A Th2-score in the tumor microenvironment as a predictive biomarker of response to Bacillus Calmette Guérin in patients with non-muscle invasive bladder carcinoma:A retrospective study

Intravesical Bacillus Calmette Guerin(BCG)is the gold standard therapy for intermediate/high-risk nonmuscle invasive bladder cancer(NMIBC).However,the response rate is~60%,and 50%of non-responders will progress to muscle-invasive disease.BCG induces massive local infiltration of inflammatory cells(Th1)and ultimately cytotoxic tumor elimination.We searched for predictive biomarker of BCG response by analyzing tumor-infiltrating lymphocyte(TIL)polarization in the tumor microenvironment(TME)in pre-treatment biopsies.Pre-treatment biopsies from patients with NMIBC who received adequate intravesical instillation of BCG(n=32)were evaluated retrospectively by immunohistochemistry.TME polarization was assessed by quantifying the T-Bet+(Th1)and GATA-3+(Th2)lymphocyte ratio(G/T),and the density and degranulation of EPX+eosinophils.In addition,PD-1/PD-L1 staining was quantified.The results correlated with BCG response.In most non-responders,Th1/Th2 markers were compared in pre-and post-BCG biopsies.ORR was 65.6%in the study population.BCG responders had a higher G/T ratio and a greater number of degranulated EPX+cells.Variables combined into a Th2-score showed a significant association with higher scores in responders(p=0.027).A Th2-score cut-off value>48.1 allowed discrimination of responders with 91%sensitivity but lower specificity.Relapse-free survival was significantly associated with the Th2-score(p=0.007).In post-BCG biopsies from recurring patients,TILs increased Th2-polarization,probably reflecting BCG failure to induce a pro-inflammatory status and,thus,a lack of response.PD-L1/PD-1 expression was not associated with the response to BCG.Our results support the hypothesis that a preexisting Th2-polarized TME predicts a better response to BCG,assuming a reversion to Th1 polarization and antitumor activity.

Histologic subtypes of non-muscle invasive bladder cancer

The majority of bladder cancers(BCs)are non-muscle invasive BCs(NMIBCs)and show the morphology of a conventional urothelial carcinoma(UC).Aberrant morphology is rare but can be observed.The classification and characterization of histologic subtypes(HS)in UC in BC have mainly been described in muscle in-vasive bladder cancer(MIBC).However,the currently used classification is ap-plied for invasive urothelial neoplasm and therefore,also valid for a subset of NMIBC.The standard transurethral diagnostic work-up misses the presence of HS in NMIBC in a considerable percentage of patients and the real prevalence is not known.HS in NMIBC are associated with an aggressive phenotype.Conse-quently,clinical guidelines categorize HS of NMIBC as“(very)high-risk”tumors and recommend offering radical cystectomy to these patients.Alternative strategies for bladder preservation can only be offered to highly selected patients and ideally within clinical trials.Novel treatment strategies and biomarkers have been established MIBC and NMIBC but have not been comprehensively invest-igated in the context of HS in NMIBC.Further evaluation prior to implementation into clinical practice is needed.

Treatment and surveillance for non-muscle-invasive bladder cancer:a clinical practice guideline(2021 edition)

Non-muscle invasive bladder cancer(NMIBC)is a major type of bladder cancer with a high incidence worldwide,resulting in a great disease burden.Treatment and surveillance are the most important part of NIMBC management.In 2018,we issued“Treatment and surveillance for non-muscle-invasive bladder cancer in China:an evidencebased clinical practice guideline”.Since then,various studies on the treatment and surveillance of NMIBC have been published.There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China.Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated.We formed a working group of clinical experts and methodologists.Through questionnaire investigation of clinicians including primary medical institutions,24 clinically concerned issues,involving transurethral resection of bladder tumor(TURBT),intravesical chemotherapy and intravesical immunotherapy of NMIBC,and follow-up and surveillance of the NMIBC patients,were determined for this guideline.Researches and recommendations on the management of NMIBC in databases,guideline development professional societies and monographs were referred to,and the European Association of Urology was used to assess the certainty of generated recommendations.Finally,we issued 29 statements,among which 22 were strong recommendations,and 7 were weak recommendations.These recommendations cover the topics of TURBT,postoperative chemotherapy after TURBT,Bacillus Calmette–Guérin(BCG)immunotherapy after TURBT,combination treatment of BCG and chemotherapy after TURBT,treatment of carcinoma in situ,radical cystectomy,treatment of NMIBC recurrence,and follow-up and surveillance.We hope these recommendations can help promote the treatment and surveillance of NMIBC in China,especially for the primary medical institutions.

