Primary hepatocellular carcinoma has an insidious onset and is difficult to be detected at an early stage. When clinically diagnosed, about 60% to 80% of patients cannot be surgically resected due to the large and multiple tumors or the combination of liver cirrhosis. Transarterial chemoembolization (TACE) is the first choice of non-surgical treatment for primary liver cancer, and TACE has been widely used since the 1980s as a local therapy. It uses iodized oil and chemotherapeutic agents (adriamycin, cisplatin, or mitomycin C) co-injected through the tumor’s nutrient artery along with gelatin sponge particles. Some authors have also used transarterial chemotherapy alternately with transarterial embolization using transcatheter hepatic artery embolization for the treatment of non-surgically resectable hepatocellular carcinoma. Randomized prospective clinical studies have demonstrated that TACE results in better outcomes than chemotherapy alone. Hepatocellular carcinoma nodules have dual blood supply from portal vein and hepatic artery, of which 95%-99% comes from hepatic artery, supplying the center and most of the peripheral blood supply of hepatocellular carcinoma tissues; portal vein supplies part of the peripheral blood supply of hepatocellular carcinoma tissues. Due to the anatomical characteristics of dual blood supply of liver, embolization of hepatic artery can reduce the blood flow of tumor by 90%, while the blood flow of normal liver tissue is only reduced by 30%-40%, which is the theoretical basis and rationale of hepatic artery embolization and ligation for the treatment of liver malignant tumors. After embolization of the main trunk of hepatic artery, the pressure of distal peripheral artery decreases, a large number of anastomotic branches reopen, and the collateral circulation of the tumor is established very quickly, which affects the efficacy of embolization. Therefore, the proximal and distal blood supply of the tumor tissue should be embolized at the same time in order to block the blood supply of the tumor more thoroughly, and the collateral circulation is more difficult to be formed, so that the efficacy of embolization of hepatocellular carcinoma can be improved. At present, the proximal and distal blood supply of hepatocellular carcinoma is embolized at the same time, and most of the end-embolizing agents used are mixed with a certain amount of chemotherapeutic drugs to be made into emulsifiers or made into microspheres with radionuclides. The terminal embolic agent not only plays the role of embolization, but also serves as the carrier of chemotherapeutic drugs and radionuclides. At the same time of embolization, the chemotherapeutic drugs carried by the embolization agent will be released slowly or the radionuclides carried by the embolization agent will be irradiated locally to the tumor, which plays a double therapeutic role for liver cancer tissues. I. Introduction of commonly used chemotherapeutic drugs and embolizing agents 1. Commonly used chemotherapeutic drugs At present, almost all chemotherapeutic drugs have been tried in the treatment of primary liver cancer. Few chemotherapeutic drugs have been clinically proven to have certain efficacy. The commonly used chemotherapeutic drugs with certain efficacy are introduced as follows: (1) 5-Fluorouracil (5Fu) and its derivatives 5Fu is an antimetabolite of uracil class, which is transformed into 5F-dump, inhibits the enzyme of deoxythymidine synthase, and prevents the conversion of uracil deoxyriboside into thymine, which is the most effective chemotherapeutic drug for primary liver cancer. It inhibits deoxythymidine synthetase and prevents the conversion of uracil deoxyriboside to thymidine, thus affecting DNA synthesis and playing an anticancer role. It is mainly an S-phase specific drug. However, 5-Fu can also penetrate into DNA and interfere with protein synthesis after it is converted into 5-fluorouracil nucleotide (5Fu) in vivo, so it also has effects on other cells in various stages. One of the reports on the efficacy of 5Fu on hepatocellular carcinoma in the literature, the general effective rate is about 15%. (2) Adriamycin (adamycndoxoubcn, ADM) ADM is an anthracycline glycoside antibiotic, which can be embedded in the double-helix structure of DNA to block the action of DNA polymerase, thus inhibiting the synthesis of DNA, and it has a killing effect on the tumor cells during the proliferation period. Due to the prominent cardiotoxic damage of ADM, it is generally believed that the total amount of up to 550mg / can produce irreversible heart failure, so it has been replaced by less toxic derivatives of epothilone (EADM).The electrocardiogram will only change when the cumulative dose of EADM reaches 1,000mg / O. It is often used in combination with other chemotherapeutic agents to treat tumors. Clinically, it is often combined with other chemotherapeutic agents for perfusion chemotherapy or mixed with iodized oil to form an emulsion, which