Metastatic Liver Cancer

　　Cancerous tumors in almost all internal organs can metastasize to the liver. Malignant tumors can directly infiltrate surrounding tissues or invade lymphatic vessels, blood vessels, and body cavities, after which cancer cells are transferred to distant sites along with lymph fluid, blood, and various cavities. The infiltration and metastasis of cancer cells mainly depend on their own malignant biological characteristics and the immune status of the body. Cancer cells have ameboid motility and can autonomously infiltrate and move within surrounding tissues. The decreased adhesion between cancer cells makes them more prone to detachment, increasing the chance of metastasis. The high expression of certain integrins may confer migratory drive to cancer cells, making it easier for them to penetrate the basement membrane. Certain adhesion molecules in the body help cancer cells to remain in the metastatic organs, and the increased activity of surface proteases on cancer cells also facilitates their infiltration and metastasis. Due to the low immune function in tumor-bearing hosts, the body cannot effectively identify and kill metastatic cancer cells. Once cancer cells remain in distant organs, they can release a variety of growth factors and their receptors. For example, vascular endothelial growth factor (VEGF) allows cancer cells to grow autonomously and unrestrictedly. This malignant biological characteristic of cancer cells is related to the genetic information they carry, such as DNA ploidy or clone level; aneuploid cancer cells are more prone to metastasis than diploid ones. The liver, due to its own anatomical and blood supply characteristics, may be more likely to provide a growth space and nutritional source for various cancer cells. The pathways for cancerous tumors in various parts of the human body to metastasize to the liver include portal vein, hepatic artery, lymphatic route, and direct infiltration.

　　Patients with metastatic liver cancer may experience weight loss and fatigue due to metabolic consumption of malignant tumors, reduced food intake, and malnutrition. Patients often have loss of appetite due to liver dysfunction and tumor compression of the gastrointestinal tract. This disease may also be complicated by upper gastrointestinal bleeding, hepatorenal syndrome, infection, and cancer fever.

　　Early liver metastasis cancer may not have obvious symptoms and signs, and in the late stage, its symptoms and signs are similar to those of primary liver cancer, but due to the absence of liver cirrhosis, it often develops more slowly than the latter and the symptoms are milder. In the early stage, the symptoms are mainly from the primary tumor, and the symptoms of the liver itself are not obvious. Most of the time, they are found during preoperative examination of the primary tumor, postoperative follow-up, or laparotomy. As the condition progresses, the tumor grows larger, and the symptoms of the liver gradually appear, such as pain, oppression, discomfort, fatigue, weight loss, fever, loss of appetite, and abdominal mass in the upper abdomen. In the late stage, jaundice, ascites, cachexia, and a few patients (mainly from the gastrointestinal tract, pancreas, etc.) have obvious symptoms of liver metastasis cancer while the primary tumor is hidden.

　　1, Symptoms and signs of primary cancer

　　They vary with the site and nature of the primary cancer, but they may be the main clinical manifestations of the patient, such as cough and chest pain in lung cancer patients, upper abdominal pain and jaundice in pancreatic cancer patients, etc. At this time, it is often the early stage of liver metastasis cancer, and it is easy to pay attention only to the primary cancer and ignore the possibility that the tumor may have already metastasized to the liver, peritoneum, lungs, and other organs.

　　2, Symptoms and signs of liver metastasis cancer

　　When the liver shows extensive metastasis or large metastatic foci, patients may present with symptoms and signs similar to primary liver cancer, such as distension or discomfort in the upper right abdomen or liver area. The liver may be enlarged, and if a cancer nodule is touched, it may be hard and possibly painful. In the late stage, jaundice, ascites, and other signs of cachexia may occur, and sometimes the above symptoms and signs may be the only manifestation of the patient, making it difficult to discover the primary tumor. Since liver metastasis cancer often does not accompany liver cirrhosis, compared with primary liver cancer, the above manifestations are slightly milder, develop more slowly, and have fewer complications.

　　3, Systemic Symptoms

　　As the condition progresses, patients may experience systemic symptoms such as fatigue, abdominal distension, loss of appetite, weight loss, fever, and these symptoms may worsen progressively.

　　In the prevention of metastatic liver cancer, it is first necessary to clarify whether liver cancer is contagious. Although there are cases of familial clustering of liver cancer in medical cases, the cause lies in the cross-infection of hepatitis, rather than the transmission of liver cancer itself. It is also necessary to prevent the transmission of viral hepatitis. When in contact with liver cancer patients, if the liver cancer is caused by hepatitis B virus, attention should be paid to protection, especially for the weak children and the elderly. However, liver cancer is not contagious, so there is no need to worry about it. In addition, it is necessary to develop good living habits and pay attention to quitting smoking and drinking.

