According to the statistics in 2008, the number of new liver cancer cases in the world is 748,000 and the number of deaths due to liver cancer is 696,000, ranking the 5th and 7th in the incidence of malignant tumors in men and women, and the 2nd and 6th in the causes of death. 50% of the new cases of liver cancer worldwide are in China, and the mortality rate of liver cancer in China ranks the 2nd among all kinds of cancer mortality.
I. Screening surveillance and diagnosis of primary liver cancer
HCC, ICC and mixed cancers, etc. HCC accounts for more than 90%, and the term “hepatocellular carcinoma” in this specification mainly refers to HCC. autoimmune diseases and cryptogenic liver disease. This guideline emphasizes early screening and early surveillance of liver cancer.
Routine screening and surveillance indicators include AFP and liver ultrasound. European and American scholars believe that the sensitivity and specificity of AFP is not high, and the 2010 edition of AASLD guidelines do not use AFP as a screening indicator. However, HCC in China is associated with HBV infection, unlike in Western countries where it is mostly HCV, alcohol and metabolic factors. The norms still use AFP as an indicator for routine surveillance screening.
The criteria still take pathological diagnosis as the gold standard for diagnosis, including hepatic occupying lesions or extrahepatic metastatic lesions or surgical resection of tissue specimens confirmed by pathological histology and (or) cytological examination. However, among all solid tumors recognized at home and abroad, HCC is the only one that can be diagnosed clinically if the tissue specimens or cytological examination cannot be obtained for special reasons. Combining with our national situation, previous domestic criteria and clinical reality, the expert group proposed to strictly grasp and jointly analyze.
1, with evidence of cirrhosis and HBV (or) HCV infection.
2, typical HCC imaging features: CT and/or MRI examinations show rapid inhomogeneous vascular enhancement of the liver occupancy in the arterial phase and rapid elution in the venous or delayed phase.
(1) HCC can be diagnosed if the liver occupancy is ≥2 cm in diameter and one of the two imaging examinations, CT and MRI, shows a liver occupancy with the features of hepatocellular carcinoma described above;
(2) If the diameter of liver occupancy is 1-2cm, both CT and MRI imaging examinations should show that the liver occupancy has the characteristics of hepatocellular carcinoma mentioned above before HCC can be diagnosed.
3. Serum AFP ≥ 400ug/L for 1 month or ≥ 200ug/L for 2 months, and exclude other causes of elevated AFP, including pregnancy, germline tumors of embryonic origin, active liver disease and secondary liver cancer.
Despite the development of clinical diagnostic criteria for HCC, due to the diversity and uncertainty of the disease, specific clinical cases still require careful identification, close follow-up or recommendation for selective hepatic arteriography or performing liver puncture biopsy. For the classification of hepatocellular carcinoma and numerous clinical staging systems, the standardization determines the application of the TNM staging (revised in 2010) and BCLC staging of the histological classification criteria of liver and intrahepatic bile duct tumors and established by WHO in 2005, which is believed to play a very positive role in standardizing the treatment behavior of primary liver cancer.
II. Comprehensive systemic treatment is the trend of liver cancer treatment
Most of the HCC patients in China are in the middle and late stage when they are found, and most of them have the background of chronic liver disease. Single surgery or other treatments can hardly solve all problems, and it is necessary to adopt multidisciplinary comprehensive treatment. The treatment of hepatocellular carcinoma has stepped from the original single treatment to the multidisciplinary integrated systemic treatment, and the treatment trend will surely greatly improve the long-term survival rate and reduce the death rate of primary liver cancer patients in China. For example, surgical resection has always been the first choice of surgeons for liver tumors, but now, after comprehensive evaluation and objective analysis of patients, including the size and number of tumors, as well as the presence of distant organ metastases and the patient’s general condition, surgery has become one of the choices in the comprehensive treatment of liver cancer.
The treatment concept of multidisciplinary participation is emphasized. Multidisciplinary standardized treatment centers have been established in foreign countries in the 1990s, while they are still not established in China. The introduction of the standardization is hoped to further promote the objective assessment of patients by multidiscipline and develop the best individualized treatment plan for patients by learning some advanced experiences from foreign countries. Comprehensive systemic treatment includes surgical treatment (hepatectomy, liver transplantation), local treatment (local ablation therapy, hepatic artery intervention), radiotherapy, systemic systemic treatment (molecular targeted drugs, systemic chemotherapy, Chinese medicine, biological therapy, basic liver disease and antiviral therapy, etc.).
