In the past 20 years, the diagnosis and treatment level of liver cancer in China has been greatly improved. According to the data of 3631 cases in 41 years from the Institute of Liver Cancer of Shanghai Medical University, the proportion of small liver cancer (≤5cm) accounted for 1.7% (2/118) in 58-67, 8.1% (29/356) in 68-77, 21.4% (153/715) in 78-87 and 36.2% (885/2442) in 88-98; the 5-year survival rates of the whole group (n=3631) were 2.8%, 7.3%, 26.9% and 50.1% respectively. Survival rates were 2.8%, 7.3%, 26.9%, and 50.1%, respectively; 10-year survival rates were 2.8%, 5.1%, 19.7%, and 35.4%, respectively. In recent years, imaging technology has developed rapidly, surgical technology has been improved, and local treatment such as radiological intervention and ultrasound intervention and biological treatment are remarkable. China’s research in certain aspects has reached international advanced or leading level.
1. Early diagnosis
Research on liver cancer markers has not made much progress. Alpha-fetoprotein (AFP) is still the best marker for qualitative diagnosis, but the positivity rate is about 70%. The combined application of multiple liver cancer markers may help to improve the diagnosis, such as AFP heteroplasm, rocket alglucosidase, abnormal prothrombin, pyruvate kinase, etc. The expression of oncogenes and anti-oncogenes in hepatocellular carcinoma is also being investigated. Studying novel liver cancer markers with high sensitivity and specificity is a daunting task before us. Imaging technology has developed rapidly in recent years. Ultrasound is still considered as the preferred method for screening and follow-up, and acoustic imaging, 3D ultrasound imaging, CTA, CTAP, iodine oil CT, spiral CT, MRI and DSA can help improve the correct diagnosis rate of small hepatocellular carcinoma.
80%-90% of liver cancers in China occur on the basis of hepatitis B → cirrhosis. AFP, liver function and B ultrasound should be included in routine examination in the diagnosis and treatment of liver disease patients; semi-annual examination for people with high risk of liver cancer and annual health examination for natural people is one of the shortcuts to detect early liver cancer.
2.Surgical treatment
Recent advances in liver cancer surgery include early resection, second-stage resection, recurrent cancer resection, first-stage resection of liver cancer in difficult areas, surgical treatment other than resection and liver transplantation.
Early detection, early diagnosis and early surgical resection are still the keys to improve the efficacy. There are 372 patients who have survived for more than 5 years in our clinic, among which 212 cases are small hepatocellular carcinoma (≤5cm), accounting for 57.0%. The smaller the tumor, the better the curative effect after surgical resection. According to 1000 cases of hepatocellular carcinoma with diameter ≤5cm that were surgically resected in our institute, the 5-year and 10-year survival rates were 64.8% and 46.3%; among them, 82.5% and 57.1% for 127 cases with diameter ≤2cm; while 37.1% and 29.2% for 1388 cases of large hepatocellular carcinoma (>5cm) in the same period.
The 5-year survival rate of surgically confirmed unresectable hepatocellular carcinoma resected in the second stage after reduction (n=99) was 63.5%. The 5-year survival rate for recurrent hepatocellular carcinoma resected (n=232) was 47.3%. Therefore, comprehensive treatment of unresectable large hepatocellular carcinoma followed by stage II resection and re-excision of recurrent carcinoma is of great significance to further improve the efficacy.
In recent years, there are more reports on stage I resection of liver cancer in difficult to resect sites at home and abroad. If the jaundice is caused by cholangiocarcinoma embolus or tumor compression, surgery can be considered to remove the bile duct embolus or place internal stent to relieve jaundice and prolong life.
Large hepatocellular carcinoma has long been not a contraindication to surgical resection. For large hepatocellular carcinoma with less cirrhosis and intact peritoneum, the first stage surgical resection of large hepatocellular carcinoma can sometimes achieve satisfactory long-term results and the risk is not necessarily great. In our case, it has been 27 years since the surgical resection of a 15-cm large hepatocellular carcinoma in the right lobe of the liver. However, it must be pointed out that most scholars do not advocate palliative resection or “tumor reduction” surgery for large hepatocellular carcinoma because of its poor efficacy.
