Long-term prophylactic effects of intravesical instillation of thiotepa and oral administration of UFT on the recurrence of superficial bladder cancer after transurethral resection

Background. We examined the long-term effects of two chemotherapeutic agents, thiotepa and UFT, a 4 : 1 mixture of uracil and tegafur (a 5-fluorouracil pro-drug), in preventing postoperative recurrence of superficial bladder cancer. Methods. The subjects of the study were 153 patients with newly diagnosed superficial bladder cancer (≦ grade 2, ≦ pT1b) who underwent transurethral resection of bladder tumors (TURbt) between November 1986 and March 1990. The patients were randomized into three groups, group 1 (intravesical instillation of thiotepa), group 2 (oral administration of UFT), and group 3 (no treatment). The initial treatment was maintained until the third recurrence or disease progression. The patients were observed until February 1997 and the findings analyzed statistically. Results. The non-recurrence rate during the 5-year period after TURbt was 85.2% in group 1, 40.3% in group 2, and 53.2% in group 3, with the rate in group 1 significantly higher than that in groups 2 and 3. Analysis of the non-recurrence rate in relation to cancer grade or stage showed that patients with grade 2, stage pT1 tumors in group 1 had a significantly higher non-recurrence rate than patients with grade 2, pT1 in tumors groups 2 and 3. Multivariate analysis by Cox's proportional hazards regression model confirmed that prophylactic treatment was the most important factor affecting the non-recurrence rate. Conclusion. Intravesical thiotepa instillation after TURbt was useful to prevent the recurrence of bladder cancer in patients with grade 2 or pT1 tumor in a 5-year period. Received: June 24, 1998 / Accepted: March 3, 1999     

经尿道膀胱肿瘤电切术对膀胱癌患者生存情况及不良反应的影响

目的：探讨经尿道膀胱肿瘤电切术（TURBt）对膀胱癌的治疗效果,分析其安全性和有效性。方法回顾性分析85例膀胱癌患者的临床资料,根据手术方式不同将患者分为膀胱部分切除组（36例）和TURBt组（49例）。观察两组患者的手术一般情况,比较两组患者术后生存率、肿瘤标志物水平和不良反应发生情况。结果TURBt组患者手术时间和术后留置导尿管时间均较膀胱部分切除组短（t=54.396、10.215,P﹤0.001）,术中出血量较膀胱部分切除组少（t=42.843,P﹤0.001）;两组患者的中位随访时间为51个月,95%CI为18～80个月;TURBt组患者的生存情况明显优于膀胱部分切除组;手术前,两组患者的肿瘤标志物水平比较,差异无统计学意义（P﹥0.05）,出院前,TURBt组患者的CEA、CA19-9和CA125水平均低于膀胱部分切除组（P﹤0.001）;TURBt组不良反应总例数少于膀胱部分切除组（P=0.001）。结论 TURBt对膀胱癌患者有较好的治疗效果,且对排尿功能影响较小,具有较好的临床应用价值。     

A comparative clinical trial of UFT treatment and intravesical adriamycin instillation to prevent recurrence of superficial bladder cancer]

UFT was administered to 27 patients with superficial bladder cancer and adriamycin administered intravesically to 26 patients with the same cancer as a measure to prevent the recurrence of the tumor following transurethral resection, and the rate of recurrence was compared between the two groups of patients. There was no significant difference between the two groups in background factors (e.g., primary or recurrent, single or multiple), histological malignancy and degree of infiltration. The non-relapsers accounted for 88.9% of patients at one year, 64.3% at two years, and 64.3% at three years in the UFT group and 96.2%, 76.8%, and 65.5%, respectively, in the adriamycin group. There was no significant difference in the rate of non-recurrence between the two groups; nor was there significant difference in the non-recurrence rate between them with respect to any of the background factors. UFT showed results which compared with those of adriamycin administered intravesically, and UFT was considered useful for preventing recurrence of superficial bladder cancer.     

