尿液核基质蛋白22在膀胱移行上皮癌筛检中的价值

目的：评价尿核基质蛋白22(NMP22)在膀胱移行上皮癌筛检中的意义。方法：采用酶联免疫法检测28例膀胱移行上皮癌、25例泌尿系良性疾病和10例泌尿系非移行上皮癌患者尿NMP22水平，并与尿脱落细胞学检查进行比较。结果：膀胱移行上皮癌患者尿NMP,,中位值为66．5u／ml，明显高于泌尿系良性疾病和非移行上皮癌，与肿瘤分期、分级、数目无关，以10u／ml为临界，诊断膀胱癌敏感性为85．7％，特异性为60％，尿脱落细胞学检查敏感性为32．1％，特异性为100％。结论：尿NMP22检测膀胱移行上皮癌敏感性、特异性均较高，可用于膀胱移行上皮癌的筛选和术后随访。     

尿核基质蛋白22和细胞角蛋白18在膀胱移行细胞癌中的表达及其临床意义

目的 探讨尿核基质蛋白22(NMP22)和细胞角蛋白18(CK18)在膀胱移行细胞癌中的表达及其临床意义.方法 采用酶联免疫吸附法(ELISA)对293例膀胱移行细胞癌、400例非移行细胞肿瘤、105例泌尿系良性病患者进行尿NMP22和CK18蛋白水平的检测.结果 膀胱移行细胞癌患者术前NMP22和CK18表达中位值分别为17.3 U/ml和484.2 U/L,非移行细胞肿瘤患者分别为6.8 U/ml和156.0 U/L,良性疾病患者分别为2.3 U/ml和66.6 U/L,3组之间进行比较,差异有统计学意义(P<0.001).以NMP22 10 U/ml和CK18 120 U/L为界值,其对膀胱移行细胞癌诊断的敏感度分别为79.2%和78.2%,特异度分别为88.6%和82.9%,两者联合检测的敏感度为91.7%.对术后患者动态观察,治疗有效患者的NMP22和CK18表达水平较治疗前明显下降,而复发、转移的患者则上升,差异有统计学意义(P<0.01).NMP22和CK18对膀胱移行细胞癌的检测有显著的相关性(r=0.689 P<0.0001).NMP22和CK18表达水平在不同病理分级和不同分期的患者中比较,差异有统计学意义(均P<0.01).结论 尿NMP22和CK18检测可作为膀胱移行细胞癌术前诊断、病情监测重要指标,两者联合检测可进一步提高敏感度.     

吉西他滨灌注联合2 μm激光治疗非浸润性膀胱癌的疗效及对相关标志物的影响

目的:探究吉西他滨灌注联合2 μm激光治疗非浸润性膀胱癌的疗效及对相关标志物的影响。方法:选取2014年2月至2017年2月收治的90例非浸润性膀胱癌患者,随机分为两组,对照组（45例）行经尿道2 μm激光治疗,观察组（45例）行吉西他滨膀胱灌注联合经尿道2 μm激光治疗。对比两组手术、住院、尿管留置时间以及术后并发症发生率,比较两组治疗前后血清趋化因子配体5（CXCL5）及尿液核基质蛋白22（NMP22）水平变化,并对比两组术后无复发生存率和肿瘤进展率。结果:观察组的手术、住院、尿管留置时间以及并发症发生率与对照组相比,差异无统计学意义（P＞0.05）;治疗后两组血清CXCL5及尿NMP22水平均降低,且观察组低于对照组（P＜0.05）;观察组的肿瘤进展率低于对照组,无复发生存率高于对照组（P＜0.05）;Kaplan-Meier生存分析结果显示,观察组与对照组的生存曲线比较,差异有统计学意义（P＜0.05）。结论:对非浸润性膀胱癌患者应用吉西他滨膀胱灌注联合经尿道2 μm激光治疗,可降低血清CXCL5及尿NMP22水平,延长患者的生存时间。     

膀胱癌患者尿液中核有丝分裂器蛋白测定的临床意义

目的探讨尿中核有丝分裂器蛋白(NMP22)的表达与膀胱肿瘤的关系.方法采用ELISA法测定32例膀胱癌、30例泌尿系良性疾病患者及15例正常人尿液中NMP22的含量.结果膀胱癌患者尿液中NMP22含量为(55.84±47.89)U/ml,明显高于泌尿系良性疾病患者(18.78±18.95)U/ml及正常人(6.97±3.82)U/ml(P＜0.01).尿液中NMP22水平与肿瘤分期、分级有关.结论检测尿液中NMP22含量可作为膀胱癌筛选和评估其生物学行为的1个指标.     