is used as a terminal embolizing agent to embolize the tumor. (3) Cisplatin (cspatn, PDD) PDD is a heavy metal complex centered on divalent platinum bound to two chlorine atoms and two ammonia molecules. It is through the formation of cross-linkages with the bases on the double helix structure of DNA, affecting the template function of DNA and inhibiting the synthesis of DNA and RNA, PDD is a non-specific drug for the cell cycle. It is often used in combination with other chemotherapeutic drugs. The main toxic reaction is that it can cause irreversible tubular necrosis. The renal damage can be avoided by paying attention to the supplementation of sufficient fluid hydration and diuretics during the application. (4) Mitomycin C (mtomycne, MMC) MMC belongs to the anticancer antibiotic class of chemotherapeutic agents, which has an anticancer effect similar to that of alkylating agents by covalently binding to DNA and cross-linking to DNA to disrupt the structure of DNA. mtomycne is widely used in Japan for the treatment of gastrointestinal tract tumors. It is often combined with other chemotherapeutic drugs or made into an emulsifier with iodized oil to embolize tumors. (5) Other chemotherapeutic agents commonly used in the treatment of primary liver cancer are etoposide (oncoside, etoposde, VP I 16-213), carboplatin or carbon platinum (cabopatn, CBDCA), tiotropium (TSPA), vincristine (vncstne, VC), hydroxycamptothecin ( hydoxycanvptothecne, HPT), etc. The clinical efficacy reported in the literature is variable and needs further observation. In the actual application, according to the patient’s specific situation, the different mechanism of action of chemotherapeutic drugs and toxicity response to adjust the chemotherapy program and dosage. 2, commonly used embolization agent Due to the progress of interventional radiology, the research of embolization agent is very active. Ideal embolic agents should have the ability to selectively and permanently stay in the trophoblastic arteries and veins around the tumor and tumor tissues, and even penetrate into the tumor cells, which are not easy to be dispersed by the blood flow, and do little damage to the normal liver tissues, and at the same time, they have the efficacy of killing the tumor cells. At present, there are many kinds of embolic agents, according to the length of embolic agent effect time, they are divided into short-acting embolic agent, medium-acting embolic agent and long-acting embolic agent; according to the location of embolic agent embolization, they are divided into proximal embolic agent and peripheral embolic agent. The commonly used clinical embolizing agents and related literature reports are now briefly introduced. (1) Oil iodide Oil iodide is the most commonly used intermediate-acting embolizing agent in the clinic, and there are two kinds of dosage forms: 10% and 40%. It can dissolve fat-soluble drugs or make emulsion with water-soluble drugs. Iodized oil is used as embolizing agent and a good carrier of drugs, with the dual role of guidance and embolization, and easy to follow up and review after treatment with CT. The emulsifier made of iodized oil and chemotherapeutic drugs can be selectively retained in liver cancer tissues for a long time and kill liver cancer cells through embolization and chemotherapy. At present, it is believed that the selective retention of iodized oil in liver cancer tissues is mainly due to the siphoning effect of trophoblastic liver cancer blood vessels; the dilated and tortuous blood vessels in liver cancer tissues; the lack of innervation in liver cancer tissues; the high permeability of blood vessels in liver cancer tissues, which makes the iodized oil easy to penetrate into the interstitial space of liver cancer tissues and even into liver cancer cells; and the lack of monocyte system and lymphatic reflux to remove the particles of iodized oil in liver cancer tissues. However, during clinical treatment, it was found that not all types of hepatocellular carcinoma had iodized oil accumulation. The author noted that infiltrating hepatocellular carcinoma, diffuse hepatocellular carcinoma, multinodular fusion hepatocellular carcinoma, massive hepatocellular carcinoma, hepatocellular carcinoma without pseudoepithelium and hepatocellular arteriography with lack of blood flow have poor iodine deposition, or even no iodine deposition. The authors believe that whether liver cancer tissues polyiodine or not is related to the type, size and tissue structure of liver cancer in addition to the above factors. Its mechanism needs to be further explored. When applying iodized oil, attention should be paid to whether there is arteriovenous fistula in hepatocellular carcinoma, because iodized oil can reach the lungs through the fistula and cause pulmonary embolism, so gelatin sponge strip or stainless steel ring can be used first to block the fistula. In addition, note that iodized oil can not flow back to other organs, so as not to cause