147例表浅性膀胱癌预后因素分析

目的：探讨表浅性膀胱癌各种因素与患者预后的关系。方法：对147例表浅性膀胱癌进行回顾性分析,结果：147例中,72例术后复发（49％）,术后5年复发率为35．4％,初诊时为多发者,直径大于3cm,分级与分期高的肿瘤术后复发率于单发者,直径小于3cm者,分级,分期低的肿瘤,术后6个月内肿瘤复发者经治疗后肿瘤再次复发的机会高,术后膀胱内灌药可以预防肿瘤复发,结论：肿瘤分级与分期高,多发肿瘤,直径大于3cm者及术后膀胱内未灌药者复发率高。     

表浅性膀胱癌预后与癌肿数目、病理分级的关系

目的探讨表浅性膀胱癌肿块数目、病理分级与患者预后的关系。方法对122例表浅性膀胱癌进行回顾性分析。结果122例中,40例术后复发,术后5年内的复发率为32.79%。初诊时肿瘤为多发者即3个及3个以上肿瘤、G3级的肿瘤术后复发的平均时间、5年内的复发率分别高于单发或双发者、G1或G2级的肿瘤。结论膀胱癌肿瘤数目、细胞分级是影响表浅性膀胱癌预后的重要因素,多发肿瘤、G3级肿瘤可能在较短时间内复发,及时行膀胱切除更为妥当。     

羟基喜树碱膀胱灌注预防表浅性膀胱癌术后复发

表浅性膀胱癌是泌尿系统常见肿瘤之一,其术后复发率高,三年内复发率可达40％～70％,其中以术后第一年复发率为最高。预防术后复发是根治表浅性膀胱癌的一个重要难题。我院自1995年2月～1998年8月共收治表浅性膀胱癌33例,经开放手术或TURBt术后膀胱内灌注羟基喜树碱(HCPT),疗效较为满意。报告如下: 1 材料和方法 1.1 临床资料 全组33例表浅性膀胱癌,男25例,女8例。年龄34岁～90岁,平均66.5岁。膀胱壁病灶为单发者26例,多发者7例。手术时为初发者28例,复发者5例。33例均在灌注前行手术治疗,其中膀胱部分切除术31例,TURBt术2例。经病理证实均为膀胱移行细胞癌,其病理分级:Ⅰ级9例,Ⅱ级12例,Ⅲ级12例。     

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.     

肌层非浸润性膀胱癌术后即刻单次灌注吡柔比星与多次灌注疗效的比较

目的: 比较肌层非浸润性膀胱癌经尿道膀胱肿瘤电切术(transurethral resection of bladder tumor,TUR-Bt)后即刻单次膀胱内灌注吡柔比星(pirarubicin,THP)与术后2周开始多次灌注方案对预防肿瘤术后复发的疗效及安全性.方法: 2003年3月-2005年6月162例肌层非浸润性膀胱癌被随机分为2组:术后即刻单次灌注组(RG组)80例,术后2周起多次定期灌药组(CG组)82例,比较2组肿瘤的复发率和不良反应.结果: 共6例失随访,有效随访病例2组各78例,随访期24～48个月.RG组20例肿瘤复发、CG组14例复发,差异无统计学意义.RG组中病理级别较高的G 2、G 3级肿瘤复发率42.5%(17/40),CG组中G 2、G 3复发率20.9%(9/43),多次灌药组复发率低于术后即刻单次灌药组.结论:与术后2周开始多次定期灌药化疗相比,术后即刻单次灌注化疗预防肿瘤复发的总体效果可能相似.但对于病理级别较高的肌层非浸润性膀胱癌(G2和G3),多次灌药也许可更好地减少术后肿瘤复发率.     