Intravesical bacillus Calmette-Guerin(BCG)in treating non-muscle invasive bladder cancer—analysis of adverse effects and effectiveness of two strains of BCG(Danish 1331 and Moscow-I)

Objective:To compare the differences in adverse effects and efficacy profile between bacillus Calmette-Guerin(BCG)Danish 1331 and BCG Moscow-I strain in management of non-muscle invasive bladder cancer.Methods:Clinical data of 188 cases of non-muscle invasive bladder cancer treated with BCG between January 2008 and December 2018 in our institute were collected prospectively and analysed retrospectively,and 114 patients who completed a minimum of 12 months of follow-up were analysed.Patient and tumor characteristics,strain of BCG,adverse effects,and tumor progression were included for analysis.Intravesical BCG was instilled in intermediate-and high-risk patients.Six weeks of induction BCG,followed by three weekly maintenance BCG at 3,6,12,18,and 24 months was advised in high-risk patients.Results:Overall 68 patients received BCG Danish 1331 strain and 46 patients received Moscow-I strain.Patient and tumor characteristics were well balanced between the two groups.The median follow-up period was 42.5 months and 34.5 months in Danish 1331 and Moscow-I groups,respectively.Adverse events like dropout rate,antitubercular treatment requirement,and need of cystectomy were higher in Moscow-I group(n=31,67.4%)when compared to Danish 1331 strain(n=33,48.5%)(p=0.046).On direct comparison between Danish 1331 and Moscow-I strain,there was similar 3-year recurrence-free survival(80.0%vs.72.9%)and 3-year progression-free survival(96.5%vs.97.8%).Conclusion:Study results suggest no significant differences between Danish 1331 and Moscow-I strain in recurrence-free survival and progression-free survival,but a significantly higher incidence of moderate to severe adverse events in BCG Moscow-I strain.

Molecular mechanisms and novel therapeutic strategies of BCG-unresponsive non-muscle invasive bladder cancer: Emerging immunotherapy has become a new choice?

Objective:THigh-risk non-invasive bladder cancer(NMIBC)has a high rate of recurrence and disease progression.At present,there are still insufficient effective prevention and treatment methods,especially for patients who have failed BCG treatment.This article reviews the research progress of the molecular mechanism of BCG unresponsive NMIBC,and summarizes the current status and prospects of emerging therapeutic strategies represented by immunotherapy,providing a theoretical basis for the immunotherapy of BCG non-reactive NMIBC.Methods:We searched the PubMed and CNKI journal full-text database search system for keywords"non-muscle invasive bladder cancer,BCG unresponsive,disease recurrence,disease progression,and immunotherapy"with 126 English and 538 Chinese articles.The literature,as well as the relevant clinical research in ClinicalTrials.gov,were integrated together to obtain the results.Results:Immunotherapy was performed in various types of tumors,and the use of immunotherapeutic drugs with different oncotargets administered alone,sequentially or in combination for the treatment of BCG-unresponsive NMIBC have achieved favorable effects,and more Clinical research is still ongoing.Conclusion:Immunotherapy is currently the most promising treatment for cancer,and it is indispensable for patients with NMIBC,both biologically and clinically.We look forward to more laboratory and clinical research in immunotherapy in the future.

