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Introduction: Incidence and mortality for bladder cancer has changed very little over the past 20 years. Approximately 40% of patients with high-risk nonmuscle invasive bladder cancer eventually recur/progress. It is important to understand the economic impact of disease recurrence/progression in bladder cancer. Our aim was to estimate and understand the direct costs associated with the treatment of bladder cancer from the payer's perspective in the USA, in the year of 2021, including costs for both newly diagnosed bladder cancer (stages 0a–IV) and recurrent patients. Methods: An economic model was constructed to calculate the number of patients receiving each treatment modality at every stage of disease and their respective costs. Epidemiological data were based on the CancerMPact Patient Metrics (PM) database and treatment modality data retrieved from CMP Treatment Architecture (TA), 2021 version. Resource utilization and costs were obtained from medical literature and public data sources. Only direct costs were considered. Results: There were an estimated 83,532 newly diagnosed patients with bladder cancer of all stages in 2021 with a projected total cost of treatment of ~$2.6 billion. Average cost per newly diagnosed patient varied from $19,521 (stage 0a) to $169,533 (metastatic disease). Cost profile differed substantially among the stages of disease. For the 75,760 patients that were expected to have a recurrence in 2021, an additional cost of ~$3.9 billion was estimated at an average cost per patient of $52,179. The expected total cost to treat newly diagnosed and newly recurrent patients is reported in this model, with the total cost in 2021 estimated to exceed $6.5 billion. Conclusions: Treatment and resource costs increase for bladder cancer as the disease recurs/progresses. More effective treatments that can delay recurrence/progression may reduce the economic burden associated with bladder cancer. Plain Language Summary: The costs of treating bladder cancer in the USA are high, expected to have exceeded $6.5 billion in the year 2021. The average cost for newly diagnosed patients ranges from $19,521 for the earliest stage of disease to $169,533 for metastatic disease. Average costs per patient increase upon disease recurrence and more effective initial treatments to delay disease recurrence or progression may reduce the costs associated with bladder cancer. [ABSTRACT FROM AUTHOR]

Objectives To investigate the relationship between single nucleotide polymorphism (SNP) of excision repair cross-complementation group 1 (ERCC1) rs11615 and the safety outcomes of cisplatin-based adjuvant chemotherapy in post-cystectomy bladder cancer patients. Methods This pilot single-center retrospective cohort research study involved 25 patients with muscle-invasive bladder cancer who were admitted to the Urology and Nephrology Center (UNC), Mansoura University, Egypt between January and December 2016. The study tried to reveal the association between SNP rs11615 in ERCC1 gene and the change from baseline characteristics in a median of 96 weeks follow-up in blood, renal, and hepatic biochemical parameters. Results Univariate analysis of the association between rs11615 and post-chemotherapy changes in uric acid and hemoglobin levels showed a statistically significant relationship. Conclusion These findings hint at possible genetic influences in response to chemotherapy, necessitating further research to understand the mechanisms and potential clinical implications. This could lead to personalized treatment plans enhancing patient care and outcomes. [ABSTRACT FROM AUTHOR]

In this study, we introduce a new four-parameter continuous probability distribution known as the Topp-Loene Gompertz Inverse Rayleigh (TLGoIRa) distribution. This novel model extends the Gompertz Inverse Rayleigh distribution. We present various mathematical properties of the distribution, including moments, moment generating functions, quantile functions, survival functions, hazard functions, reversed hazard functions, and odd functions. We also derive the distribution of order statistics, yielding both the maximum and minimum order statistics. This process of parameter estimation using the maximum likelihood estimation method is discussed. Furthermore, we present two real-life applications that illustrate the effectiveness and robustness of the TLGoIRa distribution when compared to several considered lifetime models. Our analysis reveals that the TLGoIRa distribution demonstrates superior robustness in comparison to the competing lifetime models. Additionally, the study highlights the distribution’s efficacy in fitting biomedical datasets. [ABSTRACT FROM AUTHOR]

The prognostic value of the systemic immune-inflammation index during induction (ISII) remains unclear in non-muscle-invasive bladder cancer (NMIBC) patients receiving Bacillus Calmette-Guérin (BCG). This study first found that ISII could independently predict the prognosis of NMIBC patients receiving BCG, which might help to select an optimal treatment schedule for patients with NMIBC. Background: The prognostic value of the systemic immune-inflammation index during induction (ISII) remains unclear in non-muscle-invasive bladder cancer (NMIBC) patients receiving Bacillus Calmette-Guérin (BCG). We aimed to determine and compare the prognostic value of the ISII, preoperative systemic immune-inflammation index (PSII) and their dynamic changes (PISII). Methods: This study respectively collected data from 362 NMIBC patients receiving BCG treatment in our institution. The prognostic values of PSII, ISII and PISII were analyzed by the Kaplan -Meier method and Cox proportional hazard regression models. The concordance index and receiver operating characteristic curve analysis were employed to compare the prognostic value of these 3 factors. Results: Our study enrolled 197 patients. These patients included 170 male patients, and the mean age was 64.17 years. During the follow-up time, 85 patients experienced recurrence and 55 patients found progression. According to the results of Cox multivariable analysis, PSII (P = .001) and ISII (P < .001) could independently predict the recurrence of NMIBC patients receiving BCG. Meanwhile, PSII (P = .025) and ISII (P < .001) were also independent prognostic factors of progression. Compared with PSII, ISII was associated with better accuracy for NMIBC patients receiving BCG. Conclusion: This study first found that ISII could independently predict the prognosis of NMIBC patients receiving BCG. Furthermore, we also identified that ISII was associated with higher prognostic value than PSII and PISII, which might help to select an optimal treatment schedule for patients with NMIBC. [ABSTRACT FROM AUTHOR]

Nomogram prediction of overall survival that includes LODDS in carcinoma bladder. Retrospective cohort study of 282 cases from a tertiary care centre. The nomogram has superior predictive ability and higher clinical use than AJCC system. It will help clinicians for better patient counselling, planning follow-up strategies and designing clinical trials for newer adjuvant therapy (eg immunotherapy) in patients of MIBC. Background: To develop and validate a nomogram based on LODDS (Log ODDS of positive lymph-nodes) for prediction of overall survival (OS) in post radical cystectomy (RC) patients of muscle invasive bladder cancer (MIBC). Materials and Methods: Data was retrospectively collected from 282 cases of MIBC that underwent RC from 2011 to 2017 at our institute. Significant independent predictors were identified using Cox regression model and incorporated into a nomogram to predict 1, 2, and 4-year OS. Results: Multivariate analysis showed that Neo-Adjuvant Chemo-Therapy (NACT) (P < .001), LODDS (P < .001), T-stage (Pi = .001), CCI (Charlson Comorbidity Index) (P = .034) and grade (P = .003) were independent predictors of OS. The C-index of nomogram (0.740) was higher than that of the American Joint Committee on Cancer (AJCC) staging system (0.614). The bias-corrected calibration plots showed that the predicted risks were in excellent accordance with the actual risks. The results of NRI, IDI, and DCA exhibited superior predictive capability and higher clinical use of the nomogram. Conclusion: A simple, easy to use nomogram to predict OS in cases of MIBC has been constructed. To best of our knowledge, LODDS has been incorporated for the first time. It has superior predictive ability and higher clinical use than AJCC system. It would help the clinicians for better patient counselling, planning follow-up strategies and designing a clinical trial for newer adjuvant therapy (eg immunotherapy) in post radical cystectomy patients of MIBC. [ABSTRACT FROM AUTHOR]

The inverse power Lindley distribution is employed in the realm of survival analysis to imitate human lifetime data practices. The neutrosophic inverse power Lindley distribution (NIPLD) is intended to characterize a variety of survival data with indeterminacies. The established distribution is particularly useful for modeling uncertain data that is roughly positively skewed. This work discusses the key statistical properties of the developed NIPLD, including the neutrosophic survival function, neutrosophic hazard rate, and neutrosophic moments. In addition, the neutrosophic parameters are estimated using the well-known maximum likelihood estimation approach. To find out if the predicted neutrosophic parameters were reached, a simulation study is done. Not to mention, actual data has been utilized to discuss potential NIPLD real-world applications. Real data were used to illustrate how well the proposed model performed in compared to the current distributions. [ABSTRACT FROM AUTHOR]

BACKGROUND: Smoking is one of the most popular risk factors provoking bladder cancer (BC). This research intended to estimate cigarette smoking effect involving PAF signs between smoking patients with BC and non-smoking patients with same diagnosis to define relations with pathological characteristics and their prognosis on zero-relapse and disease-associated recovery. METHODS: Two groups of smokers (n = 54) and non-smokers (n = 62) were selected. Both cohorts of patients had BC. They were evaluated utilizing NGS on 9 cancer-related genes and confirmed through the Sanger DNA sequencing and histopathological tests based on H&E staining. The factor of smoking and impact of PAF development by ELISA assay and PAF-R manifestation in terms of immunochemical evaluation on BC areas comparing to a control group (n = 30) was examined involving healthy contributors, including the use of well-designed statistical trials. RESULTS: The multivariate evaluation showed considerable rise in mutation patterns related to smoking among BC patients (group 3), increase in PAF development (***P<0.001) and vivid signs of PAF-R contrasted to non-smokers with BC (group 2) and control group (group 1). All the identified biological changes (gains/losses) were recorded at the same locations in both groups. Patients from group 3 held 3-4 various mutations, while patients from group 2 held 1-3 various mutations. Mutations were not identified in 30 respondents from control group. The most repeated mutations were identified in 3 of 9 examined genes, namely TP53, PIK3CA and PTEN, with highest rates of increase in Group 3. Moreover, histopathological tests revealed barely identifiable and abnormal traits in BC tissues, i.e. were without essential histopathological changes between groups 2 and 3. CONCLUSION: Smoking of cigarettes provokes PAF development due to urothelial inflammation and rise of mutations in 9 cancer-related genes. These are indicative factors of inducing BC. [ABSTRACT FROM AUTHOR]

