Diagnosing upper tract urothelial carcinoma: A review of the role of diagnostic ureteroscopy and novel developments over last two decades

Objective: The role of ureteroscopy in the diagnosis of upper tract urothelial carcinoma is yet to be fully determined. We aimed to provide an up to date evaluation of its role and the emerging technologies in the field.Methods: A literature search of the last two decades (from 24th May, 2001 to 24th May, 2021) was carried out identifying 147 papers for potential inclusion within this narrative review.Results: Diagnostic ureteroscopy is undeniably useful in its ability to visualise and biopsy indeterminate lesions, and to risk stratify malignant lesions that may be suitable for kidney sparing surgery. However, an increased risk of intravesical recurrence following nephroureterectomy when a prior diagnostic ureteroscopy has been performed, inadequate sampling at biopsy, complications from the procedure, and difficult ureteric access are all potential drawbacks. Furthermore, whilst generally an accurate diagnostic procedure, it risks missing carcinoma in-situ lesions. Despite this, evidence shows that routine use of ureteroscopy changes the management of patients in a large proportion of cases, preventing unnecessary surgery or facilitating kidney sparing surgery. The overall rate of complications is low, and improved biopsy techniques and the use of tissue biomarkers for improved staging and grading are encouraging. The risks of delays to definitive management and post-ureteroscopy intravesical recurrence do not seem to affect survival, and trials are in progress to determine whether intravesical therapy can mitigate the latter. Further promising techniques are being investigated to improve shortcomings, particularly in relation to improved diagnosis of carcinoma in situ and preoperative staging.Conclusion: Ureteroscopy has a role in the diagnosis of upper tract malignancy, though whether it should be used routinely is yet to be determined.

Expression of Multidrug-associated Protein, P-glycoprotein, P53 and Bcl-2 Proteins in Bladder Cancer and Clinical Implication

The expression of multidrug resistant proteins in bladder cancer and clinical implication was studied. Expression of multidrug associated protein (MRP), P glycoprotein (P gp), P53 and Bcl 2 proteins were detected by using immunohistochemical method in 40 specimens of bladder transitional cell carcinoma. The results showed that the positive rate of MRP, P gp, P53 and Bcl 2 was 52.5 %, 57.5 %, 47.5 % and 62.5 % respectively. The positive rate of MRP, P gp, P53 and Bcl 2 in the grade Ⅰ, Ⅱ and Ⅲ of tumors was 46.3 %, 38.5 %, 38.5 %, 23.1 %; 52.9 %, 39.8 %, 47.1 %, 76.4 %; 60.0 %, 80.0 %, 60.0 %, 90.0 % respectively. The positive rate of MRP, P gp, P53 and Bcl 2 in 24 primary tumor specimens was 37.5 %, 41.7 %, 33.3 %, 45.8 % and that in 16 cases in recurrent specimens receiving chemotherapy 75.0 %, 81.3 %, 68.8 %, 87.5 % respectively. It was suggested the positive rate of MRP, P gp, P53 and Bcl 2 was increased with the advance of tumor grade. The positive rate of four proteins in all recurrent cases was significantly increased ( P <0.05). The expression of MRP, P gp, P53 and Bcl 2 proteins might be the important factors for chemotherapy failure.

Superselective embolisation of bilateral superior vesical arteries for management of intractable hematuria in context of metastatic bladder cancer

Hematuria due to locally advanced or metastatic bladder cancer is a common condition and is often a management problem.Percutaneous embolisation is a mini-invasive option to handle this situation.We report a case of a patient with a metastatic bladder cancer and who presented with an abundant hematuria and severe anemia.After failure of endoscopic resections and“flush”of radiotherapy haemostatic and refusal of cystectomy by the patient,he was treated by superselective embolisation of bilateral superior bladder arteries with excellent immediate results.The technique is safe and effective in the short term.The longterm effectiveness requires further investigation.

