metastatic liver cancer
Introduction
Introduction to metastatic liver cancer Metastatic hepatic carcinoma (metastatic hepatic carcinoma) is a malignant tumor that originates from other parts of the body and metastasizes to the liver, and forms single or multiple cancerous foci in the liver. In most patients, the clinical manifestations of primary cancer precede the metastatic liver cancer, but in some patients, the origin of the primary lesion is unclear or at the same time, two or more organs including the liver are found to have tumors. basic knowledge The proportion of illness: 0.003% Susceptible people: no specific population Mode of infection: non-infectious Complications: bloating, ascites, malnutrition
Cause
Metastatic liver cancer
(1) Causes of the disease
The cancer of the whole body can be transferred to the liver almost. The malignant tumor can directly infiltrate into the surrounding tissues, or invade the lymphatic vessels, blood vessels and body cavity. Then the cancer cells are transferred to the distant with lymph, blood and various channels. The infiltration and metastasis of cancer cells mainly depend on their own malignant biological characteristics and immune status. The cancer cells have amoebic activity and can infiltrate and move to the surrounding tissues autonomously. The adhesion between cancer cells is reduced. It has a tendency to easily fall off and increases the chance of metastasis; cancer cells have high expression of certain integrins, which may confer the motility of cancer cells to migrate, making it easy to penetrate the basement membrane; some adhesion molecules of the body help cancer cells in Retention in the transferred organs; the increase in the activity of proteolytic enzymes on the surface of cancer cells is also conducive to its infiltration and metastasis. Since most of the tumor-bearing hosts have low immune function, they cannot effectively recognize and kill metastatic cancer cells, once the cancer cells are far away. The organ stays and releases a variety of growth factors and their receptors, such as vascular endothelial growth factor (VEGF), making cancer cells autonomically free. Growth, the malignant biological characteristics of cancer cells are related to the genetic information they carry, such as DNA ploidy or stemline levels. Aneuploid cancer cells are more likely to metastasize than diploid cancer cells, and the liver is itself The characteristics of anatomy and blood supply may make it easier to provide residual growth space and nutrient sources for a variety of cancer cells.
There are four types of cancer, hepatic artery, lymphatic road and direct infiltration.
Portal vein transfer
All the organs of the venous system, such as the lower esophagus, stomach, small intestine, colorectal, pancreas, gallbladder and spleen, can be transferred to the liver through the portal vein. This is important for the spread of primary cancer to the liver. Pathway, there is a report of shunting of portal vein blood flow, that is, the blood flow of the splenic vein and the inferior mesenteric vein mainly enters the left liver, and the blood flow of the superior mesenteric vein mainly flows into the right liver. The tumors of the organ belonging to these portal veins are different. The direction of blood flow is transferred to the liver of the corresponding site, but the clinical shunt of the tumor metastasis is not obvious, but the whole liver is more common in sexual metastasis, other parts such as uterus, ovary, prostate, bladder and retroperitoneal tissue. Cancer can also be transferred to the liver through the anastomosis of the body vein or portal vein; it can also be caused by tumor growth in these areas to invade the organ of the portal system and then transferred to the liver; or from the body vein to the lungs, and then from the lungs to The whole body circulates to the liver.
2. Hepatic artery transfer
Any cancer that spreads in the bloodstream can be transferred to the liver through the hepatic artery. Malignant tumors such as lung, kidney, breast, adrenal gland, thyroid, testis, ovary, nasopharynx, skin and eyes can be spread through the hepatic artery. To the liver, it is also more common to transfer to the liver.
3. Lymphatic transfer
The pelvic or retroperitoneal cancer can pass through the lymphatic vessels to the aortic and retroperitoneal lymph nodes, and then back to the liver. Gastrointestinal cancer can also be retrogradely transferred to the liver via the hilar lymph nodes, and breast cancer or lung cancer can also pass. The mediastinal lymph nodes are retrogradely transferred to the liver, but this mode of metastasis is less common. Clinically, it is more common to see gallbladder cancer metastasis to the liver along the lymphatic vessels of the gallbladder fossa.