　　Early liver metastases may not have obvious symptoms and signs, and in the late stage, the symptoms and signs are similar to those of primary liver cancer, but due to the absence of liver cirrhosis, it often develops more slowly than the latter and the symptoms are milder. The specific examination methods for this disease are as follows.

　　One, Liver Function

　　Secondary liver cancer in the subclinical stage often shows no enzymatic abnormalities, and those with clinical manifestations are often accompanied by elevated ALP, GGT, but are not helpful for the direct diagnosis of liver metastases. Even if the liver has obvious enlargement, liver function can be normal or slightly abnormal. In severe cases, serum bilirubin, alkaline phosphatase (AKP), lactate dehydrogenase (LDH), and gamma-glutamyl transpeptidase may increase, with AKP often significantly elevated and having more significance for the diagnosis of liver metastases.

　　Two, Tumor Marker Detection

　　1, Serum alpha-fetoprotein (AFP): More than 90% of patients with liver metastases have negative AFP, but a few from gastrointestinal, pancreatic, and reproductive gland cancers can be detected with low concentration AFP positivity after liver metastasis.

　　2, Serum carcinoembryonic antigen (CEA): An increase in CEA is helpful for the diagnosis of liver metastases, with a positive rate of 60% to 70% in liver metastases from colorectal cancer. After the metastasis of cancers originating from the gastrointestinal tract, breast, and lung to the liver, the serum CEA of patients can significantly increase.

　　3, CA19-9: The level of CEA often increases when pancreatic cancer metastasizes to the liver.

　　Three, Liver Virus Marker Detection

　　The detection of serum hepatitis B virus markers in patients with this disease is mostly negative.

　　Four, Imaging Examinations

　　There are various examinations such as ultrasound, CT, and magnetic resonance imaging (MRI), which are basically non-invasive and can be repeated as needed. It should not be easily excluded as a disease without positive findings after only one or a single type of examination. Ultrasound imaging often shows enhanced echoes. CT shows mixed uneven density or low density, typically presenting with a 'bull's eye' sign, and is usually not accompanied by signs of liver cirrhosis. MRI examination of liver metastases often shows uniform signal intensity, clear edges, and multiple occurrences, with a few showing 'target' or 'halo' signs. Ultrasound and CT examinations can show multiple scattered or solitary solid masses within the liver, and both can detect tumors larger than 1-2 cm in diameter.

　　V. Special examinations

　　According to the detection of selective hepatic angiography, the lower limit of the diameter of the lesion can be detected to be about 1 cm, and ultrasound imaging is about 2 cm. Therefore, early liver metastasis often presents as negative, and positive results appear only when it reaches a certain size. For those with clinical manifestations, the positive rate of various localization diagnostic methods can reach 70% to 90%, and selective peritoneal or hepatic artery angiography often shows hypovascular tumors.

　　1. Angiography: Selective hepatic angiography often shows hypovascular tumor nodules, which can detect tumors larger than 1 cm in diameter.

　　2. Liver biopsy: Fine needle liver biopsy under the guidance of B-ultrasound or CT can help clarify the diagnosis and find the primary cancer, but this method has the potential to cause intra-abdominal bleeding, so attention should be paid.

　　3. Radioisotope imaging: Areas without imaging in the radioactive isotope imaging of sulfur-containing colloids are manifested in liver metastases larger than 2.0 cm. It should be noted that this technology has a high sensitivity, but also a high rate of false positives.

　　4. Laparoscopic examination: Microscopic metastatic foci that cannot be detected by the above imaging methods can be detected.

　　Patients with metastatic liver cancer should pay attention to a diet rich in fresh vegetables and fruits, such as lemons, asparagus, almond milk, water chestnuts, jujube, garlic, red vegetables, and black fungus, which are anti-cancer substances that can block the formation of cancer cells. After the condition is stable, congee, noodles, pork liver, and other foods can be added to the patient's staple food, which should be nutritious and moistening.

　　In recent years, there have been significant advancements in the treatment of metastatic liver cancer. Due to the improvement of follow-up systems, the application of new imaging examination technologies, and the detection of serum markers, patients with metastatic liver cancer have more opportunities for early diagnosis and early treatment, and their survival rates have correspondingly improved. In the treatment of secondary liver cancer, it is necessary to combine the treatment of the primary site. At present, the treatment methods include surgical resection, chemotherapy, hepatic artery embolization chemotherapy, and biological therapy, etc.

