Primary liver cancer (hereinafter referred to as liver cancer) is a common malignant tumor in China, with the second highest annual death rate of malignant tumors after lung cancer. An important factor affecting the prognosis of hepatocellular carcinoma is the development of portal vein tumor thrombus (PVTT), the incidence of which is as high as 62.2%-90.2%, and most of them die within 3-4 months of diagnosis without treatment. So far, the formation mechanism and treatment of portal vein thrombus in hepatocellular carcinoma are still being further explored. 1.Formation mechanism Hepatocellular carcinoma is mainly supplied by hepatic artery, while the cancer cells and subfoci around the tumor are mainly supplied by portal vein. When the tumor grows up, the peripheral cancer tissues can break through the envelope to infiltrate and grow outward, and invade the branches of portal vein with thin vascular wall to form portal vein cancer thrombus. The central veins of liver lobules lack connective tissue and are easily compressed by tumor nodules and cirrhotic nodules and are occluded, so that the arterial perfusion blood of tumor tissues cannot be adequately returned, and the output blood containing cancer cells flows backward to the portal vein, forming portal vein cancer thrombus. Some scholars believe that the portal vein system is relatively low pressure and low flow rate, and the shed cancer cells can easily enter the portal vein through the artery-portal vein shunt within the tumor and form a cancer thrombus. The altered blood flow rheology in patients with hepatocellular carcinoma also contributes to the formation of portal vein cancer thrombus. Most patients with hepatocellular carcinoma have hepatic steatosis, and the deformability of red blood cells is reduced and their aggregation is increased. This makes it easy for cancer cells carried by blood to migrate from the vascular axis to the vessel wall and subsequently form cancer thrombi. In addition, compression by larger or more liver tumors, obstruction of normal lymphatic circulation in the liver, and stagnation of liver microcirculation aggravate the formation of cancer thrombus. Through the measurement of portal vein and intra-tumor hemodynamics in 96 liver cancer patients, Dong Lei et al. found that the higher the frequency and faster the speed of portal vein reflux, the more chances of portal vein cancer thrombosis, suggesting that portal vein cancer thrombosis is closely related to portal vein reflux. Some scholars believe that some angiogenic factors, such as fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and platelet-derived endothelial growth factor (PD-ECGF), promote the formation of portal vein cancer thrombus, while thrombin-regulating factor (TM) has the opposite effect. 2.Clinical characteristics If hepatocellular carcinoma is not actively treated, the survival period is generally less than 6 months, with an average of 2.7 months, and most patients die within 3 months due to rupture and bleeding of esophagogastric fundic varices or liver failure. The rupture rate of esophagogastric fundic vein in patients with portal vein trunk carcinoma embolism is as high as 48.3%. Among the pathological types, the incidence of portal vein carcinoma embolism was highest in diffuse hepatocellular carcinoma (77.8%), followed by nodular type (66.7%) and lowest in giant type (48.6%). In addition, the incidence of portal vein thrombosis was related to the site of liver cancer. The incidence of portal vein thrombosis was 77.3% in middle lobe hepatocellular carcinoma, and 58% and 35.7% in left and right hepatocellular carcinoma, respectively. Tumor size was not a determinant of portal vein thrombosis, and even surgically resected specimens of hepatocellular carcinoma less than 2 cm had a 37% incidence of thrombosis. According to the activity of tumor cells in portal vein cancer thrombus, it can be divided into 4 types: (1) proliferative type: cancer cells are actively proliferating, and proliferating tumor tissue accounts for more than 70%; (2) necrotic type: most of the cancer cells are degenerative and necrotic, and proliferating tumor tissue accounts for less than 30%; (3) mixed type: proliferating and necrotic tumor tissue accounts for about half each; (4) mechanized type: cancer thrombus is surrounded by fibrous tissue and mechanized. The composition ratios of each type were 46.7%, 18.7%, 28% and 6.7%, respectively. The portal vein cancer thrombus that is mainly necrotic can be easily detached, while the portal vein cancer thrombus that is mainly hyperplastic and below the medium branch is tightly adhered to the vessel wall and more difficult to be detached. Portal vein cancer embolus receives arterial blood supply from hepatic artery and capillary plexus around bile duct, and when the blood flow of hepatic artery is blocked, it can be supplied by portal vein. 3.Treatment Portal vein cancer embolus is an important factor of high recurrence rate after liver cancer surgery, which seriously affects the prognosis of liver cancer and is regarded as a sign of advanced stage of liver cancer, so non-surgical treatment is mostly adopted. In the past, portal vein cancer embolism was regarded as a contraindication to hepatic artery embolization chemotherapy, so patients often did not receive active treatment and died within a few months. With the development of surgical technology and in-depth research on the pathology of portal vein cancer embolism, it is now believed that as long as the conditions allow, the hepatocellular carcinoma should be removed surgically as far as possible, and the portal vein cancer embolism