三种灌注药物预防膀胱癌术后复发的疗效观察

探讨几种常用灌注药物预防膀胱癌术后复发的疗效。方法：将９３例患者分为３组，第一组用丝裂霉素Ｃ２０ｍｇ，第二组用卡介苗６０ｍｇ，第三组用ＢＣＧ６０ｍｇ加白细胞介素－２（ＩＬ－２）１００００ｕ行膀胱灌注。结论丝裂霉素Ｃ、ＢＣＧ及ＢＣＧ加ＩＬ－２膀胱灌注预防膀胱癌术后复发，疗效十分肯定，其中ＢＣＧ加ＩＬ－２灌注效果更好。     

卡介苗加白细胞介素2膀胱内灌注对外周血自然杀伤细胞,T淋？…

目的 观察膀胱肿瘤患者的细胞免疫状态及卡介苗（ＢＣＧ），白细胞介素（ＩＬ－２）联合膀胱腔灌注对其影响。方法 用＾３Ｈ－ＴｄＲ掺入法测定自然杀伤细胞（ＮＫ）活性，免疫荧光法测定Ｔ淋巴细胞亚群，ＢＣＧ，ＩＬ－２灌注前后动态观察，进行对比研究。结果 膀胱肿瘤病人外周血ＮＫ活性，Ｔ４细胞，Ｔ４／Ｔ８比值明显低于对照组，经ＢＣＧ，ＩＬ－２膀胱灌注治疗后，ＮＫ活性，Ｔ４细胞，Ｔ４／Ｔ８比值增高，ＮＫ活性，Ｔ４     

生物疗法预防膀胱癌术后复发

为评价ＢＣＧ及ＩＬ２在预防膀胱癌术后复发中的作用，联合应用ＢＣＧ膀胱灌注加ＩＬ２肌注预防膀胱癌术后复发（Ａ组）并与丝裂霉素Ｃ（Ｂ组）随机对照观察。Ａ组１４例，随访１８～２６个月，无１例复发。Ｂ组１４例，随访１５～２９个月，４例复发，两组比较有显著性差异。Ａ组治疗后外周血ＮＫ活性、ＬＡＫ活性、ＣＤ３细胞数均较治疗前有显著性升高（Ｐ＜００５），ＣＤ４细胞数，ＣＤ４／ＣＤ８值治疗后均有提高趋势。结果表明：联合应用ＢＣＧ及ＩＬ２可显著提高肌体免疫细胞功能，是预防膀胱癌术后复发较理想的疗法。     

BCG和IL－2膀胱灌注预防膀胱癌复发的疗效观察

为了解ＢＣＧ＋ＩＬ－２联合应用膀胱灌注预防膀胱癌术后复发的疗效，将６０例膀胱癌随机分为两组：一组用ＢＣＧ６０ｍｇ（常用量的１／２）＋ＩＬ－２１００００Ｕ，一组用丝裂霉素Ｃ２０ｍｇ行膀胱内灌注。随访１０～４８个月，平均３３个月，无肿瘤复发者ＢＣＧ＋ＩＬ－２组２６例（８６．７％），丝裂霉素Ｃ组２３例（７６．７％），两组比较有显著性差异。ＢＣＧ＋ＩＬ－２组除有２４小时后自限性的轻微膀胱刺激症状外，无骨髓抑制等全身毒副反应。结果表明，ＢＣＧ＋ＩＬ－２较丝裂霉素Ｃ能更有效地防止膀胱癌术后复发，且可减少ＢＣＧ剂量。     