Successful treatment of solitary bladder plasmacytoma:A case report

BACKGROUND Plasmacytoma is a rare neoplastic disorder that arises from B-lymphocytes.Solitary bladder plasmacytoma,a type of solitary extramedullary plasmacytoma,is even rarer.Treatments for solitary extramedullary plasmacytoma include surgery,chemotherapy,and radiation.However,there are no clinical trials or guidelines specifying which treatment might represent the gold standard.CASE SUMMARY We herein report a case of a 51-year-old woman with solitary bladder plasmacytoma(SBP).There remains no consensus regarding the optimal treatment for SBP.However,we successfully treated her with transurethral resection of bladder tumor followed by postoperative radiotherapy(50 Gy/25 F).The patient remained free of tumor recurrence at a 7-mo follow-up.CONCLUSION Radiation is the potential main treatment for SBP.However,surgery is also necessary.

Expression of Glutathione S-transferase π in Human Bladder Cancer

The purpose of this study was to investigate the expression of glutathione stransferase (GST) and its clinical significance in human bladder cancer. GST immunoreactivity was assessed respectively in 49 bladder cancers and 30 normal bladder mucosas by avidin biotin peroxidase complex (ABC) techniques. The corelationship of GST expression and clinical and biological feature of bladder cancer was studied. Positive GST was observed in 44 cases of bladder cancer mucosa (89.8%) and in 18 cases of normal bladder mucosa (60%). In 42 cases of stage G\-\{12\} and 7 cases of stage G\-3 cancer patients the positive GST expression rate was 80.9%(34/42) and 100%(7/7) respectively. In 14 cases of recurrent bladder cancer the total positive expression rate was 92.9% (13/14), meanwhile in 19 cases of stage T23 the positive nuclear staining was seen in 10. Higher rate of GST expression was found in bladder cancer than in normal bladder mucosa, which was implied that the resistance to chemotheraputic drugs in bladde r cancer might be related to the expression of GST. GST expression was correlated with tumor grade. Furthermore, increased intranuclear GST expression might be associated with bladder cancer progression.

Comparisons of voided urine cytology, nuclear matrix protein-22 and bladder tumor associated antigen tests for bladder cancer of geriatric male patients in Taiwan, China

Aim： To compare the results of bladder tumor associated antigen （BTA TRAK）, nuclear matrix protein 22 （NMP 22） and voided urine cytology （VUC） in detecting bladder cancer. Methods： A total of 135 elderly male and 50 healthy volunteers enrolled in this study were classified into three groups： （i） 93 patients with bladder cancer; （ii） 42 patients with urinary benign conditions; and （iii） 50 healthy volunteers. BTA TRAK and NMP 22 kits were used to detect bladder cancer. Voided urine cytology was used to compare the sensitivity and specificity of the screening tests. Results： The sensitivity and specificity of cytology, BTA TRAK and NMP 22 were 24% and 97%, 51% and 73%, 78% and 73%, respectively. The level of NMP 22 increased with tumor grading. The BTA TRAK kit has the lowest sensitivity among the screening tests. The NMP 22 with the best sensitivity can be an adjunct to cytology for evaluating bladder cancer. Conclusion： The NMP 22 test has a better correlation with the grading of the bladder cancer than BTA TRAK. As cytology units are typically not available in hospitals or in outpatient clinics, NMP 22 might be a promising tool for screening bladder cancer.

Costimulatory Molecule B7-H1 on the Immune Escape of Bladder Cancer and Its Clinical Significance

B7-H1, a recently described member of the B7 family of costimulatory molecules, is thought to be involved in tumor immune escape by inducing T-cell apoptosis. In order to investigate the relationship between B7-H1 and immune escape of bladder cancer, B7-H1 expression in 50 cases of bladder cancer was detected by using immunohistochemical method. Survival curves were con- structed using the Kaplan-Meier method and independent prognostic factors were evaluated using the Cox regression model. Our results showed that the positive rate of B7-H1 immunostaining in normal bladder tissue and bladder cancer was 0 and 72% respectively. The expression of B7-H1 was strongly associated with the pathological grade, clinical stage and recurrence （P〈0.05）. The survival rate was significantly lower in patients with B7-H1 positive group than in those with B7-H1 negative group and multi-variable analysis revealed that B7-H1 could be regarded as an independent factor in evaluating the prognosis of bladder cancer. It is concluded that the expression of B7-H1 is strongly associated with neoplastic progression and prognosis of bladder cancer. The manipulation of B7-H1 may become a beneficial target for immunotherapy in human bladder cancer.

