In China, liver cancer is a high incidence disease, which seriously endangers people’s health and poses a great burden to families and society. Its mortality rate occupies the third place among digestive tract tumors, after gastric cancer and esophageal cancer; among malignant tumors, it is the 7th in men and the 9th in women. There are about 6.35 million new cases of malignant tumors in the world every year, of which liver cancer accounts for 260,000 cases (4% of malignant tumors), of which 42.5% occur in China. Zheng Zhaomin, Department of Minimally Invasive Oncology, Shandong Qianfo Mountain Hospital
Primary liver cancer has high malignancy, rapid development and poor prognosis. Research shows that the occurrence of liver cancer is mainly related to various viral hepatitis (hepatitis B, hepatitis C, etc.), cirrhosis, aflatoxin, alcohol and drinking water pollution, etc. In China, the positive rate of serum hepatitis B markers in primary liver cancer patients is as high as 90%. Therefore, early diagnosis and treatment of high-risk groups of liver cancer (age >40 years, long history of slow hepatitis B, cirrhosis, and family history of liver cancer) are of great importance.
Diagnosis of hepatocellular carcinoma.
1.Serological tests.
AFP: It is one of the most specific methods to diagnose hepatocellular carcinoma, with a positive rate of 60-90%. In the absence of other evidence of hepatocellular carcinoma, hepatocellular carcinoma can be diagnosed if AFP is positive by convective immunoelectrophoresis or quantified >400ng/ml for more than one month, and pregnancy, active liver disease, germinal gland embryonal tumor, etc. can be excluded.
Others: γ-glutamyl transpeptidase, alkaline phosphatase and lactate dehydrogenase, due to the lack of specificity, are mostly used as auxiliary diagnostic indicators.
2.Imaging examination
(1) Ultrasound: It can show the size, shape, location of tumor and whether there is cancerous thrombus in hepatic vein or portal vein, etc. Its diagnostic rate can reach 84%, and it can detect lesions of 2 cm or smaller in diameter.
(2) Ultrasonography: It can dynamically observe the blood perfusion of intrahepatic occupancies, and has the same efficacy as enhanced CT for the ability to identify benign and malignant single small intrahepatic lesions and judge the local efficacy of liver cancer ablation.
(3) CT: High resolution can detect early hepatocellular carcinoma of about 1 cm in diameter, and the application of enhancement scan can help to differentiate it from hemangioma. It can significantly compensate for the deficiencies of ultrasound and gas obscuration.
(4) Angiography (DSA): For carcinoma with rich blood vessels, it can sometimes show occupying lesions with a diameter of 0.5 to 1 cm, and its diagnostic accuracy is up to 90%. It can determine the location, size and distribution of lesions, especially for the localization and diagnosis of small hepatocellular carcinoma, which is the most superior among various examination methods at present.
(5) MRI imaging: The diagnostic value is similar to that of CT, which can obtain cross-sectional, coronal and sagittal images, and is better than CT in differentiating benign and malignant hepatic occupying lesions, especially hepatic hemangioma, and can show hepatic veins and portal veins without enhancement. In particular, it is better than enhanced CT for the assessment of tumor activity after treatment and can be comparable to hepatic arteriography.
3.Liver biopsy
Puncture biopsy: Needle aspiration cytology by liver aspiration has definite diagnostic significance. Currently, fine needle aspiration is mostly performed under B-type ultrasound guidance, which can help improve the positive rate, but there are risks of bleeding, tumor rupture and needle metastasis.
Interventional treatment of hepatocellular carcinoma
I 1. Indications for hepatic artery embolization chemotherapy (TACE)
(1) Applied 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) middle and late stage hepatocellular carcinoma that cannot be surgically resected, without serious liver and kidney dysfunction, without complete obstruction of portal vein trunk and tumor occupancy <70%; (3) small hepatocellular carcinoma; (4) those who failed in surgery or recurred after resection; (5) control of pain, bleeding and arteriovenous fistula; ( 6) prophylactic hepatic artery chemoembolization after hepatectomy for hepatocellular carcinoma. < span="">
2. Contraindications
(1) Severe liver dysfunction, such as: severe jaundice (bilirubin >100 μmol/L), hypocoagulability, etc. massive ascites or severe cirrhosis with liver function of child grade C; (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, severe peritonitis; (4) cancer accounting for 70% or more of the whole liver (if liver function is basically normal, a small amount of iodine oil can be used for embolization in stages); (5) white blood cells <3,000; (6) (6) those with extensive metastasis; (7) those with systemic failure.
