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Item does not contain fulltext PURPOSE: To assess the uptake, accumulation, temporal stability, and spatial localization of isoflurane (ISO) in the C57BL/6 mouse, and to identify its potential interference with the detection of labeled cardiac progenitor cells using 19 F MRI/MR spectroscopy (MRS). MATERIALS AND METHODS: Objectives are demonstrated using (a) in vitro ISO tests, (b) in vivo temporal accumulation/spatial localization C57BL/6 studies (n = 3), and (c) through injections of perfluoro-crown-ether (PFCE) labeled cardiac progenitor cells into femoral muscle areas of the murine hindlimb post-mortem (n = 1) using 1 H/19 F MRI/MRS at 9.4 Tesla. Data were acquired using double-gated spoiled gradient echo images and pulse-acquire spectra. For the in vivo study, the temporal stability of ISO resonances was quantified using coefficient of variability (CV) (5 min) estimates. RESULTS: Two ISO resonances were observed in vivo that correspond to the -CF3 and -OCHF2 moieties. CV values ranged between 3.2 and 6.4% (-CF3 ) and 6.4 and 11.2% (-OCHF2 ). Reductions of the ISO dose (2.0 to 1.7%) at 80 min postinduction had insignificant effects on ISO signals (P = 0.23; P = 0.71). PFCE-labeled cells exhibited a resonance at -16.25 ppm in vitro that did not overlap with the ISO resonances, a finding that is confirmed with MRS post-mortem using injected, labeled cells. Based on 19 F MRI, similar in vivo/post-mortem ISO compartmentalization was also confirmed in peripheral and thoracic skeletal muscles. CONCLUSION: Significant ISO accumulation was observed by 19 F MRS in vivo with temporally stable signals over 90 min postinduction. ISO effects on PFCE labels are anticipated to be minimal but may be more prominent for perfluoropolyether or perfluorooctyl bromide labels. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;45:1659-1667.

Purpose: To assess the uptake, accumulation, temporal stability, and spatial localization of isoflurane (ISO) in the C57BL/6 mouse, and to identify its potential interference with the detection of labeled cardiac progenitor cells using 19F MRI/MRS. Materials and Methods: Objectives are demonstrated using a) in vitro ISO tests, b) in vivo temporal accumulation/spatial localization C57BL/6 studies (n=3), and c) through injections of perfluoro-crown-ether (PFCE)-labeled cardiac progenitor cells into femoral muscle areas of the murine hindlimb post-mortem (n=1) using 1H/19F MRI/MRS at 9.4 T. Data were acquired using double-gated spoiled gradient echo images and pulse-acquire spectra. For the in vivo study, the temporal stability of ISO resonances was quantified using coefficient of variability [CV] (5 min) estimates. Results: Two ISO resonances were observed in vivo that correspond to the -CF3 and -OCHF2 moieties. CV values ranged between 3.2–6.4% (CF3) and 6.4–11.2% (CHOF2). Reductions of the ISO dose (2.0 to 1.7%) at 80 min post-induction had insignificant effects on ISO signals (p=0.23, p=0.71). PFCE labeled cells exhibited a resonance at -16.25 ppm in vitro that did not overlap with the ISO resonances, a finding that is confirmed with MRS post-mortem using injected labeled cells. Based on 19F MRI, similar in vivo/post-mortem ISO compartmentalization was also confirmed in peripheral and thoracic skeletal muscles. Conclusion: Significant ISO accumulation was observed by 19F MRS in vivo with temporally stable signals over 90 min post-induction. ISO effects on PFCE labels are anticipated to be minimal but may be more prominent for perfluoropolyether or perfluorooctyl bromide labels.

ObjectiveCytology is an essential tool for the investigation of urinary tract malignancy. In this audit, we aimed to assess our laboratory performance in the diagnosis of upper urinary tract malignancy and to use the information provided to improve our service. MethodsWe retrieved cytology reports of upper urinary tract specimens from two periods, re-evaluated the cases, compared the reports with histology data and estimated the sensitivity, specificity and positive predictive value (PPV). In the time interval between the two periods, we adopted new terminology, established better communication with clinicians and gained experience in the field. Finally, the data from the two periods were compared. ResultsIn phase A, we estimated a sensitivity of 73%, specificity of 86% and PPV of 84.6%. As a result of the cytological re-evaluation, correlation with histology and clinical follow-up, plus communication with the clinicians during the audit, we established new terminology and a new request form. A three tiered grading system of atypia (mild, moderate and severe) was replaced by a two tiered grading system. The first category atypia probably benign corresponded to mild atypia while the second category atypia, not otherwise specified corresponded to moderate atypia. The cases diagnosed as severe atypia were reclassified as suspicious for malignancy. In phase B, the sensitivity, specificity and PPV were 75%, 89% and 90%, respectively. ConclusionsOur laboratory performance is in concordance with reported data and has been improved through this study. The audit process is extremely valuable for the identification of problems, for taking action and, finally, for the improvement of the clinical cytology service in the field of upper urinary tract malignancy. In this audit, performance in the diagnosis of upper urinary tract malignancy was assessed, with the information obtained leading to establishment of new terminology and a new request form. A re-audit demonstrated improvement in the service.

