[Therapy for male patients with sexual dysfunction]. / Therapie männlicher Sexualstörungen.

Phosphodiasterase type 5 inhibitors (sildenafil, vardenafil, tadalafil) are the first line symptomatic therapy for patients with erectile dysfunction. The patient should receive a meticolous information on the use of these drugs and their possible side effects. These drugs are safe and can be used even in patients with stable cardiovascular disease. Patients not responding to oral drugs may be offered intraurethral or intracavernous alprostadil. Vacuum constriction devices are a second line option more acceptable to older patients. Penile prosthesis are very seldom used in Switzerland and vascular surgery is a vanishing option. Testosterone substitution is seldom needed in this setting. Treatment of premature ejaculation subdivides into behavioural therapy ("stop-start" or "squeeze" technique) and drug therapy as well. Topical therapy with lidocaine/prilocaine-containing medications to be applied before sexual intercourse and a oral daily off label use therapy with selective serotonin re-uptake inhibitors (paroxetine, fluoxetine, sertraline) can be offered. Dapoxetine, a potent selective serotonin reuptake inhibitor with short half life time, is the first officially approved medication for the treatment of premature ejaculation and should be available soon in Switzerland.

The prognostic value of cytology and fluorescence in situ hybridization in the follow-up of nonmuscle-invasive bladder cancer after intravesical Bacillus Calmette-Guérin therapy.

Molecular markers reliably predicting failure or success of Bacillus Calmette-Guérin (BCG) in the treatment of nonmuscle-invasive urothelial bladder cancer (NMIBC) are lacking. The aim of our study was to evaluate the value of cytology and chromosomal aberrations detected by fluorescence in situ hybridization (FISH) in predicting failure to BCG therapy. Sixty-eight patients with NMIBC were prospectively recruited. Bladder washings collected before and after BCG instillation were analyzed by conventional cytology and by multitarget FISH assay (UroVysion, Abbott/Vysis, Des Plaines, IL) for aberrations of chromosomes 3, 7, 17 and 9p21. Persistent and recurrent bladder cancers were defined as positive events during follow-up. Twenty-six of 68 (38%) NMIBC failed to BCG. Both positive post-BCG cytology and positive post-BCG FISH were significantly associated with failure of BCG (hazard ratio (HR)= 5.1 and HR= 5.6, respectively; p < 0.001 each) when compared to those with negative results. In the subgroup of nondefinitive cytology (all except those with unequivocally positive cytology), FISH was superior to cytology as a marker of relapse (HR= 6.2 and 1.4, respectively). Cytology and FISH in post-BCG bladder washings are highly interrelated and a positive result predicts failure to BCG therapy in patients with NMIBC equally well. FISH is most useful in the diagnostically less certain cytology categories but does not provide additional information in clearly malignant cytology.

Prevention of Calcium Nephrolithiasis: The Influence of Diuresis on Calcium Oxalate Crystallization in Urine.

A high fluid intake is still the most evidence-based measure for the prevention of idiopathic stone disease. The recommendation of current guidelines on urolithiasis to increase diuresis to 2-2.5 L/day is mainly based on a single clinical study. The present paper shows the influence of diuresis on calcium oxalate (CaOx) crystallization and especially aggregation (AGN) which can explain the initial development of Ca stones on papillary calcifications as well as stone growth in the renal pelvic system. Diuresis determines the urinary transit time (UT) through the kidney and together with the afflux of Ca and Ox the state of urinary saturation with respect to CaOx being the most frequent stone mineral. High supersaturation inducing crystallization during UT and a high urinary ion concentration interfering with the inhibition of crystal AGN by urinary macromolecules seem to be critical parameters for stone formation. Using data from the literature the influence of diuresis on these parameters is evaluated for short-term recurrent stone formers (RSF), idiopathic stone patients, and healthy controls, the latter two collectives with and without excessive oxalate ingestion. This investigation suggests that a diuresis of 2 L/day may protect from stone formation even after dietary Ox excesses and in RSF. However, in RSF with a continuously high Ca and Ox afflux into urine a permanent high diuresis is required which is difficult to sustain over 24 hours.

Role of urinary cathepsin B and L in the detection of bladder urothelial cell carcinoma.

