荧光膀胱镜在尿路上皮膀胱癌中的诊断价值

目的:评估以5-氨基乙酰丙酸(5-aminolevulinic acid, 5-ALA)作为荧光剂的荧光膀胱镜检查对非肌层浸润性膀胱癌的诊断价值。方法:按照筛除纳入标准,纳入97名研究对象,膀胱灌注50 mL浓度为3%的5-ALA溶液,保留1小时后,排空膀胱后置入膀胱镜,分别在普通白光和荧光下观察,对白光和/或荧光下显示阳性或可疑区域取组织做病理活检,同时行电切术。结果:97例患者中,19例患者普通白光膀胱镜及荧光膀胱镜下检查均为阴性,剩余78例患者取156处组织进行活检,平均每例患者取2块组织。结果显示97处病理报告为尿路上皮癌。经计算得出荧光膀胱镜的敏感性为91.75%(89/97),特异性为64.41%(38/59);普通白光膀胱镜的敏感性为71.13%(69/97),特异性55.93%(33/59);P<0.05,差异具有统计学意义。结论:荧光膀胱镜在诊断尿路上皮膀胱癌上的敏感性和特异性均显著高于普通白光膀胱镜,具有较高的临床应用价值。     

THP定位诊断早期非肌层浸润性膀胱癌

目的：研究THP（吡柔比星）对非肌层浸润性膀胱癌早期的定位诊断效果。方法：选择35例已诊断膀胱癌或高度怀疑尿路上皮癌患者。病人术前及术后复查时,30mgTHP溶入50m15％葡萄糖液中,灌入已排空的膀胱中,保留15分钟,排出THP,彻底冲洗膀胱。普通膀胱镜检查,有THP吸收的非肿瘤区域取活检,无THP吸收的部位随机活检。结果：35例患者中存在非肌层浸润性膀胱癌早期的共6例。结论：THP对非肌层浸润性膀胱癌早期的定位诊断效果明确,安全性好。     

THP定位诊断早期非肌层浸润性膀胱癌

目的:研究THP(吡柔比星)对非肌层浸润性膀胱癌早期的定位诊断效果。方法:选择35例已诊断膀胱癌或高度怀疑尿路上皮癌患者。病人术前及术后复查时,30mgTHP溶入50ml 5%葡萄糖液中,灌入已排空的膀胱中,保留15分钟,排出THP,彻底冲洗膀胱。普通膀胱镜检查,有THP吸收的非肿瘤区域取活检,无THP吸收的部位随机活检。结果:35例患者中存在非肌层浸润性膀胱癌早期的共6例。结论:THP对非肌层浸润性膀胱癌早期的定位诊断效果明确,安全性好。     

吡柔比星膀胱内灌注预防非肌层浸润性膀胱尿路上皮癌复发的机制

目的 观察膀胱内灌注吡柔比星后对正常膀胱组织和膀胱癌组织细胞凋亡的影响,探讨吡柔比星膀胱内灌注预防非肌层浸润性膀胱尿路上皮癌复发的机制.方法 将40例非肌层浸润性膀胱尿路上皮癌患者随机分为3组,15例于经尿道膀胱肿瘤电切术(TUR-BT)前1h、15例于TUR-BT术前24 h行膀胱内灌注(30 mg吡柔比星,在膀胱内保留30 min),对照组10例仅行TUR-BT术.取患者的正常膀胱组织和膀胱癌组织,以荧光显微镜观察吡柔比星的分布,原位末端标记(TUNEL)法检测细胞凋亡,免疫组化染色检测bcl-2和bax的蛋白表达.结果 吡柔比星膀胱内灌注后1h,正常膀胱组织黏膜层偶见吡柔比星荧光,膀胱癌组织可见弥漫分布的吡柔比星荧光,可达肌层.24 h后,在膀胱癌组织内仍可见到吡柔比星的荧光.TUNEL检测结果显示,实验组膀胱癌的凋亡指数显著高于对照组(P<0.01).bcl-2/bax比值与凋亡指数具有相关性.结论 吡柔比星灌注化疗中可选择性作用于非肌层浸润性膀胱尿路上皮癌.通过影响膀胱癌组织bcl-2/bax表达,诱导肿瘤细胞发生凋亡,可能是吡柔比星膀胱内灌注预防非肌层浸润性膀胱尿路上皮癌复发的重要机制.     

