Detection Of Bladder Cancer Research Articles

1267 Utility of Artificial Intelligence in the Cystoscopic Detection of Bladder Cancer: A Systematic Review and Meta-Analysis

Abstract Aim Detection of suspected bladder cancer at diagnostic cystoscopy is challenging and is dependent on clinician skill. Artificial Intelligence (AI) algorithms, specifically, machine learning and deep learning, have shown promise in accurate classification of pathological images in various specialties. However, utility of AI for urothelial cancer diagnosis is unknown. Here, we aimed to systematically review the extant literature in this field and quantitively summarise the role of these algorithms in bladder cancer detection. Method The EMBASE, PubMed and CENTRAL databases were searched up to December 22nd 2020 , in accordance with the PRISMA guidelines, for studies that evaluated AI algorithms for cystoscopic diagnosis of bladder cancer. Random-effects meta-analysis was performed to summarise eligible studies. Risk of Bias was assessed using the QUADAS-2 tool. Results Five from 6715 studies met criteria for inclusion. Pooled sensitivity and specificity values were 0.93 (95% CI 0.89–0.95) and 0.93 (95% CI 0.80–0.89) respectively. Pooled positive likelihood and negative likelihood ratios were 14 (95% CI 4.3–44) and 0.08 (95% CI: 0.05–0.11), respectively. Pooled diagnostic odds ratio was 182 (95% CI 61–546). Summary AUC curve value was 0.95 (95% CI 0.93–0.97). No significant publication bias was noted. Conclusions In summary, AI algorithms performed very well in detection of bladder cancer in this pooled analysis, with high sensitivity and specificity values. However, as with other clinical AI usage, further external validation through deployment in real clinical situations is essential to assess true applicability of this novel technology.

Detection of bladder cancer using voided urine sample and by targeting genomic VPAC receptors.

Introduction:Cells exfoliated into urine from the bladder can help to diagnose the cancer. The objective of this study was to validate the hypothesis that bladder cancer could be detected noninvasively by a simple and reliable assay targeting genomic VPAC (combined vasoactive intestinal peptide and pituitary adenylate cyclase-activating peptide family of cell surface receptors) receptors expressed on the malignant bladder cancer cells shed in the voided urine.Methods:Patients ≥18 years of age with either imaging (ultrasonography/computed tomography [CT])-confirmed bladder tumors or those who have been previously treated for nonmuscle invasive bladder tumors and were visiting the department for check cystoscopy, formed the study group. Freshly voided urine sample was collected from these patients and sent for conventional cytology examination, 5-aminolevulinic acid (ALA) fluorescent urine cytology, and for positivity of VPAC receptors.Results:A total of 103 patients were prospectively included in the study. Of these, 65 patients (Group I) presented with image-diagnosed (ultrasonography and/or CT) bladder cancer. The remaining 38 patients (Group II) were previously diagnosed cases of nonmuscle invasive bladder cancer and presented for follow-up and check cystoscopy. The sensitivity for VPAC receptor positivity was 89.23% compared to conventional cytology (63.07%) and 5-ALA fluorescent urine cytology (87.69%). The specificity of VPAC receptor positivity was 100% compared to conventional cytology (100%) and 5-ALA-induced fluorescent cytology (90.47%).Conclusions:Our preliminary study shows encouraging results with VPAC receptor positivity studies, which has a high sensitivity when compared to the conventional cytology.

P26 - A large pilot study on the diagnostic performance of electronic nose in detecting Bladder Cancer

P26 - A large pilot study on the diagnostic performance of electronic nose in detecting Bladder Cancer

Combination of urinary fibrinogen β-chain and tyrosine-phosphorylated proteins for the detection of bladder cancer.