PURPOSE: We tested the hypothesis that urinary cathepsin B and L are associated with bladder cancer recurrence and invasiveness in patients with a history of nonmuscle invasive urothelial carcinoma of the bladder. MATERIALS AND METHODS: Cathepsin B and L, and NMP22 were determined in the urine specimens of 188 consecutive subjects with a history of treated urothelial carcinoma of the bladder, 31 with noncancerous urological conditions and 10 healthy subjects. Cathepsin B and L were analyzed as continuous and categorical variables based on their quartile distribution. RESULTS: Urinary cathepsin L was higher in the 122 patients with cystoscopic evidence of bladder tumor compared with levels in 107 with normal cystoscopy (median 5.9, IQR 4.4 vs 3.0, IQR 3.2, p <0.001). Higher levels of cathepsin L were associated with positive cytology assay results, higher NMP22 and T1 or greater pathological stage (each p <0.001). Area under the ROC curves of NMP22 and cathepsin L for bladder cancer detection were 0.704 (95% CI 0.637-0.772) and 0.793 (95% CI 0.736-0.850), respectively. On multivariate analysis cathepsin L, NMP22 and cytology were associated with invasive pathological stage (OR 1.29, 2.42 and 2.76, respectively, p

Urinary cytology and nuclear matrix protein 22 in the detection of bladder cancer recurrence other than transitional cell carcinoma.

OBJECTIVE: To assess the value of nuclear matrix protein-22 (NMP22), compared with urinary cytology, in predicting the recurrence of bladder cancer that is not transitional cell carcinoma (non-TCC). PATIENTS AND METHODS: We tested the sensitivity, specificity and the predictive accuracy of NMP22 in the context of non-TCC bladder cancer recurrence, and compared it to the performance of urinary cytology. The study group comprised 2687 patients with history of non-muscle-invasive bladder cancer from 10 centres across four continents. RESULTS: The mean patient age was 64.8 years and 75.4% were men; of all patients, 513 (19.1%) had positive urinary cytology, 906 (33.7%) had a positive NMP22 test (>or=10 units/mL) and 80 (3.0%) had non-TCC recurrence. Most of these, i.e. 60 (75%), were stage >or=T2. The sensitivity and specificity of urinary cytology were, respectively, 20.0% and 94.8%, vs 77.5% and 81.8% for NMP22 of >or=10 units/mL. The predictive accuracy of urinary cytology was 57.5%, vs 87.1% for NMP22 >or= 10 units/mL. A combined model that included dichotomized NMP22 and urinary cytology was 85.3% accurate. CONCLUSION: The ability of a NMP22 level of >or=10 units/mL to predict non-TCC recurrence was better than that of urinary cytology, suggesting that NMP22 might have a role in the surveillance of patients at risk of non-TCC recurrence.

Photoselective KTP laser vaporization of the prostate: first experiences with 65 procedures.

PURPOSE: To study the feasibility and efficacy of 80 W potassium-titanyl-phosphate (KTP) laser vaporization (GreenLight PV; Laserscope) of the prostate in patients suffering from voiding dysfunction secondary to benign prostatic hyperplasia (BPH) or known locally advanced prostate cancer (CaP). PATIENTS AND METHODS: Sixty-five patients with symptomatic BPH (N=57) or obstructive voiding secondary to CaP (N=8) with a mean age of 70 +/- 10 years (range 46-93 years) underwent photoselective 80 W KTP laser vaporization of the prostate. All consecutive patients, including 34 with a history of chronic urinary retention or indwelling catheter, were enrolled. Prostate specific antigen (PSA) values, prostate volume as measured by transrectal ultrasonography, urinary peak flow measurement (Qmax), postvoiding residual volume (PVR) measured transvesically, and International Prostate Symptom Score (IPSS) were assessed preoperatively, on the day of discharge, and 1 month and 3 months postoperatively. The mean preoperative prostate volume was 49 +/- 32 cc (range 15-250 cc). RESULTS: In all 65 patients, KTP laser vaporization was performed successfully, with a mean operating time of 57 +/- 25 minutes (range 10-160 minutes). No major complication occurred intraoperatively or postoperatively, and no transfusions were necessary. All patients were catheter free after 1 month. At 1 month and 3 months, the urinary peak flow had increased from 7.7 +/- 2.8 mL/sec preoperatively to 20.9 +/- 11.6 mL/sec (+171%) and 18.2 +/- 6.3 mL/sec (+136%), respectively. The IPSS decreased from 18.5 +/- 6.7 to 9.2 +/- 7.7 (-50%) and 7.2 +/- 5.9 (-61%) at 1 and 3 months, respectively. CONCLUSIONS: A 80 W KTP laser vaporization of the prostate technique instantly removes obstructive tissue. A transurethral resection-like visible cavity is the endpoint. Immediate symptom relief is achieved in a truly minimally invasive way with a very low postoperative complication rate within 3 months' follow-up.

