Introduction:Radical cystectomy with pelvic node dissection remains the standard of care for muscle-invasive bladder carcinoma(MIBC);however,there is a growing interest in bladder preservation alternatives among the e...Introduction:Radical cystectomy with pelvic node dissection remains the standard of care for muscle-invasive bladder carcinoma(MIBC);however,there is a growing interest in bladder preservation alternatives among the elderly population.Guidelines indicate that partial cystectomy(PC)combined with pelvic node dissection(LND)can be considered as an alternative in carefully selected individuals.Using the National Cancer Database,we analyzed the overall survival(OS)between PC with and without LND among octogenarians.Methods:We identified octogenarians with localized muscle-invasive bladder carcinoma(cT2-3N0M0)and urothelial histology who underwent PC with or without LND between 2004 and 2018.Based on the number of lymph nodes removed(LNR),the LND group was further subdivided into<10 and>=10 lymph node groups.A propensity-matched Kaplan-Meier survival analysis was performed to compare OS between these groups.Results:Among 2573 patients who underwent PC,492 octogenarians met our selection criteria.208(42.2%)had LND,while 284(57.8%)had no LND.Within the LND group,53(25.5%)had<10 LNR,and 155(74.5%)had>=10 LNR.The median OS for the matched LND and non-LND groups was 36.9 and 33.4 months(p=0.96),respectively.Similarly,<10 LNR and>=10 LNR had 36.9 and 43.5 months(p=0.42),respectively.Multivariate Cox regression analysis revealed no difference in the risk of mortality.Conclusion:Among octogenarians who underwent PC,there was no significant difference in OS between those with or without LND,and between<10 or>=10 LNR groups.Therefore,the role and extent of LND after PC need further exploration in this subset of the population.展开更多
Objective: To explore the current status and influencing factors of supportive care needs in patients with muscle-invasive bladder cancer after surgery, and to provide a reference for the development of targeted inter...Objective: To explore the current status and influencing factors of supportive care needs in patients with muscle-invasive bladder cancer after surgery, and to provide a reference for the development of targeted intervention strPan ategies. Methods: A general data questionnaire and supportive care needs scale were used to investigate 107 patients with muscle-invasive bladder cancer after surgery. Results: The total score of supportive care needs in patients with muscle-invasive bladder cancer after surgery was (98.48 ± 9.07). Multiple linear regression analysis showed that age, primary caregiver, medical payment method, number of hospitalizations and postoperative time were important influencing factors of supportive care needs in patients with muscle-invasive bladder cancer after surgery (P Conclusion: The supportive care needs of patients with muscle-invasive bladder cancer after surgery are at a low level. Medical staff should identify them early, pay more attention to young patients, patients without medical insurance and patients with multiple hospitalizations, and provide targeted nursing measures to meet their supportive care needs.展开更多
Objective:Non-muscle-invasive bladder cancer (NMIBC) remains a common challenge in uro-oncology with conflicting reports on recurrence risk. This study aimed to elucidate the recurrence rate of NMIBC in the Cancer Cli...Objective:Non-muscle-invasive bladder cancer (NMIBC) remains a common challenge in uro-oncology with conflicting reports on recurrence risk. This study aimed to elucidate the recurrence rate of NMIBC in the Cancer Clinic of Shahid Beheshti Hospital in Iran and to investigate related parameters affecting recurrence risk.Methods:The data of 143 patients with NMIBC, who underwent treatment between January 2017 and January 2020 and were followed up from the initial transurethral resection of bladder tumor until November 30, 2020 in our institution, were retrospectively assessed. The Cox regression analysis and Kaplan–Meier plot of recurrence-free survival were used to determine independent contributing factors for tumor recurrence.Results:Among patients with NMIBC, 83.9% were male, and 16.1% were female, with a mean age of 64.4 (standard deviation [SD] 12.9) years. During the follow-up, 71 (49.7%) patients showed tumor recurrence, with a mean recurrence time of 11.5 (SD 6.9) months. In the Chi-square test or Fisher's exact test, the age (≥65 years) (p=0.037), obesity (body mass index ≥30 kg/m^(2)) (p=0.004), no diabetes mellitus (p=0.005), smoking (current or former smoker) (p=0.001), immediate perfusion therapy (p=0.035), number of tumors (>3) (p<0.001), and tumor stage (Ta, T1, and Tis) (p=0.001) had independent significant effects on the recurrence of NMIBC. The multivariate Cox regression analysis indicated that preoperative obesity (hazards ratio [HR] 7.90;95% confidential interval [CI] 4.01–15.55;p<0.001), current or former smoking (HR 1.85;95% CI 1.07–3.20;p=0.027), and a high-grade tumor (HR 4.03;95% CI 1.59–10.25;p=0.003) were significant predictors of tumor recurrence. The Kaplan–Meier plot of recurrence-free survival showed that obesity (log-rank p<0.001), current or former smoking (log-rank p=0.001), and a high-grade tumor (log-rank p=0.006) were associated with a shorter time interval until the first tumor recurrence.Conclusion:The study found a high recurrence rate of NMIBC in Iran from January 2017 to January 2020, with the obesity, smoking history, and the high-grade tumor as contributing factors.展开更多
Objective:Conservative approaches in muscle-invasive bladder cancer(MIBC)have been evolved to avoid aggressive surgery,but are limited to elderly,frail,and patients medically unfit for surgery.Our study aimed to asses...Objective:Conservative approaches in muscle-invasive bladder cancer(MIBC)have been evolved to avoid aggressive surgery,but are limited to elderly,frail,and patients medically unfit for surgery.Our study aimed to assess the response rate of neoadjuvant chemotherapy(NACT)before radiotherapy(RT)in MIBC patients.Methods:Forty patients with urothelial carcinoma of stage T2-T4a,N0,M0 were enrolled between November 2013 and November 2015,and treated with three cycles of NACT with gemcitabine-cisplatin.Post-NACT response was assessed using Response Evaluation Criteria in Solid Tumors(RECIST)criteria.Patients who achieved complete response(CR)and partial response(PR)>50%were treated with radical RT,and those who had PR<50%,stable disease(SD),and progressive disease(PD)underwent radical cystectomy(RC).Survival analysis was done with Kaplan-Meier method and point-to-time events were analyzed with Cox-proportional hazards regression model.Results:After NACT,35(87.5%)patients achieved either PR>50%or CR,and were treated with RT.Five(12.5%)patients who had PR<50%,SD,or PD underwent RC.All patients who received radiation showed CR after 6 weeks.Median follow-up was 43 months(range:10-66 months)and median overall survival(OS)was not reached.Three-year OS,local control,and disease-free survival were 70.1%,60.9%,50.6%,respectively,and 50%of patients preserved their functioning bladder.Three-year OS rate was 88.9%in patients who achieved CR to NACT,73.1%in patients with PR≥50%and 40%in patients with PR<50%.Conclusion:NACT followed by RT provides a high probability of local response with bladder preservation in CR patients.Appropriate use of this treatment regimen in carefully selected patients may omit the need for morbid surgery.展开更多
Objective:To compare the efficacy and safety of hyperthermic intravesical chemotherapy(HIVEC)and intravesical chemotherapy(IVEC)in patients with intermediate and high risk nonmuscle-invasive bladder cancer(NMIBC)after...Objective:To compare the efficacy and safety of hyperthermic intravesical chemotherapy(HIVEC)and intravesical chemotherapy(IVEC)in patients with intermediate and high risk nonmuscle-invasive bladder cancer(NMIBC)after transurethral resection.Methods:We included 560 patients diagnosed with primary or recurrent NMIBC between April 2009 and December 2015 at 1 of 6 tertiary centers.We matched 364 intermediate or high risk cases and divided them into 2 groups:the HIVEC+IVEC group[chemohyperthermia(CHT)composed of 3 consecutive sessions followed by intravesical instillation without hyperthermia]and the IVEC group(intravesical instillation without hyperthermia).The data were recorded in the database.The primary endpoint was 2-year recurrence-free survival(RFS)in all NMIBC patients(n=364),whereas the secondary endpoints were the assessment of radical cystectomy(RC)and 5-year overall survival(OS).Results:There was a significant difference in the 2-year RFS between the two groups in all patients(n=364;HIVEC+IVEC:82.42%vs.IVEC:74.18%,P=0.038).Compared with the IVEC group,the HIVEC+IVEC group had a lower incidence of RC(P=0.0274).However,the 5-year OS was the same between the 2 groups(P=0.1434).Adverse events(AEs)occurred in 32.7%of all patients,but none of the events was serious(grades 3–4).No difference in the incidence or severity of AEs between each treatment modality was observed.Conclusions:This retrospective study showed that HIVEC+IVEC had a higher 2-year RFS and a lower incidence of RC than IVEC therapy in intermediate and high risk NMIBC patients.Both treatments were well-tolerated in a similar manner.展开更多
