ObjectiveTo evaluate systematically the effectiveness and safety of transcatheter arterial chemoembolization (TACE) in combination with lenvatinib (LEN) in the treatment of intermediate and advanced primary liver cancer (PLC). MethodsThe relevant literature was comprehensively searched in the CNKI, VIP, Ovid, Schopus, PubMed, and other databases from the establishment of the databases to March 14, 2023. The literature was obtained according to the search strategy and the inclusion and exclusion criteria, and the data were extracted and the literature quality was evaluated. The Revman 5.4 software and Stata 15.1 software were used to conduct the meta-analysis to evaluate the effect of TACE+LEN regimen on the objective response rate (ORR), disease control rate (DCR), overall survival (OS), as well as secondary outcome indicators such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alpha fetoprotein (AFP), and hypertension, diarrhea, hand-foot disease, fatigue, proteinuria, and fever for the patients with PLC. ResultsA total of 15 relevant literature was included, including 1 219 patients with PLC, 591 of whom treated with TACE+LEN and 628 treated with TACE alone. The meta-analysis results showed that the TACE+LEN regimen could increase ORR and DCR and prolong OS (P<0.01), as well as effectively decrease AFP level (P<0.01). However, TACE+LEN regimen increased the risks of hypertension, diarrhea, hand-foot disease, fatigue, and proteinuria as compared with TACE alone treatment (P<0.05). However, there were no statistical impacts on AST and ALT, or the risk of fever (P>0.05). ConclusionFrom the results of this meta-analysis, TACE+LEN regimen has a certain efficacy in treatment of intermediate and advanced PLC, but prevention of its related complications is paid attention to.
Objective To state operative details of lip-shaped hepatectomy (LSH) and evaluate its advantage in treatment of primary liver cancer (PLC).Methods LSH is one of the irregular hepatectomies. The key lies in the following five operative kinks: ①adequately mobilizing perihepatic ligaments; ②designing lip-shaped hepatic incision; ③laying sutures on both sides of the hepatic incision for traction; ④wedge-shapedly resecting the tumor and the surrounding liver; ⑤closely sewing up the hepatic cutting surface.Results Two hundreds and thirty three patients with PLC were treated by LSH between Oct. 1991 and Dec. 1997 in Zhongshan hospital, Shanghai medical university. Among them 8 cases underwent initial hepatectomy and resection for recurrence of the tumor. The operative mortality rate was 1.2%, 2 died of hepatic failure and 1 renal failure. In addition to bile leakage in 3 cases and hydropsy at the operative area in one case, no severe postoperative complications were found, such as intraperitoneal bleeding, subphrenic abscess and so on. The 1-,3-,5-year survival rates were 89.8%, 64.3% and 55.9% respectively, in 233 patients with 241 LSHs. 25 patients survived more than 5 years. The result indicated that the most advantage of LSH was to increase operative safety on the basis of guarantee of radical resection of PLC, especially to decrease some complications from hepatic cutting surface.Conclusion LSH is a relatively simple, safe, reasonable and recommendable hepatectomic modality.
ObjectiveThe present study was to investigate the value of multi-disciplinary team (MDT) model in patient with primary giant liver cancer.MethodsThe MDT model was carried out for a BCLC B stage patient who admitted in the Second Affiliated Hospital of Chongqing Medical University in July 2018. The associated references were reviewed and the treatment methods were discussed about primary giant liver cancer.ResultsAn elder man who was diagnosed as primary hepatocellular carcinoma (minor cancer) in right lobe of the liver in three years ago and took Chinese medicine orally. When the patient subsequent visited this time, the liver cancer increased about 10 cm. After discussed by MDT, the treatment method was draw up to transarterial chemoembolization (TACE) plus surgery. After received twice TACE therapies in the later 14 weeks, the tumor in right lobe had significantly shrinked and left lobe enlarged. The patient underwent laparoscopic right liver hepatectomy after the second MDT discussion in 5 months later. The patient underwent operation successfully. The operation lasted for 270 minutes, and the intraoperative blood loss was about 500 mL. The suspended red blood cells (400 mL) was infused. The patient underwent transient liver failure and recovered through hepatoprotective and symptomatic supportive treatment, and discharged on 12 days after operation. A retrospective examination of abdominal CT at 4 months postoperatively revealed a significant hyperplasia of the left lobe of the liver, and there was no sign of recurrent tumor. The patient was continue to followed up.ConclusionsThepatient with primary giant hepatocellular carcinoma who cannot underwent surgery at the first time can received TACE, and a few patients could be underwent radical operation later. MDT should be applied flexibly in the treatment of patients with huge hepatocellular carcinoma from beginning to end, so the best treatment plan should be carried out for patients.