经尿道膀胱肿瘤电切术联合吡柔比星膀胱灌注治疗对浅表性膀胱癌患者预后及血清相关因子的影响

目的：探究经尿道膀胱肿瘤电切术（ TURBt）联合吡柔比星灌注治疗对浅表性膀胱癌患者的预后及对血清相关因子的影响。方法对120例浅表性膀胱癌患者按照入院时间顺序随机分为对照组与观察组,对照组接受单纯TURBt治疗,观察组接受TURBt联合吡柔比星灌注治疗。比较2组患者术后复发率、血清肿瘤相关因子、并发症。结果观察组术后1年复发率为5．0％,明显低于对照组,P＜0．05。观察组平均复发时间明显低于对照组,P＜0．05。观察组血清中VEGF、FGF、MMP-s水平均明显低于对照组,P＜0．05。2组患者术后并发症发生率无明显统计学差异,P＞0．05。结论 TRUBt联合吡柔比星灌注治疗浅表性膀胱癌可以降低术后复发率,同时改善恶性肿瘤相关血清因子水平,且无明显不良反应,值得临床推广。     

八聚体转录因子4蛋白表达与非肌层浸润性膀胱癌的关系

目的 探讨八聚体转录因子4(Oct4)蛋白在非肌层浸润性膀胱癌中的表达情况,并分析其表达与患者临床病理特征及预后的关系.方法 采用免疫组化生物素酶标法检测87例非肌层浸润性膀胱移行细胞癌和15例癌旁正常组织中Oct4蛋白的表达情况,并结合临床资料分析Oct4蛋白的表达在膀胱癌患者中的意义.结果 正常组织中Oct4蛋白的...     

Postoperative intravesical instillation of THP for superficial bladder tumor: clinical results of prophylactic effects on the recurrence. Fukushima THP Research Group]

Intravesical instillation of pirarubicin (THP) was performed on 66 patients with superficial bladder cancer after transurethral resection to evaluate the prophylactic effect against tumor recurrence. Intravesical chemotherapy was carried out at the concentration of 20mg/40ml. THP was initially instilled three times for one week, following instillation of every two weeks for ten times, and then every one month for seven times. Bladder irritability was demonstrated 21 of 66 cases (31.8%). Although there was a case of contracted bladder, generalized side effect was no case. Eligible cases for evaluation of efficacy were 43 out of 66 patients. The non-recurrence rate (by Kaplan-Meier's method) at one and two years were 90.4% and 77.8%, respectively. Intravesical THP instillation seems to be effective for the purpose of prophylaxis against the recurrence of superficial bladder tumor.     

瘦素在非肌层浸润性膀胱癌中的表达及其意义

[目的]探讨瘦素在非肌层浸润性膀胱癌中的表达情况,组织并分析其与膀胱癌患者临床病理特征及预后的关系。[方法]收集112例膀胱移行细胞癌组织和20例正常膀胱组织的病理切片,采用免疫组化方法检测膀胱癌和正常膀胱组织中瘦素的表达。[结果]正常膀胱组织中瘦素的表达水平明显低于肿瘤组织（P=0．032）。在低级别、高级别膀胱癌中,瘦素的阳性表达率分别为43．8％、75．8％,差别有统计学意义（辟0．001）。本组随访6-102个月,其中67例出现复发。复发组与未复发组中瘦素的阳性表达率分别为70．1％和46．7％,差别有统计学意义（P=0．013）。但瘦素表达与患者年龄、性别、肿瘤数目、大小及分期无明显相关性（P〉0．05）。[结论]瘦素表达在膀胱癌组织中明显高于正常膀胱组织,瘦素的检测有助于膀胱癌诊断及预后评估。     

膀胱癌PCNA蛋白表达及其与复发的关系

[目的]探讨增殖细胞核抗原（proliferating cell nuclear antigen,PCNA）蛋白在膀胱癌中的表达情况,并分析其与临床病理特征及复发的关系。[方法]148例膀胱移行细胞癌患者标本,25例癌旁正常组织标本作为对照,采用免疫组化SP法检测PCNA蛋白的表达。[结果]癌旁正常组织中PCNA蛋白的阳性表达水平明显低于肿瘤组织（16.0%vs50.7%,P〈0.001）。PCNA蛋白的表达与膀胱癌的分级、分期、复发有关（P〈0.05）,与患者的年龄、性别、肿瘤数目及肿瘤大小无关（P〉0.05）。本组104例浅表性膀胱癌（Ta～T1）随访2～95个月,其中复发64例,复发组与未复发组PCNA蛋白的阳性表达率分别为56.3%和15.0%（P=0.001）。[结论]PCNA蛋白在膀胱癌中高表达,其高表达提示预后不良。     

