吡柔比星膀胱灌注预防浅表性膀胱癌术后复发的疗效观察

目的探讨吡柔比星（THP）膀胱内灌注预防浅表性膀胱癌术后复发的效果。方法患者随机分成两组,一组患者膀胱灌注卡介苗（BCG）（40例）,另一组膀胱灌注THP（40例）,随访6～24个月,观察两组复发情况及不良反应。结果BCG组和THP组2年复发率分别为12．5％（5／40）、14．0％（6／43）;两组间比较差异无统计学意义（x^2=0．038,P〉0．05）,而THP组不良反应发生率明显低于BCG组（x^2=9．565,P〈0．01）。结论膀胱灌注THP预防浅表性膀胱癌术后复发的疗效确切,不良反应小,安全性好。     

膀胱癌经尿道电切除术后吡柔比星膀胱灌注预防复发的临床观察

目的探讨膀胱灌注吡柔比星（THP）预防浅表性膀胱癌术后复发的安全性及疗效。方法对83例浅表性膀胱癌患者行经尿道膀胱肿瘤电切术（TURBT）,术日及术后1周开始用THP（30mg／40m1）进行膀胱内定期灌注,每次药物在膀胱内保留30～60min,每周1次,连续8次,以后每月1次,连续10次,并随访18～45个月。结果83例患者均未见明显全身性药物不良反应,仅15例出现轻微膀胱刺激症状。结论膀胱灌注THP预防浅表性膀胱癌术后复发的疗效确切,不良反应小,安全性好,是较理想的膀胱灌注化疗药物。     

卡介苗素膀胱灌注预防膀胱癌术后复发的临床研究

目的探讨卡介苗素膀胱内灌注预防膀胱癌术后复发的疗效、安全性．方法47例膀胱癌术后患者分2组。分别应用卡介苗素和卡介苗定期行膀胱内灌注，随访10～32个月，了解灌注后肿瘤复发情况及并发症。并于灌注前、后检测2组尿液中IL－2、IL－6、IL－8的变化情况．结果卡介苗膀胱灌注组肿瘤复发4例（17．4％）。副反应发生18例（78．3％），卡介苗素膀胱灌注组肿瘤复发5例（20．8％）。副反应发生率11例（45．8％），2组尿液中IL－2、IL－6、IL－8值灌注后高于灌注前（P〈0．05）．两组肿瘤复发率、IL-2、IL-6、IL-8值灌注前后比较无显著差异，副反应卡介苗组明显高于卡介苗素组（P〈0．05）．结论卡介苗素膀胱灌注预防膀胱癌术后复发的有效率与卡介苗相同，但不良反应明显减少。患者耐受性好，因此卡介苗素可成为膀胱浅表移行上皮细胞癌临床治疗和预防复发的一种有效药物．     

卡介苗素膀胱灌注预防膀胱癌术后复发的临床研究

目的探讨卡介苗素膀胱内灌注预防膀胱癌术后复发的疗效、安全性.方法 47例膀胱癌术后患者分2组,分别应用卡介苗素和卡介苗定期行膀胱内灌注,随访10～32个月,了解灌注后肿瘤复发情况及并发症,并于灌注前、后检测2组尿液中IL-2、IL-6、IL-8的变化情况.结果卡介苗膀胱灌注组肿瘤复发4例(17.4%),副反应发生18例(78.3%),卡介苗素膀胱灌注组肿瘤复发5例(20.8%),副反应发生率11例(45.8%),2组尿液中IL-2、IL-6、IL-8值灌注后高于灌注前(p<0.05).两组肿瘤复发率、IL-2、IL-6、IL-8值灌注前后比较无显著差异,副反应卡介苗组明显高于卡介苗素组(p<0.05).结论卡介苗素膀胱灌注预防膀胱癌术后复发的有效率与卡介苗相同,但不良反应明显减少,患者耐受性好,因此卡介苗素可成为膀胱浅表移行上皮细胞癌临床治疗和预防复发的一种有效药物.     