同期经尿道电切术治疗膀胱癌合并良性前列腺增生的临床分析

目的探讨同期经尿道切除膀胱肿瘤和前列腺治疗表浅性膀胱癌合并良性前列腺增生症的手术安全性和临床疗效。方法 72例表浅性膀胱癌合并良性前列腺增生症患者,先行经尿道膀胱肿瘤电切术(TURBT)切除肿瘤后同期行经尿道前列腺电切术(TURP)切除前列腺。结果患者均顺利完成手术,无膀胱穿孔和电切综合征发生,术后随访14～54个月,平均24个月,35例发生膀胱肿瘤复发,平均复发时间16个月,复发部位均不在膀胱颈口和前列腺尿道,全部再次行TURBT。结论同期经尿道切除膀胱肿瘤和前列腺治疗表浅性膀胱癌合并良性前列腺增生症手术安全、短期疗效确切,可适用于一部分年龄较大伴有严重的下尿路梗阻的且肿瘤分期、分级低的表浅性膀胱肿瘤患者。     

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。     

浅表性膀胱癌二次经尿道电切的意义

目的:探讨对表浅性膀胱癌实施二次经尿道膀胱肿瘤电切术的指征和意义。方法:以确立的二次经尿道膀胱肿瘤电切术入选标准对126例表浅性膀胱癌患者实施手术,满足条件的81例患者中32例拒绝二次手术为A组,49例在术后4周行二次经尿道膀胱肿瘤电切术为B组,2组患者术后膀胱灌注相同。所有患者随访2年,比较2组间膀胱肿瘤进展率和复发率。结果:A组患者在术后2年随访中共有14例出现复发,分别为术后半年3例,1年内8例,1年至2年间6例。B组的16.3%（8/49）患者在第二次手术时发现肿瘤。2年随访期间复发8例,其中1年内3例,1年后5例,2组间在肿瘤复发上有统计学差异。结论:二次经尿道膀胱肿瘤电切术能降低非肌层浸润性膀胱癌患者的肿瘤复发;切除标本中有无肌层是明确手术切除彻底的标志。经尿道膀胱肿瘤电切术需要经验丰富的医师实施。     

33例膀胱内灌注吡柔比星预防浅表性膀胱癌术后复发疗效观察

目的评价吡柔比星(THP)膀胱内灌注预防浅表性膀胱癌术后复发的近期疗效和不良反应。方法对33例浅表性膀胱癌患者行经尿道膀胱肿瘤电切术(TURBT),术后2周THP30mg膀胱灌注,每周1次,共8次;以后每月1次,共10个月,随访期间内行膀胱镜检查。结果30例可评价疗效,无肿瘤复发28例,复发2例,复发率为6.7%;发生不良反应者12例(40.0%),均为不同程度膀胱刺激症状。结论THP膀胱内灌注预防浅表性膀胱癌术后复发近期疗效满意,不良反应小,耐受性良好。     

膀胱偶发肿瘤的的诊断与治疗

背景与目的：膀胱偶发肿瘤的国内外报道较少，有必要总结一下膀胱偶发肿瘤的临床特点，以提高膀胱偶发肿瘤的诊治水平。方法：回顾性分析11例膀胱偶发肿瘤的临床资料。常规体检B超发现6例，膀胱镜下置放或拔双J管发现3例，经尿道前列腺电切（TURP）术中发现2例，肿瘤直径0．2～1．5cm。结果：11例均行经尿道膀胱肿瘤电切（TURBT）术，术后病理：乳头状瘤1例，内翻性乳头状瘤2例，乳头状低度恶性倾向的尿路上皮肿瘤3例，低级别的乳头状尿路上皮癌5例。所有膀胱癌患者TURBT术后接受即刻单剂膀胱灌注化疗，术后定期膀胱镜复查。随访半年至10年，复发1例。结论：膀胱偶发肿瘤中膀胱癌多见，但恶性程度低，肿瘤表浅,预后良好，术后复发率低。     

The immunomodulating effect of interferon-gamma intravesical instillations in preventing bladder cancer recurrence.

