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。     

BCG-CWS联合IL-2预防浅表性膀胱癌术后复发

目的：探讨介苗细胞壁骨架（BCG－WCS）＋白细胞介素2（IL－2）膀胱灌注预防浅表性膀胱癌术后复发的临床效果。方法56例浅表性膀胱癌局部手术后随机分为两组,每组28例。分别采用BCG－CWS加IL－2和单用丝裂霉素C（MMC）进行膀胱灌注。结果：56例随访12－30个月,平均22．9个月,BCG－WCS＋IL－2组有1例肿瘤复发,MMC组有5例肿瘤复发,两组肿瘤复发率判别有显著性意义（P＜0．05）;MMC灌注组的毒副反应较BCG－WCS＋IL－2组多。结论BCG－CWS联合IL－2预防浅表性膀胱癌术后复发疗效较好,副反应少,临床使用安全可靠。     

肌层浸润性膀胱癌保留膀胱手术后不同辅助治疗方法的疗效评价

目的探索保留膀胱手术＋动脉灌注化疗＋膀胱内灌注化疗治疗肌层浸润性膀胱癌的临床疗效。方法对经尿道膀胱肿瘤电切或膀胱部分切除术后确诊为肌层浸润性膀胱癌（T2N0M0）的168例患者,充分向患者及其家属介绍病情和治疗建议,对拒绝或不适合膀胱全切的患者经患者及其家属同意,均采用保留膀胱治疗方法,分为3个治疗组：（1）综合治疗组：68例,术后采用动脉灌注化疗＋膀胱灌注化疗;（2）动脉灌注化疗组：48例,术后仅采用动脉灌注化疗;（3）膀胱灌注化疗组：52例,术后仅采用膀胱灌注化疗。结果168例膀胱癌（T2N0M0）患者,观察期内,综合治疗组患者中92．65％（63／68）无复发及转移,7．45％（5／68）分别在术后6、8、12、18、20个月复发,2．94％（2／68）在术后6、13个月出现全身多处转移死亡,11．76％（8／88）非膀胱癌导致死亡。动脉灌注化疗组患者中79．17％（38／48）无复发及转移,20．83％（10／48）在术后1～28个月复发,4．17％（2／48）在术后9、18个月出现全身多处转移死亡,12．50％（6／48）非膀胱癌导致死亡。膀胱灌注化疗组患者中44．23％（23／52）无复发及转移,55．77％（29／52）在术后1～24个月复发,15．38％（8／52）在术后10～96个月转移而死亡,13．46％（7／52）非膀胱癌导致死亡。3组疗效按复发率任何两组间比较,均有统计学差别（P均〈0．05）。3组疗效按癌性死亡率任何两组间比较,综合治疗组与动脉灌注化疗组相比,差异无统计学意义（P均〉O．05）;综合治疗组、动脉灌注化疗组均低于膀胱灌注化疗组,差异均有统计学意义（P均〈O．05）。3组患者分组治疗后非膀胱癌导致死亡率任何两组间比较,无统计学差异（P均〉o．05）。结论肌层浸润性膀胱癌（T2N0M0）患者,采用保留膀胱手术＋髂内动脉灌注化疗＋膀胱内灌注化疗的综合治疗方法,能有效减少肿瘤复发、预防转移、提高患者的生活质量,患者易于接受,值得进一步探讨。     

保留膀胱手术后不同辅助治疗方法治疗肌层浸润性膀胱癌的疗效评价

目的：探索保留膀胱手术＋动脉灌注化疗＋膀胱内灌注化疗治疗肌层浸润性膀胱癌的临床疗效。方法：对经尿道膀胱肿瘤电切或膀胱部分切除术后确诊为肌层浸润性膀胱癌（T2N0M0）的168例患者均采用保留膀胱治疗方法,分为三个治疗组：综合治疗组68例,术后采用动脉灌注化疗＋膀胱灌注化疗;动脉灌注化疗组48例,术后仅采用动脉灌注化疗;膀胱灌注化疗组52例,术后仅采用膀胱灌注化疗。结果：观察期内,综合治疗组患者中92．6％（63／68）无复发及转移,2．9％（2／68）在术后6、13个月出现全身多处转移死亡。动脉灌注化疗组患者中79．2％（38／48）无复发及转移,4．2％（2／48）在术后9、18个月出现全身多处转移死亡。膀胱灌注化疗组患者中44．2％（23／52）无复发及转移,15．4％（8／52）在术后10～96个月转移而死亡。三组疗效按复发率任何两组间比较,差异均有统计学意义（P〈0．05）。按癌性死亡率比较,综合治疗组、动脉灌注化疗组分别与膀胱灌注化疗组的差异均有统计学意义（P〉〈0．05）。结论：肌层浸润性膀胱癌（T2N0M0）患者,采用保留膀胱手术＋髂内动脉灌注化疗＋膀胱内灌注化疗的综合治疗方法,能有效减少肿瘤复发、预防转移、提高患者的生活质量,患者易于接受,值得进一步探讨。     