口服水飞蓟宾胶囊联合吡柔比星膀胱灌注对非肌层浸润性膀胱癌患者术后复发的影响

目的:观察口服水飞蓟宾胶囊联合吡柔比星膀胱灌注对非肌层浸润性膀胱癌患者术后复发的影响。方法:将非肌层浸润性膀胱癌患者124例患者随机分为对照组62例和观察组62例,对照组给予吡柔比星膀胱灌注,观察组给予口服水飞蓟宾胶囊联合吡柔比星膀胱灌注。单因素分析性别、年龄、血尿、吸烟、肿瘤数目、肿瘤大小、肿瘤病理分级、肿瘤分期、水飞蓟宾联合吡柔比星对膀胱肿瘤复发的影响。将单因素分析可能影响肿瘤复发的因素纳入多因素Cox回归分析独立影响肿瘤复发的因素。结果:单因素分析结果提示肿瘤数目、肿瘤大小、肿瘤病理分级、肿瘤分期、水飞蓟宾联合吡柔比星可能是影响膀胱肿瘤复发的因素（P＜0.05）;多因素Cox回归分析显示肿瘤多发、T1是非肌层浸润性膀胱癌的独立危险因素（P＜0.05）,水飞蓟宾联合吡柔比星是非肌层浸润性膀胱癌的独立保护因素（P＜0.01）。结论:口服水飞蓟宾胶囊联合吡柔比星膀胱灌注对非肌层浸润性膀胱癌TUR-BT术后复发的预防效果较好,可减少患者术后早期复发率,且不增加不良反应,较为安全,值得临床推广应用。     

132例膀胱内灌注吡柔比星预防浅表性膀胱癌术后复发

目的:评价吡柔比星膀胱内灌注预防浅表性膀胱癌术后复发的有效性及安全性.方法:符合入选标准的患者于手术后2周内开始行吡柔比星膀胱灌注,每次30mg,每周1次共8次,以后每月1次共1年,定期膀胱镜检查进行随访.结果:132例浅表性膀胱移行细胞癌患者,术后平均随访时间12.2±5.74个月.肿瘤复发22例,总复发率16.7%.其中复发性肿瘤的复发率明显高于初发肿瘤(P=0.003),而不同肿瘤分期、分级及单发与多发肿瘤患者间的复发率未见明显差异.不良反应主要为尿路刺激症状和尿常规异常.结论:吡柔比星膀胱灌注预防浅表性膀胱癌术后复发的效果明确,疗效满意,患者耐受性好,是较为理想的膀胱灌注化疗药物.     

膀胱癌组织中B7-H1表达水平及其对经尿道膀胱肿瘤电切术后膀胱灌注治疗效果的影响

目的 探讨膀胱癌组织中B7-H1表达水平及其对经尿道膀胱肿瘤电切术后膀胱灌注治疗效果的影响.方法 选取20例膀胱癌患者作为研究对象,采用回顾性分析法分析所有患者的临床资料,所有膀胱癌患者均行经尿道膀胱肿瘤电切术且术后均行膀胱灌注治疗,将膀胱癌组织作为A组,将癌旁正常组织作为B组.根据资料结果比较所有研究对象的B7-H1水平以及所有膀胱癌手术患者的术后治疗情况及效果.结果 A组膀胱癌组织中B7-H1表达水平明显高于B组正常膀胱组织(P﹤0.05);不同临床分期和病理分级膀胱癌患者间B7-H1表达水平比较,差异有统计学意义,且随着临床分期和病理分级越高其B7-H1表达水平越高(P﹤0.05);膀胱癌组织B7-H1表达水平与临床分期和病理分级呈正相关(r=0.684、0.762,P﹤0.05).结论 B7-H1在膀胱癌组织中以高水平表达,且临床分期和病理分级越高B7-H1表达水平越高,可考虑作为预测膀胱癌病情发展的指标.     

