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.

TM9SF1 is implicated in promoting the proliferation and invasion of bladder cancer cells

Zhuo et al looked into the part of transmembrane 9 superfamily member 1(TM9SF1)in bladder cancer(BC),and evaluated if it can be used as a therapeutic target.They created a permanent BC cell line and tested the effects of TM9SF1 overexpression and suppression on BC cell growth,movement,invasion,and cell cycle advancement.Their results show that TM9SF1 can boost the growth,movement,and invasion of BC cells and their access into the G2/M stage of the cell cycle.This research gives a novel direction and concept for targeted therapy of BC.

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.

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.

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.

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.

术前血清sTim-3、HMGB1水平与肌层浸润性膀胱癌根治术后预后的关系

目的探讨术前血清可溶性T细胞免疫球蛋白黏蛋白分子-3(sTim-3)、高迁移率族蛋白B1(HMGB1)水平与肌层浸润性膀胱癌(MIBC)根治术后预后的关系。方法选取2019年6月至2020年6月该院收治的85例MIBC患者作为MIBC组,另选取同期在该院体检的85例健康者作为对照组。采用酶联免疫吸附试验(ELISA)检测所有受试者血清sTim-3、HMGB1水平;根据血清sTim-3、HMGB1水平均值将MIBC患者分为sTim-3高表达组(≥均值)和sTim-3低表达组(<均值)、HMGB1高表达组(≥均值)和HMGB1低表达组(<均值)。对比各组血清sTim-3、HMGB1水平,以及不同sTim-3、HMGB1水平与MIBC患者病理特征的关系。采用Pearson相关分析MIBC患者血清sTim-3水平与血清HMGB1水平的相关性;采用Kaplan-Meier生存曲线分析不同血清sTim-3、HMGB1水平MIBC患者的生存预后情况。结果MIBC组患者血清sTim-3、HMGB1水平高于对照组(P<0.05)。Pearson相关性分析结果显示,MIBC组患者血清sTim-3水平与血清HMGB1水平呈正相关(r=0.405,P<0.001)。不同年龄、性别、肿瘤最大径及是否发生淋巴结转移MIBC患者的血清sTim-3、HMGB1水平比较,差异均无统计学意义(P>0.05),而不同TNM分期、组织分级、淋巴结状态MIBC患者的血清sTim-3、HMGB1水平比较,差异均有统计学意义(P<0.05)。根据血清sTim-3、HMGB1水平的均值将85例MIBC患者分为sTim-3高表达组(≥3.67 ng/mL,n=44)和sTim-3低表达组(<3.67 ng/mL,n=41)、HMGB1高表达组(≥14.91 ng/mL,n=47)和HMGB1低表达组(<14.91 ng/mL,n=38)。Kaplan-Meier生存曲线结果显示,sTim-3低表达组患者的3年生存曲线高于sTim-3高表达组患者(Log-rankχ^(2)=6.175,P=0.013),HMGB1低表达组患者的3年生存曲线高于HMGB1高表达组患者(Log-rankχ^(2)=4.056,P=0.044)。sTim-3高表达组与sTim-3低表达组MIBC患者的3年生存率分别为52.27%、78.05%,HMGB1高表达组与HMGB1低表达组MIBC患者3年生存率分别为55.32%、76.31%。结论血清sTim-3、HMGB1在MIBC患者中呈高表达,且二者水平呈正相关,可作为评估MIBC患者预后不良的重要指标。

Changes of oncogene DKK2 and SPOCK1 expression in bladder cancer lesions and their correlation with cancer cell proliferation and invasion

Objective: To investigate the changes of oncogene Dickkopf 2 (DKK2) and sparc/osteonectin, cwcv and kazal-like domains proteoglycan 1 (SPOCK1) expression in bladder cancer lesions and their correlation with cancer cell proliferation and invasion. Methods: The bladder cancer lesions and paracancerous lesions surgically removed in our hospital between March 2016 and March 2018 were collected, and kits were used to measure the mRNA expression levels of DKK2, SPOCK1, proliferation genes and invasion genes. Results: DKK2, hyperplasia suppressor gene (HSG), p16, cell adhesion molecule-1 (CADM1), tissue inhibitor of matrix metalloproteinase 2 (TIMP2) and TIMP4 mRNA expression in bladder cancer lesions were significantly lower than those in paracancerous lesions while SPOCK1, β-catenin, CyclinD1, c-myc, Vimentin and matrix metalloproteinase 2 (MMP2) mRNA expression were significantly higher than those in paracancerous lesions;DKK2 was negatively correlated with β-catenin, CyclinD1, c-myc, Vimentin and MMP2, and positively correlated with HSG, p16, CADM1, TIMP2 and TIMP4;SPOCK1 was positively correlated with β-catenin, CyclinD1, c-myc, Vimentin and MMP2, and negatively correlated with HSG, p16, CADM1, TIMP2 and TIMP4. Conclusion: The low expression of oncogene DKK2 and the high expression of SPOCK1 in bladder cancer lesions are related to the changes of proliferation and invasion genes and may be involved in the growth of lesions.

