Asian countries. In Europe and the US, the most common cause of HCC is chronic cirrhosis due to chronic alcohol consumption because of wide-spread vaccination against Hepatitis B and C.

How is it diagnosed?

HCC may lead to symptoms such as abdominal pain, loss of appetite, anemia, nausea, fatigue and jaundice in some patients, and diagnosis is made while investigating these problems. In some patients, there are no complaints and HCC is detected incidentally on liver ultrasound, CT or MRI performed for unrelated reasons. In HCC patients, blood tests usually show a decrease in blood values and prolonged bleeding time. The most typical finding is the elevation of a substance called alpha fetoprotein (AFP) in the blood. Although this is not present in all patients, AFP elevation in a patient with cirrhosis indicates the presence of HCC.

HCC can be seen on ultrasound, CT or MRI films. On CT and MRI, HCC typically keeps the intravenous contrast media quickly and strongly and then releases it early and rapidly (washout). This finding is so important that if it is seen in a patient with known cirrhosis, diagnosis of HCC can be securely made without need for a needle biopsy. Another typical appearance is on CT and MRI is the coexistence of a suspicious mass and the thrombus (clot) of the main vein of the liver (portal vein). However, in many patients, imaging findings are not typical and needle biopsy is required for diagnosis. Biopsy should be performed by using ultrasound guided trucut (core) biopsy method.

How is it treated?

Classical treatment methods in HCC are surgery and chemotherapy. Surgical operation can be done by removing the part of the liver where tumor is located (resection) or liver transplantation. Resection is preferred if the patient does not have or early stage cirrhosis. If the patient has advanced cirrhosis, transplantation is attempted to treat both cirrhosis and cancer. Chemotherapy is not an effective treatment for HCC, but it has been shown in recent years that a drug called "Sorafenib" which prevents the vascularization of the tumor may prolong survival in patients with advanced HCC.

HCC is one of the most common types of cancer in which minimally invasive treatments are commonly and successfully used. This is due to the fact that the liver is a large organ, making it suitable for percutaneous ablation, and the normal liver tissue and cancerous tissue are fed separately, making it suitable for transarterial treatments. The minimally invasive therapies applied in HCC are divided into two groups: 1. Percutaneous ablation, 2. Transarterial treatments. Percutaneous ablation is the destruction of tumor tissue by introducing specific needles under the guidance of ultrasound and CT. Percutaneous ablation methods are widely used, but radiofrequency, microwave and alcohol ablation are the most commonly used ones for HCC. Radiofrequency and microwave are "thermal" ablation methods that kill tumor tissue by heating up to 80-120 degrees, and in HCC they are more preferred. Alcohol ablation is a "chemical" ablation method that has been used more frequently in the past and is still very useful in cases where thermal ablation cannot be applied or inadequate. No matter what method is applied, percutaneous ablation is intended to destroy the tumor with a layer of normal tissue around it. If this can be done, percutaneous ablation is as successful as surgical treatment in terms of oncologic outcomes. TFor this reason, in the treatment guidelines for HCC, percutaneous ablation is considered a (curative) method that can treat patients permanently, such as surgical resection and transplantation.

Another minimally invasive treatment group in HCC is transarterial treatments. Chemoembolization (TACE) and radioembolization (TARE) are the most common transarterial therapies for HCC. The purpose of chemoembolization is to give some chemotherapy drugs (such as doxorubucin, mitomycin) that are effective on HCC into the tumor directly via the feeding arteries after loading them into particles or a drug called lipiodol. In this way, both tumor arteries are blocked and blood is prevented from going into the tumor (embolization), and chemotherapy drugs are released into the tumor in high concentrations for weeks. Thus, by combining embolization + intraarterial chemotherapy, tumor tissue is destroyed. Chemoembolization is an effective method that has been increasingly used in HCC for decades and is included in the classical treatment guidelines. It has been shown to significantly increase survival in HCC patients.

In radioembolization, small particles that are loaded with radioactive particles called Yttrium 90 are given into the feeding artries of HCC. In this way, the tumor is exposed to a radiation dose 4-5 times higher than that of conventional radiotherapy. In addition, these particles are only given to the region where the tumor is located. Radioembolization is a more recent method than chemoembolization for HCC. Unlike chemoembolization, radioembolization can be safely applied in HCC patients with portal vein thrombosis (clotting). However, since chemoembolization and radioembolization have different mechanisms of action, it may be better to apply both treatment modalities in many patients at different times.

In general, percutaneous ablation is considered to be a permanent (curative) treatment such as surgery, and transarterial treatments are considered as palliative. However, chemoembolization may also be curative in some patients. In addition, in some patients, applying both treatment methods in succession or at the same time may give more successful results. In general, if the tumors are small in size and number, percutaneous ablation is applied, and if tumors are multiple and large, transarterial therapies such as chemoembolization and radioembolization are preferred.

Which patient should be treated?

Some treatment guidelines indicate which treatment modalities are more appropriate in HCC. Among these, the most widely accepted is BCLC (Barcelona Clinic Liver Cancer) or Barcelona Criteria. In BCLC, the HCC was divided into 5 stages according to the patient's clinical status, liver function, number and size of the tumors; namely very early, early, middle, advanced and terminal stages. In very early and early stages, approximately 30% of patients should can be treated with "curative" tools such as surgical resection, transplantation and percutaneous ablation. In the middle and advanced stages, which constitute approximately 50% of the patients with HCC, curative treatments are generally not possible. In these stages, transarterial therapies such as chemoembolization and radioembolization are applied if the patient is eligible, and chemotherapy (sorafenib) is given if the patient does not comply with these treatments. In the last stage (terminal) patients, which constitute 20% of the patients, all these treatments have more harm than benefits. In this stage patients, only supportive treatments should be applied to strengthen the body and relieve the patient's complaints.

In patients with HCC, one of the conditions required for surgical resection of the tumor is that the remaining liver volume is sufficient after surgery. However, because of the size and extent of the tumor in most patients, the liver tissue to be left in the body is smaller than desired. In such patients, some interventional procedures can be performed before surgery, and intact liver tissue can be enlarged, making subsequent surgical resection possible. There are two procedures for this purpose; 1. Portal vein embolization, 2. Radioembolization. In portal vein embolization, the portal vein of the liver lobe where HCC is located are blocked by using some materials such as particles, adhesive, coils and alcohol. While the liver lobe harbouring HCC shrinks in 1-2 months, the intact liver lobe grows as a reaction. After the healthy lobe reaches the desired size, surgery can be done and the liver lobe containing the HCC can be removed safely.

In radioembolization, a high dose of radiation is given via the hepatic artery into the liver lobe containing the tumors. This radiation reduces both the tumors and the liver lobe in size. When the radiation dose is increased too much, this shrinkage may also be advanced (radiation lobectomy). When the diseased lobe is contracted, the healthy liver lobe grows as a reaction and can reach enough volume following resection within 1-2 months. The advantage of radioembolization is that it not only makes the diseased lobe smaller, allowing the intact liver lobe to grow, but also treats the HCC by giving a high dose radiation. However, growth induction effect is less strong and requires a longer time than portal vein embolization. In some patients, both methods can be used consecutively to ensure maximum effect.

Although some HCC patients are eligible for transplantation, they are included in the waiting list because of the insufficient number of donors. The waiting period can be quite long, and if no treatment is applied during this period, the tumors may grow and the patient may become ineligible for transplantation. To prevent this, patients in the waiting list should be treated with percutaneous ablation, chemoembolization and radioembolization, and in this way, the patient may gain time and keep the possibility of liver transplantation.