Objective
To explore therapeutic effect of radiofrequency ablation (RFA) guided by contrast-enhanced ultrasound in patient with advanced primary liver cancer following transcatheter arterial chemoembolization (TACE).
Methods
The patients with advanced primary liver cancer treated with the TACE firstly from January to December 2014 in this hospital were prospectively collected, then were randomly divided into a conventional ultrasound guided RFA group (control group) and contrast-enhanced ultrasound guided RFA group (study group). The complete ablation rate, liver function, serum alpha-fetoprotein (AFP) level, and 1-, 2-, and 3-year survival rates were observed in the two groups.
Results
A total of 42 patients with advanced primary liver cancer treated with the TACE were enrolled in this study, there were 21 patients in each group. ① There were no significant differences in the baseline data such as the gender, age, BCLC stage, AFP level, and Child grade of liver function between the two groups (P>0.05). ② All the treatments were completed according to the plan, no serious complications or treatment-related death happened. The complete ablation rate of the study group was significantly higher than that of the control group (χ2=5.717, P=0.017), and the AFP level was significantly lower than that of the control group (t=2.618, P=0.012). There was no significant difference in the Child grade of liver function between the 2 groups (P>0.05). ③ The rate of repeat RFA in the study group was significantly lower than that in the control group (χ2=4.434, P=0.035), and there was no significant difference in the TACE treatment rate between the two groups (χ2=1.659, P=0.197). ④ The survival rate of the study group was significantly better than that of the control group by comparing the survival curves (χ2=3.999, P=0.046).
Conclusion
Contrast-enhanced ultrasound guided RFA is superior to conventional ultrasound guided RFA in treatment of advanced primary liver cancer following TACE.
Objective To study the effects of pcDNA3/AFP/TK/Angio fusion gene targeting therapy for human primary liver cancer in nude mice implanted with SMMC-7721. Methods Human liver cancer cell line SMMC-7721 was implanted subcutaneously in nude mice to establish experiment model. Animals bearing liver cancer were randomly divided into five groups: control group， vector group， GCV (ganciclovir) group， pcDNA3/TK/Angio group; pcDNA3/AFP/TK/Angio group. Different plasmids were directly injected into tumors and GCV was intraperitoneally administrated simultaneously according to different groups. The growth of tumors was observed and the pathology was examined as well. Serum AFP level was measured by radioimmunology, the ultrastructural change of tumor cells was studied by using electron microscopy, the expressions of MVD and VEGF were respectively detected with immunohistochemistry and the cell apoptosis in situ was detected by TUNEL. Results The success rate to establish subcutaneous implanted liver cancer model in nude mice was 100%. The tumor volume, serum AFP level, VEGF and MVD expressions of pcDNA3/TK/Angio group and pcDNA3/AFP/TK/Angio group were lower than those in control group, vector group and GCV group (P＜0.05) and more apoptosis cells could be observed. While the tumor volume, serum AFP level, VEGF and MVD expressions of pcDNA3/AFP/TK/Angio group was lower than those in pcDNA3/TK/Angio group (P＜0.05); and apoptosis index was higher than that of the latter (P＜0.05).Conclusion pcDNA3/AFP/TK/Angio fusion gene inhibits the growth of tumor remarkably and becomes a promising new biological agent to treat human primary liver cancer.