The prognostic role of prior bladder cancer (BCa) among upper tract urothelial carcinoma (UTUC) patients is still poorly addressed. We retrospectively analyzed a multicenter cohort of 1,580 patients to assess the role of prior BCa on any recurrence after radical nephroureterectomy for UTUC. Our findings show that patients with prior BCa history exhibit a significantly increased risk of any recurrence. Introduction: The prognostic role of prior history of bladder cancer (BCa) among patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) is poorly addressed. We aimed to investigate the role of prior BCa on any recurrence, distant metastases, and bladder recurrence following RNU among low-grade (LG) and high-grade (HG) UTUC patients. Patients and Methods: We retrospectively analyzed 1,580 UTUC patients treated with RNU at 8 tertiary referral centers between 1992 and 2016. Any recurrence was defined as recurrence in the urinary tract, in the resection bed, or distant metastases (defined as disease outside the urinary tract and regional lymph nodes). Time to recurrence was computed from RNU. Multivariable Cox models were generated to predict risk of any recurrence, distant metastases, and bladder recurrence according to prior BCa history, coded as no prior BCa, non-muscle-invasive (NMIBC), and muscle-invasive BCa (MIBC). Results: Median follow-up for survivors was 4 years. Overall, 71%, 25%, and 4% of patients had no prior BCa, NMIBC and MIBC. 5-year any recurrence-free survival was 61%, 41%, and 19% in LG (P < .001) and 42%, 34%, and 30% in HG patients (P = .1) with no prior BCa, NMIBC, and MIBC. On multivariable models, LG patients with NMIBC and MIBC showed a significantly higher risk of any recurrence compared to no prior BCa (both p =0.005); previous NMIBC was associated with any recurrence among HG patients (P = 0.04). 5-year distant metastases-free survival was 92%, 90%, and 87% in LG (P > .05) and 68%, 75%, and 45% in HG patients (P = .01) with no prior BCa, NMIBC, and MIBC. Previous NMIBC increased the risk of bladder recurrence among LG (P < .001) and HG (P = .003) patients. Conclusions: UTUC patients with prior history of BCa exhibit a higher risk of any recurrence after RNU. Our study provides important information which could address patient's counseling and decision-making process. [ABSTRACT FROM AUTHOR]

It remains unclear whether oncologic follow-up exacerbates or alleviates patient stress about recurrence of urologic malignancies. We administered surveys examining patient perceptions and expectations of follow-up to 337 patients with kidney, prostate, or bladder cancer presenting at least 60 days after surgery. Across all cancer types, urology patients are overall satisfied and find follow-up with urology providers to be reassuring. Introduction: In colorectal, cervical, and breast cancers, oncologic follow-up can exacerbate or alleviate patient stress about disease recurrence. Such patient experiences are less well defined for urologic malignancies. We developed a cross-sectional prospective survey study to assess kidney (Kid), prostate (Pros), and bladder (Bld) cancer patient perceptions of oncologic follow-up following surgical treatment. Patients and Methods: Patients with pTanyNanyM0 Kid, Pros, and Bld cancer presenting at least 60 days following primary surgical treatment of their cancer were eligible. Receipt of adjuvant therapy or disease recurrence were exclusion criteria. Questionnaires assessing attitudes towards follow-up and stress-reducing strategies were administered prior to revealing testing results. Analysis was performed according to cancer type and level of recurrence risk, with pathologic stage used a proxy for recurrence risk. Results: Three hundred thirty-seven patients were prospectively surveyed from 2018 to 2020: 127 (38%) Kid, 134 (40%) Pros, and 76 (23%) Bld. Patients showed satisfaction with provided strategies to combat recurrence anxiety (Kid 86%, Pros 81%, Bld 85%). However, approximately 16% of patients reported wanting, but not receiving, strategies for fear reduction. Most patients reported diagnostic tests were "Not at All" burdensome (Kid 86%, Pros 94%, Bld 82%) and disagree that fewer tests would alleviate anxiety (Kid 89%, Pros 91%, Bld 84%). The majority reported an increased sense of worry if there were no cancer follow-ups (Kid 84%, Pros 80%, Kid 81%), and preferred their specialist to their family physician to direct such care (Kid 89%, Pros 91%, Bld 95%). When stratified by recurrence risk, no significant differences existed across cancers in patients' attitudes toward follow-up. However, Pros cancer patients showed a difference in fear of recurrence ("Not at All" worried about recurrence =T2 38%, =T3, 19%; P = .04). Conclusion: Urology patients appear satisfied with their oncologic follow-up. Sixteen percent of patients sought additional strategies to combat fear, indicating opportunity for improvement. [ABSTRACT FROM AUTHOR]

Purpose: To compare the utility of a novel metal artifact reduction algorithm to standard imaging in improving visualization of key structures, diagnostic confidence, and patient-level confidence in malignancy in patients with suspected bladder cancer. Methods: Patients with hip implants undergoing CT urography for suspected bladder malignancy were enrolled. Images were reconstructed using 3 methods: (1) Filtered Back Projection (FBP), (2) Iterative Metal Artifact Reduction (iMAR), and (3) Adaptive Iterative Metal Artifact Reduction (AiMAR) strength 4. In multiple reading sessions, three radiologists graded visualization of critical anatomic structures and artifact severity (6-point scales, lower scores desirable), and diagnostic confidence in blinded fashion. They also graded patient-level confidence in malignancy based on imaging findings in each patient. Results: Thirty-two patients (8 females) with a mean age of 74.5 ± 8.5 years were included. The median (range) visualization scores for FBP, iMAR, and AiMAR were 3.6 (1.1–4.9), 1.6 (0.3–2.8), and 1.6 (0.3–2.6), respectively. Both iMAR and AiMAR had anatomic visualization and artifact scores better than FBP (P < 0.001 for both) and similar to each other (P > 0.05). Structures with the most improvement in visualization score with the use of metal artifact reduction algorithms included the obturator internus muscle, internal and external iliac nodal chains, and vagina. iMAR and AiMAR improved diagnostic confidence (P < 0.001) and patient-level confidence in malignancy (P ≤ 0.24). Conclusion: For patients with hip prostheses and suspected bladder malignancy, the use of iMAR or AiMAR was shown to significantly reduce metal artifacts, thus improving diagnostic confidence and patient-level confidence in malignancy. [ABSTRACT FROM AUTHOR]

We examined the impact of preoperative plasma potassium levels (PPLs) on outcomes in patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB), hypothesizing that potassium imbalances might influence outcomes. In this retrospective study, 501 UCB patients undergoing RC from 2009 to 2017 at a tertiary center were analyzed. Blood samples collected a week prior to surgery defined normal and abnormal PPL based on institutional standards. We assessed overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), postoperative complications, 30-day mortality, and non-organ confined disease. Kaplan-Meier estimates, Cox proportional hazards, logistic regression, and decision curve analyses (DCA) were employed. 63 (13%) patients had abnormal preoperative PPLs, with 50 (10%) elevated and 13 (2.5%) decreased. In a 59 months median follow-up, 152 (31%) had disease recurrence, 197 (39%) died from any cause, and 119 (24%) from UCB. Multivariable cox regression analyses adjusting for perioperative parameters demonstrated abnormal PPL was associated with worse OS (HR=1.9, P =0.009), CSS (HR=2.8, P <0.001) and RFS (HR=2.1; P =0.007). Elevated preoperative PPLs also demonstrated significant associations with adverse outcomes in OS, CSS, and RFS (all P <0.05). In multivariable logistic regression analyses, abnormal and elevated PPLs were not associated with 30-day mortality, major 30-day postoperative complications, positive nodal disease, pT3/4 stage, and non-organ confined disease (all P >0.05). Abnormal and elevated preoperative PPLs correlate with adverse oncologic outcomes in UCB patients treated with RC. Pending external validation, preoperative PPLs might be a cost-effective, easily obtainable supplemental biomarker for enriching accuracy of outcome prediction in this highly variable maladie. This retrospective study analyzed 501 patients undergoing radical cystectomy for bladder cancer, focusing on preoperative plasma potassium levels (PPLs). It found that abnormal and elevated PPLs are linked to worse survival outcomes. These findings suggest preoperative PPLs as a potential biomarker for patient stratification in bladder cancer treatment. [ABSTRACT FROM AUTHOR]