卡介苗防治膀胱肿瘤原位免疫细胞活化的研究

采用免疫组化技术及单克隆抗体Ｔａｃ（抗ＩＬ－２受体），Ｉ２（抗ＨＬＡ－ＤＲ抗原）及ＯＫＴ９（抗ＴＦＲ），对１７例膀胱肿瘤和２３例术后预防肿瘤复发者卡介苗（ＢＣＧ）灌注后膀胱原位单核细胞中免疫细胞的活化进行研究。ＢＣＧ灌注后，膀胱粘膜上皮出现大量ＤＲ＾＋抗原表达，膀胱粘膜上皮细胞成为抗原递呈细胞，可能是ＢＣＧ抗膀胱癌重要作用机理之一。ＢＣＧ灌注后，膀胱粘膜固有层单核细胞中的Ｔａｃ＾＋，Ｉ２＾＋，Ｔ９     

膀胱切缘注射白细胞介素2及术后灌注白细胞介素2加卡介苗预 …

目的：寻找预防膀吕术后复发的更有效方法。方法：采用术中膀胱切缘注射白细胞介素２（ＩＬ－２）和术后灌注ＩＬ－２加卡介苗（ＢＣＧ）治疗３３例膀胱癌患者。结果：随访４￣７７个月，复发率为９．１％。结论：采用此法预防膀胱癌术后复发安全有效。     

BCG和IL—2膀胱灌注预防膀胱癌复发的疗效观察

为了解ＢＣＧ与白介素２（ＩＬ２）联合应用膀胱灌注预防膀胱癌术后复发的疗效，将６８例膀胱癌随机分为两组：一组用ＢＣＧ１５０ｍｇ＋ＩＬ２１００００Ｕ，另一组单用ＢＣＧ１５０ｍｇ行膀胱内灌注。随访３～７５个月，平均３９．６个月，无肿瘤复发者ＢＣＧ＋ＩＬ２组３２例（９４％），单用ＢＣＧ组２８例（８２％），两组比较有显著性差异（Ｐ＜０．０１）。结果表明：ＢＣＧ与ＩＬ２联合应用能更有效地防止膀胱癌术后复发。     

膀胱癌患者血清可溶性白细胞介素2受体的表达及其意义

对２４例膀胱移行细胞癌患者手术前后不同时期可溶性白细胞介素２受体（ＳＩＬ－２Ｒ）表达水平、白细胞介素２（ＩＬ－２）产生能力以及自然杀伤细胞毒因子（ＮＫＣＦ）活性进行了动态观察。结果表明，膀胱移行细胞癌患者ＳＩＬ－２Ｒ表达水平明显高于正常人，且ＳＩＬ－２Ｒ随肿瘤分期增高而逐渐升高；膀胱癌患者ＩＬ－２产生能力、ＮＫＣＦ活性明显低于正常人。术后膀胱移行细胞癌患者免疫功能呈现一个暂时抑制到逐渐恢复的过程。提示机体免疫功能变化与膀胱移行细胞癌的预后密切相关     

卡介苗膀胱灌注后尿后尿白细胞介素2及肿瘤坏死因子含量测？…

目的：寻找能早期评估表浅膀胱癌术后行卡介苗（ＢＣＧ）免疫治疗效果的精确指标。方法：分析采用ＣＴＬＬ－＾３Ｈ－ＴｄＲ掺入法及夹心法酶联免疫吸附试验，测定３２例表浅膀胱癌术后行ＢＣＧ膀胱灌注者尿液中白细胞介素２（ＩＬ－２）及肿瘤坏死因子（ＴＮＦ）含量。结果：全部病例均获随访２６￣６７个月，平均４３．５个月。３２例中有６例复发（１８．７％），复发患者灌注后尿液中ＩＬ－２及ＴＮＦ含量分别为（１４．３４±６     

IL-2联合BCG膀胱灌注预防膀胱癌复发的机理研究

为探讨ＩＬ２联合ＢＣＧ膀胱灌注预防膀胱癌术后复发的机制，对比研究了ＩＬ２和ＢＣＧ联合灌注与单用ＢＣＧ灌注前后患者血、尿中ＴＮＦα水平的动态变化，并测定ＩＬ２对膀胱癌ＢＩＵ８７细胞株细胞膜ＴＮＦα受体的影响。结果发现：联合灌注组的ＴＮＦα水平显著高于ＢＣＧ组，且ＩＬ２诱导后细胞膜ＴＮＦα受体表达明显增加。提示联合灌注组机体的细胞免疫功能得到更好的改善，ＩＬ２增加了肿瘤细胞对免疫反应的应答，二者间有免疫促进及协同作用。     

