Comprehensive treatment based on surgery has become the main strategy for the treatment of primary liver cancer (hepatocellular carcinoma), among which hepatic vascular intervention with dual chemoembolization of hepatic artery and portal vein is one of the main means of non-surgical tumor therapy as well as postoperative prevention of tumor recurrence and metastasis, and has achieved better efficacy. Moreover, the effect is better than that of simple hepatic artery chemoembolization (TACE). 1. Need of portal vein chemotherapy 1.1 Blood supply of hepatocellular carcinoma 90%-95% of the blood supply of hepatocellular carcinoma comes from hepatic artery, and the center of tumor is mainly supplied by hepatic artery, while the peripheral part of tumor, as well as the cancerous tissues on the fiber envelope and extra-envelope infiltration, subfoci and portal vein cancer embolus are mainly supplied by portal vein, and these parts are the most active parts of tumor growth. Studies have shown that 38.5% of small hepatocellular carcinomas have double blood supply, and 75.3% of hepatocellular carcinomas >3cm have double blood supply. Moreover, the blood vessels of hepatocellular carcinoma do not communicate directly with the hepatic artery, but with the terminal portal vein of the tumor and the hepatic sinusoids, and the drugs perfused from the hepatic artery go to the portal vein through these anastomotic branches before entering the tumor tissue. Liu Pengcheng et al. injected iodine oil suspension into rats with hepatocellular carcinoma through the portal vein, and observed microscopically that iodine oil drops were present in the carcinoma nidus, small vessels in the carcinoma nidus, hepatic sinus and central vein. This indicates that the portal vein is involved in the blood supply of hepatocellular carcinoma, and the injection of iodized oil suspension through the portal vein can cause necrosis of hepatocellular carcinoma cells. 1.2 Blood supply of hepatocellular carcinoma after TACE There is an extensive anastomotic branch between hepatic artery and portal vein, and the blood supply cannot reach the center of tumor because the pressure of portal vein is much lower than that of hepatic artery. After TACE, the hepatic artery is embolized and the portal blood can become the main blood supply to the tumor through the anastomotic branch. This is the reason why the tumor is difficult to be completely necrotic after TACE. 1.3 Mechanisms of recurrence and metastasis of hepatocellular carcinoma Even after radical resection of hepatocellular carcinoma, small cancer foci may remain in the remaining liver that cannot be detected by visual and imaging examinations. The cancer foci may easily invade the portal vein branches at an early stage and metastasize through the portal vein. The compression of the tumor during surgery may also lead to metastasis due to the entry of tumor cells into the portal vein or the detachment of cancer thrombus. In addition, portal vein cancer thrombus is one of the main factors affecting the prognosis of hepatocellular carcinoma, which also has dual blood supply from hepatic artery and portal vein. Therefore, portal vein chemotherapy has important clinical value in preventing recurrence of hepatocellular carcinoma and portal vein metastasis. 2. Indications for portal vein chemotherapy (PVC) The characteristics of blood supply of hepatocellular carcinoma determine that only combined hepatic artery and portal vein chemotherapy can achieve better curative effect. Therefore, in clinical practice, portal vein chemotherapy is rarely performed alone. Lai Honghao et al. believed that TACE and PVC should be performed to prevent recurrence in the following cases after hepatectomy: (1) cancer foci >5 cm, no envelope, multiple cancer foci and AFP >400ug/L; (2) AFP positive patients with AFP not decreasing significantly or rebounding after decreasing 2 weeks after surgery; (3) AFP negative patients with elevated AFP after surgery. The authors concluded that portal vein chemotherapy may have a more direct effect in inoperable patients with imaging findings of portal vein cancer thrombosis as long as they have Child A and B liver function and no other significant organ insufficiency. The indications for postoperative prophylactic chemotherapy should be: (1) tumor >5 cm without envelope or incomplete envelope; (2) multiple tumors; (3) portal vein cancer thrombus; (4) cancer thrombus formation in peri-cancerous tissue on microscopic examination; (5) AFP cannot be reduced to normal after surgery or starts to rise again after reduction. Wang Xuan et al. advocate that selective portal vein chemoembolization can be considered for all patients with TACE indications for intermediate and advanced hepatocellular carcinoma, but it is not suitable for those with large amount of combined ascites, jaundice and bleeding tendency. 3. Treatment methods 3.1 Intraoperative placement of portal vein chemotherapy pump Gastric omental right vein or middle colonic vein can be selected for puncture placement, and the head of chemotherapy tube can be fixed in appropriate position according to the need, and the body of chemotherapy pump can be buried in subcutaneous tissue. If these routes fail, a biliary probe can be used to access the umbilical vein within the hepatic ligament. The portal vein can also be placed through the hepatic trauma. Postoperatively, the subcutaneous pump body is punctured or the chemotherapy tube is administered directly through the extrasystoles, followed by an appropriate amount of heparin solution to prevent clotting in the catheter. 