should be removed at the same time, and then combined with other methods such as hepatic artery and portal vein chemoembolization or infusion chemotherapy, ultrasonic intervention, radiation therapy, immunotherapy, etc., which can still achieve more satisfactory results. The advantages of this method are: ① resection of hepatocellular carcinoma prevents tumor from continuing to invade the portal vein; ② removal of cancer embolus reduces portal vein pressure, which can reduce ruptured esophagogastric fundic varices bleeding and intractable ascites; ③ increase portal vein blood supply, improve liver function and facilitate follow-up treatment; ④ avoid or reduce intrahepatic metastasis due to portal vein cancer embolus; ⑤ reduce tumor load and enhance immunity, which can improve the effect of follow-up treatment. The effect of follow-up treatment can be improved. (1) Surgical treatment For patients with hepatocellular carcinoma who meet the following surgical conditions, regardless of the location of portal vein cancer embolus, hepatectomy should be actively performed, and portal vein cancer embolus should be removed or excised at the same time: ① the patient’s general condition is good and there are no serious lesions in important organs; ② the liver function is normal or basically normal; ③ the tumor is confined to one or half lobe of the liver, no distant metastases are formed, and the 1st, 2nd and 3rd hilum is not invaded. The most commonly used and safer surgical methods are: ① For unilateral portal vein branch, first free and block the contralateral portal vein branch, and then remove the cancer embolus by suction, spatula and blood flow flushing through the opening of the portal vein stump after resection of the tumor; ② When the cancer embolus spreads to the contralateral portal vein branch or trunk, the embolus can also be removed by the above methods first, and then the contralateral portal vein branch or trunk can be dissected if it cannot be removed. If the embolus cannot be removed first, then a contralateral portal vein branch or portal vein trunk can be incised. Mei Minghui et al. treated 18 patients with hepatocellular carcinoma complicated by portal vein thrombosis with the above method, and the average survival was 15 months and the longest was 27 months after surgery, and the survival rates of six months, one year and two years after surgery were 100%, 75% and 6.7%, respectively. Fan Jia et al. reported the observation of 111 patients with hepatocellular carcinoma complicated by portal vein carcinoma embolism in group treatment. The survival rates at 1, 3 and 5 years after surgery were 61.7%, 32.3% and 22.4%, respectively, while the non-surgical group died within 3 months due to bleeding from ruptured esophagogastric fundic varices or liver failure, suggesting that surgical treatment can prolong the survival period and improve the quality of life of patients with hepatocellular carcinoma with portal vein thrombosis. At present, most of the clinics adopt the integrated treatment method of postoperative supplemented with chemotherapy and immunotherapy, which can further reduce the chance of tumor recurrence and metastasis. Minagawa et al. reported that the mean survival time of 18 patients with portal vein cancer embolism treated with surgery after TACE was (3.4±2.7) years, compared with (0.36±0.26) years for 27 patients in the TACE-only group. Therefore, surgical resection of the tumor to remove the cancer embolus followed by other methods of comprehensive treatment is an active and effective treatment for hepatocellular carcinoma combined with portal vein cancer embolus. (2) Transhepatic artery and portal vein infusion chemoembolization Since the blood supply of hepatocellular carcinoma and portal vein cancer embolism mainly comes from the hepatic artery, TACE is one of the main non-surgical treatment methods, which is also applicable to patients with portal vein cancer embolism whose hepatocellular carcinoma cannot be removed. Most of the portal vein thrombosis causes reduction of portal blood flow, but it will not completely block the portal blood flow, and it will also form rich collateral circulation when the portal blood flow is poor, so portal vein thrombosis should not be a contraindication to TACE. Cao Jue et al. performed TACE in 33 patients with hepatocellular carcinoma complicated by portal vein thrombosis, and selected 5-fluorouracil, mitomycin, and epiamycin as chemotherapeutic agents, and iodinated oil and gelatin sponge as embolic agents. The mean survival time of the chemotherapy drug + iodinated oil treatment group was 8 months, and the survival rates at six months and one year were 80% and 8%, respectively. In the chemotherapy drug + iodinated oil + gelatin sponge group, the mean survival was 14.1 months, and the six-month and one-year survival rates were 75% and 37.5%, respectively. The study of pathological anatomy found that tumor margins and subfoci are mainly supplied by portal vein, and portal vein carcinoma thrombus will also become portal vein blood supply after hepatic artery embolization, so the method of hepatocellular carcinoma complicated by portal vein carcinoma embolization via dual route of hepatic artery and portal vein infusion chemoembolization has been proposed. Zhao Ting reported 17 patients with hepatocellular carcinoma complicated by portal vein thrombosis who underwent surgical implantation of subcutaneous hepatic artery and portal vein chemo-embolization pump, and injected drugs into the hepatic artery and portal vein once every 7-10 days, 4 times for a course, and repeated the next course in 2-3 months