Wu Bowen Xu Aimin Panzeya

China Journal of Practical Surgery, February 2003, Volume 23,No. 12.

Primary liver cancer (HCC) is one of the most frequent malignant tumors in China. In recent years, remarkable achievements have been made in the treatment of HCC in China, especially the curative effect of surgical resection. After 1990s, the overall 5-year survival rate of HCC was 48.6%, of which 73.3% was small HCC. However, because most liver cancers are found late or early, they spread in the liver; Most patients with liver cancer are accompanied by severe liver cirrhosis and abnormal liver function; Due to the limitation of age or other diseases, less than 25% of patients with clinical liver cancer have the conditions for surgical resection, and the recurrence rate of liver cancer after operation is also very high. For these patients who have lost the opportunity of operation or do not have the conditions for radical resection, the comprehensive treatment of various non-surgical therapies based on intervention has been greatly developed and achieved certain results, which has become an important means to further improve the curative effect of liver cancer. Interventional therapy is the most effective method among these non-surgical treatments and is widely used in clinic.

Interventional treatment of liver cancer is a local treatment under the guidance of imaging methods. It mainly includes radiation interventional therapy and ultrasound interventional therapy. The commonly used interventional therapy methods in clinic are summarized as follows.

1, Radiointerventional Therapy for Liver Cancer

Radiointerventional therapy has been used in clinic for more than 30 years, and the main method is transcatheter arterial chemoembolization (TACE), which has been widely used and has a positive effect, and has become the first choice for non-surgical treatment of unresectable liver cancer. 95%-99% of the blood supply of liver cancer comes from hepatic artery system. After hepatic artery infusion chemotherapy, the local drug concentration of tumor can reach 100-400 times of that of the whole body, which enhances the anti-tumor effect and obviously reduces the systemic toxicity. Embolization can block the blood supply of tumor, make the tumor seriously ischemic and necrotic, and then fibrosis and atrophy, which is helpful for the second-stage resection of tumor; Local necrosis and liquefaction of tumor also help to relieve tumor pain; Studies have shown that TACE can also stimulate immune effect and improve the anti-tumor ability of the body.

Indications and contraindications of 1. 1 ace:

Indications are as follows. (1) unresectable liver cancer, no severe liver dysfunction, no complete obstruction of portal vein trunk; (2) tumor accounts for

Tumor pain, bleeding and arteriovenous fistula; (5) Preventive treatment after liver cancer resection. Contraindications: (1) liver function damage, serum total bilirubin and aspartate aminotransferase >: normal twice, moderate ascites; (2) The coagulation function is obviously abnormal, with bleeding tendency, with white blood cells ≤3.0× 109 and platelets ≤ 50×109; (3) Portal vein tumor thrombus is extensive (left and right branches) or the trunk is occluded (but it can be used as TAI); (4) Recent obvious portal hypertension or varicose bleeding of upper digestive tract; (5) liver

Tumors account for more than 70% of the whole liver (if the liver function is normal, a small amount of lipiodol can be used for embolization in stages); (6) extensive intrahepatic or extrahepatic metastasis; (7) Patients with poor general condition or serious diseases in other organs such as heart, brain, lung and kidney.

The commonly used drug for hepatic artery perfusion is 5-Fu, and cisplatin, carboplatin, mitomycin and epirubicin are selected for combined use. Commonly used embolic drugs include lipiodol, gelatin sponge and microspheres of various materials (including drugs and radioisotopes).

1.2 Complications of Radiointerventional Therapy

The common reactions after TACE include nausea, vomiting, severe pain in liver area, loss of appetite, fever and so on. Occasionally there is cholecystitis and even gallbladder gangrene and peritonitis; Gastric mucosal erosion, ulcer, esophageal variceal bleeding and liver or renal failure should be strictly prevented.

1.3 curative effect and controversial issues of radiation interventional therapy

After years of treatment practice of a large number of cases, people realize that TACE can improve the quality of life of patients and prolong their survival time.

Changhai Hospital of the Second Military Medical University and Oriental Hepatobiliary Surgery Hospital (1999) reported more than 000 cases of TACE, and the 5-year survival rates after treatment were 45%-77%, 17-22% and 6- 13% respectively. After TACE treatment, the tumor shrank and obtained two-stage resection, accounting for 6.2- 1 1.2% of the total number of TACE cases. The 5-year survival rate of patients with secondary resection is similar to that of patients with small liver cancer. After repeated TACE and comprehensive treatment, the tumor shrank and disappeared in a few cases, and some cases have survived for more than 10-20 years, achieving curative effect.