Soluble Fas--a promising novel urinary marker for the detection of recurrent superficial bladder cancer.

BACKGROUND: The objective of this study was to test the hypothesis that elevated urinary levels of soluble Fas (sFas) would aid in the surveillance of patients with a past history of nonmuscle-invasive transitional cell carcinoma (TCC) of the urinary bladder. METHODS: sFas levels were determined in cell lysates and supernatants from 2 human bladder cancer cell lines (T24 and TCC-SUP) and in voided urine from 188 consecutive patients who were at risk for TCC recurrence, 31 patients who had noncancerous urologic conditions, and 10 healthy individuals. The authors also obtained barbotage cytology and voided nuclear matrix protein 22 (NMP22) levels. sFas was analyzed continuously and categorically on the basis of its quintile distribution. RESULTS: sFas was present in cell lysates and conditioned media from both cell lines. sFas levels were found to be higher in the TCC group (n = 122 patients) compared with the control group (P < .001). Higher levels of sFas were associated with positive cytology assay results (P < .001), higher NMP22 levels (P < .001), NMP22 levels > 10 U/mL (P < .001), and tumor stage > or = T1 (P < .001). The areas under the receiver operating characteristics (ROC) curves of sFas and NMP22 for bladder cancer detection were 0.757 (95% confidence interval, 0.694-0.819) and 0.704 (95% confidence interval, 0.637-0.772), respectively. In the > 75% sensitivity region of the ROC curves, sFas was consistently more specific than NMP22. In multivariate analyses, sFas, NMP22, and cytology all were found to be associated with the presence of bladder cancer (P values < or = .009), but only sFas and cytology were associated with tumor stage > or = T1 (P values < or = .026). CONCLUSIONS: sFas was produced and released by bladder TCC cells. Urine sFas was an independent predictor of bladder cancer recurrence and invasiveness in patients who had a past history of nonmuscle invasive bladder TCC, and it outperformed NMP22.

Variability in the performance of nuclear matrix protein 22 for the detection of bladder cancer.

PURPOSE: We assessed variability in the diagnostic performance of NMP22 for detecting recurrence and progression in patients with Ta, T1, and/or CIS transitional cell carcinoma of the bladder in a large international cohort. MATERIALS AND METHODS: NMP22 voided urine levels were measured in 2,871 patients who underwent office cystoscopy for monitoring previous stage Ta, T1 and/or CIS transitional cell carcinoma at 12 participating institutions. RESULTS: Patient characteristics varied considerably among institutions. Overall 1,045 patients (36.4%) had recurrent transitional cell carcinoma (range across institutions 13.6% to 54.3%). Median NMP22 was 5.5 U/ml (range across institutions 2.5 to 18.8). Of the patients 33.5% had grade III tumors (range across institutions 20.6% to 54.0%) and 22.4% had muscle invasive tumors (range across institutions 3.2% to 38.2%). Area under the ROC curve for bladder TCC detection was 0.735 (95% CI 0.715 to 0.755, range across institutions 0.676 to 0.889). The manufacturer recommended cutoff of 10 U/ml detected 57% of cases with a 19% false-positive rate. AUC for grade III and stage T2 or greater disease was 0.806 (95% CI 0.780 to 831) and 0.864 (95% CI 0.839 to 0.890), respectively. For each NMP22 cutoff NMP22 had higher sensitivity for detecting grade III and stage T2 or greater bladder transitional cell carcinoma than for detecting any cancer. No optimal cutoffs for detecting any or aggressive bladder transitional cell carcinoma could be derived based on NMP22 values. CONCLUSIONS: There is a substantial degree of heterogeneity in the diagnostic performance of NMP22 applied to populations from different institutions. There is no clearly defined NMP22 cutoff but there is a continuum of risk for recurrence and progression.