ObjectiveTo explore the effects of hypoxia inducible factor-1 alpha (HIF-1α) on the reverse differentiation of hepatocellular carcinoma cells into liver cancer stem cells, and the maintenance of malignant biological behavior in hypoxic environment.MethodsCD133-negative cells in HepG2 cells were separated by immunomagnetic beads and divided into two groups. The cells of siRNA group were transfected with siRNA-HIF-1α to silence the expression of HIF-1α gene, while cells of the blank control group did not transfect any siRNA fragments. The two groups of cells were cultured under normal and hypoxic conditions respectively. MTT, cloning and Transwell chamber experiments were used to detect the proliferation and invasion ability of cells. Western blot and real-time PCR (RT-PCR) were used to detect the expressions of HIF-1α, CD133, CD90, and CD44 protein and mRNA in cells.ResultsMTT results showed that the cell proliferation rate increased with the prolongation of hypoxia in four groups. Compared with the blank control group at 24, 32, 40, and 48 hours, the cell proliferation rate decreased significantly after siRNA-HIF-1a transfection, on both two kinds of cultured conditions (P<0.05). The results of plate cloning experiment showed that the number of cell-forming clones increased significantly after hypoxic culture (there were significant differences between the transfected normoxic group and transfected hypoxic group, blank control normoxic group and blank control hypoxic group, P<0.05); and the formation of transfected hypoxic condition group at the same time of hypoxia was also significant (P<0.05). The number of clones were significantly less than that of the blank control group at the hypoxic condition (P<0.05). Transwell lab experiment showed that after hypoxic culture, the number of cells migrated to the inferior chamber in the transfection group was significantly reduced compared with that of the blank control group (P<0.05). Western blot and RT-PCR results showed that the expression levels of HIF-1α protein and tumor stem cell markers (CD133, CD90, and CD44 protein) in the blank control hypoxic condition group were significantly higher than those in the other three groups (P<0.05); after siRNA-HIF-1a transfection, HIF-1α mRNA and tumor stem cell markers mRNA (CD133, CD90, and CD44 mRNA) in the transfected hypoxic condition group were significantly lower than those in the transfected normal condition group and the blank control normal condition group (P<0.05).ConclusionsIn hypoxia environment, HIF-1α can promote hepatocellular carcinoma cells to differentiate into liver cancer stem cells and enhance their malignant biological behavior.
Objective To investigate the safety and feasibility of transcatheter arterial chemoembolization (TACE) assisted by transradial approach and cone beam computed tomography (CBCT) three-dimensional vascular reconstruction in the treatment of primary liver cancer. Methods The clinical data of 124 patients with primary liver cancer who underwent precision TACE via radial artery in our hospital from May 2018 to December 2019 were retrospectively collected. Results Among the 124 patients, 118 patients were successfully punctured through the left radial artery and completed the TACE operation. The operation time was (109.57±31.32) min, and the median of postoperative hospitalization was 3 d. One patient changed to the right radial artery to complete TACE due to chronic renal failure and left brachial artery and vein puncture and catheterization before operation. The operation time was 119 minutes, and the patient was discharged after 5 days of hospitalization. After successful puncture of the left radial artery in one patient, the forearm artery was twisted into a loop and the guide wire catheter failed to pass, and the right femoral artery was used to complete TACE. The operation time was 123 minutes, and the patient was discharged after 4 days of improvement. The radial artery puncture was unsuccessful in four patients, and the right femoral artery approach was used to complete the operation; the operation time was (111.66±32.77) min, and the median of postoperative hospitalization was 3 d. One of the patients successfully completed up to 5 consecutive TACE via the radial artery. All patients underwent precision TACE with superselective cannulation assisted by CBCT three-dimensional vascular reconstruction. No vascular injury andocclusion, urinary retention, subcutaneous hemorrhage, and other complications occurred in all patients. Conclusions Trans-radial arterial precision TACE is safe and effective, which can be repeated many times and has few complications and high patient comfort. It can be used as one of the routine approaches of TACE.
Objective
The aim is to sort CD90+ subpopulation cells in human liver cancer cell lines and investigate efficiency of magnetic cell sorting (MACS) on sorting the liver cancer stem cells.
Methods
①Expressions of CD90. Immunohistochemical method was used to determine the expressions of CD90 in normal liver tissues in 8 cases, liver cancer and adjacent liver cancer tissues in 58 cases. ②Screened the cell lines. Huh-7, MHCC97-H, Bel-7402, and SMMC-7721 cell lines were divided into blank control group and experimental group (5.5×105 cells per hole, 1 hole), cells of the experimental group were added with 5 μL CD90–PE while cells of the blank control group were treated with 5 μL CD90–PE non fluorescent antibody. Determined the proportion of CD90+ cells in the 2 groups by flow cytometry (FCM). ③MACS. Huh-7 and MHCC97-H cell lines were labeled with magnetic beads respectively and sorted by MACS, 1 mL cell suspensionsorted by magnetic sorting (MS) was collected as CD90– group, and 1 mL PBS after MS wash was collected as CD90+ group, as well as blank control group and experimental group. Determined the proportion of CD90+ cells in 4 groups by FCM. Two times of MACS were performed in Huh-7 cells. ④Serum free culture and serum culture. Huh-7 cells were divided into serum-free culture group and serum culture group (1 hole), and proportions of CD90+ cells were determined by FCM at 1 week after culture.
