TUR-Bt术中粘膜下多点注射IL-2联合术后灌注治疗非浸润性膀胱癌的临床研究

发布时间：2018-04-05 07:17

  本文选题：非肌层浸润性膀胱癌　切入点：免疫治疗　出处：《河北医科大学》2017年硕士论文

【摘要】：目的:1观察及探讨经尿道膀胱肿瘤电切术(Transurethral Resection of Bladder Tumor,TUR-Bt)术中膀胱粘膜下及膀胱肿瘤基底部多点注射免疫制剂白细胞介素-2(Interleukin-2,IL-2)联合术后即刻膀胱灌注化疗药物吉西他滨(Gemcitabine,GEM)治疗及预防非肌层浸润性膀胱癌(Non Muscle-Invasive Bladder Cancer,NMIBC)复发的临床效果。2探讨具有不同复发危险性的膀胱肿瘤患者在应用TUR-Bt术中膀胱粘膜下及肿瘤基底部多点注射IL-2联合术后灌注吉西他滨治疗NMIBC与传统单纯行TUR-Bt联合吉西他滨灌注的治疗后膀胱肿瘤复发率比较。方法:收集在2013年2月-2015年2月就诊于石家庄市第一医院泌尿外科且术前泌尿系彩超、泌尿系CT及磁共振成像(Magnetic resonance imaging,MRI)提示膀胱逼尿肌未见浸润的膀胱肿瘤患者,共128例。性别分布为:男性患者76例,女性患者52例。年龄分布在26-81岁,其中30岁以下患者5例,30岁-40岁患者13例,40岁-60岁患者51例,60-80岁患者54例,80岁以上患者5例,平均年龄为58.7岁。肿瘤分布:肿瘤位于膀胱侧壁者47例,后壁者32例,三角区者20例,顶部者14例,颈部者12例,多部位者3例。患者依据严格的纳入与排除标准入组,将入组患者依据随机数字表随机分为实验组和对照组。实验组患者共68例,手术中具体实施步骤为先应用尿道膀胱镜及其穿刺针于膀胱粘膜下及肿瘤基底部多点注射IL-2约20针后再改用电切镜行TUR-Bt术;对照组60例,不应用IL-2进行多点注射,仅行TUR-Bt术。术后将肿瘤组织、肿瘤基底和肿瘤周围2cm的膀胱粘膜分别送病理学检查。两组患者在病情允许的情况下,均在术后24小时内即刻膀胱灌注化疗药物吉西他滨。所有患者第一年每三个月复查膀胱镜检查及第二年每6个月复查膀胱镜检查时,实验组需要再次于正常膀胱粘膜下多点注射IL-2,对照组不作任何处理。比较两组病人于术后2年随访期内膀胱肿瘤的复发率。若术后病理结果回报为浸润性膀胱癌和原位癌者以及术后膀胱镜检查复发者,均退出本实验研究。统计学组间计数资料率的比较采用χ2检验或Fisher精确概率法。以P0.05为差异有统计学意义。结果:全部病例在2年随访结束时,实验组膀胱肿瘤复发者12例,复发率22%(15/68)。对照组膀胱肿瘤复发者25例,复发率为42%(25/60)。实验组复发率明显低于对照组,采用χ2检验比较两组间复发率存在差别,χ2值为5.704,P=0.017(P0.05),差异有统计学意义。将所有入组的膀胱肿瘤患者病历资料汇总后,回顾性分析实验数据,依据患者术后病理结果,参照膀胱肿瘤术后复发危险性评分进一步将患者归类为低危、中危、高危类别后,计算各不同复发风险类别内的实验组与对照组的膀胱肿瘤复发率的差别,得出结果为:低危患者中,实验组共19人,复发人数为3例,复发率为16%;对照组共21人,复发人数为6例,复发率为29%。中危患者中,实验组共21人,复发人数为6例,复发率为29%;对照组共19人,复发人数为9例,复发率为47%;高危患者中,实验组共28人,复发人数为6例,复发率为21%;对照组共20人,复发人数为10例,复发率为50%。采用χ2检验和Fisher精确概率法对各复发危险不同类别内的实验组与对照组术后复发率进行比较,低危患者中,两组复发率比较P=0.457,P0.05;中危患者中,两组复发率比较P=0.220,P0.05;高危患者中,两组复发率比较P=0.038,P0.05。因此,尚不能认为低危及中危患者内的实验组与对照组的复发率存在差异(P0.05);而高危患者内实验组膀胱肿瘤复发率明显低于对照组(P0.05),差异有统计学意义。结论:1 TUR-Bt术中膀胱粘膜下及肿瘤基底部多点注射IL-2联合术后灌注吉西他滨对预防非肌层浸润性膀胱癌的复发具有显著疗效。2此方法尤其对高危非肌层浸润性膀胱癌患者效果更佳。整个手术操作简单,安全性能高,患者不良反应少,具有良好的临床应用与推广价值。
[Abstract]:Objective: To investigate and observe 1 transurethral resection of bladder tumor (Transurethral Resection of Bladder Tumor, TUR-Bt) basal operation in bladder mucous membrane of bladder tumor and multiple point injection of immune agents of interleukin -2 (Interleukin-2, IL-2) instillation of chemotherapy drug gemcitabine after operation (Gemcitabine, GEM) treatment and the prevention of non muscle invasive bladder cancer (Non Muscle-Invasive Bladder Cancer, NMIBC.2) clinical effect on recurrence rate of bladder tumor recurrence in treatment of bladder cancer patients have different risk of recurrence in the bladder in the application of TUR-Bt mucosa and tumor basal multi-point injection of IL-2 combined with postoperative infusion of gemcitabine in the treatment of NMIBC with traditional TUR-Bt combined with gemcitabine after reperfusion. Methods: collected in February 2013 -2015 year in February admitted to the first hospital of Shijiazhuang city in the Department of Urology and preoperative urinary Department of ultrasound, Urinary CT and magnetic resonance imaging (Magnetic resonance imaging, MRI) suggested that patients with bladder tumor bladder detrusor no infiltration, a total of 128 cases. The gender distribution: 76 cases of male patients and 52 female