Institutional variability in the accuracy of urinary cytology for predicting recurrence of transitional cell carcinoma of the bladder.

OBJECTIVE: To assess the contemporary inter-institutional accuracy of urinary cytology in predicting the recurrence of transitional cell carcinoma (TCC) of the bladder, in a large multi-institutional cohort from four continents, as cystoscopy and urinary cytology represent the 'gold standards' for surveillance of TCC recurrences, but the ability of cytology to predict recurrence varies. PATIENTS AND METHODS: Ten institutions contributed 2542 patients with a history of superficial TCC, of whom 898 had TCC recurrence. Age- and gender-adjusted logistic regression models were used to evaluate the association between urine cytology and TCC recurrence. The predictive accuracy derived from the logistic regression model was tested using the area under the receiver operating characteristic curve. The resulting predictive accuracy estimates were internally validated with 200 bootstrap re-samples. RESULTS: The mean (range across institutions) age of the patients was 65 (48-69) years and 75 (67-87)% were men. Cytology was positive in 19 (10-38)% of patients; recurrence was identified in 35 (27-54)% of patients. The sensitivity was 38-65% across institutions. Urinary cytology varied significantly in its ability to predict recurrence of bladder cancer. Institution-specific predictive accuracy adjusted for gender and age was 0.627-0.893. Stratifying by grade and stage only partly attenuated the discrepancies between centres. CONCLUSIONS: The variability of urinary cytology results was very appreciable among the 10 centres and ranged from poor (63%) to excellent (89%).

Retroperitoneoscopic management of caliceal diverticular calculi.

INTRODUCTION: The management of caliceal diverticular calculi has changed from an open surgical approach to endoscopic management. TECHNICAL CONSIDERATIONS: Different minimally invasive treatment modalities, such as extracorporeal shock wave lithotripsy, ureteroscopy, percutaneous nephrolithotomy, laparoscopy, and retroperitoneoscopy, can be offered to the patient. We report on a retroperitoneoscopic operative technique using endosonography for location and performing nephrotomy with complete excision of the caliceal diverticulum and ligation of the diverticular neck with an Endo-loop. CONCLUSIONS: The advantages of this minimally invasive technique include total excision of the diverticulum with no risk of recurrence and easy and complete closure of the diverticular neck.

Pitfall in renal cyst surgery: serous cystadenoma of pancreas mimicking renal cyst.

Pancreatic lesions, particularly cysts, can simulate various diseases. We report a case of a 43-year-old woman with a large, symptomatic, retroperitoneal cyst misdiagnosed as a "renal cyst." During the retroperitoneoscopic marsupialization, the correct diagnosis of a pancreatic cyst was made, leading to an open pancreas tail resection. Histologic evaluation revealed serous cystadenoma. Especially in large retroperitoneal cysts on the left side, the correct diagnosis of a pancreatic cyst can be difficult.

Urinary levels of soluble e-cadherin in the detection of transitional cell carcinoma of the urinary bladder.

OBJECTIVE: To test the hypothesis that elevated urinary levels of soluble E-cadherin (sE-cadherin) would aid in the detection of transitional cell carcinoma (TCC) of the urinary bladder. METHODS: We performed sE-cadherin staining of one murine (MBT2) and four human (RT4, 5637, T24, and TCCSUP) bladder cancer cell lines. sE-cadherin levels were also determined in voided urine of 188 consecutive subjects at risk for TCC recurrence, 31 patients with other uro-pathologic conditions, and 10 healthy subjects using a commercially-available ELISA kit. sE-cadherin was analyzed continuously and categorically on the basis of its median distribution. RESULTS: Moderately and poorly differentiated bladder cancer cell lines had decreased cellular E-cadherin expression, whereas RT4, a well differentiated cell line, had preserved expression. All cell lines had measurable sE-cadherin levels in their conditioned media. The area under the ROC curve of sE-cadherin for the detection of TCC was 0.719 (95%CI, 0.637-0.801; p<0.001). Higher levels of sE-cadherin were associated with positive cytology results (p=0.012) and muscle invasive tumor stage (p=0.009). Urinary sE-cadherin was more sensitive, but less specific than urinary cytology for the detection of bladder TCC. In a multivariable logistic regression analysis, higher sE-cadherin and positive cytology were both associated with an increased risk of bladder TCC (p=0.048 and p<0.001, respectively). Combination of cytology and sE-cadherin allowed categorization of patients into three significantly different risk groups for bladder cancer. Adjustment of sE-cadherin for urinary creatinine levels did not affect any of the outcomes. CONCLUSIONS: Urinary level of sE-cadherin may add information to cytology in the detection of bladder TCC.