tissue necrosis. Because iodized oil is easily washed away by blood flow, it is often used in conjunction with gelatin sponges and other proximal embolization agents. (2) High-heat iodized oil was invented by Li Xuan of the Third Clinical Medical College of Peking University. It is to inject iodized oil heated to 110℃ into hepatic artery, which combines chemotherapy, heat therapy and embolization, and at the same time of embolizing chemotherapy, it also causes endothelial damage and occlusion of trophoblastic blood vessels of hepatocellular carcinoma, so that the embolization of hepatocellular carcinoma is more thorough. It has been successfully used in clinic and achieved better therapeutic effect.MMCms-CDDP-Iodized oil multiphase emulsion is made of MMC, CDDP and iodized oil into multiphase emulsion, and the drug release technology is used to make the two kinds of chemotherapeutic drugs in the multiphase emulsion released in different phases, so as to make full use of the chemotherapeutic drugs and kill the hepatocellular carcinoma cells more efficiently. This method was also invented by Li Xuan and successfully used in clinic. (3) Gelatin sponge Gelatin sponge can be cut into 1-2am size particles or mm thick and thin strips, mechanically blocking the lumen of blood vessels and promoting thrombus formation at the blockage place, which is a commonly used intermediate-performance embolizing agent in clinic. Because of its embolization is often the trunk of trophoblastic blood vessels of hepatocellular carcinoma, due to absorbable, easy to produce embolism distal tumor collateral circulation and embolization of vascular recirculation, so it is often used in combination with iodized oil to improve the therapeutic efficacy. (4) Anhydrous alcohol Anhydrous alcohol can destroy the endothelium, denature the protein in the blood, form a kind of coagulative mixture which is not easy to be absorbed and play the role of embolism, and it can have the role of embolism for the terminal and thicker blood vessels. When applying, attention should be paid to the super-selected tumor vessels, control the injection speed, avoid reflux caused by ectopic embolism. It should be prohibited when there is arteriovenous fistula. (5) Stainless steel ring is often used for proximal embolization of liver cancer vessels. It works by permanent mechanical embolization of blood vessels. The disadvantage is that embolization of the distal end of blood vessels often produces collateral circulation. It is often used for embolization of ruptured bleeding and arteriovenous fistula of hepatocellular carcinoma. (6) Drug microspheres or nuclide microspheres can be made into particles of different sizes of chemotherapeutic drugs or radionuclides according to the needs, and embolize the trophoblastic blood vessel branches of hepatocellular carcinoma, which can have the efficacy of chemoembolization or embolization of radiotherapy. It is more effective when combined with terminal embolization agent. (7) Other commonly used short-acting embolic agents, such as autologous blood clot, long-acting embolic agents, such as silicone rubber ball, magnetically controlled metal particles, etc., have many successful clinical reports. Indications and contraindications of TACE (1) Unresectable primary or secondary hepatocellular carcinoma (2) Recurrence after resection or lobectomy to consolidate the therapeutic effect of TACE (3) TACE before resection to improve the therapeutic effect and delay distant metastasis (2) Contraindications of TACE (1) Poor general condition (2) Serious liver dysfunction, large amount of ascites, severe cirrhosis, and the liver function belongs to Child C class (3) Leukocyte counts are not enough to prevent the liver from developing. Child Grade C. (3) White blood cells less than 3.0×/L require appropriate treatment. (4) Obvious abnormality of coagulation function. (5) Portal hypertension with reverse blood flow or complete obstruction of the main trunk of the portal vein, with few collateral vessels formed. (6) Cancer accounts for more than 70% of the whole liver and the liver function is poor. The possibility of rupture is high. Preoperative preparation 1. Routine blood routine, liver and kidney function, coagulation function, electrocardiogram and chest X-ray examination. Iodine allergy test and penicillin allergy test. 3.To the family to explain the purpose of examination and treatment and possible complications, the family agreed to sign. 4.Do a good job of explaining to the patient, so that the patient to eliminate concerns and nervousness and fear, and actively cooperate with the treatment. 5, 4h before the operation, fasting water, for the poor state of the body, should be given in advance to intravenous rehydration. IV. Precautions for intraoperative operation 1. Firstly, establish peripheral rehydration channel, input isotonic fluid, and give central antiemetic drugs such as Shufu Ning, Kang Quan, etc. 2. 