Surgical treatment of primary hepatocellular carcinoma 1.Radical hepatectomy ①Local requirements A single microscopic hepatocellular carcinoma. B single small hepatocellular carcinoma. C single outward growing large hepatocellular carcinoma or giant hepatocellular carcinoma with smooth surface, clear surrounding boundary or pseudo-envelope formation, liver tissue destroyed by tumor < 30< span="">% (can be measured by CT or MRI) or although liver: tissue destroyed by tumor > 30%, but the tumor-free side of the liver has obvious compensatory enlargement of more than 50% of the whole liver tissue. 30%, but the tumor-free side of the liver is significantly compensatory enlarged to more than 50% of the whole liver tissue.D Multiple tumors with <3< span=> tumor nodes and confined to a segment or a lobe of the liver. A complete resection of the tumor as seen by the naked eye (including preoperative examination); B minimum distance between the liver cut edge and the tumor is greater than 50px; C no carcinoma thrombus in the liver section by the naked eye and microscopic vessels; D intact tumor envelope is not restricted by the second criterion; E for two tumor foci in the liver, if they can be clearly polyclonal in origin and meet the aforementioned criteria; F for those with pulmonary metastasis and limited to unilateral, can be completely resected G for those with positive preoperative AFP and those with short-term postoperative AFP conversion. The authors emphasize the specific embodiment of the tumor-free technique and the regional hepatic blood flow blocking technique, which requires the determination of the pre After cutting line without excessive anatomical separation and dissection of the involved liver lobe (segment), control of the involved lobe (segment) portal vein branches (hepatic artery branches) and hepatic vein branches, if necessary, from the front of the inferior hepatic vena cava to the gap between the right hepatic vein and the middle hepatic vein to place a blocking band to control the hemihepatic; D minimize intraoperative bleeding and protect the patient’s immune function; E quote modern operation techniques to deal with the liver trauma, in the aforementioned control of the regional In case of traumatic bleeding, 5-0 vascular suture can be used to stop the bleeding or directly repair the traumatic surface, and the main blood vessels can be broken with mattress suture. The trauma surface can be covered with large omentum as appropriate. In addition to drug application, our department mainly applies body stem cell portal vein transplantation, which has been clinically proven to be effective and no perioperative death in the past 2 years. The metastasis rate of PLC in the last 2 years is nearly 20% per year, which indicates the importance of the above-mentioned clearance. 2.Palliative hepatectomy ①indications A3～5 multiple tumors, beyond the scope of the half liver, perform multiple limited resection; tumor is limited to 2-3 adjacent liver segments or within the half liver, imaging shows that the tumor-free liver tissue is significantly compensated enlargement, reaching more than 50% of the whole liver. b) located in the central region of the liver B): cancer, tumor-free liver tissue is significantly compensated enlargement, reaching more than 50% of the whole liver. c) with lymph node metastasis in the hepatic hilum. For those with lymph node metastasis, if the primary liver tumor can be resected, tumor resection should be done and lymph node dissection in the hilar region should be performed at the same time. If the lymph nodes are difficult to be cleared, radiofrequency ablation, microwave, freezing or injection of anhydrous ethanol can be performed intraoperatively, and radiotherapy can also be performed after surgery.D If the surrounding organs (colon, stomach, diaphragm or right adrenal gland, etc.) are invaded, if the primary liver tumor can be removed, they should be removed together with the invaded organs. For single metastatic tumor in distant organs (such as single lung metastasis), resection of primary liver cancer and resection of metastatic tumor can be done simultaneously. ②Therapeutic value A new understanding of palliative surgery. The previous abandonment of surgical resection for palliative hepatocellular carcinoma has changed. Clinical studies in multiple centers have shown that volume reduction surgery not only does not aggravate the spread of liver cancer, but also improves the general condition and facilitates the next step. It is also beneficial to improve the systemic condition and facilitate the next step of sequential comprehensive treatment, which can prolong the survival time of patients with higher quality. (3) Treatment of bile duct or vascular cancer embolus When primary liver cancer is combined with portal vein cancer embolus, the corresponding operation should be selected according to the specific situation. If the thrombus is located in the main branch or trunk of portal vein, it is suitable to perform portal vein trunk dissection to remove the thrombus and perform palliative hepatectomy at the same time. If half hepatectomy is performed, the stump of portal vein can be opened to remove the cancer embolus, and it is