Background:This study aimed to select compounds with unique inhibitory effects on muscle-invasive bladder cancer(MIBC)from coumarone derivatives with similar parent nuclear structures and to reveal their tumor-suppres...Background:This study aimed to select compounds with unique inhibitory effects on muscle-invasive bladder cancer(MIBC)from coumarone derivatives with similar parent nuclear structures and to reveal their tumor-suppressive effects using various approaches.Methods:Bladder cancer cell lines SW780 and T24,as well as human normal bladder epithelial cell line SV-HUC-1 were selected as the study model,and these urinary system cells were co-incubated with various concentrations of(S,E)-4-(4-methylbenzylidene)-3-phenylchroman-3-ol,(S,E)-4-(4-isocyanobenzylidene)-3-phenylchroman-3-ol,(S,E)-4-(4-fluorobenzylidene)-3-phenylchroman-3-ol(FPO),and(S,E)-3-phenyl-4-(4-(trifluoromethoxy)benzylidene)chroman-3-ol.Cell activity was detected using cell counting kit-8.FPO showed the strongest inhibitory effect on MIBC cells;therefore,it was selected for further experiments.We monitored the FPO-induced T24 cell morphological changes with an inverted microscope.The FPO-inhibited migration of T24 cells was examined using a cell scratch assay.We detected the clonogenic ability of T24 cells through a clone formation test and evaluated their proliferative ability using a 5-ethynyl-2’-deoxyuridine fluorescence staining kit.The inhibitory effect of FPO against the cell cycle was monitored using flow cytometry,and its suppressive effect on the DNA replication ability of T24 cells was detected using double fluorescence staining(Ki67 and phalloidin).Results:Among the four candidate coumarone derivatives,FPO showed the most significant inhibitory effect on MIBC cells and was less toxic to normal urothelial cells.FPO inhibited T24 cell growth in time and dose-dependent manners(the half-inhibitory concentration is 8μM).FPO significantly repressed the proliferation,migration,and clonogenic ability of bladder cancer T24 cells.Cell mobility was significantly inhibited by FPO:30μM FPO almost completely repressed migration occurred at after 24 h treatment.Moreover,FPO significantly suppressed the clonogenicity of bladder cancer cells in a dose-dependent manner.Mechanistically,FPO targeted the cell cycle,arresting the S and G2 phases on bladder cancer T24 cells.Conclusion:We discovered a novel anticancer chemical,FPO,and proposed a potential mechanism,through which it suppresses MIBC T24 cells by repressing the cell cycle in the S and G2 phases.This study contributes to the development of novel anticancer drugs for MIBC.展开更多
The aim of this study was to investigate the incidence of erectile dysfunction(ED)in nonmuscle-invasive bladder cancer(NMIBC)patients before and after transurethral resection(TUR)in China.Clinical data from 165 male p...The aim of this study was to investigate the incidence of erectile dysfunction(ED)in nonmuscle-invasive bladder cancer(NMIBC)patients before and after transurethral resection(TUR)in China.Clinical data from 165 male patients with NMIBC who received adjuvant intravesical chemotherapy after TUR in Neijiang First People’s Hospital(Neijiang,China)between January 2010 and June 2019 were retrospectively reviewed.The sexual function of these patients was evaluated before and 1.5 years after initial TUR by the International Index of Erectile Function-5(IIEF-5).An age-specific subanalysis was performed among the patients:<45 years old(Group 1,n=19)and≥45 years old(Group 2,n=146).Before and 1.5 years after TUR,the incidence rates of ED in Group 1 were 15.8%and 52.6%,and those in Group 2 were 54.1%and 61.0%,respectively.The difference between groups was statistically significant at the preoperative stage(15.8%vs 54.1%,P=0.002)but not at the postoperative stage(52.6%vs 61.0%,P=0.562).Compared with the preoperative stage,the incidence of ED at the postoperative stage was increased significantly in Group 1(15.8%vs 52.6%,P=0.017)but not in Group 2(54.1%vs 61.0%,P=0.345).In conclusion,the incidence of ED increased in male NMIBC patients under the age of 45 years after TUR in China.These patients should be offered professional counseling during the follow-up period.展开更多
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...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.展开更多
In order to assess the effect of long-term versus short-term intravesical chemotherapy in preventing the recurrence of patients with non-muscle-invasive bladder cancer, we searched several da- tabases with words as me...In order to assess the effect of long-term versus short-term intravesical chemotherapy in preventing the recurrence of patients with non-muscle-invasive bladder cancer, we searched several da- tabases with words as mesh terms and free text words to find all eligible randomized clinical trials （RCTs） for the Comparison of the two strategies of instillation durations. ＂Observed-Expected events re- search （O-E）＂ and ＂Variance （V）＂ for calculating hazard ratio （HR） were used in Revman 5.2 software recommended by Cochrane Collabration for data analysis. Sensitivity and subgroup analysis were se- lected to minish heterogeneity. GRADEpro 3.6 profile recommended by Cochrane Collabration was employed for quality assessment of analyses. Finally, 13 eligible RCTs with 4216 patients were in- eluded in this review and 16 comparisons from 13 trials were involved for analysis. The pooled analysis revealed no significant difference between long-term and short-term duration [HR=0.99, 95% CI （0.89, 1.11）, P=-0.89]. Within the subgroup analysis, patients benefited from long-term instillations with a start regimen of one immediate instillation [HR=0.83, 95% CI （0.69, 1.00）, P=-0.05]. But patients were not suitable to receive long-term instillations with epirubicin （EPI） [HR=1.01, 95% CI （0.91, 1.13）, P=0.78] The progression rate was not reduced after long-term instillations [HR=0.96, 95% CI （0.66, 1.39）, P=0.82]. From our results, patients should not receive introvesical chemotherapy more than half a year. In contrast, patients with one immediate instillation are preferred to have a long-term duration at least one year. Long-term instillations can not reduce the progression rate.展开更多
Objectives: Surgical specimens obtained at the time of the last transurethral resection of bladder tumor (TURBT) for patients with nonmuscle-invasive bladder cancer (NMIBC) who underwent radical cystectomy were retros...Objectives: Surgical specimens obtained at the time of the last transurethral resection of bladder tumor (TURBT) for patients with nonmuscle-invasive bladder cancer (NMIBC) who underwent radical cystectomy were retrospectively evaluated in order to investigate the relationship between pathological variation and upstaging of NMIBC. Methods and Materials: Twenty patients (19 men, 1 woman;aged 69.4 ± 12.1 (mean ± SD) years) diagnosed with NMIBC underwent radical cystectomy during follow-up. Results: Five of the 20 patients (25%) had pathological upstaging in the radical cystectomy specimens. There was a statistical association between pathological upstaging and cancer death (p = 0.002). There were three patterns of pathological variation in the upstaged specimens: 1) in patients with BCG-resistant NMIBC, urothelial carcinoma invaded through the lamina propria;2) urothelial carcinoma showed diffuse invasion beyond the deep lamina propria, and the cancer cells had infiltrated as single cells and formed nodules;3) TURBT specimens showed a micropapillary variant. Conclusions: Since these pathological variations correlated with pathological upstaging, they may provide an indication for cystectomy in NMIBC patients.展开更多