Aim:To evaluate the performance of urinary fibrinogen β-chain (FBC) – either alone or associated with urinary tyrosine-phosphorylated proteins (UPY) – as bladder cancer (BCa) diagnostic biomarker.Materials & methods:164 subjects were tested.Results:Significantly different FBC and UPY levels were found between BCa patients and controls, as well as between low-grade and high-grade cancers. The diagnostic accuracy was 0.84 for FBC and 0.87 for UPY. The combination of FBC and UPY improved the accuracy to 0.91. The addition of clinical variables (age, gender, and smoking habit) to FBC and UPY into a model for BCa prediction significantly improved the accuracy to 0.99. The combination of FBC and UPY adjusted for clinical variables associates with the highest sensitivity and good specificity.Conclusion:Urinary FBC and UPY could be used as biomarkers for BCa diagnosis.

Multiple Chromatographic Analysis of Urine in the Detection of Bladder Cancer

Bladder cancer (BC) is the most common type of carcinoma of the urological system. Recently, there has been an increasing interest in non-invasive diagnostic tumor markers due to the invasive attribute of cystoscopy, which is still considered the gold standard diagnostic method. However, markers published in the literature so far do not meet expectations for replacing cystoscopy due to their low specificity and excessively high false-positive results, which can be mainly caused by frequently occurring hematuria also in benign cases. No reliable non-invasive method has yet been identified that can distinguish patients with bladder cancer and non-malignant hematuria patients. Our work examined the possibilities of non-targeted biomarkers of urine to distinguish patients with malignant and non-malignant diseases of the bladder using 3D HPLC in combination with computer processing of multiple datasets. Urine samples from 47 patients, 23 patients with bladder cancer (BC) and 24 patients with non-malignant hematuria (NMHU), were enrolled in clinical trials. For the separation and subsequent analysis of a large number of urine components, 3D HPLC (high-performance liquid chromatography) with an absorption and fluorescence detector was used. The obtained dataset was further subjected to various uni- and multi-dimensional statistical analyses and mathematical modeling. We found 334 chromatographic peaks, of which 18 peaks were identified as significantly different for BC and NMHU patients. Using receiver operating characteristic (ROC) analysis, we assessed the informative ability of significant chromatographic peaks (90% sensitivity and 74% specificity). By logistic regression, we identified the optimal and simplified set of seven chromatographic peaks (5 absorptions plus 2 fluorescence) with strong classification power (100% sensitivity and 100% specificity) for distinguishing patients with bladder cancer and those with non-malignant hematuria. Partial least square discriminant analysis (PLS-DA) model and orthogonal projection to latent structure discriminant analysis (OPLS-DA) with 100% sensitivity and 96% specificity were used to distinguish BC and NMHU patients. Multivariate statistical analysis of urinary metabolomic profiles of patients revealed that BC patients can be discriminated from NMHU patients and the results can likely contribute to an early and non-invasive diagnosis of BC.

Multiplexed detection of bladder cancer microRNAs based on core-shell-shell magnetic quantum dot microbeads and cascade signal amplification

Bladder Cancer (BC) is the tenth most common cancer worldwide and the most malignant disease of the urinary system. The development of effective biomarkers and detection methods is of great significance for BC diagnosis and monitoring. This study demonstrated a microscopic imaging method for multiplexed detecting BC microRNAs (miRNAs) based on core-shell-shell bifunctional magnetic fluorescent beads (MFBs), with the integration of catalytic hairpin assembly (CHA) and terminal deoxynucleotidyl transferase (TdT)-mediated DNA polymerization. Assembled with quantum dots and magnetic nanoparticles, MFBs were utilized as the dual-functional carriers for optical encoding and magnetic separation. By introducing CHA-TdT cascade amplification, three encoded MFBs presented distinct changes of emissive-color, which could be decoded by the common fluorescence microscope. The strategy could reach femtomolar level for the detection of single miRNA, showing a wide linear dynamic range (6 logs). Point-mutation discrimination capability was also achieved for precise miRNA analyses. Moreover, this MFB-CHA-TdT strategy was capable of detecting BC-related miRNAs in clinical serum specimens, showing a great consistence with qRT-PCR. Overall, this work enabled multiplexed detection of miRNAs with ideal sensitivity, specificity and accuracy, which could be applied to the clinical detection and early diagnosis of BC.