Molecular Assessment of Non-Muscle Invasive and Muscle Invasive Bladder Tumors: Mapping of Putative Urothelial Stem Cells and Toll-Like Receptors (TLR) Signaling

Purpose: The main objectives of this study were to characterize and compare the urothelial stem cells (healthy and cancer cells) and TLRs features in the urinary bladder of men without lesionsand with non-muscle-invasive and muscle invasive urothelial tumors. Materials and Methods: Thirty samples of the urinary bladder of 50 to 80-year-old men, with and without diagnosis of malignant urothelial lesions were used. The 30 samples were divided into 3 groups (n = 10 per group): Normal Group;Non-Muscle Invasive Bladder Cancer Group;Muscle Invasive Bladder Cancer Group. The samples were histopathologically and immunohistochemically analyzed. The study was conducted at teaching Hospital of the University of Campinas (UNICAMP). Results: The CD44 and CD133 immunoreactivities were significantly intense in the muscle-invasive cancer group when compared to the other groups. The ABCG2 biomarker demonstrated intense immunoreactivities in both non-muscle and muscle invasive groups, and absent immunoreactivity in the normal group. All groups showed weak CD117 immunoreactivity. Putative Healthy Stem Cells (CD44/CD133/ CD117+) occurred in all groups. Putative Cancer Stem Cells (CD44/CD133/ABCG2+) only occurred in the non-muscle and muscle invasive cancer groups. TLR2 immunoreactivity was significantly lower in the non-muscle invasive cancer group and absent in the muscle invasive cancer group. TLR4 immunoreactivity was significantly lower in both cancer groups. Conclusions: This study leads us to the conclusion that putative cancer stem cell occurrence was sensitive to the decreased in TLR2 and TLR4 immunoreactivities. Also, TLR2 and TLR4 demonstrated their involvement in the regulation of the different biomarkers for putative healthy and cancer urothelial stem cells, probably acting as negative regulators of urothelial carcinogenesis. Taken together data obtained suggest that use of TLRs agonists could be a promising alternative for the treatment of non-muscle and muscle invasive bladder tumors.

Recirculating chemohyperthermia as a treatment for non-muscle invasive bladder cancer:Current and future perspectives

About 75% of all bladder cancer diagnosed are non-muscle invasive bladder cancer(NMIBC), recurring over 50% of them after transurethral resection of the bladder tumor. In order to prevent recurrences, adjuvant intravesical chemotherapy with mitomycin C and immunotherapy with bacillus Calmette-Gu-érin(BCG) is traditionally used. Unfortunately, many patients relapse after receiving these treatments and a significant proportion of them require surgery. After a one-to-three years BCG maintenance, the risk for progression at 5 years was 19.3% for T1G3 tumors. Many new treatment approaches are being investigated to increase the effectiveness of adjuvant intravesical therapy. One of the developing treatments for intermediate and high-risk NMIBC is the combination of intravesical chemotherapy and hyperthermia, called chemohyperthermia. This article provides a review of the mechanism of action, current status and indications, results and future perspectives.

Did the Scientific Innovations in the Management of Non-Muscle Invasive Bladder Cancer Patients Improve the Outcome during the Last 2 Decades?

Objectives: Previous reviews reported the outcome of each scientific modality in the management of T1 high-grade bladder cancer. The objective of this review is to assess and evaluate the available scientific modalities used during the last two decades and determine whether they were able to improve the clinical outcome. Literature Search Methodology: A systematic literature review was conducted from 2000-2020 using PubMed, Medline, Embase, and other database sites looking at randomized controlled trials (RCTs), clinical trials, research, review articles, and original articles addressing the different scientific modalities used to diagnose and manage patients with non-muscle invasive Bladder cancer (NMIBC)during the last 2 decades. More than 573 studies were retrieved following the preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and PICOS criteria (Population, Intervention, Comparators, Outcomes, and Study design). Only 85 articles were selected for review including 19 prospective trials, 44 RCTs, original articles, research articles, one review article, and clinical trials—Retrospective studies were excluded to limit bias as much as possible in the analysis. Results: Randomized controlled trials (RCTs) have become the gold standard for evaluating the efficacy of new treatments. They are considered the highest standard of evidence-based medicine and are the method of choice. Overall, we selected 85 studies for review, among them 63 prospective trials and RCTs, with a total of 21,895 patients, published between 2000 and 2020. Previously conducted studies have shown that identifying rare histological types with poor prognoses can help improve outcomes, mainly the plasmacytoid type. Many articles addressed the role of biomarkers in the early identification of patients with NMIBC for recurrence and progression—P-cadherin expression and others were used to predict recurrence and/or progression with promising results. Despite the need for modifications, risk stratification is an important tool that should be used to improve the outcome of patients with NMIBC. Some found that fluorescence diagnostic cystoscopy (FDC) and Photodynamic diagnosis (PDD) improved recurrence-free survival but not progression and outcome. All authors agree that intravesical BCG is the most effective therapy that changes the course of high-grade T1 mainly progression. Re-TURBT has become one of the recommendations of international societies, but its potential effect on survival improvement is debatable. Most of the articles showed the advantages of early cystectomy in NMIBC but all agree that the selection criteria must be clearly defined. Conclusions: This review analyzed the outcomes provided by the scientific advances in the field of management of NMIBC patients in the last two decades. Patients with T1 bladder cancer have variable outcomes because of tumor heterogeneity and clinical staging. Despite the great development in the field of diagnosis, risk stratification, and management, further large studies are mostly needed to better elucidate this subset of patients and avoid over and under-treatment.