绿激光联合THP术前膀胱灌注对治疗非肌层浸润性膀胱癌的疗效分析

目的：评价经尿道绿激光联合盐酸吡柔比星（THP）术前膀胱灌注对非肌层浸润性膀胱癌的疗效。方法：选取50例非肌层浸润性膀胱癌患者,随机分为绿激光联合术前THP膀胱灌注组28例与单纯绿激光组22例。对两组病变检出率,术后复发率等指标进行比较。结果：两组病例均一次手术成功。绿激光联合术前THP膀胱灌注组对病变检出率、术后复发率与单存绿激光组进行比较,差异有统计学意义（P〈0．05）。结论：绿激光联合术前膀胱灌注盐酸吡柔比星（THP）可提高非肌层浸润性膀胱癌病变检出减少、漏诊漏治,降低术后复发率。     

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。     

绿激光联合THP术前膀胱灌注对治疗非肌层浸润性膀胱癌的疗效分析

目的:评价经尿道绿激光联合盐酸吡柔比星(THP)术前膀胱灌注对非肌层浸润性膀胱癌的疗效。方法:选取50例非肌层浸润性膀胱癌患者,随机分为绿激光联合术前THP膀胱灌注组28例与单纯绿激光组22例。对两组病变检出率,术后复发率等指标进行比较。结果:两组病例均一次手术成功。绿激光联合术前THP膀胱灌注组对病变检出率、术后复发率与单存绿激光组进行比较,差异有统计学意义(P<0.05)。结论:绿激光联合术前膀胱灌注盐酸吡柔比星(THP)可提高非肌层浸润性膀胱癌病变检出减少、漏诊漏治,降低术后复发率。     

尿液中循环肿瘤DNA水平预测非肌层浸润性膀胱癌术后复发及进展的临床价值

目的:探讨尿液中循环肿瘤DNA（circulating tumour DNA,ctDNA）水平在非肌层浸润性膀胱癌（non-muscle-invasive bladder cancer,NMIBC）术后预测复发及进展中的临床价值。方法:选取2017年06月至2019年06月在我院收治的膀胱癌患者96例,均接受经尿道膀胱肿瘤电切术（transurethral resection of bladder tumor,TURBT）,且术后病检均证实为非肌层浸润性膀胱尿路上皮癌。根据术后病检结果分为两组:A组:高级别NMIBC患者46例,B组:低级别NMIBC患者50例。术后每个月测定患者尿液中ctDNA的水平,每3个月复查泌尿系彩超、膀胱镜及尿脱落细胞学检查,每6个月复查膀胱CT;所有患者术后均进行随访,随访期18个月,影像学或膀胱镜检查证实肿瘤临床复发或进展为肌层浸润性膀胱癌（muscle-invasive bladder cancer,MIBC）时即停止随访。结果:在随访期内共有62例患者通过膀胱镜检查或影像学手段证实肿瘤出现了复发或进展,其中A组有36例,B组有26例,两组间差异具有统计学意义（P＜0.05）;在肿瘤复发或进展的62例患者中,A组尿液ctDNA阳性患者27例,B组尿液ctDNA阳性患者21例,差异无统计学意义（P＞0.05）;两组共有63例患者在影像学及膀胱镜检查有异常之前首先从尿液中检测到了ctDNA,其中48例患者在之后的随诊复查中证实肿瘤出现了复发或进展;肿瘤进展组患者尿液中ctDNA水平显著高于复发组,差异具有统计学意义（P＜0.05）。结论:通过液态活检技术动态检测NMIBC术后患者尿液中ctDNA的水平,能更早地发现肿瘤的复发及进展,具有较高的特异性,而且与肿瘤进展存在一定的相关性,可能成为NMIBC术后辅助监测肿瘤早期复发或进展的新手段。     

新型内镜成像技术在膀胱癌诊断中的应用进展

白光膀胱镜检查是诊断及监测膀胱癌的传统方法。然而随着科学技术的不断发展,荧光膀胱镜、窄带成像、共聚焦激光内镜、光学相干断层扫描等新型内镜成像技术的出现,能够提高膀胱癌诊断的灵敏度,且其目的是辅助白光膀胱镜检查提高膀胱癌的诊断及优化临床分期,从而改善预后。     

