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: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
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
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
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
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
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
Background:Lower urinary tract symptoms(LUTS)and pain are clinically relevant problems after transurethral resection(TURBT)of nonmuscle-invasive bladder cancer.Although intravesical instillation of hyaluronic acid has...Background:Lower urinary tract symptoms(LUTS)and pain are clinically relevant problems after transurethral resection(TURBT)of nonmuscle-invasive bladder cancer.Although intravesical instillation of hyaluronic acid has already been proven to be a valid treatment for storage LUTS and pain in patients with inflammatory bladder syndrome,its effcacy in patients who undergo TURBT is unknown.This study aimed to present the results of a prospective,randomized,controlled,clinical pilot study on the safety and clinical performance of Hydeal Cyst(Fidia Farmaceutici S.p.A.,Italy),a device formulated to provide progressive,long-lasting intravesical release of hyaluronic acid.Materials and methods:Adults diagnosed with nonmuscle-invasive bladder cancer and scheduled for TURBT were included and underwent 4 visits up to 25 days after TURBT.Of the 47 patients who completed the investigation,25 participants received 2 postoperative intravesical instillations with Hydeal Cyst.The effcacy of Hydeal Cyst on storage LUTS,pain,urinary symptoms,and patients'quality of life was evaluated using validated questionnaires.Results:Although the overall LUTS were similar in the 2 experimental groups,lower micturition frequency and fewer daytime micturitions were observed in patients treated with Hydeal Cyst.These patients also showed a signifcant reduction in pain(p=0.03)3 days after catheter removal and better quality of life at the end of the study.The device was well tolerated,with no treatment-emergent adverse events of severe intensity.Conclusion:The results from this pilot study indicate a clinically meaningful improvement of symptoms after 2 instillations of Hydeal Cyst,supporting this intervention as a potentially effective treatment for LUTS and pain after TURBT.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
Objective: To analyze the impact of motivational nursing under the solution-focused approach on health behaviors in surgical care for bladder cancer patients. Methods: A sample of 72 bladder cancer patients who underw...Objective: To analyze the impact of motivational nursing under the solution-focused approach on health behaviors in surgical care for bladder cancer patients. Methods: A sample of 72 bladder cancer patients who underwent surgical treatment from September 2024 to September 2025 was randomly divided into groups using a random number table. Group A received motivational nursing under the solution-focused approach, while Group B received conventional nursing. Health behavior scores and complication indicators were compared between the two groups. Results: Group A had higher scores on the Health-Promoting Lifestyle Profile II (HPLP-Ⅱ) than Group B, with p < 0.05. The postoperative complication rate in Group A was lower than that in Group B, with p < 0.05. Conclusion: For bladder cancer patients undergoing surgery, receiving motivational nursing under the solution-focused approach can improve health behaviors, alleviate negative emotions, and is highly feasible and effective.展开更多
Objectives:To date,predictive and prognostic biomarkers for Bladder Cancer(BC)remain lacking.Existing literature underscores the potential of metabolomics as a valuable tool for biomarker identification.The primary ob...Objectives:To date,predictive and prognostic biomarkers for Bladder Cancer(BC)remain lacking.Existing literature underscores the potential of metabolomics as a valuable tool for biomarker identification.The primary objective of this study is to characterize the serum metabolic profile of BC patients undergoing platinumbased chemotherapy(Pt-CT)to identify potential biomarkers.Methods:In this pilot study,we investigated the metabolomic profiles of 14 BC patients undergoing Pt-CT in different settings.We compared their baseline profiles with those of healthy controls and tracked key metabolites throughout chemotherapy cycles.Metabolomics profiling was conducted using nuclear magnetic resonance(NMR)spectroscopy.All experiments were performed on a Bruker Avance™600 spectrometer.Results:Serum samples of BC patients had elevated levels of acetate,acetone,hypoxanthine,trimethylamine N-oxide(TMAO),glutamate,lactate,phenylalanine,and ornithine.Conversely,there were decreased levels of carnitine,choline,betaine,aspartate,threonine,2-hydroxybutyrate,2-aminobutyrate