Urinary levels of tumor-associated trypsin inhibitor (TATI) in the detection of transitional cell carcinoma of the urinary bladder.

OBJECTIVE: To assess whether urinary levels of tumor-associated trypsin inhibitor (TATI) would aid in the detection of bladder transitional cell carcinoma (TCC); and to compare diagnostic performance of urinary TATI with that of nuclear matrix protein 22 (NMP22) and barbotage cytology. METHODS: We determined TATI and NMP22 levels in voided urine from 181 subjects: 153 with previous bladder cancer, 20 with urologic pathology other than bladder cancer, and eight healthy volunteers. TATI was analyzed continuously and categorically on the basis of its quartile distribution. We also measured urinary creatinine and barbotage cytology in 173 and 154 patients, respectively. RESULTS: Urinary TATI levels were significantly higher in TCC patients with evidence of tumor on cystoscopic evaluation (n = 96) than in control subjects (n = 85; p < 0.001). Higher levels of TATI were associated with positive cytology assay results (p = 0.018), higher NMP22 levels (p < 0.001), and invasive tumor stage (p = 0.026). The area under the receiver operating characteristics (ROC) curve (AUC) of TATI for the detection of TCC was 0.712 (95%CI: 0.637-0.786). The overall AUCs for TATI and NMP22 were not statistically different from each other (p = 0.174). In the >75% sensitivity region of the ROC curves, TATI was consistently more specific than NMP22. TATI, NMP22, and cytology were independently associated with bladder cancer (p = 0.049, p = 0.040, and p < 0.001, respectively). Adjustment of TATI for urinary creatinine levels did not affect any of the outcomes. CONCLUSIONS: Urinary level of TATI may add independent information to urinary cytology and NMP22 in the detection of bladder TCC. TATI seems to outperform NMP22 for bladder TCC detection.

Retroperitoneoscopy-assisted cryoablation of renal tumors using multiple 1.5 mm ultrathin cryoprobes: a preliminary report.

OBJECTIVES: Laparoscopic cryoablation has recently been proposed as a minimally invasive nephron-sparing treatment for selected patients. We report on our experience with a retroperitoneoscopic technique using multiple ultrathin cryoprobes. METHODS: Seven patients underwent retroperitoneoscopic renal cryoablation for solid renal masses. Mean tumor size on the CT scan was 2.6 (1.5-3.5) cm. A double freeze-thaw cycle of renal cryoablation was performed under real-time ultrasound monitoring using a total of six 1.5-mm cryoprobes simultaneously. RESULTS: Cryoablation was technically successful in all patients without any need for conversion. Mean duration of surgery was 161 (130-195) minutes and mean blood loss was 107 (50-250) ml. Perioperative biopsy of the tumor confirmed renal cell carcinoma in four patients and angiomyolipoma in two patients; it was inconclusive in one case. Mean follow-up for 13.6 (4-22) months showed no evidence of residual tumor or recurrence. CONCLUSIONS: Retroperitoneoscopy-assisted cryosurgical ablation using multiple ultrathin 1.5-mm cryoprobes is a minimally invasive treatment that is suitable to treat small renal tumors.

Nomograms including nuclear matrix protein 22 for prediction of disease recurrence and progression in patients with Ta, T1 or CIS transitional cell carcinoma of the bladder.

