Aris Giannopoulos

Comparative evaluation of the diagnostic performance of the BTA stat test, NMP22 and urinary bladder cancer antigen for primary and recurrent bladder tumors

PURPOSE We compared overall sensitivity and specificity of the urinary bladder cancer antigen enzyme-linked immunosorbent assay (UBC, IDL Biotech, Sollentuna, Sweden), BTA stat test (Bion Diagnostic Sciences, Inc., Redmond, Washington) and NMP22 test kit (Matritech, Newton, Massachusetts), and the differential sensitivity regarding the histological pattern of tumors. MATERIALS AND METHODS A total of 213 patients with clinical and/or imaging signs of bladder cancer provided a single voided urine sample for the bladder cancer antigen, BTA stat test and NMP22 before cystoscopy. Of these patients 95 were monitored for superficial bladder cancer, while the remaining 118 had no history of bladder cancer. All detected bladder tumors or suspicious lesions were resected transurethrally. A group of 21 age and sex matched healthy volunteers were also evaluated with the same tests. RESULTS Bladder cancer was confirmed histologically in 118 patients, of whom primary and recurrent tumors were in 68 and 50, respectively. The optimal cutoffs calculated with receiver operating characteristics curves were 8 units per ml. for NMP22 and 12 microg./l. for bladder cancer antigen. Overall sensitivity and specificity were 72.9% and 64.6% for the BTA stat test, 63.5% and 75.0% for NMP22, and 80.5% and 80.2%, respectively, for bladder cancer antigen. Bladder cancer antigen proved significantly more sensitive than NMP22 for detecting bladder cancer (p = 0.001) but not more than the BTA stat test, while the specificity of it was significantly higher than that of the BTA stat test (p = 0.009). Bladder cancer antigen had a sensitivity of 80.7% for stage Ta tumors, which was significantly higher than NMP22 (52.6%, p = 0.001) and the BTA stat test (57.9%, p = 0.01). In grade I tumors the sensitivity of bladder cancer antigen (70%) did not differ significantly than that of the BTA stat test (50%) and NMP22 (50%, p = 0.14). Bladder cancer antigen had the least false-positive results in patients with a history of bladder cancer and negative cystoscopy, and those with urological disease other than bladder cancer. CONCLUSIONS Our data indicate that bladder cancer antigen may be a more potent diagnostic marker for bladder cancer than NMP22 and the BTA stat test based on the higher sensitivity for detecting low stage and low grade tumors, and the higher specificity. The contribution of these tests for detection of bladder cancer should still be considered adjunctive to cystoscopy.

Prevention of recurrent bacterial cystitis by intravesical administration of hyaluronic acid: a pilot study

To assess the effect of bladder instillations of hyaluronic acid (HA) on the rate of recurrence of urinary tract infection (UTI).

Comparative evaluation of the BTAstat test, NMP22, and voided urine cytology in the detection of primary and recurrent bladder tumors

OBJECTIVES This prospective study was undertaken to evaluate the diagnostic efficacy of the BTAstat test and nuclear matrix protein (NMP22) compared with voided urine cytology (VUC) in the detection of primary and recurrent bladder cancer. METHODS A total of 147 patients provided a single voided urine sample for the BTAstat test, NMP22, and cytology prior to cystoscopy. Eighty-five of them had no bladder cancer history, whereas the remaining 62 were monitored for superficial bladder cancer. A group of 21 healthy age-matched volunteers were also enrolled in the study. RESULTS Bladder cancer was confirmed histologically in 99 patients, of which 62 had primary tumors and 37 had recurrent ones. The overall sensitivity and specificity were 71.7% and 56.5% for the BTAstat test, 62.6% and 73. 9% for NMP22, and 38.4% and 94.2% for VUC. The optimal threshold value for NMP22 calculated with receiver operating characteristics curve, was 8 U/mL. BTAstat test was significantly more sensitive than VUC in detecting bladder cancer in all stage and grade subgroups, except GIII. On the contrary, NMP22 was significantly more sensitive than VUC only in stage Ta, grade I and II patients. BTAstat test had higher but not significantly different sensitivity than NMP22. CONCLUSIONS Our data indicate a superiority of both BTAstat test and NMP22 over VUC in the detection of bladder cancer. Comparing BTAstat test with NMP22, the former proved to be more sensitive, whereas the latter was more specific. Ruling out diseases with potential interference can increase the overall specificity of both tests. False-positive results of either test in patients followed up for bladder cancer seem to correspond to future recurrences.

