Primary hepatocellular carcinoma I. Histological origin: hepatocytes or intrahepatic bile duct epithelial cells Hepatocellular carcinoma has a high mortality rate, ranking third (gastric cancer, esophageal cancer) among the malignant tumors of the digestive system in China. In some rural areas, it occupies the second place. About 110,000 people die of liver cancer in China every year, accounting for 45% of liver cancer deaths worldwide. Jiangsu Qidong and Guangxi Fusui have the highest incidence rate. Overseas: there is an increasing trend of incidence in sub-Saharan Africa and the Pacific coast of Asia. Any age, most often 40-49 years old, M:F2~5:1 II. Etiology ①1/3 of PHC have a history of chronic hepatitis. ②The rate of HBsAg positivity in people with high incidence of hepatocellular carcinoma is higher than that in low incidence areas. ③Serum HBsAg and other hepatitis B markers positive rate of liver cancer patients can reach 90%, which is significantly higher than that of healthy people. ④Immunohistochemical methods show that HBV-DNA can be integrated into the DNA of host hepatocytes, and the X gene of HBV can alter the gene expression of hepatocytes. ⑤ Viral hepatitis C is also closely related to the development of hepatocellular carcinoma. Diffuse type: It is the least common, with small cancer nodules ranging from rice grain to soybean size and diffuse distribution throughout the liver, easily confused with cirrhotic pseudolobular nodules. Liver size is not obvious. Death is often due to liver failure. Massive type: Most common, with cancer diameter >125px, of which >250px is a giant mass type, which is prone to rupture. The common subtypes are: ① Monolithic type: single cancer mass with clear or irregular border and intact or incomplete envelope; ② Fusion mass type: adjacent cancer tumors fused into a mass with diameter more than 125px, and there are often scattered satellite cancer nodules in the surrounding liver tissue; ③ Multi-mass type: formed by multiple single or fused cancer tumors. Nodular type: more common, with cancer nodules of different sizes and numbers generally less than 125px, mostly in the right lobe, and poorly delineated. Most of them are combined with cirrhosis. The common subtypes are: ① Single nodule: single cancer nodule with clear boundary and envelope, surrounded by small satellite nodules; ② Fusion nodule: irregular boundary, surrounded by scattered satellite nodules; ③ Multi-nodule: scattered in different parts of the liver with clear or irregular boundary. Small carcinoma: A single carcinoma nodule with diameter <75px, or the sum of two adjacent carcinoma nodules with diameter <75px is called small hepatocellular carcinoma. Small carcinomas have clear borders and often have obvious envelopes. The most common type of hepatocellular carcinoma (90%) is hepatocellular carcinoma, in which the cancer cells develop from hepatocytes in a polygonal arrangement into nests or cords, with abundant blood sinuses between the nests or cords and no interstitial components. The cancer cells have large nuclei, obvious nucleoli, abundant cytoplasm, and tend to grow into the blood sinusoids. Cholangiocarcinoma of cholangiocarcinoma type is less common (1/50). The cancer cells develop from cholangiocarcinoma epithelial cells in a cuboidal or columnar shape, arranged in a glandular pattern, with more fibrous tissue and fewer blood sinuses. (Most cholangiocytic hepatocellular carcinomas are single masses, because of more connective tissue interstitium, grayish color, firm texture, and tend to infiltrate irregularly to the surrounding area.) Mixed type is the least common and has both structures of hepatocellular and cholangiocellular carcinoma, or shows an over-excited form, which is neither exactly like hepatocellular carcinoma nor cholangiocellular carcinoma. V. Clinical manifestations New concept of natural course: The disease starts insidiously and develops rapidly once symptoms appear. The natural course of the disease is now considered to be about 24 months. Cases detected early by methotrexate screening can be without any clinical symptoms and signs, which is called subclinical hepatocellular carcinoma. Clinical developmental changes (understanding): Pre-subclinical stage: from the beginning of the lesion to before the diagnosis of subclinical hepatocellular carcinoma is made, patients have no symptoms and signs and are difficult to be detected clinically, about 10 months on average. Subclinical stage: from the establishment of subclinical liver cancer diagnosis to the appearance of symptoms, the patient still has no symptoms and signs, the tumor is about 