Primary hepatocellular carcinoma has a high degree of malignancy, the early stage of hepatocellular carcinoma is not clinically obvious, and most patients are in the middle to late stage when they come to the hospital. Interventional treatment of hepatocellular carcinoma, namely transcatheter arterial chemoembolization (TACE), has achieved good results and is unparalleled by other treatment methods. It has been recognized as the first choice of non-surgical treatment for liver cancer.
Efficacy of TACE treatment.
Surgical resection is the preferred method of liver cancer treatment, and the survival rate can reach about 50% for small hepatocellular carcinoma 5 years after surgery. However, most hepatocellular carcinomas are already in advanced stage when diagnosed, so the surgical resection rate is low and the postoperative recurrence rate is high. It is an established fact that conventional chemotherapeutic approaches are ineffective in the treatment of hepatocellular carcinoma, and even the latest phase II study of the molecularly targeted drug sorafenib for hepatocellular carcinoma showed that the median survival of treatment was only 9.2 months [1]. In contrast, according to Takayasu et al [2], long-term follow-up of 8510 patients, the survival rates at 1, 3, 5, and 7 years for TACE treatment of advanced hepatocellular carcinoma that is no longer surgically resectable were 82%, 47%, 26%, and 16%, respectively, with a median survival time of 34 months. The overall survival rate of patients is influenced by TNM stage, liver function, AFP and other indicators. For patients with TNM stage I and grade A liver function, a five-year survival rate of 52% can be achieved, which is similar to the effect of surgical resection.
Principles and methods of TACE treatment.
The theoretical basis of interventional treatment for hepatocellular carcinoma is based on the fact that 95%-99% of the blood supply of hepatocellular carcinoma comes from the hepatic artery, while the blood supply of normal liver tissue is 70%-75% from the portal vein and only 25%-30% from the hepatic artery. On the one hand, it blocks the blood supply to the tumor, on the other hand, the chemotherapeutic drugs are slowly released to strike the tumor continuously, causing ischemic necrosis and inducing apoptosis of liver tumor cells. And the systemic toxic side effects of chemotherapeutic drugs are reduced.
The interventional operation of hepatocellular carcinoma must be performed under DSA angiography machine. Firstly, the catheter should be placed at the beginning of common hepatic artery for imaging, and the image acquisition should include arterial phase, parenchymal phase and venous phase. And consider whether additional angiograms of right or left hepatic artery, left gastric artery, inferior phrenic artery, superior mesenteric artery, etc. are needed as appropriate. After careful analysis of the angiographic image performance and clarification of the site, size, number and blood supplying arteries of the tumor, the right hepatic artery (the catheter should cross the gallbladder artery) and the left hepatic artery are chosen to give perfusion chemotherapy, respectively, and some scholars advocate using about 1/3 of the drug to achieve dual hepatic artery-portal vein intervention by perfusion through the splenic artery [5]. Chemotherapeutic drugs should be diluted to 150-200 ml and slowly injected into the target vessel. Most primary hepatocellular carcinomas are hepatocellular hepatocellular carcinomas, which have thickened blood supply arteries and abundant tumor vessels, and should be given chemoembolization. It is advocated to use microcatheter to insert the target artery branch adjacent to the tumor super-selectively, and then use super-liquid iodized oil and chemotherapeutic drugs to mix into an emulsion and slowly inject into the target vessel through the catheter. The amount of iodized oil should be considered according to the size of tumor, blood supply, presence of portal vein cancer thrombus, liver and kidney function, patient’s general condition, etc. The amount of iodine oil should be considered according to the size of the tumor, blood supply, the presence of portal vein cancer thrombus, liver and kidney function, and the patient’s systemic condition, and should be limited to lO-20 ml under fluoroscopy, usually not more than 3O ml. However, complete occlusion of the intrinsic hepatic artery should not be performed to facilitate re-TACE treatment.
The dose of drugs and the degree of embolization during interventional therapy should not be uniform. Different interventional regimens should be individualized according to the type and size of the liver tumor, the presence of portal vein cancer embolism, the degree of cirrhosis, liver function, age and systemic condition. The interval of interventional treatment depends on the follow-up, usually about 50 d each time, 3-4 times as a course of treatment. However, in principle, it should be at least 3 weeks from the recovery after the last intervention. If there is dense iodine oil deposition in the liver tumor lesion on imaging, and there is no new lesion or new progression of tumor tissue necrosis, then interventional treatment should not be performed for the time being. We often see patients who have survived for more than 3 years and have received only l or 2 interventions.