　　1. Surgical treatment: Liver lobectomy, hepatic artery ligation, and hepatectomy are available. Some scholars in the United States have reported that in patients with 3 or fewer metastatic foci, if the metastatic foci are resected and the margins are clean, the 5-year survival rate can reach 30% to 40%, and the recurrence rate of liver metastasis is less than 20%. For patients with 4 or more metastatic foci, it is rare to survive for 3 years if liver resection is performed, and the intrahepatic lesions usually increase. In the absence of extrahepatic metastasis, all visible liver metastatic lesions should be resected as much as possible, except for carcinoid tumors.

　　2. Hepatic Arterial Infusion Chemotherapy (HAI): Bterman et al. (1950) first introduced this method of treatment, which was not noticed until the 1960s, and it was widely adopted until the 1970s due to the perfection of operation techniques and the significant reduction in complications. However, the selection of drugs, indications, and administration schemes are still undefined. Currently, it is believed that HAI can be used for patients with inoperable liver metastasis without extrahepatic lesions or with small extrahepatic lesions.

　　3. Chemotherapy via Other Routes: There are two methods: systemic chemotherapy and hepatic arterial catheter chemotherapy. The former not only has poor efficacy but also severe side effects, and most late-stage patients cannot tolerate it, so it is rarely used in clinical practice. Percutaneous femoral artery puncture and hepatic arterial catheter chemotherapy drug perfusion or embolization is suitable for cases where the primary cancer cannot be cured or the primary site cannot be found, as well as for patients with widespread liver metastasis or multiple metastases outside the liver. Commonly used chemotherapy drugs include fluorouracil (5-Fu), mitomycin (MMC), doxorubicin (Adriamycin), and cisplatin, etc. Hepatic arterial embolization treatment commonly uses iodinated oil, absorbable gelatin sponge, drug microspheres or microcapsules, which can significantly improve efficacy.

　　4. Combined Chemotherapy: In the early 1980s, some people applied degradable starch microspheres to temporarily block the capillary channels of the hepatic small arteries, and then injected Carmustine (Carmustine) through the hepatic artery to increase the local drug concentration of liver tumors and reduce the leakage of drugs into the systemic circulation. Kato et al. (1981) used degradable ethyl cellulose microspheres containing mitomycin, which had the effects of blocking the branches of the hepatic small arteries and releasing drugs slowly. Although this embolic chemotherapy method is relatively reasonable, it often affects the efficacy due to the shunting of arteriovenous fistula between the tumor and normal liver tissue. Looney et al. (1979) tested arterial perfusion therapy in 18 patients with liver metastasis from colorectal cancer, with a median survival period of 8 months, among whom 2 deaths were related to treatment. Four cases of tumor disappearance were observed during reoperation or autopsy, and 1 case died of liver necrosis. Due to the high incidence and mortality rate of complications with this therapy, its application is limited. In addition, Grady (1979) applied yttrium microspheres injected through the hepatic artery as internal radiation therapy for 25 patients, among whom 17 cases showed symptom relief, and 3 died due to this therapy. Although various atherectomy therapies can obtain efficacy due to the obvious arterial blood supply of liver tumors, Ekberg et al. (1986) reported that the efficacy of long-term continuous hepatic arterial perfusion of fluorouracil (5-Fu) after temporary atherectomy therapy in patients with liver metastasis from colorectal cancer was not as good as that of using fluorouracil (5-Fu) alone. In recent years, the Second Military Medical University Oriental Hepatobiliary Surgery Hospital has achieved certain efficacy by combining hepatic arterial chemotherapy栓塞 with local injection of anhydrous ethanol in the treatment of liver metastatic cancer.

　　5. Auxiliary TherapyThis method is suitable for patients who may relapse after radical surgery for primary cancer, those for whom known anticancer drugs are indeed effective or the chance of cure is small during recurrence, and those for whom all auxiliary therapies have no adverse reactions. Most patients do not need adjuvant chemotherapy after surgery.

　　6. RadiotherapyApart from a few tumors that are sensitive to radiotherapy, such as seminoma, radiotherapy is not effective for the majority of tumors and can be used as an auxiliary treatment method, which can alleviate symptoms to some extent.

　　7. Local Treatment with Absolute Ethanol InjectionPercutaneous injection of absolute ethanol into the tumor under ultrasound guidance is a local treatment method that has emerged in recent years. It is suitable for solitary lesions within the liver, or up to a maximum of 3 lesions, with a diameter of less than 3cm. This method can cause tumor coagulation, necrosis, and fibrosis, prolong the patient's survival time, or create conditions for tumor resection surgery. Multiple treatments of a single lesion may even result in complete regression.