Objective:To systematically review the most recent scientific literature regarding modern strategies for organ preservation in the treatment of non-metastatic muscle-invasive bladder cancer.Methods:Literature search w...Objective:To systematically review the most recent scientific literature regarding modern strategies for organ preservation in the treatment of non-metastatic muscle-invasive bladder cancer.Methods:Literature search was made using PubMed,Google Scholar,EMBASE,Wiley Library,and ClinicalTrials.gov following the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement.The primary outcome was 5-year overall survival rate,which was addressed by a systematic review and meta-analysis.The risk of bias and quality of evidence were assessed according to the Cochrane Collaboration and the Grading of Recommendations,Assessment,Development and Evaluation system.Results:The evidence is consistent in showing that 5-year survival of trimodality therapy is similar to radical cystectomy in selected patients,ranging between 29%and 73%.Patients undergoing bladder-sparing therapy were found to have better outcomes in terms of quality of life and sociability than those undergoing radical cystectomy.Immunotherapy is establishing itself as a strategy for organ-preservation treatment,showing complete response rates between 42%and 100%.However,most of these results have been obtained from ongoing clinical trials.Furthermore,there are still no studies comparing the efficacy among the different available therapies.Conclusion:Although radical cystectomy remains the gold standard treatment for muscle-invasive bladder cancer,its significant morbidity has prompted the exploration of alternative therapies.In this context,bladder preservation therapies,though supported by limited literature,emerge as a potential alternative that could offer comparable oncological outcomes in selected patients.展开更多
Bladder cancer encapsulates a wide spectrum of disease severities,with non-muscle invasive bladder cancer(NMIBC)representing an entirely different entity from muscle-invasive disease.Bacillus Calmette-Guerin(BCG)is on...Bladder cancer encapsulates a wide spectrum of disease severities,with non-muscle invasive bladder cancer(NMIBC)representing an entirely different entity from muscle-invasive disease.Bacillus Calmette-Guerin(BCG)is one of the most successful intravesical treatment methods for patients diagnosed.However,a considerable pro-portion of patients fail to respond to BCG treatment.Given the propensity for recurrence in patients with high-risk bladder cancer,these patients present with surgical dilemmas.There is currently no gold standard for salvage treatment post-BCG failure or unified definition as to what that means.In this review,we discuss the mechanisms of action and pathophysiology of BCG,potential theories behind BCG failure,and the scope of novel treatments forthis surgical conundrum.展开更多
Background:Studies have classified muscle-invasive bladder cancer(MIBC)into primary(initially muscle-invasive,PMIBC)and secondary subtypes(initially non-muscle-invasive but progresses,SMIBC),for which controversial su...Background:Studies have classified muscle-invasive bladder cancer(MIBC)into primary(initially muscle-invasive,PMIBC)and secondary subtypes(initially non-muscle-invasive but progresses,SMIBC),for which controversial survival outcomes were demonstrated.This study aimed to compare the survival outcomes between PMIBC and SMIBC patients in China.Methods:Patients diagnosed with PMIBC or SMIBC at West China Hospital from January 2009 to June 2019 were retrospectively included.Kruskal-Wallis and Fisher tests were employed to compare clinicopathological characteristics.Kaplan-Meier curves and Cox competing proportional risk model were used to compare survival outcomes.Propensity score matching(PSM)was employed to reduce the bias and subgroup analysis was used to confirm the outcomes.Results:A total of 405 MIBC patients were enrolled,including 286 PMIBC and 119 SMIBC,with a mean follow-up of 27.54 and 53.30 months,respectively.The SMIBC group had a higher proportion of older patients(17.65%[21/119]vs.9.09%[26/286]),chronic disease(32.77%[39/119]vs.22.38%[64/286]),and neoadjuvant chemotherapy(19.33%[23/119]vs.8.04%[23/286]).Before matching,SMIBC had a lower risk of overall mortality(OM)(hazard ratios[HR]0.60,95%confidence interval[CI]0.41-0.85,P=0.005)and cancer-specific mortality(CSM)(HR 0.64,95%CI 0.44-0.94,P=0.022)after the initial diagnosis.However,higher risks of OM(HR 1.47,95%CI 1.02-2.10,P=0.038)and CSM(HR 1.58,95%CI 1.09-2.29,P=0.016)were observed for SMIBC once it became muscle-invasive.After PSM,the baseline characteristics of 146 patients(73 for each group)were well matched,and SMIBC was confirmed to have an increased CSM risk(HR 1.83,95%CI 1.09-3.06,P=0.021)than PMIBC after muscle invasion.Conclusions:Compared with PMIBC,SMIBC had worse survival outcomes once it became muscle-invasive.Specific attention should be paid to non-muscle-invasive bladder cancer with a high progression risk.展开更多
Aim:Patients with muscle-invasive bladder cancer(MIBC)have a low survival rate,with a 5-year survival of approximately 45%,regardless of the treatment received.The risk of death within 5 years after radical cystectomy...Aim:Patients with muscle-invasive bladder cancer(MIBC)have a low survival rate,with a 5-year survival of approximately 45%,regardless of the treatment received.The risk of death within 5 years after radical cystectomy in patients with MIBC remains as high as 60%.Over 80%of patients with bladder cancer are over 65.Therefore,identifying prognostic correlates associated with radical cystectomy in older patients with MIBC could improve survival rates.In addition,radiotherapy and chemotherapy are particularly important as adjuvant treatments for MIBC patients undergoing radical cystectomy.Therefore,this study aimed to find risk factors for cancer-specific survival(CSS)and overall survival(OS)after radical cystectomy in elderly MIBC patients.The difference in survival between radiotherapy and chemotherapy was analyzed by Kaplan-Meier(K-M)curves to provide theoretical support for whether radiotherapy is recommended for such patients.Methods:Patients 65 or older diagnosed with MIBC with radical cystectomy between 2004-2018 were obtained from the Surveillance,Epidemiology,and End Results(SEER)database.2004-2015 patients were subjected to column line plot production and internal validation,and 2016-2018 patients were subjected to external temporal validation.A single-factor COX regression model was first used to screen for prognostic correlates.Then a multi-factor COX regression model was used to screen for independent risk factors.A nomogram was constructed by using independent risk factors.The accuracy and reliability of the nomogram were examined using calibration curves,consistency index(C-index),and area under subjects(AUC)as operational characteristic curves.Decision curve analysis(DCA)was performed to evaluate the clinical value of the prediction model.Results:A total of 11,557 patients were included in this study,divided into training set(N=4,712),validation set(N=4,810)and external validation set(N=2,035).Multivariate COX regression models showed that chemotherapy,radiotherapy,TNM stage,race,and age were independent risk factors for CSS and OS patients.We constructed a nomogram to predict CSS and OS in elderly MIBC patients undergoing radical cystectomy.The C-indexes were 0.692(95%CI:0.680-0.704)and 0.690(95%CI:0.678-0.702)for the CSS training and validation sets,respectively,and 0.674 for the OS training and validation sets(95%CI:0.664-0.684)and 0.672(95%CI:0.662-0.682)for the OS training and validation sets,respectively.The C-index of the external validation set CSS was 0.731(95%CI:709-0.753),and that of OS was 0.721(95%CI:0.701-0.741),indicating that the nomogram prediction model has good discriminative power.The calibration curves and AUC also suggested that the nomogram had good accuracy and discrimination.In addition,the KM curves of propensity-matched pre-and post-radiotherapy showed that radiotherapy was detrimental to patient survival.Meanwhile,chemotherapy favored OS and short-term CSS but not long-term CSS.Conclusions:We established a nomogram to predict the CSS and OS in elderly MIBC patients undergoing radical cystectomy.After internal cross-validation and external validation,the nomogram prediction model showed good accuracy and reliability,and the DCA results showed that the nomogram has good clinical value.In addition,this study gave good suggestions on whether radiotherapy or chemotherapy is necessary for radical cystectomy in elderly MIBC patients.展开更多
The published article titled“Puerarin inhibits proliferation and induces apoptosis by upregulation of miR-16 in bladder cancer cell line T24”has been retracted from Oncology Research,Vol.26,No.8,2018,pp.1227–1234.