3. Judgment of efficacy
The indicators for judging the efficacy are divided into five categories: clinical cure, apparent improvement, improvement, temporary stability, and progress or deterioration. (1) Clinical 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, or DSA without tumor blood vessels and tumor staining. The alpha-fetoprotein was normal. The patient’s survival period is more than 5 years. (2) Obvious improvement: the mass shrinks by more than 50%, the tumor foci are densely deposited with iodine oil, and the filling area accounts for more than 80% of the mass area. Intensive CT or MRI shows that the tumor tissue is largely necrotic, with only a few tumor vessels and tumor staining at the perimeter of the tumor. The methemoglobin decreased to less than 70% of the preoperative level, and the patient survived for more than 1 year. (3) Improvement: mass shrinkage >25%; but <50 %, non-uniform deposition of iodine oil in the tumor foci, filling area <50% of the mass area. Intensive CT or MRI examination shows partial survival of tumor tissue and partial necrosis, with the necrotic area accounting for about 30 % - 50 %;. Methemoglobin decreased to less than 50% of the preoperative level, and the patient survived for more than 6 months. (4) Progression or worsening: enlargement of the mass, no iodine oil deposition in the tumor foci or scattered spots, filling area < 50% of the mass area. Intensive CT or mri examination shows that most of the tumor tissues survive, tumor blood vessels are obviously increased, tumor staining is obvious, and new tumor lesions are visible. Elevated alpha-fetoprotein. < span="">
2. 1. Indications for microwave/RF ablation, anhydrous alcohol ablation (PEI), radioactive particle (iodine-125) implantation
(1) Hepatocellular carcinoma with single tumor ≤ 6.5 cm. or 2-3 tumors with the largest lesion < 6 cm.(2) Poorly located liver tumors or located in two lobes or invading large blood vessels, which are not suitable for surgical resection. (3) Multiple metastatic carcinomas in the liver with less than 5 tumors and maximum tumor diameter <3--4cm; single metastatic carcinoma in the liver treated before surgical resection of the primary cancer. (4) Patients who cannot tolerate systemic chemotherapy and other local treatments, and whose radiotherapy effect is not significant. (5) Microscopic hepatocellular carcinoma ≤2cm, precancerous lesions. (6) Recurrence of liver tumor after resection.
2. Contraindications (1) Diffuse hepatocellular carcinoma combined with cancer embolism. (2)Severe systemic failure or decreased resistance (3)Those with active infection. (4) Uncorrected coagulation dysfunction (platelets <30×109/L, prolonged bleeding and clotting time) (5) Patients equipped with cardiac pacemaker and patients with severe aneurysm should be cautious and under the supervision of a specialist if necessary.
3.Pre-operative preparation
(1) Physical examination of the patient, medical history, cardiovascular and cerebrovascular diseases and diabetes mellitus need to understand the condition and be prepared for medication.
(2) Pre-operative enhanced CT or MRI examination to determine the size, location and number of lesions.
(3) Liver function and routine blood tests, AFP or CEA, etc.
(4) Fully introduce and explain the treatment process and complications to the patient, and obtain consent approval and signature from the patient and family.
(5) Preoperative bowel clearance is done, and the patient is fasted for more than 6 h. Analgesic valium and local anesthesia are performed for better patient cooperation.
PEI treatment is more suitable for liver tumors protruding from the surface of the liver, or near the gallbladder, gastrointestinal tract, or the roof of the diaphragm, as a useful supplement to thermal ablation treatment.
2010 NCCN guidelines for liver cancer: For resectable primary liver cancer, surgical resection and ablative therapy are equivalent.
Ablation therapy can improve the body’s immune surveillance:
1. systemic immune function: patients with hepatocellular carcinoma were severely depressed before treatment, and after heat therapy, immune function was significantly restored and enhanced.
2. CD3, CD4 cells, CD4/CD8 ratio, NK cell activity and IL-2 level decreased; while CD8 cells, SIL-2R level increased.
3. Local immune function: significantly improved before and after ablation treatment:
Ultrasound-guided aspiration biopsy of the tumor and its surrounding liver tissue migration area. Results: CD68+ and CD45RO+ cells within and around the cancer were lower than normal group in the hepatocellular carcinoma group before treatment, and CD57+ cells around the cancer foci were higher than normal group, while there was no difference between treatment groups.
