等离子电切结合膀胱热灌注化疗治疗膀胱癌疗效观察

膀胱癌是泌尿系统最常见的恶性肿瘤,非肌层浸润性膀胱癌(non-muscle invasive bladder cancer,NMIBC)主要采用经尿道膀胱肿瘤切除手术治疗.但由于膀胱恶性肿瘤具有多发性和侵袭性,单纯电切手术治疗术后膀胱癌复发率很高,通常采取术后定期膀胱灌注药物化疗或免疫治疗,以预防膀胱肿瘤的复发和进展,但总体疗效欠佳[1].近些年来开展的热灌注化疗,能充分发挥热疗和化疗的协同作用,提高对膀胱癌的治疗效果.我院于2013年引进体腔热灌注治疗机,对NMIBC患者行经尿道膀胱癌等离子电切结合膀胱热灌注化疗,治疗效果较满意.现报告如下.     

吉西他滨膀胱灌注治疗复发性非肌层浸润性膀胱癌的疗效分析

目的评价吉西他滨膀胱灌注化疗治疗表柔比星膀胱灌注化疗后复发的非肌层浸润性膀胱癌(NMIBC)的有效性及安全性。方法回顾性分析52例经尿道膀胱肿瘤切除术后表柔比星灌注化疗后复发的NMIBC患者临床资料,其中23例灌注复发后行吉西他滨辅助灌注化疗,29例继续表柔比星灌注化疗。比较两组辅助性膀胱灌注后肿瘤无复发生存率、复发间隔时间、进展率以及不良反应。结果吉西他滨辅助性膀胱灌注患者的2年肿瘤无复发生存率达65.22%,显著高于表柔比星灌注组44.83%,两者比较差异具有统计学意义(P0.05)。平均复发时间吉西他滨组[(15.87±3.36)月]明显长于表柔比星组[(10.06±3.04)月](P0.05)。两组患者进展率和进展时间比较差异均无统计学意义(P0.05)。两组不良反应发生率相当,主要表现为尿频、血尿、尿痛等,无严重不良反应。结论对于表柔比星辅助性膀胱灌注化疗后复发的NMIBC患者,给予吉西他滨辅助性膀胱灌注化疗疗效显著,能降低NMIBC复发率,延长无瘤生存时间,安全性较好。     

短期辅助膀胱内灌注化疗对比术后即刻膀胱灌注化疗对中低危非肌层浸润性膀胱癌患者复发率的影响

通过多中心前瞻性随机对照临床试验,对比术后即刻膀胱灌注与短期膀胱灌注辅助化疗对中低危非肌层浸润性膀胱癌(NMIBC)膀胱电切术(TURBT)后复发风险的影响.该试验于 2010 年 9 月经由京都府立大学医学院伦理委员会批准.106 例中低危 NMIBC 患者随机分为两组,A 组采取术后即刻膀胱灌注吡柔比星(THP)30 mg,B 组采取 THP30 mg每周膀胱灌注,连续 8 周.患者 TURBT术后每 3 个月行膀胱镜检和尿路细胞学检查以监测膀胱癌复发情况.结果显示 A、B 组患者 2 年无复发生存率分别为 65.3%和87.2%(P= 0.038).在此期间无患者发生进展,A、B 组患者的不良反应发生率分别为0 和 24.4%,未出现严重不良反应(3 级以上).综合实验结果显示,对于中低危 NIMBC 患者,THP 30 mg每周膀胱灌注,连续 8 周的方案可以降低肿瘤复发风险并且无严重毒副反应出现.可应用于中低危NIMBC患者电切术后的辅助化疗.     