4. Direct infiltration
Cancers adjacent to the liver, such as gastric cancer, transverse colon cancer, gallbladder cancer and pancreatic cancer, can be directly infiltrated by the cancer cells and spread to the liver due to cancer and liver adhesion. The right kidney and adrenal cancer can also directly invade the liver. .
(two) pathogenesis
The liver is an organ that is extremely suitable for tumor cell growth. Among them, gastrointestinal tumors are most prone to liver metastasis. This is related to the blood perfusion of the portal vein system. As for how the liver becomes the most common organ of metastatic cancer, it is not only Due to blood enrichment and lymphatic drainage, the intrinsic mechanism is still unclear. The metastasis of cancer cells is a multi-step complex process, including the loss of primary tumor cells, through the vessel wall, into the blood circulation or after the lymphatic system. Bed tissue or organ, after implantation, cancer cells grow and divide to form metastases, etc. The fine structure of the liver may also affect the occurrence of tumors. Liver blood flows through the sinusoids, sinusoidal endothelial cells and Kupffer cells play the role of cancer cells. The liver's rich dual blood supply also helps to transfer the cancer embolus to obtain nutrient supply, while the sinusoidal endothelial cells are characterized by pores of different sizes; there are Kupffer cells in the hepatic sinus, which are characterized by good capture. Granular substances in the sinusoidal blood flow, blocking the path of tumor cells in the bloodstream, accompanied by platelets of Kupffer cells are more helpful Capturing tumor cells, if tumor cells are to survive, they must pass through the sinusoidal endothelial cell layer to reach the Disse gap, otherwise they will be surrounded and destroyed by Kupffer cells, which provide excellent growth for tumor cell growth in the gap of Disse. Conditions, both nutrient-rich filtrate from the sinusoidal blood flow, and no other cell confrontation and interference, so the development of metastases in the liver is often much faster than other sites of metastases, when liver metastases occur At the time, patients are often firstly endangered by liver metastases.
It is believed that tumor cells can be multiplied by about 20 times, and can reach a distance of 1 mm, about 1 million cells, which has the ability to metastasize. At this time, the tumor nodules are still difficult to be found by modern advanced imaging examinations. The carcinoma in situ, especially the deep organs like the liver, is very difficult. When the tumor nodules are multiplied by 20 to 80 times, it can be found by modern examination methods. Therefore, tumor nodules are discovered early. In fact, the tumor has actually existed for several months to several years, during which time the tumor has the ability to metastasize.
Animal experiments suggest that 4 million tumor cells can be shed every 24 hours per gram of tumor tissue, which can be a source of metastasis, but 90% of the tumor cells quickly disappear in the circulation, and more than 99% will die soon. Therefore, the transfer is not all effective. It depends on the body's defense ability, local conditions, tumor cell biological characteristics and other factors. Most of the tumor cells that fall off into the circulation are scattered, less than 0.1%. Polymerization forms cell clumps or tumor plugs, which can establish metastatic lesions at new sites much more efficiently than dispersed cells. When establishing metastases, tumor cells need to pass through the microvascular intima to the perivascular, When the tumor nodules reach 1-3 mm, they must establish their own blood supply to maintain the need for continuous proliferation, and the metastasis can become a new source of metastasis. If there is not enough blood circulation, the tumor cells rely only on nutrients. When diffusion is maintained, the tumor cells balance between reproduction and death, and the tumor remains 1 to 3 mm in size without increasing.