吡柔比星加卡介苗膀胱灌注预防肿瘤复发的效果及尿中IL-8变化的临床意义

目的 比较吡柔比星（THP）加卡介苗或单用卡介苗膀胱灌注预防膀胱肿瘤复发的疗效，并测定灌注后IL-8的变化，探讨其与疗效的关系。方法对62例膀胱部分切除术后患者分别给予THP加卡介苗或单用卡介苗膀胱灌注预防复发，用酶联免疫学方法测定灌注前后尿中IL-8的浓度。赔果联合用药组复发率明显低于单用BCG组，两组灌注后尿中IL-8的浓度均有明显的变化，但两组之间无显著性差别。结论THP加BCG膀胱灌注可有效降低膀胱肿瘤复发率，而这一效果是作用机制不同药物的叠加作用，而不是化疗药物对免疫药物疗效的放大作用。     

膀胱内灌注纤维蛋白溶解抑制药物对卡介苗抗膀胱癌复发作用影响的临床研究

目的探讨膀胱内灌注纤维蛋白溶解抑制药物增强卡介苗（BCG）预防膀胱癌术后复发的疗效。方法将208例浅表性膀胱移行细胞癌（BTCC）患者术后随机分成5组，A组44例，定期膀胱内灌注BCG100～120mg＋氨甲苯酸（PAMBA）0．1g＋生理盐水，B组4l例，灌注BCG50～60mg＋PAMBA0.1g＋生理盐水，C组4l例，灌注BCG100～120mg＋氨基己酸（EACA）2．0g＋生理盐水，D组39例，灌注BCG50～60mg＋EACA2．0g＋生理盐水，E组43例，灌注BCG100～120mg＋生理盐水。每周1次，6次后每月1次。灌注后每3个月作膀胱镜检查，必要时取活检明确肿瘤有无复发。结果随访4～58个月，平均22个月，A～E组BTCC复发率分别为10．3％、8．6％、9．7％、9．7％和29．7％。A、B、C、D各组抗BTCC复发的疗效均明显优于E组（对照组），差异有统计学意义（P〈0．05）；B、D组预防BTCC术后复发的效果与A、C组比较差异无统计学意义。结论膀胱内灌注纤维蛋白溶解抑制药物PAMBA、EACA可增强BCG预防膀胱癌术后复发的疗效，BCG剂量减半后，疗效不降低。     

膀胱内灌注纤维蛋白溶解抑制药物对卡介苗预防膀胱癌复发的影响

目的 探讨纤维蛋白溶解抑制药物作为卡介苗（BCG）的佐剂与BCG联合膀胱内灌注治疗对BCG预防膀胱癌术后复发的影响。方法 将行手术治疗后的326例浅表性膀胱移行细胞癌（BTCC）患者随机分成A组[66例,其中经尿道膀胱肿瘤电切术（TURBT）59例、膀胱部分切除术7例]、B组（64例,其中行TURBT60例,膀胱部分切除术4例）、C组（65例,其中行TURBT61例、膀胱部分切除术4例）、D组（64例,其中行TURBT59例、膀胱部分切除术5例）及E组（67例,其中行TURBT61例、膀胱部分切除术6例）,A组患者术后定期膀胱内灌注BCG 100～120mg＋氨甲苯酸（PAMBA）0．1g,B组灌注BCG 50～60mg＋PAMBA0．1g,C组灌注BCG100～120mg＋氨基己酸（EACA）2．0g,D组灌注BCG 50～60mg＋EACA2．0g,E组灌注BCG 100～120mg,每周1次,6次后每月1次。灌注后每3个月行膀胱镜检查。结果 术后随访4～69个月,平均28．5个月,A、B、C、D组膀胱癌的复发率分别为12％（7／59）,10％（6／58）,9％（5／54）和9％（5／56）,低于E组的30％（17／57）,差异均有统计学意义（x。值分别为5．699,6．818,7．380,7．867,P值分别为0．017,0．009,0．007,0．005）;BCG剂量减少的B、D组复发率与A组、C组比较,差异无统计学意义（P〉0．05）,毒副反应发生率B、D组分别为3％（2／60）、5％（3／59）,较A、C组的11％（7／66）、13％（8／62）降低。结论 纤维蛋白溶解抑制药物PAMBA、EACA可作为BCG的佐剂,与BCG联合膀胱内灌注治疗可增强BCG预防膀胱癌术后复发的疗效,BCG剂量减半后疗效不降低。     