3-5 cm, and the diagnosis is still difficult, mostly detected by AFP census, about 4 months on average. Clinical stage: Once the clinical manifestation of liver cancer appears, it has reached the middle stage, and soon jaundice, ascites, and even extensive metastasis and cachexia appear in the late stage, about 6 months in the middle and late stage. When liver cancer develops to advanced stage, the tumor diameter reaches about 10 cm, which is difficult to be cured. Clinical manifestations of middle and late stage (a) Pain in liver area: more than 50%, pain in the right upper abdomen is the most common, which is an important symptom of the disease, and the pain is continuous or intermittent, mostly pure pain or swelling pain, which increases with the development of the disease. The lesion is located in the right lobe of the liver and shows pain in the right quadrant of the rib cage, while the lesion is located in the left lobe of the liver and shows pain in the subxiphoid region. If the tumor invades the diaphragm, the pain may spread to the right shoulder or right back; tumor growing backward to the right may cause pain in the right lumbar region. The pain is caused by the tumor growth that tenses the liver envelope. Sudden severe abdominal pain and peritoneal irritation signs are caused by rupture and bleeding of subperitoneal cancer nodules, or intra-abdominal bleeding and peritoneal irritation caused by rupture into the abdominal cavity. Enlargement of liver: progressive, hard, nodular and painful Vascular murmur can be heard in about half of the patients due to the rich and tortuous blood vessels of hepatocellular carcinoma, sudden thinning of arteries or compression of hepatic artery and abdominal aorta by cancer mass. It has diagnostic value, but is not significant for early diagnosis. Clinical manifestations of middle and late stage (2) Portal hypertension Jaundice often appears at a late stage, mostly caused by the compression of bile ducts by cancer or enlarged lymph nodes. Recently, it has been found that hepatocellular carcinoma can invade the bile duct and cause obstructive jaundice and bile duct bleeding. Jaundice can also be caused by damage to hepatocytes. Systemic manifestations of malignant tumors: progressive wasting, fever, loss of appetite, weakness, malnutrition and cachexia. The fever is mostly persistent and low, usually around 37.5-38℃, but may also be irregular or intermittent or persistent high fever. The performance may resemble liver abscess, but the fever is not accompanied by chills before, and the antibiotic treatment is ineffective. Fever is related to the absorption of tumor necrotic material, cholangitis caused by cancer compression or invasion of bile ducts, and other infections due to weakened resistance. Carcinoma syndrome is an endocrine or metabolic syndrome caused by the abnormal metabolism of the tumor itself or various effects between the cancer tissue and the body. (1) Spontaneous hypoglycemia, seen in 10-30% of patients, may be related to ectopic secretion of insulin-like substances by liver cancer cells, excessive storage of glycogen by the tumor, inhibition of insulinase production, or secretion of islet β-cell stimulating factor. (ii) Erythrocytosis, seen in 2-10% of patients; may be due to increased erythropoiesis-stimulating hormone. Hypercalcemia may be related to the secretion of ectopic parathyroid hormone by hepatocellular carcinoma tissue. Hypercalcemia associated with hepatocellular carcinoma is different from hypercalcemia associated with tumor bone metastasis, which is associated with high blood phosphorus and often has clinical signs of bone metastasis to help differentiate. When hepatocellular carcinoma is accompanied by hypercalcemia, hypercalcemia crisis may occur, such as drowsiness, mental abnormality, coma, etc. It is often misdiagnosed as hepatic encephalopathy or brain metastasis. Symptoms of metastases, VI. Staging Ⅰa single tumor with maximum diameter ≤ 75px, no cancer embolus, abdominal lymph nodes and distant metastases; liver function classification ChildA. Ⅰb single or sum of two tumors with maximum diameter ≤ 125px, in half liver, no cancer embolus, abdominal lymph nodes and distant metastases; liver function classification ChildA. Ⅱa single or sum of two tumors with maximum diameter ≤ 250px, in The sum of the maximum diameters of single or two tumors is ≤250px, in half of the liver or the sum of the maximum diameters of two tumors is ≤125px, in the left and right halves of the liver, without cancerous emboli, abdominal lymph nodes and distant metastases; liver function is graded as ChildA. Tumor status