The tumor cell transfer station is the capillary network or lymph node that drains the part. Therefore, the first stop is the liver when the visceral tumor metastasizes, but some metastases remain "latent" and do not develop into large pieces of metastasis, which may be related to the latentity of tumor cells. Related; cell latency refers to the transfer of tumor cells in the G1 phase of cell division, but retains its ability to subsequently divide, which may explain why clinically seen primary tumors have metastasis after many years of resection, and many experiments have proved Surgery, hormonal effects, impaired immune function can activate latent metastatic tumor cells, growth; clinical stimuli such as radiation, surgical trauma, pregnancy, stress, infection can also stimulate latent tumor cell activation, growth As a large tumor, the liver receives a dual blood flow supply from the portal vein and the hepatic artery. The liver metastasis can come from the portal vein and the systemic circulation, that is, the tumor cells enter the systemic circulation through the pulmonary capillaries. The blood supply of the liver metastases suggests that when the metastases grow, the growth of the tumors increases. When large, there is new angiogenesis, and the original blood vessels or normal blood vessels are occluded, early metastasis When the tumor is less than 1mm, the nutrition mainly comes from the spread of the surrounding circulation; when the tumor reaches 1-3mm, the arterial, portal vein, and mixed capillary network are formed around the tumor; when the tumor is further enlarged, the blood supply is Complicated, about 90% of the main blood supply from the hepatic artery; it has been proposed to use hepatic artery ligation to treat metastatic liver cancer; once the tumor volume reaches 1.5 ~ 3.0cm, blood supply is more complicated, from angiography and other images Learning observation, blood flow is still mainly from the hepatic artery. Due to the duality of hepatic blood supply, some metastases in the liver may show high-density shadows on the CT scan of the arteries, and some may not be displayed; likewise, in the portal vein CT Similar effects can also be seen when scanning.
The metastatic cancer nodules of the liver vary in size and number, and can be isolated from 1 to 2 nodules, but most of them are diffuse multiple nodules, which can be spread in the liver or a whole liver. The appearance of cancer nodules is mostly Grayish white, hard texture, the center of the nodule is often sag due to necrosis, and there is a clear boundary between the surrounding liver tissue, the capsule is more complete, and the cancer is located in the periphery of the liver, but also deep in the liver parenchyma.
The pathological histopathology of secondary liver cancer is similar to that of primary cancer. For example, liver metastatic carcinoma from gastric adenocarcinoma or colon adenocarcinoma may show adenocarcinoma structure in tissues. Melanoma is included in tumor tissue from ocular melanoma. It is brown or black, but in some cases it is not the case, because the tumor cells are too poorly differentiated to identify the characteristics of their primary cancer.
The secondary cancer that has metastasized to the liver via the bloodway can be small and not found, but the growth of liver metastatic cancer is very fast and invades the whole liver. The metastatic carcinoma of the liver is rarely associated with cirrhosis. Does not invade the portal vein or form a tumor thrombus, which is different from primary hepatocellular carcinoma.
Prevention
Metastatic liver cancer prevention
The preventive measures for metastatic liver cancer are as follows
First, we must prevent viral hepatitis. So far, the incidence of liver cancer in viral hepatitis has been high. The effective way to prevent viral hepatitis in China is to vaccinate hepatitis B. It can also be said that this is a way to prevent the occurrence of liver cancer.
To develop good habits. The primary prevention of liver cancer in people's good habits is to quit smoking and stop drinking. The second is to develop good eating habits, starting with food hygiene and living habits. Wash your hands and eat meals. Can not eat moldy, paste food, this type of food contains aflatoxin, this substance is carcinogenic. The last thing to emphasize is good quality sleep. From 11:00 pm to 3 am, it is the time for the liver to self-repair and metabolism. At this time, to ensure that the human body has gone to sleep, the liver can get enough rest and recover. The burden of the liver is the lightest during sleep, and the human body is lying down. The liver can enjoy more blood nourishment, and the blood flowing through the liver is the most, which is beneficial to liver repair.
Complication
Metastatic liver cancer complications Complications, abdominal distension, ascites, malnutrition
1. Loss of appetite: often caused by liver damage, tumor compression of the gastrointestinal tract.
2. Bloating: It is caused by huge tumor, ascites and liver dysfunction.
3. Weight loss, fatigue: can be caused by the metabolic consumption of malignant tumors and eating less, caused by malnutrition.