Copyright of Journal of China Medical University is the property of Journal of China Medical University Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: Our study aimed to evaluate the correlation of circular RNA SMARCA5 (circ-SMARCA5) and microRNA 432 (miR-432) with clinical characteristics and survival in bladder cancer patients. Methods: Preoperative clinicopathologic features and survival data of 156 bladder cancer patients were retrospectively reviewed. A total of 156 cases of tumor tissues, whereas 71 cases out of 156 available adjacent tissues were obtained from the Pathology Department for circ-SMARCA5 and miR-432 detections using real-time quantitative polymerase chain reaction. Results: Circ-SMARCA5 was upregulated but miR-432 was downregulated in tumor tissues compared with adjacent tissues; meanwhile, circ-SMARCA5 expression was negatively correlated with miR-432 in bladder cancer tissues. Circ-SMARCA5 high expression was correlated with larger tumor size, higher tumor stage, and lymph node (LYN) metastasis. However, miR-432 high expression was correlated with single multiplicity, smaller tumor size, lower tumor stage, less LYN metastasis in bladder cancer patients. Regarding survival, circ-SMARCA5 high expression was correlated with shorter disease-free survival (DFS) and overall survival (OS); whereas, miR-432 high expression was correlated with longer DFS and OS in bladder cancer patients. Further multivariate Cox's regression analysis displayed that circ-SMARCA5 high expression was an independent predictive factor for both worse DFS and OS in bladder cancer patients. Conclusion: Circ-SMARCA5 high expression but miR-432 low expression is correlated with advanced tumor features and poor survival of bladder cancer patients, which present as potential prognostic markers in bladder cancer. [ABSTRACT FROM AUTHOR]

Bladder cancer (BCa) is a common carcinoma of the urinary tract, which occurs in the bladder mucosa. In recent years, people have recognized that epigenetic changes such as DNA methylation play important roles in the development of BCa but the specific mechanism is unclear. In this study, we detected the methylation rates in the SOCS1 gene of 490 subjects (including 247 patients with BCa and 243 healthy controls) using the MassARRAY EpiTYPER system. Principal component analysis (PCA) was conducted with the aim of identifying common underlying patterns that could explain the largest part of common variance in methylation across units. A logistic regression model was used to assess the relation of SOCS1 methylation patterns with factors related to BCa risk. The methylation rates varied for different CpG units and were significantly different in BCa patients compared to controls. Six principal component factors were extracted by combining initial eigenvalue, explanatory power, and Scree Plot. After adjusting for age, gender, family history of bladder cancer, smoking, and drinking, we observed that Factor 1 (OR=0.051, 95% CI: 0.015-0.178, p<0.001), Factor 2 (OR=0.146, 95% CI: 0.073-0.295, p<0.001), Factor 3 (OR=0.346, 95% CI: 0.198-0.606, p<0.001), and Factor 4 (OR=0.270, 95% CI: 0.135-0.537, p<0.001) were associated with BCa. Based on follow-up results, we found that the 1-, 3-, 5-year survival rates in the hypermethylated group were lower than in the hypomethylated group. We found that several CpG units in methylation patterns were associated with the incidence of BCa showing the important DNA methylation patterns for BCa pathogenesis. Our findings provided new insights into understanding this disease and new potential targets for therapeutic intervention for BCa patients in the future. [ABSTRACT FROM AUTHOR]

The aim of this work was to study the association between three single nucleotide polymorphisms (SNP), rs 2227485 in IL-22 gene, rs 153109 and rs 17855750 in IL-27 gene and its levels in bladder cancer (BC) patients. One hundred bladder cancer patients and 100 healthy volunteers were registered in this study. Results showed a significant increase in IL- 22 and IL-27 in BC patients when compared to healthy participants, also the level of both interleukins increased significantly with progressing of the disease. The SNP rs2227485 of IL-22 was genotyped by PCR-sequencing. The results revealed high frequency of TT and T allele compared with control with a significant positive odds ratio (OR) (12 67% confidence interval (CI= 4.76- 34, P = 0.000) and T allele (OR = 3.23, CI = 2.15- 4.86 P = 0.000). Results of IL-22 concentration were estimated by ELISA which was compared with genotyping results at rs2227485 SNP. The genotyping data revealed that the mutant TT genotype showed a significant high level in patients and a significant decreasing level in healthy control. The genotyping results of rs 17855750 in IL-27 gene showed a significant positive (OR) of GG genotype (13.83) (CI = 1.42 - 5.00, P = 0.003) and G allele (3.62) (CI = 5.3-17.4, P = 0.000). While the results of IL-27 concentration revealed that the mutant TT genotype showed insignificant high level followed by GG genotype. The SNP (rs 1531109) of IL-27 showed GG genotype OR (51.19) (CI = 3.09- 847, P = 0.000) and G allele with positive OR (6) (CI = 3.5-10.30, P = 0.000) and AG genotype (2.67) (CI = 0.9-10.8, P = 0.029) and the IL-27 level showed that AG genotype with a significant higher level in patients and with a significant lowest level in the healthy control. Our results suggested that the mutant TT genotype and T allele for IL-22 rs 2227485 and GG genotype and G allele for IL-27 rs 17855750 and rs 153109 may play a role in the etiology of the bladder cancer and the patients with this genotype displayed a significant high level of IL-22. [ABSTRACT FROM AUTHOR]

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Introduction. Bladder cancer is the most common malignancy involving the urinary system. Recent research tends to emphasize the role of oxidative stress products in the carcinogenesis of bladder cancer. The level of oxidative stress can be measured by assessing the MDA levels. This study aimed to evaluate serum MDA levels in patients with bladder cancer, as well as to determine its potential role as a biomarker in the diagnosis of the disease and progression risk considerations. Methods. The study was designed as a cross-sectional study and included 90 patients, divided into three groups with 30 patients each: Ta, T1and T2-T4 group, based on histopathological findings after transurethral resection of the tumor. The control group included 30 healthy volunteers. MDA level was determined using the spectrophotometric method. Results. Serum MDA level in patients with bladder cancer [0.86 (0.78-1.05) µmol/L] was significantly higher than the serum MDA level in control group [0.70 (0.69-0.72) µmol/L] (p < 0.001). Serum MDA level in Ta group [0.73 (0.70-1.05) µmol/L], T1 group [0.85 (0.80-1.12) µmol/L] and in T2-T4 group [0.91 (0.84-1.04) µmol/L] was significantly higher than the serum MDA level in control group [0.70 (0.69-0.72) µmol/L] (p < 0.01). MDA level in T1 and T2-T4 group was significantly higher than the MDA level in Ta group (p < 0.01). No significant difference was observed in MDA level between T1 and T2-T4 group (p = NS). A statistically significant positive correlation was found between tumor size and serum MDA level in patients with bladder cancer (rho = 0.254 p < 0.01). Conclusions. The results of the present study suggest that MDA serum level might play a significant role as a biomarker in the diagnosis of bladder cancer, as well as in the monitoring of its progression. [ABSTRACT FROM AUTHOR]

Objective: Patients with ANCA-associated vasculitides (AAV) exhibit higher rates of malignancy than the general population. We assessed whether the cancer risk is increased in a well-characterized population-based cohort of AAV in southern Sweden, followed for a median time of 8 years.Methods: With case record review, the outcomes and malignancy development in a cohort of 195 patients with AAV [granulomatosis with polyangiitis (GPA), microscopic polyangiitis, and eosinophilic GPA] diagnosed between 1997 and 2010 were assessed. The patients were followed until death or December 31, 2015. The age- and sex-standardized incidence ratios (SIR) were estimated using the Swedish population data as a reference.Results: During the observation period of about 1500 person-years, we found 60 cancers in 52 of the 195 patients. SIR (95% CI) was 2.8 (2.1-3.6) for cancers at all sites, 1.8 (1.3-2.5) for all cancers excluding squamous cell carcinoma (SCC), 12.9 (8.4-18.8) for SCC, 4.3 (1.4-10.0) for bladder cancer, and 7.0 (1.4-20.5) for pancreatic cancer. Cumulative doses of cyclophosphamide (CYC) < 10 g were not associated with higher incidence of cancers other than SCC (SIR 1.63, 95% CI 0.8-2.9).Conclusion: In contrast to previous publications assessing malignancy risk in patients with AAV, we show in this population-based cohort of patients a persistent increased risk for overall malignancy, bladder cancer, and pancreatic cancer as well as a markedly increased risk for SCC. There was no increase in incidence of cancers other than SCC for those treated with < 10 g CYC. [ABSTRACT FROM AUTHOR]

