目的 探讨吉西他滨与吡柔比星序贯膀胱灌注治疗行尿道膀胱肿瘤切除术（TURBT）的非肌层浸润性膀胱癌（NMIBC）患者的临床疗效以及对患者尿液肿瘤标志物和外周血中性粒细胞与淋巴细胞比值（NLR）、T淋巴细胞亚群水平的影响。方法 回顾性收集濮阳市油田总医院2018年1月—2021年2月收治的80例NMIBC患者为研究对象，按治疗方案不同将患者分为对照组和试验组，每组各40例。两组均行相同的TURBT治疗，术后均即刻开始膀胱灌注化疗。试验组给予吉西他滨与吡柔比星序贯膀胱灌注治疗，首次膀胱灌注使用注射用盐酸吡柔比星30 mg＋5%葡萄糖注射液，稀释至质量浓度为1 mg·mL^-1的溶液，通过导尿管注入膀胱内，夹闭导尿管，保留1 h；第2次使用注射用盐酸吉西他滨1 000 mg＋0.9%氯化钠注射液50 mL，经导尿管注入膀胱内，夹闭导尿管，保留1 h；两种药物交替使用。对照组单用注射用盐酸吡柔比星膀胱灌注治疗，每次用法用量同试验组。两组均规律膀胱灌注治疗，开始时每周1次，持续8周，随后每月1次，共计10次。治疗后对所有患者进行至少12个月的追踪随访，比较两组肿瘤复发情况。治疗前和治疗后12个月测定两组患者尿液肿瘤标志物［细胞角蛋白19片段抗原（CYFRA21-1）、癌胚抗原（CEA）、糖类抗原125（CA125）］水平；检查血常规，计算外周血NLR；采用流式细胞仪检测外周血T淋巴细胞亚群分布情况。并统计两组治疗期间不良反应发生情况。结果 试验组治疗后12个月内肿瘤复发率为5.0%，显著低于对照组的20.0%（P<0.05）。两组治疗后12个月尿液CYFRA21-1、CEA和CA125水平均较治疗前显著降低（P<0.05），且均以试验组的下降更显著（P<0.05）。两组治疗后12个月外周血NLR和外周血CD8⁺T细胞水平均较治疗前显著降低（P<0.05），外周血CD4⁺T细胞水平、CD4⁺/CD8⁺均较治疗前显著升高（P<0.05）；且与同期对照组相比，试验组治疗后12个月外周血NLR和外周血CD8⁺T细胞水平均显著降低（P<0.05），外周血CD4⁺T细胞水平、CD4⁺/CD8⁺均显著升高（P<0.05）。治疗期间，两组膀胱刺激症状、血尿、发热、胃肠道反应及肝肾功能异常的总发生率比较，差异均无统计学意义（P>0.05）。结论 吉西他滨与吡柔比星序贯膀胱灌注联合TURBT能有效降低NMIBC患者外周血NLR，改善T淋巴细胞亚群水平，下调尿液肿瘤标志物表达水平，降低术后复发风险，且不加重不良反应。

Objective To investigate the clinical efficacy of gemcitabine and pirarubicin sequential intravesical instillation in the treatment of non-muscle invasive bladder cancer (NMIBC) patients undergoing transurethral resection of bladder tumor (TURBT), as well as the effect of treatment on the levels of urinary tumor markers, peripheral blood neutrophil to lymphocyte ratio (NLR), and T lymphocyte subsets. Methods A toal of 80 patients with NMIBC admitted to Puyang Oilfield General Hospital from January 2018 to February 2021 were retrospectively collected as the research objects. The patients were divided into control group and experimental group according to different treatment schemes, with 40 patients in each group. Patients in both groups were treated with the same TURBT, and intravesical instillation chemotherapy was started immediately after operation. In the experimental group, gemcitabine and pirarubicin were given for sequential intravesical instillation therapy. For the first intravesical instillation, Pirarubicin Hydrochloride 30 mg+5% glucose injection was used, diluted to a solution with a mass concentration of 1 mg·mL^-1, injected into the bladder through a catheter, clamped the catheter, and retained for one hour. For the second time, use Gemcitabine Hydrochloride for Injection 1 000 mg+0.9% sodium chloride injection 50 mL, inject it into the bladder through a catheter, clamp the catheter, and keep it for one hour. The two drugs are used alternately. Patients in the control group were treated with intravesical instillation of Pirarubicin Hydrochloride for Injection only, and the dosage of each use was the same as that of the experimental group. Both groups received regular bladder perfusion therapy, once a week at the beginning, lasting for eight weeks, and then once a month, a total of 10 times. After treatment, all patients were followed up for at least 12 months to compare the tumor recurrence between the two groups. Urine tumor markers (CYFRA21-1, CEA, CA125) were measured before and 12 months after treatment in both groups. Check the blood routine and calculate the peripheral blood NLR. The distribution of T lymphocyte subsets in peripheral blood was detected by flow cytometry. The adverse reactions of the two groups during the treatment were counted. Results The tumor recurrence rate in the experimental group was 5.0% within 12 months after treatment, which was significantly lower than that in the control group (20.0%, P<0.05). The levels of CYFRA21-1, CEA and CA125 in urine of the two groups 12 months after treatment were significantly lower than those before treatment (P<0.05), and the decrease in the experimental group was more significant (P<0.05). The levels of peripheral blood NLR and peripheral blood CD8⁺T cells in the two groups 12 months after treatment were significantly lower than those before treatment (P<0.05), and the levels of peripheral blood CD4⁺T cells and CD4⁺/CD8⁺were significantly higher than those before treatment (P<0.05). Compared with the control group in the same period, the levels of peripheral blood NLR and peripheral blood CD8⁺T cells in the experimental group were significantly decreased 12 months after treatment (P<0.05), and the levels of peripheral blood CD4⁺T cells and CD4⁺/CD8⁺were significantly increased (P<0.05). During the treatment, there was no significant difference between the two groups in the total incidence of bladder irritation symptoms, hematuria, fever, gastrointestinal reactions, and liver and kidney dysfunction (P>0.05). Conclusion Gemcitabine and pirarubicin sequential intravesical instillation combined with TURBT can effectively reduce the peripheral blood NLR, improve the level of T lymphocyte subsets, lower the level of tumor markers in urine, reduce the risk of recurrence after operation, and do not aggravate adverse reactions in patients with NMIBC.

R979.1