How to fight the recurrence and metastasis of liver cancer before and after liver transplantation? This is the doubt and concern of many liver cancer patients and their families.
Recently, He Yifeng, deputy chief physician of the Department of Liver Surgery of Zhongshan Hospital Affiliated to Fudan University, was a guest in the live broadcast room of "Dialogue with Famous Doctor Lin Xin" of the media of the Medical Federation, and conducted a live broadcast with the theme of "How to Fight Tumor Recurrence and Metastasis Before and After Liver Transplantation for Liver Cancer", discussing the related issues of tumor recurrence and metastasis before and after liver transplantation that netizens are concerned about.
Liver transplantation is one of the curative treatments for liver cancer
The incidence of liver cancer in mainland China is the highest in the world, with 20 to 40 new cases per 100,000 people every year, accounting for half of the total incidence in the world. As a result, more than 300,000 patients die of liver cancer every year, making liver cancer the malignant tumor with the highest incidence and mortality among men under the age of 60.
Director He Yifeng pointed out, "Among all the types of cancer, liver cancer is still in the third place, and among all the treatments of liver cancer, liver transplantation is one of the radical means for the treatment of liver cancer. ”
Despite the continuous advancement of liver transplantation technology, postoperative recurrence is still the main problem faced by liver transplantation for liver cancer. According to statistics, the recurrence rate of liver cancer in mainland China has reached 20% in 5 years after liver transplantation. Once the tumor recurs, it is often characterized by multiple occurrences and distant metastasis, which makes the treatment extremely difficult and lacks effective treatment methods.
What is the timing and location of recurrence of liver cancer after liver transplantation?
After liver transplantation, there is a certain time pattern for tumor recurrence, with about 75% of recurrences occurring within the first two years after transplantation, and only 10% of recurrences occur after four years.
According to the literature, there are two main types of recurrence: recurrence that occurs in the liver graft itself, which accounts for about 15-40%, and extrahepatic recurrence, which accounts for 50-60%. In extrahepatic recurrence, the organs most commonly involved include the lungs, bones, lymph nodes, and adrenal glands. More worryingly, more than half of all recurrent cases involve multiple organs, making treatment more complex and difficult.
In addition, recurrence after liver transplantation can also be divided into two states: systemic recurrence and oligorecurrence, and there is a great difference in the treatment effect of these two states, although the recurrence of tumors after liver transplantation is complex, Director He Yifeng said, "Zhongshan Hospital affiliated to Fudan University (hereinafter referred to as Fudan Zhongshan) is in a leading position in the field of liver cancer diagnosis and treatment in China, and we have started to do liver transplantation since 2001, and so far we have done about 3,300 cases, and the number of cases per year is about 200. Among them, hepatocellular carcinoma patients account for about 65% of the total. For liver transplant patients who meet the "Shanghai Fudan criteria", their 5-year survival rate is as high as 80%. ”
Fudan Zhongshan's exploration in the prevention and treatment of recurrence and metastasis of liver transplantation for liver cancer
1. Receptor selection and indication optimization
The most classic indication is established by the Milan liver transplantation standard, the maximum diameter of a single tumor in the liver is not more than 5cm, and the maximum diameter of the largest lesion is not more than 3cm in the case of multiple tumors at the same time; There are no large vascular invasions, no lymph nodes or extrahepatic metastases.
Director He Yifeng pointed out, "This standard is relatively strict, because if the tumor is only 5 cm, there are many tumors, if it is a tumor of 6 cm or larger, it has no known indications, and many patients lose the opportunity for liver transplantation." ”
However, with the continuous development and improvement of the indication criteria for liver transplantation for liver cancer, Fudan Zhongshan Hospital put forward the "Shanghai Fudan Criteria" for the indications of liver transplantation for liver cancer suitable for China's national conditions: the diameter of a single tumor is ≤9cm, the diameter of multiple tumors is ≤ 3 and each ≤ is 5cm, the total diameter of all tumors is ≤9cm, and there is no macrovascular invasion, lymph node metastasis and extrahepatic metastasis.
Shanghai Fudan criteria have been relaxed in terms of tumor size and number, and multiple factors such as AFP level and tumor pathological differentiation have been comprehensively considered to more comprehensively evaluate the patient's transplantation conditions.
2. Wait for treatment while donating liver
Director He Yifeng said, "While patients are waiting for a donor liver, some treatment is needed to prevent the tumor from progressing beyond the indication. ”
For patients who meet the indications for liver transplantation for liver cancer, bridging therapy while waiting for liver transplantation is very important, and it is also related to the risk of liver cancer recurrence after liver transplantation. Bridging therapies include: hepatic arterial chemoembolization (TACE), yttrium-90 radioembolization, ablation therapy, radiotherapy and systemic anti-tumor therapy, among which yttrium-90 transarterial radiotherapy embolization has shown significant therapeutic effect for patients with T3 liver cancer. This treatment is capable of targeting tumors with a precision strike and is up to 58% effective.
In addition, if the tumor is relatively small and the waiting time is expected to be less than 6 months, the economic-cost ratio of using targeted drugs is optimal.
For patients with liver cancer that are not indicated, direct transplantation can lead to tumor recurrence, so de-escalation therapy is required first, i.e., measures to reduce tumor size or tumor biological activity.
3. Predictive transplantation of recurrence after transplantation
Postoperative recurrence can be predicted by a number of indicators, such as tumor characteristics, preoperative MELD score, AFP, etc. After liver transplantation, CTC can be followed up to warn of metastasis recurrence in advance, and Fudan Zhongshan independently developed magnetic labeled cell dynamic capture technology to detect CTC, which can achieve efficient, accurate and standardized interpretation of CTC, which can effectively detect CTC of liver cancer and identify malignant tumors.
4. Individualized use of immunosuppressants
Cylex values were used to determine the immune status of liver transplant patients with liver cancer, and the safe range of detection values for liver transplant patients with liver cancer was 175-300 ng/ml. This value represents the ATP content in CD4+ T cells, which can be used to monitor tumor recurrence after surgery to ensure that immune function is at a safe level.
5. Intervention and treatment of recurrence and metastasis after transplantation
For high-risk patients who exceed the "Fudan criteria" or have microvascular invasion, aggressive intervention can help reduce the risk of recurrence. Patients who have relapsed should be treated with surgery, topical, and systemic therapy to prolong survival, but overtreatment should be avoided. In addition, in patients with liver cancer beyond the Milan standard, lenvatinib after transplantation was effective in reducing tumor recurrence.
In 2006, Fudan Zhongshan pioneered the use of rapamycin as an immunosuppressive program to prevent tumor recurrence after transplantation, and the combination of rapamycin and sorafenib reduced the risk of recurrence by 28% and had a synergistic anti-cancer effect. At the same time, Director He Yifeng emphasized the therapeutic effect of yttrium-90 selective internal radiation therapy (90Y-SIRT) in the treatment of recurrence after liver transplantation, "The necrosis degree of 90Y-SIRT on tumors, including prolonging the overall survival of patients, and the effect on local treatment can reach a relatively good level, and the safety is also relatively good." ”
Finally, after liver transplantation for liver cancer, in order to avoid recurrence and metastasis and achieve long-term survival after surgery, patients need to actively cooperate with the doctor's treatment while maintaining an optimistic attitude. In addition, it is also necessary to pay attention to daily care and maintenance, and develop good living habits. I believe that with the joint efforts of both doctors and patients, we will be able to overcome the disease and usher in a better future!
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