Most patients with primary liver cancer are not indicated for surgery when they are found, and only 28% of them can be surgically resected. The average survival of patients with intermediate to advanced hepatocellular carcinoma that cannot be surgically resected is only 3-6 months. Although hepatic artery infusion chemotherapy (HAI) and embolization (HAE) have achieved good results in the treatment of inoperable intermediate and advanced hepatocellular carcinoma and have been recognized as the first choice of non-surgical treatment for hepatocellular carcinoma, the long-term efficacy is not satisfactory, and the survival rate of ≥5 years is only 9.0%~16.2%. Although interventional treatment for liver cancer has been carried out in China for nearly 20 years, it is not standardized, such as the mastering of indications and the method of interventional treatment are not consistent, which not only affects the efficacy, but also causes unnecessary waste of drugs.
After nearly 5 years, we have successfully completed the task and developed an effective standardized program of comprehensive interventional treatment for liver cancer. The main contents are as follows.
I. Strictly grasp the indications for hepatocellular carcinoma interventional therapy
1. Indications for hepatic artery chemotherapy (HAI)
① Primary or secondary hepatocellular carcinoma that has lost the opportunity of surgery;
②Poor liver function or difficulty in super-selective cannulation;
③Prophylactic hepatic artery infusion chemotherapy for recurrence of hepatocellular carcinoma after surgery or postoperative.
2.Contraindication to HAI
No absolute contraindication
For systemic failure, severe liver dysfunction, massive ascites, severe jaundice, leukocyte 120U (depending on the size of the tumor)], hypocoagulation, etc. Massive ascites or severe cirrhosis, 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;
③Infection, such as liver abscess;
④ carcinoma occupying 70% or more of the whole liver (if liver function is basically normal, or if a small amount of iodine oil is used for embolization in stages);
⑤ If there are 3 leukocytes, the right subclavian vein can be punctured percutaneously, and the catheter can be left in the common pulmonary artery, and the chemotherapy can be continuously perfused with an external drug box (“pump”). The method of continuous infusion chemotherapy via “pump”: drug 5-Fu
500mg, CDDP20mg, MMC4mg, each drug was added to 100ml of 5% glucose water once a day for 5 days, and EADM20mg, 10mg on the 1st and 5th day respectively, was added to 100ml of 5% glucose water. After an interval of 4 to 5 weeks, the chemotherapy will be infused continuously via “pump” again.
Interventional treatment for hepatocellular carcinoma with portal hypertension: Due to cirrhotic lesion, hepatic artery-portal fistula or portal vein blockage caused by tumor, portal hypertension can occur and even gastrointestinal hemorrhage can occur. Treatment methods.
① Subcutaneous injection of 200μg of santodine (100μg/time, twice a day) daily 2 days before and 3 days after the intervention to reduce the portal vein pressure. If the hepatocellular carcinoma lesion is not on the puncture tract, TIPS or PTPE can also be performed as appropriate to reduce portal vein pressure and prevent variceal rupture and bleeding. Splenic artery embolization can also reduce portal hypertension.
Partial splenic artery embolization is feasible at the same time of TAE treatment to relieve hypersplenism.
2. Super-selective cannulation with microcatheters to protect patients’ liver function
Most primary hepatocellular carcinomas occur on the basis of post-hepatitis cirrhosis, and their liver function is often abnormal or at critical value. Although interventional therapy has good efficacy on liver tumors, it also inevitably damages liver function of patients. With the use of microcatheter super-selective cannulation technique, chemotherapy and embolization can be successfully administered from the target vascular branch, which can effectively control the tumor and protect the patient’s liver function. For three tumors, the microcatheter needs to be inserted into the right or left hepatic artery, avoiding the gallbladder artery. At the same time, the side branch blood supply artery of the tumor should be searched and treated.
3. Develop an optimal “individualized” plan
According to the type and size of each pathogenic liver tumor, the presence or absence of portal vein cancer embolism, the degree of cirrhosis, liver function, age and systemic condition, different interventional treatment plans are formulated for each individual. For example, for elderly patients with hepatocellular carcinoma (≥65 years old) or those with severe cirrhosis, they should be super-selectively cannulated in the tumor-feeding artery and given simple chemoembolization; while for patients with hepatocellular carcinoma who are found to have dense iodine oil deposition in most of the lesions with only small marginal iodine oil defects during the follow-up after TAE, they can be injected with anhydrous alcohol directly under ultrasound guidance.
The interval of interventional treatment depends on the follow-up. Usually, the interval between each intervention is 50 days to 3 months, and in principle, it is at least 3 weeks from the recovery of the patient after the last intervention. If there is dense iodine oil deposition in the liver tumor lesion, necrosis of tumor tissue and no new lesion or no new progress, then interventional treatment is not allowed for the time being.
Comprehensive treatment in the interval of interventional therapy: it is appropriate to adopt liver protection, improve immunity and Chinese medicine to support the root. Traditional Chinese medicine: 2 weeks after intervention, the application can be started. The principle is to support and consolidate the essence, tonify Qi, improve immunity and regulate. Drugs that attack toxicity with toxicity, soften hardness and disperse nodules, activate blood circulation and remove blood stasis, and clear heat and detoxify are prohibited.
Measures to improve immunity: interferon, thymidine, transfer factor, interleukin II, tumor necrosis factor, LAK cells, shiitake mushroom polysaccharide, Paulkia, etc. Two to three drugs can be used alone or in combination.
IV. Development of indicators and protocols for efficacy observation and analysis
Clinical observation and laboratory examination, the former refers to the changes of symptoms and signs, the latter includes AFP level, immune index, blood routine of liver function, etc.
Ultrasound and color multispectral ultrasound are simple and easy to perform, which can observe the tumor shrinkage and understand the blood flow in the tumor lesion. The follow-up imaging examination is usually performed 30-35 days after TACE.
After the first intervention, CT examination is usually performed. If CT shows tumor shrinkage, dense iodine oil deposition in the tumor and no new lesions, color multispectral ultrasound examination will be performed after 1 month interval. If the ultrasound examination shows that the tumor continues to shrink or the situation is the same as before, MRI examination can be performed after another 1 month interval to understand the survival of tumor tissue. The choice of imaging examination depends on the purpose of examination and the patient’s financial situation. Based on the clinical observation, laboratory and imaging results, the further treatment plan of the patient will be considered.
The indicators for determining the efficacy are divided into five categories: clinical cure, significant improvement, improvement, temporary stability, progression or deterioration
①Clinical cure: tumor lesions disappear or shrink more than 75%, iodine oil deposition in tumor lesions is dense, MRI examination shows complete necrosis of tumor tissues, no tumor blood vessels and tumor staining in DSA. A-fetoprotein is normal. The patient’s survival period reaches more than 5 years.
(2) Significantly improved: the mass shrunk by more than 50%, iodine oil deposited in the tumor foci, and the filling area is more than 80% of the mass area; MRI examination shows that the tumor tissue is mostly necrotic, and there are only a few tumor vessels and tumor staining in the tumor periphery. Methemoglobin decreased to less than 70% of the preoperative level. The patient survives for more than 1 year.
(iii) Improvement: ≥25% shrinkage of the mass.