Bladder cancer remains a significant global health challenge,requiring repeated treatments and surveillance and potentially morbid therapies,particularly in advanced and recurrent stages.Exosomes,small extracellular v...Bladder cancer remains a significant global health challenge,requiring repeated treatments and surveillance and potentially morbid therapies,particularly in advanced and recurrent stages.Exosomes,small extracellular vesicles central to intercellular communication,have emerged as innovative tools in cancer diagnostics,prognosis,and therapy.Their role in modulating the immune response and the tumor microenvironment makes them particularly attractive for cancer immunotherapy.This review provides a comprehensive overview of exosome biology,with a focus on their role in immune modulation and potential therapeutic applications.We explore the progress and challenges of exosome-based immunotherapy in cancer,followed by a discussion on the current state of bladder cancer immunotherapy.Additionally,we highlight the roles of exosomes in bladder cancer,emphasizing their diagnostic and prognostic applications.Despite promising preclinical studies and a growing number of clinical trials in other cancers,exosome-based therapies remain underexplored in bladder cancer.We discuss the current clinical trials related to exosomes in bladder cancer and propose their potential future role in immunotherapy.Finally,we address the challenges and opportunities in translating exosome-based therapies from bench to bedside,emphasizing the need for further preclinical and clinical investigations.This review emphasized the potential of exosome-based immunotherapy as a transformative approach for bladder cancer diagnosis and treatment.展开更多
BACKGROUNDΒ-elemene is widely used to treat a variety of cancers,including bladder cancer(BLCA).However,the anti-cancer target,effective constituents and mechanism was unclear.AIM To investigate the therapeutic effec...BACKGROUNDΒ-elemene is widely used to treat a variety of cancers,including bladder cancer(BLCA).However,the anti-cancer target,effective constituents and mechanism was unclear.AIM To investigate the therapeutic effect and underlying mechanism ofβ-elemene in BLCA.METHODS We first mined the GEPIA2 database to explore the association between the GM3(ST3 Beta-Galactoside Alpha-2,3-Sialyltransferase 5,GM3,ST3GAL5)gene and BLCA.Second,we performed in vitro experiments using BLCA cells to verify the inhibitory effect and targets therapy ofβ-elemene on BLCA.RESULTS Our results revealed a significantly reduced expression of GM3 in BLCA tissues.Notably,BLCA patients with higher GM3 expression exhibited prolonged overall survival and disease-free survival.In vitro studies demonstrated thatβ-elemene significantly affected BLCA cell viability,leading to a marked upregulation of GM3 expression,increased apoptotic cell populations,and a notable reduction in cell migration and invasion.WB analysis showed thatβ-elemene enhanced GM3 protein expression while simultaneously decreasing phosphorylated epidermal growth factor receptor(p-EGFR)levels.Additionally,overexpression or RNAi of GM3 in BLCA cells resulted in corresponding changes in epidermal growth factor receptor and p-EGFR expression levels.CONCLUSION This study provides preliminary evidence for further investigation into the molecular mechanisms ofβ-elemene in the treatment of BLCA.展开更多
Background:Studies have reported the special value of PANoptosis in cancer,but there is no study on the prognostic and therapeutic effects of PANoptosis in bladder cancer(BLCA).This study aimed to explore the role of ...Background:Studies have reported the special value of PANoptosis in cancer,but there is no study on the prognostic and therapeutic effects of PANoptosis in bladder cancer(BLCA).This study aimed to explore the role of PANoptosis in BLCA heterogeneity and its impact on clinical outcomes and immunotherapy response while establishing a robust prognostic model based on PANoptosis-related features.Methods:Gene expression profiles and clinical data were collected from public databases.Spatial heterogeneity of cell death pathways in BLCA was evaluated.Consensus clustering was performed based on identified PANoptosis genes.Cell death pathway scores,molecular,and pathway activation differences between different groups were compared.Protein-protein interaction(PPI)network construction was constructed,and immune-related gene sets,tumor immune dysfunction and exclusion(TIDE)scores,and SubMap analysis were used to evaluate immunomodulator expression and immunotherapy efficacy.Ten machine learning algorithms were utilized to develop the most accurate predictive risk model,and a nomogram was created for clinical application.Results:BLCA demonstrated a spatially heterogeneous distribution of pyroptosis,apoptosis,and necroptosis.Notably,T effector cells significantly colocalized with total apoptosis.Two PANoptosis modes were identified:high PANoptosis(high.PANO)and low PANoptosis(low.PANO).High.PANO was associated with worse clinical outcomes and advanced tumor stage,and increased activation of immune-related and cell death pathways.It also showed increased infiltration of immune cells,elevated expression of immunomodulatory factors,and enhanced responsiveness to the immunotherapy.The PANoptosis-related machine learning prognostic signature(PMLS)exhibited strong predictive power for outcomes in BLCA.CSPG4 was identified as a key gene underlying prognostic and therapeutic differences.Conclusion:PANoptosis shapes distinct prognostic and immunological phenotypes in BLCA.PMLS offers a reliable prognostic tool.CSPG4 may represent a potential therapeutic target in PANoptosis-driven BLCA.展开更多
Background:Bladder cancer prognosis remains suboptimal despite advancements in research.Current molecular subtyping methods are resource-intensive,highlighting the need for efficient,cost-effective approaches to predi...Background:Bladder cancer prognosis remains suboptimal despite advancements in research.Current molecular subtyping methods are resource-intensive,highlighting the need for efficient,cost-effective approaches to predict BCa molecular subtypes.Method:We developed a predictive model for BCa molecular subtypes using machine learning(ML)and pathomics derived from Hematoxylin-Eosin stained pathological slides.A cohort of 353 patients from TCGA was employed,and image features were extracted for analysis.Pathomic signatures were constructed using the LASSO Cox regression algorithm,and a pathomic-clinical nomogram was developed and validated in training and testing cohorts.Results:Seventy distinct image features were identified from 150 pathomic signatures.The model demonstrated robust predictive ability,with AUCs of 0.833 and 0.822 in the training and validation cohorts,respectively.The addition of pathomic score,N stage,and M stage improved the model’s discrimination,achieving AUCs of 0.877 and 0.794 in the training and validation cohorts.Limitations include the lack of an external validation cohort.Conclusion:Our ML-based pathomics model shows promise in predicting BCa molecular subtypes and has the potential to enhance prognosis prediction and inform treatment strategies,marking a significant step towards precision medicine for BCa.展开更多
Objective:Bladder cancer(BCa)is a prevalent malignant tumor in the urinary system.Molecular subtyping,utilizing molecular characteristics,represents a novel classification system that has demonstrated its efficacy in ...Objective:Bladder cancer(BCa)is a prevalent malignant tumor in the urinary system.Molecular subtyping,utilizing molecular characteristics,represents a novel classification system that has demonstrated its efficacy in tumor diagnosis and treatment.Given the critical role of molecular subtyping in the BCa treatment,acquiring a comprehensive understanding is imperative for guiding treatment decisions,optimizing risk assessment systems,and ultimately improving patient prognosis.Methods:In this review,we provide a comprehensive overview of the research progress in molecular subtyping of BCa,with a primary focus on discussing its utility in guiding various treatment modalities including neoadjuvant chemotherapy,neoadjuvant immunotherapy,and targeted therapy.In addition,this review also covers the trimodality treatment,antibody-drug conjugates,and the treatment of small cell BCa.Results:We present a comprehensive overview of the responsiveness or resistance of different molecular subtypes of BCa to various therapeutic modalities.The basal subtype demonstrates favorable sensitivity to neoadjuvant chemotherapy across multiple classification systems,whereas the luminal infiltrated subtype exhibits potential susceptibility to immunotherapy.In terms of targeted therapy,the basal-like and the basal/squamous subtypes in some classifications have shown notable responsiveness to epidermal growth factor receptor-targeted therapy.Moreover,the luminal subtype in the University of Texas M.D.Anderson Cancer Center classification,the luminal papillary subtypes according to the Cancer Genome Atlas Research Network classification in 2017,and the luminal unstable type in the 2019 Molecular Subtyping classification show potential for the fibroblast growth factor receptor 3-targeted treatment.Conclusion:The significance and impact of BCa molecular subtyping in guiding treatment,evaluating progression,and predicting prognosis are increasingly acknowledged.Accurate subtyping and broad application can bring good benefits to clinical decision-making,risk assessment,and prognostic evaluation.展开更多
文摘Introduction:Radical cystectomy with pelvic node dissection remains the standard of care for muscle-invasive bladder carcinoma(MIBC);however,there is a growing interest in bladder preservation alternatives among the elderly population.Guidelines indicate that partial cystectomy(PC)combined with pelvic node dissection(LND)can be considered as an alternative in carefully selected individuals.Using the National Cancer Database,we analyzed the overall survival(OS)between PC with and without LND among octogenarians.Methods:We identified octogenarians with localized muscle-invasive bladder carcinoma(cT2-3N0M0)and urothelial histology who underwent PC with or without LND between 2004 and 2018.Based on the number of lymph nodes removed(LNR),the LND group was further subdivided into<10 and>=10 lymph node groups.A propensity-matched Kaplan-Meier survival analysis was performed to compare OS between these groups.Results:Among 2573 patients who underwent PC,492 octogenarians met our selection criteria.208(42.2%)had LND,while 284(57.8%)had no LND.Within the LND group,53(25.5%)had<10 LNR,and 155(74.5%)had>=10 LNR.The median OS for the matched LND and non-LND groups was 36.9 and 33.4 months(p=0.96),respectively.Similarly,<10 LNR and>=10 LNR had 36.9 and 43.5 months(p=0.42),respectively.Multivariate Cox regression analysis revealed no difference in the risk of mortality.Conclusion:Among octogenarians who underwent PC,there was no significant difference in OS between those with or without LND,and between<10 or>=10 LNR groups.Therefore,the role and extent of LND after PC need further exploration in this subset of the population.