regardless, with portal vein branch, hepatic vein or bile duct cancer embolus and/or liver function grade ChildB. IIIa tumor status regardless, with portal vein trunk or inferior vena cava cancer embolus, abdominal lymph nodes or distant metastasis; liver function grade ChildA or B. IIIb tumor status regardless, with cancer embolus and metastasis regardless; liver function grade ChildC. VII. Complications Hepatic encephalopathy accounts for approximately one-third of the causes of death. Upper gastrointestinal bleeding accounts for about 15% of the causes of death. Rupture of cancer nodules accounts for about 10% of the causes of death and is the most urgent and serious complication of hepatocellular carcinoma. A small amount of bleeding is manifested as bloody ascites, while a large amount of bleeding can lead to shock or even rapid death. Secondary infections are easy to be complicated by various infections, such as pneumonia, sepsis, intestinal infection and mycobacterial infection, especially when the white blood cell is reduced after chemotherapy or radiotherapy. AFP 2. Imaging: Ultrasound is preferred. CT is the preferred non-invasive diagnostic method to supplement ultrasound to estimate the extent of lesions, CT scan plus enhancement is the routine, and CTA and CTAP are the most effective methods to confirm the diagnosis of suspicious lesions or small hepatocellular carcinoma. Plain scan: confined hypodense area, can show 50px, positive rate over 90%. Enhancement: it can show tumor below 25px. MRI is better than CT. X-ray hepatic angiography DSA>25px Radionuclide liver imaging is qualitative and localized, and lesions within 50px are still difficult to show. Diagnosis Three elements are emphasized in the diagnosis of hepatocellular carcinoma: history of chronic liver disease; fetoprotein; and hepatic occupying lesions, which are the main basis for the diagnosis of primary hepatocellular carcinoma. High-risk groups: history of hepatitis for more than 5 years, positive hepatitis B or C viral markers, and over 35 years old. Early diagnosis is a prerequisite for primary liver cancer to obtain early treatment. Once typical symptoms and signs of liver cancer appear, the diagnosis is not difficult, but it is often not early. Diagnostic methods of liver cancer include qualitative diagnosis and localization diagnosis. Diagnostic criteria of the 8th National Hepatocellular Carcinoma Symposium in Guangzhou in September 2001 1.AFP≥400μg/L, which can exclude pregnancy, germline embryonic tumor, active liver disease and metastatic hepatocellular carcinoma, and can palpate the liver with enlarged, hard and large nodular masses or occupying lesions with features of hepatocellular carcinoma on imaging. 2.AFP＜400μg/L can exclude pregnancy, germline embryonic tumor, active liver disease and metastatic hepatocellular carcinoma, and there are two types of occupying lesions with hepatocellular carcinoma characteristics on imaging or two types of hepatocellular carcinoma markers (DCP, GGT II, AFU and CA19-9, etc.) positive and one type of occupying lesions with hepatocellular carcinoma characteristics on imaging. 3. Those with clinical manifestations of hepatocellular carcinoma and definite extrahepatic metastatic lesions (including bloody ascites visible to the naked eye or cancer cells found in it) and can exclude metastatic hepatocellular carcinoma. The smaller the tumor, the higher the five-year survival rate. Palliative surgical treatment is suitable for larger tumors or scattered distribution or close to large blood vessel area, or combined with cirrhosis restriction which cannot be resected, such as hepatic artery ligation and/or hepatic artery cannulation chemotherapy, freezing, laser therapy, microwave therapy, intraoperative hepatic artery embolization therapy or anhydrous alcohol intratumoral injection, etc. Sometimes, it can shrink the tumor and decrease the serum AFP, providing the opportunity for two-step resection. Interventional therapy such as hepatic artery embolization, hepatic artery embolization chemotherapy (TAE), anhydrous alcohol injection (PEI), etc. ml=R3/2PICTURE Radiotherapy is suitable for unresectable hepatocellular carcinoma whose tumor is still limited Chemotherapy with cisplatin (CDDP) as the first choice, commonly used are 5Fu, adriamycin (ADM) and its derivatives, mitomycin, VP16 and methotrexate, etc. Other biological, immunological and Chinese medicine Other biological, immunological and traditional Chinese medicine are also used in combination with surgery, chemotherapy and radiotherapy to reduce the suppression of immunity and destroy residual tumor cells.