I. Interventional treatment of hepatocellular carcinoma–hepatic artery perfusion chemoembolization
1.Basic principles
(1) It is required to be performed under digital subtraction angiography machine.
(2) Clinical indications must be strictly mastered.
(3) The standardization and individualization of treatment must be emphasized.
2.Applicable groups
(1) Patients with intermediate and advanced primary liver cancer that cannot be surgically resected.
(2) Patients who can be surgically resected but cannot or do not want to undergo surgery due to other reasons (e.g. advanced age, severe cirrhosis, etc.). (b) For the above-mentioned patients, interventional therapy can be the preferred method in non-surgical treatment.
Domestic clinical experience shows that hepatic artery intervention is effective for giant hepatocellular carcinoma with relatively intact envelope and large hepatocellular carcinoma, but for hepatocellular carcinoma that can be surgically resected, surgical resection is preferred. The main influencing factors of interventional therapy are.
①serum AFP level.
②whether the tumor lesion has intact envelope and clear boundary.
③The presence of cancer thrombus in portal vein.
3.Indications
(1) The main indications for TACE are middle and advanced HCC that cannot be surgically resected, without serious liver and kidney dysfunction, including
(i) Macroscopic hepatocellular carcinoma: the proportion of tumor occupying the whole liver <70%.
② multiple nodular hepatocellular carcinoma.
③ portal vein trunk not completely obstructed, or although completely obstructed but compensatory collateral vessel formation between hepatic artery and portal vein.
④ those with failed surgical procedures or postoperative recurrence
(⑤) Liver function classification (Child-Pugh) grade A or B, ECOG score 0-2.
(6) bleeding from ruptured liver tumor and bleeding from portal hypertension caused by hepatic artery-portal artery static shunt.
(2) It is applied before liver tumor resection, which can shrink the tumor and facilitate second-stage resection, and at the same time can clarify the number of lesions.
(3) Small hepatocellular carcinoma, but not suitable for or unwilling to undergo surgery, local radiofrequency or microwave ablation treatment.
(4) Control of local pain and bleeding as well as embolization of arteriovenous impotence.
(5) After resection of hepatocellular carcinoma, to prevent recurrence.
4. Contraindications.
(1) Severe hepatic dysfunction (Child-Pugh grade C).
(2) Severely diminished coagulation function, which cannot be corrected.
(3) Complete embolization of the portal vein trunk by cancer embolus with few collateral vessel formation.
(4) Combined with active infection and cannot be treated simultaneously.
(5) Extensive distant tumor metastasis with estimated survival <3 months.
(6) Those with malignancy or multi-organ failure.
(7) tumors accounting for ≥70% of the whole liver cancer foci; if liver function is basically normal, a small amount of iodine oil emulsion may be considered for fractional embolization.
(8) Significant reduction of peripheral blood leukocytes and platelets, leukocytes <3,0×109/L (not absolutely contraindicated, such as those with hypersplenism, which is different from chemotherapeutic leukopenia), platelets <60×109/L.
5.Key points and classification of operation procedures.
Basic operations: hepatic arteriography, usually using the Seldinger method, percutaneous puncture femoral artery cannulation, catheter placed in the abdominal trunk or common hepatic artery imaging, imaging image acquisition should include the arterial phase, parenchymal phase and venous phase; superior mesenteric artery imaging should be done, pay attention to the search for collateral blood supply.
Hepatic artery embolization chemotherapy (TACE): Hepatic artery infusion chemotherapy (TAI) and hepatic artery embolization (TAE) are performed simultaneously to improve the efficacy of treatment. TACE can effectively block the arterial blood supply of hepatocellular carcinoma, while releasing high concentrations of chemotherapeutic drugs to combat the tumor, causing ischemic necrosis and shrinkage, with less impact on normal liver tissue. Evidence-based medical evidence has shown that TACE can effectively control the growth of hepatocellular carcinoma, significantly prolong the survival of patients, and benefit patients with hepatocellular carcinoma, which has become the first and most effective treatment method for middle and advanced hepatocellular carcinoma that cannot be surgically resected.
Before TACE, we should analyze the imaging performance, clarify the tumor site, size, number and blood supplying artery, and then super-select the cannula to the right hepatic artery and left hepatic artery to give perfusion chemotherapy respectively. The head end of the catheter should cross the gallbladder, the right gastric artery and the gastroretinal artery and other vessels. The chemotherapeutic drug should be appropriately diluted and slowly injected into the target vessel, and the infusion time should not be <20 5-20="">30 ml. For patients with hepatocellular carcinoma whose blood supply arteries are significantly thickened, the addition of granular embolic agents (such as gelatin sponge or microspheres) after iodine oil emulsion embolization is usually recommended. Embolization should try to embolize all the feeding vessels of the tumor in order to de-vascularize the tumor. Care should be taken not to completely occlude the intrinsic hepatic artery to facilitate re-TACE treatment.
The main factors affecting the long-term efficacy of TACE include the degree of cirrhosis, the functional status of the liver and the tumor condition (size, grade, pathological type, portal vein cancer thrombus, and arteriovenous fistula). In addition, TACE treatment itself has certain limitations, which are mainly manifested as.
(1) TACE is often difficult to achieve complete necrosis of tumor due to incomplete embolization and establishment of tumor collateral vessels;
②After TACE treatment, due to ischemia and hypoxia of tumor tissue, the level of hypoxia-inducible factor (HIF) in residual tumor increases, which leads to high expression of vascular endothelial growth factor (VEGF). These factors can lead to intrahepatic tumor recurrence and distant metastasis.