顺铂注射液膀胱灌注预防膀胱癌术后复发

目的：探讨顺铂(PDD)注射液在预防膀胱癌术后复发中的作用。方法：对行保留膀胱手术治疗的28例膀胱癌患，术后采用PDD注射液60mg／次定期膀胱灌注，总疗程2a。结果：28例均获随访，随访时间20月～37月，平均20．4月。复发2例，复发率为7．1％(2／28)；并发尿道狭窄3例。结论：PDD注射液膀胱灌注预防膀胱癌术后复发具有较好的临床效果及较少的毒副作用，值得临床推广使用。     

膀胱癌术后沙培林膀胱灌注的临床疗效观察

目的　观察沙培林膀胱灌注预防膀胱癌术后复发的疗效及并发症 .方法　 4 2例膀胱癌术后患者应用沙培林定期行膀胱内灌注 ,并随访 8～ 2 4个月 ,了解灌注后肿瘤复发情况及并发症 .结果　肿瘤复发率为 14 .3% (6 /42 ) ,无肿瘤复发率为 85 .7% (36 /42 ) ,并发症发生率为 11.9% (5 /42 ) .结论　沙培林膀胱灌注预防膀胱癌术后复发的有效率高 ,不良反应小 ,患者耐受性好 ,值得临床推广应用 .     

膀胱癌术后沙培林膀胱灌注的临床疗效观察

目的观察沙培林膀胱灌注预防膀胱癌术后复发的疗效及并发症.方法 42例膀胱癌术后患者应用沙培林定期行膀胱内灌注,并随访8～24个月,了解灌注后肿瘤复发情况及并发症.结果肿瘤复发率为14.3%(6/42),无肿瘤复发率为85.7%(36/42),并发症发生率为11.9%(5/42).结论沙培林膀胱灌注预防膀胱癌术后复发的有效率高,不良反应小,患者耐受性好,值得临床推广应用.     

浸润性膀胱癌保留膀胱综合治疗的短期疗效分析

目的:探讨T2N0M0 、T3N0M0原发性浸润性膀胱癌三种不同治疗方案的近期临床疗效.方法:134例原发性浸润性膀胱癌患者,按术式分为3组,单纯治疗组(S组) 56例行单纯保留膀胱手术,术后常规行丝裂霉素或羟基喜树碱膀胱灌注6个月以上,其中T2N0M0 28例,T3N0M0 28例;综合治疗(I组) 37例行保留膀胱手术、术后行静脉吉西他滨和顺铂化疗,并常规行丝裂霉素或羟基喜树碱膀胱灌注6个月以上,其中T2N0M0 16例,T3N0M0 21例;根治组(R组)41例行根治性手术,其中T2N0M0 20例,T3N0M0 21例.比较3组患者的三年总体生存率以及相同临床分期患者的三年生存率.结果:S组三年总体生存率为39.29%,T2N0M0患者三年生存率为42.86%,T3N0M0为39.26%;I组三年总体生存率为70.27% 、T2N0M0患者三年生存率为75.00%、T3N0M0为66.67% ;R组三年总体年生存率为75.61%,T2N0M0患者三年生存率为80.00%,T3N0M0为71.24%.S组与I组间三年生存率比较差异有统计学意义(P＜0.05),I组与R组间比较差异无统计学意义(P＞0.05).结论:T2N0M0 、T3N0M0临床分期的原发性浸润性膀胱癌患者,综合治疗与根治治疗近期临床疗效无统计学差异.因此建议采用保留膀胱的综合方法治疗,以提高患者生活质量.     

经尿道膀胱肿瘤电切术后膀胱痉挛的护理

目的经尿道膀胱肿瘤电切术后膀胱痉挛的患者进行整体护理,针对病人特点制定相应的护理措施,促进恢复,提高生活质量。方法根据病人情况制定详细的护理措施,重视病人的心理护理,严防并发症的发生。结果本组病人恢复良好。结论对经尿道膀胱肿瘤电切术后膀胱痉挛的患者进行整体护理可以给病人的回复创造条件,帮助患者早日康复。     

GSTT1 as a prognosticator for recurrence and progression in patients with non-muscle-invasive bladder cancer