Diagnostic accuracy of NMP-52, NMP-22 and urine cytology in the diagnosis of bladder cancer

Bladder cancer (BC) is the most important tumor problem of urologic cancer. Therefore, noninvasive urinary biomarkers were used for diagnosis of BC. However, the new biomarkers failed to reach higher accuracy. The aim of this study was to assess the diagnostic efficacy of nuclear matrix protein-22 (NMP- 22), nuclear matrix protein-52 (NMP-52), urinary cytology and to investigate combinations of urine NMP-52 with urinary cytology as noninvasive biomarkers to increase diagnostic performance of bladder cancer at different grades and stages. Overall, there were 156 subjects (62 BC, 54 cystitis patients and 40 healthy volunteers). The NMP-22 and NMP-52 were quantified in urine samples by ELISA. The urinary cytology is used by some physicians routinely for diagnosis of BC. The sensitivity and specificity for NMP-52 were 94% and 82%, for NMP-22 69% and 80.8% and for cytology 56% and 94.6% respectively and also, both urinary NMP-22 and NMP-52 have extremely significant relation (p<0.0001) to BC vs. healthy individuals and cystitis patients. Moreover, the combination of NMP- 52 with urinary cytology could predict all BC stages and grade with 95.6% sensitivity and 94.3% specificity. In conclusion, NMP-52 and urinary cytology in combination improve diagnostic performance for BC detection in different pathological types.

Urine DNA for monitoring chemoradiotherapy response in muscle-invasive bladder cancer: a pilot study.

Accumulating evidence infers the utility of DNA-based urine biomarkers for initial detection of bladder cancer (BC) and surveillance of non-muscle-invasive BC. We have previously described gene panels with utility for these indications, identifying UBC-associated mutations in 96% of all BCs such that the associated urine test is not reliant upon the initial identification of mutations in primary tumour tissue.

Deregulated molecular genetic pathways in urinary bladder cancer with the importance of molecular biomarkers in diagnosis and follow-up- A comprehensive and updated review

This article reviews and compares various currently available non-invasive, molecular biomarker-based tests for bladder cancer (BC) detection, and evaluates other potential molecules that may be used for BC diagnosis and surveillance. Currently, urinary cytology and periodic cystoscopies are clinically recommended for the diagnosis and monitoring of BC. Though highly specific, urinary cytology lacks sensitivity, whereas cystoscopies are invasive tests that are uncomfortable for the patient. Molecular biomarkers associated with BC progression form the basis for various available non-invasive tests. Urinary proteins like NMP22, MCM5 and Human complement factor-H related protein (BTA) are detected by ELISA/Immunochromatographic assay devices (NMP22, BTA, ADXBLADDER). Chromosomal abnormalities reported in BC -aneuploidy in chromosomes 3, 7, and 17 and deletions in chromosome 9- are detected by the Fluorescence in situ Hybridization based UroVysion test. Tumor antigens like sulfated mucin glycoproteins and glycosylated CEA help to light up urothelial carcinoma cells exfoliated into urine (uCyt+). Mutations in TERTp, FGFR3, KRAS, HRAS, TP53, CDKN2A, ERBB2 and PIK3CA contribute to BC progression and these are detected in tumor DNA by RT-qPCR, NGS and/or Sanger sequencing-based assays (Uromonitor, UroSEEK, AssureMDX). mRNA levels of genomic markers frequently deregulated in BC like IGFBP5, HOXA13, MDK, CDC2, CXCR5, IGF2, ABL1, CRH, UPK1B and ANXA10 are assesed by CxBladder and Xpert Bladder Cancer Monitor. BC associated changes in DNA methylation are detected by real time PCR and NGS based assays (EpiCheck, UroMark, AssureMDX). These tests have not yet been formally indicted into clinical practice but can serve as sensitive indicators for early diagnosis, disease monitoring, and treatment response in BC. Keywords: bladder cancer, biomarkers, non-invasive tests, molecular events in bladder cancer, genetic changes in bladder cancer