八聚体转录因子4蛋白表达与非肌层浸润性膀胱癌的关系

目的 探讨八聚体转录因子4(Oct4)蛋白在非肌层浸润性膀胱癌中的表达情况,并分析其表达与患者临床病理特征及预后的关系.方法 采用免疫组化生物素酶标法检测87例非肌层浸润性膀胱移行细胞癌和15例癌旁正常组织中Oct4蛋白的表达情况,并结合临床资料分析Oct4蛋白的表达在膀胱癌患者中的意义.结果 正常组织中Oct4蛋白的表达水平明显低于肿瘤组织(P＜0.01).G1级、G2级、G3级膀胱癌的Oct4蛋白阳性表达率分别为40.7％、69.4％、91.7％,差异有统计学意义(P＜0.01).所有患者随访3～78个月,其中63例出现复发,复发组与未复发组中Oct4蛋白的阳性表达率分别为77.8％和37.5％,差异有统计学意义(P＜0.0l);21例复发患者出现进展,进展组与未进展组中Oct4蛋白的阳性表达率分别为71.4％和65.2％,差异无统计学意义(P＞0.05).Oct4蛋白的表达与患者的年龄、性别、肿瘤的数目及大小无明显相关性(P＞0.05).结论 Oct4蛋白检测有助于早期发现膀胱肿瘤,并可用来判断肿瘤的恶性分化程度及检测患者术后的复发情况.     

原位膀胱癌动物模型的建立及应用

背景与目的:表浅性膀胱癌术后膀胱灌注丝裂霉素等药物进行化疗,肿瘤仍有较高的复发率.有研究报道往膀胱内灌注小型干扰RNA(siRNA)可抑制裸鼠膀胱肿瘤生长.本研究目的是建立荷人膀胱癌的原位动物模型,通过磁共振成像(magnetic resonance imaging,MRI)监测肿瘤生长过程,并利用此模型评价靶向Survivin的干扰质粒对丝裂霉素的增效作用.方法:直视下经尿道机械损伤BALB/c裸鼠膀胱粘膜,将人膀胱癌细胞T24经尿道种植于25只裸鼠膀胱,建立荷人膀胱癌原位动物模型.以钆-二乙三胺五乙酸作为膀胱造影剂,用MRI监测肿瘤的生长,同时取裸鼠膀胱组织标本行HE染色进行病理学检查.同法建立膀胱癌裸鼠动物模型18只,分为对照组、丝裂霉素组和联合组3组,每周两次膀胱灌注,联合组为靶向Survivin的干扰质粒和丝裂霉素交替用药;膀胱灌注6次后荷瘤膀胱称重.结果:25只裸鼠在种植T24细胞后均形成膀胱肿瘤.种植后7天裸鼠膀胱MRI检查无明显变化,14、21、28天MRI检查均可发现膀胱不同程度的充盈缺损,MRI图像与肿瘤实际大小吻合.病理检查显示:种植后7天,肿瘤生长于裸鼠膀胱粘膜或浅层肌肉;14～28天局限于肌层;35天时侵及浆膜层.丝裂霉素组和联合组的抑瘤率分别为33.45%、56.34%,联合组优于丝裂霉素组(P＜0.05).结论:成功建立了裸鼠原位膀胱癌动物模型,肿瘤生长基本模拟了人膀胱癌的发生、发展过程;MRI检查可作为对裸鼠膀胱原位肿瘤动态观察的可靠方法.靶向Survivin的干扰质粒增加了丝裂霉素的抗肿瘤作用.     

