1. Symptoms.
Pre-subclinical stage of hepatocellular carcinoma refers to the period from the beginning of lesion to the diagnosis of subclinical hepatocellular carcinoma, when patients have no clinical symptoms and signs and are difficult to be detected clinically, usually about 10 months. In the subclinical stage (early stage) of hepatocellular carcinoma, the tumor is about 3-5 cm, most patients still have no typical symptoms and the diagnosis is still difficult, mostly detected by serum AFP census for about 8 months on average, during which a few patients can have symptoms related to chronic underlying liver disease such as epigastric stuffiness, abdominal pain, weakness and loss of appetite. Therefore, those who have high-risk factors and develop the above conditions should be alerted to the possibility of liver cancer. Once the typical symptoms appear, the disease has already reached the intermediate or advanced stage of liver cancer, at which time, the disease develops rapidly, about 3-6 months in total, and its main manifestations are
(1) Pain in liver area. Pain in the right upper abdomen is the most common and is an important symptom of the disease. It is often intermittent or persistent vague, dull or distending pain, which increases with the development of the disease. If the tumor invades the diaphragm, the pain may spread to the right shoulder or the right back; a tumor growing backward to the right may cause pain in the right lumbar region. The cause of pain is mainly due to the tumor growth which makes the liver envelope tense. Sudden onset of severe abdominal pain and peritoneal irritation may be caused by peritoneal irritation due to rupture and bleeding of subperitoneal cancer nodules.
(2) Loss of appetite. Symptoms such as epigastric fullness after meals, indigestion, nausea, vomiting and diarrhea are easily ignored because of the lack of specificity.
(3) Wasting and weakness. The whole body is weak, and a few patients in advanced stage may present with cachexia.
(4) Fever. It is common, mostly persistent low fever, 37.5-38℃, but it may be irregular or intermittent, persistent or chills type fever, similar to liver abscess, but no chills before fever, and antibiotic treatment is ineffective. The fever is mostly cancer fever, which is related to the absorption of tumor necrotic material; sometimes it can be caused by cholangitis due to the compression or invasion of bile duct by cancer, or fever due to other infections combined with weakened resistance.
(5) Symptoms of extra-hepatic metastases. For example, lung metastasis may cause cough and hemoptysis; pleural metastasis may cause chest pain and bloody pleural effusion; bone metastasis may cause bone pain or pathological fracture, etc.
(6) Jaundice, bleeding tendency (gingival, nasal bleeding and subcutaneous bruises), upper gastrointestinal bleeding, hepatic encephalopathy and hepatic and renal failure are often seen in advanced stage patients.
(7) Concomitant cancer syndrome is a syndrome of endocrine or metabolic disorders caused by the abnormal metabolism of liver cancer tissue itself or the multiple effects of cancer tissue on the body. The clinical manifestations are diverse and lack of specificity, including spontaneous hypoglycemia, erythrocytosis, hyperlipidemia, hypercalcemia, precocious puberty, gonadotropin secretion syndrome, cutaneous porphyria, abnormal fibrinogenemia and carcinoid syndrome, but they are relatively rare.
2. Physical signs.
In the early stage of hepatocellular carcinoma, most patients do not have obvious positive signs, and only a few patients can be found with mild hepatomegaly, jaundice and skin pruritus on physical examination, which should be non-specific manifestations of the underlying liver disease. In mid- to late-stage hepatocellular carcinoma, jaundice, hepatomegaly (hard texture, uneven surface, with or without nodules, vascular murmur) and peritoneal effusion are common. If the background of pre-existing hepatitis and cirrhosis is present, liver palms, spider nevus, red nevus, abdominal wall varices and splenomegaly can be found.
(1) Liver enlargement: It is often progressively enlarged, with hard texture, uneven surface, nodules of different sizes or even giant lumps, with clear margins and often painful to touch and pressure of varying degrees. If the hepatocellular carcinoma protrudes to the right subcostal arch or subxiphoid process, the corresponding area can be seen to be locally full and elevated.
(2) Vascular murmur: Due to the rich and tortuous blood vessels of hepatocellular carcinoma and the sudden thinning of arteries or the compression of hepatic artery and abdominal aorta by cancer mass, about half of the patients can hear wind-like vascular murmur in the corresponding area.
(3) Jaundice: yellowish scleral staining of the skin, often in the late stage, mostly due to bile duct obstruction caused by cancer or enlarged lymph nodes, or due to hepatocellular damage.
(4) Portal hypertension: Patients with hepatocellular carcinoma mostly have a background of cirrhosis, so they often have portal hypertension and splenomegaly. Hematochezia is a late manifestation of peritoneal fluid, usually leaking fluid, and hematochezia is mostly caused by cancer breaking into the peritoneal cavity or by peritoneal metastasis.
3.Infiltration and metastasis.
(1) Intrahepatic metastasis: initially, most hepatocellular carcinomas are intrahepatic metastases, which easily invade the portal vein and its branches and form tumor embolus, and then cause multiple metastases in the liver. If the stem branch of portal vein is obstructed, it will often cause or aggravate the original portal hypertension.
(2) Extrahepatic metastasis.
(1) Hematogenous metastasis, lung metastasis is the most common, and it may also metastasize to the pleura, adrenal gland, kidney and bone.
(2) Lymphatic metastasis, with metastasis to the hilar lymph nodes being the most common.
(iii) Implantation metastasis, which is relatively rare, may occasionally be implanted in the peritoneum, diaphragm and chest cavity, causing bloody abdominal and pleural effusion; ovarian metastasis may occur in women, forming larger masses.
4.Common complications.
(1) Upper gastrointestinal bleeding: hepatocellular carcinoma often has hepatitis and cirrhosis background accompanied by portal hypertension, while portal vein and hepatic vein cancer thrombus can further aggravate portal hypertension, so it often causes bleeding from varices of middle and lower esophagus or fundus. If cancer cells invade the bile duct, it may cause biliary bleeding, vomiting blood and black stool. Some patients may bleed extensively due to gastrointestinal mucous membrane erosion, ulceration and coagulation dysfunction, which may lead to shock and hepatic coma.
(2) Hepatic nephropathy and hepatic encephalopathy (hepatic coma): In advanced stage of hepatocellular carcinoma, especially diffuse hepatocellular carcinoma, hepatic insufficiency or even failure can occur, causing hepatorenal syndrome, i.e. functional acute renal failure, which mainly manifests as significant oliguria, lower blood pressure, accompanied by hyponatremia, hypokalemia and azotemia, and often progresses. Hepatic encephalopathy, i.e. hepatic coma, is often a manifestation of end-stage hepatocellular carcinoma, often induced by gastrointestinal bleeding, massive diuretics, electrolyte disturbance and secondary infection.
(3) Rupture and bleeding of hepatocellular carcinoma nodes: It is the most urgent and serious complication of hepatocellular carcinoma. Therefore, gentle palpation is recommended during clinical examination and no forceful pressure should be applied. The rupture of cancer nodules can be confined to the subhepatic peritoneum, causing acute pain and rapid enlargement of the liver, and soft masses can be palpated locally. A small amount of bleeding can be manifested as bloody peritoneal fluid, while a large amount of bleeding can lead to shock or even rapid death.
(4) Secondary infection: Patients with hepatocellular carcinoma have weakened resistance due to long-term consumption and bed-rest, especially after chemotherapy or radiotherapy when their white blood cells are reduced, which can easily be complicated by various infections such as pneumonia, intestinal infection, fungal infection and sepsis.