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.

LAT1表达水平与非肌层浸润性膀胱癌患者术后复发风险的相关性研究

目的:探讨L型氨基酸转运蛋白1(L-type amino acid transporter 1,LAT)表达水平与非肌层浸润性膀胱癌患者术后复发风险的相关性。方法:选取2021年2月至2022年2月于重庆医科大学附属永川医院接受手术治疗的非肌层浸润性膀胱癌患者108例作为研究对象,采用反转录酶聚合酶链反应测定膀胱癌组织(取自肿瘤所在部位区域)和癌旁组织(取自邻近正常区域组织)LAT1表达含量,对比膀胱癌组织和癌旁组织LAT1表达水平。同时根据膀胱癌组织LAT1表达含量的二分位数将所有患者分为高表达组和低表达组,对比2组临床病理参数。随访观察12个月观察2组术后复发情况,采用Kaplan-Meier曲线分析对比2组术后复发风险,使用多变量Cox比例风险回归模型确定术后复发的影响因素。结果:膀胱癌组织LAT1表达水平(1.80±0.35)较配对的癌旁组织LAT1表达水平(1.05±0.17)高(P<0.05);LAT1高表达组吸烟史、临床分期T_1占比较LAT1低表达组高(P<0.05);108例膀胱肿瘤患者术后的平均随访时间为(10.84±1.94)个月,其中33例复发,复发率为30.56%。KaplanMeier曲线显示,LAT1高表达组患者总体复发率较LAT1低表达组高(log-rank χ^(2)=4.382,P=0.036);多因素Cox回归分析显示,吸烟史(HR=6.539,95%CI=2.439~17.531)、临床分期为T_1期(HR=3.658,95%CI=1.808~7.398)、LAT1高表达(HR=3.425,95%CI=1.631~7.191)为非肌层浸润性膀胱癌患者术后复发的危险因素(P<0.05)。结论:LAT1在膀胱癌组织中表达水平高,高LAT1表达水平可能与膀胱癌患者术后复发风险增加有关。

非肌层浸润性膀胱癌TURBT治疗患者血清UBC1和DJ-1表达水平及其对预后预测价值研究

目的研究非肌层浸润性膀胱癌(non-muscle invasive bladder cancer,NMIBC)患者血清长链非编码RNA尿路上皮癌相关基因1[(LncRNA)upregulated in bladder cancer 1,UBC1]、帕金森病相关蛋白-1(DJ-1)的表达情况,分析两者对NMIBC患者预后的影响。方法选择2018年2月~2019年2月于河南科技大学第一附属医院接受经尿道膀胱肿瘤电切(TURBT)治疗的120例NMIBC患者为研究对象(NMIBC组),以同期健康体检的60例健康人群为对照组。应用实时荧光定量PCR检测各组血清UBC1水平。应用酶联免疫吸附实验检测各组血清DJ-1水平。比较不同临床病理特征NMIBC患者血清UBC1和DJ-1表达差异。Kaplan-Meier生存曲线分析血清UBC1和DJ-1表达对NMIBC患者无进展生存预后的影响。单因素及多因素COX回归分析影响NMIBC患者无进展生存预后的因素。结果相比于对照组,NMIBC组血清UBC1(4.19±0.48 vs 1.27±0.29)和DJ-1(8.62±3.60 ng/ml vs 4.31±1.07 ng/ml)水平升高,差异具有统计学意义(t=43.300,12.117,均P<0.05)。肿瘤T1期、高级别NMIBC患者血清中UBC1(5.21±0.56,5.11±0.53),DJ-1(11.28±3.98 ng/ml,10.50±3.87 ng/ml)表达分别高于Ta/Tis期、低级别患者(3.79±0.43,3.64±0.44;7.34±3.04ng/ml,7.49±3.23 ng/ml),差异具有统计学意义(t=15.314,5.966;16.393,4.584,均P<0.05)。UBC1高表达组和低表达组患者的平均无进展生存时间分别为28.17±3.68个月和33.59±3.32个月。UBC1高表达组患者累积无进展生存时间低于UBC1低表达组患者,差异具有统计学意义(Log-Rank testχ^(2)=6.681,P<0.05)。DJ-1高表达组和低表达组平均无进展生存时间分别为27.34±3.29个月和34.27±3.54个月。DJ-1高表达组患者累积无进展生存时间低于DJ-1低表达组患者,差异具有统计学意义(Log-Rank testχ^(2)=11.262,P<0.05)。肿瘤分期T1期(HR=1.613,95%CI=1.223~2.126)、肿瘤分级高级别(HR=1.917,95%CI=1.314~2.799),UBC1高表达(HR=1.937,95%CI=1.229~2.745)和DJ-1高表达(HR=1.738,95%CI=1.246~2.426)是影响NMIBC患者无进展生存预后的独立危险因素。结论NMIBC患者血清UBC1和DJ-1表达升高,两者表达与肿瘤分期及肿瘤分级有关,是影响NMIBC患者无进展生存预后的独立因素。

