Liver cancer is the second most common cause of death from cancer worldwide.
Every year this disease kills about 746,000 people in the world, and 782,000 new cases are diagnosed. The ratio of mortality to incidence is 0.95. This factor makes the liver cancer one of the most feared diseases in the world. Only 4.6% of the diseased survive.
Cancerous liver damage can be primary, i.e. originating from cells of hepatic structures, and secondary - proliferation in the liver of secondary metastatic tumor sites of cancer cells that came to the liver from other viscera. Metastatic tumors of the liver are recorded 20 times more often than primary, because the liver is the filter through the blood running from the internal organs passes.
Causes of liver cancer:
Gender. Men are more likely to develop liver cancer than women.
Hepatitis B or C are important risk factors for liver cancer. There are also some hereditary diseases that increase the risk of developing liver cancer.
Cirrhosis is a result of the formation of scar tissue in the liver that often leads to cancer. The most common causes of cirrhosis are alcohol and hepatitis B and C.
Tobacco use. There is a relationship between smoking and the development of liver cancer, the risk increases with simultaneous use of alcohol.
Aflatoxins. High liver cancer risk is associated with consumption of the products affected by aflatoxin B1 (mitotoxin of Аspergilis flavus fungus) as a result of improper storage (peanuts, wheat, soybeans, corn, rice, etc.).
Anabolic steroid. Male hormones are used by some athletes. Long-term use of anabolic hormones may slightly increase the risk of developing liver cancer.
Arsenic. In some parts of the world consumption of water contaminated with arsenic increases the risk of liver cancer.
Symptoms of liver cancer
- Weight loss for no apparent reason
- Prolonged lack of appetite
- Feeling of fullness when receiving a small amount of food
- Increasing size of the liver, or identification of tumor in the liver
- Prolonged pain in the abdomen
- Yellowish-green color of the skin and eyes (jaundice)
- Strengthening of weakness in the presence of hepatitis or cirrhosis
Methods of diagnosis of liver cancer
Ultrasonography (US) can detect a tumor and in some cases, its type.
Computed tomography (CT) is very effective in the diagnosis of hepatic tumors. In some cases, to improve the image of the liver, a contrast agent is administered intravenously.
Magnetic resonance imaging (MRI) allows not only detecting a tumor in the liver, but also sometimes makes it possible to distinguish malignant tumors from benign.
Angiography. A contrast agent is administered into the artery that can detect blood vessels supplying the liver tumor, and decide on the scope of surgery.
Laparoscopy. Through a small incision in the abdomen a special device is introduced that allows inspecting the liver and other organs, as well as make a biopsy (take a piece of tumor tissue for examination).
Biopsy. At suspicion on liver cancer only a biopsy of the tumor makes it possible to make a definitive diagnose.
Blood tests. Determination of alpha-fetoprotein (AFP) in blood is useful both at the stage of liver tumors diagnostic and after the treatment to judge the efficacy and possible relapse.
Treatment of liver cancer
Methods of brachytherapy with radionuclide 90Y microspheres.
Method of brachytherapy (interstitial radiation therapy) is based on the introduction of a suspension of microspheres containing radionuclide 90Y, by means of a catheter through an artery under X-ray control into the liver tissue. Yttrium-90 (90Y) is a pure beta emitter, produced by neutron bombardment of yttrium-89. The average path of beta particles in tissues is 2.5 mm, and the maximum path is less than 1 cm. 1 GBq 90Y dose in the source location provides the absorbed dose of 50 Gy. 94% of the absorbed dose is received by the tumor nidus within the first 11 days.
Empirical calculation of the introduced activity is carried out using two different methods: the base one and the body area method (according to the instructions for use).
Control of introduced activity
Yttrium-90 activity is determined by radiometry at the dose calibration device. It is necessary to monitor that all the required activity is taken from the transport vial. Calculation of the introduced activity is necessary to carry out with an adjustment for the radioactive decay from the date of manufacture of the introduced activity until its implantation into a patient.
All handling and treatment of radioactive microspheres should be carried out by specially trained personnel. Working with the microspheres is carried out under sterile conditions in compliance with the standard radiation protection measures and the use of special equipment.
Preparing for implantation
Before the procedure it is necessary to determine the function of the liver and kidneys, which is done by evaluating the serum bilirubin and creatinine. Also qualitative and quantitative studies with cancer markers specific to the target tumor are conducted. Increased serum bilirubin above 20 mg/l is considered a relative contraindication to 90Y microsphere treatment. In the presence of nephatony it is necessary to minimize or eliminate the use of contrast media based on iodine.
Dosimetry planning is based on CT and (or) MRI data, to assess the volume of the liver and tumor lesions, the state of the portal vein and the possible extrahepatic spread of the process. A three-phase CT for visualizing the volume ratios and evaluation of interposition of normal parenchyma and tumor tissue is conducted. Also the information on the structure of the portal vein and aberrant arterial vessels is assessed. The prevalence of the disease is usually characterized as unilobar or bilobar decease, however, to assess the liver angioarchitectonics, arteriography is of greater value than CT. Ascites identified by CT indicates poor liver reserve ability or metastases in the peritoneum, the two states are signs of poor prognosis of the disease.