2.Puncture the femoral artery according to Seldinger’s method, and strive to be accurate and successful in one puncture. Strictly execute aseptic operation. 3.The operation process should be carried out under TV monitoring, so as to avoid the catheter mistakenly in the arterial entrapment or folding in the lumen of the vessel. 4.After adjusting the direction of the catheter, the first choice of abdominal arteriography, to understand the scope of the tumor and blood supply, but also pay attention to whether the portal vein is smooth, whether the combination of arteriovenous fistulae, and sometimes should also pay attention to the variability of the origin of the hepatic artery. According to the results of hepatic arteriography, combined with the patient’s general condition and laboratory tests, the treatment plan should be selected on a case-by-case basis. 5.After chemoembolization, arterial subtraction imaging should be done to understand the changes of blood supply of the lesion and the distribution of iodine oil after embolization of hepatocellular carcinoma. 6.After extubation, the puncture site should be fully compressed for 10-15an, and then pressurized bandage should be applied after releasing the puncture hole without bleeding. Postoperative treatment 1, local pressure bandage, lying down for 24h. 2, because the contrast agent, iodized oil and chemotherapeutic drugs have damage to the liver and kidney function, postoperative liver diuretic, anti-infection and symptomatic treatment should be given. 3, pay attention to the changes of vital signs, pay attention to the dressing with or without blood seepage and subcutaneous bruising, pay attention to the dorsalis pedis arterial pulsation. For those with changes in vital signs, the cause should be investigated early, except for intra-abdominal and puncture site bleeding. If the dorsalis pedis artery pulsation is weakened or disappeared, it should be considered whether the local pressure bandage is too tight, or whether it is thrombosis at the puncture site, and should be treated accordingly. Postoperative complications and treatment 1, technical operation of the complications (1) puncture site bleeding, local hematoma or the formation of pseudo aneurysm The main reasons are unskilled technical operation, repeated puncture, postoperative puncture point compression and hemostasis is not sufficient, heparin is overdosed, coagulation mechanism disorders, etc. The main points of prevention are accurate puncture, repeated puncture, postoperative puncture point compression and hemostasis is not sufficient, heparin is overdosed, coagulation mechanism disorders. The main points of prevention are accurate puncture, postoperative local compression and adequate hemostasis. Once bleeding or hematoma formation is found, quickly reapply pressure bandage while removing the cause. For larger hematoma, hematoma removal and vascular breach repair should be carried out immediately. (2) Vasospasm, arterial endothelial damage, catheter into the arterial entrapment or catheter kinking The key point of prevention is to skillfully catheterize the technology, and the operation process should be carried out gently, meticulously and patiently under the TV monitor. 2, embolic material reflux complications, including splenic, renal infarction, gastroduodenitis, erosion or ulcer, gastrointestinal bleeding, acute pancreatitis, acute cholecystitis, gallbladder necrosis or even perforation. The main manifestation is epigastric pain, and the examination shows limited peritonitis. It should be closely observed and treated with anti-inflammatory and symptomatic treatments, and usually improves after about a week of treatment. If peritonitis aggravated, high fever, blood increased, should consider gallbladder or digestive tract perforation, if necessary, should be surgical treatment. The main point of prevention is that when embolizing amputation tumor, the catheter should be super-selected as far as possible, and the injection of embolic agent should be carried out slowly under the TV surveillance to prevent the backflow of embolic agent. Complications arising from embolizing agents and chemotherapeutic drugs (1) Post-embolization syndrome is mainly manifested as nausea, vomiting, fever, pain in the liver area, etc. The cause is the combination of embolizing agents and chemotherapeutic drugs. The cause is chemotherapeutic drugs and tumor necrosis or organ ischemia, edema caused by limited peritonitis. Generally, it can be gradually relieved in 3-5d after treatment, and some patients’ symptoms can last for 2-3 weeks or even longer. Treatment should be hepatoprotective, anti-inflammatory and symptomatic, while paying attention to the prevention and management of complications. Wang Jiangyun and Li Yanhao retrospectively analyzed the fever of 45 patients after 60 cases of hepatocellular carcinoma treated by TACE, and also used multiple regression to analyze the influencing factors affecting fever after TACE. The results proved that iodine oil dosage