There are still many shortcomings and difficulties in TACE treatment, which affect its curative effect. (1) Treatment of patients with portal vein tumor thrombus. Liver cancer complicated with portal vein tumor thrombus can reach 62.2-90.2%. If such patients give up treatment, their survival time is only 3-6 months. Therefore, TACE treatment of portal vein branch tumor thrombus is the consensus of domestic and foreign literature. At present, there are different opinions about whether TACE is suitable for the treatment of portal vein tumor thrombus, and quite a few domestic authors hold negative opinions. According to the observation and study of more than 1000 TACE cases in Changhai Hospital of the Second Military Medical University and Oriental Hepatobiliary Surgery Hospital 10000, the blood supply of portal vein was not completely blocked by tumor thrombus in the portal vein. Even if it is completely blocked, many tortuous venules have been formed around it to enter the liver, and these collateral circulation can still maintain the blood supply of the liver after TACE. Ralls found that even in the same patient, the blood flow from portal vein to liver was not constant. When the hepatic artery blood flow is blocked, the portal vein blood flow from the liver will become blood flowing to the liver to meet the needs of liver blood supply. In addition, the liver can extract a high proportion of oxygen from portal vein blood to improve the more effective utilization of portal vein circulation, which shows that the liver has the ability to prevent ischemic necrosis. Therefore, we think that patients with portal vein tumor thrombus generally have good liver function.

TACE can safely pass through the dangerous period. It has also been suggested that the treatment of hepatocellular carcinoma with portal vein tumor thrombus by injecting IL-2 through portal vein puncture combined with TACE can improve the curative effect of patients. (2) At present, there are different opinions on whether TACE should be performed before resectable liver cancer. Most authors believe that preoperative TACE is not necessary for liver cancer that can be radically resected in one stage, especially for a single tumor with a diameter less than 5 cm. For the larger tumor (> > 10cm), there is no capsule, the boundary is unclear, and it is close to the large blood vessels in the liver; It is difficult to perform radical resection for liver cancer with subclinical lesions or multiple nodules around it. On the contrary, it is easy to relapse in a short time after surgical stimulation, spread faster than before operation, and promote extrahepatic metastasis. This kind of tumor should be treated with TACE before operation. If the tumor is obviously shrunk, the surrounding subclinical lesions are necrotic, and the inflammatory capsule is formed around the tumor, so that the boundary becomes clear, it can be resected again, and its 5-year survival rate is 62.65438 0%. If the tumor does not shrink after TACE treatment and does not meet the conditions of radical resection, we believe that the survival time of continuing comprehensive non-surgical treatment is still longer than that of barely palliative surgical resection. (3) Selective preventive TACE after hepatectomy is an important method to improve the curative effect of liver cancer. The main function of TACE after operation is to confirm whether there are residual small cancer foci after operation through DSA, and further kill them. It has been reported that the prospective control study of TACE treatment for high-risk postoperative recurrence cases (tumor without capsule, satellite nodules, failure to reach the standard of radical resection, high PCNA index or strong positive expression of p53) shows that TACE group and postoperative simple radical treatment.

Compared with the resection group, the recurrence rate of the former decreased from 52.3% to 62.5%, and the 4-year survival rate increased from 33.5% to 53.7%, which improved the curative effect. (4) Factors affecting the curative effect of TACE. In recent years, some scholars have conducted a prospective randomized controlled study, and think that TACE can really kill tumors and improve the curative effect of advanced liver cancer, but a considerable number of cases show the limitations of this therapy, and even show worse curative effect. Studies have shown that after TACE treatment, although more than 50% of the tumor tissues of 73% patients with liver cancer are necrotic, only 5% of the tumor tissues are completely necrotic, and the remaining cancer cells will have or produce stronger proliferation and invasion ability. For example, some cases have multiple or diffuse disseminated lesions in the liver, and some cases have multiple metastatic lesions in the lungs within a short time after TACE. In addition, the liver cancer nodules and the area around the capsule are supplied by the portal vein. After TACE, there are often surviving cancer cells around the tumor or under the capsule, the blood supply of peripheral collateral is established quickly, and the residual cancer tissue proliferates quickly. Patients with liver cancer are often accompanied by cirrhosis and portal hypertension. After TACE, most patients have liver function damage, and some patients have serious complications such as upper gastrointestinal bleeding and liver failure. Repeated TACE treatment will cause liver atrophy and severe decompensation of liver function, which will further aggravate the disease. It has also been reported that TACE can not prevent intrahepatic metastasis caused by portal vein tumor thrombus, make drug embolization incomplete, and even promote intrahepatic dissemination and metastasis. In addition, tumor size, tumor blood supply and liver function are all factors that affect the curative effect of TACE.

1.4 How to further improve the curative effect of TACE

In view of the above factors affecting the curative effect of TACE, besides improving the surgical method, comprehensive therapy based on TACE is also adopted to improve the curative effect. For example, micro-guide wires are used for fine superselective insertion into hepatic segments with tumors or even hepatic subsegments or distal tumor feeding arteries.