PURPOSE: The purpose is to investigate the prophylactic effect of intravesically instillated recombinant IFN-gamma against recurrence of superficial transitional cell carcinoma of the bladder and to evaluate its effect in local immune response, presumably mediating its therapeutic efficacy. EXPERIMENTAL DESIGN: We prospectively randomized in two groups 123 patients with initially diagnosed superficial transitional cell carcinoma and stage Ta, T1, grade 2 tumors, who underwent transurethral tumor resection (TUR). In group A, 60 patients received IFN-gamma (1.5 x 10(7) IU/instillation), whereas 63 patients, consisting of the control group B, received mitomycin C (40 mg/instillation). The annual administration schedule consisted of eight weekly followed by four biweekly and then by eight monthly instillations for both regimens. We also analyzed the immunophenotype of the intratumoral and intramural leukocytes by immunohistochemical and flow-cytometric techniques. To this purpose, tumor samples were obtained at TUR and random biopsies at TUR and during cystoscopy at 6 and 12 months, and bladder washings were collected before TUR and at preselected time points. RESULTS: In group A, 44 of 60 (73.4%) patients, and in group B, 36 of 63 (57.2%) patients, were tumor free during the median follow-up period of 26.5 months (range, 3-49 months). IFN-gamma was well tolerated. Six months after starting treatment, follicular cystitis was detected in patients responding to IFN-gamma. After IFN-gamma instillations, statistically significant increases in T cells, T-helper cells, T-cytotoxic cells, natural killer cells, and total leukocytes, as well as in the number of B cells expressing intercellular adhesion molecule-1 and total leukocytes expressing HLA-DR, were observed by flow cytometry in tissue specimens and bladder washings. CONCLUSIONS: Recombinant IFN-gamma appears to be effective against stage Ta, T1, grade 2 bladder tumors' recurrence. Recruitment and activation of intramural leukocytes seem to be involved in the mechanism of IFN-gamma action.     

MRP-1/CD9和HSP60在膀胱癌中的表达

目的:探讨MRP-1/CD9和HSP60的表达与膀胱癌发生发展的关系.方法:应用免疫组织化学技术(SP法)检测CD9和HSP60在75例膀胱移行细胞癌标本,15例正常膀胱组织中的表达.结果:CD9和HSP60在正常膀胱组织均高表达,41.2%和42.7%的膀胱癌对CD9和HSP60显示了表达减低.不同临床分期和病理分级的膀胱癌中CD9的表达有差异(P＜0.05),根据预后表浅性膀胱癌的复发浸润组和非浸润组中CD9和HSP60表达有差异(P＜0.05).结论:CD9和HSP60可能与膀胱癌的发生发展有关,它们可能作为判断膀胱癌预后的新指标.     

Intravesical adjuvant chemotherapy for superficial transitional cell bladder carcinoma: results of a randomized trial with epirubicin comparing short-term versus long-term maintenance treatment

PURPOSE: Intravesical instillation of epirubicin (EPI) is one of the most effective adjuvant therapies for non-muscle-invasive bladder cancer after transurethral resection. We evaluated the optimal duration of EPI instillation in a multi-institution prospective randomized clinical study. METHODS: Between June 1995 and May 1998, a total of 125 patients with superficial bladder cancer (transitional cell carcinoma grade 1 or 2) were enrolled in this study, and 102 patients were fully evaluated for recurrence. Two protocols for intravesical therapy (arm A - 30 mg EPI/30 ml saline 19 times over 1 year; arm B - 30 mg EPI/30 ml 12 times over 5 months) were established. Instillations were given every week for 4 weeks and then every 2 weeks for 4 months in arm B. After 5 months of treatment, maintenance was performed with seven further instillations (one every month for 7 months) in arm A. The analyzed background factors were the therapeutic method, gender, history (primary or recurrent tumor), stage (T classification), grade, number of tumors, and tumor size. RESULTS: There were no significant differences in the analyzed background factors between the two arms, and there were no serious side effects in the study. In an intent-to-treat analysis, the overall 3-year recurrence-free survival rates were 48.5% in arm A and 55.1% in arm B. The difference between the two groups was not significant. CONCLUSIONS: This analysis indicated that extended prophylactic maintenance instillation of EPI was not significantly effective in reducing bladder cancer recurrence.     

