THP在早期非肌层侵润性膀胱癌定位诊断与治疗中的临床应用

目的：探讨THP在早期非肌层侵润性膀胱癌定位诊断与治疗中的临床应用价值。方法：已诊断非肌层侵润性膀胱癌患者45例,术中均实行THP膀胱灌注,灌注后15min置入膀胱镜,观察膀胱内粘膜,将THP橙色染色区域作为实验组进行活检,其他未染色区域作为对照组随机活检,活检组织行病理检查。TUR—BT术后将45例患者随机分为3组。在不同的时间点开始灌注（术后即刻、术后6小时、术后7天）,比较复发率和平均复发时间。结粜：两组间比较具有统计学意义（P〈0.05）恶性粘膜吸收THP敏感度和特异度分别为100％、63．5％;TUR-BT术后即刻灌注及6小时后灌注的总复发率明显低于术后7天灌注,差异有统计学意义（P〈0．05）。结论：THP对非肌层侵润性膀胱癌早期定位诊断准确、安全性好,同时术后早期灌注THp可以降低肿瘤的复发率,值得临床推广。     

TUR-BT术后膀胱灌注A群链球菌联合丝裂霉素治疗高危非肌层浸润性膀胱癌的疗效观察

目的：总结经尿道膀胱肿瘤电切（TUR-BT）术后辅以沙培林（注射用A群链球菌）联合丝裂霉素（MMC）膀胱内灌注治疗高危膀胱癌的疗效。方法：回顾性研究2009年1月~2012年8月我院收治的符合高危非肌层浸润性膀胱癌患64例,观察组：TUR-BT术后行沙培林联合MMC膀胱内灌注化疗32例,对照组;MMC单药灌注32例。结果：观察组患者,平均年龄63.7岁,治疗随访时间为6~54个月,中位时间27.3个月。治疗随访期间有3例患者出现膀胱内肿瘤复发（9.3%）,1例患者疾病进展,发展为肌层浸润性膀胱癌,于术后7个月死亡（3.1%）。与对照组患者相比,疾病复发率及进展率均明显改善。结论：高危非肌层浸润膀胱癌临床复发率、进展率高,TUR-BT术后沙培林联合MMC膀胱内灌注通过局部化疗及免疫治疗联合,可有效控制疾病的复发和进展,降低患者接受膀胱部分切除或膀胱全切手术的机率,值得推广。     

TURis-Bt术前膀胱灌注表柔比星治疗NMIUC的临床疗效观察

目的:探讨TURis-Bt术前膀胱灌注表柔比星治疗非肌层浸润性膀胱癌(NMIUC)的临床疗效。方法:选取2008年9月至2012年1月潍坊市中医院和上海交通大学附属第一人民医院泌尿外科收治的76例NMIUC患者,并将其随机分为观察组(TURis-Bt术前膀胱灌注表柔比星+术后常规灌注组)41例和对照组(TURis-Bt术后常规表柔比星膀胱灌注组)35例。灌注前将50mg表柔比星溶解于50ml 5%葡萄糖注射液,术前膀胱保留灌注30分钟后膀胱镜观察肿瘤组织及周围膀胱粘膜染色情况,将表柔比星橙染的膀胱粘膜活检并行TURis-Bt;对照组取瘤旁2 cm处及其他部位膀胱粘膜多点活检。比较两组的原位癌(CIS)、非典型性增生及腺性膀胱炎等病变检出率和术后肿瘤的复发率。结果:观察组患者瘤旁膀胱粘膜橙染56处,其中7处病理证实为膀胱原位癌、5处为非典型性增生、11处为腺性膀胱炎;对照组患者膀胱原位癌1处、非典型性增生3处、腺性膀胱炎2处,两组病变阳性率分别为41.1%(23/56)和13.4%(17/127),差异有显著统计学意义(P0.01)。观察组与对照组术后2年内肿瘤复发率分别为10.3%(4/39)和35.3%(12/34),差异有统计学意义(P0.05)。结论:TURis-Bt术前膀胱灌注表柔比星能提高NMIUC病变的早期检出率并降低肿瘤术后复发率。     

非肌层侵润性膀胱癌的治疗

膀胱癌是一种全球性疾病。在我国泌尿外科肿瘤中的发病率和死亡率均占首位,非肌层侵润性膀胱癌占初发膀胱肿瘤的70%。对膀胱癌的研究已成为目前学术界的热点话题。目前学界对于非肌层侵润性膀胱癌主要采用以外科手术为主的综合治疗方案。为探讨该类肿瘤的治疗方法,本文就近年来对非肌层侵润性膀胱癌的各种治疗措施进行了比较系统的阐述。我们希望能尽可能的找到高效低风险并且经济的方法,为膀胱癌的诊断和治疗提供新途径。     