髓磷脂蛋白零样蛋白1对膀胱癌细胞增殖、迁移和侵袭的影响

目的探讨髓磷脂蛋白零样蛋白1(MPZL1)对膀胱癌T24细胞增殖、迁移和侵袭能力的影响。方法通过siRNA转染敲低膀胱癌T24细胞中MPZL1的表达,构建抑制MPZL1表达的膀胱癌细胞实验模型,将细胞分成si-NC的对照组和si-MPZL1实验组。通过ualcan数据库在线分析MPZL1基因在TCGA数据库膀胱癌患者中表达情况。CCK-8实验和平板克隆实验检测膀胱癌细胞增殖的变化,划痕实验和Transwell实验检测膀胱癌细胞迁移和侵袭的变化。结果MPZL1基因在膀胱癌患者中高表达,且随着临床分期的进展,其表达量呈现上升趋势,MPZL1基因高表达与膀胱癌的生存时间缩短有明显相关性。抑制MPZL1表达可抑制膀胱癌T24细胞的增殖、迁移和侵袭能力。结论敲低膀胱癌T24细胞中MPZL1表达,可抑制膀胱癌细胞的增殖、迁移和侵袭能力。

血清CXCL5、sICAM-1与非肌层浸润性膀胱癌患者术后转归的相关性

目的探析血清趋化因子配体5(CXCL5)、可溶性细胞间黏附分子-1(sICAM-1)与非肌层浸润性膀胱癌(NMIBC)患者术后转归的关系。方法采用便利抽样法,选取118例接受手术治疗的NMIBC患者,术后对患者进行为期1年的随访,观察患者无瘤生存期。比较不同CXCL5、sICAM-1水平的患者临床病理特征和无瘤生存期情况;采用COX回归验证血清CXCL5、sICAM-1水平与患者术后无瘤生存期的关系;采用Kaplan-Meier生存分析检验不同CXCL5、sICAM-1水平患者的无瘤生存期。结果经双变量Pearson相关系数检验,NMIBC患者血清CXCL5、sICAM-1水平之间呈正相关(γ=0.328,P<0.001)。血清CXCL5、sICAM-1高表达组中NMP22≥10 U/ml、低分化患者占比高于低表达组,差异有统计学意义(P<0.05);但血清CXCL5、sICAM-1不同表达组的年龄、性别、TNM分期、病灶大小及病灶数量比较,差异无统计学意义(P>0.05)。118例NMIBC患者中,经为期1年的随访,有34例出现复发,复发率为28.81%;经单因素和多因素COX回归分析结果显示,血清CXCL5、sICAM-1水平与NMIBC患者无瘤生存情况有关(P<0.05);血清CXCL5、sICAM-1水平高表达组的总体无瘤生存时间均低于低表达组,差异有统计学意义(P<0.05)。结论血清CXCL5、sICAM-1水平与NMIBC患者术后转归具有一定的相关性。

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.