Correlative Expression of Glutathion S-Transferase-π and Multidrug Resistance Associated Protein in Bladder Transitional Cell Carcinoma

In order to elucidate the mechanisms of multidrug resistance (MDR) in bladder cancer, the expression of glutathione S-transferase-π (GST-π) and multidrug resistance associated protein (MRP) in tissue samples resected from 44 patients and 6 normal bladder mucosa as control was de- tected by using immunohistochemical method, and the results were analyzed by computer-assisted im- age analyzing system (IAS) to achieve semi-quantitative data. In addition, correlation between the expression of both factors was studied. The results showed that the positive expression rate of GST- π and MRP in bladder cancer was 72. 7 % (32/44) and 68. 2 % (30/44) respectively, significantly higher than those in normal bladder mucosa, being 16. 7% and 33. 3% respectively. The rate of GST-πpositive staining was increased correspondingly with tumor grade and stage elevated, being higher in recurrent tumors treated by chemotherapy, but not significantly (P>0. 05). There was no significant differences between the expression of MRP and tumors' behaviors and clinical characters. However, the results demonstrated that the correlation between the expression of both resistant fac- tors was very evident (r=0. 695, P<0. 0025). It was suggested that the activation of GST-π and MRP might occur during malignant transformation of normal mucosa, but tumors' differentiation and progression could not be the unique factors that influenced both overexpression. Chemotherapy might be another important reason. The correlation of both indicated that there was a common mech- anism regulating their expression probably, which made them play a pivotal role in chemotherapy drug resistance of bladder cancers.

Detection of Smac expression in bladder cancer and its clinical significance

Objective： To detect the expression of second mitochondria-derived activator of caspase （Smac） in bladder cancer and discuss its clinical significance. Methods： Smac was detected in 15 specimens of normal bladder epithelium and 72 specimens of bladder cancer by reverse transcription-polymerase chain reaction （RT-PCR） and immunohistochemistry at the level of gene and protein, respectively. Results： The differences of both Smac protein and mRNA expressions between normal mucous membrane of bladder and grade i bladder cancer had no statistical significance （ P 〉 0.05 ）. The expressions of Smac protein and its mRNA in bladder cancer decreased gradually with the advance of bladder cancer （ P 〈 0.01 and P 〈 0.05, respectively）. In invasive bladder cancer, the expressions of Smac protein and its mRNA were higher than those in superficial bladder cancer （ P 〈 0.01）. Conclusions： Normal bladder epithelium has high expression of Smac while bladder cancer has low expression of Smac. The expression of Smac is closely related to the grade and stage of bladder cancer. Detection of Smac expression helps to judge the grade and stage of bladder cancer and Smac gene might become a valid target for gene therapy of bladder cancer.

ALTERATION OF G1-CYCLINS (D1 AND E) IN TRANSITIONAL CELL CARCINOMA OF HUMAN URINARY BLADDER WITH INFECTION OF HPV-18

Objective: This study was designed to investigate differential pattern of G1-cyclins (D1 and E) in transitional cell carcinoma (TCC) of human urinary bladder with or without human papillomavirus-18 (HPV-18) infection. Methods: Immunohistochemistry method was used in the detection of the expression of G1-cyclins in 57 cases of TCC (7 normal bladders as control), and HPV-18 DNA was found in 29 cases by polymerases chain reaction (PCR). Results: Cyclin D1 expression was found in 41 of 57 (71.93%) TCCs and it was reverse associated with HPV (x 2=8.21, P<0.05). And cyclin D1 expression was found in 16 of 29 (55.17%) in HPV-18 infection group and 25 of 28 (89.29%) in non-HPV infection group. Cyclin E expression was detected in 36 of 57 (63.16%) and the association between the cyclin E expression and HPV infection was not found (x2=0.52, P>0.05). Cyclin E expression was found in 17 of 29 (56.82%) in HPV-18 infection group and 19 of 28 (67.86%) in non-HPV infection group. There was obvious difference in the cyclin D1 and cyclin E expression between the TCC and normal tissue (x 2=7.46, P<0.05; x 2=7.45, P<0.05, respectively). Conclusion: These data demonstrated that HPV infection altered the control of G1 cell cycle. And changes of G1 cell cycle regulatory proteins, either by interaction of cellular protein with viral oncoproteins or by changes in the cellular proteins themselves, may be critical for carcinogenesis of TCC of urinary bladder.