with the following drugs: mitomycin 6-18mg, 5-fluorouracil 0.5-1.5g, cisplatin 30-60mg, iodine oil 10ml. Ultrasound showed that 29% of the patients had disappeared and 41% of the patients had shrunken portal vein cancer thrombus. For patients with poor liver function who are not suitable for hepatic artery embolization, hepatic artery perfusion chemotherapy can be chosen. itamoto et al. administered hepatic artery implantable chemotherapy pump perfusion chemotherapy to 7 such patients, with cisplatin 10 mg and 5-fluorouracil 250 mg daily for 24 h from day 1 to day 5, and continued with the next course after 2 days, for at least 3 courses. The AFP decreased in all AFP-positive patients after treatment, including 2 cases to normal, 6 cases with different degrees of liver tumor shrinkage, and 3 cases with reduction or disappearance of portal vein cancer thrombus, with mean and median survival of 8 and 7.5 months, respectively. (3) Ultrasound-guided percutaneous transhepatic portal vein puncture or cannulation Ultrasound-guided percutaneous hepatic puncture has become increasingly mature and is widely used in the diagnosis and treatment of hepatobiliary diseases. Direct injection of anhydrous alcohol through ultrasound-guided portal vein puncture can cause tumor cells to become dehydrated, metabolism is blocked and degenerative necrosis occurs, and the blood supply vessels of the cancer thrombus are also destroyed, which accelerates the necrosis of the cancer thrombus. Lin et al. reported 18 cases of portal vein cancer thrombus treated with ultrasound-guided anhydrous alcohol injection, 1-2 times per week, 5-7 times for a course of treatment, with 6-12 months follow-up, 7 cases (38.9%) of cancer thrombus disappeared and 8 cases (44.4%) of cancer thrombus shrunk or stopped development. Iodine oil and chemotherapeutic drugs injected into the portal vein with the same puncture method is also one of the common methods. A mixture of iodine oil 5-10ml plus epiaminomycin 30-60mg, mitomycin 10mg and 5-fluorouracil 1.0g was injected into the portal vein cancer thrombus once every 2-3 weeks for 3-5 times, and the portal vein cancer thrombus disappeared in 2 out of 5 cases and became smaller in 1 case, and the abnormal blood flow signal under ultrasound disappeared. The portal vein cancer thrombus puncture should be successful at one time to avoid multiple punctures of the portal vein that may cause increased pain or bleeding. If the chemotherapy tube is retained after successful portal vein puncture, the drug can be repeatedly administered, reducing the complications such as bleeding and infection that may occur with repeated portal vein punctures. In the authors’ department, a total of four patients have undergone hepatic artery chemoembolization + percutaneous portal vein puncture with tube placement chemotherapy since May 2001 without any complications. One case of portal vein cancer thrombus disappeared, shrunk or did not change significantly, and the other case of hepatocellular carcinoma was resected at stage II surgery, and the portal vein cancer thrombus was completely necrotic on pathological examination. In the first case, the efficacy was found to be satisfactory. During treatment, the patient’s liver moved longitudinally during respiration, which often caused the chemotherapy tube to exit the portal vein and bend or fold between the liver and the abdominal wall, thus necessitating re-piercing the tube. Liu Yuanshui et al. used ultrasound to observe the longitudinal mobility of the liver under calm breathing in normal and cirrhotic patients, respectively. (4) Radiation therapy Hepatocellular carcinoma is not sensitive to radiation therapy, but radiation therapy can still be considered for patients with hepatocellular carcinoma who have acceptable liver function and are not indicated for surgery, and may achieve better results. Lin Junhua et al. treated 18 patients with hepatocellular carcinoma with portal vein thrombosis with 60 cobalt or high-energy X-rays as whole liver mobile strip radiotherapy, and among the 9 cases with mean tissue irradiation (mTD) >25Gy in liver, 4 cases of thrombosis disappeared and the others did not see any growth of thrombosis. 10 cases were effective. In the Tazawa study, the median survival after radiotherapy was significantly longer in patients with Child A liver function than in those with poorer liver function. Therefore, radiotherapy should be used with caution in patients with severe cirrhosis and poor liver function. (5) Other treatment methods Recently, argon helium knife ultra-low temperature cryosurgery combined with double perfusion of hepatic artery and portal vein has achieved more satisfactory results in the treatment of hepatocellular carcinoma complicated by portal vein thrombosis. In animal experiments, ultrasound ablation was found to be effective in ablating portal vein cancer thrombus and also effective in killing cancer cells, but no clinical application has been reported. Comprehensive treatment can indeed relieve patients’ symptoms such as abdominal pain and distension, reduce complications such as upper gastrointestinal bleeding, and achieve more satisfactory recent efficacy. However, the prognosis of hepatocellular carcinoma complicated by portal vein carcinoma thrombosis is still very poor, and the medium- and long-term efficacy of the existing treatment methods is not yet satisfactory. Choosing a more individualized treatment plan according to each patient’s specific condition will further reduce the complications during treatment, improve patients’ quality of life, and enhance the medium- and long-term outcomes.