not necessary to remove the embolus through incision of portal vein trunk. If the thrombus is located in a branch of the portal vein above the second level, it can be removed together with the branch of the portal vein at the same time of resection of the liver tumor. If the tumor is found to be unresectable, intraoperative chemotherapy with selective hepatic artery cannulation or portal vein cannulation, cryotherapy or radiofrequency therapy can be performed after the portal vein trunk is incised to remove the embolus. In case of combined with vena cava thrombosis, the vena cava can be cut to remove the thrombosis under the blockage of whole liver blood flow, and the liver tumor can be removed at the same time. The surgical treatment principle of primary hepatocellular carcinoma combined with bile duct cancer embolus is basically the same as that of combined portal vein cancer embolus, that is, if the cancer embolus is located in left hepatic duct or right hepatic duct, common hepatic duct or common bile duct, the cancer embolus can be removed by ductotomy and palliative hepatectomy can be performed at the same time. If the thrombus is located in a small branch of the hepatic duct above the second level, it can be removed together with the branch of the hepatic duct at the same time, without removing the thrombus through incision of the common bile duct. If the tumor is found to be unresectable, intraoperative chemotherapy with selective hepatic artery cannulation, cryotherapy or radiofrequency therapy can be performed after removing the cancer embolus from the bile duct and placing T-tube for drainage. 3.Liver transplantation for hepatocellular carcinoma ①Indications The selection of patients is strictly in accordance with the criteria, currently the Milan criteria, California criteria and Pittsburgh criteria are applied. Domestic standards have not been recognized yet. In short, liver transplantation for hepatocellular carcinoma with minimal hepatocellular carcinoma and severe cirrhosis; vascular invasion or lymph node metastasis should be listed as absolute contraindications; larger hepatocellular carcinoma with better local conditions can be tried. ②Current status In the surgical treatment of hepatocellular carcinoma, liver transplantation can be complemented with partial hepatectomy. Most of the liver cancers have lost the chance of radical resection when they are discovered, mostly because of the poor compensatory function of the liver and the quantity, location and distribution of the tumor are not suitable for partial hepatectomy. Liver transplantation can remove cirrhosis, hepatitis B, cancerous foci and precancerous lesions together. However, the disadvantages of liver transplantation are also obvious, such as non-functional transplanted liver after surgery, infection, lack of donor, long waiting time for donor, lifelong application of immunosuppressive drugs, and high cost of treatment. There are few domestic and foreign data comparing the advantages and disadvantages of liver transplantation and partial hepatectomy in the treatment of hepatocellular carcinoma, and retrospective analysis of several centers has shown that both have similar surgical efficacy. However, the results are not accurate because of the different patients selected. The reported 5-year survival rate after transplantation is 20% to 30%, with the best outcomes seen in fibrous lamellar hepatocellular carcinoma, microscopic hepatocellular carcinoma and even small intrahepatic foci (opportunistic tumors, incidentaloma) found only after total hepatectomy. Because both treatments have different indications, it is difficult to conduct a prospective randomized controlled study (PCT) to make a more scientific judgment. (iii) Application of living liver transplantation (LDLT) Living liver transplantation (LDLT) has expanded the source of donor to a certain extent, but its value in the treatment of liver cancer needs to be further confirmed, except for the risks of both donor and recipient brought by the surgery itself. There are reports of superiority of LDLT in early-stage hepatocellular carcinoma such as waiting for a cadaveric liver donor for more than 7 months. Currently, two issues require special attention in LDLT for HCC, one is the indication for surgery, which most authors advocate should be the same as for cadaveric liver transplantation, and the other is the timing, as the expansion of donor sources may shorten the waiting time for a donor, which can lead to some of those who are suitable for total liver transplantation being converted to LDLT. Due to the lack of definite efficacy of LDLT for liver cancer, the lack of comparison with other treatment methods such as partial hepatectomy, whole liver transplantation and minimally invasive treatment, and the malignant biological characteristics of liver cancer such as multicentric occurrence and early intravascular invasion, LDLT should be applied with great caution to prevent early recurrence and metastasis of liver cancer after LDLT. 4.Laparoscopic hepatectomy Laparoscopic hepatectomy for hepatocellular carcinoma has not been widely carried out in China. This is mainly because the liver is rich in blood supply, so it is difficult to block