and histidine when compared with healthy controls.Throughout the CT course,hypoxanthine,glutamate,and aspartate levels increased,while acetone,acetate and TMAO levels decreased.Conclusions:The results of our study confirm perturbations in several metabolic pathways in the serum samples of BC patients,including glycolysis,fatty acid,purine,and amino acid metabolism.Additionally,TMAO may contribute to BC development by fostering a pro-inflammatory and oxidative stress state.Furthermore,monitoring these metabolites could serve as a valuable tool for predicting treatment response.To the best of our knowledge,no metabolomic studies have assessed BC patients undergoing CT with longitudinal monitoring to identify changes in the metabolic profile induced by treatment.展开更多
Objective:While cisplatin-based chemotherapy is pivotal for advanced bladder cancer,acquired resistance remains a major obstacle.This study investigates key molecular drivers of this resistance and potential reversal ...Objective:While cisplatin-based chemotherapy is pivotal for advanced bladder cancer,acquired resistance remains a major obstacle.This study investigates key molecular drivers of this resistance and potential reversal strategies.Methods:We established GC(Gemcitabine and Cisplatin)-resistant T24-R and UC3-R cell lines from T24 and UM-UC-3(UC3)cells.Transcriptomic and proteomic analyses identified differentially expressed molecules.Apoptosis and cell viability were assessed by flow cytometry and CCK-8(Cell Counting Kit-8)assays,while RT-qPCR(Reverse Transcription Quantitative Polymerase Chain Reaction)and Western blot analyzed gene and protein expression.Immunofluorescence evaluated FAK(Focal Adhesion Kinase)phosphorylation,and a xenograft mouse model validated the findings in vivo.Results:Integrated transcriptomic and proteomic analysis identified FN1(fibronectin)as a consistently upregulated top candidate in resistant cells(T24-R transcript log_(2)FC=2.8,protein log_(2)FC=0.9;UC3-R transcript log_(2)FC=3.7;all p<0.001).Knockdown of FN1 reduced chemoresistance(Resistance Index:5.2 in T24-R and 2.0 in UC3-R cells,p<0.001)and enhanced apoptosis(approximately 4.5-fold in T24-R and 7.5-fold in UC3-R,p<0.001).ITGB4(Integrin Subunit Beta 4)was upregulated in resistant cells(transcript log_(2)FC:4.2 in T24-R and 3.03 in UC3-R;protein log_(2)FC:0.67 in T24-R;all p<0.01).Critically,ITGB4 knockdown abolished the chemoresistance promoted by exogenous FN1,which was associated with increased FAK(Y397)phosphorylation.Conclusion:Our results demonstrate that the FN1-ITGB4 axis drives chemoresistance in bladder cancer via FAK signaling.Targeting this axis represents a promising strategy to overcome chemoresistance.展开更多
Objectives:Bladder cancer(BCa)progression is closely linked to the immune microenvironment.However,the key molecules that regulate this microenvironment and their specific mechanisms remain poorly understood.This stud...Objectives:Bladder cancer(BCa)progression is closely linked to the immune microenvironment.However,the key molecules that regulate this microenvironment and their specific mechanisms remain poorly understood.This study aims to identify a key molecule and elucidate its mechanisms,providing a theoretical basis for identifying novel therapeutic targets.Methods:Immune microenvironment-related genes in BCa were identified using The Cancer Genome Atlas and Shanghai Tenth People’s Hospital datasets.Proteasome 26S subunit non-ATPase 2(PSMD2)expression was validated via quantitative polymerase chain reaction(qPCR),Western blot(WB)analysis,and immunofluorescence(IF).In vitro and in vivo experiments confirmed the role of PSMD2 in cell proliferation,invasion,and migration.Kyoto encyclopedia of genes and genomes(KEGG)and Gene Ontology(GO)analyses were conducted to assess PSMD2’s influence on immune microenvironment remodeling.A pathomics model predicted PSMD2 expression in patients with BCa.Results:PSMD2 was identified as a critical factor in BCa,with high expression correlating with poor prognosis and tumor progression.Mechanistically,PSMD2 enhances malignancy by promoting mitogen-activated protein kinase kinase(MEK)and extracellular signal-regulated kinase(ERK)phosphorylation within the mitogen-activated protein kinase(MAPK)signaling pathway.Combined bioinformatics and experimental analyses reveal that PSMD2 downregulates chemokine(C-X-C motif)ligand 14(CXCL14)expression and secretion via the MAPK pathway,thereby remodeling the immune microenvironment and driving tumor progression.Pathomics analysis further supports the potential of PSMD2 expression as a predictive marker in BCa tissues.Conclusion:PSMD2 is overexpressed in BCa and significantly correlates with poor prognosis and tumor progression.It promotes malignant development and immune microenvironment remodeling through the MAPK pathway.Pathological analysis can predict PSMD2 expression,offering valuable insights into immunotherapy responses and survival outcomes.展开更多
