经尿道等离子膀胱肿瘤电切术中膀胱黏膜下注射吉西他滨联合补充维生素A和维生素B_(1)对非肌层浸润性膀胱癌的疗效

Effect of submucosal injection of gemcitabine into bladder during transurethral resection of bladder tumor combined with vitamin A and vitamin B_(1)supplementation on non-muscle invasive bladder cancer

目的探究经尿道等离子膀胱肿瘤电切术中膀胱黏膜下注射吉西他滨联合补充维生素A(VitA)和维生素B_(1)(VitB_(1))治疗非肌层浸润性膀胱癌(NMIBC)的有效性及安全性。方法术前检测行经尿道等离子膀胱肿瘤电切术^(+)术中膀胱黏膜下注射吉西他滨的100例NMIBC患者血清VitA和VitB_(1)水平,并以100例健康志愿者作对照。上述NMIBC患者依据血清VitA和VitB_(1)水平分为维生素缺乏组(A组)和正常组(C组),两组又分为A1、C1组(术后口服VitA和VitB_(1))和A2、C2组(术后不口服VitA和VitB_(1)),每组20例。比较A1、A2、C1、C2四组术后1年和2年的无肿瘤复发率、无尿荧光原位杂交(FISH)复发率以及术后1年内不良反应发生率,观察四组术前和术后1年外周血T淋巴细胞亚群变化。结果与健康志愿者相比,NMIBC患者血清VitA和VitB_(1)水平均降低(P<0.05)。与A2组相比,A1组术后1年和2年无肿瘤复发率和无尿FISH复发率升高(P<0.01)。四组均未发生严重不良反应。与术前相比,A1组术后1年外周血CD4^(+)T淋巴细胞百分比和CD4^(+)/CD8^(+)T淋巴细胞比值升高,CD8^(+)T淋巴细胞百分比降低(P<0.01)。结论NMIBC患者可能存在VitA和VitB_(1)缺乏。对缺乏VitA和VitB_(1)的NMIBC患者采用经尿道等离子膀胱肿瘤电切术中黏膜下注射吉西他滨联合补充VitA和VitB_(1)可有效降低NMIBC复发率,可能与诱导患者体内CD4^(+)T淋巴细胞分化有关。

Objective To investigate the efficacy and safety of submucosal injection of gemcitabine into bladder during transurethral resection of bladder tumor combined with vitamin A(VitA)and vitamin B_(1)(VitB_(1))supplementation in the treatment of non-muscle invasive bladder cancer(NMIBC).Methods Serum levels of VitA and VitB_(1)in 100NMIBC patients underwent transurethral resection of bladder tumor plus intraoperative submucosal injection of gemcitabine into bladder were detected before surgery.Another 100healthy volunteers were taken as the controls.The NMIBC patients were divided into two groups of A(vitamin deficiency)and C(without vitamin deficiency)based on serum levels of VitA and VitB_(1).Group A and C were subdivided into four groups of A1,C1(receiving postoperative oral supplementation of VitA and VitB_(1))and A2,C2(not receiving postoperative oral supplementation of VitA and VitB_(1))with 20cases each.The tumor recurrence-free rate and urine fluorescence in situ hybridization(FISH)recurrence-free rate at 1and 2years after surgery and incidence of adverse reactions within 1year after surgery were compared among four groups of A1,A2,C1and C2.The changes of T lymphocyte subsets in peripheral blood were detected before and 1year after surgery in the four groups.Results Compared with healthy volunteers,serum levels of VitA and VitB_(1)in NMIBC patients were decreased(P<0.05).Compared with group A2,group A1had a higher tumor recurrence-free rate and urine FISH recurrence-free rate at 1and 2years after surgery(P<0.01).No serious adverse reactions occurred in the four groups.Compared with before surgery,the percentage of CD4^(+)T lymphocyte subsets and CD4^(+)/CD8^(+)T lymphocyte ratio in peripheral blood of group A1were increased,while the percentage of CD8^(+)T lymphocyte subsets was decreased 1year after surgery(P<0.01).Conclusion NMIBC patients may have VitA and VitB_(1)deficiency.For NMIBC patients lacking VitA and VitB_(1),intraoperative submucosal injection of gemcitabine during transurethral resection of bladder tumor combined with VitA and VitB_(1)supplementation can effectively reduce the recurrence rate of NMIBC,which may be related to inducing CD4^(+)T lymphocyte differentiation.