The Clinical Research Of Fluorouracil Sustained Release Implant To Gastric Cancer During Radical Resection

Objective:Fluorouracil sustained release implant is a new type of the regional chemotherapeutic drug,slowly,stably,continually and constantly acting on residual tumor cells at cancerous lesion area by its slow-releasing potential and targeting property characteristics during radical resection to improve the curative effect of chemotherapy.This study investigates the clinical therapeutic effect and safety of fluorouracil sustained release implant after surgery.Methods:This study is a retrospective study,collecting 79 cases of gastric cancer who were admitted to the Department of Gastrointestinal Surgery of Yan’an University affiliated hospital.All of them underwent open radical resection of gastric cancer（D₂）from March1,2015 to March 1,2016.They were separated into the observation group and the control group according to whether implanted fluorouracil sustained release implant.the observation group was implanted with fluorouracil sustained release implant（n=39）in surgery,and the control group was not implanted with fluorouracil sustained release implant（n=40）.By comparing the changes of serum tumor markers carcinoembryonic antigen（CEA）,carbohydrate antigen 19-9（CA19-9）,carbohydrate antigen 72-4（CA72-4）before surgery and at 4 weeks after surgery,and one year and two years survival rate and recurrence rate of the two groups after surgery observing the curative effect of fluorouracil sustained release implant.By comparing two groups’baseline level of white blood cell count（WBC）,absolute neutrophil count（ANC）,hemoglobin（HB）and platelet count（PLT）,and changes at 1 week after surgery according to WHO bone marrow suppression index analyzing the condition of bone marrow suppression after implanting fluorouracil sustained release implant in surgery.By comparing the changes of alanine aminotransferase（ALT）,aspartate aminotransferase（AST）and total bilirubin（TBIL）before and at 1 week after surgery according to WHO grade of drug-induced liver injury（NCI-CTC version 3.0）in two groups,evaluating the liver damage after implanting fluorouracil sustained release implant in surgery.By comparing the changes of serum cystatin C（CysC）,retinol binding protein（RBP）,serum creatinine（CRE）and blood urea nitrogen（BUN）before and at 1 week after surgery evaluating the renal damage after implanting fluorouracil sustained release implant in surgery.By comparing the incidence of gastrointestinal symptoms and postoperative complication such as postoperative adhesive ileus,intra-abdominal infection,anastomotic leak,intra-abdominal hemorrhage and incision infection,evaluating the safety of implanting fluorouracil sustained release implant in surgery.Using SPSS19.0 statistical software package for data analysis.Measured data were expressed as mean±standard deviation（±SD）.Two independent samples t-test were used for comparison between the two groups;count data were expressed as relative numbers,using standard chi square test;Kaplan-Meier survival curve was used for describing survival rate and relapse rate,estimated by the log-rank test.According to the test level ofα=0.05,P<0.05 was considered statistically significant.Results:1.Comparison of gender composition,tumor location,pathological type,clinical stage,radical resection method,and lymph node metastasis ratio between the two groups were all P>0.05.Comparison of preoperative WBC,ANC,HB,PLT,AST,ALT,TBIL,CysC,RBP,BUN,CRE,CEA,CA19-9,and CA72-4 between the two groups were all P>0.05.There was no statistical difference in baseline data between the two groups.2.There was no significant change in CEA concentration（P>0.05）before and at 4weeks after operation in the control group.The CEA concentration was significantly lower（P<0.05）at 4 weeks after operation than before in the observation group.The CEA concentration in the observation group was also significantly lower than the control group（P<0.05）after the operation.The CA19-9 and CA72-4 concentrations were significantly decreased after the surgery in the observation group and the control group（P<0.05）than before;There was no significant difference in the concentration of CA19-9and CA72-4 between the two groups(P>0.05 after the surgery.There was no significant difference in postoperative 1-year survival rate（P>0.05）between the two groups,and there was a significant difference in postoperative 2-year survival rate（P<0.05）.There was no significant difference in postoperative 1-year recurrence rate（P>0.05）between the two groups.There was significant difference（P<0.05）in postoperative 2-year recurrence rate between the two groups.3.There was no significant difference in HB,WBC,ANC,and PLT between the two groups at 1 week after surgery（P>0.05）.There was no significant difference in postoperative bone marrow suppression index between the two groups（P>0.05）.4.There was no significant difference in TBIL,ALT and AST between the two groups（P>0.05）at 1 week after surgery.There was no significant difference in postoperative grade of drug-induced liver injury between the two groups（P>0.05）.5.There was no significant difference in CysC,RBP,CRE,and BUN between the two groups at 1 week after surgery（P>0.05）.There was no significant difference in the positive rate of postoperative renal damage between the two groups（P>0.05）.There was no significant difference in the incidence of gastrointestinal symptoms after surgery between the two groups（P>0.05）.There was no significant difference in complications of postoperative adhesive ileus,intra-abdominal infection,anastomotic leak,intra-abdominal hemorrhage and incision infection between the two groups（P>0.05）.Conclusions:1.Surgical treatment is the main factor of decreasing the concentration of CEA,CA19-9 and CA72-4.Implanting fluorouracil sustained release implant in surgery can make the degree of CEA decline more obvious at 4 weeks after operation.The effect of fluorouracil sustained release implant on the concentration of CA19-9 and CA72-4requires more long-term observation.Implanting fluorouracil sustained release implant in surgery can increase the postoperative survival rate,reduce the recurrence rate,and improve the treatment effect.2.Implanting fluorouracil sustained release implant did not cause obvious damage to the hematopoietic system and no significant myelosuppression occurred.Implanting fluorouracil sustained release implant did not cause significant hepatic and renal damage.3.Implanting fluorouracil sustained release implant did not cause adverse affection on the recovery of the digestive system,and did not cause significant damage to the digestive system;Implanting fluorouracil sustained release implant also did not increase postoperative short-term complications happened.In summary,this study shows that Implanting fluorouracil sustained release implant in surgery can improve the curative effect,reduce recurrence rate and improve the prognosis with good safety.