Background: Conventional transurethral resection of urinary bladder tumour (TURBT) using a wire loop diathermy violates the basic principle of oncological surgery, i.e. dissection through normal tissue. However, in the en bloc technique, the tumour is removed as a single specimen. We compared the quality of specimen and recurrence rate at three months (first check cystoscopy) in both the en bloc and conventional resection techniques. Methods: The subject accrual was done from June 1st, 2017 till June 30th, 2019 at a tertiary care hospital. Patients with newly diagnosed bladder tumour, solitary or multiple â?¤3 cm were included in the study. Patients with carcinoma in situ, prior TURBT, or muscle-invasive bladder cancer were excluded. Eighty-two patients were available for final analysis, 41 in each group. Results: Mean age, gender ratio, tumour features (grade, stage, median number, and size) were comparable in the two groups. Median Operative time [interquartile range- (IQR)] was 30 (25-39.5) minutes in the en bloc group as compared to 45 (33-63.5) minutes in the conventional group (p < 0.001). The detrusor muscle was seen at the base of the primary tumour in all 41 (100%) en bloc cases as compared to 23 (56%) cases in the conventional group (p<0.001). Overall recurrence at the first surveillance cystoscopy was 17%, with an insignificant difference between the groups. Recurrence at primary site was 19.5% in conventional TURBT compared to en bloc resection (n=1, 2.4%), (p = 0.013). Conclusion: En bloc resection decreases the recurrence rate at the primary site. En bloc TURBT is a safe technique, providing high-quality specimens for histopathological evaluation and reducing the need for the second TURBT. [ABSTRACT FROM AUTHOR]

Background: Electronic collection of patient-reported outcomes (ePROs) is becoming widespread in health care, but the implementation into routine cancer care during therapy remains to be seen. Especially, little is known of the use and success of electronic reporting during active cancer treatment in fragile and comorbid patients. The aim of this study was to test the feasibility of ePRO and its incorporation into routine cancer care, measured by physician compliance, for a fragile and comorbid bladder cancer (BC) population receiving chemo- or immunotherapy.Methods: All BC patients initiating treatment for locally advanced or metastatic bladder cancer at Rigshospitalet or Herlev Hospital, Denmark, were approached during an 8 month period. Exclusion criteria were patients not speaking Danish or not being signed up for electronic communication with health authorities. Enrolled patients were prompted to complete weekly ePROs from home. Patients completed the European Organisation for Research and Treatment of Cancer's general quality of life questionnaire, QLQ-C30, and the module for muscle-invasive bladder cancer QLQ-BLM30, the Hospital Anxiety and Depression Scale, HADS, and selected items from the Patient Reported-Outcomes version of the Common Terminology Criteria of Adverse Events (PRO-CTCAE), in total 158 questions weekly. If failing to report when prompted, patients were sent two e-mail reminders. Patients were informed that the physician would have an overview of the reported ePROs at their following clinical visits. Physicians were at all clinical visits informed to look at the ePROs in a software solution separate from the medical records. Physicians were logged to check their compliance to the task. No continuous surveillance of ePROs was established.Results: Of 91 patients screened for enrolment, 19 patients (21%) were not found eligible for standard treatment, eight patients (9%) were not signed up for electronic communication with the health authorities and nine patients (10%) declined participation. Another six patients did not meet other inclusion criteria. In total 49 BC patients were enrolled, 29 initiating chemotherapy and 20 initiating immunotherapy. A total of 466 electronic questionnaires were completed. The overall adherence of the patients to complete ePROs was at an expected level for an elderly cancer population (75%) and remained above 70% until the 6th cycle of treatment. The physician' compliance was in contrast low (0-52%) throughout the course of treatment.Conclusions: Electronic reporting of PROs is feasible in a fragile and comorbid population of patients during routine active cancer treatment. Despite clear implementation strategies the physician compliance remained low throughout the study proving the need for further implementation strategies. [ABSTRACT FROM AUTHOR]

We assessed the association between metabolic health status and the incidence of bladder cancer using nationally representative data from the National Health Insurance System and National Health Checkups (NHC) databases in South Korea. Data for 11,781,768 men who participated in the NHC between 2009 and 2012 were analysed. The normal-weight and physically obese categories were defined as body mass indexes (BMI) < 25 and ≥25 kg/m2, respectively. Metabolically obese was defined as the presence of ≥3 components of metabolic syndrome. The participants were stratified into metabolically healthy, normal-weight (MHNW); metabolically obese, normal-weight (MONW); metabolically healthy, obese (MHO); metabolically obese, obese (MOO). Multivariate-adjusted Cox regression analysis was conducted to examine the association between metabolic health status and the incidence of bladder cancer. The study participants included 17,777 men newly registered with bladder cancer. Analysis according to metabolic health status classification revealed a higher multivariable-adjusted hazard ratio in the MOO, MONW group than in the MHO group (1.307 [95% CI: 1.258–1.358], 1.183 [95% CI: 1.137–1.231] and 1.066 [95% CI: 1.017–1.119], respectively; hazard ratios given relative to MHNW group) We found an association between metabolic health status and the incidence of bladder cancer, with an increasing risk according to the number of metabolic health status components. [ABSTRACT FROM AUTHOR]

In this work, mesoporous strontium titanate nanoparticles (SrTiO3 NPs) were synthesized through a single-step combustion process and were characterized by FT-IR, XRD, SEM-EDX, and TEM. The effects of main parameters that may influence the extraction process (i.e., pH, sorbent amount, time of extraction, eluting agent, and the presence concomitant ions) were investigated. The optimum extraction was achieved at pH 6, 50 mg of sorbent, 20-min shaking time, and 4.0 mL of 0.1 mol L−1 thiourea as desorption agent. Under these conditions, the maximum adsorption capacity was 155.6 mg g−1 with a preconcentration factor of 250 (for a 1000 mL sample solution). The calibration graph was linear up to 1000 μg L−1 and the limit of detection was 1.75 μg L−1. The precision (as relative standard deviation) was 2.53% (n = 10). The procedure was employed for the preconcentration of Pb2+ from blood and urine samples of bladder cancer patients before its determination by FAAS. [ABSTRACT FROM AUTHOR]

Abstract Cystoscopy and histology are the gold standards for detection of bladder cancer. However, these methods are highly subjective, expensive, and invasive. We have developed a non-invasive method for the diagnosis of bladder cancer by detecting telomerase activity in human urine. Telomerase substrate (TS) primer is elongated with repeating sequences of (TTAGGG)n in the presence of telomerase. The elongated primer can trigger hybridization chain reaction between two hairpins H1 and H2, result in the aggregation of AuNPs due to the hybridization between the tail sequence on H1 (or H2) and DNA-AuNPs probe, and accompany with the increase of hydrodynamic diameter of AuNPs, which can be measured with dynamic light scattering (DLS). The biosensor displayed a detection limit of 4 MCF-7 cells (a signal-to-noise ratio of 3) and a dynamic range of 10–1000 cells. Moreover, only urine specimens from bladder cancer patients induced a significant change in the average hydrodynamic diameter, indicating its specificity for the non-invasive diagnosis of bladder cancer. Graphical abstract Image 1 Highlights • A non-invasive method for the diagnosis of bladder cancer was developed by determinating the telomerase activity in human urine. • The telomerase activity was estimated based upon hybridization chain reaction and dynamic light scattering. • The proposed method had a dynamic range of 10–1000 cells, and a detection limit of 4 MCF-7 cells. • The proposed method had a high specificity for non-invasive diagnosis of bladder cancer. [ABSTRACT FROM AUTHOR]

Objective: To examine the incidence of perioperative complications after radical cystectomy (RC) and assess their impact on 90‐day postoperative mortality during the index stay and upon readmission. Patients and methods: A total of 57 553 patients with bladder cancer (unweighted cohort: 9137 patients) treated with RC, at 360 hospitals in the USA between 2005 and 2013 within the Premier Healthcare Database, were used for analysis. The 90‐day perioperative mortality was the primary outcome. Multivariable regression was used to predict the probability of mortality; models were adjusted for patient, hospital, and surgical characteristics. Results: An increase in the number of complications resulted in an increasing predicted probability of mortality, with a precipitous increase if patients had four or more complications compared to one complication during hospitalisation following RC (index stay; 1.0–9.7%, P < 0.001) and during readmission (2.0–13.1%, P < 0.001). A readmission complication nearly doubled the predicted probability of postoperative mortality as compared to an initial complication (3.9% vs 7.4%, P < 0.001). During the initial hospitalisation cardiac‐ (odds ratio [OR] 3.1, 95% confidence interval [CI] 1.9–5.1), pulmonary‐ (OR 4.8, 95% CI 2.8–8.4), and renal‐related (OR 3.6, 95% CI 2–6.7) complications had the most significant impact on the odds of mortality across categories examined. Conclusions: The number and nature of complications have a distinct impact on mortality after RC. As complications increase there is an associated increase in perioperative mortality. [ABSTRACT FROM AUTHOR]

Objective: To quantify the use of downstream studies following staging bone scans in patients with muscle-invasive bladder cancer. Bone scans may be obtained in high-risk bladder cancer patients prior to radical cystectomy to exclude bone metastases. However, false-positive bone scans can occur, resulting in the need for additional studies.Patients and Methods: Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified 4404 patients diagnosed with muscle-invasive bladder cancer from 2004 to 2011. We further identified those who underwent a bone scan prior to treatment within 6 months of diagnosis and prior to any treatment with cystectomy, radiotherapy, or chemotherapy. We determined the proportion of patients who underwent a subsequent study (bone X-ray, bone CT, bone MRI, and/or bone biopsy) within 3 months of the bone scan and prior to treatment.Results: Among patients diagnosed with muscle-invasive bladder cancer, 1373 (31%) had a staging bone scan of whom 26% received a downstream study (n = 213). Overall, 61 patients (7%) received downstream bone-specific X-rays, more than 141 patients (>17%) received bone-specific CTs, and 28 patients (3%) received bone-specific MRIs. The use of bone biopsy was rare (n < 11; <1%). The total cost of all downstream studies was $103,468. Furthermore, there was a one-month delay in treatment for those who received a downstream study compared to those who did not (P < 0.001).Conclusion: Use of bone scan in the staging of muscle-invasive bladder cancer often results in the need for additional downstream studies. The delay in treatment and cost burden of downstream studies highlights a potential disadvantage of the routine use of this staging modality. [ABSTRACT FROM AUTHOR]

