Secondary liver cancer is also called metastatic liver cancer. Malignant tumors occurring in various parts of the human body can metastasize to the liver through the blood or lymphatic system, and tumors from neighboring organs can even directly infiltrate the liver, forming secondary liver cancer. In this case, the liver is often an innocent victim, which has nothing wrong with itself, but is only involved by other tumors. In contrast, the liver of primary liver cancer patients mostly has the basis of hepatitis or cirrhosis, and liver cancer is just the result of long-term liver disease. The appearance of liver metastasis means the spread of the primary tumor and is a danger signal, but the progress of modern technology has changed this situation. I. Etiology and classification 1. How do cancer cells metastasize to the liver? Cancer cells invade the liver mainly through the blood circulation system. The liver is an organ with high blood flow, and there are two systems in the human body that supply blood to the liver. One of them is the portal vein system, where the venous blood from all organs in the abdominal cavity including stomach, small intestine, colorectum, pancreas, and spleen converge to the portal vein, and then return to the liver to send the absorbed nutrients to the liver to synthesize various substances necessary for the human body, and to detoxify the toxins produced by human metabolism by the liver. Also the primary malignant tumor cells of these organs can flow directly to the liver through this pathway and then stay in the liver to form metastases. The second blood supply system to the liver is the hepatic arterial system, where fresh oxygen-rich blood supplied from the heart flows into the liver via the aorta, the celiac trunk artery, the common hepatic artery, and the innominate hepatic artery. Primary malignant tumor cells from extra-abdominal organs such as lung, breast, kidney, ovary, etc. are usually returned to the heart and transferred to the liver via the arterial system. In addition, organs such as gallbladder, stomach, adrenal glands and bile ducts, which are close to liver, can easily spread to liver, the “old neighbor”, after their primary malignant tumors have grown to a certain extent, forming the so-called infiltrative metastasis. 2. How do cancer cells form metastases in the liver? When a malignant tumor grows to a diameter greater than 2 cm, a large number of cancer cells can be released into the blood circulation every day, and these cancer cells can eventually reach the liver by “following the flow”. The nodes of the liver are like a thick blood-soaked sponge, with a high blood flow and a slow flow rate, so the tumor cells can easily enter the liver parenchyma and stay there. The more malignant tumor cells that reach the liver can secrete certain growth factors to promote the proliferation of their own tumor cells and stimulate the growth of new capillaries around them, thus gradually forming independent tumor cell masses, which can form metastatic lesions visible to the naked eye in a short time. Symptoms and hazards Generally speaking, the clinical manifestations of secondary hepatocellular carcinoma are often lighter and the development of the disease process is more hidden. When the number of cancer tumors is small and the volume is not large, the symptoms caused by primary cancer of other organs are often the main manifestations of secondary liver cancer, such as blood in stool, emaciation, abdominal distension and intestinal obstruction in colorectal cancer, jaundice, abdominal pain or back pain in pancreatic cancer, breast lumps in breast cancer, abdominal pain and black stool in stomach cancer, cough, hemoptysis and chest pain in lung cancer, etc. However, after the metastatic lesions in the liver grow gradually, the patient may also develop manifestations similar to primary liver cancer such as wasting, weakness, pain in the liver area, liver mass, or even ascites and jaundice. Rarely, certain extrahepatic tumors with high malignancy may not be large in size but have diffuse metastasis in the liver, with obvious enlargement of the liver and swelling of the liver area, which are sometimes difficult to distinguish from primary liver cancer. Ancillary examinations and diagnosis (a) Ancillary examinations 1. Most patients, because they have no obvious symptoms in the liver, are often found to have metastatic lesions in the liver during routine abdominal examinations after the discovery of tumors in other areas. Or the extrahepatic malignant tumor has been surgically removed and the patient finds the liver metastasis during the regular review every few months in the outpatient clinic. The examination means are mainly ultrasound, enhanced CT or MRI of the abdomen, especially the latter two examinations can directly detect the liver mass and clarify the number and size of metastases. 2. Physical examination may not reveal anything specific, except in the case of many very large metastases, where the doctor may feel the enlarged liver with pressure pain in the liver area. 3. Sometimes, due to the inability to determine the nature of the liver mass, or suspicion of metastases in other areas, or in order to find the hidden primary malignant tumor causing metastatic liver cancer, a whole-body PET-CT scan can be performed. 