端粒酶活性检测在膀胱肿瘤早期诊断中的应用

目的：探讨检测端粒酶活性在膀胱癌早期诊断中的临床意义。方法：采用TRAP-PCR-ELISA法检测32例膀胱癌患者尿液和膀胱冲洗液中脱落细胞、膀胱癌组织、20例正常膀胱组织及14例非膀胱肿瘤患者尿液脱落细胞中端粒酶活性，并行尿脱落细胞学检查。结果：32例膀胱癌患者尿液脱落细胞、膀胱冲洗液脱落细胞、膀胱癌组织中端粒酶活性阳性率分别为65．6％（21／32）、71．9％（23／32）和84．0％（27／32），20例正常膀胱组织端粒酶活性均为阴性，14例非膀胱肿瘤患者尿液中1例端粒酶活性阳性。端粒酶活性阳性表达与肿瘤的分级、分期之间差异无明显相关性（P〉0．05），敏感性明显高于脱落细胞病理学检查。结论：尿液、膀胱冲洗液脱落细胞端粒酶活性测定敏感性较高．可用于膀胱癌的早期诊断。     

膀胱癌组织中TopoⅡα表达水平及与TURBT术后复发的关系

目的:探讨膀胱癌组织中拓扑异构酶Ⅱα（TopoⅡα）表达水平及与经尿道膀胱肿瘤电切术（TURBT）后复发的关系。方法:选取在我院泌尿外科确诊为膀胱癌并行TURBT术的患者90例,术后采用吡柔比星注射液膀胱灌注治疗,根据TopoⅡα表达情况将90例膀胱癌患者分为TopoⅡα高表达组和TopoⅡα低表达组,比较TopoⅡα的表达情况与膀胱癌患者临床病理特征的关系,进行TopoⅡα的表达与吡柔比星膀胱灌注治疗的预后分析。结果:90例膀胱癌患者中有57例TopoⅡα 高表达,高表达率为63.33%;膀胱癌患者TopoⅡα 高表达率与年龄、肿瘤数目、肿瘤大小和病理分级等临床病理特征参数显著相关（P<0.05）。TopoⅡα高表达组患者1、2、3年复发率（8.77%、14.04%、17.54%）明显低于TopoⅡα低表达组（27.27%、39.39%、51.52%）,TopoⅡα高表达组平均复发时间显著高于TopoⅡα低表达组,差异均有统计学意义（P<0.05）。Cox回归分析显示:肿瘤多发、肿瘤大小＞2 cm、病理分级和TopoⅡα低表达等4个因素为膀胱癌患者复发的独立危险因素（P<0.05）。结论:TopoⅡα表达与膀胱癌患者年龄、肿瘤数目、肿瘤大小和病理分级等显著相关,在TURBT术后对TopoⅡα高表达患者给予吡柔比星注射液膀胱灌注治疗可以显著减少复发率。     

术前新辅助化疗治疗浸润性膀胱癌疗效观察

目的:观察术前新辅助化疗治疗浸润性膀胱癌的临床疗效。方法:对27例平均年龄68岁、有全膀胱切除指征而无法耐受或不愿接受膀胱全切的浸润性膀胱癌患者行骼内动脉化疗并栓塞联合手术治疗,观察膀胱保留率、降级降期率、肿瘤复发率,Kaplan-Meier 法计算总生存率、无瘤生存率,并绘制生存曲线。结果:髂内动脉化疗、栓塞后,22例患者膀胱肿瘤缩小约81.5% ,无变化5 例;肿瘤临床分期降低21例（有效率77.8%）,无变化6 例;病理分级降低12例（降级率44.4%）,分级不变15例。共24例患者得以保留膀胱,其中21例行经尿道膀胱肿瘤切除术（transurethral resection of the bladder ,TURB）,3 例行膀胱部分切除术（膀胱保留率88.9%）。 3 例接受根治性膀胱全切术。术后1、2、3、5 年分别复发4 例（14.8%）、7 例（25.9%）、11例（40.7%）、14例（51.9%）。 2 例随访11个月和23个月发现肿瘤远处转移后死亡,1 例膀胱切口种植转移,局部切除后再发,带瘤生存,术后3 年死于肿瘤进展,2 例腺癌5 年内死于肿瘤进展。至随访截止日期,死于术后肿瘤进展共5 例。27例患者1、2、3、5 年无瘤生存率分别为88.9% 、73.6% 、58.1% 、41.4% ,5 年总生存率66.0% 。结论:有选择地对部分浸润性膀胱癌患者施行术前髂内动脉灌注化疗、栓塞,联合手术等综合性治疗措施以保留功能性膀胱确实可行,但合理评价其在浸润性膀胱癌治疗中的应用价值尚需要进一步研究证实。      