The aim of the present study was to identify and test a urine marker panel of genes involved in DNA methylation and histone modification for the detection of urothelial carcinoma of the bladder (UCB). RNA samples obtained from the voided urine of 227 patients with asymptomatic microscopic haematuria (AMH) were analysed. Gene array analysis was performed on 18 randomly selected cDNA samples, which revealed that histone deacetylase 9 (HDAC9), HDAC3, tRNA (cytosine-5-)-methyltransferase1 and DNA methyltransferase 1 were differentially expressed between patients with UCB and control subjects. Subsequently, reverse transcription-quantitative polymerase chain reaction analysis was employed to test the performance of the identified four-gene panel on the remaining 209 cDNA samples. In this targeted discovery cohort, all four genes were significantly associated with UCB on univariable analyses [each odds ratio (OR) >2, P<0.05], but only HDAC3 was significant following multivariable analysis (OR=2.8, P=0.011). The addition of HDAC3 to a base risk factor model improved its accuracy by 1.4%. These data suggest that urinary HDAC3 is associated with the presence of UCB in patients with AMH; however, HDAC3 improved the accuracy of the established risk factors only to a marginal extent. [ABSTRACT FROM AUTHOR]

Objectives: To describe the rate and determinants of palliative care use amongst Medicare beneficiaries with bladder cancer and encourage a national dialogue on improving coordinated urological, oncological, and palliative care in patients with genitourinary malignancies. Patients and methods: Using Surveillance, Epidemiology, and End Results‐Medicare data, we identified patients diagnosed with muscle‐invasive bladder cancer (MIBC) between 2008 and 2013. Our primary outcome was receipt of palliative care, defined as the presence of a claim submitted by a Hospice and Palliative Medicine subspecialist. We examined determinants of palliative care use using logistic regression analysis. Results: Over the study period, 7303 patients were diagnosed with MIBC and 262 (3.6%) received palliative care. Of 2185 patients with advanced bladder cancer, defined as either T4, N+, or M+ disease, 90 (4.1%) received palliative care. Most patients that received palliative care (>80%, >210/262) did so within 24 months of diagnosis. On multivariable analysis, patients receiving palliative care were more likely to be younger, female, have greater comorbidity, live in the central USA, and have undergone radical cystectomy as opposed to a bladder‐sparing approach. The adjusted probability of receiving palliative care did not significantly change over time. Conclusions: Palliative care provides a host of benefits for patients with cancer, including improved spirituality, decrease in disease‐specific symptoms, and better functional status. However, despite strong evidence for incorporating palliative care into standard oncological care, use in patients with bladder cancer is low at 4%. This study provides a conservative baseline estimate of current palliative care use and should serve as a foundation to further investigate physician‐, patient‐, and system‐level barriers to this care. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between smoking status and pathological response to cisplatin‐based neoadjuvant chemotherapy (NAC) and survival outcomes in patients with muscle‐invasive bladder cancer (MIBC) treated with radical cystectomy (RC). Patients and Methods: We reviewed 201 patients treated with NAC and RC for cT2–cT4N0M0 BC between 01/1999 and 01/2015. Smoking status was categorised as: 'never', 'former', and 'current' smoker. Pathological response to NAC was defined as: complete (ypT0N0), partial (ypTis/Ta/T1, N0), and no response (ypT2–4 or ypN+). Clinicopathological characteristics were analysed according to smoking status. Logistic regression analyses tested the association between smoking status and pathological response to NAC. Cox regression analyses tested risk factors associated with recurrence, overall (OM) and cancer‐specific mortality (CSM). Results: Overall, there were 58 (28.9%) never smokers, 87 (43.3%) former smokers, and 56 (27.9%) current smokers. No response to NAC was more frequently noted in current smokers (73.2%; P = 0.007). Former smoker (odds ratio [OR] 2.28; P = 0.024) and current smoker statuses (OR 4.52; P < 0.001) were significantly associated with no response to NAC, after adjusting for age, gender, Charlson Comorbidity Index, and clinical stage. Similarly, current smoking status (hazard ratio [HR] 2.14; P = 0.03) and extravesical pathological tumour stage (HR 3.31; P < 0.001) were independently associated with an increased risk of recurrence after RC. Conclusion: Cigarette smoking was significantly associated with adverse pathological response to cisplatin‐based NAC in patients with MIBC treated with RC. Current smokers were at significantly higher risk of disease recurrence as compared to former and never smokers. [ABSTRACT FROM AUTHOR]

Abstract As a tumor metastasis suppressor gene, LASS2 has been found to be negatively associated with the stage of bladder cancer and overall survival of patients. However, the mechanisms regulating LASS2 in bladder cancer remain poorly understood. Here, we aim to identify a miRNA that targets LASS2 from bladder cancer-associated miRNAs and to reveal its potential functions in bladder cancer cells. Through miRNA microarray and bioinformatics analyses, we identified miR-3622a as a negative regulator of LASS2. The expression levels of miR-3622a in bladder cancer tissues were negatively correlated with the overall survival of patients. Overexpression of miR-3622a significantly increased the proliferation and invasion abilities of bladder cancer cells. In conclusion, our results indicate that miR-3622a promotes the proliferation and invasion of bladder cancer cells by downregulating LASS2. Highlights • miR-3622a is upregulated in bladder urothelial carcinoma. • miR-3622a target LASS2 and decrease the expression of LASS2 • Upregulation of miR-3622a enhances the proliferation and invasion abilities of bladder cancer cells. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors are effective in treating a variety of malignancies, including metastatic bladder cancer. A generally accepted hypothesis suggests that immune checkpoint inhibitors induce tumor regressions by reactivating a population of endogenous tumor-infiltrating lymphocytes (TILs) that recognize cancer neoantigens. Although previous studies have identified neoantigen-reactive TILs from several types of cancer, no study to date has shown whether neoantigen-reactive TILs can be found in bladder tumors. To address this, we generated TIL cultures from patients with primary bladder cancer and tested their ability to recognize tumor-specific mutations. We found that CD4+ TILs from one patient recognized mutated C-terminal binding protein 1 in an MHC class II-restricted manner. This finding suggests that neoantigen-reactive TILs reside in bladder cancer, which may help explain the effectiveness of immune checkpoint blockade in this disease and also provides a rationale for the future use of adoptive T cell therapy targeting neoantigens in bladder cancer. [ABSTRACT FROM AUTHOR]

Endogenous aldehydes (EAs) formed by the free-radical-mediated reaction are regarded as potential biological markers of several diseases. In this work, an automated and solvent-free analytical method was developed for quantitative analysis of seven EAs (C1–C7) in human blood by using gas chromatography–mass spectrometry coupled with a headspace generator sampler (HS-GC–MS). A 1:4 (blood:water) dilution and the 1,2‑dibromopropane internal standard were introduced to reduce the influence of the matrix effect from complex biological fluids. The sample preparation steps were simplified. Various experimental parameters for derivatization and extraction conditions were studied such as HS extraction temperature and time, the amount of derivatization reagent, pH and the salt effect. Under these optimum conditions, seven low-mass aldehydes were separated and analyzed within 10 min. Additionally, this method achieved limits of detection in the range of 0.0692–0.864 μg/L, an excellent linearity with correlation coefficients higher than 0.9996 and appropriate repeatability and reproducibility values (RSD < 12% at low, middle and high levels). The HS-GC–MS method was applied to measure the concentrations of the seven aldehydes in blood from bladder cancer patients (n = 15) and control subjects (n = 15). Compared with the control subjects, the levels of butanal (p < 0.01), formaldehyde, acetaldehyde, propanal, pentanal, hexanal and heptanal (all p < 0.001) were increased significantly, indicating that EAs may be useful as biomarkers in the early diagnosis of bladder cancer. • HS-GC–MS for determination of seven aldehydes in human blood. • Simple, automatic and environmentally friendly method. • Aldehydes were detected with good accuracy in human blood. • Internal calibration for quantification of aldehydes in diluted blank blood. • Higher concentrations of aldehydes were detected in the blood of bladder cancer patients than in the blood of control subjects. [ABSTRACT FROM AUTHOR]