4. In order to understand the function of the liver and provide necessary data for the next possible liver surgery, blood and urine routine, coagulation function and liver function (mainly looking at bilirubin, albumin and transaminases) tests should be performed. To differentiate from primary hepatocellular carcinoma, virological tests for alpha-fetoprotein, hepatitis B or C are also necessary. (2) Differential diagnosis 1. The main differentiation is with primary liver cancer Secondary liver cancer usually has no symptoms of serious liver lesions, and even liver function tests may still be normal when the liver is obviously enlarged. Compared with primary liver cancer, secondary liver cancer has relatively slow development and mild symptoms, and often manifests as multiple nodular lesions. The main method of differentiation is to check whether there are primary cancer foci in organs other than the liver, and methotrexate is usually negative. When it is really difficult to differentiate, only then should we consider to do a puncture biopsy of the mass for pathological examination 2. CT of the pelvis can detect lesions of the rectum and ovaries and uterus. Blood tumor markers are available in sets, which are simple and quick, and are auxiliary tools for imaging examinations. If it is really difficult to detect, PET-CT, though more expensive, can indeed provide valuable clues. Secondary hepatocellular carcinoma may be a single nodule, but most of them are multiple nodules, and since the lesion has metastasized to the liver, it means that the primary carcinoma is already in advanced stage, and the previous view is that it cannot be removed surgically and there is no special treatment. With the development of modern medical level, surgical techniques, adjuvant chemotherapeutic drugs and post-surgical intensive care support treatment means have made rapid progress, and the treatment philosophy of our doctors has also changed a lot. Nowadays, many metastatic liver cancers are already treatable diseases. As a representative example, we will talk about the treatment characteristics of metastatic liver cancer in detail. (1) Liver metastasis of colorectal cancer Colorectal cancer (colorectal cancer) is a malignant tumor with high incidence in China. In recent years, radical surgery for colorectal cancer has become more and more standardized and improved with the efforts of surgeons, but only about 60% of patients can survive for more than 5 years after surgery, and liver metastasis is the most important problem affecting the long-term survival of colorectal cancer patients. Indeed, half of the patients will develop liver metastasis sooner or later after surgery, and this percentage is very high. Because all the blood from the gastrointestinal tract flows to the liver, so if the tumor penetrates the blood vessel wall during the growth process, there will be cancer cells running to the liver with the blood flow and planted down, which can easily form metastatic cancer in the liver. But fortunately, the growth rate of liver metastases of colorectal cancer is relatively slow, and only isolated metastatic lesions are usually formed in the liver, which rarely continue to spread in the liver again, which creates conditions for surgical resection. It has been 70 years since the first case of resection of liver metastases from rectal cancer in 1940, and the actual efficacy proves that surgical resection is still the most effective treatment for liver metastases from colorectal cancer, and it is also the only way to cure the tumor. Forty to fifty percent of patients with liver metastases that can be surgically resected can achieve long-term survival. In other words, the development of liver metastases in colorectal cancer patients does not mean the end of the world, nor is it the beginning of the countdown of life. On the contrary, through active scientific and targeted treatment, it is entirely possible for us and everyone to work together to completely defeat the disease of colorectal cancer. In the past 70 years, due to the great progress of surgical technology and the accumulation of experience of our hepatobiliary surgeons, the size, number and growth site of metastatic liver cancer in the liver are no longer factors that affect whether a patient can be operated or not, and many former forbidden areas for surgery have been broken. It can be said that most metastatic liver cancers can be removed as long as enough liver can be preserved after surgery (usually more than 30%). If there are metastases outside the liver, those that can be removed can also be removed, such as pulmonary metastases, abdominal implant metastases, lymph nodes metastases in the liver portal, etc. can be removed. Some patients are found to have liver metastases along with colorectal cancer, which should be treated separately according to the situation. If the patient’s liver function and physical condition allow, according to the current technology, it can be removed in one operation. If emergency surgery is needed because the tumor is blocking the intestine, we do not recommend simultaneous resection of metastatic cancer due to the lack of perfect preoperative