TACE combined with thermal ablation therapy.
Advantages.
1. improved tumor necrosis rate.
2. thermal ablation helped to increase the effect of chemotherapeutic drugs.
3. elimination of the heat sink effect after embolization.
4. tumor shrinkage and more complete ablation after bolus iodine oil plugging.
5. It plays the role of tracer positioning, which is beneficial to the accurate positioning and puncture during ablation.
4. Judgment of therapeutic effect
(1) AFP: for those with high AFP before microwave/RF ablation of primary liver cancer, whether AFP is reduced to normal range is an important marker to judge complete tumor necrosis after ablation. If AFP turns negative and maintains for a period of time, and then becomes positive again, the possibility of recurrence or metastasis should be highly alerted.
(2) Ultrasonography: Color Doppler flow imaging technology can sensitively display the blood flow signal around and inside the tumor; energy Doppler ultrasound can continuously and dynamically display the trophoblastic vessels of the tumor, which can more comprehensively display the changes of tumor blood flow distribution before and after treatment, and has greater clinical application value for the judgment of ablation efficacy of liver cancer. Ultrasonography can make timely judgment on the extent of coagulation and the presence or absence of residual blood flow in the tumor to decide whether to terminate the treatment. It can also accurately guide the placement of microwave or radiofrequency electrodes on the residual tumor site, which has the incomparable application value of CT and MRI.
(3) CT examination: Spiral CT plays an important role in judging the ablation scope, the presence of residual cancer and whether it recurs after treatment. Immediately after ablation of hepatocellular carcinoma, if the tumor undergoes coagulative complete necrosis, the CT scan will show a well-defined, homogeneous low-density area, with no enhancement in all phases of enhancement scan, and a very thin circumferential enhancement can be seen in the periphery, at which time the necrotic scope of treatment is larger than the scope of the lesion before treatment. The necrotic lesions of hepatocellular carcinoma after ablation are always hypodense during CT follow-up and do not strengthen in all stages on enhanced CT or MRI, which are pathologically based on the absence of blood supply after tumor thermal coagulation and necrosis.
Traditional treatment methods have limitations
1. Only targeting local lesions: local treatment cannot solve the systemic problem.
2. Only for imaging visible lesions: existing examination methods need further improvement; 60-70% of recurrence cases are due to microscopic metastases already present at the time of surgery
3. Partial loss of treatment timing – feeding the tiger: stubbornly applying treatment that is not sensitive to the treatment
4. Blind pursuit of “cure” causes serious damage to the organism: traumatic, with great impact on patients’ nutrition, bone marrow hematopoiesis and quality of life; over-treatment – some patients do not die of tumor, but of therapeutic damage.
Multidisciplinary comprehensive treatment (MDT) has emerged
With the further understanding of tumor diseases, the treatment of tumor has experienced from single medical-surgical treatment to integrated treatment with various methods such as interventional, radiotherapy, chemotherapy, immunotherapy and targeting.
In recent years, the American Society of Clinical Oncology (ASCO) is vigorously promoting this concept and approach worldwide, hoping to further improve the effectiveness of tumor treatment.
It is hoped that this can further improve the effectiveness of tumor treatment by fully utilizing the advantages of each discipline of oncology treatment, avoiding adverse effects, and providing the best individualized treatment plan for patients.
Principles of integrated multidisciplinary treatment
Minimize tumor load: 1. Tumor suppression (TACE, chemotherapy, radiotherapy) 2. Tumor reduction (physical ablation: microwave, radiofrequency, Helio knife, Ar-He knife; chemical ablation: PEI; surgery) 3. In situ tumor destruction (ablation, surgery)
Maximize the preservation of the body and improve the quality of life: 1. Enhance the immunity of the body: Chinese medicine to support the root; Western medicine to enhance immunity; 2. Treat the lesion precisely to minimize the damage to the normal body; 3.
The corresponding changes in the concept of tumor treatment.
1. The traditional concept of “curing tumor” should be changed to “survival with tumor”.
2. To control tumor, maintain good quality of life and prolong life.
3. Complete remission, partial remission, and stable disease are considered as effective treatment.
In conclusion, prolonging overall survival time (OS) is the ultimate goal of tumor treatment.