According to the World Health Organization (WHO), at least 550,000 people die of liver cancer each year, and 75% of these people (about 400,000) are from Southeast Asian and Pacific Rim countries. Approximately 80% of liver cancer patients are transformed by chronic hepatitis B, most of whom were infected with the hepatitis B virus at birth and in early childhood, and the rest develop chronic hepatitis C.
Treatment of liver cancer is more challenging than other cancers because, in addition to the cancer, many patients’ livers have been damaged by chronic hepatitis, resulting in cirrhosis and varying degrees of liver failure. Failure to take into account the patient’s unstable liver condition when treating liver cancer may hasten the patient’s death. Many patients die from liver failure due to poor liver function. When treating patients, it is important to weigh the pros and cons of different treatments and the dangers of liver failure, and to consider how it will improve the patient’s quality of life.
Although surgical resection is the treatment of choice in the treatment of liver cancer, the key to satisfactory outcome is early diagnosis. Historically, it is difficult to detect liver cancer at early stage, and once detected, it is mostly in middle or late stage. According to the statistics, the surgical resection rate is 5%-25%, and the survival rate is only 30% in 1 year after surgery, and the quality of survival is poor. Interventional treatment mainly based on hepatic artery chemoembolization (TACE) has achieved definite efficacy and is considered as the preferred method in non-surgical treatment of hepatocellular carcinoma, and has become an effective measure before second-stage surgery. In addition, with the emergence of microcatheter super-selective cannulation technology, local interventional treatment of tumor can be performed without basically damaging normal liver tissues, which is of great clinical significance for patients with combined cirrhosis and poor liver function reserve.
Interventional treatment of hepatocellular carcinoma is a method of inserting specially designed puncture needles and catheters into the tumor area of liver for diagnosis and treatment under the guidance of DSA machine. It has gained more clinical experience and therefore developed rapidly, and now it has become an effective means of treatment for liver cancer.
Interventional treatment for hepatocellular carcinoma is feasible for the following patients.
(1) Primary or metastatic liver cancer that is considered inoperable for various reasons, or small liver cancer that the patient does not want to have surgery.
(2) As a preparation before surgery, interventional treatment can shrink liver cancer and make surgery easy to remove, in addition to reduce tumor spread and recurrence after intervention.
(3) Patients with incomplete resection of hepatocellular carcinoma, postoperative recurrence or failure of other methods of treatment.
(4)Rupture and bleeding of liver cancer lesion.
(5) Prophylactic intervention after resection of hepatocellular carcinoma.
(6) No serious impairment of liver or kidney function.
(7) Patients without severe jaundice and ascites.
(8) Patients with good general condition and no serious bleeding disorders.
The effectiveness of interventional therapy is determined by the characteristics of blood supply of hepatocellular carcinoma. Normally, the liver is supplied with blood by hepatic artery and portal vein, of which portal vein supply accounts for 75% to 80% and hepatic artery supply accounts for 20% to 25%. The blood supply of hepatocellular carcinoma is exactly the opposite, with more than 90% to 95% of the blood supply from hepatic artery and very little blood supply from portal vein. This brings convenience to the treatment. Through hepatic artery cannulation, drugs can directly enter liver cancer tissues to increase the local drug concentration and kill cancer cells. In addition, some embolic substances such as iodine oil and gelatin sponge are applied to embolize the blood supply artery of liver cancer to cut off its nutritional effect, and the tumor tissue will be necrosed, thus achieving the purpose of treatment.
In the past 20 years, interventional scholars at home and abroad have done a lot of work and achieved promising results in the interventional treatment of liver cancer, and explored many effective interventional treatment methods. They are broadly divided into two categories: percutaneous transvascular treatment techniques and percutaneous non-vascular treatment techniques.
I. Percutaneous transvascular treatment techniques
TAE was developed on the basis of super-selective hepatic arteriography, and the clinical application of this method was first reported by Goldstein in 1976. In China, Professor Lin Gui of Shanghai Zhongshan Hospital first reported the clinical application of using TAE for HCC in 1983. Later, with the development and application of various embolic agents, TAE has been increasingly used clinically for palliative treatment of inoperable or postoperative recurrent hepatocellular carcinoma cases, and has even become an optional method alongside with surgical resection. In recent years, based on the technology of TAE, many new embolization methods have been carried out and promoted clinically with good therapeutic effects, such as: combined hepatic artery-portal vein embolization (TAPVE), hepatic subsegmental embolization (THSAE), etc.