Clinical efficacy of distigmine bromide in the treatment of patients with underactive detrusor

Purpose: The aim of this study was to assess the clinical efficacy of distigmine bromide, an anti-cholinesterase agent, deemed to improve detrusor function thereby restoring normal voiding patterns in patients suffering from detrusor underactivity. Materials and methods: A total of 27 patients (11 men and 16 women) with poor detrusor function were included in the study. The diagnosis was established using pressure-flow studies. All patients received distigmine bromide at a dose of 5 mg three times daily for 4 weeks and re-attended for a follow-up urodynamic investigation. The results of baseline pressure-flow studies were compared to those after completion of treatment. Results: Treatment with distigmine bromide resulted in a statistically significant reduction of residual volume and percent residual volume, obviating the need for intermittent self-catheterisation in 11 patients. In addition, maximum flow rate and detrusor pressure at maximum flow increased, although not significantly. The drug was generally well tolerated by the majority of patients. Conclusion: Distigmine bromide shows clinical efficacy in patients with poor detrusor function and may therefore be used alternatively in selected cases.

Urinary Basic Fibroblast Growth Factor in Bladder Cancer Patients

Introduction: Angiogenesis plays a significant role in the growth and progress of cancer, thus we evaluated the levels of urinary basic fibroblast growth factor (bFGF) in bladder cancer (Ca) patients and investigated any possible correlation between this angiogenic factor with tumor stage and grade. Materials and Methods: Urine samples from 41 patients with bladder Ca, 11 patients with history of bladder Ca but negative follow-up cystoscopy, 18 patients with benign prostate hyperplasia (BPH) and 15 normal healthy volunteers were assayed using an enzyme-linked immunosorbent assay for bFGF. Resulting values were normalized against urine creatinine and expressed as pg/g. Results: The median urinary bFGF level of patients with active disease, history of bladder carcinoma and negative follow-up cystoscopy, BPH, and healthy volunteers were 2,717, 1,009, 1,414 and 1,100 pg/g, respectively. There was a statistically significant difference between median bFGF levels of patients with active bladder Ca and those of the other groups (p = 0.000). Eleven patients with invasive bladder Ca had a median bFGF value of 6,880 pg/g that was significantly increased (p = 0.002) compared to the median of 2,312 pg/g of those with superficial tumors (Ta 14, T1 16). Grades 1, 2 and 3 carcinoma were found in 5, 19 and 17 patients which had a median bFGF of 2,717, 1,762 and 3,617 pg/g, respectively, but the difference was not statistically significant (p = 0.13). Conclusions: Our results confirm the implication of bFGF in the biology of bladder cancer, and demonstrate that urinary bFGF concentration seems to be significantly related to the stage but not to the grade of the disease supporting the proposed mechanisms of release of bFGF. Further studies are required in order to validate the potential clinical applications of bFGF for specific groups of bladder cancer patients.

ORTHOTOPIC BLADDER SUBSTITUTION AFTER RADICAL CYSTECTOMY: 5 YEARS OF EXPERIENCE WITH A NOVEL PERSONAL MODIFICATION OF THE ILEAL S POUCH

PURPOSE We report a 5-year experience with 52 patients who underwent radical cystoprostatectomy for bladder cancer and orthotopic bladder substitution using a novel personal modification of the S pouch. MATERIALS AND METHODS From September 1995 to December 1999, 52 men 36 to 72 years old (mean age 63) underwent bladder substitution with an S pouch. They were followed until September 2000. The pouch was constructed with a 36 cm. segment of ileum with the whole length used for the reservoir. The ureters were directly anastomosed with one above the other in the mid segment of the pouch without any antireflux procedure. Complications were documented and classified as early or up to 3 months postoperatively and late, and further subdivided by the relationship to neobladder construction. Continence and voiding pattern were evaluated by personal interview and neobladder function was urodynamically assessed. Mean followup in our patients was 30 months. RESULTS The most common of the 5 early and 9 late neobladder related complications were persistent urine leakage and reflux, respectively. There was no reflux greater than grade III in the 4 patients with reflux (5 refluxing ureters) and no functional disorders. We observed 12 early and 5 late complications unrelated to the neobladder. Open reoperation was required in 5 cases. Good or satisfactory daytime and nighttime continence was reported by 95% and 88% of our patients, respectively. By year 1 postoperatively 91% of our patients voided at an interval of 3 to 5 hours during the day. Mean maximum neobladder capacity was 672 ml. and mean post-void residual was 30 ml. by year 3 postoperatively. Two patients required self-catheterization once daily and mild hyperchloremia without acidosis developed in 2. CONCLUSIONS The advantages of our modified S pouch are technical simplicity, substantially shorter operative time and decreased bowel length required. It is associated with an acceptable complication rate and functional parameters with subsequent patient satisfaction and good quality of life.

