| ObjectiveIn this study, the transplanted hepatomas in Walker-256-bearing rats were firstly modeled. Next, the neoplasms were resected completely and then the experimenters implanted a self-made portal vein infusion pump for infusing of different doses of Licartin combined with PVIC(FOLFOX). We wanted to provide the theoretical basis for the clinical application of this new regimen by evaluations of the safety, efficacy and feasibility of the combination schemes.Materials and methodsAt first,100male SD rats were injected in left lobe of liver with concentrated ascites, which was contained a large number of Walker-256tumor cells. A week later, the rats, whose diameter of tumor in the range of2.0-3.0cm was proved by CT scanning, were selected for the resection of the tumor and the homemade portal vein infusion pump were implanted subsequently. The survival rats after7days were randomly divided into A, B, C groups. They would treat with different schemes as follows:Group A(low dose Licartin and PVIC):infused Licartin (2.5mCi/kg) through the portal vein pump and FOLFOX chemotherapy; Group B(high dose Licartin and PVIC):infused Licartin (5.0mCi/kg) through the portal vein pump and FOLFOX chemotherapy; Group C(PVIC):infused FOLFOX chemotherapy through the portal vein pump. We observed the general condition of rats around each operation. Blood test, assessments of liver, kidney and thyroid functions shoud be also taken. CT scanning was used to understand the growth and metastasis of tumor and SPECT scan for the distribution of isotope. Liver, lung and other metastatic lesions were cut for pathological examination after death. Finally, survival data of all rats were collected for analyzing of survival.ResultsIn this study, we carried out three experiments:implantation of hepatoma, resection of the tumor and implantation of the pump, infusion of Licartin and FOLFOX chemotherapy. The operations of rats went will with satisfactorily anesthesia, and they got a good recovery in postoperative. Body weight of rats in the whole experiment showed the trend of decline.Implantation of hepatoma with injection of ascites was a simple way while the tumor formation rate is95.7%.46rats were infused after the resection and implantation of the pump a week later(18rats in group A,18rats in group B,10rats in group C).Blood test after the infusion7days later showed that the WBC count in group A and B were decreased significantly, group B was lower than that of group A and group C (P=0.043). However, group C was normal. The WBC count was basically returned to normal14days later. RBC count and PLT count had a little change during the infusion (P>0.05).Assessments of liver function showed that AST and ALT counts were increased (P=0.024and0.104). Group A and B were higher than group C, and ALT count of group B was higher than group A (P＜0.001). AST and ALT counts were decreased7days later while AST was faster than ALT. The difference of TBIL count in each group showed no significance (P>0.05). Assessments of kidney function showed that BUN and Cr counts had no significant changes during the infusion (P>0.05).Assessments of thyroid function showed that FT3and FT4counts were significantly lower than that before infusion (P＜0.001), by contrast, TSH count was significantly higher than preoperative (P＜0.001). The injury of thyroid function in group B was higher than group A (P＜0.001). The counts were basically returned to normal14days later. Group C had a little change during the infusion (P>0.05).SPECT scan after infusion5min later showed that no nuclide was concentrated in the liver; however, they concentrated in the thyroid. SPECT scan after infusion21days later showed that the nuclide was accumulated in the relapsed tumor.CT scan was used a week later after the implantation showed that about63%of the diameter was in the range of2.0-3.Ocm. Group B has the least rate of recurrence and metastasis than group A, and the biggest is group C. The regimen has no relationship between the TNM stage (P=0.371).Pathologic examination showed the tumor cells had a increasing of mitotic, the atypia is also clearly. The cells had a dense distribution. Immunohistochemical staining showed that the AFP, CEA, Hepa and Glypican-3were also negative. Ki-67was positive (40%).All rats were killed within48days after infusion. Survival analysis showed that MST of three groups was27days,39days and24days. The survival time of group B was longer than group A and C (P<0.001). There was a certain relationship between TNM stage and survival time, the survival time of phase Ⅲ and Ⅳ was shorter in Ⅰ stage and Ⅱ stage (P=0.005and0.000). Cox regression analysis showed that group B is the favorable factor (βB=—1.604,RRB=0.201), while group C is the harmful factor (βC=0.838, RRc=2.311).ConclusionsIn this study, we evaluated the safety and efficacy of the combination regimen through the transplanted hepatoma in Walker-256-bearing rats.1. Implantation of hepatoma with injection of ascites had a higher formation rate and a more simple operation.2. The combination regimen could improve the survival effectively after liver resection for hepatocellular carcinoma in rats, especially in rats with advanced carcinoma.3. Adverse reactions of the combination regimen were mainly a transient inhibition of bone marrow and injury of liver function, they would return to normal after1-2weeks generally.4. The combination regimen had a better curative effect than portal vein chemotherapy.5. The low dose (5.0mCi/kg) regimen had not only a better curative effect, but also a bigger adverse reactions than the small dose (2.5mCi/kg).To sum up, in our opinion, the new regimen of infusion of Licartin combined with portal vein chemotherapy (FOLFOX regimen) was a safe, effective scheme of the prophylaxis and treatment of recurrence after resection of hepatocellular carcinoma and was worthy of further study. |
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