非肌层侵润性膀胱癌的治疗

膀胱癌是一种全球性疾病。在我国泌尿外科肿瘤中的发病率和死亡率均占首位,非肌层侵润性膀胱癌占初发膀胱肿瘤的70%。对膀胱癌的研究已成为目前学术界的热点话题。目前学界对于非肌层侵润性膀胱癌主要采用以外科手术为主的综合治疗方案。为探讨该类肿瘤的治疗方法,本文就近年来对非肌层侵润性膀胱癌的各种治疗措施进行了比较系统的阐述。我们希望能尽可能的找到高效低风险并且经济的方法,为膀胱癌的诊断和治疗提供新途径。     

动脉插管化疗配合膀胱灌注治疗复发性、多发性、表浅性膀胱癌

目的:探讨腹壁下动脉插管化疗(inferior-epigastric artery chemotherapy,IAC)配合吡柔比星(THP)膀胱灌注治疗复发性、多发性和表浅性膀胱癌的疗效。方法:对12例复发性、多发性和表浅性膀胱移行细胞癌患者术后行腹壁下动脉插管化疗3个疗程后,开始行吡柔比星膀胱灌注,每次30 mg,每周1次共12次,以后每2周1次共6次,以后每月1次共6次,第二年重复,第三年每月一次。定期膀胱镜检查,进行随访。结果:12例复发性、多发性、浅表性膀胱移行细胞癌患者,术后随访时间24-48个月,肿瘤复发1例,复发率8.3%。不良反应主要为术后小膀胱,尿路刺激症状和尿常规异常。结论:腹壁下动脉插管化疗配合吡柔比星膀胱灌注治疗复发性、多发性和表浅性膀胱癌的效果明确,疗效满意,患者耐受性好,值得临床推广应用。     

TURBT术后灌注不同剂量丝裂霉素对肿瘤复发的影响

目的:探讨经尿道膀胱肿瘤电切术(Transurethral resection of bladder tumor,TURBT)术后灌注不同剂量丝裂霉素对非肌层浸润性膀胱肿瘤(Non-muscularized invasive bladder tumor,NIMBC)复发率的影响。方法:选择三原县医院2013年1月至2016年12月收治的90例NIMBC患者,根据入院先后顺序分为A、B、C三组,A组TURBT后即刻给予20 mg丝裂霉素,B组给予30 mg丝裂霉素,C组给予40 mg丝裂霉素,对比三组患者术后不同时间点的复发率、平均复发时间、膀胱刺激综合征及其他不良反应。结果:三组术后不同时间点NIMBC复发率为A组B组C组。术后12个月、18个月、24个月时A组的复发率明显高于C组(P0.05),其余时间点组间对比无统计学意义(P0.05)。三组膀胱刺激综合征发生率C组B组A组,但组间对比无统计学意义(P0.05)。三组患者均完成丝裂霉素灌注治疗,未出现因严重膀胱刺激征无法耐受而中断膀胱治疗者。本研究所有患者灌注后未发现骨髓抑制、肝肾功能异常者。结论:TURBT术后即刻应用40 mg丝裂霉素,可显著降低患者的NIMBC复发率,通过术前、术后服用琥珀酸索利那新,可降低患者的膀胱刺激综合征,辅助患者完成TURBT术后丝裂霉素灌注化疗。     

经尿道绿激光汽化术治疗非肌层浸润性膀胱肿瘤疗效观察

目的:探讨经尿道绿激光气化术治疗非肌层浸润性膀胱肿瘤患者的治疗效果及近期并发症及复发率.方法:采用经尿道绿激光气化术治疗71例非肌层浸润性膀胱肿瘤患者,观察手术时间、手术并发症、手术后留置导尿时间、近期并发症及复发率.结果:全部患者手术成功.手术时间90± 16.5min,术中出血50±15ml.术中未见并发症的发生.术后留置导尿2±0.5天,均未予膀胱冲洗.无尿路感染发生.全部患者随访12-84月,结果有3例复发,复发率4.22％.未见尿道狭窄、挛缩性膀胱等远期并发症的发生.结论:经尿道绿激光汽化术治疗非肌层浸润性膀胱肿瘤患者安全可行、有效,并发症少,复发率低,但手术时间长.     

