Armin Pycha

CAN URINE BOUND DIAGNOSTIC TESTS REPLACE CYSTOSCOPY IN THE MANAGEMENT OF BLADDER CANCER

PURPOSEnWe compare the diagnostic value of NMP22 and BTA stat testing, and QUANTICYT computer assisted dual parameter image analysis to cytology and cystoscopy in patients who had symptoms suggestive of transitional cell cancer or were being followed after treatment for that disease.nnnMATERIALS AND METHODSnWe prospectively evaluated voided urine and/or barbotage specimens from 291 patients a mean of 65.2 years old. All voided urine samples were evaluated by quick staining and standard cytology, the BTA stat 1-step qualitative assay (which detects a bladder tumor associated antigen) and the NMP22 test (which detects a nuclear mitotic apparatus protein). In addition, barbotage specimens were evaluated by QUANTICYT computer assisted dual parameter image analysis. All patients underwent subsequent cystoscopy and biopsy evaluation of any suspicious lesion. Sensitivity, specificity, and the predictive value of positive and negative results were determined in correlation with endoscopic and histological findings.nnnRESULTSnIn 91 patients with histologically proved transitional cell carcinoma overall sensitivity was 48, 57, 58, 59 and 59% for the NMP22 test, the BTA stat test, rapid staining cytology of barbotage samples, rapid staining cytology of voided urine specimens and image analysis, respectively. For histological grades 1 to 3 underlying transitional cell carcinoma sensitivity was 17, 61 and 90% for urinary cytology, 48, 58 and 63% for the BTA stat test, and 52, 45 and 50% for the NMP22 test, respectively. Specificity was 100% for cytology, 93% for image analysis, 70% for the NMP22 test and 68% for the BTA stat test.nnnCONCLUSIONSnImmunological markers are superior to cytological evaluation and image analysis for detecting low grade transitional cell carcinoma but they have low specificity and sensitivity in grade 3 transitional cell carcinoma. Urine bound diagnostic tools cannot replace cystoscopy.

IMMUNOCYT1: A NEW TOOL FOR DETECTING TRANSITIONAL CELL CANCER OF THE URINARY TRACT

PURPOSEnThe limitations of cytology and the invasiveness of cystoscopy for detecting bladder cancer generate increasing interest in noninvasive, urine bound diagnostic tools. We assessed the diagnostic value of the newly developed immunocytochemical test, Immunocyt, which detects cellular markers specific for transitional cell cancer in the voided urine of patients with bladder cancer.nnnMATERIALS AND METHODSnParticipating in our prospective study were 264 consecutive patients with a mean age of 65.9 years, including 114 in whom symptoms were suggestive of bladder cancer and 150 who were being followed after complete transurethral resection of superficial transitional cell carcinoma. Voided urine specimens were evaluated by standard cytology and the Immunocyt test, which traces the monoclonal antibodies M344, LDQ10 and 19A211 against transitional cell carcinoma in exfoliated urothelial cells. In all cases cystoscopy was subsequently performed and any suspicious lesion was evaluated by biopsy.nnnRESULTSnHistologically proved transitional cell carcinoma was found in 79 patients. Immunocyt with cytology had 89.9% sensitivity overall (84, 88 and 96.5% in grades 1 to 3 disease, respectively). A total of 34 (43%), 3 (3.8%) and 34 (43%) cases were positive on Immunocyt only, cytology only and both evaluations, respectively. In 8 cases (10.1%) both tests were negative. Overall Immunocyt only was 86.1% sensitive (84, 84 and 89.6% in grades 1 to 3 disease, respectively) and 79.4% specific. Overall cytology only was 46.8% sensitive (4, 52 and 79.3% in grades 1 to 3 disease, respectively) and 98.2% specific.nnnCONCLUSIONSnImmunocyt is a noninvasive, highly sensitive test for detecting transitional cell carcinoma of all grades and stages. When combined with conventional urinary cytology, it may replace cystoscopy in select patients, especially in followup protocols of low grade transitional cell carcinoma.