Surgical treatments other than resection are gradually gaining ground. These treatments include hepatic artery ligation, intubation, freezing, microwave, intraoperative injection of anhydrous alcohol and so on. The 5-year survival rate of cryotherapy for 235 cases of hepatocellular carcinoma in our institute was 39.8%, including 55.4% for 80 cases of small hepatocellular carcinoma. Hepatic artery cannulation + ligation-based combination therapy (n=124) seems to be better than palliative surgical resection (n=176), with 5-year survival rates of 18.1% and 12.5%, respectively.
Liver transplantation has developed rapidly in recent years. To date, the number of liver transplants worldwide has exceeded 60,000 cases with a maximum survival of 29 years. In China, liver transplantation has been carried out since 1971, and the total number of cases so far has exceeded 100, with the longest survival of more than 4 years. In recent years, foreign countries have reported that liver transplantation is more effective than resection for small hepatocellular carcinoma. Because liver transplantation not only removes liver cancer, but also removes the soil (cirrhosis) in which liver cancer occurs in multiple centers.
3.Interventional treatment
In view of the fact that more and more small hepatocellular carcinomas are found in recent years, but they are not suitable for surgical resection because of the combination of cirrhosis, and even if they are resected, they will recur soon. Therefore, local treatment will have a strong vitality for a long time in the future. Intervention as a “minimally invasive” surgery has been emphasized in recent years, and “radiological intervention” has also been developing rapidly in recent years, and it can shrink some unresectable large hepatocellular carcinoma and make it available for second-stage surgery. Therefore, for resectable hepatocellular carcinoma, whether it is large or small, interventional treatment is generally advocated as much as possible. It not only has good curative effect but also has high quality of life.
4.Research on recurrence and metastasis
Recurrent metastasis after hepatocellular carcinoma surgery has become one of the main obstacles affecting the long-term curative effect. The recurrence rate of liver cancer 5 years after radical resection is 54.1%-64.5%, and 43.5% for small liver cancer. For this reason, this topic will become a major hot spot for liver cancer research in the 21st century. The two important aspects of hepatocellular carcinoma are unicentric occurrence (invasiveness of hepatocellular carcinoma) and multicentric occurrence (etiological prevention).
Our institute was the first in China and abroad to establish animal models and cell lines for high and low metastasis of human hepatocellular carcinoma, which provided valuable models for hepatocellular carcinoma metastasis research. Some promising predictive indicators and interventions have been identified in experimental studies, but a lot of research needs to be done before they can become routine clinical treatment measures. From the clinical perspective, regular long-term follow-up after surgery is an important way to detect subclinical recurrence and metastasis, and reoperative resection is the main method to further improve the long-term outcome.
All three of our cases with isolated metastatic lung cancer resected have survived 24 years and 11 months, 24 years and 7 months, and 24 years and 6 months to date. In recent years, some preoperative, intraoperative and postoperative methods to prevent recurrent metastasis have also been reported clinically, but persuasive, rigorous prospective randomized grouping is rarely reported and deserves further study.
5.Looking to the 21st century
In recent years, clinical research and long-term efficacy of liver cancer in China have made great progress. Early diagnosis and treatment of small hepatocellular carcinoma play an important role in improving the outcome, which has been recognized internationally. However, it cannot be denied that, due to many reasons, it is still difficult to carry out large-scale screening in China, so unresectable large liver cancers will still constitute the majority for quite a long time in the future. At present, it is difficult to find a single effective treatment for liver cancer, for which comprehensive treatment has important practical significance.
The former includes hepatic artery ligation, cannulation and embolization, portal vein cannulation, intraoperative freezing, microwave, laser, intra-tumor injection of anhydrous alcohol, etc.; the latter includes ultrasound intervention, radiation intervention and biological therapy, etc. Multimodal sequential integrated treatment is more effective than single treatment. The purpose of comprehensive treatment is to reduce the size of the tumor and obtain second-stage resection, to prolong the survival period with tumor, and to prevent postoperative recurrence and metastasis. In-depth study of safe, reliable and easy bleeding control techniques during hepatectomy and management of portal vein thrombosis in combination with hepatocellular carcinoma are of practical significance.
There is a lack of adequate and effective clinical evaluation index for liver function reserve, which also needs to be further explored. Research on recurrent metastasis of hepatocellular carcinoma has just started. The prevention and treatment of recurrent metastasis of hepatocellular carcinoma is a very complex and extensive challenge, and is also a critical battle in the fight against hepatocellular carcinoma. So far, the literature has reported that the recurrence and metastasis rules of various solid tumors are also applicable to hepatocellular carcinoma, but the special rules of hepatocellular carcinoma have not yet been found, which is worth further study.