Clinical Efficacy Of Preoperative Neoadjuvant Therapy For Hepatocellular Carcinoma

Background and purpose Hepatocellular carcinoma(HCC)is one of the malignant tumors with high morbidity and mortality worldwide.In China,it has long ranked first in the world.Although surgery can be curative,only a minority of patients(about 30%)can undergo radical surgery on their initial dignosis.In recent years,with the development of treatment concepts and treatment methods,more and more clinically effective therapy methods have been used in clinical practice.Among them,neoadjuvant therapy for HCC has attracted the attention of clinicians,providing new treatment options for improving the prognosis of resectable HCC,transformation of unresectable HCC,and descending or bridging before liver transplant.Although neoadjuvant therapy may improve the prognosis of patients,there is still no unified standard.The dual blood supply of the liver makes it of special significance in the occurrence and treatment of tumors.Different from the blood supply of normal liver tissue,the hepatic arterial supply of tumor tissue reaches 95-99%,which has also become the theoretical basis for transcatheter arterial chemoembolization(TACE).Molecular targeted therapy and immunotherapy show high antitumor activity and objective response rate(ORR),which makes it an important therapy option for patients with advanced HCC.For resectable and potentially resectable patients,the development of individualized combined therapy plans and timely and effective intervention have become an important strategy for the treatment of HCC.This study explored the difference in the curative effect between two specific methods of neoadjuvant therapy for HCC in the real world and surgery alone,and also studied the changes of tumor-related immune cells after neoadjuvant therapy and its impact on the prognosis of patients.The choice of neoadjuvant therapy provides technical support and theoretical basis.Methods According to the inclusion and exclusion criteria,patients were selected in the Hepatobiliary and Pancreatic Center of Nanjing Drum Tower Hospital from January 2019 to January 2022,who received preoperative TACE combined therapy(lenvatinib and/or immunotherapy),preoperative TACE transformation therapy and single surgery.Before treatment,the general condition,hematological examination,imaging examination and puncture pathology of neoadjuvant therapy patients were recorded before treatment;The treatment effect is evaluated and recorded according to the corresponding standard,and the intraoperative and follow-up results of all patients were recorded.The clinical intervention effects of different neoadjuvant therapy methods,the surgical methods and intraoperative conditions of patients with different preoperative treatment methods were compared;Univariate COX regression analysis was performed using the Kaplan-Meier method.Finally,multivariate COX regression analysis was performed to determine the independent risk factors affecting the postoperative recurrence-free survival(RFS)and overall survival(OS),and the influence of immune-related cells on the prognosis of patients was also clarified.Results 1.The efficacy of neoadjuvant therapy The effective rate(67%)in the TACE combined therapy was higher than that in the preoperative TACE group(47%).5 patients in the combined therapy group were transformed from giant liver cancer to non-giant liver cancer,and 4 patients in the preoperative TACE group were giant liver cancer to non-giant liver cancer.And based on the pathological remission,the TACE combined therapy group was superior to the preoperative TACE group.2.Surgical treatment There was a statistically significant difference in the operation time between the neoadjuvant therapy group and the single surgery group,and the hospitalization time was significantly prolonged(P<0.05).The preoperative TACE group and the TACE combined therapy group had statistical differences in the operation time and hepatic porta occlusion time(P<0.05).3.Univariate and multivariate analysis of prognosis of HCC Prognostic analysis showed that preoperative neoadjuvant therapy could improve the recurrence and prolong metastasis time of tumor,which was statistically significant between the two groups(P=0.035),but which did not improve the final outcome of patients(P=0.74).Alcohol consumption,tumor number,microvascular invasion,portal vein tumor thrombus,tumor diameter,penetration of liver capsule,TNM stage and postoperative AFP and PIVKA-II elevations were associated with postoperative survival.Alcohol consumption,tumor number,microvascular invasion and liver capsule Whether penetration together affects the final prognosis of patients.Neoadjuvant therapy,patient age,tumor number,microvascular invasion,portal vein tumor thrombus,tumor diameter,TNM stage postoperative AFP and PIVKA-II elevations were associated with postoperative recurrence,tumor number,microvascular invasion and postoperative AFP and PIVKA-II elevations collectively affect postoperative recurrence in patients.4.Immunohistochemical results There were significant differences in CD8,CD20,CD34,CD56 and CD68 between tumor tissue and adjacent tissue(P<0.05).There were significant differences in tumor tissue CD20,CD34,CD56 and CD68 between neoadjuvant therapy group and single surgery group(P<0.05).CD8,CD34 and CD56 were closely related to RFS(P<0.05).Conclusion Neoadjuvant therapy promotes tumor cell necrosis and achieves tumor downstaging,but it may increase the difficulty of surgery;Neoadjuvant therapy can prolong the RFS of patients,however it does not improve the OS of patients;the TACE combined therapy is more effective than the preoperative TACE group in controlling tumor.High expression of CD8 and CD56 inhibits tumor progression and prolongs RFS of patients,while high expression of CD34 promotes tumor progression and shortens RFS of patients.