文摘Objective: To explore the current status and influencing factors of supportive care needs in patients with muscle-invasive bladder cancer after surgery, and to provide a reference for the development of targeted intervention strPan ategies. Methods: A general data questionnaire and supportive care needs scale were used to investigate 107 patients with muscle-invasive bladder cancer after surgery. Results: The total score of supportive care needs in patients with muscle-invasive bladder cancer after surgery was (98.48 ± 9.07). Multiple linear regression analysis showed that age, primary caregiver, medical payment method, number of hospitalizations and postoperative time were important influencing factors of supportive care needs in patients with muscle-invasive bladder cancer after surgery (P Conclusion: The supportive care needs of patients with muscle-invasive bladder cancer after surgery are at a low level. Medical staff should identify them early, pay more attention to young patients, patients without medical insurance and patients with multiple hospitalizations, and provide targeted nursing measures to meet their supportive care needs.
文摘Objective:Non-muscle-invasive bladder cancer (NMIBC) remains a common challenge in uro-oncology with conflicting reports on recurrence risk. This study aimed to elucidate the recurrence rate of NMIBC in the Cancer Clinic of Shahid Beheshti Hospital in Iran and to investigate related parameters affecting recurrence risk.Methods:The data of 143 patients with NMIBC, who underwent treatment between January 2017 and January 2020 and were followed up from the initial transurethral resection of bladder tumor until November 30, 2020 in our institution, were retrospectively assessed. The Cox regression analysis and Kaplan–Meier plot of recurrence-free survival were used to determine independent contributing factors for tumor recurrence.Results:Among patients with NMIBC, 83.9% were male, and 16.1% were female, with a mean age of 64.4 (standard deviation [SD] 12.9) years. During the follow-up, 71 (49.7%) patients showed tumor recurrence, with a mean recurrence time of 11.5 (SD 6.9) months. In the Chi-square test or Fisher's exact test, the age (≥65 years) (p=0.037), obesity (body mass index ≥30 kg/m^(2)) (p=0.004), no diabetes mellitus (p=0.005), smoking (current or former smoker) (p=0.001), immediate perfusion therapy (p=0.035), number of tumors (>3) (p<0.001), and tumor stage (Ta, T1, and Tis) (p=0.001) had independent significant effects on the recurrence of NMIBC. The multivariate Cox regression analysis indicated that preoperative obesity (hazards ratio [HR] 7.90;95% confidential interval [CI] 4.01–15.55;p<0.001), current or former smoking (HR 1.85;95% CI 1.07–3.20;p=0.027), and a high-grade tumor (HR 4.03;95% CI 1.59–10.25;p=0.003) were significant predictors of tumor recurrence. The Kaplan–Meier plot of recurrence-free survival showed that obesity (log-rank p<0.001), current or former smoking (log-rank p=0.001), and a high-grade tumor (log-rank p=0.006) were associated with a shorter time interval until the first tumor recurrence.Conclusion:The study found a high recurrence rate of NMIBC in Iran from January 2017 to January 2020, with the obesity, smoking history, and the high-grade tumor as contributing factors.
文摘Objective:Conservative approaches in muscle-invasive bladder cancer(MIBC)have been evolved to avoid aggressive surgery,but are limited to elderly,frail,and patients medically unfit for surgery.Our study aimed to assess the response rate of neoadjuvant chemotherapy(NACT)before radiotherapy(RT)in MIBC patients.Methods:Forty patients with urothelial carcinoma of stage T2-T4a,N0,M0 were enrolled between November 2013 and November 2015,and treated with three cycles of NACT with gemcitabine-cisplatin.Post-NACT response was assessed using Response Evaluation Criteria in Solid Tumors(RECIST)criteria.Patients who achieved complete response(CR)and partial response(PR)>50%were treated with radical RT,and those who had PR<50%,stable disease(SD),and progressive disease(PD)underwent radical cystectomy(RC).Survival analysis was done with Kaplan-Meier method and point-to-time events were analyzed with Cox-proportional hazards regression model.Results:After NACT,35(87.5%)patients achieved either PR>50%or CR,and were treated with RT.Five(12.5%)patients who had PR<50%,SD,or PD underwent RC.All patients who received radiation showed CR after 6 weeks.Median follow-up was 43 months(range:10-66 months)and median overall survival(OS)was not reached.Three-year OS,local control,and disease-free survival were 70.1%,60.9%,50.6%,respectively,and 50%of patients preserved their functioning bladder.Three-year OS rate was 88.9%in patients who achieved CR to NACT,73.1%in patients with PR≥50%and 40%in patients with PR<50%.Conclusion:NACT followed by RT provides a high probability of local response with bladder preservation in CR patients.Appropriate use of this treatment regimen in carefully selected patients may omit the need for morbid surgery.
基金supported by the National Natural Science Foundation of China(Grant No.81972918)the Guangzhou Key Medical Discipline Construction Project Fund+1 种基金the Guangzhou Major Clinical Technology Program(Grant No.2019ZD16)the Guanzhou Municipal Special Clinical Technology Project(Grant No.2019TS40)。
文摘Objective:To compare the efficacy and safety of hyperthermic intravesical chemotherapy(HIVEC)and intravesical chemotherapy(IVEC)in patients with intermediate and high risk nonmuscle-invasive bladder cancer(NMIBC)after transurethral resection.Methods:We included 560 patients diagnosed with primary or recurrent NMIBC between April 2009 and December 2015 at 1 of 6 tertiary centers.We matched 364 intermediate or high risk cases and divided them into 2 groups:the HIVEC+IVEC group[chemohyperthermia(CHT)composed of 3 consecutive sessions followed by intravesical instillation without hyperthermia]and the IVEC group(intravesical instillation without hyperthermia).The data were recorded in the database.The primary endpoint was 2-year recurrence-free survival(RFS)in all NMIBC patients(n=364),whereas the secondary endpoints were the assessment of radical cystectomy(RC)and 5-year overall survival(OS).Results:There was a significant difference in the 2-year RFS between the two groups in all patients(n=364;HIVEC+IVEC:82.42%vs.IVEC:74.18%,P=0.038).Compared with the IVEC group,the HIVEC+IVEC group had a lower incidence of RC(P=0.0274).However,the 5-year OS was the same between the 2 groups(P=0.1434).Adverse events(AEs)occurred in 32.7%of all patients,but none of the events was serious(grades 3–4).No difference in the incidence or severity of AEs between each treatment modality was observed.Conclusions:This retrospective study showed that HIVEC+IVEC had a higher 2-year RFS and a lower incidence of RC than IVEC therapy in intermediate and high risk NMIBC patients.Both treatments were well-tolerated in a similar manner.