2, combined hepatic artery-portal vein embolization (TAPVE) TAE is performed simultaneously with percutaneous portal vein puncture to embolize the portal branch of the segment where the tumor is located, and this technique is often monitored by real-time television fluoroscopy. The rate of necrosis was higher than that of the TAE group.
In the study of Wallace, iodine oil mixed with anhydrous ethanol in a certain ratio could also be used to embolize the portal vein. The same purpose can be achieved. Coaxial catheterization, drug-assisted methods (e.g., vasoconstrictors), or direct superselective catheter insertion are often used. It is indicated in cases where the tumor is located in a single or a few hepatic segments or subsegments, with or without subfoci, or in patients who are not suitable for conventional hepatic artery embolization due to severe abnormal liver function.
4 .Temporary blockade of hepatic vein followed by hepatic artery chemoembolization (TAE-THVO) is indicated for limited hepatic lobar and segmental tumors and those with arteriovenous fistula. The arteriogram under the blocked hepatic vein was found to have an increase in the number of arteries in the picture by Kim Saw-right and others. This method can avoid the embolic agent into the body circulation and make TAE treatment feasible for patients with arteriovenous fistula, while increasing the concentration of local chemotherapeutic agents and playing the role of TAPVE.
5.sandwich therapy is to embolize the distal segment of the hepatic artery with iodine oil, infuse chemotherapeutic drugs, and then embolize the proximal segment of the artery. Clinical studies have shown that this method can cause complete necrosis of small tumors and a significant decrease in AFP.
6.Multiple arterial perfusion embolization Hepatocellular carcinoma often has parasitic artery or vagus artery, embolization of these side branches while embolizing hepatic artery can greatly improve the efficacy.
7.Permanent hepatic artery embolization Studies have shown that the internal diameter of arteries embolized by different embolic agents varies. The artery embolized by gelatin sponge particles is in the middle artery of 1200-1500μm; while microspheres and alcohol can enter the micro-artery of about 100μm in diameter and are not absorbed, some scholars call the embolization performed by such embolic agents permanent hepatic artery embolization.
8, hepatic arterial infusion (transcatheter arterialinfusion, TAI) TAI technique was applied in the clinic before TAE. However, TAI alone has poor effect on the treatment of hepatocellular carcinoma, and is rarely used alone in clinical application. Some scholars use balloon to block the blood flow for intra-arterial drug perfusion, which can increase the drug concentration in the tumor area (30 times), and the drug stays for a long time, and the effect is better than general perfusion. Yang Jijin et al. achieved better efficacy by heating and reperfusion of chemotherapeutic drugs for the treatment of hepatocellular carcinoma in rats. Some scholars have also used arterial pressure boosting method to perfuse chemotherapeutic drugs by taking advantage of the poor response of tumor arteries to vasoactive substances.
9.implantable port system The implantation of catheter and perfusion pump can be done by surgical opening or via femoral or subclavian artery, and Pentecost suggested that the establishment of the catheter system could allow high local drug concentration in the liver. Shan Hong et al. applied this method to treat metastatic hepatocellular carcinoma and found that those with liver metastases from gastrointestinal cancer had better outcomes, with a median survival of 17.6 months and 1 and 2 year survival rates of 68.4% and 39.5%, respectively.
10.Intra-arterial embolization combined with internal radiation therapy This method can not only embolize and block the blood supply of tumor more thoroughly, but also implement radiation killing effect in tumor tissues with high concentration and uniform distribution of internal radiation source, which has low local radiation reaction. The 90Y glass microspheres and 32P glass microspheres made in China have been used in clinical practice and have achieved satisfactory efficacy. In addition, in order to block the parasitic blood vessels of hepatocellular carcinoma, Iwamoto used silicone rubber film implanted on the surface of liver, and then performed TAE and portal perfusion treatment, which prolonged the survival of patients, and some people called this method as isolation therapy.
II. Percutaneous non-vascular treatment techniques
1.Chemotherapy
(1) Percutaneous ethanol injection therapy (PEI) In 1983, Sugiura et al. successfully treated experimental liver cancer foci in mice by injecting anhydrous ethanol, and after Livraghi reported the clinical application of anhydrous ethanol for small liver cancer in 1983, this method was gradually promoted. Clinical studies of such cases were also reported by Liu Limin et al. in China. In addition, some scholars have shown that anhydrous ethanol injection at 60℃～70℃ can induce tumor necrosis, which is called HOT PEI. the ideal indication for PEI is tumor diameter ≤75px and no more than 3 nodules. Its main disadvantages are that it requires multiple punctures, multiple sessions and multiple amounts of anhydrous ethanol, and it cannot kill tumors that cannot be detected by current imaging, and it is not ideal for blood-rich and giant hepatocellular carcinoma.