吉西他滨膀胱灌注预防高危非肌层浸润性膀胱癌术后复发的疗效观察

目的观察吉西他滨膀胱灌注预防高危非肌层性浸润膀胱癌术后复发的疗效。方法90例高危非肌层浸润性膀胱癌经尿道膀胱肿瘤电切(TURBt)术后患者随机分为两组,每组45例,分别采用吉西他滨(治疗组)和吡柔比星(对照组)膀胱灌注。术后定期行膀胱镜检查,观察两组患者肿瘤复发情况及不良反应。结果治疗组患者随访期间有7例复发,总复发率为15.5%;对照组患者随访期间有16例复发,总复发率为35.5%,两组差异有统计学意义(P<0.05)。治疗组发生不良反应10例,对照组发生不良反应9例,主要为尿频、尿急、尿痛和血尿等,对症治疗后缓解,两组患者均未发生严重不良反应。结论 TURBt术后膀胱灌注吉西他滨预防高危非肌层浸润性膀胱癌术后复发的疗效确切,患者耐受性好,是较理想的膀胱灌注化疗药。     

ALA fluorescent diagnosis of bladder cancer

Application of 5-aminolauvulin acid (ALA) fluorescence allows to detect not only exophytic tumors of the bladder but also flat, small tumors-satellites and preneoplastic changes of the bladder. 175 biopsies were performed in 53 patients with suspected superficial tumor of the bladder. 3 hours before surgery all the patients were intravesically instilled 50 ml 3% ALA solution. Cystoscopy employed white and blue light. Visual registration of exophytic masses and red fluorescence of the suspected sites was registered and consequently compared to the histological findings. 96 of 100 sites with malignancy/dysplasia showed red fluorescence. In 13% patients cancer and mucosal dysplasia were detected only under the blue light and were missed by standard cystoscopy. Residual red fluorescence of the resection margins was observed in 41% patients after TUR. Sensitivity of ALA-fluorescent detection reached 96%, specificity 52%. ALA-induced fluorescent diagnosis is more effective than standard cystoscopy. It is most effective in diagnosis of dysplasias, carcinoma in situ, flat, small, multiple superficial tumors of the bladder during primary TUR.     

Detection and clinical outcome of urinary bladder cancer with 5-aminolevulinic acid-induced fluorescence cystoscopy : A multicenter randomized, double-blind, placebo-controlled trial

BACKGROUND:

The medical community lacks results from prospective controlled multicenter studies of the diagnostic efficacy of 5‐aminolevulinic acid (5‐ALA) cystoscopy on tumor recurrence in patients with superficial bladder tumors.

METHODS:

A prospective randomized, double‐blind, placebo‐controlled study was conducted in 370 patients with nonmuscle‐invasive urinary bladder carcinoma who received either 5‐ALA (n = 187) or a placebo (n = 183) intravesically before cystoscopy. Each group underwent cystoscopy under visible white light and under fluorescent light followed by transurethral tumor resection. The primary study objective was to evaluate the 12‐month recurrence‐free survival.

RESULTS:

Slightly more patients with tumors were detected by using 5‐ALA than by using the placebo (88.5% vs 84.7%). The mean numbers of tumor specimens per patient were 1.8 (5‐ALA) and 1.6 (placebo). Intrapatient comparison of fluorescent light versus white light cystoscopy in patients randomized to receive 5‐ALA showed a higher tumor detection rate with fluorescent light than with white light cystoscopy. In patients receiving 5‐ALA cystoscopy, the percentage of lesions that would not have been detected in these patients by white light cystoscopy ranged between 10.9% (pT1) and 55.9% (atypia). Progression‐free survival was 89.4% (5‐ALA) and 89.0% (placebo) (P = .9101), and recurrence‐free survival 12 months after tumor resection was 64.0% (5‐ALA) and 72.8% (placebo) (P = .2216).

CONCLUSIONS:

In comparison to the placebo, 5‐ALA cystoscopy did not increase the rates of recurrence‐free or progression‐free survival 12 months after tumor resection. Although more tumors per patient were detected in the 5‐ALA group, the higher detection rate did not translate into differences in long‐term outcome. Cancer 2011. © 2010 American Cancer Society.     