Clinical study of G3 superficial bladder cancer without concomitant CIS treated with conservative therapy

OBJECTIVE: The treatment for superficial G3 transitional cell carcinoma (TCC) of the urinary bladder remains controversial. It is important to reveal the clinical features of superficial G3 bladder cancer that can be treated conservatively. PATIENTS AND METHODS: A total of 39 patients with primary superficial bladder cancer (Ta, T1) with G3 components but without concomitant carcinoma in situ (CIS), who had been treated initially with transurethral resection (TUR), were retrospectively analyzed for factors related to tumor recurrence, progression and survival. The patients were 34 males and five females whose age ranged from 49 to 85 years (average, 68 years). Initial tumor stages were Ta in one patient and T1 in 38. Initial treatments were TUR alone in 18 patients and TUR with adjuvant therapy (intravesical chemotherapy or BCG therapy) in 21. Factors examined included age, gender, morphology, size and number of tumors and adjuvant therapies. RESULTS: Follow-up periods were 3-138 months (median, 37 months). Tumor recurrence, progression and cancer death were observed in 23, seven and four cases, respectively. The 5-year progression-free rate (75%) and survival rate (83%) in 39 patients with G3 did not show a statistically significant difference from those of the 109 patients with G1 or the 187 patients with G2 superficial bladder cancer who were treated with TUR initially. Only the rate of recurrence of patients with G3 was significantly higher than that of patients with G2 or G1. Adjuvant therapies reduced the recurrence rate of the patients with G3. Only tumor morphology, papillary or non-papillary, affected both the progression-free rate and the survival rate of patients with G3. There were no statistically significant differences associated with other factors. CONCLUSION: The results suggest that superficial G3 bladder cancer could be treated with TUR initially, especially for papillary tumors.     

吡柔比星(THP)膀胱灌注预防膀胱癌术后复发的疗效观察

目的;分析１９９８年６月－１９９９年８月间２２例浅表性膀胱癌患者行膀胱部分切除术或行ＴＵＲ－Ｂｔ及电灼术后采用吡柔比星膀胱灌注预防肿瘤复发。方法：ＴＨＰ３０ｍｇ,每周一次,连用８周,而后每月１次,连用８个月。结果：总疗程１０个月,平均随访９．７个月,复发率１３．６％。结论：ＴＨＰ用于临床,效果好,不良反应少,给药方便,值得临床推广应用。     

吡柔比星膀胱灌注预防膀胱癌术后复发临床观察

目的:分析2002年6月~2005年8月间158例浅表性膀胱癌患者行膀胱部分切除术或行TUR-Bt术后采用吡柔比星(THP)膀胱灌注预防肿瘤复发。方法:THP30mg,每周1次,连用8周,而后每月1次,连用10个月,总疗程12个月。结果:所有患者均获6~24个月的随访。平均随访12.3个月。复发20例,复发率12.8%。结论:THP用于膀胱灌注预防膀胱癌术后复发有较好的疗效,不良反应少,给药方便,值得临床推广应用。     

丝裂霉素膀胱灌注预防浅表性膀胱肿瘤复发的远期疗效观察

目的 观察丝裂霉素预防浅表性膀胱肿瘤复发的远期疗效。方法 将１９８０年１月￣１９９１年１２月的８６例浅生膀胱肿瘤患者分为丝裂霉素组（手术＋丝裂霉素灌注）和对照组（单纯手术）,对两组的肿瘤术后复发率、病理分期和细胞分级进行对比观察。结果 丝霉素组７１例,对照组１５例,术后肿瘤复发率分别为４０．８％和６６．７％。丝裂霉素组在术后６月、１２月、２４月、３６月和６０月以上的无瘤率分别为８５．９％,７６．１     

恶性膀胱非尿路上皮肿瘤（附10例报告）

目的探讨恶性膀胱非尿路上皮肿瘤的诊断及治疗。方法回顾性分析10例恶性膀胱非尿路上皮肿瘤的临床资料。行膀胱全切术6例,膀胱部分切除术1例,经尿道膀胱肿瘤电切术（TURBt）2例,1例膀胱小细胞癌因广泛浸润仅作探查活检术。结果恶性膀胱非尿路上皮肿瘤占同期恶性膀胱肿瘤的4.5%。10例随访2月-5年,术后平均生存时间17.4月。结论恶性膀胱非尿路上皮肿瘤临床少见,预后差,膀胱全切术是首选的手术方式,新辅助化疗或术后放化疗可提高疗效。     

膀胱癌治疗体会(附165例报告)