Usefulness of advanced monoenergetic reconstruction technique in dual-energy computed tomography for detecting bladder cancer

PurposeDetecting bladder cancer (BC) in routine CT images is important but is sometimes difficult when cancer is small. We evaluated the ability of 40-keV advanced monoenergetic images to depict BC.Materials and methodsFifty-two patients with a median age of 74 years (range 45–92) who were diagnosed as BC with transurethral resection or cystectomy, were included. They were examined with contrast-enhanced dual-energy CT (DE-CT) and advanced virtual monoenergetic images (40 keV) were reconstructed. For evaluating depictability of BC on 40-keV or virtual-120-kVp images, the difference in CT number between the cancer and bladder wall (BC–BW value) were calculated. We also subjectively assessed depictability of BC in virtual-120-kVp and 40-keV images using a 4-grade Likert scale (3: clear, 0: not visualized).ResultsIn 42 of 52 patients, BC–BW values could be calculated because BC was detected on CT images. The mean BC–BW value at 40 keV was significantly higher than that of virtual 120 kVp [80.5 ± 54 (SD) vs. 11.4 ± 12.5 HU, P < 0.01]. Average scores of subjective evaluations in the virtual-120-kVp and 40-keV images were 1.7 ± 1.2 and 2.1 ± 1.2, respectively (P < 0.001).ConclusionThe advanced monoenergetic reconstruction technique reconstructed using DE-CT image is useful to depict BC.

An Artificial Intelligence System for the Detection of Bladder Cancer via Cystoscopy: A Multicenter Diagnostic Study.

Cystoscopy plays an important role in bladder cancer (BCa) diagnosis and treatment, but its sensitivity needs improvement. Artificial intelligence has shown promise in endoscopy, but few cystoscopic applications have been reported. We report a Cystoscopy Artificial Intelligence Diagnostic System (CAIDS) for BCa diagnosis. In total, 69 204 images from 10 729 consecutive patients from 6 hospitals were collected and divided into training, internal validation, and external validation sets. The CAIDS was built using a pyramid scene parsing network and transfer learning. A subset (n = 260) of the validation sets was used for a performance comparison between the CAIDS and urologists for complex lesion detection. The diagnostic accuracy, sensitivity, specificity, and positive and negative predictive values and 95% confidence intervals (CIs) were calculated using the Clopper-Pearson method. The diagnostic accuracies of the CAIDS were 0.977 (95% CI = 0.974 to 0.979) in the internal validation set and 0.990 (95% CI = 0.979 to 0.996), 0.982 (95% CI = 0.974 to 0.988), 0.978 (95% CI = 0.959 to 0.989), and 0.991 (95% CI = 0.987 to 0.994) in different external validation sets. In the CAIDS vs urologists' comparisons, the CAIDS showed high accuracy and sensitivity (accuracy = 0.939, 95% CI = 0.902 to 0.964; sensitivity = 0.954, 95% CI = 0.902 to 0.983) with a short latency of 12 seconds, much more accurate and quicker than the expert urologists. The CAIDS achieved accurate BCa detection with a short latency. The CAIDS may provide many clinical benefits, from increasing the diagnostic accuracy for BCa, even for commonly misdiagnosed cases such as flat cancerous tissue (carcinoma in situ), to reducing the operation time for cystoscopy.