PURPOSE: We developed and validated nomograms that accurately predict disease recurrence and progression in patients with Ta, T1, or CIS transitional cell carcinoma (TCC) of the bladder using a large international cohort. METHODS: Univariate and multivariate logistic regression models targeted histologically confirmed disease recurrence, and focused on 2,542 patients with bladder TCC from 10 participating centers. Variables consisted of pre-cystoscopy voided urine Nuclear Matrix Protein 22 (NMP22) assay, urine cytology, age and gender. Resulting nomograms were internally validated with bootstrapping. Nomogram performance was explored graphically with Loess smoothing plots. RESULTS: Overall 957 patients had recurrent TCC. Tumor grade and stage was available for 898 patients, including 24% grade I, 43% grade II, and 33% grade III; 45% stage Ta, 32% T1 and/or CIS, and 23% T2 or greater. Bootstrap corrected predictive accuracy for any TCC recurrence was 0.842; grade III Ta/T1 or CIS was 0.869; and T2 or higher stage TCC of any grade was 0.858. Virtually perfect performance characteristics were observed for the nomograms predicting any TCC recurrence or grade III Ta/T1 or CIS. The nomogram predicting T2 or higher stage TCC overestimated the observed probability for predicted values greater than 45%. CONCLUSIONS: We developed and internally validated nomograms that incorporate urinary NMP22, cytology, age and gender to predict with high accuracy the probability of disease recurrence and progression in patients with Ta, T1, and/or CIS bladder TCC. These nomograms could provide a means for individualizing followup in patients with Ta, T1, CIS bladder TCC.

Primary testicular amyloidosis mimicking tumor in a cryptorchid testis.

We present a case of primary testicular amyloidosis mimicking tumor in a cryptorchid testis. Examination revealed the absence of a palpable testis in the left hemiscrotum. The laboratory evaluation showed azoospermia and a low testosterone level. The radiologic investigation demonstrated a heterogeneous left inguinal mass suspicious for tumor in a cryptorchid testis. After radical orchiectomy, the histologic evaluation revealed primary amyloidosis of the testis. The pathogenesis and clinical presentation of testicular amyloidosis are reviewed.

The patient's self-evaluation better predicts the degree of erectile dysfunction than the response to intracavernous alprostadil testing.

OBJECTIVES: A modern baseline assessment of erectile dysfunction (ED) should be individualized, reliable, noninvasive and cost-efficient. Appraisal based on the patient's self-evaluation may be the method of choice. METHODS: Using a self-report method, 63 consecutive ED patients were prospectively investigated. Semiquantitative parameters on 7 criteria were assessed, and an intracavernous injection test with alprostadil was performed. Performances of self-reporting and intracavernous testing in predicting penetrative ability were compared. RESULTS: Twenty-three (37%) men had erection insufficient for penetration even with manual assistance, 26 (41%) men needed manual assistance and 14 (22%) could penetrate without manual assistance but erection was not sufficient for satisfaction. In addition to impaired penetrative ability, 6 criteria (intercourse frequency, patient's and partner's satisfaction, penile rigidity, duration of erection and need for extra stimulation) deteriorated over time (p < 0.006). Patient self-evaluation criteria such as intercourse per week, patient satisfaction, penile rigidity, duration of erection and time between consultation and last satisfactory intercourse showed discriminating differences in accordance with the 3 subgroups of penetrative ability (p < 0.02). Intracavernous testing could not reproduce the degree of erectile deficit as experienced during intercourse (p = 0.21). In a logistic regression model, criteria best characterizing penetrative ability were penile rigidity, time between consultation and last unsuccessful intercourse, and degree of satisfaction (p < 0.0001). CONCLUSIONS: The patient's self-evaluation by semiquantitative parameters on criteria characterizing sexual erections better predicts the penetrative ability than the response to an intracavernous injection. These criteria quantify both the objective degree of ED and the patient's apprehension. Consequently, patients may undergo immediate treatment without further testing.

Urinary levels of urokinase-type plasminogen activator and its receptor in the detection of bladder carcinoma.

BACKGROUND: The authors found previously that plasma levels of urokinase-type plasminogen activator (uPA) and its receptor (uPAR) were elevated in patients with bladder carcinoma and were associated with features of biologically aggressive disease. In the current study, they tested the hypothesis that elevated urinary levels of uPA and uPAR would predict the presence of bladder malignancy by comparing the performance of uPA and uPAR with the performance of bladder wash-out cytology in the noninvasive diagnosis of bladder tumors. METHODS: An enzyme-linked immunosorbent assay was used to compare levels of uPA and uPAR in urine that was collected before cystoscopy from 122 patients with bladder carcinoma and from 107 participants in a control group. Seventy-two patients had clinical Tis or Ta transitional cell carcinoma, and 50 patients had invasive disease (>or= T1); 85 patients had clinical Grade 1-2 tumors, and 37 patients had Grade 3 tumors. For cytology, only high grade was considered positive. RESULTS: Urinary levels of uPA and uPAR were higher in patients with bladder carcinoma compared with levels in the control group (P < 0.001 and P = 0.016, respectively). However, only uPA levels were elevated in patients with abnormal urinary cytology (P = 0.006). After controlling for cytology (odds ratio [OR], 10.182; 95% confidence interval [95%CI], 4.451-23.291; P < 0.001), uPAR (P for trend = 0.168), and age (P = 0.091), those in the highest quartile for uPA had an increased risk of bladder carcinoma compared with those in the lowest quartile (OR, 3.022; 95%CI, 1.295-7.054; P for trend = 0.031). CONCLUSIONS: The current findings suggest that urinary levels of uPA, but not uPAR, are related to the risk of bladder carcinoma. The study confirmed the central role of urinary cytology in the noninvasive diagnosis of bladder carcinoma.