the blood flow in the hepatic hilum under laparoscopy, and bleeding is difficult to control; the boundary between cancer and normal liver tissue is not easy to judge, which increases the chance of residual cancer tissue at the cutting edge and the incidence of metastasis and recurrence of liver cancer. At present, most of the tumor sites where laparoscopic hepatectomy has been performed are located on the liver surface of segments II, III, IV, V and VI of the liver. For hepatic tumors located on the diaphragmatic and deep surfaces of segments I, II and VIII of the liver, and adjacent to the vena cava fossa and major hepatic vein branches, laparoscopic hepatectomy is generally not used. Hand-assisted laparoscopic hepatectomy for hepatocellular carcinoma can solve the problems such as difficulty of hepatic portal block. It has the advantages of good hemostasis effect and complete resection of tumor margins, thus further developing the application of laparoscopy in hepatectomy for hepatocellular carcinoma. 5.Surgical treatment of primary hepatocellular carcinoma combined with portal hypertension (1) for those with obvious splenomegaly and hypersplenism (WBC below 3×109/L, platelets below 50×109/L), splenectomy can be performed at the same time; (2) for those with obvious esophagogastric fundic varices, especially for those who have had hemorrhage from ruptured esophagogastric fundic varices, peripancreatic vascular dissection can be considered at the same time, and for those with severe If the patient has severe gastric mucosal lesions, splenorenal shunt or other types of selective portosystemic shunt should be performed if the patient’s intraoperative condition allows. 6. Remedial surgery for primary hepatocellular carcinoma ① Hepatic artery ligation, chemotherapy window and portal vein chemotherapy window. Theoretically, the imaging technology is quite advanced and there is no problem of inadequate preoperative evaluation, and there are many comprehensive treatment methods, so this kind of encounter surgery should not occur. However, the clinical situation is not entirely like this, and with the unbalanced medical development in different places, this procedure still has some value clinically. If the tumor is large and confined to a certain lobe (segment), portal vein ligation of that lobe (segment) can be added to facilitate compensatory hypertrophy of the healthy side of the liver, which may create the opportunity for stage II surgery. ②Surgical treatment of ruptured hepatocellular carcinoma nodes Resection of ruptured carcinoma nodes is the most effective method to stop bleeding, followed by hepatic artery ligation with tamponade to stop bleeding. Attention should be paid to comprehensive evaluation to ensure that the patient can benefit from the surgery. (iii) Stage II reoperation Very few patients after interventional treatment, radiofrequency treatment or patients with obvious compensatory hypertrophy on the healthy side after vascular treatment on the affected side and significant tumor shrinkage may be given the opportunity for stage II surgery, and should lose no time to undergo surgery, which is superior to other treatment methods. In recent years, many significant advances have been made in liver cancer research, but the overall 5-year survival rate of liver cancer is still less than 5%, and even the recurrence rate of metastasis 1 year after radical resection is as high as 35%. The high recurrence rate of liver cancer in early postoperative period has become the most important obstacle to improve the treatment effect of liver cancer. The commonly referred recurrence of liver cancer is the recurrence caused by intrahepatic metastasis of liver cancer cells through portal system. Incomplete surgical resection of hepatocellular carcinoma, resulting in residual cancer cells, as well as lesions of multifocal origin, which are already in precancerous stage at the time of initial surgery, and synchronous or asynchronous tumor recurrence after surgery, are not true recurrence. Recurrence and metastasis of hepatocellular carcinoma is a very complicated research topic, which involves many factors such as genetic and other biological characteristics of the tumor itself, the growth status and location of the tumor, the presence or absence of concomitant hepatitis and hepatic sclerosis background, the immune function of the individual patient, the surgical operation, the size of the trauma, the perioperative management, and the postoperative treatment. At present, reoperative resection is the preferred method for the treatment of recurrent hepatocellular carcinoma. Recent research on postoperative recurrent metastasis of liver cancer will certainly lead to significant changes in the development of liver cancer surgery in the 21st century. Non-surgical treatment of primary liver cancer 1. Interventional treatment ① Tumors are multiple and scattered in the left and right hepatic halves: ② Tumors are large, but the tumor-free side of the liver does not have compensatory enlargement, and the volume is less than 50% of the whole liver; ③ There is no cancer thrombus in the portal vein of the healthy side of the liver or there is cancer thrombus, but there is still blood flow