Maintenance therapy for superficial bladder cancer

Transurethral resection remains the standard for first-line treatment of transitional cell carcinoma of the bladder. This technique clearly defines the pathologic grade and is essential in determining the clinical stage of the bladder tumor. Intravesical therapy is an important adjunct to transurethral resection in the management of patients with superficial bladder cancer, many of whom are at risk for disease recurrence and progression. Pharmacotherapy consisting of cytotoxic and immunomodulating agents has demonstrated utility against superficial transitional cell carcinoma. Bacillus Calmette-Guérin and mitomycin (Mutamycin) remain the more commonly used and most effective agents in the prophylaxis against recurrence and progression of superficial bladder transitional cell carcinoma. Many studies have examined their efficacy at different schedules. This article reviews the traditional intravesical agents that are useful in the therapy and prophylaxis of superficial transitional cell carcinoma of the bladder. It also addresses their long-term efficacy when used as maintenance therapy in higher-risk patients.     

Intravesical therapy for superficial bladder cancer

Approximately 54,400 new cases of transitional cell carcinoma of the bladder were reported in the United States in 1999, with an estimated 12,500 deaths attributable to this cancer. Close to 75% of all bladder tumors are confined to the urothelium (stage Ta, or carcinoma in situ), and nearly 30% of papillary tumors invade the lamina propria (stage T1). The majority of superficial tumors are low grade with low rates of progression. Transurethral resection is the standard initial treatment for transitional cell carcinoma. Intravesical therapy is an important adjunct to transurethral resection in patients with superficial bladder cancer, many of whom are at risk for disease recurrence and progression. Cytotoxic and immunomodulating agents and, more recently, photosensitizers have demonstrated utility against superficial transitional cell carcinoma. Many studies have assessed and continue to examine the efficacy of various agents at different doses and in different combinations and schedules. Recently, valrubicin (Valstar) won Food and Drug Administration (FDA) approval only for the treatment of refractory carcinoma in situ. However, bacillus Calmette-Guérin (BCG) and mitomycin (Mutamycin) remain the most commonly used, most effective agents available for prophylaxis against recurrence and subsequent progression of superficial bladder cancer. This article reviews traditional and alternative intravesical agents useful in the therapy and prophylaxis of superficial transitional cell carcinoma of the bladder.     

Superficial bladder cancer: the primacy of grade in the development of invasive disease

Tumor characteristics thought to predict for development of deep muscle invasion after resection of superficial bladder cancer were retrospectively analyzed in 252 patients with transitional cell carcinoma of the bladder at Stanford University Medical Center. Stage 0 patients accounted for 190 of the patient population (75.5%), while stage A and B1 comprised 51 (20%) and 11 (4.5%), respectively. The median follow-up time was 62 months. Forty-three patients subsequently developed deep muscle invasion; these included 24 (12.6%), 14 (27.5%), and 5 (45.5%) of stage 0, A, and B1 patients (P = .002), or 15 (10%), 15 (9%), and 13 (33%) of grade 1, 2, and 3 tumors (P = .001), respectively. When analyzed by univariate logistic regression, grade (P = .0001) and stage (P = .0118) were significant predictors for invasive disease. Site of tumor and number of tumors at presentation were not significant factors for invasion deep into the bladder wall. When multiple logistic regression was performed, only grade remained as a significant tumor variable to predict for invasive disease (P less than .0091). Risk of invasive disease did not appear to increase with increasing number of recurrences, remaining at approximately an 11% invasion rate through 12 recurrences. In this analysis, grade was the most significant tumor variable in superficial bladder cancer predicting for the development of invasive carcinoma. Future clinical trials for definitive or adjuvant therapy of this disease must stratify for this variable.     