诱导膀胱灌注化疗阶段患者的生存质量现状及其影响因素分析

<正>膀胱癌是泌尿系统常见恶性肿瘤之一,其中约70%～80%膀胱癌为非肌层浸润性膀胱癌(nonmuscle invasive bladder cancer, NMIBC)^[1],经尿道膀胱肿瘤切除术辅以术后膀胱灌注化疗为NMIBC的临床首选治疗方案^[2]。吡柔比星(pirarubicin,THP)为蒽环类药物的半合成药物,通常用于膀胱灌注化疗。它能够嵌入肿瘤细胞DNA链中,抑制DNA聚合酶的活性,     

膀胱内灌注化疗药物的方法改进及效果观察

目的探讨膀胱肿瘤患者行经尿道膀胱肿瘤电切术(transurethral resection of bladder,TURBT)术后膀胱内灌注化疗药物的个体细化灌注方法及护理效果。方法 112例TURBT后行膀胱内灌注化疗药物的非浸润性膀胱肿瘤患者,按治疗时间段先后分为对照组(49例)和观察组(63例),对照组采取常规膀胱内化疗药物灌注;观察组根据患者的个人情况采取个性化的膀胱内化疗药物灌注方法,包括灌注前评估患者情况,选择合适的尿管,灌注药物加温,灌注药物的个性化排出方式及拔除尿管的时间等。观察两组患者按规定完成全程灌注的治疗依从性、排尿不适症状等情况。结果观察组患者膀胱痉挛性疼痛程度评分明显低于对照组,生活质量指数评分及按规定完成全程膀胱灌注治疗的依从率明显高于对照组。结论 TURBT术后膀胱内灌注化疗药物应根据患者的具体情况采取个性化的灌注方法,可减少患者排尿不适症状,提高患者治疗的依从性及生存质量,达到膀胱肿瘤治疗的目的。     

吉西他滨与表柔比星灌注化疗对非肌层浸润性膀胱癌患者的疗效对比

目的:比较吉西他滨与表柔比星膀胱灌注化疗对非肌层浸润性膀胱癌(NMIBC)患者的疗效及安全性。方法:回顾性分析2014年10月至2017年10月温州医科大学附属温岭医院86例经尿道膀胱肿瘤切除术(TURBT)后行膀胱灌注化疗的NMIBC患者的临床资料。其中42例采用吉西他滨灌注(吉西他滨组),44例采用表柔比星灌注(表...     

中性粒/淋巴细胞比值对非肌层浸润性膀胱癌膀胱灌注化疗疗效的预测价值

目的 评价中性粒/淋巴细胞比值(neutrophil to lymphocyte ratio,NLR)对非肌层浸润性膀胱癌（non-muscle invasive bladder cancer,NMIBC）患者行膀胱灌注化疗疗效的预测价值。方法 收集2012年6月至2014年12月于本院行膀胱灌注化疗的63例NMIBC患者的临床病例资料并进行随访研究。研究主要终点为膀胱肿瘤复发或出现疾病进展。比较在随访过程中复发患者与无复发患者在TURBT术前NLR,化疗第1个月NLR以及NLR差值（化疗第1月NLR-TURBT术前NLR）方面的差异。结果 63例行膀胱灌注化疗的患者在随访过程中共21例患者出现复发,复发的中位时间为9个月。复发患者TURBT术前NLR及化疗第1个月NLR的平均值分别为（2.34±1.28）与（2.65±0.95）,与无复发患者（2.75±1.68）与（2.24±1.05）相比,差异无统计学意义（P>0.05）。而无复发患者NLR差值的平均值为（-0.51±1.64）,与复发患者（0.31±1.20）相比明显下降,差异有统计学意义（P<0.05）。结论 NLR差值可作为一项简单可信的预后指标用以评价NMIBC患者行膀胱灌注化疗的疗效。膀胱灌注化疗过程中NLR下降越明显的患者可获得更多的临床获益。     

