Surgical resection is the most effective treatment for primary hepatocellular carcinoma (PHCC), TACE (percutaneous hepatic artery catheter chemoembolization) is the most widespread treatment measure, and RAF and PEI are effective supplements to hepatocellular carcinoma treatment; the principle of primary hepatocellular carcinoma treatment is sequential integration and rational use of various methods; the advantage of TACE is that it can control the progression of hepatocellular carcinoma lesions, treat hepatocellular carcinoma that cannot be surgically resected, and the lesions The number of cases that can be resected in the second stage after intervention is 6.2%-11.2% of TACE.
Interventional therapy is currently recognized as the main treatment for unresectable intermediate and advanced hepatocellular carcinoma, and it has achieved obvious effects in inhibiting tumor growth and improving patient survival rate. Studies have shown that tumor and normal tissue ischemia and hypoxia after TACE can cause tumor cells and peritumor normal cells to secrete pro-angiogenic substances such as VEGF, FGF, etc., which cause the formation of tumor vascular collateral circulation and increase the difficulty of TACE treatment again.
These factors have other side effects such as.
(1) increase of vascular permeability, which increases the possibility of metastasis.
(2) Inhibition of tumor apoptosis and longevity of residual tumor cells.
(3) Pro-proliferative effect of tumor, which is prone to induce recurrence.
Strategies to reduce angiogenesis after TACE include:
(1) Try to achieve complete embolization treatment, such as performing segmental embolization.
(2) Use of strong embolic agents under super-selective intubation: e.g. iodine oil + anhydrous ethanol, etc.
(3) Addition of local ablation therapy after TACE, with special attention to effective local treatment of the tumor peripheral area.
(4) Addition of anti-angiogenic therapy.
Studies have shown that the gene expression of residual hepatocellular carcinoma cells and normal liver tissue cells has changed after TACE, and some of these changes have promoted the adaptability to treatment, so that some hepatocellular carcinoma cells have shown “ischemic resistance” and “embolization resistance”, which are manifested in the following aspects (1) TACE can promote residual hepatocellular carcinoma cells:
(1) TACE can promote the expression of angiogenesis-related factors in residual tumor cells, and our animal experimental study showed that the expression of VEGF and bFGF in residual liver tumor foci was enhanced after TACE, and the density of microvessels was increased; foreign scholars found that the VEGF content in blood was transiently increased after TACE for hepatocellular carcinoma, and the VEGF expression in cancer cells and peritumor hepatocytes in stage II surgical resection specimens was enhanced. expression was enhanced.
(2) Enhanced proliferative activity of unembolized tumor cells after TACE.
(3) The unembolized portion of the liver showed compensatory proliferation and enhanced proliferative activity after TACE. All these indicate that the recurrence and metastatic potential of residual hepatocellular carcinoma after TACE is increased, and the normal liver tissue also has the soil for hepatocarcinogenesis. At present, research on the biological behavior of residual hepatocellular carcinoma after TACE has just begun, and there are still many unresolved problems.
After many years of treatment practice, domestic and international literature recognized that TACE can improve patients’ quality of life and prolong survival, and TACE is safer and has fewer serious complications. 1 to 3 years survival rates of PHCC patients treated with TACE are 60.4%, 42.9% and 28%, respectively. Tumor shrinkage and second-stage resection after TACE treatment accounted for about 6.2% to 11.2% of the total number of TACE cases, and the 5-year survival rate of those with second-stage resection was similar to that of those with small hepatocellular carcinoma resection. In a few cases, the tumor shrinks and disappears after multiple TACE and comprehensive therapy, and some of them have survived for more than 10-20 years and achieved the basic curative effect. For hepatocellular carcinoma that can be surgically resected, there are divergent opinions both at home and abroad on whether to perform TACE before surgery.
Studies have shown that after TACE, although more than 50% of tumor tissues in 73% of patients with hepatocellular carcinoma are necrotic, only 5% are completely necrotic, and the remaining cancer cells will have or produce stronger proliferation and invasion ability. For example, in some cases, multiple or diffuse disseminated foci appear within a short period of time after TACE, and in some cases, multiple metastases appear in the lung; in addition, there are often surviving cancer cells in the area around the nodes or under the envelope of hepatocellular carcinoma, and with the rapid establishment of peripheral collateral blood supply, the residual cancer tissues proliferate quickly; patients with hepatocellular carcinoma are often accompanied by cirrhosis and portal hypertension, etc. After TACE, most patients will have liver function impairment, and some of them may have upper gastrointestinal tract hemorrhage and liver failure. In addition, the size of the tumor, blood supply and the patient’s liver function are all factors that affect the efficacy of TACE.
In conclusion, for inoperable primary hepatocellular carcinoma, the patient’s condition should be firstly considered comprehensively, and then combined with the advantages and disadvantages of various therapies, comprehensive treatment should be implemented to obtain the best efficacy, and comprehensive interventional therapy will become the trend of treating malignant tumors. To obtain breakthroughs in various interventional methods for the treatment of PHCC, they must be combined with molecular biology and clinical high technology to effectively improve the clinical efficacy of hepatocellular carcinoma treatment.
Chua et al. from Australia systematically reviewed all the clinical research literature published in recent years regarding the preoperative administration of TACE for resectable hepatocellular carcinoma. A total of 3927 patients were counted in the literature, of which 1293 were given TACE preoperatively, and the postoperative DFS (tumor-free survival), OS (overall survival), necrosis rate of pathological specimens and operative mortality of both groups were analyzed, and it was concluded that However, more clinical literature suggests that preoperative administration of TACE is not recommended for resectable hepatocellular carcinoma, especially for patients with early-stage hepatocellular carcinoma and hepatocellular carcinoma without a background of cirrhosis. Preoperative administration of TACE for resectable hepatocellular carcinoma decreases the long-term survival of patients and may also lead to tumor progression and liver failure.
Our experience is that TACE treatment is chosen for patients with poor liver reserve function (ICGR15 > 25%), huge tumor resection that may lose more liver volume making the patient intolerant to surgery, advanced age that cannot tolerate surgery, and suspicion of metastatic lesions in the liver. It should be emphasized that the establishment of tumor collateral circulation after TACE is the main factor of recurrence and metastasis of liver cancer and poor prognosis of liver cancer patients. TACE treatment can induce the establishment of extrahepatic collateral circulation, 17.9% after 3-4 times and 56.4% after 5-6 times; TACE can hardly cause complete necrosis of liver tumor tissues, and tumor specimens resected in the second stage show a necrosis rate of about 22%, while it should be noted that in the second stage TACE patients at the time of surgical resection have the following characteristics.
1. intraoperative formation of more obvious adhesions around the lesion after multiple TACE treatments.
2, patients with a background of hepatitis cirrhosis, inflammatory adhesions around the liver lesion will be more pronounced.
3. although the tumor volume is significantly reduced after TACE treatment, the intraoperative fibrous envelope of the tumor is not clear.
4. after TACE treatment, the liver tissue is more brittle and the trauma surface is more likely to bleed.
5. the functional state of the liver after TACE treatment is more prone to postoperative complications of liver dysfunction such as ascites, pleural fluid, and hypoproteinemia.
6. the recurrence and metastatic potential of residual liver cancer after TACE is increased, while liver tissues with hepatitis cirrhosis background also have the soil for hepatocellular carcinogenesis.
7. emphasis on the impact of biological behavior of residual liver cancer foci on patients’ long-term survival. Therefore, if patients have been given the opportunity of second-stage surgery after TACE treatment, they should actively choose surgical resection or radiofrequency ablation treatment that can completely cure the disease.