Primary liver cancer (referred to as liver cancer) mainly includes hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The incidence and mortality of liver cancer in my country are ranked 4th and 3rd among malignant tumors respectively. Individualized treatment is the key to further improving the level of treatment of liver cancer. Surgery is an important method for the treatment of liver cancer, but three bottlenecks restrict the further improvement of the curative effect: the biological heterogeneity of liver cancer is extremely strong, and the precise selection of treatment methods is more difficult; liver cancer is very easy to invade the microvessels, and the recurrence rate of patients after surgery High; Intrahepatic cholangiocarcinoma is highly malignant, difficult to treat, and the patient’s survival time is extremely short.
For more than ten years, in response to these problems, the team of Professor Shen Feng from the Eastern Hepatobiliary Surgery Hospital affiliated to Naval Military Medical University took the lead in proposing to develop individualized surgical treatment based on the establishment of an individualized prognostic prediction model and tools to improve the efficacy and reduce the recurrence rate from different aspects , Prolong the survival time of patients. On the 2018 Shanghai Science and Technology Progress Awards, the project “Establishment and Application of Individualized Surgical Treatment Strategies for Liver Cancer” led by Professor Shen Feng won the first prize.
Individualized surgical treatment to improve the curative effect of liver cancer
Professor subsidiary Eastern Hepatobiliary Surgery Hospital experts interviewed Naval Military Medical University, Shen Feng
outside the Eastern Hepatobiliary Surgery, Affiliated Hospital, vice president Shen Feng Naval Military Medical University, chief physician, Professor, International Association of hepatobiliary and pancreatic, liver Branch of the Chinese Medical Science Deputy leader of the Surgery Group, member of the Standing Committee of the Liver Cancer Professional Committee of the Chinese Medical Doctor Association, deputy chairman of the Liver Cancer Professional Committee of the Chinese Anti-Cancer Association, and vice chairman of the General Surgeon Branch of the Shanghai Medical Doctor Association. Good at hepatobiliary and pancreatic diseases, especially surgical treatment of liver cancer.
Key sentence: Using various liver cancer prediction models, individualized and precise surgical treatment can be carried out, which can improve the curative effect from different links, reduce the recurrence rate, and prolong the survival time of patients.
Establish 8 prediction models for liver cancer to lay the foundation for individualized treatment
The occurrence and development process of liver cancer is very complicated, and choosing the most appropriate treatment plan for each patient is not a small problem for doctors. In response to early, massive, multiple, recurrent liver cancer and distant metastasis of liver cancer, Professor Shen’s team changed the traditional methods based on tumor staging and established 8 individualized prognostic prediction models (nominal or nomogram). grading system). Among them, the model established with preoperative data improves the accuracy of treatment selection; the model established based on postoperative pathology clarifies the key subjects of postoperative monitoring, realizes the individualized selection of adjuvant treatment measures, and improves the treatment of liver cancer. effectiveness.
In the past, the recurrence rate of patients with early liver cancer was more than 50% after 5 years, and the prognosis was extremely difficult to predict. In 2014, Professor Shen Feng’s team took the lead in establishing an artificial neural network model and an individualized prognostic nomogram for predicting the prognosis of early liver cancer surgical resection. According to the above model, doctors can identify patients with high risk of recurrence, and timely anti-recurrence treatment can significantly reduce the recurrence rate of patients and prolong survival time.
More than 70% of liver cancer patients in my country are in the middle and advanced stages when they are discovered, and they are mainly characterized by huge tumors. Surgical resection of giant liver cancer is more risky. Whether to choose surgical treatment is mainly based on the doctor’s experience in the past. In 2015, Professor Shen Feng’s team conducted a prospective analysis of 554 cases of hepatectomy for giant liver cancer, and established a nomogram model to accurately predict the surgical outcome before surgery. For patients with poor estimated efficacy, other effective treatments can be selected.
”Multiple occurrence is another major feature of advanced liver cancer. In the past, more than 10 indications for surgical resection of multiple liver cancers have been reported internationally, but they are all based on traditional tumor staging and the accuracy is poor.” Professor Shen Feng said, “Our team took the lead in proposing the basis. The biological characteristics of multiple hepatocellular carcinoma-the origin of the tumor establishes the indications for surgery (the patients with intrahepatic metastasis have very poor surgical efficacy, and the patients with multiple centers have good surgical efficacy). Originally proposed to use the largest lesion diameter and the smallest lesion in multiple liver cancer The difference in diameter indicates the origin of liver cancer, and it is confirmed by molecular pathology to establish a new indication for surgical resection of liver cancer—NDR score.” This innovation was published in 2016 in Annals of Surgery (Annals of Surgery) . Verified by peers, the predictive accuracy of NDR score ranks first, which is significantly better than BCLC staging, TNM staging and other standards.
Re-resection of recurrent liver cancer is an important contribution to the field of liver surgery in my country, but it has not been widely accepted internationally. The main reason is that it is difficult to determine the patients who are suitable for re-resection. If the selection is not appropriate, it will make the patient suffer from an operation. In this regard, Professor Shen Feng’s team analyzed the data of 635 patients with resection of recurrent liver cancer, and screened out independent risk factors that affect the 5-year survival rate after surgery, and established a preoperative prognosis prediction nomogram to determine whether to choose “re-resection”. “Excision” provides a scientific basis.
In addition, the incidence of distant metastasis after liver cancer surgery is 14%-25.5%, and the patient’s survival period is extremely short. If it can be accurately predicted and prevented in time, the prognosis can be significantly improved. The Shen Feng team conducted long-term observations on 578 patients (136 of them had extrahepatic metastasis), and innovatively established an individualized scoring model for patients with high risk of distant metastasis, with good accuracy. Since liver cancer lung metastasis is the most common, the team conducted a multi-center study and established a nomogram of liver cancer lung metastasis.