MP38-06 PREDICTIVE ROLE OF SERUM INFLAMMATORY CYTOKINES IN DETECTION OF BLADDER CANCER

You have accessJournal of UrologyBladder Cancer: Epidemiology & Evaluation I (MP38)1 Sep 2021MP38-06 PREDICTIVE ROLE OF SERUM INFLAMMATORY CYTOKINES IN DETECTION OF BLADDER CANCER Mervat Soliman, Ahmed Elkashef, Marwan Anas, Mona El Wassefy, Youssef Mohamed Mosaad, Shereen Salah Metwally, and Yasser Osman Mervat SolimanMervat Soliman More articles by this author , Ahmed ElkashefAhmed Elkashef More articles by this author , Marwan AnasMarwan Anas More articles by this author , Mona El WassefyMona El Wassefy More articles by this author , Youssef Mohamed MosaadYoussef Mohamed Mosaad More articles by this author , Shereen Salah MetwallyShereen Salah Metwally More articles by this author , and Yasser OsmanYasser Osman More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002053.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Inflammation plays a critical role in cellular damage causing various diseases, including cancers. Bladder cancer (BC) is the one of most common cancers worldwide that represents a major cause of morbidity and mortality. However, early diagnosis of BC may improve the natural history of the disease. Therefore, we assessed the role of serum inflammatory cytokine levels in detection of BC. METHODS: 120 individuals (60 BC patients and 60 healthy controls) were included in the study. Blood samples were collected, so total RNA extract was isolated and analyzed by a reverse transcriptase-polymerase chain reaction assay for detection of interleukin (IL)-6, IL-12, IL-27 and tumor necrosis factor (TNF)-α levels. Tissue samples were also collected by transurethral resection (TUR) for routine histopathological examination. RESULTS: The study included 104 males (86.6%) and 16 females (13.4%). Mean ages were 66.4±8.8 years old. BC patients significantly showed higher levels of IL-6 and TNF-α expression and lower expression levels of IL-27 relative to the healthy controls (p ˂0.001). Multivariate logistic regression identified IL-6, IL-27 and TNF-α as independent predictors for BC (table 1). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and overall accuracy of IL-6, IL-12, IL-27 and TNF-α were shown in table 2 and figure 1. CONCLUSIONS: Serum inflammatory cytokines; IL-6, IL-27 and TNF-α might be regarded as promising useful biomarkers to predict BC. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e694-e694 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mervat Soliman More articles by this author Ahmed Elkashef More articles by this author Marwan Anas More articles by this author Mona El Wassefy More articles by this author Youssef Mohamed Mosaad More articles by this author Shereen Salah Metwally More articles by this author Yasser Osman More articles by this author Expand All Advertisement Loading ...