Clinical application of NMP22 in the management of transitional cell carcinoma of the bladder

The combination of a noninvasive, quantitative immunoassay, NMP22, with voided urinary cytology prior to cystoscopy was evaluated in patients with urothelial transitional cell carcinoma. Fifty-six patients with a history of transitional cell carcinoma were evaluated. Voided urine was obtained for NMP22 and cytology prior to cystoscopy. One hundred and twenty-three NMP22 assays, 124 cytologies, and 124 cystoscopies were performed. The type of anesthesia used for cystoscopic evaluation was determined by the NMP22 value in 30 patients. Cystoscopy results were considered positive on biopsy-confirmed malignancy. The reference value used for NMP22 was 10.0 U/ml. NMP22, cytology, and the combination of NMP22 and cytology were compared to cystoscopy and to pathologic grading and staging. Thirty-four recurrent transitional cell carcinoma episodes occurred; 22 were low-grade (I-II), and 12 were high-grade (III-IV). Twenty-seven were stage Ta; four were T1; and three were T3b or 4. Within this group, NMP22 detected low- and high-grade tumors equally, as compared to cytology, which was sensitive only to high-grade tumors. Nineteen patients were NMP22-negative and underwent cystoscopy under topical anesthesia; 17 were tumor-free. Eleven patients were NMP22-positive and had anesthesia, and all had visible lesions, which were subjected to biopsy and were resected. Six lesions were tumors, five were inflammatory. Overall sensitivity of combined NMP22 and cytology was 70%; specificity was 72%; positive predictive value was 54%; and negative predictive value was 77%. An accurate assessment of the risk of a bladder cancer can be obtained with NMP22, cytology, and cystoscopy in patients with a history of bladder cancer. NMP22 values can be used to determine the level of anesthesia for cystoscopy in patients with a history of bladder cancer.     

Comparison of NMP22 BladderChek test and urine cytology for the detection of recurrent bladder cancer

OBJECTIVE: To assess the clinical performance of the NMP22 BladderChek test, which is a qualitative test, and to compare it with voided urine cytology for the detection of recurrent bladder cancer. We also evaluated whether cystoscopy can be omitted from the surveillance protocol by combining the two tests. METHODS: A total of 131 patients with a history of superficial transitional cell carcinoma of the bladder provided urine samples before a cystoscopic examination. Urine samples were assayed for the presence of NMP22 using the NMP22 BladderChek test and cytology was performed by a cytopathologist. Selected patients underwent a biopsy, with appropriate additional therapy. Results of the two tests were compared with that the results of cystoscopy, which was retained as the gold standard. For positive biopsies, the results of the NMP22 test and cytology were also correlated with the tumor stage and grade. RESULTS: Of the 46 recurrences detected by cystoscopy, the NMP22 test was positive in 39 cases and cytology in 19 cases. The sensitivity of the NMP22 test was 85%, which was significantly greater than that of cytology (41%). In particular, for low-risk tumors it was eight times more sensitive than cytology. The specificities of the NMP22 test and cytology were 77 and 96%, respectively. Combining the two tests increased overall sensitivity to 91%. However, 9% of the tumors were still not detected. CONCLUSION: The NMP22 BladderChek test is an in vitro qualitative test that is easily available and cheap; it can be performed by a urologist in the office and results can be interpreted within 30 min. The NMP22 test is superior to cytology for all grades and stages in the detection of recurrence in patients with a history of superficial bladder cancer. Our study indicates that the NMP22 test can be used as a substitute for urine cytology. The NMP22 test cannot replace cystoscopy, but it can be used as an adjunct to cystoscopy in the surveillance protocol for patients with superficial bladder cancer.     