Bladder cancer (BC) is one of the most common malignant tumors in the urinary system. The discovery of prognostic biomarkers is still one of the major challenges to improve clinical treatment of BC patients. In order to assist biologists and clinicians in easily evaluating the prognostic potency of genes in BC patients, we developed a user-friendly Online consensus Survival tool for bladder cancer (OSblca), to analyze the prognostic value of genes. The OSblca includes gene expression profiles of 1,075 BC patients and their respective clinical follow-up information. The clinical follow-up data include overall survival (OS), disease specific survival (DSS), disease free interval (DFI), and progression free interval (PFI). To analyze the prognostic value of a gene, users only need to input the official gene symbol and then click the "Kaplan-Meier plot" button, and Kaplan-Meier curve with the hazard ratio, 95% confidence intervals and log-rank P -value are generated and graphically displayed on the website using default options. For advanced analysis, users could limit their analysis by confounding factors including data source, survival type, TNM stage, histological type, smoking history, gender, lymph invasion, and race, which are set up as optional parameters to meet the specific needs of different researchers. To test the performance of the web server, we have tested and validated its reliability using previously reported prognostic biomarkers, including KPNA2, TP53 , and MYC etc., which had their prognostic values validated as reported in OSblca. In conclusion, OSblca is a useful tool to evaluate and discover novel prognostic biomarkers in BC. The web server can be accessed at http://bioinfo.henu.edu.cn/BLCA/BLCAList.jsp. [ABSTRACT FROM AUTHOR]

Purpose: As we begin to leverage Big Data in health care settings and particularly in assessing patient-reported outcomes, there is a need for novel analytics to address unique challenges. One such challenge is in coding transcribed interview data, typically free-text entries of statements made during a face-to-face interview. Latent Dirichlet Allocation (LDA) offers statistical rigor and consistency in automating the interpretation of patients' expressed concerns and coping strategies.Methods: LDA was applied to interview data collected as part of a prospective, longitudinal study of QOL in N = 211 patients undergoing radical cystectomy and urinary diversion for bladder cancer. LDA analyzed personal goal statements to extract the latent topics and themes, stratified by time, and on things patients wanted to accomplish and prevent. Model comparison metrics determined the number of topics to extract.Results: LDA extracted seven latent topics. Prior to surgery, patients' priorities were primarily in cancer surgery and recovery. Six months after the surgery, they were replaced by goals on regaining a sense of normalcy, to resume work, to enjoy life more fully, and to appreciate friends and family more. LDA model parameters showed changing priorities, e.g., immediate concerns on surgery and resuming employment decreased post-surgery and were replaced by concerns over cancer recurrence and a desire to remain healthy and strong.Conclusions: Novel Big Data analytics such as LDA offer the possibility of summarizing personal goals without the need for conventional fixed-length measures and resource-intensive qualitative data coding. [ABSTRACT FROM AUTHOR]

BACKGROUND: This study aimed to investigate the correlation of BRCA2 gene mutation and prognosis as well as variant genes in patients with invasive urothelial carcinoma of the bladder. It predicted and explored the possible mechanism and clinical value of BRCA2 in the occurrence and development of tumors. METHODS: Data sets of patients with bladder cancer were collected from the Cancer Genome Atlas (TCGA) database. Also the gene expression profile data and clinical information of the BRCA2 mutation group and non-BRCA2 mutation group were downloaded. RESULTS: The prognosis of the BRCA2 mutation group was better than that of the non-mutant group. Among the down-regulated genes, the following genes showed significant differences between the two groups: CCL22, CYP2B6, CYP2E1, CYP4F2, HTR1E, HTR1F, KLRC1, NAPSA, SELL, SFTPA1, SFTPA2, SFTPB, SFTPC and STRA8, while the following genes among the up-regulated genes showed significant differences between the two groups: ELAVL3, NOTUM, TRH and VIP. Meanwhile, the following gene sets were highly enriched in BRCA2: cell cycle, DNA replication, homologous recombination, oocyte meiosis, ubiquitin-mediated proteolysis, base excision repair, progestin mediated oocyte maturation, basal transcription factor, biosynthesis of N polysaccharide, mismatch repair, sliceosome, purine metabolism as well as P53 and neurotrophic factor signaling pathway, etc. CONCLUSION: These findings suggested that the BRCA2 gene mutation is a good prognostic factor and can be used as a gene to predict the prognosis in the bladder cancer patients. [ABSTRACT FROM AUTHOR]

Doublecortin-like kinase 1 (DCLK1) has been characterized as a novel potential cancer stem cell (CSC) marker in several types of cancer. It is considered as one of the most specific markers for distinguishing colorectal CSCs from normal stem cells. Yet, there are limited reports on the role of DCLK1 as a putative CSC marker in bladder cancer. Using immunohistochemistry, DCLK1 expression was examined in a well-defined tissue microarray series of 472 bladder cancer tissues. The association between DCLK1 protein expression and clinicopathological features, as well as survival outcomes, was assessed. Our findings showed strong, moderate, and weak DCLK1 expression in 123 (26.1%), 230 (48.7%), and 119 (25.2%) of the bladder cancer specimens, respectively. Higher expression of DCLK1 was significantly associated with increase in histological grade (P ≤.001), pT stage (P =.014), lamina propria (P =.006), and lamina propria/muscularis (L/M) involvement (P =.014). On multivariate analysis, pT stage (P <.001), histological grade (P =.021), and lamina propria involvement (P =.001) were independent prognostic factors in DCLK1 expression. Moreover, the expression of DCLK1 was found to be an independent marker of poor prognosis for disease- specific survival (DSS) (P =.048) in bladder carcinomas. Our observations showed that DCLK1 expression was associated with more aggressive tumor behavior, more advanced disease, and poorer DSS in patients with bladder carcinomas. However, any potential clinical applications of DCLK1 as a novel target molecule in bladder cancer patients would require further investigations. • Higher expression of DCLK1was associated with increase in grade in bladder cancer. • Also, higher DCLK1 expression was associated with increase in pT stage. • Finally, higher DCLK1 expression was associated with more aggressive tumor behavior. • Increased expression of DCLK1 is associated with poor DSS in bladder cancer. • DCKL1 was an independent poor prognostic factor for DSS in bladder cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: Patients and their families utilize online resources when dealing with a diagnosis of bladder cancer. Many patients have questions regarding clinical management options. Online research forums may help researchers and providers identify research areas of interest. Our objective was to review online forums and identify research questions that are important to patients and families impacted by bladder cancer diagnosis. Methods: We reviewed 1 month of online content from the Bladder Cancer Advocacy Network Inspire online community (https://www.inspire.com/groups/bladder-cancer-advocacy-network). Using affinity diagramming, we categorized the submitted content from patient users into themes stratified by the cancer severity of the patient user (non-muscle-invasive bladder cancer, muscle-invasive bladder cancer, metastatic bladder cancer). We categorized the content by the audience of forum posts (i.e., inwardly directed, those seeking support, vs. outwardly directed, those sharing personal experiences) and constructed comparative effectiveness research questions from the submitted content. Results: From 14 July 2014 to 14 August 2014, a total of 394 forum posts were collected, of which 3 were excluded from analysis due to non-relevant content, leaving 391 comments for final analysis. Almost 38% of posts involved muscle-invasive bladder cancer and 25% of posts were from people other than the patient. Inwardly and outwardly directed posts were commonly related to clinical treatment concerns. Conclusions: Review of online patient-generated content may offer insight into comparative effectiveness research topics of importance to bladder cancer patients. A more formalized process may better represent research priorities among bladder cancer patients. [ABSTRACT FROM AUTHOR]

Cyclin D2/D3 (CCND2/3) are core components of the machinery that drives cell cycle progression and therefore, are associated with tumorigenesis. Currently, there are contradictory evidences on the function of CCND2/3 in tumorigenesis. Thus, we conducted a comprehensive meta‐analysis to derive a precise predictive value of CCND2/3 in various tumors. We searched PubMed, EMBASE, Web of Science for eligible studies up to October 8, 2018. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) of OS or DFS/PFS/RFS were calculated using Forest plot analysis to demonstrate their associations. A total of 14 studies were ultimately included in this meta‐analysis. Our results indicated CCND2/3 played an oncogenic role in all of the cancer patients (CCND2: pooled HR = 2.21, 95% CI: 1.67‐2.93; CCND3: pooled HR = 2.29, 95% CI: 1.05‐5.03). In tumor subgroup, CCND2 was associated with shorter OS in patients with gastric cancer (HR = 2.20, 95% CI: 1.66‐2.92), whereas it might be a tumor suppressor in NSCLC (HR = 0.28, 95% CI: 0.12‐0.64). In addition, CCND3 was correlated to reduced OS in breast cancer patients (HR = 1.64, 95% CI: 1.07‐2.52) and shorter DFS/PFS/RFS in bladder cancer patients (HR = 4.60, 95% CI: 1.89‐12.57). Taken together, CCND2/3 could be the promising biomarkers for predicting the prognosis of patients with malignant neoplasms. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs) have been considered to mediate occurrence and development of human cancers, generally acting as microRNA (miRNA) sponges to regulate downstream genes expression. However, the aberrant expression profile and dysfunction of circRNAs in human bladder cancer remain to be investigated. The present study aims to elucidate the potential role and molecular mechanism of circACVR2A in regulating the proliferation and metastasis of bladder cancer. Methods: circACVR2A (hsa_circ_0001073) was identified by RNA-sequencing and validated by quantitative real-time polymerase chain reaction and agarose gel electrophoresis. The role of circACVR2A in bladder cancer was assessed both in vitro and in vivo. Biotin-coupled probe pull down assay, biotin-coupled microRNA capture, dual-luciferase reporter assay, and fluorescence in situ hybridization were conducted to evaluate the interaction between circACVR2A and microRNAs. Results: The expression of circACVR2A was lower in bladder cancer tissues and cell lines. The down-regulation of circACVR2A was positively correlated with aggressive clinicopathological characteristics, and circACVR2A served as an independent risk factor for overall survival in bladder cancer patients after cystectomy. Our in vivo and in vitro data indicated that circACVR2A suppressed the proliferation, migration and invasion of bladder cancer cells. Mechanistically, we found that circACVR2A could directly interact with miR-626 and act as a miRNA sponge to regulate EYA4 expression. Conclusions: circACVR2A functions as a tumor suppressor to inhibit bladder cancer cell proliferation and metastasis through miR-626/EYA4 axis, suggesting that circACVR2A is a potential prognostic biomarker and therapeutic target for bladder cancer. [ABSTRACT FROM AUTHOR]