膀胱癌经尿道电切除术后吡柔比星膀胱灌注预防复发临床观察

目的:探讨吡柔比星膀胱内灌注预防膀胱癌术后复发的疗效、安全性。方法:45例膀胱癌经尿道电气化术后患者分2组,分别用吡柔比星和卡介苗定期行膀胱内灌注,随访10～33个月,了解灌注后肿瘤复发情况及并发症。结果:卡介苗组复发率为13.6%(3/22),副反应率为81.8%(18/22);吡柔比星复发率为13.0%(3/23),副反应率为91.3%(21/23),两组肿瘤复发率、并发症无显著差异,但卡介苗严重副反应高于吡柔比星(P<0.05)。结论:吡柔比星膀胱灌注预防膀胱癌复发的有效率与卡介苗相同,但严重副反应明显减少,是一种有效的药物。     

Urinary interleukin-8 predicts the response of standard and low dose intravesical bacillus Calmette-Guerin (modified Danish 1331 strain) for superficial bladder cancer

PURPOSE: We determined whether the proinflammatory cytokine interleukin-8 (IL-8) can serve as a predictor for the response to standard (120 mg.) and low (40 mg.) dose intravesical bacillus Calmette-Guerin (BCG) (modified Danish 1331 strain) for managing superficial bladder cancer in patients at risk for recurrence and progression. MATERIALS AND METHODS: We randomized 26 patients with superficial bladder cancer to receive a 6-week course of standard dose 120 mg. or low dose 40 mg. intravesical BCG. Voided urine samples were collected immediately before and after (2 and 4 hours) BCG instillation. Urine samples were centrifuged at 1,500 rpm for 8 minutes and stored at -80C. IL-8 was measured using a commercial enzyme-linked immunosorbent assay. Patients were monitored for recurrence, progression and side effects of BCG treatment at 3-month intervals. RESULTS: At a median followup of 24 months (range 12 to 30), 5 and 6 patients who received a standard and low dose, respectively had disease recurrence and/or progression (nonresponders). At 4 hours after BCG mean Il-8 levels plus or minus SD were significantly higher in responders than in nonresponders (1,099.33 +/- 708.51 versus 261.82 +/- 182.66 pg./ml., p = 0.001). There was no difference at 4 hours in mean IL-8 levels in the standard and low dose groups (596.92 +/- 546 and 893 +/- 798.67 pg./ml., respectively, p = 0.28). In all patients who remained disease-free IL-8 levels were greater than 400 pg./ml. In 9 of the 11 patients with disease recurrence/progression IL-8 levels were less than 400 pg./ml. CONCLUSIONS: IL-8 secretion after the initial intravesical BCG instillation strongly correlates with the possibility of future recurrence/progression. The quantitative IL-8 response to low and standard dose intravesical BCG (Danish 1331) is similar.     