持续膀胱热灌注化疗技术方法的建立

目的：应用自主开发研制的BR-TRG-I型体腔热灌注治疗仪对膀胱癌患者进行膀胱内温热灌注化疗,探索并建立一种规范化持续循环恒温灌注的膀胱热灌注化疗技术方法。方法：对我院2009年3月～2010年9月收治的10例膀胱癌患者进行膀胱热灌注化疗,每例治疗1～4次,共治疗25例次。术前经尿道插入三腔导尿管至膀胱后固定,夹闭流出管,以其中一腔接灌注管,剩下一腔接流出管。灌注术在手术室或重症监护室内即可完成,术前仅需适当镇静止痛处理,无需特殊麻醉;灌注速度控制在150ml／min,灌注时间为40min,治疗温度为（45．O±0．2）℃,化疗药物选择丝裂霉素C（MMC）60mg,灌注液总量600ml;在灌注过程中实时监测患者生命体征。结果：10例患者膀胱热灌注化疗均顺利,调试仪器及放置导尿管、灌注管和引流管平均时间20min,灌注过程中能够实现持续循环恒温灌注,患者生命体征平稳,无与膀胱热灌注化疗相关的不良反应发生。结论：应用BR-TRG-I型体腔热灌注治疗仪对膀胱癌患者进行膀胱热灌注化疗,其技术方法安全可行,能够实现膀胱内持续循环恒温灌注化疗,有着很好的临床应用前景。     

膀胱灌注化疗患者的全程连续护理管理

目的探讨全程连续护理管理对膀胱肿瘤患者术后行膀胱灌注化疗的影响。方法将58例膀胱肿瘤患者按收治的病区分为观察组(n=30)和对照组(n=28)。对照组给予常规护理,观察组实施全程连续护理管理。结果随访1年,观察组膀胱灌注并发症发生率显著低于对照组,膀胱灌注完全遵医行为及满意度显著高于对照组(均P0.01)。结论全程连续护理管理可提高膀胱灌注治疗患者的遵医行为,降低灌注所致并发症的发生,提升患者满意度。     

BR-TRG-I型体腔热灌注治疗仪实施膀胱内温热灌注化疗的疗效观察

目的:探讨BR-TRG-I型体腔热灌注治疗仪实施膀胱内温热灌注化疗治疗高复发表浅性膀胱移行细胞癌的效果。方法:选取2011年3月~2014年10月收治的高复发表浅性膀胱移行细胞癌患者90例,随机分为研究组(n=45)和对照组(n=45)。对照组患者术后24小时内行膀胱灌注,研究组患者术后3天行丝裂霉素膀胱腔内热灌注化疗。结果:研究组患者膀胱局部复发率为33.3%(15/45),显著低于对照组的77.8%(35/45)(P0.05);复发时间和复发间期均显著长于对照组(P0.05);复发肿瘤个数显著少于对照组(P0.05)。结论:BR-TRG-I型体腔热灌注治疗仪实施膀胱内温热灌注化疗治疗高复发表浅性膀胱移行细胞癌患者效果显著,值得在临床推广。     

Long-term efficacy of hyperthermic intravesical chemotherapy for BCG-unresponsive non-muscle invasive bladder cancer

BackgroundThe recommended treatment for patients with Bacillus Calmette-Guérin (BCG) unresponsive non-muscle invasive bladder cancer (NMIBC) is radical cystectomy (RC). However, many patients refuse, or are unfit for RC. Therefore, alternative bladder-sparing treatment modalities are needed for BCG-unresponsive NMIBC. In this study we sought to assess the long-term efficacy of hyperthermic intravesical chemotherapy (HIVEC) as alternative to radical cystectomy in BCG-unresponsive non-muscle invasive bladder cancer patients.Methods and materialsRetrospectively collected data from 56 patients with BCG-unresponsive NMIBC who received ≥5 HIVEC instillations between October 2014 and March 2020 was analyzed. All patients met the BCG-unresponsive criteria according to the current EAU guideline on NMIBC 2020. Patients were followed-up with cystoscopy and/or bladder biopsies, urine cytology and annually CT-urography. The Primary outcome was the high grade (HG) recurrence-free survival (RFS), defined as the time from the first HIVEC instillation until histologically confirmed intravesical recurrence or last follow-up. The Kaplan Meier method was used to estimate survival outcomes. Secondary outcomes were: complete response rate (CR), adverse events (AE), assessed by the Common Terminology Criteria for Adverse Events v5.0 (CTCAE) and tumor progression to muscle invasive disease or distant metastases.ResultsThe median follow-up was 32.2 months (IQR 13.7–44.8). The 1- and 2-year HG-RFS was 53% (SE:6.8) and 35% (SE:6.9), respectively. The CR for patients with CIS was 70% (21/30) at 6 months. Overall, 80% of the population developed an AE, only 1 was classified as CTCAE ≥3. Limitation of this study was the small sample size.ConclusionHIVEC resulted in a 2-year HG-RFS of 35% for BCG-unresponsive NMIBC patients without severe side-effects and therefore HIVEC seems to be an alternative treatment option for patients who refuse or are unfit for RC.     