Aim:Intravesical Bacille Calmette-Guérin(BCG)is the mainstay adjuvant treatment of non-muscle-invasive bladder cancer.However,one third of the patients on BCG regimen relapse within the first year of treatment.Th...Aim:Intravesical Bacille Calmette-Guérin(BCG)is the mainstay adjuvant treatment of non-muscle-invasive bladder cancer.However,one third of the patients on BCG regimen relapse within the first year of treatment.This study aimed at identifying biomarkers to predict response to BCG treatment.Methods:Gene expression was analyzed in blood cells of 58 patients treated with BCG through six consecutive weekly instillations and then at month 3,6,9,and 12.Cytokines tumor necrosis factor(TNF)-α,interleukin(IL)-10,interferon(IFN)-γ,IL-1β,IL-2,IL-4,and IL-6;chemokines CCL2,CCL3,CCL8,CXCL9,and IP-10;and mediators of cytotoxicity CTLA4,Fas-L,Perf,GNLY,NOS2A,and HMOX-1 were analyzed before the 1st and the 6th week instillation and 24 h after to assess fast(within 24 h)and prolonged changes resulting from treatment.Results:BCG instillation led to fast-increased expression of IL-1β,TNF-α,and IL-10 genes.When compared to relapsing patients,patients with no relapses within one year showed significantly lower expression of IL-1βat 1st week and less IFN-γ,HMOX-1,and GNLY at week 6.HMOX-1 and GNLY were independent predictive biomarkers,and values above the cut-off≥110 and≥13.0‰mRNA,respectively,were considered prejudicial factors.Patients with two HMOX-1 and GNLY factors had highest(66.7%)relapsing risk.Conclusion:Assessing immunomodulators’expression in blood allows the establishment of predictive cut-off values and identification of probabilities for patients’relapses after BCG treatment.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: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.
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.
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Background:Lower urinary tract symptoms(LUTS)and pain are clinically relevant problems after transurethral resection(TURBT)of nonmuscle-invasive bladder cancer.Although intravesical instillation of hyaluronic acid has already been proven to be a valid treatment for storage LUTS and pain in patients with inflammatory bladder syndrome,its effcacy in patients who undergo TURBT is unknown.This study aimed to present the results of a prospective,randomized,controlled,clinical pilot study on the safety and clinical performance of Hydeal Cyst(Fidia Farmaceutici S.p.A.,Italy),a device formulated to provide progressive,long-lasting intravesical release of hyaluronic acid.Materials and methods:Adults diagnosed with nonmuscle-invasive bladder cancer and scheduled for TURBT were included and underwent 4 visits up to 25 days after TURBT.Of the 47 patients who completed the investigation,25 participants received 2 postoperative intravesical instillations with Hydeal Cyst.The effcacy of Hydeal Cyst on storage LUTS,pain,urinary symptoms,and patients'quality of life was evaluated using validated questionnaires.Results:Although the overall LUTS were similar in the 2 experimental groups,lower micturition frequency and fewer daytime micturitions were observed in patients treated with Hydeal Cyst.These patients also showed a signifcant reduction in pain(p=0.03)3 days after catheter removal and better quality of life at the end of the study.The device was well tolerated,with no treatment-emergent adverse events of severe intensity.Conclusion:The results from this pilot study indicate a clinically meaningful improvement of symptoms after 2 instillations of Hydeal Cyst,supporting this intervention as a potentially effective treatment for LUTS and pain after TURBT.
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Objective: To analyze the impact of motivational nursing under the solution-focused approach on health behaviors in surgical care for bladder cancer patients. Methods: A sample of 72 bladder cancer patients who underwent surgical treatment from September 2024 to September 2025 was randomly divided into groups using a random number table. Group A received motivational nursing under the solution-focused approach, while Group B received conventional nursing. Health behavior scores and complication indicators were compared between the two groups. Results: Group A had higher scores on the Health-Promoting Lifestyle Profile II (HPLP-Ⅱ) than Group B, with p < 0.05. The postoperative complication rate in Group A was lower than that in Group B, with p < 0.05. Conclusion: For bladder cancer patients undergoing surgery, receiving motivational nursing under the solution-focused approach can improve health behaviors, alleviate negative emotions, and is highly feasible and effective.