Can intravesical bacillus Calmette-Guerin reduce recurrence in patients with non-muscle invasive bladder cancer？ An update and cumulative meta-analysis

Approximately 70% of newly diagnosed bladder tumors are non-muscle invasive bladder cancer （NMIBC）. NMIBC accounts for approximately 80% of total bladder cancer cases. Bacillus Calmette-Guerin （BCG） instillation and maintenance is considered as the standard adjuvant treatment for superficial bladder cancer. A number of randomized studies have focused on the benefit of maintenance therapy following initial BCG induction. To provide further insights into the effect of intravesical instillation on recurrence in patients with NMIBC, we analyzed this relationship by conducting an updated detailed meta-analysis. Evidence suggested that adjuvant intravesical BCG with maintenance treatment is significantly effective for the prophylaxis of tumor recurrence in patients with NMIBC.

Narrow band imaging for bladder cancer

Narrow band imaging(NBI)is a newly developed technology aiming to provide additional endoscopic information for patients with bladder cancer.This review focuses on the diagnostic accuracy and treatment outcome using NBI cystoscopy for the treatment of nonmuscle invasive bladder cancer.Current results showed improved sensitivity of NBI cystoscopy compared to conventional white light cystoscopy,although lower specificity and increased false-positive results were reported using NBI cystoscopy.The treatment outcome using NBI technology in transurethral resection of bladder tumor had a positive impact while decreased number of residual tumors and tumor recurrence at follow-up were reported.In the future,the application of NBI technology might refine the treatment and follow-up protocol in patients with non-muscle invasive bladder cancer.However,this large scale prospective studies are required to confirm the real cost-effectiveness of this new technology.

Markers for Diagnosis and Progression in Bladder Cancer

Bladder cancer is a common disease that is often detected late and has a high rate of recurrence and progression. The current standard of care for the primary detection and follow-up of NMIBC consists of urethro-cystoscopy associated with cytology. However, several clinical risk factors have been claimed to predict recurrence and progression, these factors have a predictive value on a population basis, but no parameter has been found that reliably predicts how an individual patient’s tumor will behave. In the last years many markers have been described in order to decrease the number of cystoscopies and try to provide individualized risk-stratified decision-making. We have focused our review in tumor markers for primary diagnosis, surveillance of non-muscle-invasive bladder cancer, and predicting progression to muscle-invasive disease. After our review, we can conclude that to the date no non-invasive biomarker has proven to be sensitive and specific enough to replace cystoscopy, neither in the diagnosis nor in the follow-up. On the other hand, promising results have been reported of potential biomarkers for predicting recurrence, early progression and poor response to BCG, new studies should be promoted to validate these results and make possible to incorporate markers as a new tool in clinical guidelines.