The aging lower urinary tract: a comparative urodynamic study of men and women

OBJECTIVESnThe fact that aging women report similar voiding symptoms as age-matched men prompted us to compare age-related changes of urodynamic parameters in both sexes.nnnMETHODSnFour hundred thirty-six patients (253 men and 183 women) 40 years of age or older underwent the following investigations: free uroflowmetry, measurement of postvoid residual volume, and full urodynamic testing, including a pressure-flow study (pQs). Additional investigations were a urethral pressure profile in women and quantification of prostate volume by transrectal ultrasonography in men. All men were referred for lower urinary tract symptoms suspicious of bladder outflow obstruction and women predominantly for urinary incontinence. Patients with previous surgery of the lower urinary tract (prostate, bladder, urethra) and those taking medication with a major effect on voiding function (alpha-receptor blockers, 5 alpha-reductase inhibitors, anticholinergic agents) were excluded.nnnRESULTSnThe mean +/- standard deviation (SD) age in the female (f) population (n = 183) was 59 +/- 16 years (range 40 to 93), in the male population (m) (n = 253) 67 +/- 9 years (range 40 to 90). In both sexes, we observed a statistically significant increase of postvoid residual volume (f: P = 0.0001; m: P = 0.02) and a decrease of peak flow rate (f: P = 0.019; m: P = 0.014), average flow rate (f: P = 0.007; m: P = 0.04), voided volume (f: P = 0.007; m: P = 0.002), and bladder capacity determined by urodynamics (f: P = 0.003; m: P = 0.0004) with progressing age. In both sexes, there were no age-related changes (P >0.05), demonstrable for maximum detrusor pressure and detrusor pressure at peak flow rate. In women, there was a significant decrease of functional urethral length (P = 0.012) and maximum urethral closing pressure (P = 0.0001) with higher age; in men, the prostate volume increased significantly with age (P = 0.0001). With respect to detrusor instability, we observed an increase in men from 23.4% (40 to 60 years) to 46.7% (more than 80 years) (P = 0.004), whereas in women no significant age-related changes were present (P >0.05).nnnCONCLUSIONSnThese data show that age-associated urodynamic changes in both sexes are comparable for a number of parameters. They provide an explanation for the fact that aging women report comparable voiding symptoms as men and suggest a primary, non-sex-specific aging process of the urinary bladder.

USE OF PERIPHERAL NEUROMODULATION OF THE S3 REGION FOR TREATMENT OF DETRUSOR OVERACTIVITY: A URODYNAMIC-BASED STUDY

OBJECTIVESnTo determine the efficacy of peripheral neuromodulation of the S3 region in patients with urgency-frequency syndrome due to an overactive bladder.nnnMETHODSnFifteen patients (11 women and 4 men) with urgency-frequency syndrome, as documented by a voiding chart, were diagnosed with overactive bladder. Pelvic pain was assessed by a visual analogue scale (VAS). Full urodynamic workup was performed before and after 12 peripheral stimulations with a 9-V monopolar generator, the so-called Stoller Afferent Nerve Stimulator (SANS). Follow-up was for a mean (SD) of 10.9 (4 to 15) months.nnnRESULTSnReduction in pain was achieved in all patients, with a decrease in VAS from a mean (SD) of 7.6 (5 to 10) to 3.1 (1 to 7) (P = 0.00049). Seven patients (46.7%) had a complete response and were considered cured, 3 (20.0%) showed significant improvement, and 5 (33.3%) were classified as nonresponders. Urodynamic evidence of bladder instability, evident in all patients before treatment, was eliminated in 76.9% of patients. In all patients, mean (SD) total bladder capacity increased significantly from 197 (35 to 349) to 252 (78 to 384) mL (P = 0.00795), mean (SD) volume at first bladder sensation from 95 (16 to 174) to 133 (32 to 214) mL (P = 0.00166), and mean (SD) bladder volume at normal desire to void from 133 (27 to 217) to 188 (47 to 296) mL (P = 0.00232). In the responding group, the mean (SD) total numbers of voids was reduced from 16.1 (9 to 24) times during the day and 4.4 (2 to 6) times during the night to 8.3 (6 to 10) and 1.4 (1 to 2) times (P = 0.002539), respectively. No complications from treatment were observed.nnnCONCLUSIONSnPeripheral neuromodulation of the S3 region can successfully treat patients with urgency-frequency syndrome due to an overactive bladder.

Does extended lymphadenectomy increase the morbidity of radical cystectomy

To report the events during and after radical cystectomy and urinary diversion for bladder cancer, in terms of major and minor complications, comparing a minimal with an extended lymphadenectomy, as more lymph nodes obtained during radical cystectomy may improve staging and thus the outcome.

Dehydroepiandrosterone in the treatment of erectile dysfunction: a prospective, double-blind, randomized, placebo-controlled study