Clinical outcome of conservative therapy for stage T1, grade 3 transitional cell carcinoma of the bladder

BACKGROUND: The objective of this study was to retrospectively investigate the effectiveness of transurethral resection of bladder tumor (TURBT) and intravesical instillation therapy for stage T1, grade 3 (T1G3) transitional cell carcinoma (TCC) of the urinary bladder. METHODS: Between January 1995 and December 1997, 97 patients with T1G3 TCC of the urinary bladder were treated by TURBT and adjuvant intravesical instillation with bacillus Calmette-Guérin (BCG) or other anticancer agents. The recurrence-free survival rates were evaluated according to several clinicopathological factors. The cases that progressed to muscle invasive disease were also analysed. RESULTS: In this series, the median follow-up period was 25 months (range, 5- 41) after the initial TURBT. Intravesical recurrence was noted in 44 patients (45%), and the 1, 2, and 3 year recurrence-free survival rates were 72%, 58%, and 42%, respectively. Multivariate analyses revealed that the risk of intravesical recurrence was significantly higher for patients who did not receive BCG therapy, irrespective of age, gender, tumor size, multiplicity, pathological stage, concomitant carcinoma in situ, and lymphovascular involvement. Moreover, after a median of 10 months, disease progression occurred in seven patients (7%), of which only one patient was treated by BCG therapy after initial TURBT. CONCLUSION: These findings suggest that intravesical instillation with BCG combined with TURBT is an effective conservative treatment for T1G3 TCC of the bladder. Patients with negative prognostic factors should be treated by BCG rather than other anticancer agents after TURBT.     

Detection of interleukin 2 in the urine of patients with superficial bladder tumors after treatment with intravesical BCG

Adjuvant intravesical BCG therapy is an effective means of treating superficial bladder tumors. The mechanism by which BCG mediates antitumor activity is not known; however, clinical and animal studies suggest that immunological responsiveness to BCG antigens correlates with antitumor activity. In this report the detection of interleukin 2 (IL-2, a lymphokine produced in response to BCG) in urine specimens of patients treated with intravesical BCG is reported. Patients with superficial transitional cell carcinoma of the bladder received intravesical BCG once each week for six weeks. No intradermal injections were administered. Urine specimens were obtained prior to BCG instillation and four, eight and 24 hours afterwards. The specimens were dialysed, concentrated five-fold and assayed for the presence of IL-2 in a biological assay using an IL-2 dependent cultured T-cell line. IL-2 was detected in urine but not serum after intravesical BCG instillation. IL-2 was characterized by absorption against an IL-2-dependent T cell line and neutralization by monoclonal anti-IL-2 antibodies. No IL-2 was detected in specimens obtained prior to BCG instillation or from donors with no detectable bladder pathology. One of 10 urine specimens from patients with urinary tract infections had detectable IL-2 levels. IL-2 production generally peaked during the fourth to sixth intravesical BCG treatment. Production was short-term in that IL-2 levels peaked four to eight hours after BCG instillation and were rarely (six of 54 specimens) observed 24 hours after instillation. Mean IL-2 levels were higher in patients who were rendered tumor free after BCG therapy but statistical significance was not achieved. Ten of 12 patients (83%) who responded to BCG therapy had urine IL-2 levels greater than or equal to 1.6 units/ml. at least once during the six week treatment period while two of six (33%) patients not responding to therapy had similar urine IL-2 levels. These results show that intravesical BCG therapy induces the production of lymphokines including IL-2. The presence of BCG-induced lymphokines may be associated with anti-tumor activity.     

Prophylactic intravesical BCG for bladder tumor after surgery of upper tract urothelial carcinoma

We report the result of prophylactic intravesical instillation of BCG after surgery of upper tract urothelial carcinoma. The BCG Tokyo 172 strain was given preoperatively and/or postoperatively, as a rule, in a dose of 80 mg in 30 ml saline instilled into the bladder. Only one (14.3%) of the 7 patients with intravesical BCG developed bladder tumor at 14 month after surgery, while (45.4%) of 11 patients who did not receive intravesical BCG suffered from bladder tumor within 2 years after surgery. Prophylactic intravesical instillation of BCG reduced significantly (p less than 0.005) the recurrence of bladder tumor after the surgery of renal pelvis and ureteral tumor.