Although polymorphisms in glutathione S-transferase (GST) have been associated with the risk of bladder cancer (BC), few reports provide information about the development of BC. The aim of the present study was to investigate the effect of homozygous glutathione S-transferase-μ (GSTM1) and glutathione S-transferase-&phis; (GSTT1) deletions as prognostic markers in non-muscle-invasive bladder cancer (NMIBC). A total of 241 patients with primary NMIBC were enrolled in this study. GSTM1 and GSTT1 polymorphisms were analyzed by multiplex polymerase chain reaction (PCR) using blood genomic DNA. The results were compared with clinicopathological parameters. The prognostic significance of the GSTs was evaluated by Kaplan-Meier and multivariate Cox regression model. A statistically significant association between genotype and histopathological parameter was not observed. The patients with the GSTT1-positive genotype had significantly reduced recurrence- and progression-free survival than those with the GSTT1-null genotype (log-rank test, p < 0.05, respectively). Recurrenceand progressionfree survival were not related to the GSTM1 genotypes. In multivariate regression analysis, the GSTT1positive genotype was the independent predictor for recurrence [hazard ratio (HR), 1.631; p = 0.043] and progression (HR, 3.418; p = 0.006). These results suggested that the GSTT1 genotype could be a useful prognostic marker for recurrence and progression in NMIBC.     

Chromosomal aberrations associated with invasion in papillary superficial bladder cancer

Non-invasive and invasive papillary transitional cell carcinomas of stages pTa and pT1 represent the first steps of tumour progression in bladder cancer. In order to analyse different chromosomal alterations of pTa and pT1 superficial bladder cancer, 46 tumour specimens were examined by comparative genomic hybridization (CGH). Losses of chromosome 9 material (11/20) and gains of chromosome 17 material (6/20) were frequently found in pTa tumours. Stage pT1 tumours were characterized by gains of chromosome 1q (14/26; including amplification at 1q21–q24 in three cases) and chromosome 17 material (15/26), as well as by losses of 11p (15/26) and 11q (13/26). Other loci frequently showing losses in pT1 tumours were 2q (9/26), 4q (10/26), 5q (9/26), 8p (10/26), 9p (9/26), 9q (12/26), 10q (8/26), 17p (7/26), and 18q (8/26). Amplifications were detected at 8q21/22, 5q21, 7q36, 10p14, 10p12, 10q25, 12q12, and 12q14. The most striking differences between grade 2 pTa and pT1 tumours were gains of 1q (P<0·01) and losses at 2q (P<0·025), 10q (P<0·05), 11p (P<0·01), 11q (P<0·01), and 17p (P<0·05), as well as the total number of aberrations (pTa grade 2: 4·1; pT1 grade 2: 8·6 aberrations per tumour). These data show characteristic chromosomal aberrations associated with invasion in superficial bladder cancer. © 1998 John Wiley & Sons, Ltd.     

膀胱过度活动症及间质性膀胱炎膀胱灌注治疗的研究进展

膀胱过度活动症(overactive bladder,OAB)与间质性膀胱炎/膀胱疼痛综合征(interstitial cystitis/painful bladder syndrome,IC/PBS)是妇科泌尿临床上缺乏特异性诊断指标的两种常见膀胱疾病,均有尿频、尿急、夜尿增多症状,给患者的日常生活、身心健康带去严重困扰,然而其病因均不明确.近年来,随着人们对生活质量要求的提高,OAB及IC/PBS越来越得到重视.     

E-cadherin promoter polymorphism (C-160A) and risk of recurrence in patients with superficial bladder cancer

Tumor recurrence is a hallmark of superficial bladder cancer. Currently, a molecular marker for bladder cancer recurrence is lacking. E-cadherin plays an important role in epithelial development and in the establishment and maintenance of cell-cell adhesion and tissue architecture. The purpose of this study is to investigate the association of an E-cadherin promoter polymorphism (CDH1c-160a) with the risk of bladder cancer recurrence. This study included 302 patients with superficial bladder cancer. Genomic DNA was extracted from peripheral blood lymphocytes and genotyping was performed using Taqman assay. Clinical data were collected by medical chart review. Cox proportional hazard model was used to estimate the hazard ratios (HRs) associated with genotypes while adjusting for age, gender, smoking status, tumor stage and grade where appropriate. During a median follow-up of 27.65 months, 151 patients experienced disease recurrence. Subsequent analyses were restricted to Caucasians only due to the small sample size of other ethnic groups (13 in recurrence group and 15 in non-recurrence group). Among the 274 Caucasian patients, 138 developed recurrence during the same length of follow-up time. In Caucasian patients, having at least one variant A allele conferred a 32% reduction in recurrence risk (adjusted HR: 0.68; 95% CI: 0.48-0.96). The median recurrence-free survival for patients carrying at least one variant A allele was significantly longer than that for patients with a homozygous CC genotype (40.4 vs 12.5 months, p=0.04). Our findings suggest that the E-cadherin promoter polymorphism may be a valuable molecular marker for bladder cancer recurrence.     