Safety and efficacy of intensive instillation of low-dose pirarubicin vs. bacillus Calmette-Guérin in patients with high-risk non-muscle-invasive bladder cancer

ObjectivesTo evaluate the safety and efficacy of intensive intravesical instillation of low-dose pirarubicin (THP) for 6 times vs. bacillus Calmette-Guérin (BCG) without maintenance therapy after transurethral resection of bladder tumor (TURBT) in patients with primary high-risk non-muscle-invasive bladder cancer (NMIBC).Materials and MethodsWe retrospectively evaluated 370 patients with primary high-risk NMIBC who underwent TURBT from November 1993 to April 2019. The patients were divided into 2 groups: patients treated with intravesical instillation of BCG without maintenance therapy (BCG group) and intensive intravesical instillation of low-dose (20 mg) THP for 6 times within 10 days after TURBT (THP group). Safety was assessed using the Common Terminology Criteria for Adverse Events version 5.0. Background-adjusted multivariate analyses were performed to evaluate the effect of intensive intravesical instillation of low-dose THP on oncological outcomes, including intravesical recurrence-free survival (RFS), upper urinary tract RFS, muscle-invasive bladder cancer-free survival, metastasis-free survival, cancer-specific survival, and overall survival.ResultsOf the 370 patients with primary high-risk NMIBC, 180 (49%) and 190 (51%) were stratified into the BCG and THP groups, respectively. The incidence rate of adverse events of any grade in the BCG group was significantly higher than that in the THP group (P < 0.001). In the background-adjusted multivariate analyses, no significant differences were observed in oncological outcomes between the BCG and THP groups.ConclusionsIntensive intravesical instillation of low-dose THP for 6 times may be one of the treatment options in view of safety and efficacy after TURBT in patients with primary high-risk NMIBC.     

Conductive hyperthermic chemotherapy versus electromotive drug administration of mitomycin C as intravesical adjuvant treatment of patients with intermediate or high-risk non-muscle invasive bladder cancer

BackgroundDevices that increase the penetration of intravesical chemotherapeutic agents have been developed as alternatives to the use of bacillus Calmette–Guérin, in short supply at a time of increasing global incidence of non-muscle invasive bladder cancer (NMIBC).We performed a prospective observational study to compare 2 of these devices in the treatment of patients with high- and intermediate-risk NMIBC. The primary endpoint was the recurrence-free rate. Secondary endpoints were the rate of progression and adverse events.MethodsAfter undergoing transurethral bladder resection, 98 patients were selected to receive 1 of 2 treatments: hyperthermic intravesical chemotherapy (HIVEC) treatment with 40 mg of mitomycin C (MMC) using Combat BRS System V2.0 at 43 ± 0.5°C and 200 ml/min for 60 minutes (56 patients) or electromotive drug administration (EMDA) with 40 mg of MMC at 20 mA for 30 minutes (42 patients). The treatment schemes were similar: 6 weekly instillations as induction and 6-monthly instillations as maintenance. The recurrence rates were evaluated at 6 and 12 months and the progression rates at 12 months.ResultsThe recurrence-free rate at 12 months was 91,1% in the HIVEC group and 88.1% in the EMDA group (P ≥ 0.05). After the 12-month follow-up, only 1 progression occurred in each treatment group. In terms of adverse events, no significant differences were found between the treatments.ConclusionsHIVEC and EMDA techniques are comparable in terms of recurrence, progression and adverse events at 12 months in the treatment of patients with high- and intermediate-risk NMIBC.     