Given that most bladder cancers (BCs) are diagnosed in advanced stages with poor prognosis, this study aims to find novel biomarkers associated with the progression and prognosis in patients with BC. 1,779 differentially expressed genes (DEGs) between BC samples and normal bladder tissues were identified in total. Then, 24 DEGs were regarded as candidate hub genes by constructing a protein–protein interaction (PPI) network and a random forest model. Among them, six genes (BUB1B, CCNB1, CDK1, ISG15, KIF15, and RAD54L) were eventually identified by using five analysis methods (one-way Analysis of Variance analysis, spearman correlation analysis, distance correlation analysis, receiver operating characteristic curve, and expression values comparison), which were correlated with the progression and prognosis of BC. Moreover, the validation of hub genes was conducted based on GSE13507, Oncomine, and CBioPortal. Results of univariate Cox regression analysis showed that the expression levels of all the hub genes were influence features of overall survival (OS) and cancer specific survival (CSS) based on GSE13507, and we further established a six-gene signature based on the expression levels of the six genes and their Cox regression coefficients. This signature showed good potential for clinical application suggested by survival analysis (OS: Hazard Ratio = 0.484, 95%CI: 0.298–0.786; P = 0.0034; CSS: Hazard Ratio = 0.244, 95%CI: 0.121–0.493, P < 0.0001) and decision curve analysis. In conclusion, our study indicates that six hub genes have great predictive value for the prognosis and progression of BC and may contribute to the exploration of further basic and clinical research of BC. [ABSTRACT FROM AUTHOR]

Objective: To conduct a systematic synthesis of the literature evaluating the use of the Internet and social media by people with bladder cancer (BCa) and their carers, and to synthesize the evidence on the quality of available online resources for patients with BCa. Methods: We selected studies published between January 2000 and September 2018, written in the English language and meeting the inclusion criteria. Data sources included PubMed, PsycINFO, EMBASE, Web of Science and Scopus. Results: A total of 15 studies were included in the review. Four studies explored patterns of Internet use among patients with BCa, five studies investigated social media use related to BCa and six studies evaluated the quality of online resources available for patients with BCa. Evidence in all these three dimensions was limited in its ability to establish rigorously if use of the Internet, social media and online resources for BCa is effective in improving the care outcomes for patients with BCa. Conclusion: Our review emphasizes the forgotten status of BCa by establishing that, despite its high global incidence, it remains underrepresented in the building of evidence on patient information needs and the possible role of online spaces. Our synthesis establishes that further research is needed to examine the full impact of online information and social media use on the health management of people with BCa. [ABSTRACT FROM AUTHOR]

Purpose: Trimodality therapy with maximal transurethral resection of bladder tumor and definitive chemoradiation reserving cystectomy for salvage of local recurrence is an accepted treatment alternative to upfront cystectomy for selected patients with muscle-invasive bladder cancer. There is a need for molecular biomarkers to predict which patients will respond to bladder preservation therapy.Methods and Materials: We sought to identify biomarkers with the ability to predict response to chemoradiation and survival after selective bladder preservation therapy in a cohort of 40 patients using a microRNA profiling approach. In vitro experiments were performed using transitional cell carcinoma lines CRL1749, HTB5, and HTB4.Results: We identified a panel of microRNAs associated with overall survival in our bladder preservation cohort and in the TCGA cohort. We also identified several microRNAs, including miR-23a and miR-27a, microRNAs of the miR-23a cluster, to be suggestively associated with complete response to chemoradiation therapy. The microRNAs were significantly associated with overall survival in The Cancer Genome Atlas cohort. In vitro studies suggest that the functional roles of miR-23a and miR-27a involve targeting the SFRP1 protein, a negative regulator of the Wnt signaling pathway. The upregulation of β-catenin in the Wnt signaling pathway mediated proliferation, migration, invasion, and sensitivity to radiation and cisplatin treatment in bladder cancer cells.Conclusions: Our results indicate that miR-23a and miR-27a act as oncomirs, and once independently validated, they may help appropriately triage selected bladder cancer patients to individualize treatment. [ABSTRACT FROM AUTHOR]

Objectives: To analyze outcomes of patients > 85 years with de novo bladder cancer (BCa). To compare outcomes of high grade (HG) non-muscle invasive BCa (NMIBC) treated with standard therapies versus palliative management. Methods: Retrospective revision of 65 patients > 85 years who underwent transurethral resection of the bladder (TURB) for de novo BCa. According to functional status each patient was offered a standard or palliative management after TURB. Results: Median age was 87.3 years (85.2–95.4) and 51 were men (78.5%). Twenty-eight (43%) were American Society of Anesthesiologists (ASA) II and 37 ASA III–IV (57%). Pathological examination: 29 pTx-pTa (44.6%), 28 pT1 (43.1%) and 8 pT2 (12.3%). Twenty were low grade (30.8%) and 45 HG (69.2%). Among 37 HG NMIBC patients, 43% followed standard therapies (BCG or re-staging TURB + BCG), and 57% a palliative management (no oncological treatments). With a median follow-up of 20 months (3–108), 2 (12.5%) died in standard group compared to 11 (52.4%) in palliative. In univariate analysis, age (p = 0.024), stage (p = 0.009), and standard management (p = 0.019) were related to overall survival (OS). In multivariate, standard management was an independent prognostic factor of OS (hazard ratio 0.164, 95% CI 0.036–0.744, p = 0.048). Conclusions: Advanced age should not be a contraindication for standard therapies in BCa. A geriatric assessment could identify patients who may benefit from adjuvant therapies after TURB. [ABSTRACT FROM AUTHOR]

Introduction: According to TNM staging, pathological T4ab are comprehensive of the invasion of prostate, seminal vesicles, uterus or vagina and pelvic or abdominal wall. However, few data are available on the perioperative and oncological outcomes of specific organ invasion. Materials and Methods: A total of 917 consecutive bladder cancer (BCa) patients treated with radical cystectomy (RC) at a single institution between 1990 and 2015 were studies. Cox regression analyses were used to stratify pT4ab according to the site of invasion and survival. Results: Overall, 176 (19.2%) and 40 (4.4%) patients harbored pT4a or pT4b disease. Specifically, 84 (9.2%) patients reported prostate and/or SVI invasion, 62 (6.8%) prostate only, 16 (1.7%) uterus, 14 (1.5%) vaginal, 24 (2.6%) pelvic wall, and 16 (1.7%) abdominal wall invasion. The median follow-up in pT4 patients was 48 months. The 1-year cancer-specific mortality (CSM) rates were 71, 65, 24, 50, 50, and 72%, for vaginal, uterus, prostate only, prostate and/or seminal vesicles, pelvic wall, and abdominal wall invasions, respectively. At multivariable Cox regression, the invasion of prostate only (hazard ratio [HR] 3.53), prostate and/or SVI (HR 4.98), uterus (HR 7.16), vagina (HR 6.12), pelvic (HR 11.81), abdominal (8.36) were associated with adverse CSM. Conclusions: Our study described the differences in survival related to invasion site in pT4 patients, confirming poor survival expectancies in this subgroup. Patients with prostate invasion only seem to be associated with better survival than those affected by concomitant invasion of seminal vesicles. Uterus and vaginal invasions were associated with poor survival outcomes. Patients Summary: In this study, we looked at the outcome of locally advanced invasive BCa (stage pT4) in patients treated with RC at a tertiary referral hospital. We analyzed the differences in survival related to the specific organ invasion. We confirmed poor survival in this subgroup of patients. Only patients who had prostate invasion only seem to have a better survival. [ABSTRACT FROM AUTHOR]

Changes in the expression of miR-490-5p, miR-148a-3p and miR-608 in bladder cancer tissues were studied. A total of 30 patients with bladder cancer who had surgical resection in the Hunan Provincial People's Hospital (Changsha, China) from April 2015 to August 2016 were selected. RT-qPCR was used to detect the expression levels of miR-490-5p, miR-148a-3p and miR-608. The expression vectors of miR-490-5p, miR-148a-3p and miR-608 were respectively transfected and divided into three groups: blank cell group, gene transfection group (groups A-C) and negative transfection group (NC group). CCK8 was used to detect cell proliferation and flow cytometry was used to detect the condition of apoptosis of each group, and the Transwell chamber was used to detect the invasion ability of the cells. After the transfection, the expression level of miR-490-5p in group A was significantly higher than that in the NC and blank groups, and the expression level of miR-148a-3p in group B was significantly higher than that in the NC and blank groups. The expression level of miR-608 in group C was significantly higher than that in the NC and blank groups (P<0.001). The survival rates of the cells in groups A-C were significantly lower than those in the NC and blank groups at 48 and 72 h (P<0.001). After the transfection, the number of invasive cells and the apoptosis rates in groups A-C were significantly higher than those in the NC and blank groups (P<0.05). miR-490-5p, miR-148a-3p and miR-608 promoted proliferation of bladder cancer T24 cells and inhibited apoptosis of the cells and showed potential to become a new target for the future treatment of bladder cancer. [ABSTRACT FROM AUTHOR]