荧光原位杂交技术对膀胱癌诊断价值的Meta分析

目的 对已发表的使用荧光原位杂交(FISH)技术对膀胱癌患者的诊断性试验进行系统评价,比较其是否在诊断效能上优于传统的尿液细胞学检查.方法 检索相关文献,根据纳入标准筛选文献,利用Meta-DiSc软件分别计算FISH检查组和细胞学检查组灵敏度、特异度、似然比和诊断性比数比.绘制总受试者工作特征曲线,计算曲线下面积,估计总诊断精确度.结果 有14篇文献被纳入,FISH检测膀胱癌总灵敏度为0.69(95%CI 0.66～0.73),特异度为0.84(95%CI 0.81～0.86),总受试者工作特征曲线的曲线下面积为0.87;细胞学检查检测膀胱癌总灵敏度为0.46(95%CI 0.42～0.51),特异度为0.88(95%CI 0.84～0.90),总受试者工作特征曲线的曲线下面积为0.81.FISH检查在总体诊断效能上与细胞学检查差异无统计学意义(P>0.05).结论 FISH检查对膀胱癌的诊断灵敏度高于细胞学检查,但尚不能证实FISH技术检查膀胱癌对初发患者和随访患者混合构成的人群具有较高价值.     

Local immunostimulation induced by intravesical administration of autologous interferon-gamma-activated macrophages in patients with superficial bladder cancer

We conducted a phase I/II clinical trial of the safety and efficacy of intravesical administration of autologous IFN-gamma-activated macrophages (MAK) in patients with superficial bladder cancer. Monocyte-derived MAK cells were prepared in vitro and patients received six instillations of 1.4 x 10(8) to 2.5 x 10(8) cells, once a week, for five consecutive weeks. Treatment was well tolerated, with seven grade 1 and five Grade 2 protocol-related adverse effects. Nine out of 17 included patients had no recurrences during the year following the first instillation of MAK. The aim of the present study was to search for immune parameters related to local immunostimulation induced by MAK. Monitoring of the patients showed that urinary IL-8, GM-CSF and, to a lesser extent, IL-18 were increased following MAK instillations, with inter-individual differences. The urinary IL-8 level was about 10-fold higher than that observed for other cytokines, and its biological activity was reflected by a concomitant increase of urinary elastase, indicating neutrophil activation and degranulation. We also showed that nine out of 12 patients investigated presented an increase of urinary neopterin, a marker of IFN-gamma-activated macrophages, 7 days after MAK instillation, while serum neopterin levels were almost stable. These results are in line with persistence of activated macrophages in the bladder wall after infusions. Moreover, there was evidence of macrophages in urine smears 2 months after the sixth MAK instillation, and the score of macrophages correlated with the quantity of neutrophils in the urine. Overall, this study provides evidence of a local immunostimulation induced by this novel and safe immunotherapeutic approach of MAK instillations in patients with superficial bladder cancer.     