Choice of hepatic cancer resection and liver transplantation
The postoperative long-term survival rate of patients with surgically resectable intermediate and advanced HCC is significantly higher than that of non-surgical or palliative patients. As with all international guidelines for the treatment of hepatocellular carcinoma, hepatectomy is still preferred for hepatocellular carcinoma suitable for surgical resection. Under the premise of fully pursuing the thoroughness and safety of resection, we should do a good job of preoperative comprehensive assessment of liver function reserve and selection of indications, improvement of intraoperative techniques and postoperative prevention and treatment of recurrence and metastasis. Regardless of the size, number of tumors, presence or absence of portal or hepatic vein carcinoma thrombus or bile duct carcinoma thrombus, liver function Child-Pugh score of grade A can then be used to estimate the expected residual liver volume after resection by imaging techniques, and patients with residual liver volume accounting for more than 40% of the standard liver volume are recommended for surgical resection. The controversy over whether to choose liver transplantation for the surgical treatment of hepatocellular carcinoma focuses on whether to perform liver transplantation in patients with resectable limited hepatocellular carcinoma with good liver function compensation.
In the case of liver cancer combined with cirrhosis with loss of liver function (Child-Pugh grade C) and eligible for transplantation, there is no controversy that liver transplantation is preferred. As of July 1, 2012, the total number of registered cases of liver transplantation in China is 22,244, of which liver transplantation for liver cancer accounts for about 50% of patients. Based on the international liver transplantation criteria for liver cancer, China has expanded the indications for liver transplantation for liver cancer, providing many liver cancer patients with the possibility of radical cure and hope for long-term survival. However, we should also see that in the national situation of increasing scarcity of donor livers and the lack of uniform standards for liver transplantation for liver cancer in China, we should still adopt the principle of “no promotion, no priority” for liver transplantation for intermediate and advanced liver cancer, with a view to obtaining donor livers for patients with benign liver disease and early-stage liver cancer who may be able to achieve long-term survival.
This guideline excludes patients with good liver function who can tolerate hepatectomy from the indications for liver transplantation for the time being. For the applicable criteria of liver transplantation for liver cancer, after thorough discussion by the expert group, this guideline recommends the adoption of the criteria, that is, a single tumor diameter ≤ 6 or 5 cm, or the number of multiple tumors ≤ 3 and each tumor diameter ≤ 4 or 5 cm, the total diameter of all tumors ≤ 8 cm, without the invasion of blood vessels and lymph nodes.
The choice of surgery and local treatment
Ablation therapy is a treatment method to kill tumor tissues directly by physical or chemical methods with the help of medical imaging technology to guide the targeting of tumor.
Ablation therapy, surgical resection and liver transplantation are effective treatments for liver cancer, which have strict indications and contraindications. There is a clinical controversy whether surgical treatment or percutaneous ablation therapy is preferred for hepatocellular carcinoma below 5 cm. In recent years, it has been continuously reported in the literature that RFA and MWA are minimally invasive, safe, and have satisfactory efficacy, and can achieve long-term survival outcomes similar to those of surgical resection in the treatment of small liver cancers. In terms of treatment outcomes, two randomized controlled studies have shown no significant difference in survival between those treated with ablation and those undergoing surgical resection, but surgery is more advantageous in terms of tumor-free survival and recurrence rates.
The recommendation of this guideline is to first recommend surgical resection for patients with a single tumor <5 cm in diameter or two to three tumors with a maximum tumor diameter ≤3 cm. Based on the existing evidence of evidence-based medicine, ablation can also be considered for patients with tumors ≤3 cm in maximum diameter. For larger hepatocellular carcinoma (>5 cm), whether multi-point or staged ablation or open or laparoscopic ablation can be performed, there is no sufficient evidence for reference, so it is not recommended.
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. However, after hepatectomy or liver transplantation, in order to prevent recurrence and metastasis of hepatocellular carcinoma, TAI or TACE treatment can be considered according to the patient’s postoperative recovery.
V. Choice of surgery and other treatment methods
Radiotherapy and chemotherapy are the basic treatments for malignant tumors and are commonly used clinically for palliative treatment of hepatocellular carcinoma. However, with the development of precise radiotherapy technology and the introduction of new generation chemotherapeutic drugs, radiotherapy and chemotherapy have become valuable for advanced patients with extrahepatic metastases, patients with limited lesions but not suitable for surgery and TACE, and patients with portal vein trunk or inferior vena cava thrombosis to control the disease and benefit survival.
Molecular targeted drug therapy: Hepatocellular carcinoma has become a new research hotspot and has received high attention and importance. Multicenter phase III clinical studies have shown that sorafenib, a molecularly targeted drug, can delay the progression of HCC and significantly prolong the survival of patients with advanced disease, and has a better safety profile. Studies on sorafenib as an adjuvant therapy after radical resection or local ablation, whether sorafenib can prolong the survival of liver cancer patients after liver transplantation, and whether sorafenib can prevent recurrence and metastasis of liver cancer in patients with vascular invasion after hepatectomy have been approved by EMEA, FDA and SFDA. Studies on whether sorafenib can prevent recurrence and metastasis of hepatocellular carcinoma, and studies on the combination of sorafenib with hepatic artery intervention are underway in some large centers. Other new molecularly targeted drugs are also expected.
Chinese medicine taking tonics can help reduce the toxicity of radiotherapy and chemotherapy, improve cancer-related symptoms and quality of life, and possibly prolong survival, and can be an important adjunct to liver cancer treatment.