4. Fever: caused by tumor tissue necrosis, co-infection and tumor metabolites.
Symptom
Metastatic liver cancer symptoms Common symptoms refractory ascites cachexia liver function dysfunction liver pain liver metastasis loss of appetite fatigue bloodway dissemination pain unexplained metastases
There are no obvious symptoms and signs in the early stage of liver metastasis. The symptoms and signs of the liver are similar to those of the primary liver cancer. However, because there is no cirrhosis, the symptoms are slower and the symptoms are milder. The early symptoms are mainly the primary tumor. The symptoms of the liver itself are not obvious. Most of them are preoperatively examined in primary cancer. After follow-up or laparotomy, it is found that as the disease progresses, the tumor enlarges and the symptoms of the liver gradually manifest, such as pain in the liver area. Discomfort discomfort, fatigue, weight loss, fever, loss of appetite and upper abdominal mass, etc., in the late stage, jaundice, ascites, cachexia, and a small number of patients (mainly from the gastrointestinal, pancreas, etc.) liver metastasis of cancer, and the primary lesion Hidden and not obvious.
1. Symptoms and signs of primary cancer
It varies with the location and nature of the original cancer, but it may be the patient's main clinical manifestations, such as cough and chest pain in patients with lung cancer, upper abdominal pain and jaundice in patients with pancreatic cancer, which is often the early stage of liver metastasis. It is easy to pay attention only to the primary cancer and neglect the cancer. The liver, peritoneum, lungs and other organs may have metastasized.
2. Symptoms and signs of liver metastases
When the liver is extensively metastasized or the metastases are large, the patient may have symptoms and signs similar to those of primary liver cancer: pain or discomfort in the right upper abdomen or liver area, enlargement of the liver, such as touching the cancer nodules, the texture is hard and It may be tender; in the advanced stage, there may be jaundice, ascites and other dyscrasia. Sometimes the above symptoms and signs may be the only manifestation of the patient and it is difficult to find the primary lesion. Because liver metastases do not involve cirrhosis, Compared with primary liver cancer, the above-mentioned performance is slightly milder, the development is slower, and the complications are less.
3. Systemic symptoms
As the disease progresses, the patient may experience systemic symptoms such as fatigue, bloating, loss of appetite, weight loss, fever, and progressive aggravation.
Examine
Examination of metastatic liver cancer
Liver function
Subclinical secondary liver cancer often has no enzymatic abnormalities. Clinical manifestations are associated with ALP and GGT, but it does not help the direct diagnosis of liver metastases. Even if the liver has obvious enlargement, liver function is also Can be normal or mild abnormalities; severe cases may have elevated serum bilirubin, alkaline phosphatase (AKP), lactate dehydrogenase (LDH) and -glutamyl transpeptidase, of which AKP tends to rise significantly High and more meaningful for the diagnosis of liver metastatic cancer.
2. Tumor marker detection
Serum alpha-fetoprotein (AFP): More than 90% of patients with hepatic metastatic carcinoma are AFP-negative, but a small number of cancers from the digestive tract, pancreas and gonads can be detected as low-positive AFP.
Serum carcinoembryonic antigen (CEA): elevated CEA contributes to the diagnosis of liver metastases, CEA positive rate of liver metastases in colorectal cancer is as high as 60% to 70%, in the primary metastasis of the gastrointestinal, breast and lung cancer After the liver, the patient's serum CEA can be significantly increased.
CA19-9: It can often be elevated when pancreatic cancer metastasizes to the liver.
3. Detection of liver virus markers
The detection of serum hepatitis B virus markers in patients with this disease is mostly negative.
4. Imaging examination
There are B-ultrasound, CT, magnetic resonance imaging (MRI), etc. These tests are basically non-invasive, and can be repeatedly checked as needed. It should not be performed only once or one test without positive findings. The disease is easily excluded. Like multi-present enhanced echo; CT manifests as density or low density of mixed unevenness, typical appearance of "bull eye" sign, and more often without cirrhosis sign; MRI examination of liver metastases often shows uniform signal intensity, side clear, multiple, A few have "target" signs or "bright ring" signs, B-ultrasound and CT examination can show multiple scattered or single-shot solid occupations in the liver, and two can find cancers with diameters above 1 ~ 2cm.