PD-1/PD-L1在膀胱癌患者外周血T细胞和肿瘤细胞表达

【目的】探讨PD-1/PD-L1在膀胱肿瘤患者外周血T细胞和膀胱肿瘤细胞上表达的特点及临床意义。【方法】选取我科收治的64例原发性膀胱癌患者作为实验组(浅表性46例,浸润性18例),对照组为正常人群,共15例。分别取外周血,通过流式细胞仪检测CD8^+T淋巴细胞表明PD-1的表达量;另外取肿瘤患者膀胱癌组织和正常人群的膀胱肿瘤行免疫组化检测膀胱细胞或膀胱肿瘤细胞表面PD-L1的表达情况。【结果】膀胱癌患者外周血中CD8^+T淋巴细胞PD-1的表达量明显高于对照组[(2.25±0.60)%vs(0.68±0.17)%,P<0.001],其中浸润性膀胱癌患者外周血T细胞PD-1的表达高于浅表性膀胱癌患者[(3.04±0.46)%vs(0.68±0.17)%,P<0.001];膀胱肿瘤细胞和正常膀胱组织细胞PD-L1的表达率分别为:40.6%(26/64)和0(0/15,P<0.001),其中浸润性膀胱肿瘤细胞与浅表性膀胱肿瘤细胞PD-L1的表达率无明显差异(41.3%vs38.8%,P>0.01)。【结论】外周血中PD-1在CD8^+T细胞的表达水平可间接反映膀胱癌的进展程度,膀胱肿瘤细胞表面高表达PD-L1,但与肿瘤的进展无相关。

T淋巴瘤侵袭转移诱导因子1在膀胱癌组织中的表达及其与膀胱癌复发的关系

目的探讨T淋巴瘤侵袭转移诱导因子1(Tiam1)在膀胱癌组织中的表达及其与膀胱癌复发的关系。方法选择50例正常膀胱及233例膀胱癌组织,采用免疫组化、实时定量聚合酶链式反应、蛋白免疫印迹法分别检测Tiam1蛋白表达阳性及Tiam1mRNA、Tiam1蛋白相对表达情况,并分析膀胱癌Tiam1蛋白表达阳性与阴性患者的病理特征。结果膀胱癌组织中的Tiam1蛋白表达阳性率及Tiam1mRNA、Tiam1蛋白相对表达量均高于正常膀胱癌组织(均P<0.05)。膀胱癌Tiam1蛋白阳性表达组和Tiam1蛋白阴性表达组的病理分级、病理分期、淋巴结转移及复发率比较,差异均有统计学意义(均P<0.05);Cox回归分析结果显示,肿瘤高分级、病理高分期、淋巴结转移阳性及Tiam1蛋白表达阳性是膀胱癌患者复发的危险因素(均P<0.05)。结论Tiam1在膀胱癌中表达升高,且Tiam1蛋白表达阳性与膀胱癌复发密切相关。

非小细胞肺癌中Tiam-1的表达及其临床病理意义

目的:探讨T淋巴瘤侵袭和转移诱导蛋白(Tiam-1)在非小细胞肺癌(NSCLC)中的表达及临床意义。方法:应用免疫组化S-P法检测86例NSCLC病理标本的Tiam-1表达情况。结果:NSCLC中Tiam-1的表达阳性率为55.8%,与年龄、性别、组织学类型及分化程度间均无明显相关性(P>0.05)。Tima1阳性表达率与患者PTNM分期及淋巴结转移密切相关(P<0.05)。在获得术后随访的47例患者中,生存期<3年者19例,阳性表达15例,生存期≥3年者28例,阳性表达9例,两组间差异有统计学意义(P<0.01)。结论:Tiam-1过度表达与NSCLC的发展、淋巴结转移及预后有密切关系,有可能作为临床评估NSCLC进展及预测肿瘤转移潜能和预后的指标。

膀胱癌组织中Tiam1表达与膀胱癌进展及复发的关系

目的通过免疫组化SP法及RT-PCR方法检测膀胱癌组织T淋巴瘤侵袭转移诱导因子1(T-lymphoma invasion and metastasis inducing factor 1,Tiam1)表达,探讨Tiam1与膀胱癌发展及复发的关系。方法应用免疫组化SP法及RT-PCR方法检测50例正常膀胱及233例膀胱癌患者肿瘤组织中Tiam1表达变化,分析膀胱癌组织中Tiam1表达与膀胱癌分期、分级、复发的关系及其预测价值。结果正常膀胱组织及膀胱癌中均有Tiam1蛋白及RNA的不同表达,膀胱癌组织中呈过表达(P<0.05),高分期、高分级、淋巴结阳性及复发患者Tiam1表达量分别高于低分期、淋巴结阴性及无复发患者(P<0.05);多因素相关分析表明,Tiam1是膀胱癌患者进展及复发的独立危险因素。结论 Tiam1对膀胱癌预后有重要意义。