文摘Objectives:To date,predictive and prognostic biomarkers for Bladder Cancer(BC)remain lacking.Existing literature underscores the potential of metabolomics as a valuable tool for biomarker identification.The primary objective of this study is to characterize the serum metabolic profile of BC patients undergoing platinumbased chemotherapy(Pt-CT)to identify potential biomarkers.Methods:In this pilot study,we investigated the metabolomic profiles of 14 BC patients undergoing Pt-CT in different settings.We compared their baseline profiles with those of healthy controls and tracked key metabolites throughout chemotherapy cycles.Metabolomics profiling was conducted using nuclear magnetic resonance(NMR)spectroscopy.All experiments were performed on a Bruker Avance™600 spectrometer.Results:Serum samples of BC patients had elevated levels of acetate,acetone,hypoxanthine,trimethylamine N-oxide(TMAO),glutamate,lactate,phenylalanine,and ornithine.Conversely,there were decreased levels of carnitine,choline,betaine,aspartate,threonine,2-hydroxybutyrate,2-aminobutyrate and histidine when compared with healthy controls.Throughout the CT course,hypoxanthine,glutamate,and aspartate levels increased,while acetone,acetate and TMAO levels decreased.Conclusions:The results of our study confirm perturbations in several metabolic pathways in the serum samples of BC patients,including glycolysis,fatty acid,purine,and amino acid metabolism.Additionally,TMAO may contribute to BC development by fostering a pro-inflammatory and oxidative stress state.Furthermore,monitoring these metabolites could serve as a valuable tool for predicting treatment response.To the best of our knowledge,no metabolomic studies have assessed BC patients undergoing CT with longitudinal monitoring to identify changes in the metabolic profile induced by treatment.
基金supported by grants from the National Natural Science Foundation of China(82372881 to Weiyang He)the Chongqing Biomedicine Key R&D Project(CSTB2021TIAD-KPX0041 to Weiyang He).
文摘Objective:While cisplatin-based chemotherapy is pivotal for advanced bladder cancer,acquired resistance remains a major obstacle.This study investigates key molecular drivers of this resistance and potential reversal strategies.Methods:We established GC(Gemcitabine and Cisplatin)-resistant T24-R and UC3-R cell lines from T24 and UM-UC-3(UC3)cells.Transcriptomic and proteomic analyses identified differentially expressed molecules.Apoptosis and cell viability were assessed by flow cytometry and CCK-8(Cell Counting Kit-8)assays,while RT-qPCR(Reverse Transcription Quantitative Polymerase Chain Reaction)and Western blot analyzed gene and protein expression.Immunofluorescence evaluated FAK(Focal Adhesion Kinase)phosphorylation,and a xenograft mouse model validated the findings in vivo.Results:Integrated transcriptomic and proteomic analysis identified FN1(fibronectin)as a consistently upregulated top candidate in resistant cells(T24-R transcript log_(2)FC=2.8,protein log_(2)FC=0.9;UC3-R transcript log_(2)FC=3.7;all p<0.001).Knockdown of FN1 reduced chemoresistance(Resistance Index:5.2 in T24-R and 2.0 in UC3-R cells,p<0.001)and enhanced apoptosis(approximately 4.5-fold in T24-R and 7.5-fold in UC3-R,p<0.001).ITGB4(Integrin Subunit Beta 4)was upregulated in resistant cells(transcript log_(2)FC:4.2 in T24-R and 3.03 in UC3-R;protein log_(2)FC:0.67 in T24-R;all p<0.01).Critically,ITGB4 knockdown abolished the chemoresistance promoted by exogenous FN1,which was associated with increased FAK(Y397)phosphorylation.Conclusion:Our results demonstrate that the FN1-ITGB4 axis drives chemoresistance in bladder cancer via FAK signaling.Targeting this axis represents a promising strategy to overcome chemoresistance.