CLINICAL SIGNIFICANCE OF TELOMERASE ACTIVITY AND PERIPHERAL VENOUS BLOOD CK-20 EXPRESSION IN BLADDER TRANSITIONAL CELL CARCINOMA

Objective: The relationship between peripheral blood CK-20 mRNA expression and tissue telomerase activity in bladder transitional cell carcinoma (TCCB) was investigated to evaluate the feasibility of their combined detection in early-stage diagnosis and prognosis estimation of TCCB. Methods: the blood CK-20 was detected by semi-nested RT-PCR and telomerase activity in tumor tissue was examined with silver-stained TRAP reaction. Results: the blood CK-20 expression and tissue telomerase activity in TCCB were 41% and 93% respectively. No statistical significance was detected among pathological grading and clinical staging (P>0.05). Positive correlation was shown between CK-20 expression and telomerase activity with the pathologic grade or clinical stage. Conclusion: combined use of blood CK-20 and tissue telomerase activity detections might be of great importance for clinical diagnosis, treatment and prognosis evaluation.

SMALL CELL CARCINOMA OF THE URINARY BLADDER: THREE CASES REPORT

To study the clinical features of patients with primary small cell carcinoma (SCC) of the bladder and to improve the diagnosis and treatment. Methods: Clinical data of 3 cases with primary SCC of the bladder were discussed and the pathology, diagnosis, treatment and prognosis were reviewed. Results: 3 cases of primary SCC of the bladder were presented. Of them the diagnosis was confirmed by pathological examination after operation (2 cases) and biopsy (1 case). One case with stage T4M1 died after three months?chemotherapy. One case with stage T2M0 underwent partial cystectomy and was treated with chemotherapy and one year later died of miocardial infarction. Another case with stage T4M0 underwent radical cystectomy and postoperative irradiation therapy. The patient was alive and had no recurrence of symptoms during two years follow-up. Conclusion: Primary SCC of the urinary bladder is highly malignant. Radical cystectomy combined with radiotherapy appears to be the efficient treatment. Chemotherapy seems to be of no significant effect.

Cell softness reveals tumorigenic potential via ITGB8/AKT/glycolysis signaling in a mice model of orthotopic bladder cancer

Background:Bladder cancer,characterized by a high potential of tumor recurrence,has high lifelong monitoring and treatment costs.To date,tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types.Nonetheless,the existence of soft tumor cells in bladder tumors remains elusive.Thus,our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods:The stiffness of bladder cancer cells was determined by atomic force microscopy(AFM).The modified microfluidic chip was utilized to separate soft cells,and the 3D Matrigel culture system was to maintain the softness of tumor cells.Expression patterns of integrinβ8(ITGB8),protein kinase B(AKT),and mammalian target of rapamycin(mTOR)were determined by Western blotting.Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59(TRIM59).The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models.Results:Using our newly designed microfluidic approach,we identified a small fraction of soft tumor cells in bladder cancer cells.More importantly,the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens,in which the number of soft tumor cells was associated with tumor relapse.Furthermore,we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells.Simultaneously,we detected a remarkable up-regulation in ITGB8,TRIM59,and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions:The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness.Meanwhile,the soft tumor cells become more sensitive to chemotherapy after stiffening,that offers new insights for hampering tumor progression and recurrence.

Oral microbiota in the oral-genitourinary axis:identifying periodontitis as a potential risk of genitourinary cancers

Periodontitis has been proposed as a novel risk factor of genitourinary cancers:although periodontitis and genitourinary cancers are two totally distinct types of disorders,epidemiological and clinical studies,have established associations between them.Dysbiosis of oral microbiota has already been established as a major factor contributing to periodontitis.Recent emerging epidemiological evidence and the detection of oral microbiota in genitourinary organs indicate the presence of an oral-genitourinary axis and oral microbiota may be involved in the pathogenesis of genitourinary cancers.Therefore,oral microbiota provides the bridge between periodontitis and genitourinary cancers.We have carried out this narrative review which summarizes epidemiological studies exploring the association between periodontitis and genitourinary cancers.We have also highlighted the current evidence demonstrating the capacity of oral microbiota to regulate almost all hallmarks of cancer,and proposed the potential mechanisms of oral microbiota in the development of genitourinary cancers.