The addition of urinary urokinase-type plasminogen activator to urinary nuclear matrix protein 22 and cytology improves the detection of bladder cancer.

PURPOSE: We have previously reported that urinary urokinase-type plasminogen activator (uPA) and its receptor (uPAR) are elevated in patients with bladder cancer. In the current study we tested the hypothesis that urinary uPA and uPAR would add to the predictive ability of urinary nuclear matrix protein 22 (NMP22) and cytology for the diagnosis of bladder cancer. MATERIALS AND METHODS: Urinary uPA, uPAR and NMP22 were measured in voided specimens obtained before cystoscopy in 229 consecutive subjects at risk for transitional cell carcinoma (TCC), of whom 122 (53%) were found to have bladder TCC. Bladder washout samples for cytology were also collected in 191 subjects. Associations with TCC were tested by logistic regression. Nonparametric ROC curves were generated and AUCs were compared. RESULTS: Urinary uPA, uPAR and NMP22 were higher in patients with TCC than in controls (p <0.001, 0.016 and <0.001, respectively), while uPA (test for trend p = 0.018) was associated with the risk of TCC after adjusting for NMP22 (p = 0.028), urinary cytology (p <0.001), age (p = 0.107) and uPAR (test for trend p = 0.756). The overall AUC for determining TCC was not different between uPA and NMP22 (0.746 and 0.714, p = 0.092). However, in the high sensitivity region of the ROC curve the AUC of uPA was larger than that of NMP22. CONCLUSIONS: Adding uPA to NMP22 and cytology improves their ability to predict bladder TCC by a statistically and prognostically substantial margin. An approach using multiple biomarkers may improve the diagnostic accuracy of voided urinary diagnostic tests.

Preoperative plasma soluble E-cadherin predicts metastases to lymph nodes and prognosis in patients undergoing radical cystectomy.

PURPOSE: We have previously reported that high urinary levels of soluble E-cadherin (sE-cadherin) are associated with an increased risk of bladder cancer. We determined whether plasma levels of sE-cadherin are associated with bladder cancer stage and prognosis. MATERIALS AND METHODS: The study group consisted of 50 patients who underwent radical cystectomy for muscle invasive cancer or intravesical therapy refractory Tis, Ta, or T1 bladder cancer; and 40 men without cancer. Preoperative plasma levels of sE-cadherin were measured using a commercially available enzyme-linked immunosorbent assay kit. RESULTS: Plasma sE-cadherin was higher in patients with bladder cancer than in healthy subjects (p <0.0001) and it was elevated in patients with metastases to regional and distant lymph nodes (p = 0.019 and 0.024, respectively). When adjusted for the effects of clinical stage and grade, preoperative sE-cadherin was independently associated with metastases to regional lymph nodes (p = 0.028) and disease progression (p = 0.006) but not with bladder cancer mortality. In postoperative models preoperative sE-cadherin and lymph node metastases were associated with disease progression (p = 0.017 and 0.042, respectively) after adjusting for the effects of pathological stage, grade and lymphovascular invasion but only lymph node metastases were associated with cancer specific mortality (p = 0.007). CONCLUSIONS: Higher plasma sE-cadherin is associated with bladder cancer. Higher preoperative plasma sE-cadherin has the potential to identify patients with metastases to regional and distant lymph nodes who are at increased risk for failure of local therapy with curative intent. These patients may benefit from more extensive lymph node dissection and/or combined modality treatment regimens.