was the primary factor leading to fever after TACE, and the addition of embolization agent would aggravate the fever, and the systemic state and local state of the liver before the treatment, including Okuda stage, the age of patient and tumor type are also factors that affect fever. (2) Acute hepatic failure After hepatic artery chemoembolization, most patients have transient liver function abnormality and a small amount of chest and abdominal fluid occurs. After hepatoprotection, diuresis and symptomatic treatment, it can be restored to the level before chemoembolization within two weeks. If jaundice continues to worsen and ascites increases, the possibility of acute liver failure should be considered. The reasons include the mastery of the indications, whether the tumor vascular embolization agent is over-selected during the operation and whether the dose of embolized chemotherapy drugs is reasonable. The key to prevention is to strictly grasp the indications for embolization chemotherapy; appropriate preoperative hepatoprotective treatment; intraoperative super-selection of tumor vessels as far as possible, combined with the specific conditions of the patient to determine the amount of chemotherapy and embolization agent; continue appropriate postoperative hepatoprotective treatment. For acute liver failure caused by chemoembolization, albumin, fresh plasma, hepatocyte growth factor, vitamins, potassium and magnesium menthylate should be given as active treatment. If necessary, artificial liver treatment can achieve better therapeutic effect. (3) Hepatic infarction and liver abscess Hepatic artery chemoembolization can cause necrosis of tumor tissue and part of normal liver tissue, which can become the hotbed of secondary infection.Antibiotics should be used routinely and prophylactically after TACE. For patients with prolonged postoperative fever, ultrasound or CT examination should be performed to alert the occurrence of liver abscess. Once abscess formation is detected, puncture and tube drainage can be performed. (4) Renal failure Because contrast agents and chemotherapeutic drugs are damaging to the kidneys, attention should be paid to urine output after TACE, and appropriate hydration and diuretic therapy should be given to avoid renal failure. Hepatic artery chemoembolization treatment strategy Because of the differences in tumor stage, tumor size and type, tumor blood supply type, liver function and systemic status of patients with primary liver cancer, the method of chemoembolization and drug dosage can not be uniform, and the choice of treatment plan should be made on a case-by-case basis. The specific implementation plan mainly determines the type of hepatic arteriography tumor blood supply, the degree of tumor polyiodization, the size of the tumor, the patient’s liver function and systemic condition. 1.Tumor terminal embolization The embolization part is tumor tissue and trophoblastic blood vessels around the tumor. Commonly used embolizing agents are iodine oil, hot iodine oil, gelatin sponge powder and various drug microspheres. The main indications are nodular and massive hepatocellular carcinoma, rich blood supply of tumor in hepatic arteriography, and good tumor polyiodization. For multinodular hepatocellular carcinoma, terminal embolic agent can be injected from the hepatic innominate artery, and single-nodular or massive hepatocellular carcinoma can be injected into the terminal embolic agent from the super-selected tumor trophoblastic artery, and the injection should be discontinued when the tumor is completely filled with the embolic agent or the blood flow in the tumor trophoblastic artery is slow or stagnant. The thicker tumor trophoblastic artery should then be embolized with gelatin sponge strips, which has the best efficacy. Tumor central embolization Embolization site for the hepatic artery above the second branch of the large blood vessels, commonly used embolization agents are gelatin sponge strips, steel wire ring and a variety of microspheres, etc. The main adaptation to the tumor trophoblastic artery imaging lack of blood flow or stagnation. It is mainly adapted to giant and nodular hepatocellular carcinoma that lacks blood flow and does not gather iodine in hepatic artery imaging. Because of the easy generation of tumor collateral circulation, regular hepatic arteriography is needed, and the newborn collateral vessels of the tumor should be embolized at the same time. Embolization of hepatic segment The site of embolization is the hepatic segment where the tumor is located. Commonly used embolization is iodized oil and gelatin sponge. It is mainly adapted to nodular hepatocellular carcinoma with lack of blood flow and no iodine collection. 