Indications for TACE treatment
Interventional treatment for hepatocellular carcinoma can result in high drug concentration in the tumor area; combined with the use of embolic agents to block the blood supply to the tumor, it can lead to ischemic necrosis and apoptosis of tumor cells. However, the adverse effects of chemotherapeutic drugs on liver and kidney functions, gastrointestinal tract, bone marrow, etc. should not be neglected. The indications of patients for interventional treatment should be considered comprehensively according to their clinical manifestations, imaging and laboratory test results. Interventional procedures done without indications for interventional therapy are harmful, aggravate the disease, and even accelerate the death of the patient.
Indications.
(1) Application before resection of liver tumor, which can shrink the tumor and facilitate resection, and at the same time can clarify the number of lesions and control metastasis.
(2) Intermediate and advanced hepatocellular carcinoma that cannot be surgically resected, without severe liver and kidney dysfunction, without complete obstruction of the main portal vein, and with tumor occupancy <70%.
(3) Small hepatocellular carcinoma.
(4) Those who failed in surgery or recurred after resection.
(5) Control of pain, bleeding and arteriovenous impotence.
(6) Prophylactic hepatic artery chemoembolization after hepatectomy for hepatocellular carcinoma.
Contraindications
(1) Severe liver dysfunction, such as: severe jaundice [bilirubin >51tanol/L, AI >120U (depending on tumor size)], hypocoagulability, etc. Massive ascites or severe cirrhosis with liver function of Child C grade.
(2) Portal hypertension with reverse blood flow and complete obstruction of the main trunk of the portal vein with little formation of collateral vessels.
(3) Infection, such as liver abscess.
(4) cancer occupying 70% or more of the whole liver (if liver function is basically normal, embolization with a small amount of iodine oil can be used in stages)
(5) Leukocytes <3,000.
(6) Those with extensive metastases throughout the body
(7) systemic failure.
Efficacy observation index after TACE
The observation of efficacy after hepatocellular carcinoma intervention mainly includes two aspects.
(1) Imaging follow-up examination: It is usually performed 30-35 days after TACE to understand the extent of liver tumor shrinkage and the presence of new lesions through imaging examination. Color B-ultrasound is simple and easy to perform, which can observe the change of tumor volume and compare with the pre-interventional treatment, and also can dynamically observe the colored blood flow into the tumor lesion. Especially, the T2-weighted image of MR and MR enhancement are unique in determining the surviving tumor lesions.
(2) Blood and biochemical examination: including AFP value, immune index (CD3, CD4, CD8, NK cell count) and liver and kidney function. Based on the results of the above tests, the patient’s further treatment plan will be considered comprehensively.
TACE combined with other local treatments
Because TACE cannot necrotize the huge tumor at one time, multiple treatments are needed, and chemotherapy and embolization drugs will inevitably bring damage to normal liver parenchyma, aggravate liver function damage, promote cirrhosis, and eventually affect patients’ quality of life and survival, so TACE has been combined with other local tumor treatments (such as PEI, RAF) for several years to achieve better treatment results.
Radiofrenquency ablation (RFA) has a synergistic effect before the first TACE. The hepatic artery chemoembolization reduces the blood supply to the tumor, decreases the cooling effect of blood in the hepatic artery during thermal ablation, and increases the necrotic range of the tumor during thermal ablation; on the other hand, the thermal effect during thermal ablation improves the uptake of chemotherapeutic drugs by the tumor tissue and the sensitivity to chemotherapeutic drugs. On the other hand, the thermal effect of thermal ablation improves the uptake of chemotherapy drugs and the sensitivity of tumor tissue to chemotherapy drugs. For liver tumor lesions after interventional treatment, if iodine oil deposition is not dense or tumor is still alive on MR examination, radiofrequency ablation treatment should be added [7, 8].
Combination of TACE and surgery
Interventional treatment is preferred for large hepatocellular carcinoma that cannot be surgically resected, and after shrinking by TACE treatment, most scholars advocate second-stage surgical resection, but surgical indications should be strictly mastered. In 102 cases of large hepatocellular carcinoma in Shanghai Zhongshan Hospital, the 5-year survival rate reached 52% with the longest case having survived for 16 years after shrinkage by TACE treatment. We advocate preventive interventional treatment after liver tumor surgery in order to achieve early detection and treatment of small recurrent foci, reduce recurrence after surgery and prolong patients’ survival. In a study conducted at Shanghai Changhai Hospital on 120 patients with post-surgical liver cancer, the tumor recurrence rate at 1 year after surgery was 17.6% (12/68) in the prophylactic infusion chemotherapy group, compared with 32.7% (17/52) in the control group.
In conclusion, TACE treatment is the primary treatment for unresectable liver cancer, and standardized TACE treatment for liver cancer combined with PEI, RFA and other local treatments and surgical procedures will further improve the therapeutic effect and the survival of liver cancer patients.