through the portal branch; ④ There is no cancer thrombus in the intrahepatic bile duct and extrahepatic bile duct; ⑤ Tumors recur after hepatectomy, and it is not suitable or the patient is not willing to operate again; ⑥ The patient is not willing to operate again. ⑥In principle, preoperative intervention is not required for resectable hepatocellular carcinoma; ⑦ Interventional treatment can be used in radical resection cases. (2) less than 3 intrahepatic lesions, each not more than 3.0; (3) gastrointestinal cancer, breast cancer and lung cancer, etc., have been removed from the primary extrahepatic foci, and the metastases are less than 5.0 in diameter and less than 3 in number; (4) no surgical indications, such as (4) Patients without surgical indications, such as old and frail or with other organ insufficiency, who refuse surgery or delay surgery; (5) Patients with combined cirrhosis, liver function of Child A or B grade, pylorus – without large amount of ascites. Surgical resection of hepatocellular carcinoma is now mature, but the biological characteristic of high recurrence and metastasis rate of hepatocellular carcinoma is still a bottleneck preventing further improvement of the prognosis of small hepatocellular carcinoma resection, and the overall 5-year survival rate of hepatocellular carcinoma remains low. For small hepatocellular carcinoma, especially those with severe cirrhosis or located in the hilar region near large blood vessels, RFA is the most popular non-surgical treatment method in terms of survival rate, recurrence rate, ease of operation and complications. At present, surgical resection of small hepatocellular carcinoma is facing the challenge of minimally invasive tumor treatment with wide indications and few contraindications, especially RFA technology. It is foreseeable that minimally invasive treatment will play a more and more important role in the treatment of hepatocellular carcinoma. 3.Other interstitial treatments ① anhydrous ethanol intratumoral injection, which is suitable for single tumor or multiple nodal tumors, but the cancer foci do not exceed 5; liver cancer that has recently recurred after hepatic resection, which is not suitable or the patient is not willing to undergo another hepatic resection; ② freezing, microwave, laser and other treatments: the indications are the same as above. The mainstream of radiotherapy for hepatocellular carcinoma is three-dimensional conformal radiotherapy, which cannot combine tumor control probability (TCP) and normaltissue complication probability (NTCP). However, 3D conformal radiotherapy can better balance TCP and NTCP, and safely increase the radiation dose in the target area up to 90Gy. 5.Chemotherapy for primary liver cancer The commonly used chemotherapeutic drugs for liver cancer include: fluorouracil and its derivatives, insecure cyclic drugs adriamycin, epiamycin and pyrimethamine, platinum drugs cisplatin and carboplatin, mitomycin and hydroxycamptothecin. In recent years, new drugs such as paclitaxel, topotecan, platinum dihydrochloride and gemcitabine have been used in clinical practice. At present, chemotherapy is generally in the exploration stage, and it is necessary to find more effective drugs, more reasonable combination treatment plan and drug route to better protect liver function and inhibit tumor multidrug resistance. 6.Chinese and Western herbal medicine treatment Chinese medicine treatment for primary liver cancer occupies a certain position in the treatment of liver cancer, and the general public has always admired Chinese medicine and herbal medicine treatment, which is involved in almost the whole treatment process. In the author’s opinion, the purpose of Chinese medicine and herbal medicine in the treatment of liver cancer is firstly to protect the liver and improve the systemic condition to correct the immune function; secondly, it is the anti-tumor treatment, but in recent years, its anti-tumor effect has indeed been observed in clinical practice. Biological therapy for primary liver cancer Biological therapy for liver cancer is a new treatment modality based on modern immunology and molecular biology, using biomolecules, genes and other natural or chemically synthesized drugs to treat and prevent tumors by regulating the body’s own intrinsic immune defense mechanism. The main methods include gene therapy, immunotherapy, targeted therapy and so on. The current hot spots of gene therapy research for liver cancer are: endostatin gene among oncogenes, caspase-3, TRAIL and survivin among apoptosis genes, interferon, interleukin and TNF among immune enhancement genes. The hot spot of immunotherapy is the research of liver cancer vaccine. Nowadays, there are mainly methods of introducing cytokines, introducing liver cancer-related genes and dendritic cell vaccine, etc. Phase I-III liver cancer vaccine clinical trials are currently underway worldwide. Among targeted therapies, the use of oral Bifidobacterium longum as a targeting vehicle and the use of endostatin for effective treatment of hepatocellular carcinoma have been newly reported. Some progress has been made recently in the biological treatment of liver cancer, but further exploration and optimization are needed.