基金supported by National Nature Science Foundation of China(82172978)Taishan Scholars Program of Shandong Province(Grant No.tsqn201909147)+1 种基金the Key Project at Central Government Level:the ability establishment of sustainable use for valuable Chinese medicine resources(2060302)the Student Innovation Training Program in Jining Medical University(cx2021116).
文摘Background:This study aimed to select compounds with unique inhibitory effects on muscle-invasive bladder cancer(MIBC)from coumarone derivatives with similar parent nuclear structures and to reveal their tumor-suppressive effects using various approaches.Methods:Bladder cancer cell lines SW780 and T24,as well as human normal bladder epithelial cell line SV-HUC-1 were selected as the study model,and these urinary system cells were co-incubated with various concentrations of(S,E)-4-(4-methylbenzylidene)-3-phenylchroman-3-ol,(S,E)-4-(4-isocyanobenzylidene)-3-phenylchroman-3-ol,(S,E)-4-(4-fluorobenzylidene)-3-phenylchroman-3-ol(FPO),and(S,E)-3-phenyl-4-(4-(trifluoromethoxy)benzylidene)chroman-3-ol.Cell activity was detected using cell counting kit-8.FPO showed the strongest inhibitory effect on MIBC cells;therefore,it was selected for further experiments.We monitored the FPO-induced T24 cell morphological changes with an inverted microscope.The FPO-inhibited migration of T24 cells was examined using a cell scratch assay.We detected the clonogenic ability of T24 cells through a clone formation test and evaluated their proliferative ability using a 5-ethynyl-2’-deoxyuridine fluorescence staining kit.The inhibitory effect of FPO against the cell cycle was monitored using flow cytometry,and its suppressive effect on the DNA replication ability of T24 cells was detected using double fluorescence staining(Ki67 and phalloidin).Results:Among the four candidate coumarone derivatives,FPO showed the most significant inhibitory effect on MIBC cells and was less toxic to normal urothelial cells.FPO inhibited T24 cell growth in time and dose-dependent manners(the half-inhibitory concentration is 8μM).FPO significantly repressed the proliferation,migration,and clonogenic ability of bladder cancer T24 cells.Cell mobility was significantly inhibited by FPO:30μM FPO almost completely repressed migration occurred at after 24 h treatment.Moreover,FPO significantly suppressed the clonogenicity of bladder cancer cells in a dose-dependent manner.Mechanistically,FPO targeted the cell cycle,arresting the S and G2 phases on bladder cancer T24 cells.Conclusion:We discovered a novel anticancer chemical,FPO,and proposed a potential mechanism,through which it suppresses MIBC T24 cells by repressing the cell cycle in the S and G2 phases.This study contributes to the development of novel anticancer drugs for MIBC.
文摘The aim of this study was to investigate the incidence of erectile dysfunction(ED)in nonmuscle-invasive bladder cancer(NMIBC)patients before and after transurethral resection(TUR)in China.Clinical data from 165 male patients with NMIBC who received adjuvant intravesical chemotherapy after TUR in Neijiang First People’s Hospital(Neijiang,China)between January 2010 and June 2019 were retrospectively reviewed.The sexual function of these patients was evaluated before and 1.5 years after initial TUR by the International Index of Erectile Function-5(IIEF-5).An age-specific subanalysis was performed among the patients:<45 years old(Group 1,n=19)and≥45 years old(Group 2,n=146).Before and 1.5 years after TUR,the incidence rates of ED in Group 1 were 15.8%and 52.6%,and those in Group 2 were 54.1%and 61.0%,respectively.The difference between groups was statistically significant at the preoperative stage(15.8%vs 54.1%,P=0.002)but not at the postoperative stage(52.6%vs 61.0%,P=0.562).Compared with the preoperative stage,the incidence of ED at the postoperative stage was increased significantly in Group 1(15.8%vs 52.6%,P=0.017)but not in Group 2(54.1%vs 61.0%,P=0.345).In conclusion,the incidence of ED increased in male NMIBC patients under the age of 45 years after TUR in China.These patients should be offered professional counseling during the follow-up period.
基金suppor ted by the National Key Research and Development Plan of China(Technology helps Economy 2020,2016YFC0106300)the National Natural Science Foundation of China(82174230)the Major Program Fund of Technical Innovation Project of Department of Science and Technology of Hubei Province(2016ACAl52)。
文摘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.
文摘In order to assess the effect of long-term versus short-term intravesical chemotherapy in preventing the recurrence of patients with non-muscle-invasive bladder cancer, we searched several da- tabases with words as mesh terms and free text words to find all eligible randomized clinical trials （RCTs） for the Comparison of the two strategies of instillation durations. ＂Observed-Expected events re- search （O-E）＂ and ＂Variance （V）＂ for calculating hazard ratio （HR） were used in Revman 5.2 software recommended by Cochrane Collabration for data analysis. Sensitivity and subgroup analysis were se- lected to minish heterogeneity. GRADEpro 3.6 profile recommended by Cochrane Collabration was employed for quality assessment of analyses. Finally, 13 eligible RCTs with 4216 patients were in- eluded in this review and 16 comparisons from 13 trials were involved for analysis. The pooled analysis revealed no significant difference between long-term and short-term duration [HR=0.99, 95% CI （0.89, 1.11）, P=-0.89]. Within the subgroup analysis, patients benefited from long-term instillations with a start regimen of one immediate instillation [HR=0.83, 95% CI （0.69, 1.00）, P=-0.05]. But patients were not suitable to receive long-term instillations with epirubicin （EPI） [HR=1.01, 95% CI （0.91, 1.13）, P=0.78] The progression rate was not reduced after long-term instillations [HR=0.96, 95% CI （0.66, 1.39）, P=0.82]. From our results, patients should not receive introvesical chemotherapy more than half a year. In contrast, patients with one immediate instillation are preferred to have a long-term duration at least one year. Long-term instillations can not reduce the progression rate.
文摘Objectives: Surgical specimens obtained at the time of the last transurethral resection of bladder tumor (TURBT) for patients with nonmuscle-invasive bladder cancer (NMIBC) who underwent radical cystectomy were retrospectively evaluated in order to investigate the relationship between pathological variation and upstaging of NMIBC. Methods and Materials: Twenty patients (19 men, 1 woman;aged 69.4 ± 12.1 (mean ± SD) years) diagnosed with NMIBC underwent radical cystectomy during follow-up. Results: Five of the 20 patients (25%) had pathological upstaging in the radical cystectomy specimens. There was a statistical association between pathological upstaging and cancer death (p = 0.002). There were three patterns of pathological variation in the upstaged specimens: 1) in patients with BCG-resistant NMIBC, urothelial carcinoma invaded through the lamina propria;2) urothelial carcinoma showed diffuse invasion beyond the deep lamina propria, and the cancer cells had infiltrated as single cells and formed nodules;3) TURBT specimens showed a micropapillary variant. Conclusions: Since these pathological variations correlated with pathological upstaging, they may provide an indication for cystectomy in NMIBC patients.