Abstract Background A fast, noninvasive test with high sensitivity (SN) and a negative predictive value (NPV), which is able to detect recurrences in bladder cancer (BC) patients, is needed. A newly developed urine assay, Xpert Bladder Cancer Monitor (Xpert), measures five mRNA targets (ABL1, CRH, IGF2, UPK1B, and ANXA10) that are frequently overexpressed in BC. Objective To validate Xpert characteristics in patients previously diagnosed with non-muscle-invasive BC. Design, setting, and participants Voided precystoscopy urine samples were prospectively collected at 22 sites. Xpert, cytology, and UroVysion were performed. If cystoscopy was suspicious for BC, a histologic examination was performed. Additionally, technical validation was performed and specificity was determined in patients without a history or clinical evidence of BC. Outcome measurements and statistical analysis Test characteristics were calculated based on cystoscopy and histology results, and compared between Xpert, cytology, and UroVysion. Results and limitations Of the eligible patients, 239 with a history of BC had results for all assays. The mean age was 71 yr; 190 patients were male, 53 never smoked, and 64% had previous intravesical immunotherapy (35%) or chemotherapy (29%). Forty-three cases of recurrences occurred. Xpert had overall SN of 74% (95% confidence interval [CI]: 60–85) and 83% (95% CI: 64–93) for high-grade (HG) tumors. The NPV was 93% (95% CI: 89–96) overall and 98% (95% CI: 94–99) for HG tumors. Specificity was 80% (95% CI: 73–85). Xpert SN and NPV were superior to those of cytology and UroVysion. Specificity in non-BC individuals (n = 508) was 95% (95% CI: 93–97). Conclusions Xpert has an improved NPV compared with UroVysion and cytology in patients under follow-up for BC. It represents a promising tool for excluding BC in these patients, reducing the need for cystoscopy. Patient summary Xpert is an easy-to-perform urine test with good performance compared with standard urine tests. It should help optimize the follow-up of recurrent bladder cancer patients. Take Home Message The Xpert test is a mRNA-based urine assay for bladder cancer detection. In recurrent bladder cancer patients, its test characteristics compare favorably with those of UroVysion and cytology. It represents a promising tool for excluding cancer, thus reducing the need for cystoscopy. [ABSTRACT FROM AUTHOR]

Purpose: Autophagy is a major catabolic system by which eukaryotic cells undergo self-degradation of damaged, defective, or unwanted intracellular components. An abnormal autophagic level is implicated in the pathogenesis of multiple diseases, including cancers. The aim of this study is to explore the prognostic value of autophagy in bladder cancer (BC), which is a major cause of cancer-related death globally. Patients and methods: First, 27 differentially expressed autophagy-related genes (ARGs) were identified in BC patients based on The Cancer Genome Atlas (TCGA) database. Functional enrichment analyses hinted that autophagy may act in a tumor-suppressive role in the initiation of BC. Then, the Cox proportional hazard regression model were employed to identify three key prognostic ARGs (JUN, MYC, and ITGA3), which were related with overall survival (OS) significantly in BC. The three genes represented important clinical significance and prognostic value in BC. Then a prognostic index (PI) was constructed. Results: The PI was constructed based on the three genes, and significantly stratified BC patients into high- and low-risk groups in terms of OS (HR=1.610, 95% CI=1.200–2.160, P=0.002). PI remained as an independent prognostic factor in multivariate analyses (HR=2.355, 95% CI=1.483–3.739, P<0.001). When integrated with clinical characteristics of age and stage, an autophagy-clinical prognostic index (ACPI) was finally validated, which had improved performance in predicting OS of BC patients (HR=2.669, 95% CI=1.986–3.587, P<0.001). The ACPI was confirmed in datasets of GSE13507 (HR=7.389, 95% CI=3.645–14.980, P<0.001) and GSE31684 (HR=1.665, 95% CI=0.872–3.179, P=0.122). Conclusion: This study provides a potential prognostic signature for predicting prognosis of BC patients and molecular insights of autophagy in BC. [ABSTRACT FROM AUTHOR]

Background: T1 high-grade non-muscle invasive bladder cancer has a high recurrence rate and progression. The treatment options have some controversy. Objective: To evaluate the progression of T1 high-grade non-muscle invasive bladder cancer in Ramathibodi Hospital and determine the prognostic factors that contribute to muscle invasive disease. Materials and Methods: The authors retrospectively reviewed 70 patients diagnosed as T1 high-grade bladder cancer from 1,270 bladder cancer patients in Ramathibodi Hospital between 2007 and 2017. The primary objective was to evaluate the progression rate and related prognostic factors. The authors analyzed the risk factors contributing to the progressive muscle invasive disease. The authors also analyzed the survival rate between the progressive group and the non-progressive group. Finally, the role of early cystectomy in T1 high-grade bladder cancer was also analyzed. Results: The mean age was 68 years old and the mean follow-up time was 40.1 months. The recurrence rate was 55.7% (39/70). The risk factors of recurrence were no muscle at the initial tumor resection and history of intravesical BCG instillation before diagnosis of T1 high-grade cancer. The progression rate was 14.3% (10/70). There was no significant risk factor contributing to progressing the disease. The median survival of non-progressive group was 45.2 months and progressive group was 18.2 months (p=0.002). The authors performed early radical cystectomy in 14 patients and there was no difference in overall survival between the non-progressive disease group and the early cystectomy group. Conclusion: Lack of muscle at the initial resection and prior intravesical BCG instillation were the risk factors of the recurrence of T1 high-grade bladder cancer. It is obvious that progressive disease is the strongest impact on survival and early radical cystectomy does not improve survival if it was the non-progressive disease. Further studies are needed to identify the risk factors that can differentiate between non-progressive and progressive disease. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the impact of an eight‐item surgical checklist (SC) on the recurrence‐free survival (RFS) of patients with non‐muscle‐invasive bladder cancer (NMIBC) undergoing transurethral resection of bladder tumour (TURBT). Patients and Methods: A group of urologists at two tertiary referral centres, with expertise in bladder cancer, identified eight critical items that should be performed in every high‐quality TURBT. An eight‐item SC was prospectively implemented into clinical practice and the operative reports of TURBTs performed before and after implementation were reviewed. Results from both institutions were combined to estimate the impact of introducing the SC on oncological outcomes. Multivariable logistic and Cox hazards regression analyses were performed to evaluate the impact of the SC on the presence of detrusor muscle in the TURBT specimen and on RFS, respectively. Results: The operative reports of 266 TURBTs performed after the SC implementation were reviewed and compared to those of 281 TURBTs performed prior to the SC introduction. The SC was independently associated with a significant improvement in RFS (P = 0.02). However, the introduction of the SC was not significantly associated with the presence of detrusor muscle in the surgical specimen (P = 0.4). Conclusion: The use of an eight‐item SC during TURBT in clinical practice increases the quality of operative reports thereby potentially improving individualised risk‐stratification and care resulting in lower disease recurrence rates. Therefore, the introduction of a SC can be recommended to enhance oncological outcomes by improving surgical standardisation and operative reporting. [ABSTRACT FROM AUTHOR]

Background: There are race-based differences in bladder cancer survival. To better understand this phenomenon, this study was designed to assess the statistical contributions of tumor, treatment, and access variables to race-based differences in survival.Methods: Data were extracted from the National Cancer Data Base on black and white adults with muscle-invasive bladder cancer from 2004 to 2015. The impact of tumor, access, and treatment variables on differences in survival was inferred by the performance of sequential propensity score-weighted analyses in which black and white patients were balanced with respect to demographics and health status (comorbidities) tumor characteristics, treatment, and access-related variables. The propensity score-weighted hazard of death (black vs white) was calculated after each iteration.Results: This study identified 44,577 patients with a median follow-up of 77 months. After demographics and health status were balanced, black race was associated with 18% worse mortality (hazard ratio, 1.18; 95% confidence interval [CI], 1.12-1.25; P < .001). Balancing by tumor characteristics reduced this to 16%, balancing by treatment reduced this to 10%, and balancing by access-related variables resulted in no difference. Access-related variables explained 40% (95% CI, 22.9%-57.0%) of the excess risk of death in blacks, whereas treatment factors explained 35% (95% CI, 22.2%-46.9%). The contribution of tumor characteristics was not significant.Conclusions: In the models, differences in survival for black and white patients with bladder cancer are best explained by disparities in access and treatment, not tumor characteristics. Access to care is likely a key factor in racial disparities in cancer. [ABSTRACT FROM AUTHOR]