4. Sandwich chemotherapy embolization This method is one of the commonly used clinical methods. Specifically, the emulsifier of iodized oil and chemotherapeutic drugs is used to embolize tumor tissues and terminal trophoblastic blood vessels first, followed by instillation of high-dose chemotherapeutic drugs, and finally embolization of the trunk of tumor trophoblastic arteries with gelatine sponge strips and so on, so as to prevent iodized oil emulsion from being washed away by the blood flow. It is mainly adapted to giant and nodular hepatocellular carcinoma with good iodine polymerization of rich blood transport. Dual embolization of hepatic artery and portal vein The specific method is to embolize the tumor tissues and trophoblastic vessels via hepatic artery first, and then percutaneous portal vein puncture to embolize the blood vessels supplying the tumor from portal vein. Both can be performed at the same time or after a 2-week interval. Because percutaneous hepatic portal vein puncture is more complicated, it is now mostly replaced by PE. This method is mostly applied to those who have iodine oil embolization, most of the tumor tissues are polyiodinated and there are defects in the periphery. Embolization radiotherapy Using microspheres labeled with radionuclides to embolize tumor tissues and tumor blood vessels, which can play the dual therapeutic roles of embolization and internal irradiation. Embolization can be carried out in stages according to the situation, so as to achieve the purpose of embolizing the tumor and avoid the possible serious side effects, as well as to cause less damage to the organism. Embolization of collateral blood vessels of the tumor Sometimes there are multiple trophoblastic blood vessels in liver cancer tissues, such as collateral tumor blood vessels originated from superior mesenteric artery or inferior phrenic artery, etc. Particularly after the original trunk of the tumor blood vessels has been embolized, collateral circulation is more likely to be formed, and should be embolized one by one after angiography is discovered. Evaluation indexes of chemoembolization efficacy (1) Tumor markers Serum AFP concentration change is the simplest and most effective index to observe the efficacy of chemoembolization, except for AFP-negative patients. In preoperative AFP-positive patients, the serum AFP value should decrease significantly after 7FACE treatment, consistent with tumor shrinkage on imaging review. If the tumor shrinks in imaging and there is no change in AFP, attention should be paid to the presence of other metastatic foci; if there is no change in AFP and imaging, it suggests that TACE treatment should be repeated or the effect of TACE treatment is not good, which needs to be coordinated with other treatments; if the AFP rises again after decreasing in TACE, it suggests that the tumor is recurrent or metastasized to other sites, and TACE should be repeated and relevant examinations should be conducted at the same time. (2) Measurement of tumor size Ultrasound is economical, practical and effective, and can be operated repeatedly to determine the therapeutic effect by measuring the tumor size and the change of tumor blood flow signal before and after treatment.CT is the most ideal review method after TACE, which can intuitively compare the change of tumor size before and after treatment, and understand the distribution of iodized oil in the tumor tissue and non-tumor tissue. The extent to which the tumor tissue is filled with iodized oil can be used as a basis for determining the efficacy of the treatment, the next TACE treatment, and whether to adopt other methods of treatment. Meanwhile, iodized oil CT can also detect subfoci and metastatic foci.M Postoperative review is also helpful in the evaluation of efficacy after TACE.T. Enhanced signal within the tumor on the weighted image suggests liquefied necrosis of the tumor; decreased signal suggests coagulative necrosis of the tumor; and elevated or decreased signal around the tumor responds to edema or granulation tissue. If the signals on both T, and T: weighted images are reduced, it suggests coagulative necrosis of the tumor tissue, with no viable tissue. Although hepatic arteriography is an invasive test with certain risks, it has been widely used in the diagnosis and treatment of some tumors due to the proficiency of clinicians and clinical needs. Hepatic arteriography can visualize the changes of tumor blood vessels after TACE, whether there are new tumor blood vessels and tumor collateral circulation, whether there are new tumors and metastatic foci, and also carry out treatment at the same time. (3) Symptoms and signs Mainly include pain in the liver area, improvement of abdominal distension and loss of appetite, weight gain, and shrinkage or disappearance of the original epigastric mass. (4) Survival rate Survival rate is the most meaningful indicator reflecting the efficacy of TACE. It can be compared with the survival rate of other treatment methods. Summarize and compare the survival rate of various treatment methods. The difference in efficacy of various treatments can be obtained, providing a basis for clinicians and patients to reasonably choose the treatment program.