卡介苗与丝裂霉素C膀胱灌注预防浅表性膀胱癌复发疗效及毒性比较的Meta分析

目的比较卡介苗（BCG）与丝裂霉素C（MMC）膀胱灌注治疗对浅表性膀胱癌复发的预防作用及治疗毒性等方面的特点。方法收集国内外关于BCG与MMC膀胱灌注治疗浅表性膀胱癌的比较性研究文献，对结果进行统计学综合分析（Meta分析）。采用优势比（OR）及其95％可信区间（95％CI）作为评价比较疗效及毒性差异的指标。统计学分析采用RevMan4．2软件。结果共收集国内外17个临床研究，包括1600例进行BCG、1503例进行MMC膀胱灌注治疗的患者被纳入分析。最大随访期内，BCG治疗组与MMC治疗组分别有599例（37．4％）、684例（45．5％）复发。Meta分析显示，BCG与MMC膀胱灌注治疗预防肿瘤复发的疗效差异有统计学意义，BCG显著优于MMC（OR0．58，95％CI 0．42～0．80，P=0．0009）。8个较详细报道治疗副作用的比较研究中，Meta分析显示膀胱炎发生率BCG组显著高于MMC组（OR1．97，95％CI 1．31～2．98，P=0．001）。结论BCG膀胱灌注预防浅表性膀胱癌复发作用优于MMC，可以显著减少肿瘤复发，但膀胱炎发生率明显高于MMC。     

小剂量结核菌素与羟基喜树碱交替膀胱灌注预防膀胱癌术后复发的临床观察

目的 探讨羟基喜树碱（HCPT）、小剂量结核菌素（BCG）交替膀胱灌注预防膀胱癌术后复发的效果.方法 选择312例膀胱癌术后患者,随机分为HCPT和小剂量BCG交替膀胱灌注组（A组）、HCPT膀胱灌注组（B组）各156例.A组：术后第7d用HCPT 10mg＋生理盐水20 mL膀胱灌注,第14d用BCG 10mg＋生理盐水40mL膀胱灌注;之后每隔3d交替灌注1次,至术后第56d;术后第63d开始,每隔1周交替灌注1次,各灌注8次;术后第183d开始,每隔15d交替灌注1次,各灌注8次;术后第438d开始,每隔1个月交替灌注1次至术后2年.B组：自术后第7d起,用HCPT 10mg＋生理盐水20mL膀胱灌注,每周灌注1次,至术后第56d;术后第70d开始,每隔2周灌注1次,共8次;术后第198d开始,每隔1个月灌注1次,共8次;术后第468d开始,每隔2个月灌注1次至术后2年.各种药物灌注剂量同首次灌注.分别观察两组0～18、19 ～24、25 ～60个月的肿瘤复发率及毒副反应.结果 随访60个月,A组复发率分别为0（0～18个月）、3.21％（19 ～24个月）、18.67％（25～60个月）,B组分别为11.54％、7.10％、20.13％,两组0～18个月的复发率比较差异有统计学意义（P＜0.05）;两组均出现非细菌性膀胱炎、血尿、低热、血象异常等毒副反应,但两组比较差异均无统计学意义（P＞0.05）.结论 HCPT和小剂量BCG交替膀胱灌注预防膀胱癌术后复发效果较好,毒副反应较轻且发生率低.     