目的:总结不同治疗方法治疗膀胱癌的效果。方法:回顾分析165例膀胱癌患者的临床治疗资料,经尿道膀胱肿瘤电灼手术93例,膀胱部分切除手术51例,膀胱切除肠管代膀胱手术21例,所有患者术后都行膀胱局部化疗。结果:165例膀胱癌,随访1~5年,复发29例,复发率17.6%。结论:选择正确的手术方式,注意处理好术前、术中和术后细节,可降低膀胱癌的复发率。     

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。     

Intravesical combination chemotherapy with mitomycin C and doxorubicin for superficial bladder cancer: a randomized trial of maintenance versus no maintenance following a complete response

Between November 1986 and April 1989, 101 patients with superficial bladder cancer were treated with intravesical instillations of mitomycin C on day 1 and doxorubicin on day 2 of each week for 5 consecutive weeks. Of 61 complete responders, 23 patients with carcinoma in situ and 28 with papillary cancer were randomly assigned to a non-maintenance group or to a group receiving maintenance therapy consisting of monthly instillations of the same drugs for 12 months. The 2-year non-recurrence rate calculated for patients with carcinoma in situ was significantly better in the maintenance group than in the non-maintenance group. A similar tendency was observed for patients with papillary cancer, although the difference was not significant. Side effects were considerable, with moderate to severe bladder irritation occurring in approximately half of the patients. In addition to our previous findings, the present results indicate that this intravesical combination chemotherapy is effective in eliminating superficial bladder cancers and that since the effect is not durable, even in complete responders, maintenance therapy is necessary to reduce subsequent tumor recurrence.Presented at the 4th International Conference on Treatment of Urinary Tract Tumors with Adriamycin/Farmorubicin, 16–17 November 1990, Osaka, Japan     

浅表膀胱肿瘤电切术后不同灌注药物的疗效比较

目的：比较浅表膀胱肿瘤经尿道膀胱肿瘤电切术后不同灌注药物的疗效及意义。方法：117例浅表膀胱肿瘤经尿道膀胱肿瘤电切术后的患者,随机分为四组：卡介苗组（n=26）;丝裂霉素组（n=27）;多柔比星组（n=27）;羟基喜树碱组（n=37）。结果：卡介苗组,比裂霉素组,多柔比星组,羟基喜树碱组的三年复发率为分别为30．77％,40．74％,33．33％,24．32％。各组比较,羟基喜树碱组均低于其他三组,且与丝裂霉素组,多柔吡星组比较有显著性差异,P＜0．05）。结论：浅表性膀胱肿瘤经尿道膀胱肿瘤电切术后,应用羟基喜树碱膀胱内灌注可降低术后复发率,延长无瘤生存期。     

Management of superficial recurrences in an irradiated bladder after combined-modality organ-preserving therapy

PURPOSE: Standard treatment for superficial bladder cancer is transurethral resection of the bladder tumor (TURBT) followed by intravesical therapy. Little is known about the biologic behavior and treatment response of superficial disease within an irradiated bladder. We specifically analyzed patients who developed superficial recurrence after TURBT and radiotherapy or radiochemotherapy. PATIENTS AND METHODS: Between 1982 and 2006, a total of 531 consecutive patients with invasive bladder cancer were treated by using various bladder-sparing protocols at our institution. Of these, 389 (76%) achieved a complete response after TURBT and radiotherapy/radiochemotherapy. During follow-up, 68 of 389 patients (17%) developed a superficial local relapse (< or = T1) and form the subject of this study. RESULTS: Sixty-four of 68 patients underwent conservative TURBT with or without intravesical treatment (4 patients underwent immediate cystectomy): 31 of 64 patients (48%) had no further bladder recurrence, 21 (33%) experienced additional superficial recurrences, and 12 (19%) ultimately progressed to muscle-invasive disease. Disease-specific survival rates were 87% and 72% at 5 and 10 years, respectively. Compared with 255 patients without local bladder relapse after primary treatment, no significant difference was found for disease-specific survival rates (72% after superficial vs. 79% without local relapse at 10 years, p = 0.78). However, significantly fewer patients with a superficial relapse survived with their native bladder (50% after superficial vs. 76% without local relapse at 10 years, p < 0.001). CONCLUSION: A further bladder-sparing approach with TURBT and intravesical therapy is reasonable for patients with superficial relapse after combined-modality treatment without compromising survival. However, these patients are at greater risk of requiring late cystectomy.