Liver carcinoid tumors

　　First, Etiology

　　The etiology of this disease is unknown and it develops slowly.

　　Second, Pathogenesis

　　Liver carcinoid tumors have neuroendocrine characteristics, belong to APUD tumors, and can secrete a variety of peptides and biogenic amines, including serotonin, pancreatic polypeptide (PP), insulin, somatostatin, gastrin, adrenocorticotropic hormone (ACTH), gonadotropin, prostaglandin, calcitonin, and others. Among them, gastrin and pancreatic polypeptide (PP) are the most common in liver carcinoid tumors and are the main material basis for the development of carcinoid syndrome in a few patients.

　　The histological origin of liver carcinoids is not yet clear, and it is generally believed that there are several possible causes:

　　1. Originating from ectopic pancreatic tissue.

　　2. Originating from scattered neuroectodermal cells in the foregut and embryonic remnants, or from primitive pluripotent stem cells.

　　3. Originating from the primitive neuroendocrine plate.

　　4. Originating from the epithelial cells of metaplastic endocrine cells.

　　Liver carcinoids are often located in the right lobe of the liver, mostly one to two nodules, a few with multiple nodules, with a diameter of 1-17cm, the cut surface showing pink-brown or gray-yellow, with irregular areas of hemorrhage in the tumor center, and necrosis is rare. The tumor is soft or firm, contains more cystic cavities, and the boundary between the tumor and the liver substance is clear. The surrounding liver tissue usually does not have liver cirrhosis. The tumor is composed of uniform small polygonal or cuboidal cells, with clear cell boundaries and cells arranged in islet-like, nest-like, strip-like, cord-like, or lattice-like structures, separated by fine soft fibrous matrix. Immunohistochemical examination shows strong positivity in argentaffin staining, argentophilic staining, and chromaffin staining; epithelial membrane antigen (EMA), chromogranin A (CgA), and neurospecific esterase (NSE) are often positive. Electron microscopy shows electron-dense granules in the cytoplasm with a diameter of 100-200nm. Liver carcinoids often occur early in liver metastasis or local lymph node metastasis, with distant metastasis being rare.

　　1. Some patients have symptoms such as loss of appetite, poor digestion, abdominal distension, nausea, and vomiting, and a few patients have complications such as gastric or duodenal bulb ulcers.

　　2. Advanced cases often have anorexia, weight loss, fatigue, and fever.

　　Liver carcinoids are insidious in onset. In the early stage, when the tumor is very small, there may be no symptoms or signs. When the carcinoid grows to a certain extent, it can cause local symptoms (often caused by mechanical factors).

　　1. Local symptoms:Pain in the upper right abdomen or liver area is the most common, presenting as intermittent or persistent, dull or distending pain.

　　2. Gastrointestinal symptoms:Some patients have symptoms such as loss of appetite, poor digestion, abdominal distension, nausea, and vomiting, and a few patients have complications such as gastric or duodenal bulb ulcers, so they may have symptoms of peptic ulcers, even vomiting blood or black stools.

　　3. General symptoms:Although immunohistochemical examination proves that there are ectopic neuroendocrine products at the cellular level in liver carcinoids, due to their insufficient quantity or defects in quality, they often cannot activate target organs to exert biological effects. Therefore, the majority of liver carcinoids do not show clinical manifestations of abnormal increase in neuroendocrine products, and only a few cases present with carcinoid syndrome, Zollinger-Ellison syndrome, ectopic ACTH syndrome, refractory hypoglycemia, and other symptoms.

　　4. Other symptoms:Advanced cases often have symptoms such as anorexia, weight loss, fatigue, and fever.

　　5. Signs:Hepatomegaly is the most common sign, with the liver texture being relatively hard, the surface and edges irregular, often nodular, and a few tumors deeply buried within the liver substance may have a smooth liver surface with or without obvious tenderness.

　　The prognosis of this disease depends on the location of the primary tumor, the extent and degree of metastasis, and the effectiveness of surgical treatment. It is generally believed that carcinoid tumors grow slowly, and even if the condition is late, they should be removed as much as possible, and the efficacy is still good. Carcinoid tumors in the appendix and rectum are often without metastasis and easy to be removed and cured, with the best prognosis. The 5-year survival rate after surgery is 99% and 83%. The prognosis of patients with carcinoid syndrome caused by gastric and ileal carcinoid tumors is also good. After radical treatment, they can survive for 5 to 25 years. The prognosis of carcinoid syndrome caused by bronchial and colonic carcinoid tumors is poor, with a survival time of only 1 to 2 years, and most die due to heart, lung, and liver dysfunction. Since the cause of this disease has not been fully elucidated, attention should be paid to some dietary and environmental risk factors that cause tumors.