MP16-15 CLINICAL VALIDATION OF URINE DNA-BASED PENK METHYLATION TEST FOR DETECTING BLADDER CANCER IN HEMATURIA PATIENTS

You have accessJournal of UrologyBladder Cancer: Non-invasive II (MP16)1 Sep 2021MP16-15 CLINICAL VALIDATION OF URINE DNA-BASED PENK METHYLATION TEST FOR DETECTING BLADDER CANCER IN HEMATURIA PATIENTS Jae Sung Lim, Bo-Ram Bang, Justin J. Lee, Ki Hak Song, TaeJeong Oh, Yang-Yei Seo, Min A Woo, Safedin Beqaj, and Sungwhan An Jae Sung LimJae Sung Lim More articles by this author , Bo-Ram BangBo-Ram Bang More articles by this author , Justin J. LeeJustin J. Lee More articles by this author , Ki Hak SongKi Hak Song More articles by this author , TaeJeong OhTaeJeong Oh More articles by this author , Yang-Yei SeoYang-Yei Seo More articles by this author , Min A WooMin A Woo More articles by this author , Safedin BeqajSafedin Beqaj More articles by this author , and Sungwhan AnSungwhan An More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002001.15AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Hematuria patients are evaluated by cystoscopy to confirm the presence of bladder cancer (BCa). However, a large majority of cystoscopies are deemed unnecessary because only 5-20% of hematuria patients are diagnosed with BCa. Urine cytology has suboptimal sensitivity to triage hematuria patients for cystoscopy. As such, the development of a highly sensitive urine-based test for the early detection of BCa in hematuria patients is imperative. Our previous study identified aberrant methylation of the PENK gene (mePENK) as a specific biomarker for BCa and showed that a real-time PCR-based methylation assay for mePENK in urine sediments is a promising solution to early detection of BCa. This study was aimed to demonstrate the clinical validity of urine DNA-based mePENK assay as a useful adjunct to cystoscopy. METHODS: Two independent training and validation studies were conducted. Urine samples were collected from hematuria patients before cystoscopy or surgical treatment. Control urine samples were collected from hematuria patients without BCa. For the PENK methylation assay, two steps of PCR reactions were required: Liner Target Enrichment (LTE) and methylation specific real time PCR (qMSP) coupled with bisulfite conversion. RESULTS: The training set of the clinical study showed that sensitivity of the PENK methylation assay by LTE/qMSP was 91.0% with a specificity of 96.0% in detecting Ta high-grade and all stages of BCa from hematuria patients (Fig. 1). The prospectively designed validation study showed that the urine-based mePENK test demonstrated a sensitivity of 93.0% with a specificity of 92.0% in detecting all of Ta high-grade, Tis, and all stages of BCa from hematuria patients (Fig. 2, interim data). CONCLUSIONS: This study suggests that the urine DNA-based PENK methylation test possesses high potential to be a routine adjunct to cystoscopy in primary diagnostic settings. Use of the PENK methylation test could prevent unnecessary cystoscopy. Source of Funding: This study was sponsored by Genomictree, Inc © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e302-e303 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jae Sung Lim More articles by this author Bo-Ram Bang More articles by this author Justin J. Lee More articles by this author Ki Hak Song More articles by this author TaeJeong Oh More articles by this author Yang-Yei Seo More articles by this author Min A Woo More articles by this author Safedin Beqaj More articles by this author Sungwhan An More articles by this author Expand All Advertisement Loading ...

Performance of Narrow Band Imaging (NBI) and Photodynamic Diagnosis (PDD) Fluorescence Imaging Compared to White Light Cystoscopy (WLC) in Detecting Non-Muscle Invasive Bladder Cancer: A Systematic Review and Lesion-Level Diagnostic Meta-Analysis.

Simple SummaryBladder cancer is one of the most common malignancies in the United States with a majority of patients diagnosed with non-muscle invasive bladder cancer (NMIBC). Despite early detection and regular surveillance of most cases, recurrence and progression rates remain high. The aim of our systematic review and meta-analysis was to compare the sensitivity, specificity, and oncologic outcomes of photodynamic diagnosis (PDD) fluorescence, narrow band imaging (NBI), and conventional white light cystoscopy (WLC) in detecting NMIBC. Through the collection of prospective and randomized controlled trials, we demonstrated that tumor resection with either PDD and NBI exhibited greater diagnostic sensitivity compared to WLC alone. Our findings underscore the value of integrating these enhanced technologies as a part of the standard care for patients with suspected or confirmed NMIBC.Despite early detection and regular surveillance of non-muscle invasive bladder cancer (NMIBC), recurrence and progression rates remain exceedingly high for this highly prevalent malignancy. Limited visualization of malignant lesions with standard cystoscopy and associated false-negative biopsy rates have been the driving force for investigating alternative and adjunctive technologies for improved cystoscopy. The aim of our systematic review and meta-analysis was to compare the sensitivity, specificity, and oncologic outcomes of photodynamic diagnosis (PDD) fluorescence, narrow band imaging (NBI), and conventional white light cystoscopy (WLC) in detecting NMIBC. Out of 1,087 studies reviewed, 17 prospective non-randomized and randomized controlled trials met inclusion criteria for the study. We demonstrated that tumor resection with either PDD and NBI exhibited lower recurrence rates and greater diagnostic sensitivity compared to WLC alone. NBI demonstrated superior disease sensitivity and specificity as compared to WLC and an overall greater hierarchical summary receiver operative characteristic. Our findings are consistent with emerging guidelines and underscore the value of integrating these enhanced technologies as a part of the standard care for patients with suspected or confirmed NMIBC.