膀胱尿路上皮癌HER2表达及临床病理分析

目的探讨膀胱尿路上皮癌(bladder urothelial carcinoma,BUC)中HER2的表达情况,并分析其临床意义。方法收集膀胱非浸润性低级别BUC 27例、非浸润性高级别BUC 5例、浸润性高级别BUC 60例,采用免疫组化MaxVision法法检测各组织样本中HER2蛋白的表达,并分析HER2表达与临床病理特征的关系。通过GEPIA数据库或直接在肿瘤基因组图谱(The Cancer Genome Atlas,TCGA)中分析HER2(ERBB2)表达与BUC的关系。结果浸润性高级别BUC中HER22+/3+表达率(26.67%,16/60)显著高于非浸润性低级别BUC(7.41%,2/27)和非浸润性高级别BUC(0,0/5)(P<0.05)。多灶性浸润性高级别BUC中HER22+/3+表达率(75.00%,6/8)显著高于单灶性患者(19.23%,10/52)(P<0.05)。各组织学亚型中HER22+/3+表达率差异有统计学意义(P<0.05),其中普通型为30%(6/20)、腺样分化型为57.14%(4/7)、微乳头型为66.67%(4/6)、浆细胞样型为100.00%(2/2),余亚型均为0/1+。HER2表达与其他临床病理特征均无明显相关性(P>0.05)。GEPIA数据库中,BUC肿瘤组织中HER2(ERBB2)表达高于正常组织(P>0.05),HER2(ERBB2)高表达患者的总生存期(overall survival,OS)低于HER2(ERBB2)低表达(P>0.05);对TCGA数据进行Cox单因素分析显示:年龄、分期、T和N越高的患者OS较短。结论浸润性高级别BUC中HER22+/3+表达率高于非浸润性低级别和高级别BUC,并与肿瘤个数、组织学亚型密切相关,提示结合HER2表达状态、肿瘤个数和组织学亚型或有助于筛选出可能从HER2靶向治疗中获益的浸润性高级别BUC患者。

DARS2调控EGFR促进膀胱癌的EMT、迁移及侵袭

目的探讨线粒体天冬氨酰-tRNA合成酶2(DARS2)对膀胱癌细胞上皮间质转化(EMT)、迁移及侵袭的作用及其机制。方法利用TIMER和GEPIA数据库分析DARS2在膀胱尿路上皮癌(BLCA)中的表达及其与临床病理分期的关系。RT-qPCR检测人正常膀胱上皮细胞SV-HUC-1,膀胱癌细胞5637、T24和TCCSUP中DARS2 mRNA水平。TCCSUP细胞分为:control组(未转染)、si-NC组(转染阴性对照siRNA)、si-DARS2-1组(胞转染DARS2 siRNA-1)、si-DARS2组(转染DARS2 siRNA-2)、si-DARS2+Vector组(转染DARS2 siRNA-2+空载质粒)和si-DARS2+OE-EGFR组(转染DARS2 siRNA-2+EGFR过表达质粒)。Western blot检测DARS2,EMT标志蛋白E-cadherin、N-cadherin、Vimentin及EGFR的表达水平。Transwell侵袭和细胞划痕实验分别检测细胞侵袭能力和迁移能力。结果DARS2 mRNA水平在BLCA中显著上调,并与病理分期正相关(F=3.57,P=0.0289)。与永生化人正常膀胱上皮SV-HUC-1细胞相比,DARS2在5637、T24和TCCSUP膀胱癌细胞中表达水平显著升高(P<0.05)。与si-NC组相比,si-DARS2组中E-cadherin表达水平显著上调(P<0.05),N-cadherin、Vimentin和EGFR蛋白表达水平显著下调(P<0.05);与si-NC组相比,si-DARS2组细胞侵袭数目和细胞迁移率显著降低(P<0.01)。与si-DARS2+Vector组相比,si-DARS2+OE-EGFR组E-cadherin蛋白表达水平显著下降(P<0.05),N-cadherin和Vimentin蛋白表达水平显著升高(P<0.05),细胞侵袭数目和细胞迁移率显著增加(P<0.01)。结论敲低DARS2通过下调EGFR表达抑制膀胱癌的EMT、侵袭及迁移。