诱导式卡介苗膀胱灌注预防膀胱癌术后复发的效应

背景与目的:膀胱灌注疗法是预防浅表性膀胱癌术后复发的重要辅助措施.但是复发率仍然较高.本研究旨在评价联合应用羟基喜树碱(hydroxycamptothecin,HYD)和卡介苗(bacillus Calmette-Guerin,BCG)膀胱腔内灌注对预防膀胱癌术后复发的疗效.方法:45例膀胱乳头状移行细胞癌患者行经尿道电切术或膀胱部分切除术后分为两组:联合治疗组24例,术后1周内行HYD膀胱腔内单次灌注,第2周后开始定期行腔内灌注BCG;BCG组21例,术后1周开始灌注BCG,并定期进行灌注治疗.定期膀胱镜检查、尿细胞学检查和随访.结果:45例术后随访24个月,BCG组3例分别于术后2、10、12个月复发,复发率14.28%(3/21).其余18例未见复发;联合治疗组未见复发,两组比较,差异有统计学意义(P<0.05).两组均无严重不良反应和并发症.结论:HYD早期单次膀胱内灌注联合BCG定期膀胱内灌注的免疫化学疗法对预防膀胱乳头状移行细胞癌术后复发疗效较好.不良反应不明显.有较高的临床应用价值.     

MIB-1 as a proliferative marker in transitional cell carcinoma of the bladder: clinical significance and comparison with other prognostic factors

BACKGROUND: Staging and grading of transitional cell carcinoma of the bladder are generally viewed as indicators of prognosis and form the basis of therapy, but they do not predict outcome accurately. This study was designed to evaluate the value for predicting recurrence, progression, and survival of proliferation fraction in transitional cell carcinoma of the bladder determined by immunostaining of histopathologic specimens with the monoclonal antigen MIB-1. METHODS: In a prospectively followed group of 301 patients with transitional cell carcinoma of the bladder, formalin fixed tumor specimens were immunostained and the MIB-1 labeling index was determined. Crude survival, progression free survival, and recurrence free survival (for patients with Ta and T1 tumors) were assessed in univariate and multivariate analysis according to stage, grade, mitotic index of the tumor, and patient age. The median value of continuous variables was used as a cutoff point in statistical analysis. RESULTS: In univariate analysis there was a strong association between all included factors and crude survival, progression free survival, and recurrence free survival with a median follow-up period of 60 months. In multivariate analysis, crude survival and progression free survival were determined by stage (P = 0.0001) and age (P = 0.0001). Recurrence free survival for patients with Ta and T1 tumors was determined by MIB-1 labeling index (P = 0.0317), mitotic index (P = 0.0229), and age (P = 0.0001). CONCLUSIONS: MIB-1 immunostaining in transitional cell carcinoma of the bladder correlated well with grade, stage, and clinical outcome. In multivariate analysis, proliferation fraction had prognostic value in predicting recurrence free survival for patients with Ta and T1 tumors, whereas stage and age appeared to be predictors of progression free survival.     

Flow cytometric analysis of DNA content in human bladder tumors and irrigation fluids

Flow cytometry (FCM) was used to study the DNA distribution of 99 tumor biopsy specimens and 41 bladder irrigation samples from patients with transitional cell carcinoma of the bladder. For tumor biopsy and cystectomy specimens, the frequency of aneuploidy increased with advancing tumor stage and grade. All T0 tumors were diploid. Twenty-seven percent of T1, 71.4% of T2, and 75% of T3 and T4 tumors were aneuploid. All Grade I tumors were diploid. Thirty percent of Grade II and 76.9% of Grade III tumors were aneuploid. The frequency of aneuploidy of tumors in the early stages (Ta, T1) is similar to the incidence of subsequent progression by these tumors described in the literature. For irrigation fluids, the relationship between grade and stage and the frequency of aneuploidy was similar to the relationship seen with tumor specimens. All four patients with only carcinoma in situ had aneuploid cells in their irrigations. The comparison of FCM data of bladder biopsy and bladder irrigation from the same cystoscopic evaluation suggests adequate representation of tumor cells in the irrigation fluids for almost all cases. The authors conclude that DNA ploidy analysis by FCM appears useful in a clinically important group of patients with aneuploid superficial tumors of moderate or high grade. Bladder irrigation analysis appears useful in the follow-up of patients with a history of carcinoma in situ and those with aneuploid tumors.