Feasibility of Photodynamic Diagnosis for Challenging TURBt Cases Including Muscle Invasive Bladder Cancer,BCG Failure or 2nd-TUR

Background: Despite widely adopted standard methods for follow-up including cystoscopy plus cytology,recurrence rates of non muscle-invasive bladder cancer (NMIBC) have not improved over the past decades, stillranging from 60% through 70%. Hence, widely acceptable surveillance strategies with excellent sensitivity areneeded. Early recurrence has led to the development of a novel cystoscopy technique utilizing photodynamicdiagnosis (PDD). Although, no studies have evaluated the efficacy of PDD for patients of MIBC, BCG failure or2nd-transurethelial resection (TUR). Materials and Methods: The present study was performed from October2012 through May 2013. IRB approved 25 patients initially underwent a cystoscopy examination of white lightand blue light followed by the resection of tumors identified. Resections were performed from bladder mucosaareas considered suspicious at PDD, along with PDD negative normal bladder mucosa area resected by randombiopsy. Specimens were divided into two groups, PDD positive and negative. Primary endpoints were sensitivityand specificity. Results: A total of 147 specimens extracted from 25 patients were included in the analysis. Some45 out of 92 PDD-positive specimens were confirmed to have bladder cancer, and 51 out of PDD-negative 55specimens were confirmed to be cancer negative. The sensitivity of PDD was 91.8% (45/49) and specificity was52.0% (51/98). The sensitivity:specificity was 89.5% (17/19) : 47.6% (30/63) in 12 2nd-TUR patients, 90.5%(19/21) : 61.1% (11/18) in seven MIBC patients, and 95.0% (19/20) : 48.5% (16/33) in eight failed BCG cases.Conclusions: PDD-TURBT has high sensitivity to diagnose BC even for 2nd-TUR, MIBC or BCG failure cases.     

Accuracy of Preoperative Urinary Symptoms,Urinalysis, Computed Tomography and Cystoscopic Findings for the Diagnosis of Urinary Bladder Invasion in Patients with Colorectal Cancer

Background: To determine the accuracy of preoperative urinary symptoms, urinalysis, computed tomography (CT) and cystoscopic findings for the diagnosis of urinary bladder invasion in patients with colorectal cancer. Materials and Methods: Records of patients with colorectal cancer and a suspicion of bladder invasion, who underwent tumor resection with partial or total cystectomy between 2002 and 2013 at the Faculty of Medicine Siriraj Hospital, were reviewed. Correlations between preoperative urinary symptoms, urinalysis, cystoscopicfinding, CT imaging and final pathological reports were analyzed. Results: This study included 90 eligible cases (71% male). The most common site of primary colorectal cancer was the sigmoid colon (44%), followed by the rectum (33%). Final pathological reports showed definite bladder invasion in 53 cases (59%). Significant features for predicting definite tumor invasion were gross hematuria (OR 13.6, sensitivity 39%, specificity 73%), and visible tumor during cystoscopy (OR 5.33, sensitivity 50%, specificity 84%). Predictive signs in CT imagingwere gross tumor invasion (OR 7.07, sensitivity 89%, specificity 46%), abnormal enhancing mass at bladder wall (OR 4.09, sensitivity 68%, specificity 66%), irregular bladder mucosa (OR 3.53, sensitivity 70%, specificity 60% ), and loss of perivesical fat plane (OR 3.17, sensitivity 81%, specificity 43%). However, urinary analysis and other urinary tract symptoms were poor predictors of bladder involvement. Conclusions: The present study demonstrated that the most relevant preoperative predictors of definite bladder invasion in patients with colorectal cancer are gross hematuria, a visible tumor during cystoscopy, and abnormal CT findings.     

Diagnostic value of fibronectin and mutant p53 in the urine of patients with bladder cancer: impact on clinicopathological features and disease recurrence

Development of new methods for bladder cancer detection is required because cystoscopy is invasive, and voided urine cytology (VUC) has low sensitivity. The aim of this study was to evaluate the diagnostic performance of urinary fibronectin and mutant p53 in comparison with VUC in the detection of bladder cancer. This study included 100 patients diagnosed with bladder cancer, 93 patients with benign urological disorders and 47 healthy volunteers. The urine supernatant was used for determination of fibronectin by ELISA, while urine sediment was used for cytology and detection of mutant p53 by PCR-SSCP followed by DNA sequencing. The sensitivity and specificity were 59% and 91.4% for VUC, 82% and 84.3% for fibronectin, and 37% and 100% for mutant p53; combination of the three parameters increased sensitivity to 95% but specificity was only 78.6%. A significant association was observed between disease recurrence and mutant p53, stage and lymph node involvement. Our results indicate that fibronectin had the highest sensitivity compared to VUC and mutant p53 in bladder cancer detection; however, mutant p53 had superior specificity compared to VUC and fibronectin. Mutant p53 is associated with disease recurrence and hence it has a significant prognostic role in bladder cancer.     