examination data and the high chance of surgical infection, and priority should be given to ensure the successful resection of the primary colorectal cancer and the rapid recovery of the patient. Within 2 years after resection of metastatic liver cancer, there may be recurrence in 60% of cases, and about 1/3 of them are still present in the liver. Don’t be discouraged and don’t be afraid, as long as the conditions allow, it can be treated by surgery again, and the overall survival after resection is similar to the initial liver resection. Of course, surgery is not a panacea, and we surgeons need reinforcements in the face of a tough enemy, and that is a comprehensive treatment involving multiple disciplines. For example, preoperative and postoperative radiotherapy and chemotherapy, different protocols are chosen for different patients. For those patients who cannot undergo open surgery can also use less invasive radiofrequency or microwave ablation methods, which can destroy smaller size liver metastases in certain areas with a long needle outside the body (without open surgery). Therefore, when colorectal cancer patients have liver metastases, they should not despair and be pessimistic, knowing that this is a disease that has a chance to be cured. What we should do is not to seek medical advice and recipes, but to go to a regular professional hepatobiliary surgeon in time to actively fight for treatment opportunities. (2) Liver metastasis of breast cancer Breast cancer is a systemic disease, the incidence of which is on the rise in recent years, and the peak age of incidence is moving forward. The survival rate after liver metastasis is only 30%, therefore, the effect of treating liver metastases after breast cancer surgery directly affects the overall treatment of breast cancer. However, breast cancer is one of the most effective tumors among solid tumors in terms of systemic chemotherapy, and effective systemic chemotherapy is still the preferred treatment option for liver metastases from breast cancer, with conventional drugs such as anthracycline antibiotics, paclitaxel, 5-fluorouracil and vincristine. In particular, paclitaxel is the most important anti-breast cancer chemotherapy drug developed after the 20th century, and it has high efficacy when used alone. If the tumor is gradually limited after applying chemotherapy and the liver function is good, surgical resection or using ablation therapy to destroy the tumor can still be considered. (3) Liver metastasis in ovarian cancer The development of liver metastasis in ovarian cancer usually indicates that the disease has progressed to advanced stage, especially when the liver metastases are multiple and the chemotherapy is not sensitive, the treatment will be very difficult. Fortunately, most ovarian cancers are sensitive to chemotherapeutic drugs, and with the help of chemotherapy, resection of liver metastases becomes meaningful. Clinical practice also proves that for resectable liver metastases, aggressive surgery can significantly prolong the survival time of patients. Therefore, if there is a chance of radical resection, staged surgery is still recommended, and the survival rate can be increased from 10% in the past to even 90%. Therefore, we should cherish the opportunity of surgery for these patients and consider active surgical treatment. （These tumors are less malignant, including carcinoid tumors and malignant islet cell tumors of the pancreas (the tumor suffered by Steve Jobs, the godfather of Apple), and so on. Take carcinoid tumors of the gastrointestinal tract as an example, the tumors themselves are slow-growing, less invasive and less malignant, and surgical resection is the main treatment. If liver metastasis has occurred, liver lobectomy or injection of anhydrous alcohol into the mass can be performed at the same time. The degree of radical resection affects the survival time after surgery, but even palliative resection (major or partial resection of the tumor) can still significantly improve the patient’s symptoms and quality of life. Carcinoid tissues contain a large number of growth inhibitor receptors, and for those who cannot be resected radically, the use of growth inhibitor analogues has good efficacy and can be used as the first-line treatment drug. (e) Liver metastasis of lung cancer Liver metastasis is the most common site of hematogenous metastasis of lung cancer, and the condition of patients with liver metastasis often progresses rapidly. Most of the liver metastases appear within 12 months after the diagnosis of lung cancer, while those suitable for surgery are less common. Chemotherapy is the main means, and radiotherapy technology has advanced rapidly and also plays an increasingly important role in the treatment of liver metastases. Chemotherapy via femoral artery puncture with bronchial artery perfusion for primary foci and hepatic artery perfusion can prolong survival time, so it is a more effective treatment method at present, especially arterial chemotherapy has small adverse effects and exact effects, which is easily accepted by patients. However, the key to reduce the incidence of liver metastasis still lies in the early detection, early diagnosis and early comprehensive treatment of lung cancer.