For the preoperative assessment of vascular architectonics of the liver and the effectiveness of the procedure arteriography of the superior mesenteric, celiac and hepatic branches is performed. The objective is to ensure that the microspheres reach the goal. The study involves identifying the location of the arteries, as well as the need of embolization of the gastro-duodenal artery, right gastric artery or any other additional artery to prevent the microspheres from getting into the blood supply in the gastrointestinal tract.
The presence of altered vascular anatomy can greatly affect the surgery plan. Achieving good results of treatment with 90Y microspheres is prevented by stenosis or slow blood flow in the hepatic artery, which can cause vascular embolization and reflux in extrahepatic collaterals.
Complications associated with hepatic and pulmonary and hepatic gastroduodenal bypass can be avoided if preoperative scintigraphy is conducted with albumin microaggregates - 99mTc-MAA (5 - 6 mCi) pre-inserted into the renal artery to assess the possible ways of distribution of 90Y microspheres.
MAA are albumin microaggregates having a particle size of 20-40 nm. Technetium 99mTc labeled MAA allow simulating distribution of microspheres introduced into the hepatic artery, and evaluating the presence and degree of blood bypass, as well as the ratio of the blood supply of the tumor itself and the surrounding parenchyma, which is important when calculating the dose.
The degree of bypass is expressed as a percentage and can be calculated by calculating the ratio of the accumulated activity of the radiopharmaceutical in the lung to that in the liver. If the degree of hepato-pulmonary bypass exceeds 20% of the introduced activity, or if there is a risk that due to bypass the lung dose exceeds 30 Gy, the patient should not undergo the implantation of 90Y microspheres. An exclusion criterion is also an increase in the blood flow to the gastrointestinal tract, which cannot be managed either by embolization or moving the catheter.
Implantation is performed under continuous X-ray control in the X-ray operation room. When choosing a catheter for administration of the microspheres it is necessary to be guided by the following principles: the internal diameter of the catheter should not be less than 0.5 mm. The increased resistance to fluid current due to low catheter lumen can cause stasis of the microspheres in the infusion system and, consequently, underexposure of the tumor to the radiation. Since microspheres delivery to the tumor lesions depends on the blood flow, the catheter must not obstruct the lumen of the vessel in which the microspheres are introduced. Before use the entire infusion system is filled with saline to expel air bubbles. The volume of each infusion is 20 cm3 (1 syringe) under pressure of 70-100 kPa. It is recommended that at least 3 infusions (60cm3) are carried out, the introduction pressure should not exceed 200 kPa. To minimize the potentially high radiation exposure to the hands of medical personnel, it is recommended to use forceps to move parts of the system at the end of infusion. Percentage of actually introduced 90Y activity is calculated as the difference between the measured activity of the vial with the microspheres prior to implantation and the activity of radioactive waste collected after the procedure.
During the infusion all the contents of the vial with the microspheres is administered to the patient. The patient is transferred to a regular room, as the 90Y activity introduced in the body does not pose radiation hazards to others, including to other patients in the same room. Antibiotics are prescribed. In the absence of complications the patient may be discharged under outpatient observation.
Selection of patients for brachytherapy with 90Y microspheres.
Neoadjuvant or independent brachytherapy in case of:
- Unresectable liver cancer,
- Unresectable metastatic liver tumors at other sites.
- inability of the hepatic artery catheterization (patients with vascular abnormalities, portal vein thrombosis or hemorrhagic disease),
- severe liver or respiratory failure,
- hepatic and pulmonary and gastrointestinal and hepatic shunts, the presence of which, after administration of the drug causes serious or even fatal complications, such as radial pneumonia and numerous gastrointestinal ulcers. However, these complications can be avoided if preoperative scintigraphy with 99mTc-MAA, administered into the hepatic artery and allowing assessing possible ways of distribution of 90Y microsphere, is conducted.
Hepatopneumonic bypass surgery
Pathological arteriovenous communications are developed in peritumoral tissues. The microspheres administered into the hepatic artery, pass the tumor tissue through these shunts and though hepatic veins enter the heart and then the lungs where the embolism of the smallest pulmonary arterioles takes place. With an increase in the caliber of the shunt the amount of the radioactive drug entering the lungs also increases, causing clinically manifested radial pneumonitis. Lung radiation dose less than 30 Gy causes no complications, and the bypass level can be easily estimated from the results of the preliminary scintigraphy.
Hepato-gastrointestinal bypass surgery
Part of small, even nameless arteries that supply blood to the digestive tract, come from the hepatic artery, and this is within the norm. This is most common with gastroduodenal and right gastric artery. During the injection microspheres may accidentally get into these vessels, causing embolization of small arteries of the gastrointestinal tract in the submucosal layer of the stomach and intestines. There is a combination of the effects of ischemia and radiation exposure, leading to ulceration, and often medical correction of this process is impossible. During preliminary scintigraphy with 99mTc-MAA these arterioles are preventively embolized, thus limiting the possibility of extrahepatic spread of the drug, and once again confirming the need for this procedure in the preoperative period.