The impact of single-nucleotide polymorphisms on intravesical recurrence after bacillus Calmette–Guérin therapy for non-muscle invasive bladder cancer in a genome-wide association study

ObjectiveBacillus Calmette–Guérin (BCG) instillation therapy is widely used to reduce intravesical recurrence in non-muscle invasive bladder cancer (NMIBC). In this study, we aimed to reveal the genetic variations associated with intravesical recurrence after BCG therapy for NMIBC in a genome-wide association study (GWAS).Materials and methodsThis study included Japanese patients with NMIBC, in whom genomic DNA was obtained from whole blood samples. The association between genetic variation and treatment failure was analyzed by GWAS in 44 patients treated with BCG instillation as a discovery cohort. Candidate single-nucleotide polymorphisms (SNPs) were examined separately in 47 patients treated with BCG instillation and in 62 patients treated with chemotherapeutic agent instillation as validation studies.ResultsAmong the 44 patients in the discovery cohort, 14 cases experienced intravesical recurrent diseases. GWAS identified 12 candidate SNPs (rs9374832, rs35176001, rs363765, rs2127120, rs4277759, rs73664140, rs1607282, rs12141654, rs4541358, rs6986852, rs12373386, and rs17637903). In the validation study, a genetic risk stratification model using the number of risk alleles in rs363765 and rs6986852 discriminated the risk of intravesical recurrence after BCG therapy, but not after non-BCG therapy.ConclusionThis study suggested that several SNPs were associated with intravesical recurrence after BCG therapy for NMIBC. A genetic risk model may be useful to predict intravesical recurrence after BCG therapy, warranting further research and development for clinical application.     

Challenging the EAU Guidelines on Non–Muscle-Invasive Bladder Cancer (NMIBC): Single Instillation of Chemotherapy After Transurethral Resection of NMIBC and Chemotherapy Versus Bacillus Calmette-Guérin in Treatment of Intermediate-Risk Tumours

ContextAlthough the 2008 European Association of Urology (EAU) guidelines provide an excellent evidence-based framework for the management of non–muscle-invasive bladder cancer (NMIBC), some topics have been questioned and discussed by many authors and remain controversial.ObjectiveTo comment on the current EAU guidelines on NMIBC by taking into account new data published in 2009 in peer-reviewed urologic journals and once again discussing relevant data that were available when the guidelines were prepared.Evidence acquisitionTwo important guidelines have been challenged: (1) the use of a single instillation of a chemotherapeutic agent after transurethral resection (TUR) in all patients with NMIBC and (2) chemotherapy versus bacillus Calmette-Guérin (BCG) in the treatment of intermediate-risk tumours. The most important recent publications (2009), including randomised studies and meta-analyses, have been considered and evaluated.Evidence synthesisBased on a review of the current EAU guidelines and recent literature, a single instillation of a chemotherapeutic agent after TUR should be administered only in primary, solitary, low-grade NMIBCs. The first-line treatment of intermediate-risk tumours should be the instillation of BCG once a week for 6 wk, followed by maintenance for 1–3 yr. Mitomycin C is still the first treatment of choice for intermediate-risk and low-risk NMIBC patients (single, recurrent, low-grade tumour).ConclusionsA complete TUR of the bladder tumour plus immediate, postoperative, chemotherapeutic instillation is recommended for all patients with primary, solitary NMIBC, except in those with bladder wall perforation. For these low-risk tumours, no further therapy is required. For intermediate-risk disease, intravesical induction BCG plus maintenance should be considered the first choice, while intravesical chemotherapy should be considered for intermediate-risk and low-risk tumours (single, recurrent, low-grade NMIBC). In these patients, one immediate single instillation of chemotherapy should not be administered after TUR.     

Intravesical drug delivery for dysfunctional bladder

The bladder is a hollow organ that can be treated locally by transurethral catheter for intravesical drug instillation or cystoscopy for intravesical drug injection. With advancing technology, local organ‐specific therapy and drug delivery is of expanding interest for treating dysfunctional bladder, including interstitial cystitis/bladder pain syndrome, overactive bladder and sterile hemorrhagic cystitis after chemotherapy or pelvic radiation. Intravesical therapy has shown varying degrees of efficacy and safety in treating interstitial cystitis/bladder pain syndrome, overactive bladder and hemorrhagic cystitis with new modalities being developed. Intravesical (regional) therapy has several advantages than oral (systemic) therapy, including high local concentration and less systemic toxicity. In recent years, intravesical delivery of biotechnological products including neurotoxins and immunosuppressive agents, and delivery platform including liposomes has shown promise for lower urinary tract symptoms. This review considers the current status of intravesical therapy in dysfunctional bladder including interstitial cystitis/bladder pain syndrome, overactive bladder and hemorrhagic cystitis with special attention to lipid based novel drug‐delivery.     