文摘Objective:To systematically review the most recent scientific literature regarding modern strategies for organ preservation in the treatment of non-metastatic muscle-invasive bladder cancer.Methods:Literature search was made using PubMed,Google Scholar,EMBASE,Wiley Library,and ClinicalTrials.gov following the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement.The primary outcome was 5-year overall survival rate,which was addressed by a systematic review and meta-analysis.The risk of bias and quality of evidence were assessed according to the Cochrane Collaboration and the Grading of Recommendations,Assessment,Development and Evaluation system.Results:The evidence is consistent in showing that 5-year survival of trimodality therapy is similar to radical cystectomy in selected patients,ranging between 29%and 73%.Patients undergoing bladder-sparing therapy were found to have better outcomes in terms of quality of life and sociability than those undergoing radical cystectomy.Immunotherapy is establishing itself as a strategy for organ-preservation treatment,showing complete response rates between 42%and 100%.However,most of these results have been obtained from ongoing clinical trials.Furthermore,there are still no studies comparing the efficacy among the different available therapies.Conclusion:Although radical cystectomy remains the gold standard treatment for muscle-invasive bladder cancer,its significant morbidity has prompted the exploration of alternative therapies.In this context,bladder preservation therapies,though supported by limited literature,emerge as a potential alternative that could offer comparable oncological outcomes in selected patients.
文摘Bladder cancer encapsulates a wide spectrum of disease severities,with non-muscle invasive bladder cancer(NMIBC)representing an entirely different entity from muscle-invasive disease.Bacillus Calmette-Guerin(BCG)is one of the most successful intravesical treatment methods for patients diagnosed.However,a considerable pro-portion of patients fail to respond to BCG treatment.Given the propensity for recurrence in patients with high-risk bladder cancer,these patients present with surgical dilemmas.There is currently no gold standard for salvage treatment post-BCG failure or unified definition as to what that means.In this review,we discuss the mechanisms of action and pathophysiology of BCG,potential theories behind BCG failure,and the scope of novel treatments forthis surgical conundrum.
基金China Post-doctoral Science Foundation(No.2021M692306,No.2022T150455)PostDoctor Re-search Project of West China Hospital of Sichuan University(No.2021HXBH025)
文摘Background:Studies have classified muscle-invasive bladder cancer(MIBC)into primary(initially muscle-invasive,PMIBC)and secondary subtypes(initially non-muscle-invasive but progresses,SMIBC),for which controversial survival outcomes were demonstrated.This study aimed to compare the survival outcomes between PMIBC and SMIBC patients in China.Methods:Patients diagnosed with PMIBC or SMIBC at West China Hospital from January 2009 to June 2019 were retrospectively included.Kruskal-Wallis and Fisher tests were employed to compare clinicopathological characteristics.Kaplan-Meier curves and Cox competing proportional risk model were used to compare survival outcomes.Propensity score matching(PSM)was employed to reduce the bias and subgroup analysis was used to confirm the outcomes.Results:A total of 405 MIBC patients were enrolled,including 286 PMIBC and 119 SMIBC,with a mean follow-up of 27.54 and 53.30 months,respectively.The SMIBC group had a higher proportion of older patients(17.65%[21/119]vs.9.09%[26/286]),chronic disease(32.77%[39/119]vs.22.38%[64/286]),and neoadjuvant chemotherapy(19.33%[23/119]vs.8.04%[23/286]).Before matching,SMIBC had a lower risk of overall mortality(OM)(hazard ratios[HR]0.60,95%confidence interval[CI]0.41-0.85,P=0.005)and cancer-specific mortality(CSM)(HR 0.64,95%CI 0.44-0.94,P=0.022)after the initial diagnosis.However,higher risks of OM(HR 1.47,95%CI 1.02-2.10,P=0.038)and CSM(HR 1.58,95%CI 1.09-2.29,P=0.016)were observed for SMIBC once it became muscle-invasive.After PSM,the baseline characteristics of 146 patients(73 for each group)were well matched,and SMIBC was confirmed to have an increased CSM risk(HR 1.83,95%CI 1.09-3.06,P=0.021)than PMIBC after muscle invasion.Conclusions:Compared with PMIBC,SMIBC had worse survival outcomes once it became muscle-invasive.Specific attention should be paid to non-muscle-invasive bladder cancer with a high progression risk.
基金The study was supported by:Scientific Research Foundation of Education Department of Yunnan Province(No.2023J0295)Kunming Medical University Joint Project of Department of Science and Technology of Yunnan Province(No.02301AY070001-108)+3 种基金Kunming City Health Science and Technology Talent“1000”training Project(No.2020-SW(Reserve)-112)Kunming Health and Health Commission Health Research Project(No.2020-0201-001)Kunming Medical Joint Project of Yunnan Science and Technology Department(No.202001 AY070001-271)Open Research Fund of Clinical Research Center for Children’s Health and Diseases of Yunnan Province(2022-ETYY-YJ-03).
文摘Aim:Patients with muscle-invasive bladder cancer(MIBC)have a low survival rate,with a 5-year survival of approximately 45%,regardless of the treatment received.The risk of death within 5 years after radical cystectomy in patients with MIBC remains as high as 60%.Over 80%of patients with bladder cancer are over 65.Therefore,identifying prognostic correlates associated with radical cystectomy in older patients with MIBC could improve survival rates.In addition,radiotherapy and chemotherapy are particularly important as adjuvant treatments for MIBC patients undergoing radical cystectomy.Therefore,this study aimed to find risk factors for cancer-specific survival(CSS)and overall survival(OS)after radical cystectomy in elderly MIBC patients.The difference in survival between radiotherapy and chemotherapy was analyzed by Kaplan-Meier(K-M)curves to provide theoretical support for whether radiotherapy is recommended for such patients.Methods:Patients 65 or older diagnosed with MIBC with radical cystectomy between 2004-2018 were obtained from the Surveillance,Epidemiology,and End Results(SEER)database.2004-2015 patients were subjected to column line plot production and internal validation,and 2016-2018 patients were subjected to external temporal validation.A single-factor COX regression model was first used to screen for prognostic correlates.Then a multi-factor COX regression model was used to screen for independent risk factors.A nomogram was constructed by using independent risk factors.The accuracy and reliability of the nomogram were examined using calibration curves,consistency index(C-index),and area under subjects(AUC)as operational characteristic curves.Decision curve analysis(DCA)was performed to evaluate the clinical value of the prediction model.Results:A total of 11,557 patients were included in this study,divided into training set(N=4,712),validation set(N=4,810)and external validation set(N=2,035).Multivariate COX regression models showed that chemotherapy,radiotherapy,TNM stage,race,and age were independent risk factors for CSS and OS patients.We constructed a nomogram to predict CSS and OS in elderly MIBC patients undergoing radical cystectomy.The C-indexes were 0.692(95%CI:0.680-0.704)and 0.690(95%CI:0.678-0.702)for the CSS training and validation sets,respectively,and 0.674 for the OS training and validation sets(95%CI:0.664-0.684)and 0.672(95%CI:0.662-0.682)for the OS training and validation sets,respectively.The C-index of the external validation set CSS was 0.731(95%CI:709-0.753),and that of OS was 0.721(95%CI:0.701-0.741),indicating that the nomogram prediction model has good discriminative power.The calibration curves and AUC also suggested that the nomogram had good accuracy and discrimination.In addition,the KM curves of propensity-matched pre-and post-radiotherapy showed that radiotherapy was detrimental to patient survival.Meanwhile,chemotherapy favored OS and short-term CSS but not long-term CSS.Conclusions:We established a nomogram to predict the CSS and OS in elderly MIBC patients undergoing radical cystectomy.After internal cross-validation and external validation,the nomogram prediction model showed good accuracy and reliability,and the DCA results showed that the nomogram has good clinical value.In addition,this study gave good suggestions on whether radiotherapy or chemotherapy is necessary for radical cystectomy in elderly MIBC patients.
文摘The published article titled“Puerarin inhibits proliferation and induces apoptosis by upregulation of miR-16 in bladder cancer cell line T24”has been retracted from Oncology Research,Vol.26,No.8,2018,pp.1227–1234.
基金funded by start-up funds from the University of Chicago.