Diagnostic approach for cancer cells in urine sediments by 5‐aminolevulinic acid‐based photodynamic detection in bladder cancer

Bladder urothelial carcinoma is diagnosed and followed up after transurethral resection using a combination of cystoscopy, urine cytology and urine biomarkers at regular intervals. However, cystoscopy can overlook flat lesions like carcinoma in situ, and the sensitivity of urinary tests is poor in low‐grade tumors. There is an emergent need for an objective and easy urinary diagnostic test for the management of bladder cancer. In this study, three different modalities for 5‐aminolevulinic acid (ALA)‐based photodynamic diagnostic tests were used. We developed a compact‐size, desktop‐type device quantifying red fluorescence in cell suspensions, named “Cellular Fluorescence Analysis Unit” (CFAU). Urine samples from 58 patients with bladder cancer were centrifuged, and urine sediments were then treated with ALA. ALA‐treated sediments were subjected to three fluorescence detection assays, including the CFAU assay. The overall sensitivities of conventional cytology, BTA, NMP22, fluorescence cytology, fluorescent spectrophotometric assay and CFAU assay were 48%, 33%, 40%, 86%, 86% and 87%, respectively. Three different ALA‐based assays showed high sensitivity and specificity. The ALA‐based assay detected low‐grade and low‐stage bladder urothelial cells at shigher rate (68–80% sensitivity) than conventional urine cytology, BTA and NMP22 (8–20% sensitivity). Our findings demonstrate that the ALA‐based fluorescence detection assay is promising tool for the management of bladder cancer. Development of a rapid and automated device for ALA‐based photodynamic assay is necessary to avoid the variability induced by troublesome steps and low stability of specimens.     

Soluble Fas--a promising novel urinary marker for the detection of recurrent superficial bladder cancer

BACKGROUND: The objective of this study was to test the hypothesis that elevated urinary levels of soluble Fas (sFas) would aid in the surveillance of patients with a past history of nonmuscle-invasive transitional cell carcinoma (TCC) of the urinary bladder. METHODS: sFas levels were determined in cell lysates and supernatants from 2 human bladder cancer cell lines (T24 and TCC-SUP) and in voided urine from 188 consecutive patients who were at risk for TCC recurrence, 31 patients who had noncancerous urologic conditions, and 10 healthy individuals. The authors also obtained barbotage cytology and voided nuclear matrix protein 22 (NMP22) levels. sFas was analyzed continuously and categorically on the basis of its quintile distribution. RESULTS: sFas was present in cell lysates and conditioned media from both cell lines. sFas levels were found to be higher in the TCC group (n = 122 patients) compared with the control group (P < .001). Higher levels of sFas were associated with positive cytology assay results (P < .001), higher NMP22 levels (P < .001), NMP22 levels > 10 U/mL (P < .001), and tumor stage > or = T1 (P < .001). The areas under the receiver operating characteristics (ROC) curves of sFas and NMP22 for bladder cancer detection were 0.757 (95% confidence interval, 0.694-0.819) and 0.704 (95% confidence interval, 0.637-0.772), respectively. In the > 75% sensitivity region of the ROC curves, sFas was consistently more specific than NMP22. In multivariate analyses, sFas, NMP22, and cytology all were found to be associated with the presence of bladder cancer (P values < or = .009), but only sFas and cytology were associated with tumor stage > or = T1 (P values < or = .026). CONCLUSIONS: sFas was produced and released by bladder TCC cells. Urine sFas was an independent predictor of bladder cancer recurrence and invasiveness in patients who had a past history of nonmuscle invasive bladder TCC, and it outperformed NMP22.     