p-AKT与VEGF、HER-2在膀胱浸润性尿路上皮癌中的表达及其与患者预后关系研究

目的探讨磷酸化蛋白激酶B(p-AKT)与血管内皮生长因子(VEGF)、人表皮生长因子受体2(HER-2)在膀胱浸润性尿路上皮癌中的表达及其与患者预后的关系。方法用免疫组织化学染色(IHC)和荧光原位杂交(FISH)检测69例膀胱浸润性尿路上皮癌、20例膀胱黏膜良性组织(慢性炎症、乳头状瘤组织)中p-AKT、VEGF、HER-2蛋白的表达。结果膀胱浸润性尿路上皮癌中p-AKT、VEGF、HER-2表达均显著高于膀胱良性组织的表达(P<0.05);p-AKT、VEGF和HER-2在高级别浸润性尿路上皮癌中的表达均显著高于低级别浸润性尿路上皮癌中的表达(P<0.05);p-AKT在后期复发的患者中的表达高于未复发患者(P<0.05);浸润性尿路上皮癌患者中p-AKT与VEGF、HER-2的表达均呈显著正相关(P<0.05);p-AKT、VEGF和HER-2蛋白表达阳性的患者生存率均明显低于阴性表达患者的生存率(P<0.05)。结论p-AKT、VEGF及HER-2蛋白均可能参与了膀胱浸润性尿路上皮癌的发生发展,并且与患者的预后相关,可能成为膀胱尿路上皮癌的预后指标;膀胱浸润性尿路上皮癌中p-AKT与VEGF、HER-2可能存在相互调节关系。

Nectin-4在浸润性膀胱尿路上皮癌中的表达及其临床意义

目的研究Nectin-4在浸润性膀胱尿路上皮癌(BUC)组织中的表达及其临床意义,为BUC的临床诊断提供参考。方法应用免疫组织化学染色(IHC)法及RNAscope技术检测60例浸润性BUC及40例膀胱黏膜慢性炎组织中Nectin-4的表达,分析对比两种方法的检测结果,并探讨其与浸润性BUC临床病理特征的关系。在此基础上进一步分析BUC组织中Nectin-4蛋白表达与人类表皮生长因子受体2(Her-2)及程序性死亡因子配体1(PD-L1)的相关性。结果IHC法检测Nectin-4蛋白在浸润性BUC组及炎症组中的阳性表达率分别为78.33%(47/60)、17.50%(7/40);RNAscope技术检测Nectin-4 mRNA在浸润性BUC组及炎症组中表达的阳性表达率分别为83.33%(50/60)、12.50%(5/40);两种方法检测浸润性BUC组及炎症组中Nectin-4表达的Kappa值分别为0.732及0.610,一致性一般;Nectin-4蛋白在浸润性BUC中的表达与肌层浸润、组织学分级、脉管癌栓、淋巴结转移、临床分期相关(P<0.05);Nectin-4 mRNA在浸润性BUC中的表达与肿瘤最大径、肌层浸润、组织学分级、脉管癌栓、淋巴结转移、临床分期相关(P<0.05);Nectin-4在浸润性BUC中的高表达和Her-2表达呈正相关(P=0.002),与PD-L1表达无相关性(P>0.05)。结论Nectin-4在浸润性BUC中高表达,且通常和不良预后的病理参数相关,检测浸润性BUC中Nectin-4表达将有助于指导其临床的诊治。

前列腺特异性膜抗原在膀胱尿路上皮癌中的表达及临床意义

目的探讨前列腺特异性膜抗原(PSMA)在膀胱尿路上皮癌(BUC)中的表达及临床意义。方法选取2021年1月至2022年8月郑州大学附属郑州中心医院病理诊断为BUC的石蜡标本40例、正常膀胱组织的石蜡标本19例,分别进行石蜡切片,免疫组化法检测PSMA的表达情况,并分析PSMA表达与BUC患者临床病理特征及微血管密度(MVD)的关系。结果BUC患者中PSMA高表达率(62.50%)高于正常膀胱组织(31.58%),差异有统计学意义(χ^(2)=4.940,P=0.026)。在BUC患者中,PSMA高表达组肌层浸润率(92.00%)高于PSMA低表达组(60.00%),差异有统计学意义(χ^(2)=4.167,P=0.041);PSMA高表达组MVD(6.36±2.49)高于PSMA低表达组(2.38±1.26),差异有统计学意义(t=3.190,P=0.013)。结论PSMA在BUC中表达异常增高,且PSMA高表达与肌层浸润和MVD密切相关,在BUC患者预后评估及靶向诊疗中具有重要意义。