聚维酮联合阿霉素体外抑制膀胱癌细胞T24生长并预防膀胱癌患者术后复发

目的探讨聚维酮(PVP)联合阿霉素(ADM)对人膀胱癌细胞株T24的作用及预防膀胱癌术后复发的疗效。方法MTT法检测细胞生长抑制率,流式细胞仪检测细胞周期和黏附作用。对231例浅表膀胱癌患者术后膀胱灌注PVP ADM(实验组)或生理盐水 ADM(对照组),观察预防复发效果。结果2·5%PVP作用24h和72h细胞生长抑制率为15·11%和49·57%;7·5%浓度时,抑制率升为35·42%和79·66%。单用0·25mg/LADM作用48h抑制率为39·05%;合用2·5%和7·5%PVP抑制率升为68·51%和88·39%。5%PVP能使T24细胞的G0/G1期比率下降和G2/M期比率上升。PVP能提高抗鼠IgG1对T24细胞的黏附作用。194例患者获随访,实验组复发率明显降低,复发时间明显延长(均P<0·01)。结论PVP通过阻滞细胞周期G2/M期和增强黏附作用来抑制T24细胞生长,与ADM联合具有协同作用。PVP联合ADM膀胱灌注预防浅表膀胱癌术后复发疗效确切,副作用少。     

Bacillus Calmette-Guérin-treated superficial bladder cancer: correlation of morphology with immunophenotyping

Thirty-five biopsies from 19 patients with superficial transitional cell carcinoma of the bladder, treated with intravesical bacillus Calmette-Guérin (BCG), were assessed histologically and immunohistochemically. Pretreatment biopsies were available for comparison in all cases and five cases of non-specific cystitis were also examined. The inflammatory infiltrate was assessed with a streptavidin-biotin-peroxidase method using UCHL1, MT1, LN3, L26, HAM56, MAC387, Leu7 and anti-S100 in paraffin sections, and in 18 specimens were frozen tissues were available, Leu1, 2, 3, 4, 14, OKT10, HLA-DR and anti-Tac antibodies were applied. Post-treatment bladder biopsies showed severe oedema and a variable degree of inflammation. A granulomatous inflammation was seen in 11 cases, with granulomas present in six prostatic biopsies and acid-fast bacilli in two cases. The lymphoid infiltrate in all biopsies were largely T lymphocytes with a predominance of T helper cells present, often as a band-like infiltrate pressing against the residual epithelium, or the denuded bladder surface, and distributed in the vicinity of the granulomas. Activated lymphocytes were prominent in seven cases, although a moderate infiltrate of such cells was seen in all instances. Tac antigen was only occasionally expressed, and in a few NK cells were present among the infiltrates. In eight cases, HLA-DR was expressed in epithelial cells following BCG treatment, whereas all pre-treatment epithelial were negative.     

Humoral response against heat shock proteins and other mycobacterial antigens after intravesical treatment with bacille Calmette–Guérin (BCG) in patients with superficial bladder cancer

Few studies have analysed the antibody response during intravesical BCG immunotherapy for superficial bladder cancer. We have examined the evolution in serum antibody response against several heat shock proteins (hsp), including the recombinant mycobacterial hsp65 and the native protein P64 from BCG, GroEL from Escherichia coli (hsp60 family), recombinant mycobacterial hsp70 and the E. coli DnaK (hsp70 family), against purified protein derivative of tuberculin (PPD) and the AG85 complex of Mycobacterium bovis BCG, as well as against tetanus toxoid in 42 patients with a superficial bladder tumour, 28 treated with six intravesical BCG instillations and 14 patients used as controls. We also analysed the lymphoproliferative response of peripheral blood mononuclear cells against PPD in this population. Data of antibody responses at 6 weeks post BCG were available in all 28 patients, and at 4 month follow up in 17 patients. All patients who demonstrated a significant increase in IgG antibodies against PPD at 4 months follow up had a significant increase already at 6 weeks of follow up. In contrast, IgG antibodies against hsp increased significantly from 6 weeks to 4 months post-treatment. A significant increase in IgG antibodies against PPD, hsp65, P64, GroEL, and hsp70 at 4 months follow up was observed in 10/17, 8/17, 10/17, 4/17 and 8/17 patients. Native P64 protein elicited a higher antibody response than recombinant mycobacterial hsp65. No increase in antibody response was observed against Dnak from E. coli, against AG85 or tetanus toxoid after BCG therapy. An increase in IgG antibodies against P64 at 4 months follow up compared with pretreatment values was found to be a significant predictor of tumour recurrence (P< 0.01). Further studies with a larger number of patients are needed to confirm the value of the antibody response against P64 as a clinical independent prognostic factor.