Photodynamic diagnostics of nonmuscle invasive bladder cancer

The review is devoted to the application of photodynamic diagnosis of non-muscle invasive bladder cancer. The recent data on the mechanism of action of photosensitizers, the method of performing fluorescence cystoscopy are presented, and the results of clinical studies of the application of photodynamic diagnostics in practical medicine are presented. It has been shown that photodynamic diagnostics significantly increases the efficiency of detecting bladder cancer in comparison with standard cystoscopy. The application of this method is especially valuable in cases of carcinoma in situ and multifocal growth of urothelial tumors. Improvement in diagnostics makes it possible to increase the radicality of surgical treatment and to increase the duration of the relapse-free period.

Apolipoprotein A1 as a novel urinary biomarker for diagnosis of bladder cancer: A systematic review and meta-analysis.

Introduction:The emergence of urinary biomarkers for bladder cancer diagnosis could provide a reliable and less invasive diagnostic method. It could be also used as an adjuvant to the current gold standards of cytology and cystoscopy to improve diagnostic accuracy and decrease the percentage of false positives.Methods:We searched PubMed, SCOPUS, and Web of Science up to March 18, 2020. We selected four studies that assessed the diagnostic accuracy of urinary apolipoprotein A1 (ApoA-1) in detecting bladder cancer and met the inclusion and exclusion criteria. Two authors independently extracted the data and performed quality assessment of the studies.Results:Four studies with 771 participants were selected; 417 were bladder cancer patients and 354 were controls. Bladder cancer was either transitional cell carcinoma or squamous cell carcinoma, the stages varied between Ta to T3, and the grades varied between G1 and G3. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 90.7%, 90%, 9.478, 0.1, and 99.424, respectively. Summary receiver operating characteristic curve showed an area under the curve of 0.9544 and Q* index of 0.8965.Conclusions:ApoA-1 showed high sensitivity and specificity, so it could be a useful biomarker in diagnosis of bladder cancer.

Diagnostic and prognostic role of BTA, NMP22, survivin and cytology in urothelial carcinoma.

BackgroundCytology is a recommended noninvasive urine test for the detection and surveillance of bladder cancer and upper-tract urothelial carcinoma. It is however characterized by poor sensitivity in low-grade tumors. This study aims to determine the diagnostic and prognostic role of BTA, BTA-stat, NMP22, and Survivin.MethodsUrine samples were collected from a total of 105 patients (bladder cancer (n=61), upper-tract urothelial carcinoma (n=44), and controls (n=52). The samples were directly assessed using cytology, BTA-stat (Qualitative test), BTA (chemiluminescence test), NMP22 (Qualitative test), and Survivin (enzyme-linked immunosorbent assay). Cancer progression and recurrence were assessed after a median follow-up of 32 months (4–47 months). Univariate and multivariate analyses were performed using Kaplan-Meier survival analysis and Cox proportional hazards regression.ResultsThe triple combination of Survivin + BTA + Cytology was the most promising model for discriminating bladder cancer or upper-tract urothelial carcinoma from controls (UTUC group: the area under the curve value 0.97, sensitivity 86%, specificity 96%; BC group: the area under the curve value 0.86 sensitivity 67%, specificity 96%). Univariate survival analysis, showed Cytology (P=0.02; HR=5.35) and Survivin (HR=3.24; P=0.03) to have a significant association with the progression-free survival, while Survivin (HR=4.15; P=0.04) was statistically associated with cancer-specific survival in the bladder cancer group. The multivariable analysis did not show any of these markers as independent prognostic factors.ConclusionsThese biomarkers showed a higher sensitivity than cytology, but a poorer specificity. All biomarkers exhibited good diagnostic performance in both bladder cancer and upper-tract urothelial carcinoma. Combining Survivin + BTA + Cytology was superior to the use of a single marker or combining other biomarkers.