NMP22肿瘤标志物诊断尿路上皮癌的初步评价

目的：探讨基质蛋白（ＮＭＰ２２）对尿路上皮癌临床诊断的价值。方法：应用酶联免疫法检测２８例尿路上皮癌及４例非尿路上皮肿瘤术前尿液的ＮＭＰ２２的含量。结果：尿路上皮癌ＮＭＰ２２的阳性率为７１．４％，其与病理分级、分期无明显相关性，而尿细胞学阳性率为３２．１％，４例非尿路上皮癌患者尿ＮＭＰ２２含量检测结果的为阴性。结论：尿液ＮＭＰ２２含量的测定有助于尿路上皮癌的诊断，且快速方便。     

尿脱落细胞学检查在原发性输尿管癌诊断中的意义

目的:探讨尿脱落细胞学检查(免疫荧光法)阳性率与原发性输尿管癌分级、分期关系.方法:对手术证实原发性输尿管癌的104个病例的临床资料进行回顾性分析,对术前尿脱落细胞学检查阳性率与术后病理分级、分期进行比较并做统计学处理.结果:原发性输尿管癌的尿脱落细胞学检查总阳性率为34.26%,高恶性组的尿脱落细胞学检查总阳性率为43.59%,低恶性组的尿脱落细胞学检查总阳性率为11.54%,其差异有统计学意义x2=8.740,P=0.003.输尿管下段、高恶性的原发癌尿脱落细胞学检查其高分期与低分期的阳性率差异有统计学意义x2-10.628.P=0.001.高恶性的原发性输尿管癌其高分期与低分期的阳性率差异有统计学意x2=5.678,P=0.017.对于低分期(Ⅰ～Ⅱ)的原发性输尿管癌高恶性与低恶性的阳性率的差异有统计学意义,X2=12.860,P=0.001.结论:高分级、低分期的原发性输尿管癌尿中更易找到癌细胞,即阳性率更高.     

Role of NMP22 Bladder Check Test in Early Detection of Bladder Cancer with Recurrence

AIM: To assess clinical utility of NMP22 Bladder Chek Test and to compare it with voided urine cytologyand cystoscopy in early detection of Bladder Cancer. Material & Methods: A total of 115 patients of follow upcases of Bladder Cancer were enrolled in this study. Urine samples were assayed for the presence of NMP22using NMP22 Bladder Chek Test and Cytology was performed by a cytopathologist. The diagnosis, determinedfrom the Cystoscopic findings and biopsy findings of the suspicious lesion was considered as the gold standard.For positive biopsies, the results of the NMP22 Test and cytology were also correlated with tumour grade andstage. Results: Mean age of the patients was 57.2 years for males and 55.3 years for females. A total of 59 casesof Bladder Cancer (TCC) were diagnosed among which NMP22 test was positive in 48 cases and cytology in26 cases. The sensitivity and specificities of NMP22 Test in recurrent bladder cases was 81.3% and 92% whichwas significantly greater than that of cytology 44% and 96.1% respectively. In non-invasive lesions of BladderCancer (TCC), NMP22 Test and Cytology was positive in 71.8% and 42.8% of cases respectively. In muscleinvasivelesions, NMP22 Test was positive in 82.2% and 44.4% cases were positive for cytology. The sensitivityof the NMP22 test was 81.3%, which was significantly greater than that of cytology 44%. Conclusion: TheNMP22 Bladder Check is a new point of care diagnostic test for urinary bladder cancer. The results of our studyhave shown that the NMP22 can be used as a substitute for urine cytology as we detected high sensitivity andspecificity of NMP22 in recurrent bladder cases.     

Urinary tumor marker for urothelial cancer]

The urinary tumor markers BTA, BFP and NMP22 used for urothelial cancer in Japan are reviewed briefly. We also evaluate and compare the sensitivity and specificity of BTA, BFP and NMP22 with urine cytology in detecting bladder cancer in 24 of our patients. The results showed that the sensitivity with urine cytology, BTA, BFP and NMP22 was 37, 54, 66 and 62% respectively. The specificity of BTA, BFP and NMP22 with urine cytology was 100, 65, 60 and 70% respectively. The sensitivity with BTA, BFP and NMP22 for urothelial cancer was higher than that with urine cytology. However, all except for urine cytology showed high false positive rates (83-90%) for urinary tract infection. These markers may thus complement urine cytology, which has a low sensitivity for urothelial cancer. Quite possibly they could act as low-cost and useful tumor markers, which could in turn reduce the number of invasive cystoscopic examinations. However, considering their high false positive rates for benign disease such as urinary tract infection, we must acknowledge that an ideal urothelial tumor marker, which is simple, non-invasive, inexpensive and accurate with high sensitivity and specificity has yet to be developed.