α-干扰素加丝裂霉素C膀胱灌注防治浅表性膀胱癌复发的研究

目的：提高膀胱癌的治疗效果,降低膀胱癌术后复发率。方法：42例膀胱癌患者术后分为两组：（1）α－干扰素＋丝裂霉素C组20例,α-干扰素3000万IU＋丝裂霉素C40mg 生理盐水40ml膀胱灌注,（2）丝裂霉素C组22例,丝裂霉素C40mg 生理盐水40ml膀胱灌注。每周1次,连续6次,然后每2周1次,连续6次,以后每月一次连续2年。结果：随访6－30个月（中位数18个月）,α-干扰素＋丝裂霉素C组复发2例,复发率为10％,丝裂霉素C组复发8例,复发率为36％,两组比较差别有显著性意义（卡方检验,P＜0．05）。结论：α-干扰素＋丝裂霉素C膀胱灌注防治浅表性膀胱癌术后复发疗效优于单用丝裂霉素C灌注。     

非肌层浸润性膀胱癌行经尿道膀胱肿瘤切除术联合卡介苗灌注后复发危险因素分析

目的：探索非肌层浸润性膀胱癌(NMIBC)行经尿道膀胱肿瘤切除术(TURBT)联合卡介苗(BCG)灌注后复发的危险因素。方法：选取我院近5年行膀胱内BCG灌注患者作为研究对象,收集患者人口学特征、组织分级、TNM分期、肿瘤是否多发、是否有膀胱癌病史、BCG灌注后尿FISH结果、BCG灌注后复发和进展等临床资料。归纳和总结队列资料特征,应用Cox比例风险回归分析识别复发或进展的危险因素。结果：研究共纳入69例患者,男性58(84.06%)例,女性11(15.94%)例,中位年龄64(55.25～70.00)岁。根据BCG灌注后是否复发分为复发组10例和非复发组59例。BCG灌注后FISH阳性患者均复发,阴性患者均未复发。与非复发组比较,复发组在性别、年龄、膀胱内非BCG灌注史、BCG灌注不良反应等方面均未见明显差异（P>0.05）,但TNM分期晚、组织分化差、有膀胱癌病史、肿瘤多发、BCG灌注后FISH阳性的患者更容易复发（P<0.05）。单因素Cox回归分析显示FISH阳性、TNM分期、肿瘤多发与肿瘤复发及进展密切相关（P<0.05）,但组织学分级与疾病的进展未见相关...     

经尿道电切术与钬激光消融术治疗浅表膀胱肿瘤疗效比较

目的：评价经尿道膀胱肿瘤电切术（TURBT）与钬激光膀胱肿瘤消融术（HLABT）加盐酸表柔比星辅助灌注治疗对浅表膀胱肿瘤（pTa、pT1）的疗效。方法：采用非随机临床对照研究,比较2004年8月～2008年8月采用TURBT（43例）与HLABT（40例）治疗83例浅表膀胱肿瘤患者的并发症及辅助灌注化疗后肿瘤复发率和副反应发生率。所有患者术后6h内即刻灌注盐酸表柔比星50mg,规范持续灌注1年。常规每3个月行膀胱B超及尿细胞学检查,可疑者行尿道膀胱镜检查,6个月一次膀胱镜检查,随访30（12～42）个月。结果：TURBT与HLABT平均手术时间分别为（34．3±16．1）min与（38．5±19．3）min,差异无统计学意义（P〉0．05）。两组手术并发症发生率分别27％（12／43）、12．5％（5／40）,差异有统计学意义（P〈0．01）。两组术后灌注化疗副反应发生率18／43（41．9％）、15／40（37．5％）,差异无统计学意义（P〉0．05）。两组肿瘤复发率分别为23．2％（10／43）和27．5％（11／40）,差异无统计学意义（P〉0．05）。结论：HLABT与TURBT术后盐酸表柔比星辅助灌注治疗浅表性膀胱肿瘤的疗效相当,在手术时间、术后灌注化疗副反应发生率、肿瘤复发率等方面差异无统计学意义,肿瘤分期分级仍是浅表膀胱肿瘤预后主要因素。术后并发症的差异主要来自闭孔神经反射的发生率不同。     

卡介苗、丝裂霉素C交替膀胱灌注预防浅表性膀胱癌术后复发

目的探讨卡介苗、丝裂霉素C交替膀胱内灌注预防浅表性膀胱癌术后复发的疗效。方法回顾性总结分析32例浅表性膀胱癌患者的临床资料,术后应用卡介苗（BCG）120mg、丝裂霉素C（MMC）40mg交替膀胱灌注,每周1次共8次,再每月1次,持续10个月。结果随访12～36个月,32例患者中2例复发（6．3％）,所有患者均能耐受上述治疗,2例应用BCG后出现轻度膀胱刺激症状,另有2例镜下血尿。结论BCG、MMC交替膀胱内灌注,预防浅表性膀胱癌术后复发效果满意,患者耐受性好、毒副作用轻,临床应用安全可靠。     

Study on enhancement of fibronectin-mediated bacillus Calmette-Guérin attachment to urinary bladder wall in rabbits