荧光原位杂交和尿细胞学检查对膀胱癌诊断意义的Meta分析

背景与目的：目前膀胱癌疗效和监测的主要方法是膀胱镜和尿细胞学检查,前者为侵人性检查,令患者感到不适;后者虽无创且特异性高．但敏感性太低,且受主观因素影响大。本研究拟对中、英文有关比较荧光原位杂交（fluorescence in situ hybridization,FISH）和尿细胞学检查诊断膀胱癌研究的结果进行系统分析,以明确FISH对膀胱癌的诊断意义。方法：采用Cochrane系统评价方法,MEDLINE（1966年1月～2008年6月）、EMBASE（1988年1月。2008年6月）、Cochrane图书馆、中国生物医学期刊文献数据库（CMCC,1979年。2008年6月）、CNKI数字图书馆（1979年1月～2008年6月）进行有关FISH和尿细胞学检查诊断膀胱癌文献的检索、质量评价和资料提取,采用MetaDiScl．4软件进行Meta分析。结果：共检索到相关研究242篇,排除230篇,符合纳入标准12篇进入Meta分析,涉及研究对象3430例。异质性检验提示无阈值效应,但存在其它原因导致的异质性。按随机效应模型进行Meta分析．FISH和尿细胞学诊断膀胱癌的准确度指标敏感度、特异度、阳性似然比、阴性似然比以及诊断优势比等汇总及95％C1分别为74％（71％-77％）VS．57％（54％-61％）、88％（86％-90％）VS．85％ （83％-87％）、6．18（3．56～10．73）VS．4．15（2．78～6．20）、0．29（0．19～0．45）VS．0．51（0．41～0．63）及24．17（9．33～62．64）VS．9．59（5．91～15．57）。FISH和尿脱落细胞学检查的敏感度随肿瘤分级、分期的升高而增高。综合受试者工作特征曲线下面积分别为0．8938、0．8247．Q^＊值分别为0．7847、0．7226。结论：FISH诊断膀胱癌的准确度较高,但对高分期的敏感度较细胞学低,目前尚不能取代传统的尿细胞学检查,但可作为膀胱癌术前诊断、术后监测和随访的指标。     

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.     

Assessment of microsatellite instability in urine in the detection of transitional-cell carcinoma of the bladder

Loss of heterozygosity (LOH) and alterations in microsatellite DNA markers have been reported in bladder-cancer tumors. We have studied, in a blinded fashion, using PCR-based microsatellite analysis, genetic alterations of cells exfoliated in urine of 59 Caucasian patients and control patients; 31 with initially confirmed bladder transitional-cell carcinoma (TCC), 17 with signs and symptoms suggestive of bladder cancer, 6 control patients who underwent renal transplantation, and 5 control patients with urolithiasis. Microsatellite analysis of cells exfoliated in the urine allowed the diagnosis of 83% (10/12) of patients with bladder TCC recurrence confirmed by cystoscopy, while 100% of patients followed up for transitional-cell carcinoma of the bladder for up to 12 months without evidence of tumor recurrence upon routine cystoscopy showed no microsatellite alterations. None of the patients without neoplasia (negative controls) had any microsatellite alterations, whereas all patients who underwent renal transplantation had additional new alleles corresponding to contamination with donor's renal and urothelial cells (positive controls). No control patients had any evidence of transitional-cell carcinoma by cystoscopy. Our results provide objective evidence that non-invasive molecular detection of bladder TCC by microsatellite analysis is reproducible with a sensitivity of 83% and a specificity of 100% in Caucasian patients. This non-invasive procedure represents a potential clinical tool for the detection and the screening of bladder TCC. Int. J. Cancer (Pred. Oncol.) 79:629–633, 1998. © 1998 Wiley-Liss, Inc.