OBJECTIVESnIn 1994, the Massachusetts Male Aging Study presented an inverse correlation of the serum levels of dehydroepiandrosterone (DHEA) and the incidence of erectile dysfunction (ED). We evaluated the efficacy of DHEA replacement in the treatment of ED in a prospective, double-blind, randomized, placebo-controlled study.nnnMETHODSnThe inclusion criteria included ED, normal physical and neurologic examinations, serum levels of testosterone, dihydrotestosterone, prolactin, and prostate-specific antigen (PSA) within the normal range, and a serum DHEA sulfate level below 1.5 micromol/L. Also all patients had a full erection after a pharmacologic erection test with 10O microg prostaglandin E1; pharmacocavernosography showed no visualization in corporeal venous structures. Forty patients from our impotence clinic were recruited and randomly divided into two groups of 20 patients each. Group 1 was treated with an oral dose of 50 mg DHEA and group 2 with a placebo one time a day for 6 months. The International Index of Erectile Function (IIEF), a 15-item questionnaire, was used to rate the success of this therapy.nnnRESULTSnTherapy response was defined as the ability to achieve or maintain an erection sufficient for satisfactory sexual performance according to the National Institutes of Health Consensus Development Panel on Impotence. DHEA treatment was associated with higher mean scores for all five domains of the IIEF. There was no impact of DHEA treatment on the mean serum levels of PSA, prolactin, testosterone, the mean prostate volume, and the mean postvoid residual urine volume.nnnCONCLUSIONSnOur results suggest that oral DHEA treatment may be of benefit in the treatment of ED. Although our patient data base is too small to do relevant statistical analysis, we believe that our data show a biologically obvious trend that justifies further extended studies.

The international prostate symptom score in both sexes: A urodynamics‐based comparison

The aim of our study was to determine the urodynamic basis for the observation that aging women report comparable benign prostatic hyperplasia (BPH) symptom scores as age‐matched men. Sixty‐seven women (mean age, 60.4 ± 1.5 years; mean ± standard error of the mean) and 70 age‐matched men (mean age, 63.7 ± 0.9 years; P > 0.05) entered this prospective study. Men were referred for the diagnostic workup of lower urinary tract symptoms (LUTS) due to BPH and women predominantly for urinary incontinence. All patients completed the International Prostate Symptom score (IPSS) with quality‐of‐life assessment and underwent a detailed clinical and urodynamic evaluation including a multichannel pressure‐flow study. Results of the IPSS, quality‐of‐life assessment, and irritative and obstructive component of the IPSS were correlated with urodynamic findings and the respective data were compared in both sexes. The mean IPSS was 15.7 for men and 13.0 for women (P = 0.02), quality‐of‐life score was higher in women (4.2 vs. 3.4; P = 0.0008). The irritative score was significantly higher in women (8.7 vs. 6.8; P = 0.003). Incidence of detrusor instability (DI), however, was higher in men (women, 38.1%; men, 48.6%; P = 0.015) and bladder capacity was higher in women (425 vs. 333 ml; P = 0.0001). There was no correlation between incidence and degree of DI with the irritative score in both sexes. The obstructive score was significantly higher in men (8.8 vs. 4.4; P = 0.0001). Ninety‐one percent (64/70) of men had urodynamically documented bladder outlet obstruction (BOO), whereas this was the case in only 9% (6/67) of women. In parallel to the irritative score, we could not identify a correlation between the degree of urodynamically proven BOO and the obstructive score in both sexes. This urodynamics‐based comparison fails to give an explanation for the observation that aging women report similar BPH scores as men. These data suggest that other mechanisms, such as changes in diurnal urine production, structural alterations of the aging detrusor, endocrine disturbances affecting lower urinary tract function, and subtle urodynamic changes are responsible. Neurourol. Urodynam. 18:173–182, 1999.

Modified Laparoscopic Nephroureterectomy for Treatment of Upper Urinary Tract Transitional Cell Cancer Is Not Associated with an Increased Risk of Tumour Recurrence

INTRODUCTIONnLaparoscopic nephroureterectomy reduces the morbidity of surgical management of urinary tract transitional cell carcinoma (TCC), but a potentially increased risk for local tumour spreading was reported. We evaluated results obtained from patients undergoing a modified laparoscopic approach and open procedures in this respect.nnnPATIENTS AND METHODSnBetween January 2000 and March 2002 we performed 19 modified laparoscopic nephroureterectomies (LNU) with open intact specimen retrieval in conjunction with open distal ureter and bladder cuff removal and 15 open standard nephroureterectomies (ONU). Staging lymphadenectomy was performed in 14/19 (73.7%) patients with LNU and in 6/15 (40.0%) with ONU. In all patients operating time, blood loss, complications, pain score (VAS) and data in respect to tumour recurrence were analysed. Mean follow-up was 22.1+/-9.2 (range 14-34) months for LNU and 23.1+/-8.8 (14-36) for ONU respectively.nnnRESULTSnIn LNU and ONU pathological features were 12 pT1 vs. 10 pT1, 2 pT2 vs. 2 pT2 and 5 pT3 vs. 3 pT3, respectively. All patients had TCC and were R0 at final histology. Four patients with LNU had lymph node involvement, one in ONU. LNU had decreased operating times (p=0.057), blood loss (p=0.018), complications (p=0.001) and VAS scores (p=0.001). One tumour recurrence occurred in LNU, associated with a pT3b pN2 G3 TCC at final histology. One patient with ONU had local tumour recurrence at the site of the bladder cuff. No port-site metastasis occurred during follow-up with LNU.nnnCONCLUSIONnImproved peri-operative results and same cancer control as compared to open surgery by this modified LNU was not associated with an increased risk for tumour recurrence, since strict non-touch preparation, avoiding of urine spillage and intact specimen retrieval prevents tumour seeding. However, results from long term studies are still warranted to clarify this issue.