patients. The age distribution at the age of 26-81, among which 5 cases were under 30 years old, 30 years old -40 years old 13 patients 40 -60 years old in 51 patients, 60-80 patients with 54 cases, 5 cases of patients over 80 years old, the average age was 58.7. Tumor distribution: 47 cases of bladder wall tumor in 32 cases, the posterior wall, 20 cases of the Delta region, the top 14 cases, 12 cases of neck, 3 cases part of patients. According to the strict inclusion and exclusion criteria into the group, the patients according to the random number table, randomly divided into experimental group and control group. The experimental group were 68 cases of surgery in the specific implementation steps for the first application of transurethral cystoscope and puncture needle in the basilar part of the bladder mucosa and tumor multi point injection about 20 IL-2 after the needle TUR-Bt electricity cut mirror operation; 60 cases in the control group, no IL-2 application of multiple point injection, only TUR-Bt was performed after operation. The tumor tissue, tumor and tumor of bladder mucosa around the basal 2cm were sent for pathological examination. Two patients in the condition permitting, both in the immediate intravesical chemotherapy gemcitabine 24 hours after surgery. All patients first year every three months by cystoscopy and two years every 6 months by cystoscopy, the experimental group again in normal bladder mucosa under multi-point injection of IL-2, the control group without any treatment. Compared two groups of patients after 2 years follow-up during the period of bladder tumor recurrence rate. If the postoperative pathology results for invasive bladder cancer and carcinoma in situ and postoperative cystoscopy recurrence, were withdrawn from the study. The rate of count data between groups were compared using chi square test or Fisher exact probability 2. In P0.05 the difference was statistically significant. Results: all cases at the end of the 2 years of follow-up, 12 cases of experimental group bladder tumor recurrence, the recurrence rate was 22% (15/68). The control group of 25 cases of bladder tumor recurrence, the recurrence rate was 42% (25/60). The recurrence rate of experimental group was significantly lower than the control group, using chi square 2 test to compare the recurrence rate between two groups are different, 2 x = 5.704, P=0.017 (P0.05), the difference was statistically significant. All the medical records of patients with bladder cancer were pooled, retrospective analysis of experimental data, according to the patient's postoperative pathological results, according to the postoperative recurrence of bladder cancer risk score will be further patients classified as low risk, moderate risk, high risk category, calculate the different risk of recurrence in the experimental group and control group differences in the rate of recurrence of bladder cancer, the results are: low risk patients in the experimental group, a total of 19 people, the number of 3 cases of recurrence, the recurrence rate was 16%; the control group 鍏，

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