Results
①The positive rate of CD90 was 0 (0/8), 65.5% (38/58), and 20.7% (12/58) in normal liver tissues, liver cancer tissues, and adjacent liver cancer tissues respectively, and the positive rate of CD90 was higher in liver cancer tissues than those of normal liver tissues (χ2=6.78, P<0.05) and adjacent liver cancer tissues (χ2=20.83, P<0.05). ②For Huh-7, MHCC97-H, SMMC-7721, and Bel7402 cell lines, the proportions of CD90+ cells in the experimental group was 0.851%, 1.090%, 2.710%, and 4.050% respectively, the proportions of CD90+ cells in the blank control group was 0.241%, 0.688%, 1.890%, and 2.080% respectively, so we chose Huh-7 and MHCC97-H cell lines to perform MACS. ③Results of MACS for Huh-7 cell line. For the first MACS, the proportions of CD90+ cells in the blank control group, experimental group, CD90– group, and CD90+ group was 0.241%, 0.851%, 0.574%, and 1.100% respectively. For the second MACS, the proportions of CD90+ cells in the blank control group, experimental group, CD90– group, and CD90+ group was 0.032%, 0.961%, 0.426%, and 9.700% respectively.
Conclusions
The normal liver tissues do not express the CD90, but the liver cancer tissues express CD90 highly. There is a few CD90+ cells in Huh-7 and MHCC97-H liver cancer cell lines. The MACS has a certain effect on improving the proportion of CD90+ cells in the cell lines. The serum-free suspension culture has no effect on enriching CD90+ cells.
In order to guarantee the safety and accuracy of the whole treating process as well as better link up of each section during the treatment, we did research in order to establish a project concerning the process quality control (PQC) of treating liver cancer with CyberKnife. From the safety and accuracy point of view, we divided the whole process of treating liver cancer with CyberKnife into ten links, i.e. the registration of patients' information, the implantation of fiducial markers, fixation of body posture, CT localization, target delineation, design of the treatment plan, quality assurance in physics, implementation of the treatment plan, inspection on the correctness and data archiving. We analyzed the possible mistakes in each link and the consequences brought by them. To smoothly connect all the links, a special part "Attention" was added between every two links. Various wrong operations which may influence the safety and accuracy of treatment were illustrated, and the consequences brought by them were also explained. The "Attention" part among links offers important information for the next step, and gives us reminding and warnings. The project of quality control covers all the important links when treating liver cancer with CyberKnife. It offers regulations, reminding and warning for us so that the safety and accuracy of treatment can be guaranteed, and the work of all staff could be closely connected.
ObjectiveTo summarize the progress of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and evolution of surgical procedure improvement, so as to summarize experience in selecting appropriate surgical method for patients. MethodThe domestic and foreign literature on the evolution of ALPPS surgical procedure improvement in recent years was reviewed. ResultsIn the decade since the emergence of ALPPS, the ALPPS had been rapidly developed in the hepatobiliary surgery. The ALPPS promoted a rapid increase in future liver remnant during a relatively shorter period to contribute to resectability of liver tumors and reduce the rate of postoperative liver failure, the patients with intermediate to advanced and huge liver cancer could obtain the surgical radical resection. In recent years, the domestic and foreign experts had refined the ALPPS procedure, which mainly focused on the operation of hepatic section separation and hepatic artery flow restriction in stage Ⅰ surgery, including partial ALPPS, radiofrequency ablation ALPPS, tourniquet ALPPS, transcatheter arterial embolization ALPPS, hepatic artery ringed and operation ALPPS, as well as laparoscopic ALPPS and robotic ALPPS with minimally invasive approach. ConclusionsDespite the ongoing controversy over ALPPS, with the continuous progress and innovation of improved procedures and the utilization of laparoscope and robot in surgery, the trauma of ALPPS surgery has a further reduction, and the morbidity and mortality have gradually been decreased. It is believed that with the continuous advancement and improvement of ALPPS surgery technology, the indications and safety of ALPPS will be further enhanced, bringing hope to more patients with intermediate to advanced liver cancer with huge tumors.