　　1. Blood

　　The serotonin content in the serum of a few patients rises to 0.5-3mg/L (the normal value is 0.1-0.3mg/L). Recently, it has been reported that detecting the activity and expression of tryptophan hydroxylase in the serum and tissues of patients by immunohistochemical and biochemical methods can also help with the diagnosis of carcinoid tumors.

　　2. Urine

　　A few patients excrete more than 40mg of 5-hydroxyindoleacetic acid (5-HIAA) per day in urine (the normal value is not more than 10mg per day). When the excretion of 5-HIAA in urine is greater than 30mg/d, add 1-nitrosopyrrole reagent, and the urine turns purple to black. Certain drugs (such as thiazides and mandelic acid derivatives) or foods rich in tryptophan (such as pears, bananas, pineapples, tomatoes, eggplants, walnuts, etc.) should not be taken within 24 hours before the urine 5-HIAA test to avoid false-negative or false-positive results.

　　3. MRI:During MRI examination, the T1-weighted image often appears as a low signal area, and the T2-weighted image often appears as a high signal area, among which there are some areas with even higher signal.

　　4. Imaging examination:The characteristic change in the imaging of liver carcinoid tumors is the presence of multiple small cystic lesions within the mass, but it cannot be distinguished whether it is primary or metastatic carcinoid tumor from the imaging.

　　5. Electron microscopy examination:The diagnosis of liver carcinoid tumors is usually based on immunohistochemistry and electron microscopy examination to prove that tumor cells have the characteristics of carcinoid tumors, thus obtaining the final diagnosis.

　　1. Eat on time and in appropriate amounts. Do not overeat or have a preference for certain foods. Have a planned intake of nutrition and calories.

　　2. Eat more vegetables and fruits rich in vitamin A and C. Regularly eat foods containing substances that inhibit cancer cells, such as cabbage, spinach, mushrooms, etc.

　　3. Eat less refined rice and flour, and more coarse grains, corn, beans, and other杂粮.

　　4. Low-fat diet. Eat lean meat, eggs, and yogurt regularly. Eat less salted, smoked, grilled, burned, and deteriorated food.

　　5. Regularly consume dried fruit foods such as walnuts, pumpkin seeds, watermelon seeds, peanuts, raisins, etc. They are rich in various vitamins, trace elements, dietary fiber, protein, and unsaturated fatty acids, with high nutritional value.

　　I. Treatment

　　1. Surgical Treatment:The treatment of liver metastasis is mainly surgical treatment, and surgical resection is currently the most effective method. Early resection of the primary lesion is the key to improving survival rate, and the surgical effect is much better than that of primary liver cancer. Liver lobectomy can be expected to be completely cured in early cases.

　　2. Hepatic Artery Embolization Chemotherapy (TACE):Hepatic artery embolization chemotherapy (TACE) is a non-surgical tumor treatment method developed in the 1980s. In recent years, it has achieved relatively satisfactory results in the treatment of liver metastasis and is the first choice among non-surgical treatment methods. It usually uses iodized oil mixed with chemotherapy drugs to embolize the blood supply of the distal tumor, and then uses gelatin sponge to embolize the proximal hepatic artery, making it difficult to establish collateral circulation, leading to ischemic necrosis of the tumor tissue. Commonly used chemotherapy drugs include CDDP 80-100mg, mitomycin (MMC) 16-20mg, doxorubicin (ADM) 40-60mg, and 5-fluorouracil (5-FU) 1000mg. Hepatic artery embolization chemotherapy should be performed every 4-6 weeks, and repeated multiple times for better effect.

　　3. Systemic Chemotherapy:For patients who cannot be surgically removed or are not suitable for hepatic artery embolization chemotherapy, systemic chemotherapy can be chosen, but the efficacy is poor, and the side effects of chemotherapy are significant, which are prone to gastrointestinal reactions and hematopoietic function inhibition. Commonly used chemotherapy drugs include: 5-fluorouracil (5-FU) or its derivatives (FT-207), mitomycin, doxorubicin, cyclophosphamide, and streptomycin.

　　4. Radiotherapy:Liver metastasis is not very sensitive to radiotherapy, and the adjacent organs of the liver are easily damaged by radiation, so the therapeutic effect is often not satisfactory. For patients who cannot be surgically removed, radiotherapy can be applied, which has certain therapeutic effects. If radiotherapy is combined with chemotherapy, traditional Chinese medicine, or other supportive therapies, the effect will be better.

　　5. Supportive Treatment:When patients have nausea, vomiting, or eat less, intravenous点滴glucose can be administered according to the condition to provide the body with essential calories. Vitamin C, Vitamin B6, and potassium chloride are infused at the same time. In necessary cases, the application of a mixture of amino acids, albumin, and blood transfusion can be given to patients with significant anemia.

　　II. Prognosis

　　The prognosis of liver metastasis is better than that of liver cancer. After active comprehensive treatment, including surgery and chemotherapy, most patients survive for more than 4 years.