豚鼠膀胱内Cajal样间质细胞的分布情况研究

目的:观察Cajal样间质细胞(ICCs)在成年豚鼠膀胱的分布情况.方法:取5只成年豚鼠膀胱,制作全层冰冻切片,行ICCs特异性标志物c-kit免疫荧光染色,按粘膜层、粘膜下层和肌层进行统计分析.结果:豚鼠膀胱内可见c-kit免疫阳性细胞,胞体呈梭形,两端伸出长的突起,其形态与肠壁肌层Cajal细胞相似.且肌层和粘膜下层多于粘膜层.结论:豚鼠膀胱存在Cajal样间质细胞,并在肌层高表达,可能参与膀胱自主节律性运动的调控,调节逼尿肌的运动,为"神经-Cajal样间质细胞-肌肉"单元的形成提供组织学基础.     

膀胱灌注吡柔比星治疗膀胱癌的护理

膀胱癌是泌尿系统最常见的肿瘤,其中70%~80%为表浅性膀胱癌[1]。据文献报道,经尿道膀胱肿瘤电切(TUR)术后膀胱肿瘤复发率达50%~70%,其中10%~30%的复发病例伴有恶性程度增高或浸润能力增强[2]。术后膀胱内灌注药物治疗可降低和延缓肿瘤复发,防止肿瘤发生浸润,提高患者生存率和生     

Molecular pathogenesis of non muscle-invasive bladder cancer: implications for novel targeted therapies

Approximately 70% to 80% of patients with urothelial carcinomas of the bladder are initially diagnosed with non-muscle invasive disease. Superficial, non-muscle invasive bladder cancers (NMIBCs) are managed with cystoscopic transurethral resection of all visible lesions followed by intravesical chemotherapy and/or immunotherapy. Despite this treatment, up to 70% of these tumors will recur within five years and 15% will ultimately progress to muscle-invasive disease, suggesting that novel therapeutic strategies are necessary. Recent studies have greatly advanced our understanding of urothelial carcinogenesis and have highlighted the distinct molecular pathogenesis of NMIBCs versus muscle-invasive bladder tumors. It is now clear that diverse genetic and epigenetic events are driving the oncogenesis of NMIBCs, thereby attesting to their potential as therapeutic targets for these tumors. This article reviews the molecular pathogenesis of NMIBCs, discusses recently completed and ongoing clinical trials and anticipates the future direction of molecular targeted agents in this disease.     

吡柔比星预防浅表性膀胱癌术后复发的疗效观察

目的：比较吡柔比星与吉西他滨膀胱内灌注预防浅表性膀胱癌术后复发的疗效。方法：40 例浅表性膀胱癌患者根据随机抽 签法分为治疗组与对照组各20 例,所有患者都采用经尿道膀胱肿瘤电切方法,对照组用吉西他滨,治疗组用吡柔比星进行膀胱 灌注,比较两组患者术后复发率的不同。结果：所有患者都完成治疗,随访1 年,治疗组的复发率为5.0 %,对照组为25.0 %,治疗 组的复发率明显低于对照组,对比差异明显,有统计学意义(P<0.05)。经过观察,治疗组的膀胱刺激症状、骨髓抑制、尿道狭窄等不 良反应总体发生率明显少于对照组,两者比较有统计学意义(P<0.05)。结论：相对于吉西他滨,吡柔比星膀胱内灌注预防浅表性膀 胱癌术后复发有很好的效果,不良反应少,在临床上需要根据患者的实际情况来选择不同的灌注药物。     

Down‐regulation of PKM2 enhances anticancer efficiency of THP on bladder cancer

Pyruvate kinase M2 (PKM2) regulates the final step of glycolysis levels that are correlated with the sensitivity of anticancer chemotherapeutic drugs. THP is one of the major drugs used in non‐muscle‐invasive bladder cancer instillation chemotherapy. However, low response ratio of THP (19.7%) treatment to human genitourinary tumours using collagen gel matrix has been observed. This study aims to investigate the effect of down‐regulation of PKM2 on THP efficiency. Via inhibitor or siRNA, the effects of reduced PKM2 on the efficiency of THP were determined in 2 human and 1 murine bladder cancer cell lines, using MTT, cologenic and fluorescence approaches. Molecular mechanisms of PKM2 on THP sensitization were explored by probing p‐AMPK and p‐STAT3 levels via WB. Syngeneic orthotopic bladder tumour model was applied to evaluate this efficiency in vivo, analysed by Kaplan‐Meier survival curves, body and bladder weights plus immunohistochemistric tumour biomarkers. PKM2 was overexpressed in bladder cancer cells and tissues, and down‐regulation of PKM2 enhanced the sensitivity of THP in vitro. Activation of AMPK is essential for THP to exert anti‐bladder cancer activities. On the other hand, down‐regulating PKM2 activates AMPK and inhibits STAT3, correlated with THP sensitivity. Compared with THP alone (400 μmol L^?1, 50 μL), the combination with metformin (60 mmol L^?1, 50 μL) stopped growth of bladder cancer completely in vivo (combination group VS normal group P = .078). Down‐regulating the expression of PKM2 enhances the anticancer efficiency of THP. This study provides a new insight for improving the chemotherapeutic effect of THP.     

