| Background: Primary hepatocellular carcinoma has no obvious symptoms in its early stage and is mostly found in advanced stage.Transarterial chemoembolization(TACE)is the standard treatment for advanced stage hepatocellular carcinoma,and nearly half of liver cancer patients will adopt this method.TACE is a therapeutic method in which an embolic agent is injected into the tumor blood supply target artery through a catheter to make the target artery occlusive,so as to achieve the therapeutic purpose.Currently,two TACE technologies have been clinically applied,including conventional TACE(c-TACE)and drug-eluting bead TACE(DEB-TACE,D-TACE).c-TACE uses iodide oil as an embolic agent,while D-TACE uses drug-eluting bead loaded particles as an embolic agent.The size of embolization particles commonly used in clinic is usually between 100-300 μm,which is called microsphere(MP).It is believed that TACE therapy has entered the era of microsphere from the era of iodide oil.Some scholars have found that the smaller the MP size,the more it can penetrate into vessels with very fine embolization.However,when the MP size is less than 40μm,it is easy to be washed away and transported to normal liver lobe or other organs,resulting in embolization failure and other serious adverse events.Therefore,their size is strictly limited to more than 40μm to ensure safety.Objective: In recent years,a new polymer embolic agent,called phosphate binder sevelamer,has been introduced into the study of interventional therapy for liver cancer,which is a common oral drug currently used in the treatment of hyperphosphatemia and other diseases.The experimental design was to change the drug administration mode and embolize the blood supply vessels of liver cancer through arteries,thus inducing intratumoral inorganic phosphate(Pi)deficiency,and combine with other clinical chemotherapy drugs to increase the accumulation of chemotherapy drugs in tumor cells,enhance the tumor cytotoxicity of chemotherapy drugs and promote the apoptosis of tumor cells.The combination of the embolic agent and chemotherapy was found to be more effective than conventional TACE.The Sevelam ultrafine particles(0.2-0.5μm)used in the above series of work are against the "40μm" rule of MP,so it is necessary to check whether they are safe and effective.In this paper,we studied the therapeutic efficacy and safety of transarterial sevelamer embolization(TASE)in the VX2 rabbit hepatoma model.We also challenged the special MP of Sevelam to see if it could break the "40 μm" rule.Methods: In the first study,three groups of tumor bearing rabbits were given blank beads(polyvinyl alcohol embolized microspheres,100-300 μm),fluorescent polystyrene microspheres(10,100 μm),and Sevelam particles via arteries,respectively,to evaluate the intrahepatic and extraperhepatic permeability of MP of different types and sizes.In the second study,serum chemistry,histopathology,and tumor necrosis rates were compared in four groups,sham surgery(saline),TASE,c-TACE,and D-TACE(n=6/ group),in order to clarify the safety and therapeutic efficacy of preclinical TASE tests relative to other techniques.Results: In the first study,the "40 μm" rule was validated in both blank beads and glowing polystyrene microspheres,but it was not applicable to Sevelam embolization,as no spread of Sevelam ultrafine particles from the VX2 rabbit tumor lesion was observed,and only residual particles were found in the embolized vessels.However,the pathological results of the second study showed that the tumor volume of the surviving rabbits in the TASE group was smaller than that in the other groups 2weeks after the operation,indicating that the treatment effect was better,and no other adverse events were found except for a short-term stress response(which could be reflected by blood biochemical indicators).The results of these two studies indicate that Sevelam is a safe and effective embolic agent,and transarterial Sevelam embolization is expected to replace current MP-based embolic therapy techniques. |
PDF Full Text Request