INTERRELATIONSHIPS OF BLADDER COMPLIANCE WITH AGE, DETRUSOR INSTABILITY, AND OBSTRUCTION IN ELDERLY MEN WITH LOWER URINARY TRACT SYMPTOMS

Data on the interrelationships of bladder compliance (BC), detrusor instability (DI), and bladder outflow obstruction (BOO) in elderly men with lower urinary tract symptoms (LUTS) are scarce and were therefore assessed in this study. Principle inclusion criteria for this study were men aged ⩾50 years suffering from LUTS as defined by an International Prostate Symptoms Score (IPSS) of ⩾7 and a peak flow rate (Qmax) of ⩽15 ml/sec. Patients with previous surgery of the bladder, prostate, or urethra as well as a pathological neurourological status were excluded from this study. The following parameters were studied in all patients: IPSS, prostate volume calculated by transrectal ultrasonography, free uroflow study, post‐void residual volume determined by transurethral catheterization, and a multichannel pressure flow study (pQS). A group of 170 men were included in the analysis. The mean BC in the overall group was 32 ± 2 ml/cm H2O (mean ± standard error of the mean [SEM]; range, 4–100 ml/cm H2O). In 36.5% of patients, BC was significantly reduced (⩽20 ml/cm H2O), and in a further 37.1%, it ranged from 20 to 40 ml/cm H2O. BC decreased statistically significantly (p < 0.05) in patients with advanced age, lower Qmax, higher voiding pressures, and larger prostates. In men with DI (n = 61), mean BC was significantly lower (22 ± 3 ml/cm H2O) compared to those without (37 ± 3 ml/cm H2O; p = 0.001; n = 109). Patients with severe BOO as defined by a linear passive urethral resistance relationship of ⩾3 (n = 109), had a significantly lower BC (23 ± 2 ml/cm H2O) compared to those without or minimal obstruction only (39 ± 3 ml/cm H2O; p = 0.0002; n = 61). Stepwise logistic regression analysis revealed that DI, a low bladder capacity, and a high maximum detrusor pressure were independent predictors of markedly reduced BC (<20 ml/cm H2O). BC is decreased in elderly men with high voiding pressures, BOO, and DI. The mechanism leading to the reduction of BC under these circumstances is largely unknown and could result from cytostructural alterations of the detrusor and changes in detrusor innervation. Neurourol. Urodynam. 18:3–15, 1999.

Detection of upper urinary tract transitional cell carcinoma with ImmunoCyt: a preliminary report.

OBJECTIVESnTo assess the clinical performance of ImmunoCyt in the detection of upper urinary tract transitional cell carcinoma (UT-TCC). This newly developed immunocytochemical test detects three cellular markers specific for TCC.nnnMETHODSnThirty-seven patients with symptoms and/or findings on imaging suggestive of UT tumors were prospectively evaluated. All patients underwent a standard cytologic evaluation and ImmunoCyt testing of voided urine, as well as imaging studies. Urine samples were also obtained from the UT of 32 patients by ureteral catheterization and tested by cytologic analysis and ImmunoCyt.nnnRESULTSnSixteen patients had UT-TCC as documented by the final histologic evaluation. The sensitivity of testing the voided urine from 37 patients was 50% for cytologic analysis, 75% for ImmunoCyt, and 87% for both methods combined. The cytologic evaluation detected no G1, 1 (17%) of 6 G2, and 7 (100%) of 7 G3 tumors. ImmunoCyt detected 1 (33%) of 3 G1, 6 (100%) of 6 G2, and 5 (71%) of 7 G3 tumors. The sensitivity in the 32 urine samples obtained from the UT was 82% for cytologic analysis, 91% for ImmunoCyt, and 100% for both methods combined. Cytologic analysis detected all G2 and G3 (100% sensitivity) and no G1 tumors. ImmunoCyt detected 2 (100% sensitivity) of 2 G1, 4 (100%) of 4 G2, and 4 (80%) of 5 G3 tumors. The test specificity, calculated in 21 patients free of TCC, was 100% for cytologic analysis in voided and ureteral urine specimens and 95% and 100% for ImmunoCyt in voided and ureteral urine samples, respectively.nnnCONCLUSIONSnThe results of this preliminary study show that ImmunoCyt complements cytologic analysis in detecting UT-TCC, mainly because of its high sensitivity to low-grade TCC. The combination of cytologic testing and ImmunoCyt gives 100% sensitivity in detecting UT-TCC in UT urine samples.