Overall and recurrence-free survival among black and white bladder cancer patients in an equal-access health system

BackgroundWhile the incidence of bladder cancer is twice as high among whites than among blacks, mortality is higher among blacks than whites. Unequal access to medical care may be an important factor. Insufficient access to care could delay cancer detection and treatment, which can result in worse survival. The purpose of this study was to evaluate whether survival differed between black and white bladder cancer patients in the Department of Defense (DoD), which provides universal healthcare to all beneficiaries regardless of racial background.MethodsThis study was based on data from the U.S. DoD Automated Central Tumor Registry (ACTUR). White and black patients histologically diagnosed with bladder cancer between 1990 and 2004 were included in the study and followed to the end of 2007. The outcomes were all-cause mortality and recurrence. We assessed the relationship between race and outcomes of interest using Cox proportional hazard ratios (HRs) for all, non-muscle invasive (NMIBC), and muscle invasive (MIBC) bladder cancers, separately.ResultsThe survival of black and white individuals did not differ statistically. No significant racial differences in survival (HR: 0.96, 95% CI: 0.76–1.22) or recurrence-free survival (HR: 0.94, 95% CI: 0.69–1.30) were observed after adjustment for demographic variables, tumor characteristics, and treatment. Similar findings were observed for NMIBC and MIBC patients, respectively.ConclusionBlack patients were more likely to present with MIBC than white patients. However, white and black patients with bladder cancer were not significantly different in overall and recurrence-free survival regardless of muscle invasion. Our study suggests the importance of equal access to healthcare in reducing racial disparities in bladder cancer survival.     

Production of MCP-1 and RANTES in bladder cancer patients after bacillus Calmette-Guerin immunotherapy

Bacillus Calmette-Guerin (BCG) therapy induces a local immunological response mediated by cellular immune and inflammatory reactions that enhance its anti-tumor efficacy in bladder cancer. Monocyte chemotactic protein-1 (MCP-1) and the "regulated on activation normal T expressed and secreted" chemokine (RANTES) are potent chemotactic molecules that attract monocytes and memory T cells. MCP-1 and RANTES levels in patients with superficial bladder cancer treated with intravesical instillations of BCG are significantly higher than in untreated cancer patients and controls. In the present study, the subjects were divided into three groups: (1) control subjects; (2) bladder cancer patients who did not receive BCG treatment; (3) bladder cancer patients who received intravesical administration of BCG. No differences in the basal production and expression of MCP-1 and RANTES mRNA were observed between BCG-treated and untreated patients. BCG treatment influenced the monocyte response to phytohemagglutinin (PHA) and BCG stimulation. After 24-h incubation, monocytes from BCG-treated bladder cancer patients released more MCP-1 and RANTES than those from untreated bladder cancer patients and controls. The anti-tumor effects of BCG observed in superficial bladder cancer therapy may depend on stimulation of the investigated chemokines, which attract monocytes/macrophages and memory T cells.     

Establishment of orthotopic mouse superficial bladder tumor model for studies on intravesical treatments

Various animal models of bladder tumor have been developed for the preclinical evaluation of therapeutic modalities for the treatment of bladder cancers. The ideal model for the investigation of therapeutic effects of proposed novel intravesical treatments requires the mass of the implanted tumor to be confined to the urothelium of the bladder at least for the initial phase. However, previously reported bladder tumor models are not suitable for the evaluation of intravesical therapies for the treatment of superficial bladder cancer, since the muscle invasive tumors have developed from the beginnings of the experiments. These models are too aggressive to study local treatment effects. In the current study, we demonstrated that careful instillation of MBT-2 mouse bladder cancer cells into the bladder of a syngenic C3H/HeJ mouse could establish a superficial bladder tumor with an incidence of 100%. The procedure and technique for handling animals are simple for standard animal investigators. Maintenance of the in vitro conditions of MBT-2 cells without contamination of Mycoplasma and careful selection of the substrain of C3H mouse seem to be essential for stable tumor establishment. This bladder tumor model appeared to be easy to reproduce among several investigators in different institutions. The orthotopic bladder tumor model, which was confined to urothelium, lets us evaluate various intravesical treatment strategies.