[關(guān)鍵詞]
[摘要]
目的 探討吉西他濱與吡柔比星序貫膀胱灌注治療行尿道膀胱腫瘤切除術(shù)(TURBT)的非肌層浸潤性膀胱癌(NMIBC)患者的臨床療效以及對患者尿液腫瘤標志物和外周血中性粒細胞與淋巴細胞比值(NLR)、T淋巴細胞亞群水平的影響。方法 回顧性收集濮陽市油田總醫(yī)院2018年1月—2021年2月收治的80例NMIBC患者為研究對象,按治療方案不同將患者分為對照組和試驗組,每組各40例。兩組均行相同的TURBT治療,術(shù)后均即刻開始膀胱灌注化療。試驗組給予吉西他濱與吡柔比星序貫膀胱灌注治療,首次膀胱灌注使用注射用鹽酸吡柔比星30 mg+5%葡萄糖注射液,稀釋至質(zhì)量濃度為1 mg·mL-1的溶液,通過導(dǎo)尿管注入膀胱內(nèi),夾閉導(dǎo)尿管,保留1 h;第2次使用注射用鹽酸吉西他濱1 000 mg+0.9%氯化鈉注射液50 mL,經(jīng)導(dǎo)尿管注入膀胱內(nèi),夾閉導(dǎo)尿管,保留1 h;兩種藥物交替使用。對照組單用注射用鹽酸吡柔比星膀胱灌注治療,每次用法用量同試驗組。兩組均規(guī)律膀胱灌注治療,開始時每周1次,持續(xù)8周,隨后每月1次,共計10次。治療后對所有患者進行至少12個月的追蹤隨訪,比較兩組腫瘤復(fù)發(fā)情況。治療前和治療后12個月測定兩組患者尿液腫瘤標志物[細胞角蛋白19片段抗原(CYFRA21-1)、癌胚抗原(CEA)、糖類抗原125(CA125)]水平;檢查血常規(guī),計算外周血NLR;采用流式細胞儀檢測外周血T淋巴細胞亞群分布情況。并統(tǒng)計兩組治療期間不良反應(yīng)發(fā)生情況。結(jié)果 試驗組治療后12個月內(nèi)腫瘤復(fù)發(fā)率為5.0%,顯著低于對照組的20.0%(P<0.05)。兩組治療后12個月尿液CYFRA21-1、CEA和CA125水平均較治療前顯著降低(P<0.05),且均以試驗組的下降更顯著(P<0.05)。兩組治療后12個月外周血NLR和外周血CD8+T細胞水平均較治療前顯著降低(P<0.05),外周血CD4+T細胞水平、CD4+/CD8+均較治療前顯著升高(P<0.05);且與同期對照組相比,試驗組治療后12個月外周血NLR和外周血CD8+T細胞水平均顯著降低(P<0.05),外周血CD4+T細胞水平、CD4+/CD8+均顯著升高(P<0.05)。治療期間,兩組膀胱刺激癥狀、血尿、發(fā)熱、胃腸道反應(yīng)及肝腎功能異常的總發(fā)生率比較,差異均無統(tǒng)計學(xué)意義(P>0.05)。結(jié)論 吉西他濱與吡柔比星序貫膀胱灌注聯(lián)合TURBT能有效降低NMIBC患者外周血NLR,改善T淋巴細胞亞群水平,下調(diào)尿液腫瘤標志物表達水平,降低術(shù)后復(fù)發(fā)風(fēng)險,且不加重不良反應(yīng)。
[Key word]
[Abstract]
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.
[中圖分類號]
R979.1
[基金項目]