6. Common adverse effects after TACE
Post-embolization syndrome is the most common adverse effect of TACE treatment, mainly manifested as fever, pain, nausea and vomiting. Fever and pain are caused by local tissue ischemia and necrosis after the hepatic artery is embolized, while nausea and vomiting are mainly related to chemotherapy drugs. In addition, there are other common adverse effects such as bleeding at the puncture site, white blood cell drop, transient liver function abnormalities, renal function impairment and difficulty in urination. Generally speaking, the adverse reactions after interventional therapy will last for 5-7 days, and most patients can fully recover after symptomatic treatment.
7.Follow-up and treatment interval
It is generally recommended to review CT and/or MRI, etc. at 4-6 weeks after the first hepatic artery intervention; as for the follow-up review, it can be 1-3 months apart depending on the patient’s specific situation. The frequency of intervention should depend on the follow-up results. If the imaging shows dense iodine oil deposits in the liver at 4-6 weeks after the intervention, necrosis of the tumor tissue and no enlargement and no new lesions, no further intervention should be done for the time being. The interval between the initial 2-3 interventions can be short. Thereafter, the treatment interval should be prolonged in the absence of tumor progression to ensure the recovery of liver function. During the treatment interval, the survival of liver tumor can be evaluated using CT and/or MRI dynamic enhancement scans to decide whether another interventional treatment is needed. If the tumor continues to progress after several times of interventional treatment, consideration should be given to switching to or combining with other treatment methods, such as surgery, local ablation and systemic therapy.
II. Suggestions of multidisciplinary comprehensive treatment model for hepatocellular carcinoma
Due to the special characteristics of HCC, which occurs on the basis of chronic liver disease or liver cirrhosis, highly malignant and complex and difficult to treat, special emphasis is placed on multidisciplinary standardized and comprehensive treatment; and on this basis, individualized treatment is advocated for different patients or different stages of the same patient. Some domestic scholars have proposed that patients with liver cancer can be divided into two categories of ECOG score 0-2 and 3-4 to adopt different treatment strategies according to their physical condition and ECOG scoring system.
For patients with major branches of portal vein (main portal vein and grade 1/2 branches), radiotherapy and/or portal stent implantation and TACE are recommended if complete resection of the tumor and the carcinoma thrombus is expected to be impossible; when the tumor and the carcinoma thrombus can be removed in one piece, “surgical resection of liver cancer, portal vein embolization, chemotherapy pump implantation + postoperative portal vein heparin flushing, continuous perfusion Chemotherapy + TACE” can significantly improve the survival rate and reduce the recurrence rate of postoperative metastasis in patients with hepatocellular carcinoma combined with portal vein cancer embolism. For patients with cancer embolism in inferior vena cava, if it is caused by tumor compression and the patients are asymptomatic, they can be treated with TACE without stent placement and observe whether the tumor can shrink. If the cancer embolism is caused by tumor invasion of inferior vena cava, it is recommended to place inferior vena cava stent or stent at the same time of TACE, and can be combined with radiation therapy.
C. Treatment of underlying disease
When choosing treatment for HCC, we should emphasize the treatment of underlying liver disease (chronic hepatitis B, cirrhosis and liver dysfunction), and pay attention to the examination and monitoring of viral load when performing surgical resection or liver transplantation, local ablation, TAI/TACE, radiotherapy and systemic therapy (molecular targeted drug therapy and chemotherapy), and consider the prophylactic application of antiviral drugs; at the same time, after hepatectomy In addition, standardized antiviral therapy is also advocated.
In conclusion, early detection, diagnosis and treatment of HCC must be given high priority; the principle of standardized and comprehensive treatment should be followed, which emphasizes the importance of taking a multidisciplinary approach based on the underlying disease, the pathological type of tumor, the site and extent of invasion (clinical stage), portal or inferior vena cava thrombosis and distant metastases, combined with the general condition (PS ECOG score) and the functional status of the patient’s organs (especially the degree of liver function compensation). In addition, we adopt multidisciplinary team (MDT) model, carry out extensive and in-depth multidisciplinary communication, discussion and cooperation, formulate the best individualized treatment plan for patients, and select or combine surgery, hepatic artery intervention, local ablation, radiotherapy, systemic therapy (molecular targeted therapy, chemotherapy, biological therapy, Chinese medicine and anti-cancer treatment) in a planned and reasonable manner. In order to avoid inappropriate or excessive treatment, we should select or combine various methods such as surgery, hepatic artery intervention, local ablation, radiotherapy, systemic therapy (molecular targeted therapy, chemotherapy, biological therapy, Chinese medicine and antiviral therapy, etc.) and symptomatic treatment to maximize tumor control, improve overall efficacy, improve patients’ quality of life, and achieve the goal of prolonging survival or striving for eradication. Meanwhile, individualized treatment based on molecular typing of liver cancer may be an important direction for future development.
IV. Follow up
For patients with hepatocellular carcinoma, regular follow-up through dynamic observation of patients’ symptoms, signs and adjuvant examinations (mainly serum AFP and imaging examinations) is emphasized, and disease development, recurrence or treatment-related adverse reactions should be monitored. It is generally believed that the frequency of follow-up should be every 3-4 months within 3 years after treatment; every 4-6 months during 3-5 years; and can be changed to 6-12 months if it is still normal after 5 years.