基金supported by the National Natural Science Foundation of China Commission,Youth Project(No.82203150,No.82302304)Anhui Health Commission Research Project(No.2024Aa30184)+7 种基金The Bengbu City Health and Medical Research Project(BBWK2024A103)Cultivation grant for clinical and basic integration research of Shanghai Tenth People’s Hospital(SYYYRH2025020)Doctoral Workstation Foundation of Guangdong Second Provincial General Hospital,China(Grant No.2022BSGZ011)Elevate Engineering Foundation of Guangdong Second Provincial General Hospital,China(Grant No.TJGC2022009)Science and Technology Program of Guangzhou,China(2024A04J4159)China Postdoctoral Science Foundation(2021M702137)Natural Science Foundation of Chongqing(cstc2021jcyj-msxmX1176)Chongming District Sustainable Development Science and Technology Innovation Initiative Project(CKY2022-30).
文摘Objectives:Bladder cancer(BCa)progression is closely linked to the immune microenvironment.However,the key molecules that regulate this microenvironment and their specific mechanisms remain poorly understood.This study aims to identify a key molecule and elucidate its mechanisms,providing a theoretical basis for identifying novel therapeutic targets.Methods:Immune microenvironment-related genes in BCa were identified using The Cancer Genome Atlas and Shanghai Tenth People’s Hospital datasets.Proteasome 26S subunit non-ATPase 2(PSMD2)expression was validated via quantitative polymerase chain reaction(qPCR),Western blot(WB)analysis,and immunofluorescence(IF).In vitro and in vivo experiments confirmed the role of PSMD2 in cell proliferation,invasion,and migration.Kyoto encyclopedia of genes and genomes(KEGG)and Gene Ontology(GO)analyses were conducted to assess PSMD2’s influence on immune microenvironment remodeling.A pathomics model predicted PSMD2 expression in patients with BCa.Results:PSMD2 was identified as a critical factor in BCa,with high expression correlating with poor prognosis and tumor progression.Mechanistically,PSMD2 enhances malignancy by promoting mitogen-activated protein kinase kinase(MEK)and extracellular signal-regulated kinase(ERK)phosphorylation within the mitogen-activated protein kinase(MAPK)signaling pathway.Combined bioinformatics and experimental analyses reveal that PSMD2 downregulates chemokine(C-X-C motif)ligand 14(CXCL14)expression and secretion via the MAPK pathway,thereby remodeling the immune microenvironment and driving tumor progression.Pathomics analysis further supports the potential of PSMD2 expression as a predictive marker in BCa tissues.Conclusion:PSMD2 is overexpressed in BCa and significantly correlates with poor prognosis and tumor progression.It promotes malignant development and immune microenvironment remodeling through the MAPK pathway.Pathological analysis can predict PSMD2 expression,offering valuable insights into immunotherapy responses and survival outcomes.
基金supported by a grant of Astellas Pharma,obtained after application.
文摘Aim:Intravesical Bacille Calmette-Guérin(BCG)is the mainstay adjuvant treatment of non-muscle-invasive bladder cancer.However,one third of the patients on BCG regimen relapse within the first year of treatment.This study aimed at identifying biomarkers to predict response to BCG treatment.Methods:Gene expression was analyzed in blood cells of 58 patients treated with BCG through six consecutive weekly instillations and then at month 3,6,9,and 12.Cytokines tumor necrosis factor(TNF)-α,interleukin(IL)-10,interferon(IFN)-γ,IL-1β,IL-2,IL-4,and IL-6;chemokines CCL2,CCL3,CCL8,CXCL9,and IP-10;and mediators of cytotoxicity CTLA4,Fas-L,Perf,GNLY,NOS2A,and HMOX-1 were analyzed before the 1st and the 6th week instillation and 24 h after to assess fast(within 24 h)and prolonged changes resulting from treatment.Results:BCG instillation led to fast-increased expression of IL-1β,TNF-α,and IL-10 genes.When compared to relapsing patients,patients with no relapses within one year showed significantly lower expression of IL-1βat 1st week and less IFN-γ,HMOX-1,and GNLY at week 6.HMOX-1 and GNLY were independent predictive biomarkers,and values above the cut-off≥110 and≥13.0‰mRNA,respectively,were considered prejudicial factors.Patients with two HMOX-1 and GNLY factors had highest(66.7%)relapsing risk.Conclusion:Assessing immunomodulators’expression in blood allows the establishment of predictive cut-off values and identification of probabilities for patients’relapses after BCG treatment.