3.2 Ultrasound-guided percutaneous portal vein puncture injection or tube placement The intrahepatic portal vein branch is punctured under ultrasound guidance, and the drug is injected after drawing back blood or the chemotherapy tube is left in place in the same way as jugular vein placement for repeated continuous drug administration. 3.3 Intraperitoneal tube chemotherapy The drug in the abdominal cavity is absorbed by the greater omentum and flows back into the portal vein, so that there is a high blood concentration in the portal vein, which can play the role of portal chemotherapy. A deep venous catheter is placed in the lower abdomen, led through the skin and fixed outside the body, and sealed with a heparin cap. The head of the portal vein chemotherapy pump can also be placed in the abdominal cavity, with the pump body buried under the skin, and the drug can be administered through the punctured pump body. For cases with ascites, peritoneal puncture placement is feasible. Chemotherapeutic drugs are diluted with 500~1000ml (reduced as appropriate in the presence of ascites) of saline and then rapidly dripped into the peritoneal cavity through the chemotherapy tube, with changes in body position to enable the chemotherapeutic drugs to be distributed throughout the peritoneal cavity. In the case of infusion of more irritating drugs, such as mitomycin, lidocaine can be infused first to alleviate the symptoms of abdominal pain. 3.4 Chemotherapy via splenic artery during TACE The catheter is placed at the opening of the splenic artery while TACE is performed, and the injected drug is returned to the portal vein via the splenic vein to play a chemotherapeutic role. The amount of drug used in the splenic artery is 1/2 of that in the hepatic artery, and the simultaneous treatment with TACE can significantly improve the treatment effect of portal vein cancer embolism and the survival rate within 3 years. 3.5 Laparoscopic portal vein pump placement Laparoscopic pump placement is less invasive than open surgery. Li Zhenya et al. performed 18 cases of hepatocellular carcinoma with laparoscopic placement of hepatic artery and portal vein pumps for chemoembolization by pulling the right gastroretinal artery and the dissected hepatic round ligament near the liver from the puncture hole and placing the pumps outside the abdominal wall, all of which achieved satisfactory results without complications caused by laparoscopic operation. 4, drug regimen Commonly used chemotherapeutic drugs and dosage are adriamycin (epi-adriamycin, epirubicin, piroplatin) 20~40mg, platinum (carboplatin, platinum) 100~200mg, 5-Fu, FUDR 500~1500mg, mitomycin 10~20mg, hydroxycamptothecin 10~20mg, Jianzhe 600~1000mg. mostly with 5-Fu as the basis. The dosage is increased or decreased according to the liver function and tumor size. The commonly used embolic agents include super liquefied iodine oil, gelatin sponge, etc. The dose of portal vein is the same as that of hepatic artery, but the dose is reduced by half, or only perfusion chemotherapy is administered, and the interval depends on the recovery of liver function after TACE. Immunologically active cells can also be infused during chemotherapy to kill tumor cells. Liu Guangzhong reported that the total efficiency of treatment of intermediate to advanced hepatocellular carcinoma with autologous LAK cells/IL-2 and chemotherapeutic drugs via hepatic artery and portal vein infusion reached 85.7%. Since glucocorticoids have important functions such as changing microcirculatory function and counteracting vascular permeability factor, protecting subcellular structure and enhancing lysosomal membrane stability, they are often used for portal vein infusion to reduce liver damage caused by chemotherapy, but they also have immunosuppressive effects, which may be detrimental to tumor control and should be used with caution. 5. Efficacy 5.1 Middle and late stage liver cancer For middle and late stage liver cancer that cannot be resected surgically, as long as the liver function is good, the treatment method of TACE+PVC is often used and has achieved good efficacy. Li Ling et al. reported four patients with hepatocellular carcinoma treated with TACE and injected 20-30 mg of carboplatin into the portal vein at regular intervals every day, and continued chemotherapy with a total of 4-5 g of 5-Fu dripped into the portal vein for five consecutive days, and the masses of all patients were significantly reduced, and the cancer thrombus of the main portal vein disappeared in one case. It was found that double chemoembolization of primary hepatocellular carcinoma by transcatheter hepatic artery and B-ultrasound-guided portal vein was more effective than TACE alone, and the total efficiency of TACE+PVE and TACE groups were 57.2% and 37.5% in 209 patients, and the rates of disappearance+shrinkage of portal vein cancer thrombus were 68.8% and 22.2%, respectively. 95.6%, 59.6% and 39.1%, respectively, while the latter were 65.1%, 36.3% and 20.5%, respectively, which were significantly different (p<0.05). Tan Xuyan et al [15] reported that local treatment (microwave, anhydrous alcohol injection) combined with portal vein chemotherapy in 20 cases of moderately advanced hepatocellular carcinoma resulted in 100% survival rate at 1 year and 90% survival rate at 2 years. 