To clarify whether intravesical usage of fibrin clot stabilizer epsilon-aminocaproic acid (EACA) or p-aminomethyl benzoic acid (PAMBA) and different injuries enhance fibronectin (FN)-mediated bacillus Calmette-Guérin (BCG) attachment to bladder wall. Thirty New Zealand male white rabbits were randomly divided into five groups and the bladder wall of each rabbit was injured by electrocautery, cryocautery or knife cutting on left lateral wall, right lateral wall and posterior wall in different groups, respectively. Different drug was instilled into the bladder: Group A: pure PBS; B: PBS and radiolabeled BCG (³H-BCG); C: EACA and ³H-BCG; D: PAMBA and ³H-BCG; E: heparin and ³H-BCG. After instillation, each injured and non-injured bladder wall were surgically harvested and digested. The quantity of BCG attachment was detected by liquid scintillation counter (scintillation times per min, STPM). Quantity of BCG attachment to injured bladder wall was significantly (P < 0.01) greater than that of non-injured one, no matter which injury was performed. The BCG attachment to bladder wall in Group C or Group D was significantly (P < 0.05) greater than that of Group B. The quantity of BCG attachment to bladder of Group E was significantly (P < 0.05) less than that of Group B, C and D, respectively. Intravesical instillation of fibrin clot stabilizer (PAMBA, EACA) enhances FN-mediated BCG attachment to bladder wall while heparin inhibits this process. Injuries; e.g., cutting, cryocautery or electrocautery of bladder wall can significantly increase BCG attachment to the bladder wall.     

增强卡介苗与膀胱壁结合力的实验研究

目的为提高卡介苗的抗肿瘤作用提供实验依据. 方法家兔30只,膀胱内分别行切割伤、电灼伤、冷冻伤后随机分成5组,每组6只.A组膀胱内单纯灌注磷酸盐缓冲液;B组膀胱内灌注磷酸盐缓冲液+同位素标记后的卡介苗(3H-卡介苗);C组灌注氨基已酸+3H-卡介苗;D组灌注氨甲苯酸+ 3H-卡介苗;E组灌注肝素+3H-卡介苗.随后切取各损伤处及未损伤处膀胱壁,消化后以液体闪烁计数器测定3H-卡介苗的结合量 (单位次/min). 结果卡介苗在膀胱壁损伤处的结合量远高于未损伤处; C组、D组卡介苗的结合量(27809±6580、 28772±6058)明显高于B组 (12462±2412); 与B组比较(χ2分别为5.12、5.09,均P＜0.01),差异均有非常显著意义.而E组卡介苗结合量则明显低于B组,也远低于C组与D组,统计学检验差异亦有非常显著意义. 结论对家兔膀胱内灌注纤维蛋白溶解抑制剂可增强卡介苗与其膀胱壁的结合力,而纤溶促进剂肝素则作用相反,提示前者可提高卡介苗的抗肿瘤作用.     

Significance of the Preoperative Intravesical Instillation of Doxorubicin and the Oral Administration of 5-Fluorouracil in Preventing Recurrence After a Transurethral Resection of Superficial Bladder Cancer

Background : The postoperative intravesical instillation of doxorubicin (ADM) has a preventative effect on recurrence after a transurethral resection (TUR) of superficial bladder cancer. However, the significance of preoperative ADM instillation remains unclear. Although the oral administration of 5-fluorouracil (5-FU) has been observed to show some clinical response against bladder cancer, its preventative effect on the recurrence of superficial bladder cancer after TUR is unknown. Methods: Patients were randomized into 4 groups. All 4 groups received postoperative ADM instillation. In addition, patients in groups C and D received preoperative ADM instillation, whereas patients in groups B and D additionally received oral 5-FU postoperatively. The nonrecurrence rate and side effects were both compared among the 4 groups.
Results : Of the 282 patients registered, 200 were evaluable, with a median follow-up period of 21.4 months. There were no significant differences in the characteristics of the patients among the 4 groups. Group C (pre- and postoperative ADM) showed a significantly longer disease-free interval than group A (postoperative ADM alone). However, there was no significant difference in the disease-free interval between groups A and B (postoperative ADM plus 5-FU), or between groups C and D (pre- and postoperative ADM plus 5-FU). Bladder irritation symptoms were the most frequently noted side effect encountered in all groups, but the severity was generally mild.
Conclusions : Preoperative ADM instillation was found to prevent recurrence to a greater extent than the usual postoperative instillation alone, whereas oral 5-FU was found to have no additional beneficial effect on the disease-free interval in patients with superficial bladder cancer.     