Pulse, so that the tumor is completely necrotic under the action of high-concentration chemotherapy drugs, and the blood vessels are embolized to the maximum extent by high-dose embolic agents; If there is arterial-portal vein fistula of tumor blood vessels, embolic agent can enter the portal vein branch, which will block the blood supply of tumor-bearing artery and portal vein branch, resulting in complete necrosis of tumor, and at the same time protect liver tissue to the maximum extent; In addition, paying attention to the treatment of parasitic blood vessels is a measure to improve the curative effect of TACE.

In recent years, it has been reported in China that TACE injected radioisotopes through hepatic artery catheter and treated liver cancer with internal irradiation on the basis of chemoembolization. The 3-year and 5-year survival rates increased to 74% and 56%. Since Kan et al. put forward that liver cancer has dual blood supply, the clinical research reports of dual chemotherapy of hepatic artery and portal vein have increased. It is reported that the two-year survival rate of liver cancer can be improved from 265,438 0% to 39.6% after dual chemotherapy of hepatic artery and portal vein and intratumoral injection of lipiodol and ethanol. There are also studies on temporary occlusion of tumor hepatic vein with balloon catheter and superselective TACE, and its curative effect is significantly higher than that of TACE alone. However, this new technology has a short development time and few cases, so it is difficult to evaluate.

In addition, high-dose lipiodol embolization, high-temperature lipiodol thermal embolization or TACE combined with traditional Chinese medicine (cinobufotalin, camptothecin, etc. ), or TACE combined with radiotherapy, absolute ethanol injection, microwave coagulation or radiofrequency ablation, combined with immunity and traditional Chinese medicine treatment can further improve the curative effect on liver cancer.

2. Ultrasound interventional therapy for liver cancer.

Due to various reasons, such as abnormal liver function, other serious diseases, tumor location and size, etc. For liver cancer that cannot be treated surgically for the time being, local treatment can be performed under the guidance of B-ultrasound, including intratumoral drug injection, microwave coagulation, radiofrequency ablation, argon-helium knife local freezing, etc. In recent years, this therapy has been widely carried out at home and abroad, and has made rapid progress.

2. 1 percutaneous intratumoral drug injection

Drugs for injection include anhydrous ethanol, acetic acid, high-temperature distilled water or brine, etc. Among them, intratumoral ethanol injection (PEI) is a simple, safe, widely indicated and effective method for the treatment of liver cancer, which has attracted clinical attention and been widely used. The Oriental Hepatobiliary Surgery Hospital of the Second Military Medical University summarized 2000 cases of liver cancer. After 3 1000 PEI treatments, the tumor necrosis reduction rate can reach 6 1.5-87.9%, and the 2-,3-and 5-year survival rates of tumors with diameters less than 3 cm can reach 85%, 80% and 55%, and the curative effect is no less than that of radical surgery. The 2-year and 3-year survival rates of patients over 5 cm also reached 37.8% and 65,438+05%, which prolonged the survival time of patients. The author thinks that if TACE can be combined with other therapies, the curative effect can be further improved. Intratumoral injection of 15-50% acetic acid has stronger tissue permeability and larger infiltration range than PEI, and the damage to tumor tissue is more than 1 times of PEI, and the dosage and times of injection are less than PEI. Dodd and other studies have reported that the 3-year and 5-year survival rates of acetic acid in the treatment of small liver cancer can reach 79% and 49%, which can completely replace surgical resection.

In recent years, there have been reports of intratumoral injection of high temperature distilled water (PHDI) or normal saline at home and abroad. The curative effect is similar to that of PEI, but it has few side effects and high safety. It is reported that after PHDI treatment, the tumor necrosis rate reached 865,438 0.2% (56/69).

The curative effect on liver cancer with diameter less than 6 cm is better than PEI. However, due to the large amount of injection and the high pressure in the tumor, whether it will cause complications such as tumor spread and how effective it is remains to be observed by a large number of cases.

2.2 radiofrequency ablation therapy

This is a new technology for minimally invasive treatment of liver cancer. In recent years, there are many domestic and foreign literature reports, and the curative effect is quite positive. Rossi et al reported that the median survival time of 39 cases of small hepatocellular carcinoma with nodule diameter less than 4 cm and 1 1 metastatic hepatocellular carcinoma was 44 months after radiofrequency treatment, with an average follow-up of about 22.6 months, and the local recurrence rate was less than 10%. The 1, 3-and 5-year survival rates of primary liver cancer in this group were 94%, 68% and 40% respectively. Oriental Hepatobiliary Surgery Hospital of the Second Military Medical University (200 1) reported that 63 cases of liver cancer < 5 cm were treated by radio frequency, and the total effective rate was 96.4%. The tumor was completely solidified and necrotic, and 59 cases survived for more than 1 year (still under follow-up). It is considered that radiofrequency treatment of small hepatocellular carcinoma can achieve the same effect as radical resection. Another group of domestic reports also believe that the necrosis rate of liver cancer with a diameter of ≤3cm can reach 90- 100%, with good curative effect and prolonged survival. This therapy is suitable for patients with poor liver function, old age or unsuitable for surgical treatment; Or the tumor is located in the center of the liver, in the hilar area; Or recurrent liver cancer with difficult operation (< 5 cm, especially < 3 cm); Large liver cancer without surgical indications can also be tried, and combined with TACE comprehensive treatment can improve the curative effect. Although+therapy has the advantages of safety, wide indications and reliable curative effect, we should also pay attention to complications such as puncture bleeding, abscess formation, adjacent organ damage and perforation. Tumors with jaundice, ascites, coagulation dysfunction, huge masses and close relationship with biliary tract should be considered taboo.