Transferrin receptor cluster of differentiation 71: A potential novel target for bladder cancer

Cluster of differentiation 71 (CD71) is important to the proliferation of many tumors and could be a potential target for tumor diagnosis. This study aimed to investigate the level of CD71 expression in bladder cancer (BC) tissues and urine samples for initial detection of BC. Eighty-seven bladder tumor tissues and 219 urine samples were collected from patients diagnosed with BC in the Urology Department of the Second Affiliated Hospital of Kunming Medical University. Quantitative real-time reverse transcription PCR (qRT-PCR), immunohistochemistry (IHC), and enzyme-linked immunosorbent assay were used to detect the gene and protein expression levels of CD71 in BC tissues and urine samples. Chi-square test was then carried out for analyses. Compared with non-BC samples, the expression levels of CD71 in BC tissues and urine increased significantly ( P&lt; 0.050). In conclusion, CD71 was highly expressed in BC tissues and urine. Thus, the concentrations of urine CD71 could be a new target for clinical detection of BC.

IMPLICATIONS AND POTENTIAL ROLE OF HUMAN TELOMERASE REVERSE TRANSCRIPTASE (HTERT) IN BLADDER CARCINOGENESIS

Bladder cancer is a heterogeneous disease and ranks as 10th most common cancer worldwide. Urothelial carcinoma (UC) is the most common histologic type of BC and majority constitute of papillary tumors that are well-differentiated (low-grade). Several genetic changes may occur in bladder cancer, but hTERT promoter mutations and its expression has been detected in most cases of transitional cell carcinoma. Numerous researches have led to the findings which suggest that the hTERT promoter mutations in conjunction with the common polymorphism and hTERT expression have potential of being used as clinical biomarkers in bladder cancer. Further studies need to explore the potential use of hTERT gene in bladder cancer detection, diagnosis and prognosis. This review focuses on the role of hTERT in bladder tumors in the backdrop of various studies published.

Early Photodynamic Diagnosis Cystoscopy After Bacillus Calmette-Guérin (BCG) Induction for High-Risk Nonmuscle Invasive Bladder Cancer Significantly Increased the Detection of BCG Refractory Tumors.

Objectives: To compare the detection rate of Bacillus Calmette-Guérin (BCG) refractory tumors between white light cystoscopy (WL-C) and Photodynamic Diagnosis cystoscopy (PDD-C). Materials and Methods: We performed a monocentric retrospective study that included all consecutive patients with high-risk nonmuscle-invasive bladder cancer (NMIBC) diagnosed from January 2017 to January 2021. All patients had an initial transurethral resection of bladder tumor (TURBT) with photodynamic diagnosis ± restaging TURBT if needed, followed by full-dose BCG induction. Within 8 weeks following BCG induction, all patients had both WL-C and PDD-C under general anesthesia ± TURBT in case of suspicious lesion. The primary end point was the detection of bladder cancer (BC) at post-BCG cystoscopy. Results: A total of 136 consecutive patients met inclusion criteria. Initial BC characteristics were: 35.6% of T1 tumor, 92.6% high grade, and 48.6% associated CIS. BC was diagnosed in 33/136 cases (24%) at early PDD-C after BCG induction: 77% Ta, 23% T1, 56% associated CIS, 68% high grade, and 6% muscle-invasive bladder cancer. Sensibility and Specificity of WL-C and PDD-C: 41% vs 91% (p < 0.001) and 86% vs 75% (p = 0.001). PDD-C detected 16 additional tumors: 81.3% Ta, 18.7% T1, 75% associated CIS, and 75% high grade. Conclusions: Systematic use of PDD after BCG induction increased the detection of BCG-refractory tumors and led to significant modification in the treatment of high-risk NMIBC. Future studies are needed to evaluate long-term oncologic benefit of early PDD reevaluation and its cost-effectiveness.