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。     

ＭＭＣ和ＢＣＧ交替灌注防治膀胱癌术后复发

目的：观察丝裂霉素Ｃ（ＭＭＣ）和卡介苗（ＢＣＧ）化学免疫预防膀胱癌术后复发的疗效。方法：对８６例浅表性膀胱癌患者术后应用ＭＭＣ２０mg和ＢＣＧ６０mg,每周１次进行交替膀胱藻注,共灌注１２次,以后每间隔３个月灌注１次,持续２年,结果：随记２．４－８年,平均４．８４年,肿瘤复发率为８．１％,结论：ＭＭＣ和ＢＣＧ交替膀胱灌注可减少膀胱癌术后复发率。     

卡介苗联合白细胞介素-2膀胱灌注预防膀胱癌复发机理的研究

目的探讨卡介苗（ＢＣＧ）联合白细胞介素－２（ＩＬ－２）膀胱灌注预防膀胱癌复发的机理。方法对３５例膀胱移行细胞癌术后患者分别行ＢＣＧ和ＢＣＧ加ＩＬ－２膀胱灌注,随访１４～２２个月,复发率分别为３１．２５％和２１．０５％。结果应用ＩＬ－２加ＢＣＧ膀胱灌注６周后,外周血天然杀伤细胞激活因子（ＮＫＣＦ）活性明显增强,在ＮＫＣＦ活性与ＩＬ－２活性间有显著正相关变化。结论ＩＬ－２加ＢＣＧ膀胱灌注预防膀胱癌复发作用明显优于单纯用ＢＣＧ,ＩＬ－２和ＢＣＧ两者间有免疫促进和协同作用。     

Ablative and prophylactic effects of BCG Tokyo 172 strain for intravesical treatment in patients with superficial bladder cancer and carcinoma in situ of the bladder. Bladder cancer BCG Study Group]

We investigated the effects of intravesical instillation of BCG Tokyo 172 strain on patients with superficial bladder cancer and CIS of the bladder for tumor ablation and prophylaxis. This is the first controlled multicenter study for governmental approval of BCG Tokyo 172 strain for the treatment of superficial bladder cancer and CIS of the bladder. One hundred-fifty-seven patients (125 with Ta or T1, and 32 with CIS) were treated by 80 mg of BCG diluted in 40 ml of saline, once a week for 8 weeks. The dose and interval adopted in this multicenter study was determined by the previous Phase II study conducted by the same Study Group. Out of 125 superficial tumor Ta, T1, 83 (66.4%) showed complete disappearance of the tumor (CR) and 26 (20.8%) partial disappearance (PR), and out of 32 CIS, 27 (84.4%) showed CR and 2 (6.3%) PR. Among those patients showing CR, and PR who were treated with additional TUR-Bt, 98 patients were randomised for a controlled study of prophylactic BCG instillation. Prophylactic treatment consisted of 40 mg of BCG diluted in 40 ml of saline, monthly for 12 months. Forty-two patients were assigned to the treatment group, whereas the remaining 56 to the control group without any prophylactic instillation. Three cases showed tumor recurrence during the prophylactic phase. Twenty-five cases could not be treated for the whole course of prophylactic instillation mainly due to bladder irritable symptoms. Recurrent free curves were compared till 1050 days after the initiation of the study. However, there was no significant difference between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

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。     

Prophylaxis of superficial bladder tumor with the intravesical instillation of bacillus Calmette-Guerin or anti-cancer agents. A retrospective study]

It was retrospectively analyzed whether intravesical instillation of bacillus Calmette-Guerin (BCG) or anti-cancer agents had prophylactic effect or not after removal of superficial bladder tumors. The results over a follow-up period ranging from 6 to 40 months showed 23.8 per cent recurrence in group 1 patients treated with BCG (21 patients), 46.7 per cent recurrence in group 2 treated with anti-cancer agents (45 patients) and 52.3 per cent recurrence in the group 3 (127 patients) which were not received any intravesical drugs. Long-term results among the 3 groups calculated with Kaplan-Meier method demonstrated that the instillation of BCG or of anti-cancer agents was more useful for prophylaxis, compared with the actuarial non-recurrence rates of group 3. The instillation of BCG showed good prophylactic effects especially in recurrent, grade 2 and pTa bladder tumors. The instillation of anti-cancer agents showed to provide prolonged protection from recurrence, but the instillation of BCG did not.