5. Special inspection
According to the detection of selective hepatic angiography, the lower limit of the diameter of the lesion can be detected as 1cm, and the ultrasound imaging is about 2cm. Therefore, the early liver metastasis is mostly negative, and the positive result will appear when it is increased to a certain size. In the performance, the positive rate of various localization diagnosis methods can reach 70% to 90%, and selective abdominal or hepatic angiography often shows less vascular tumors.
(1) Angiography: Feasible selective hepatic angiography is often shown as a small vascular tumor nodule, and tumors with a diameter of 1 cm or more can be found.
(2) Liver biopsy: Fine-needle biopsy biopsy under B-ultrasound or CT guidance helps to confirm the diagnosis and search for primary cancer, but this method may cause intra-abdominal hemorrhage, and should be noted.
(3) Radionuclide development: liver metastases over 2.0 cm appear as non-developing areas on the development of radionuclides containing sulfur colloids. It should be noted that the sensitivity of this technique is high, but the false positive rate is also Very high.
(4) Laparoscopy: microscopic metastases not detected by the above imaging methods can be detected.
Diagnosis
Diagnostic differentiation of metastatic liver cancer
diagnosis
The key to the diagnosis of liver metastases is to determine the primary tumor, and there are clinical manifestations, which can be diagnosed according to the following points:
1. Most patients with a history of primary tumors or clinical manifestations of liver cancer, with colorectal cancer, gastric cancer, pancreatic cancer, etc. are most common.
2. There is often no chronic liver disease background, no obvious other liver function abnormalities and enzymology positive, such as HBV markers can be negative, more considered secondary liver cancer.
3. At the time of physical examination, the cancer nodules are harder and the liver is softer.
4. Imaging often shows substantial liver-occupying lesions, mostly scattered or multiple, similar in size, "bull-eye" sign can be seen in ultrasound imaging, and there is no cirrhosis, and hepatic angiography is rare.
5. Primary disease surgery found that liver metastasis can sometimes encounter metastatic liver cancer with unknown primary tumor, only the performance of metastases.
6. Laparoscopic or hepatic puncture confirms that the diagnosis depends on pathology.
Differential diagnosis
Primary liver cancer
More than 1 background of liver disease, hepatitis B or hepatitis C markers are often positive;
2 often accompanied by cirrhosis;
3 blood AFP is often significantly elevated;
4B super-normal display of substantial heterogeneous light groups, some with halo;
5 color super often shows a rich blood flow, can measure the arterial spectrum, the resistance index is often greater than 0.60;
The arterial phase of the 6CT enhanced scan often shows an enhancement effect, but the venous phase enhancement effect is weakened, showing the characteristics of "fast forward and fast out";
7 portal vein tumor thrombus is almost a characteristic sign of primary liver cancer.
Hepatic cavernous hemangioma
1 slow development, long course of disease, and mild clinical manifestations are generally better;
2 Hepatitis B and hepatitis C markers are often negative;
3CEA, AFP are negative;
4B is mostly a strong echo light group with a mesh structure inside;
5 color ultrasound examination does not show rich color blood flow, rare arterial spectrum;
The 6CT enhanced scan shows that the contrast agent is filled, the periphery spreads to the center, and the delayed phase image is still high density;
7 liver blood pool scan positive.
3. Liver abscess
1 often has a history of extrahepatic (especially biliary) infection;
2 often have chills, high fever;
3 often have pain in the liver area, physical examination may have pain in the liver area;
4 The total number of white blood cells and neutrophils often increase;
5B super can exhibit low echo occupancy, sometimes visible liquid level;
6CT can be seen in low-density occupancy, and there is no enhancement after injection of contrast agent;
7 If necessary, perform a liver puncture examination, sometimes pus.
4. Hepatic sarcoma
There is no history of primary cancer, such as hepatic angiosarcoma often has a history of exposure to chemical reagents such as vinyl chloride, and the lesions are limited.
5. Liver cyst
The medical history is long, the symptoms are light, and the ultrasound examination has a liquid level.