3 out of 6 cases of portal vein carcinoma thrombus shrank and 2 cases disappeared. tace+pve also shrunk large hepatocellular carcinoma, thus giving some cases the opportunity for stage II surgery. 5.2 Prevention of postoperative recurrence Li Honghao et al [6] reported that combined TACE and PVC after radical resection of primary hepatocellular carcinoma could significantly reduce the postoperative recurrence rate and improve the postoperative survival rate, and the results were better than postoperative TACE alone. the 2-year recurrence rate after TACE+ PVC was 8.7%, which was significantly lower than the 20% in the TACE alone group. The 2-year survival rate of the former was 91.3%, which was significantly higher than that of the latter, which was 80%, compared with only 75% in the group without postoperative chemotherapy. Fan Jia et al. compared the effects and efficacy of different modes of chemotherapy and different routes of administration on postoperative chemotherapy for hepatocellular carcinoma combined with portal vein thrombosis, and the mean survival times of the portal vein infusion (PVI) and PVI+hepatic artery infusion (HAI) groups were 14 and 17 months, respectively, which were significantly higher than that of the postoperative group without chemotherapy at 7 months, while the mean survival times of the push-in chemotherapy and continuous infusion chemotherapy groups were 13 and 19 months, respectively. There was a significant difference, suggesting that PVI or PVI+HAI could significantly prolong the survival time after surgery for hepatocellular carcinoma, while the efficacy of continuous infusion chemotherapy was significantly better than that of push chemotherapy. The mean postoperative tumor-free survival was 21 months in group A, 11 months in group B, and 19 months in group C. The intrahepatic recurrence rates within 2 years were 19%, 62%, and 24%, respectively. This method can effectively reduce the possibility of hepatocellular carcinoma dissemination through the portal vein caused by the compression of the hepatocellular carcinoma tissue during surgery because the portal vein of the hepatic segment where the hepatocellular carcinoma is located is blocked, and at the same time, the hepatic segment can be completely resected by staining the hepatic segment where the tumor is located, so that the subclinical carcinoma foci that may exist in the segment can be removed together. Intraoperative injection of embolic agent along with portal vein chemotherapy, followed by resection of hepatocellular carcinoma, also has positive significance in preventing intrahepatic metastasis of hepatocellular carcinoma after surgery. 6. Main complications 6.1 Upper gastrointestinal bleeding Most patients with hepatocellular carcinoma have cirrhosis, hypersplenism, portal hypertension and impaired synthesis of coagulation factors, which are prone to bleeding, and chemotherapeutic drugs can directly penetrate into the mucosa of gastrointestinal tract through blood vessels and damage mucosal tissues and induce bleeding. Once bleeding occurs, chemotherapy should be stopped and hemostatic drugs such as thrombinogen complex and fibrinogen should be applied, and if necessary, hemostasis should be stopped by compression with a three-lumen tube. 6.2 Liver failure Before chemotherapy, the patient's liver reserve function should be fully evaluated and used to decide the type of drug, dose and treatment interval. Before and after chemotherapy, the liver function should be protected with polarizing fluid, branched-chain amino acids, vitamin C, Simethicone, Glycine, albumin, etc. If available, supplemented with hyperbaric oxygen therapy can significantly reduce the damage to liver function caused by chemotherapy. 6.3 Abdominal hemorrhage The removal of the catheter after percutaneous transhepatic portal vein puncture chemotherapy may cause abdominal hemorrhage, the author first withdrew the catheter tip into the portal vein to the liver parenchyma when removing the catheter, and then removed the catheter the next day, no abdominal hemorrhage occurred. 6.4 Drug leakage This is related to the operator's chemotherapy pump puncture technique. Use a special needle to puncture the central part of the drug pump vertically up to the bottom of the drug pump, if you are not sure whether it is in place you can push saline first to observe whether there is leakage around the pump. Special attention should be paid to strongly corrosive drugs such as epi-amycin and mitomycin to avoid skin necrosis. In the case of portal vein chemotherapy, the drug can enter the tumor area directly, which can increase the local drug concentration. At the same time, due to the relatively low pressure and slow flow rate of portal vein, the drug stays longer in the tumor area, which can improve the chemotherapy effect. If portal vein embolization is performed at the same time, the liver lobe or segment where the tumor is located can be atrophied, while the healthy side of the liver can be compensated to enlarge, which increases the chance of second-stage surgery. Portal vein chemotherapy is important to prevent recurrence and metastasis of hepatocellular carcinoma and prolong the survival of middle and late stage hepatocellular carcinoma.