经尿道针状电极膀胱肿瘤整块切除术与经尿道钬激光膀胱肿瘤切除术治疗非肌层浸润性膀胱癌的治疗效果和安全性比较

目的评价经尿道针状电极膀胱肿瘤整块切除术与经尿道钬激光膀胱肿瘤切除术治疗非肌层浸润性膀胱癌的治疗效果和安全性。方法选取首都医科大学附属北京友谊医院自2015年3月至2017年10月收治的113例非肌层浸润性膀胱癌患者,依据手术方法分为针状电极经尿道膀胱肿瘤整块切除术组(针状电极组63例)和钬激光膀胱肿瘤切除术组(激光组50例)。对比两组患者手术时间、术中出血量、膀胱冲洗时间、尿管留置时间、住院时间及术后随访期复发率,所得数据进行统计学分析。结果 113例患者均成功完成手术,无中转开放手术,无输血病例,无膀胱穿孔病例。所有病例病理均可满足病理分期要求,其中Ta期31例,T1期82例。低级别尿路上皮癌77例,高级别尿路上皮癌36例。所有病例术后随访时间3~22个月,平均随访时间(11.4±5.8)个月。针状电极组肿瘤复发6例(9.5%,6/63),激光组复发7例(14%,7/50),两组均无病理分期进展者。两组患者手术时间、术中出血量、膀胱冲洗时间、尿管留置时间、住院时间及术后随访期复发率比较,差异无统计学意义(P>0.05)。结论经尿道针状电极膀胱肿瘤整块切除术治疗非肌层浸润性膀胱癌安全有效,可以有效避免由于闭孔神经反射引起的膀胱穿孔等严重合并症,切除标本满足病理分期要求。

膀胱部分切除术结合放化疗治疗肌层浸润性膀胱癌的疗效

目的回顾性分析膀胱部分切除术（PC）结合放化疗治疗肌层浸润性膀胱癌（MIBC）的疗效。方法收集2002年1月—2007年12月MIBC患者136例,男108例,女28例,平均年龄为（65.9±12.1）岁。分入两组：PC组100例,其中T2期74例,T3期16例,T4期10例。根治性膀胱全切除术（RC）组36例,其中T2期12例,T3期20例,T4期4例。术后对PC组T3、T4期患者加行以顺铂为主的放化疗。随访3~66个月,平均随访时间为（33.1±1.2）个月。采用Kaplan-Meier法和log-rank检验比较两组的生存情况,多因素Cox回归模型分析与MIBC生存和复发相关的预后因素。采用欧洲癌症研究与治疗组织（EORTC）的生存质量测定量表（QLQ-C30）和MIBC生存质量测定量表（QLQ-BLM30）评估患者的生存质量。结果 MIBC患者5年肿瘤特异性生存率为64.7%（88/136）,其中PC组为68.0%（68/100）,显著高于RC组的55.6%（20/36,P〈0.05）。PC组术后发生局部复发60例（60.0%）,其中非MIBC复发46例（76.7%,46/60）,MIBC复发14例（23.3%,14/60）;术后16个月内发生局部复发75.0%（45/60）。Cox回归分析显示,肿瘤数量〉3个（RR=2.718,95%CI为1.455~5.079,P=0.002）和浸润性的生长方式（RR=4.537,95%CI为1.573~13.081,P=0.005）是膀胱癌局部复发的独立预后因素。多因素分析显示,肿瘤数量〉3个（RR=4.109,95%CI为1.676~10.072,P=0.002）,脉管侵袭（RR=6.089,95%CI为2.038~18.246,P=0.001）和PC加输尿管再植术（RR=0.129,95%CI为0.027~0.627,P=0.011）是保留膀胱手术治疗MIBC后肿瘤特异性生存相关的独立预后指标,其中PC加输尿管再植是术后患者生存的保护因素。与MIBC生存相关的独立因素包括脉管侵袭（RR=4.176,95%CI为2.152~8.105,P=0.000）、肿瘤数量〉3个（RR=3.610,95%CI为1.887~6.906,P=0.000）、有膀胱肿瘤病史（RR=2.714,95%CI为1.400~5.263,P=0.003）和高龄（〉70岁,RR=2.609,95%CI1.440~4.729,P=0.002）。PC组的躯体功能和社会功能评分均显著高于RC组（P值分别〈0.05、0.01）,且经济困难、疲劳、失眠和体象障碍评分均显著低于RC组（P值分别〈0.01、0.05）。结论 PC结合放化疗是治疗MIBC的有效方法,患者可获得与RC相似甚至更高的生存率和更好的生存质量。肿瘤数量〉3个的患者不宜行保留膀胱的手术。