Lymphoepithelioma‐like carcinoma of the bladder

During 1997 and 1998, 156 new patients with bladder tumour were diagnosed and treated in our institution. Three of these patients (0.2%) had tumours with lymphoepithelial features. All were men presenting with macroscopic haematuria and urgency. A solitary bladder tumour was diagnosed in all and treated by TURBT. In the ®rst two patients, pathology showed lymphoepithelioma-like carcinoma (LELC), pT3a and pT1, respectively. Patient 1 received systemic combination chemotherapy and patient 2 intravesical instillations with epirubicin. In patient 3, the pathology after TURBT initially showed a grade III stage pT2 TCC. Radical cystoprostatectomy followed and a LELC was detected with bladder muscle invasion, and an incidental Gleason score 4 prostate adenocarcinoma. All three tumours were composed of sheets or nests of malignant cells with large pleomorphic nuclei and prominent nucleoli. The lymphoid background consisted of mature lymphocytes mixed with plasma cells and histiocytes and occasionally neutrophils and eosinophils (Fig. 1a). Immunostaining with mAbs against low molecular weight cytokeratins and EMA showed positivity within most LELC tumour cells (.Fig. 1b). Hybridization to Epstein±Barr virusencoded RNA was negative in all cases. No evidence of tumour recurrence has been reported in any patient to date (with a follow-up of 34, 28 and 32 months for patients 1±3, respectively).

Pharmacokinetics of clarithromycin in the prostate: implications for the treatment of chronic abacterial prostatitis.

PURPOSE We studied the pharmacokinetics of orally administered clarithromycin in prostatic tissue to define its role in the treatment of chronic abacterial prostatitis caused by intracellular pathogens. MATERIALS AND METHODS A total of 45 men receiving 3 oral doses of 750 mg. clarithromycin at 12-hour intervals underwent suprapubic prostatectomy for benign prostate hyperplasia 4, 5, 6 and 7 hours after the last drug dose in 13, 12, 10 and 10 patients, respectively. Concentrations were determined in the prostate tissue and in plasma by an agar diffusion assay. RESULTS A mean peak level of clarithromycin of 3.22 and 3.08 microg./gm. of tissue was achieved 4 hours after the third drug dose at the center and periphery of the adenoma, respectively. Tissue levels remained statistically superior to plasma levels at all intervals. CONCLUSIONS The oral administration of clarithromycin achieved a prostate level much higher than the minimal inhibitory concentration of clarithromycin for the intracellular pathogens of chronic prostatitis. Thus, clarithromycin may be considered for treating chronic abacterial prostatitis.

Adjuvant Intravesical Mitoxantrone versus Recombinant Interferon-α after Transurethral Resection of Superficial Bladder Cancer: A Randomized Prospective Study

Objective: To determine the efficacy and safety of two different doses of intravesical mitoxantrone and of recombinant interferon-α (IFNα-2b), instilled after transurethral resection (TUR) of superficial transitional cell carcinoma (TCC) of the bladder. Material and Methods: 208 patients (mean age 62.05 years) with primary or recurrent superficial (TaG1, T1G1, T1G2) bladder cancer were randomly allocated into four groups, after TUR of all visible tumors. Group A (45 patients) received no further therapy; group B (56 patients) received 10 mg of mitoxantrone (6 weekly and 20 fortnightly instillations), group C (54 patients) 20 mg of mitoxantrone (3 fortnightly and 10 monthly instillations) and group D (53 patients) received 100 MU of IFNα-2b (8 weekly, 8 fortnightly and 6 monthly instillations). Results: During the follow-up (mean 21.09 months), 29 (64.44%) patients in group A had recurrence, compared with 19 (33.92%) in group B, 17 (31.48%) in group C and 15 (28.3%) patients in group D (p < 0.005). Furthermore, the differences in simple recurrence rates were statistically more significant (p < 0.05), when group A was compared with the three other groups in the terms of T1G2, recurrent and multiple neoplasms. Twenty-nine patients (10, 7, 8, and 4 in groups A–D) experienced tumor progression, and the differences between the four groups were not statistically significant (p > 0.05). The mean recurrence time was 9.03 months in group A, 13.74 in group B, 14.24 in group C and 17.4 months in group D (p < 0.001), and the recurrence rate per 100 patient-months was 4.39, 1.57, 1.48 and 1.06, respectively (p < 0.05). Toxicity (grade 1–3) was recorded in 23.21% in group B, in 31.48% in group C and in 9.43% in group D (p < 0.01). Conclusion: The two doses of mitoxantrone resulted in similar efficacy for the prevention of superficial bladder cancer recurrences, with the dose of 10 mg of mitoxantrone being related to fewer side effects. In comparison with mitoxantrone, the adjuvant intravesical immunotherapy with 100 MU of IFNα-2b showed a better combination of efficacy and safety.

Non-endothelial KDR/flk-1 expression is associated with increased survival of patients with urothelial bladder carcinomas.

Aims:  To investigate the immunohistochemical expression of KDR/flk‐1 in a series of 114 urothelial bladder carcinomas in relation to clinicopathological parameters, Ki67, p53 and Bcl‐2 protein expression and patient survival. KDR/flk‐1 is a high‐affinity tyrosine kinase receptor for vascular endothelial growth factor (VEGF), on vascular endothelium. However, there is increasing evidence that KDR/flk‐1 is also expressed by normal non‐endothelial and tumour cells.