To prevent liver cancer from recurring, there are plans to implement and methods to measure
High recurrence rate is a major feature of liver cancer. So, which patients are more likely to relapse? How can we prevent or reduce recurrence? Professor Shen Feng introduced: “Microvascular invasion (MVI) is an important pathological sign of liver cancer invasion and metastasis. We have studied the relevant mechanisms and comprehensively applied adjuvant interventional therapy, chemotherapy, and iodine-125 to patients with positive postoperative pathological MVI. Five anti-recurrence treatment measures, including internal irradiation and antiviral therapy, have improved the 5-year tumor-free survival rate of
patients .” However, it is difficult to find out whether the liver cancer patient has microvascular invasion before surgery and requires surgery. The diagnosis was confirmed by pathological examination. Shen Feng believes that if the risk of microvascular invasion in patients with liver cancer can be predicted before surgery, it can not only guide the early prevention of recurrence before surgery, but also the accurate selection of surgical methods. To this end, Professor Shen Feng’s team screened and obtained 7 risk factors for MVI among 1,004 cases of early liver cancer, and constructed the first international MVI individualized predictive scoring model. Professor Shen Feng said: “Through prediction, we can choose individualized treatment plans that help reduce the risk of recurrence based on the risk of MVI in different patients. For example, use a wide margin for high-risk patients with MVI (the margin is ≥ 1 cm from the edge of the tumor). ) The method of resection, or interventional treatment before surgery.”
“Traditional views believe that blood transfusion during liver cancer surgery can lead to a decline in the patient’s immune function and increase the risk of recurrence. Through a large sample analysis, we first proposed that a reasonable blood transfusion during liver cancer resection Increase the new viewpoint of recurrence.” Professor Shen Feng said, “This discovery provides an important basis for follow-up mechanism research, and also enables some patients to avoid unnecessary trauma and economic burden.”
Systematic innovation to enable patients with intrahepatic cholangiocarcinoma to live longer
Among the malignant tumors of the liver, intrahepatic cholangiocarcinoma is the most aggressive, the most difficult to treat, and the patient’s prognosis is the worst. For many years, surgical resection is the only effective treatment method for intrahepatic cholangiocarcinoma, but the treatment strategy and technology are not yet mature, especially the lack of individualized treatment exploration. To this end, the team of Professor Shen Feng carried out systematic innovation.
First of all, the team first proposed that complete resection of the lesion and no cancer cells under the margin microscope are the basic conditions for long-term survival; ensuring that the margin is more than 1 cm from the edge of the tumor is the key to significantly improving the survival rate.
Secondly, it is proposed that patients with large or multiple intrahepatic cholangiocarcinoma can also benefit from surgical resection. Previous views believed that most of the larger intrahepatic cholangiocarcinomas have metastasized, and surgical resection cannot prolong the survival of patients. Professor Shen Feng’s team found through an international multi-center study that surgical resection is still safe and effective for large (diameter ≥ 7 cm) or multiple intrahepatic cholangiocarcinoma, and such patients should be given the opportunity for surgery.
Third, the team found that reducing postoperative complications of intrahepatic cholangiocarcinoma and reducing the severity of complications can improve the long-term survival rate of patients. At the same time, the team proposed specific measures to provide an important basis for improving the overall efficacy.
Fourth, in response to the problem that intrahepatic cholangiocarcinoma is prone to recurrence and metastasis, the team established the first nomogram in the world to predict the survival of patients after surgery. It can accurately determine the prognosis of patients, guide individualized treatment, and prevent recurrence. Studies have found that transcatheter arterial chemoembolization (TACE) treatment for postoperative patients with a higher risk of recurrence and metastasis can significantly improve the survival rate and reduce the recurrence rate.
Fifth, the team is the first internationally to establish a screening scoring system for re-resection of recurrent intrahepatic cholangiocarcinoma to accurately select patients suitable for re-surgical resection. On this basis, the team found through an international multi-center study that a combination of re-excision, ablation, chemotherapy, and TACE multi-modal treatment can further improve the efficacy.
After the above innovations, the 5-year survival rate of patients with intrahepatic cholangiocarcinoma treated by Professor Shen Feng’s team reached 35.2% and the 10-year survival rate was 8.4%, both of which are at the international leading level. Related research has been included in the National Comprehensive Cancer Network (NCCN) Guidelines for Hepatobiliary Cancer, the American Hepatobiliary and Pancreatic Association (AHPBA) Expert Consensus on the Treatment of Intrahepatic Cholangiocarcinoma, and the European Society of Liver (EASL) Guidelines for the Diagnosis and Treatment of Intrahepatic Cholangiocarcinoma, etc., which have effectively promoted intrahepatic cancer. Progress in the treatment of cholangiocarcinoma.
Hepatitis B, intrahepatic bile duct stones and infection are the main causes of intrahepatic cholangiocarcinoma in my country. In 2017, the team of Professor Shen Feng proposed that differentiated surgical treatment should be carried out according to different causes. Their study found that intrahepatic cholangiocarcinoma associated with stones is more aggressive and has a significantly worse prognosis than intrahepatic cholangiocarcinoma associated with hepatitis B. Therefore, during surgical resection, the margin should be expanded as much as possible, and lymph node dissection should be performed. Chemotherapy was performed after surgery. In addition, they found through research that anti-hepatitis B virus treatment can inhibit the aggressiveness of hepatitis B-related intrahepatic cholangiocarcinoma and improve the 5-year survival rate of patients after surgery.