Robot-assisted laparoscopic radical cystectomy with complete intracorporeal urinary diversion

Robot-assisted radical cystectomy with intracorporeal urinary diversion(RARCICUD)has only recently been explored as a viable surgical option for patients with muscle-invasive bladder cancer seeking satisfactory oncologic control while benefiting from minimally invasive surgical techniques.Inspired by earlier open and laparoscopic work,initial descriptions of RARC-ICUD were published in 2003,and have since been followed by multiple larger case series which have suggested promising outcomes for our patients.However,the rate of adoption has remained relatively slow when compared to other robotassisted procedures such as the radical prostatectomy,likely owing to longer operative times,operative complexity,costs,and uncertainty regarding oncologic efficacy.The operative technique for RARC-ICUD has evolved over the past decade and several high-volume centers have shared tips to improve efficiency and make the operation possible for a growing number of urologists.Though there are still questions regarding economic costs,effectiveness,and generalizability of outcomes reported in published data,a growing dataset has brought us ever closer to the answers.Here,we present our current operative technique for RARC-ICUD and discuss the state of the literature so that the urologist may hold an informed discussion with his or her patients.

Intravesical Instillation in Pure Line LEW Rats and Nude Mice

In order to study bladder intravesical instillation methods in pure line LEW rats and nude mice, female LEW rats and nude mice aged 2 to 4 weeks were sacrificed. Their urethra and bladder were observed under anatomical microscopy. A trochar was prepared according to the outline and an- gle of the urethra. Ink was poured into female rats and nude mice bladder though urethra. Filling and staining of bladder were observed and evaluated under anatomical microscopy. Status and urethral injury of rats and mice were observed. The results showed that urethra anatomic structure of rats and nude mice was different from that of human urethra. When bladder was filled with ink and became blue, liquid was not seen to leak out. The success rate of intubation was high (100%). Living activi- ties of animals weren’t influenced by intravesical instillation. It was concluded that bladder irrigation might be a kind of valid and utilizable method in pure line rat and nude mouse empirical study. The model may be a more effective tool for study of bladder tumor.

Modified Ureterosigmoidostomy

Objective To introduce an operation procedure and evaluate the continence diversion results of the modified ureterosigmoidostomy after radical cystectomy. Methods Fourteen cases of bladder cancer or prostate carcinoma were operated on with modified Sigma pouch from Feb, 1998 to Dec, 1999. A longitudinal incision about 25 cm on the sigmoid wall was done to form a low pressure pouch. The vertex of the new pouch was fixed to sacrum. Both ends of ureters were anastomosed side to side and to form a big nipple and inserted into the top of pouch for 2 to 3 centimeters.Results It took about sixty five minutes to create a new low pressure pouch after radical cystectomy. Early complication of was found in two cases postoperatively, and cured with temporary colonostomy. Hydronephrosis and hypokalemia in one patient were cured by percutaneous anterograde ureter dilatation with balloon and oral replacement of potassium salt. All patients displayed urinary continence. No symptomatic renal infection or hypercholoraemic acidosis occurred. Conclusion Modified ureterosigmoidostomy is a safe procedure of urinary diversion and provides a big volume, low intravesical pressure pouch. The patients are free from the troublesome urine bag, intermittert catheterization, and upper urinary tracts are protected effectively. The quality of life is satisfied.

XIAP as a prognostic marker of early recurrence of nonmuscular invasive bladder cancer

Background Dysregulation of apoptosis has been implicated not only in carcinogenesis and tumor progression but also in tumor recurrence. We investigated whether the expression of X-linked inhibitor of apoptosis （XIAP） might predict early recurrence in patients with non-muscular invasive bladder cancer. Methods The cohort comprised 176 consecutive patients with primary superficial bladder cancer treated with transurethral resection. Immunohistochemical staining using the standard avidin-bioUn-peroxidase technique and RT-PCR were used to detect XIAP protein and mRNA expressions in cancer tissues. The relationship between XIAP expression and clinicopathological characteristics, cancer recurrence were analyzed. Results XIAP expression was observed in 108 cases （61.4%） and no expression in 68. There was no correlation between XIAP expression rate and the tumor pathological grade, but was an apparent trend toward the increased XIAP levels from well （G1） to poor （G3） differentiated cancer. Eighty-two （46.6%） patients experienced tumor recurrence at a mean of 28.6 months of the follow-up; 66 of them expressed XIAP （61.1%） and 16 were XIAP negative （23.5%）. Twelve patients presented with invasive disease at the time of relapse and all of them expressed XIAP. Patients without XIAP expression or with low tumor grades had significantly higher recurrence-free survival than those with XIAP expression （log rank test ,P=-0.0015） or high tumor grades （log rank test P〈0.001）. Multivariate analysis revealed that XIAP expression, tumor grade, and tumor number were independent predictors for the recurrence of non-muscular invasive bladder cancer （P=-0.004, 0.016, and 0.043, respectively）. Conclusions XIAP may be considered as a new independent prognostic marker for early recurrence of non-muscular invasive bladder cancer.