Intravesical instillation of capsaicin in urology: A review of the literature.

OBJECTIVES: Interest in the intravesical instillation of capsaicin is growing among urologists. Its efficacy on detrusor hyperreflexia, hypersensitive bladder disorders and bladder pain has been reported in several studies. However, the lack of common evaluation parameters and the absence of consensus concerning a protocol of instillation hamper the interpretation of results. The purpose of this review is to better delineate the indications and optimum protocol for intravesical use of capsaicin. METHODS: Eight open and two placebo-controlled human clinical trials were analyzed. All 200 patients involved had lower urinary tract disorders. RESULTS: Clinical or urodynamic symptoms improved in 84.3% of the patients who received intravesical capsaicin for neurogenic hyperreflexic bladder, a significantly greater efficacy than that of placebo. Capsaicin may also be beneficial in patients who have non-neurogenic disorders. Whether or not the patients has a neurologic deficit, side effects appear during and in the period immediately following instillation. CONCLUSIONS: Intravesical capsaicin appears to be indicated in neurogenic hyperreflexic bladder, but is less effective against detrusor instability, hypersensitive bladder disorders or pelvic pain. The best instillation protocol and long-term tolerance remain to be established.     

Experience with Newer Intravesical Chemotherapy for High-Risk Non-Muscle-Invasive Bladder Cancer

The definitive treatment for patients with high-risk non-muscle-invasive bladder cancer (NMIBC) who fail to respond to intravesical bacillus Calmette-Guérin (BCG) is cystectomy. However, many patients who experience recurrence after BCG are either poor operative candidates or refuse surgery due to the long-term impact on their quality of life. In the last decade, there has been an increased interest in alternative intravesical therapies, and several novel chemotherapeutics have emerged as promising agents for high-risk NMIBC patients unable or unwilling to undergo cystectomy. Additionally, extended treatment regimens with combined induction and maintenance therapy have been investigated, and may increase the durability of response to these new agents, as has been shown for conventional intravesical therapy.     

Maintenance intravesical bacillus Calmette‐Guérin instillation for Ta,T1 cancer and carcinoma in situ of the bladder: Randomized controlled trial by the BCG Tokyo Strain Study Group

Objectives: We carried out a prospective, randomized, controlled trial to investigate the efficacy and safety of both induction and maintenance therapy with intravesical instillation of bacillus Calmette‐Guérin (BCG) for high‐risk non‐muscle invasive bladder cancer (NMIBC). Methods: Intravesical instillation of 80 mg Tokyo strain was given to patients with high‐risk NMIBC, including carcinoma in situ (CIS), once weekly for eight consecutive weeks as induction therapy. Patients who achieved complete response (CR) were randomly assigned to either the maintenance group or the observation group. Results: A total of 90 patients were enrolled. After induction therapy, 75% of the patients achieved CR and 53 of them were enrolled in the randomized comparative phase. A total of four maintenance instillations were given. Median follow‐up was 26.5 and 28.7 months after randomization in the maintenance and the observation group, respectively. Although it was not statistically significant, the 2‐year recurrence‐free survival rate in the maintenance group (95.8%) was higher than that in the observation group (74.1%, P = 0.078). Univariate analysis identified maintenance therapy as a significant factor influencing recurrence. During induction therapy, 82.2% of patients experienced urination‐related adverse drug reactions, but most events were not serious. There were fewer adverse drug reactions with maintenance therapy than with induction therapy. Neither induction therapy nor maintenance therapy reduced patients’ quality of life (QOL). Conclusions: These findings show high levels of efficacy and safety of BCG induction treatment for high‐risk NMIBC, and suggest that the number of maintenance instillations could probably be reduced without reducing treatment efficacy or influencing QOL.