(2) Percutaneous acetic acidinjection therapy (PAI) is similar to PEI in terms of puncture technique, treatment method and mechanism of action, but the dose and number of treatments used are significantly reduced. Zhuang Zhenwu used 50% acetic acid and anhydrous ethanol to treat Walkar-256 rat liver cancer, and the quantitative analysis of tumor necrosis was 90%-100% and 64%-90%, suggesting that 50% acetic acid can replace anhydrous ethanol to achieve better efficacy.
(3) direct injectionchemotherapy (DICT) Some scholars advocate adding ultrasound-guided DICT after TAI/TAE, and believe that its survival rate is higher than that of single treatment, but there is no large group of cases reported.
2.Physical treatment
(1) Percutaneous hot water or saline injection therapy (PHOT or PSIT) In 1993, Ohishi used hot water and in 1994, Honda used hot saline to treat hepatocellular carcinoma with satisfactory tumor necrosis results and no significant toxic side effects. or PSIT is roughly the same operation technique as PEI. The main principle is that high temperature directly causes protein coagulation and kills tumor cells, which can be safely used for the treatment of liver cancer with larger diameter.
(2) Percutaneous laser-induced thermotherapy (LITT) In 1985, Hashimoto first reported US-guided percutaneous LITT for hepatocellular carcinoma, and other scholars have subsequently done related clinical studies, which concluded that the tumor necrosis rate of this method could reach 74.3% without serious The tumor necrosis rate can reach 74.3% without serious complications.
(3) percutaneous microwave hyperthermia therapy (PMHT) US-guided percutaneous microwave hyperthermia therapy is performed by inserting a microwave electrode needle connected to a microwave tissue coagulator into the tumor, and then choosing the appropriate power and emission time for microwave treatment according to the size of the tumor. This method is mostly used in recent years to treat patients with liver cancer who have failed TAE/TAI, and Dong Baowei et al. believe that this is a safe and effective method for non-surgical treatment of liver cancer.
(4) Percutaneous radio-frequency ablation (RFA) In recent years, RFA has been reported in the literature to be mainly used for the treatment of small hepatocellular carcinoma and metastases. Therefore, it can be used in combination with TAI or TAE. Recently, some scholars have proposed some modified measures, such as RFA + temporary portal vein obstruction, bipolar radiofrequency electrocautery, etc., in order to improve the efficacy and promote tumor tissue necrosis.
(5) Percutaneous cryoablation (PCA) was first reported by D′Agostino in 1995. Although this method has efficacy, it is not better than other methods and has many troubles, so it is not widely used in clinical practice.
(6) electrochemotherapy (ECHT) is less reported for hepatocellular carcinoma treated by percutaneous hepatic puncture under CT or MR guidance, which is based on the theory of biological closed circuit and has the characteristics of wide range and ability to kill cancerous tissues at one time, but it is not effective for multiple, diffuse lesions and masses near the hilar structure. .
3.percutaneous intratumoral injection of radionuclide Many scholars use CT or US guided intratumoral injection of 131Ⅰ, which has certain effect, but no breakthrough has been seen.
Looking into the future, interventional methods for hepatocellular carcinoma will be promising. With the breakthrough of nanotechnology in the 1990s, nanotechnology can be used to infuse nanoparticle-drug complexes into the hepatic artery to achieve targeting effects in the 21st century, and the combination of nanotechnology and molecular biology technology will also be the focus of research in the 21st century. In addition, with the continuous development and application of angiogenesis inhibitors and the research of genes related to apoptosis of liver cancer cells, gene therapy and anti-tumor vascular therapy will surely bring gospel to liver cancer patients. Intra-arterial perfusion of anticancer agents alone has low efficacy and high response. When conditions permit, the use of microcatheters for super-selective, segmental TACE is the future direction of development.
The application of Chinese anticancer agents in liver cancer interventions and the application of new embolic agents such as drug-containing microspheres and 90Y glass spheres need to be further developed and promoted. Some non-vascular interventional methods such as PEI, RFA, ECHT, etc. will also be effective options and reasonable comprehensive treatments for hepatocellular carcinoma in the future. Continuous infusion of biochemotherapy drugs via implantable drug cartridge catheter system has a bright clinical application prospect for removing residual cancer cells and reducing recurrence rate. In conclusion, with the development of medical science and the continuous exploration of medical doctors, the level of comprehensive diagnosis and treatment of liver cancer will continue to improve, which will bring more and more powerful gospel to liver cancer patients.