Effect of small interfering RNA targeting survivin gene on biological behaviour of bladder cancer

Background Bladder cancer is the most common type of urinary system tumours. It is frequently associated with genetic mutations that deregulate the cell cycle and render these tumours resistant to apoptosis. Survivin, a newly discovered member inhibitor of apoptosis protein （IAP） family in several human cancers, by inducing cell proliferation and inhibiting apoptosis is frequently activated in bladder cancer. We studied the influence of small interfering RNA （siRNA） targeting survivin on the biological behaviour of bladder cancer cells. Methods A double strand survivin target sequence specific siRNA was designed and synthesized. After transfection of bladder cancer cell line T24 by siRNA/liposome complex with increasing concentrations （50-200 nmol/L）, the transfectant cells were intratumourally injected at different doses （5 μg or 50 μg）. The effects were measured in vitro and in vivo.Results The selected siRNA efficiently down-regulated survivin mRNA expression in a dose and time dependent manner. The maximal effect was achieved at the concentration of 100 nmol/L, at which survivin expression level was down-regulated by 75.91%. The inhibition rate of cell growth was 55.29% （P〈0.01） and the markedly increased apoptotic rate was 45.70% （P〈0.01）. In vivo intratumoural injection of 50 μg siRNA-survivin could notably orevent the growth of bladder cancer （P〈0.01） in xenografted animals.Conclusion The application of siRNA-survivin could markedly inhibit survivin expression in bladder cancer cell line by inducing apoptosis and inhibiting the growth of the tumour. It may become a new gene therapy tool for bladder cancer.

Comparison of seven screening methods in the diagnosis of bladder cancer

Background We compared the validity （evaluated by sensitivity and specificity）, reliability （evaluated by reproducibility） and yield （evaluated by predictive value, examining complexity and cost） of individual and combined tests for bladder tumour antigen stat （BTAstat）, nuclear matrix protein 22 （NMP22）, hyaluronic acid （HA）, survivin, CD44v6, vascular endothelial growth factor （VEGF）, and voided urine cytology （VUC） in detecting bladder cancer. And at the same time we evaluated the clinical value of these seven detecting methods in the diagnosis of bladder cancer. Methods The six markers and VUC were detected in the urine of cancer group （151 patients with bladder cancer） and two control groups （50 patients with benign urological diseases and 50 healthy controls）. The sensitivity, specificity, predictive value, reproducibility, examining complexity and checking cost of each marker and combined markers were calculated. Results There was a significant difference between bladder cancer group and the two control groups. The sensitivity, specificity and positive predictive value were as follows： VUC （36.4%, 100.0%, 100%）, BTAstat （76.8%, 87.0%, 89.9%）, NMP22 （77.5%, 81.0%, 86.0%）, HA （82.8%, 83.0%, 88.0%）, survivin （70.2%, 85.0%, 87.6%）, CD44v6 （50.3%, 79.0%, 78.4%）, and VEGF （68.2%, 93.0%, 93.6%）. The highest sensitivities were 91.4% for NMP22＋BTAstat and HA＋NMP22, whereas the combined marker with the lowest sensitivity （62.3%） was VUC＋CD44v6. The highest specificity was 93.0% for the combined use of VUC＋VEGF and HA＋CD44v6 had the lowest specificity （73.0%）. The most convenient examining method was the detection for BTAstat, the lowest cost was the detection for HA, and the best reproducibility were the detection for BTAstat and VUC. Conclusions All the markers have obvious clinical value in diagnosis of bladder cancer. The use of BTAstat＋HA or NMP22＋BTAstat are better examining methods in terms of validity, reliability, and yield.