膀胱部分切除术在肌层浸润性膀胱癌治疗中的价值

目的探讨膀胱部分切除术在肌层浸润性膀胱癌治疗中的价值。方法回顾性分析105例肌层浸润性膀胱癌患者的临床资料,均接受了以膀胱部分切除术为主的综合治疗。通过术前评估,选择临床分期T2～3期、无盆腔淋巴结转移、瘤体位于膀胱顶部/侧壁/后壁/前壁、有安全外科切缘、切除肿瘤后有足够膀胱容量的患者接受治疗。男性78例、女性27例,中位年龄63岁。膀胱部分切除术中用羟基喜树碱浸泡膀胱及切口,11例同时行双侧盆腔淋巴结清扫。肿瘤中位直径2.3cm,病理分期为T2期41例、T3期61例、T4期3例,病理分级为高级别67例、低级别38例。76例(72.3%)接受了综合治疗,其中20例肿瘤较大的患者行新辅助治疗,56例病理为T3～4期/脉管瘤栓/盆腔淋巴结转移的患者接受了辅助治疗。结果本组无围手术期死亡的患者,1例(1.0%)外科切缘阳性,未见切口种植。20例新辅助治疗的患者总反应率50.0%。95例患者获得随访,中位随访期34个月(9～70个月)。29例(30.5%)局部复发,其中16例行挽救性膀胱切除术。本组5年生存率53.5%。结论选择合适的肌层浸润性膀胱癌患者,采取以膀胱部分切除术为主的综合治疗疗效较为满意,患者需严密随诊。

术前新辅助化疗治疗浸润性膀胱癌疗效观察

目的:观察术前新辅助化疗治疗浸润性膀胱癌的临床疗效。方法:对27例平均年龄68岁、有全膀胱切除指征而无法耐受或不愿接受膀胱全切的浸润性膀胱癌患者行骼内动脉化疗并栓塞联合手术治疗,观察膀胱保留率、降级降期率、肿瘤复发率,Kaplan-Meier法计算总生存率、无瘤生存率,并绘制生存曲线。结果:髂内动脉化疗、栓塞后,22例患者膀胱肿瘤缩小约81.5%,无变化5例;肿瘤临床分期降低21例(有效率77.8%),无变化6例;病理分级降低12例(降级率44.4%),分级不变15例。共24例患者得以保留膀胱,其中21例行经尿道膀胱肿瘤切除术(transurethral resection of the bladder,TURB),3例行膀胱部分切除术(膀胱保留率88.9%)。3例接受根治性膀胱全切术。术后1、2、3、5年分别复发4例(14.8%)、7例(25.9%)、11例(40.7%)、14例(51.9%)。2例随访11个月和23个月发现肿瘤远处转移后死亡,1例膀胱切口种植转移,局部切除后再发,带瘤生存,术后3年死于肿瘤进展,2例腺癌5年内死于肿瘤进展。至随访截止日期,死于术后肿瘤进展共5例。27例患者1、2、3、5年无瘤生存率分别为88.9%、73.6%、58.1%、41.4%,5年总生存率66.0%。结论:有选择地对部分浸润性膀胱癌患者施行术前髂内动脉灌注化疗、栓塞,联合手术等综合性治疗措施以保留功能性膀胱确实可行,但合理评价其在浸润性膀胱癌治疗中的应用价值尚需要进一步研究证实。