文摘Bladder cancer remains a significant global health challenge,requiring repeated treatments and surveillance and potentially morbid therapies,particularly in advanced and recurrent stages.Exosomes,small extracellular vesicles central to intercellular communication,have emerged as innovative tools in cancer diagnostics,prognosis,and therapy.Their role in modulating the immune response and the tumor microenvironment makes them particularly attractive for cancer immunotherapy.This review provides a comprehensive overview of exosome biology,with a focus on their role in immune modulation and potential therapeutic applications.We explore the progress and challenges of exosome-based immunotherapy in cancer,followed by a discussion on the current state of bladder cancer immunotherapy.Additionally,we highlight the roles of exosomes in bladder cancer,emphasizing their diagnostic and prognostic applications.Despite promising preclinical studies and a growing number of clinical trials in other cancers,exosome-based therapies remain underexplored in bladder cancer.We discuss the current clinical trials related to exosomes in bladder cancer and propose their potential future role in immunotherapy.Finally,we address the challenges and opportunities in translating exosome-based therapies from bench to bedside,emphasizing the need for further preclinical and clinical investigations.This review emphasized the potential of exosome-based immunotherapy as a transformative approach for bladder cancer diagnosis and treatment.
基金Supported by the Zhejiang Provincial Traditional Chinese Medicine Foundation,No.2021ZA021 and No.2022ZZ005.
文摘BACKGROUNDΒ-elemene is widely used to treat a variety of cancers,including bladder cancer(BLCA).However,the anti-cancer target,effective constituents and mechanism was unclear.AIM To investigate the therapeutic effect and underlying mechanism ofβ-elemene in BLCA.METHODS We first mined the GEPIA2 database to explore the association between the GM3(ST3 Beta-Galactoside Alpha-2,3-Sialyltransferase 5,GM3,ST3GAL5)gene and BLCA.Second,we performed in vitro experiments using BLCA cells to verify the inhibitory effect and targets therapy ofβ-elemene on BLCA.RESULTS Our results revealed a significantly reduced expression of GM3 in BLCA tissues.Notably,BLCA patients with higher GM3 expression exhibited prolonged overall survival and disease-free survival.In vitro studies demonstrated thatβ-elemene significantly affected BLCA cell viability,leading to a marked upregulation of GM3 expression,increased apoptotic cell populations,and a notable reduction in cell migration and invasion.WB analysis showed thatβ-elemene enhanced GM3 protein expression while simultaneously decreasing phosphorylated epidermal growth factor receptor(p-EGFR)levels.Additionally,overexpression or RNAi of GM3 in BLCA cells resulted in corresponding changes in epidermal growth factor receptor and p-EGFR expression levels.CONCLUSION This study provides preliminary evidence for further investigation into the molecular mechanisms ofβ-elemene in the treatment of BLCA.
基金supported by grants from the National Natural Science Foundation of China(No.82172741)Shanghai Municipal Health Bureau(No.2020CXJQ03).
文摘Background:Studies have reported the special value of PANoptosis in cancer,but there is no study on the prognostic and therapeutic effects of PANoptosis in bladder cancer(BLCA).This study aimed to explore the role of PANoptosis in BLCA heterogeneity and its impact on clinical outcomes and immunotherapy response while establishing a robust prognostic model based on PANoptosis-related features.Methods:Gene expression profiles and clinical data were collected from public databases.Spatial heterogeneity of cell death pathways in BLCA was evaluated.Consensus clustering was performed based on identified PANoptosis genes.Cell death pathway scores,molecular,and pathway activation differences between different groups were compared.Protein-protein interaction(PPI)network construction was constructed,and immune-related gene sets,tumor immune dysfunction and exclusion(TIDE)scores,and SubMap analysis were used to evaluate immunomodulator expression and immunotherapy efficacy.Ten machine learning algorithms were utilized to develop the most accurate predictive risk model,and a nomogram was created for clinical application.Results:BLCA demonstrated a spatially heterogeneous distribution of pyroptosis,apoptosis,and necroptosis.Notably,T effector cells significantly colocalized with total apoptosis.Two PANoptosis modes were identified:high PANoptosis(high.PANO)and low PANoptosis(low.PANO).High.PANO was associated with worse clinical outcomes and advanced tumor stage,and increased activation of immune-related and cell death pathways.It also showed increased infiltration of immune cells,elevated expression of immunomodulatory factors,and enhanced responsiveness to the immunotherapy.The PANoptosis-related machine learning prognostic signature(PMLS)exhibited strong predictive power for outcomes in BLCA.CSPG4 was identified as a key gene underlying prognostic and therapeutic differences.Conclusion:PANoptosis shapes distinct prognostic and immunological phenotypes in BLCA.PMLS offers a reliable prognostic tool.CSPG4 may represent a potential therapeutic target in PANoptosis-driven BLCA.
基金supported by the Guangzhou Municipal Basic Research Program Jointly Funded by City,University,and Enterprise Special Project(2024A03J0907)the Natural Science Foundation of Guangdong Province(2024A1515013201)+1 种基金the National Natural Science Foundation of China(82203720,82203188,82002682,81972731,81773026,81972383)the Science and Technology Project of Zhongshan Municipality(No.2024B1032).
文摘Background:Bladder cancer prognosis remains suboptimal despite advancements in research.Current molecular subtyping methods are resource-intensive,highlighting the need for efficient,cost-effective approaches to predict BCa molecular subtypes.Method:We developed a predictive model for BCa molecular subtypes using machine learning(ML)and pathomics derived from Hematoxylin-Eosin stained pathological slides.A cohort of 353 patients from TCGA was employed,and image features were extracted for analysis.Pathomic signatures were constructed using the LASSO Cox regression algorithm,and a pathomic-clinical nomogram was developed and validated in training and testing cohorts.Results:Seventy distinct image features were identified from 150 pathomic signatures.The model demonstrated robust predictive ability,with AUCs of 0.833 and 0.822 in the training and validation cohorts,respectively.The addition of pathomic score,N stage,and M stage improved the model’s discrimination,achieving AUCs of 0.877 and 0.794 in the training and validation cohorts.Limitations include the lack of an external validation cohort.Conclusion:Our ML-based pathomics model shows promise in predicting BCa molecular subtypes and has the potential to enhance prognosis prediction and inform treatment strategies,marking a significant step towards precision medicine for BCa.
基金supported by the grants from the National Natural Science Foundation of China(82273132 to Liu B).
文摘Objective:Bladder cancer(BCa)is a prevalent malignant tumor in the urinary system.Molecular subtyping,utilizing molecular characteristics,represents a novel classification system that has demonstrated its efficacy in tumor diagnosis and treatment.Given the critical role of molecular subtyping in the BCa treatment,acquiring a comprehensive understanding is imperative for guiding treatment decisions,optimizing risk assessment systems,and ultimately improving patient prognosis.Methods:In this review,we provide a comprehensive overview of the research progress in molecular subtyping of BCa,with a primary focus on discussing its utility in guiding various treatment modalities including neoadjuvant chemotherapy,neoadjuvant immunotherapy,and targeted therapy.In addition,this review also covers the trimodality treatment,antibody-drug conjugates,and the treatment of small cell BCa.Results:We present a comprehensive overview of the responsiveness or resistance of different molecular subtypes of BCa to various therapeutic modalities.The basal subtype demonstrates favorable sensitivity to neoadjuvant chemotherapy across multiple classification systems,whereas the luminal infiltrated subtype exhibits potential susceptibility to immunotherapy.In terms of targeted therapy,the basal-like and the basal/squamous subtypes in some classifications have shown notable responsiveness to epidermal growth factor receptor-targeted therapy.Moreover,the luminal subtype in the University of Texas M.D.Anderson Cancer Center classification,the luminal papillary subtypes according to the Cancer Genome Atlas Research Network classification in 2017,and the luminal unstable type in the 2019 Molecular Subtyping classification show potential for the fibroblast growth factor receptor 3-targeted treatment.Conclusion:The significance and impact of BCa molecular subtyping in guiding treatment,evaluating progression,and predicting prognosis are increasingly acknowledged.Accurate subtyping and broad application can bring good benefits to clinical decision-making,risk assessment,and prognostic evaluation.