2.3 microwave curing (MCT) therapy

Through the thermal effect of microwave, the tumor tissue is heated to above 50℃, resulting in tumor tissue coagulation and necrosis. This therapy is used at home and abroad.

After years of application, it has achieved remarkable curative effect.

SATO reported that MCT was used to treat 19 cases of unresectable liver cancer (diameter 5-9 cm). 3 1 lesion, 28 cases were completely ablated and cured, 2 cases survived for a long time, 10 cases survived without tumor 10-64 months, and 3 cases survived with tumor 17-22 months. A domestic group reported 27 cases of 44 hepatocellular carcinoma nodules with a diameter less than 3 cm. After MCT treatment, the complete tumor ablation rate was 95.5%, and the 2-,3-year survival rates were 96.2%, 8 1 .4% and 8 1.4%, respectively, which indicated that MCT had satisfactory curative effect on tumors, especially for patients with liver cirrhosis and severe liver function. It is also reported that this therapy can lead to complications, such as liver failure, bleeding, damage to peripheral organs, especially biliary tract. Attention should be paid to the selection of indications and careful operation.

2.4 targeted cryoablation with argon-helium knife

Cryotherapy for liver cancer has been carried out for many years at home and abroad, and achieved certain results. Cryopreservation with argon-helium knife is a new technology developed in recent years.

A new cryotherapy technique developed in clinic, argon-helium knife is inserted into liver tumor tissue through four or eight insulated superconducting knives, which can be used alone or in combination. Because the superconducting knife is hollow, when high-pressure argon gas is output, the tip area is cooled to-1 40℃ within1min, and the tumor tissue is ice-spherical, and frozen for15-20min. The ideal treatment is to see that the ice hockey is beyond the tumor range 1cm or more under B-ultrasound. After freezing, turn on the helium heating system to raise the temperature of the knife tip, thaw the diseased area, and rise to 20-45℃ within a few minutes. When thawing, the ice hockey will expand and burst, which can also cause serious damage to tumor tissue, and then repeat the above cycle.

The indications of this therapy are: (1) The patient is in good health and has no other important diseases; (2) Normal or slightly abnormal liver function, children A or B; (3) There are less than 3 tumors with a diameter of less than 5 cm; (4) for some reason can't perform surgery or

Patients with poor efficacy of other therapies. For larger tumors, multiple superconducting knives can be tried successively, or multi-point puncture treatment during operation, and postoperative treatment combined with TACE can still achieve good results. During argon-helium knife laparotomy, because it is operated under direct vision, 5-8cm large diameter superconducting knife can be used for multi-point puncture. This therapy can also be used for large tumors in the semi-liver. Foreign authors reported that many metastatic liver cancers were treated by cryotherapy. Foreign authors reported 123 cases of metastatic liver cancer. After treatment, the 5-year survival rate was 44%, the 5-year disease-free survival rate was 30%, and the 10-year survival rate was 19%. For large hepatocellular carcinoma > 5 cm, TACE treatment still has a considerable cure rate and obviously prolongs the survival time of patients. The authors found that the immune indexes such as CD3+, CA4+, CD8+ and NK cells increased significantly after operation, suggesting that this therapy can stimulate the immune function of the body and enhance the anti-tumor effect. Three cases (primary 2 1 case, metastatic 21case) of liver cancer were treated by argon-helium knife in Shanghai Oriental Hepatobiliary Surgery Hospital. The diameter of liver cancer is less than 5 cm. After treatment, AFP turned negative to 80%, and CT and MRI reexamination showed that the tumor necrosis rate was 66.7%. Because this therapy has the advantages of less trauma, quick recovery, no influence on the immune function of the body, and often good curative effect, this new technology has gradually developed in China. Complications include needle track or hepatic capsule bleeding, upper gastrointestinal bleeding, adjacent organ damage, hemoglobinuria and even renal insufficiency. For the treatment of large tumors, infusion or electric blanket should be used to prevent intraoperative cold shock; After operation, alkaline urine and diuresis were used to protect the kidney. How to upload files