Relapsed urothelial cancer represents an unmet medical need. Vinflunine is a third-generation antimicrotubuline inhibitor and is currently the only approved drug for secondline treatment across the European Union. We conducted a retrospective analysis assessing the efficacy and safety of vinflunine in 71 Greek patients with relapsed urothelial cancer who were treated between 2005 and 2014. An overall 84% of our patients received vinflunine as second-line treatment, 77% had a performance status of Eastern Cooperative Oncology Group scale 0 or 1, and 30% had liver metastasis at the time of vinflunine administration. A median of four cycles of vinflunine were administered (range 1-16). The most common reported adverse events were constipation, fatigue, and anemia. Median progression-free survival was 6.2 months (95% confidence interval: 4.4-8.8) and overall survival was 11.9 months (95% confidence interval: 7.4-21). Two patients (3%) achieved a complete remission, seven a partial remission (10%), and 22 (31%) had stable disease according to an intention-to-treat analysis. Hemoglobin level less than 10 g/dl and Eastern Cooperative Oncology Group performance status greater than 1 were independent adverse prognostic factors. Stratification according to the Bellmunt risk model was also associated with progression-free survival and overall survival in our population. Vinflunine appears to be a safe and effective treatment modality for relapsed urothelial cancer. More effective therapies and more accurate prognostic algorithms should be sought. © 2015 Wolters Kluwer Health, Inc. All rights reserved.

In our multicenter retrospective analysis in 186 patients with metastatic renal cell carcinoma (mRCC) and synchronous metastases treated with sunitinib, we examined the role of cytoreductive nephrectomy (CN) in this clinical setting. CN proved to have a beneficial prognostic effect in survival independent of other diseaseor patient-related factors. CN remains a reasonable option for mRCC patients scheduled to be treated with vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKIs). Introduction/Background: The aim of this study was to evaluate the prognostic role of CN in patients with mRCC and synchronous metastases treated with the VEGF receptor TKI, sunitinib. Patients and Methods: Patients with a diagnosis of metastases before, at the time of, or within 3 months from the diagnosis of renal cell carcinoma (RCC) and first-line treatment with sunitinib were included. Baseline characteristics were correlated with overall survival (OS) according to hazard ratios estimated from univariate Cox proportional hazards models. Significant factors were then included in a multivariate Cox proportional hazards model. Results: One hundred eighty-six patients treated between January 2006 and March 2012 were selected. Thirty-six (19%) had not undergone CN. CN was offered to younger patients with better prognoses. Patients who underwent CN lived significantly longer than patients without CN (median OS, 23.9 [95% confidence interval (CI), 20.8-28.8] vs. 9 [95% CI, 4-16.4] months; P < .001). Multivariate analysis showed that CN had an independent prognostic significance. No specific subgroup benefiting from CN was identified. Conclusion: CN was an independent favorable prognostic factor in patients with synchronous metastases from RCC, treated with sunitinib. Information regarding the selection of mRCC patients likely to benefit from CN might be derived by ongoing phase III trials. © 2014 Elsevier Inc. All rights reserved.

Our goal is to describe our experience in the difficulties encountered during radical cystectomy for muscle invasive bladder cancer in patients with contemporary pelvic kidney. Two patients with muscle invasive bladder cancer and contemporary pelvic kidney were subjected to radical cystectomy and extended lymphadenectomy with conversion to an ileal pouch. In both cases, lymphadenectomy was the first step after entering the true pelvis. In order to proceed to the cystoprostatectomy, careful dissection of the ectopic renal vessels and proper mobilization of the kidney were performed. In both cases, an ileal pouch was our choice. The pelvic kidney is the most common sight of renal ectopia. The etiology is the aborted ascent of the fetal kidney from its initial position in the pelvis. This is the first case series describing radical cystectomy for muscle invasive urothelial carcinoma of the bladder in patients with a pelvic kidney.

Background: Recently, several polymorphisms located on human chromosome 8q24 were found to be associated with prostate cancer risk with different frequency and incidence among the investigated populations. The authors conducted a prostate cancer case-control study in the Greek population to evaluate the association of the single nucleotide polymorphism (SNP) rs6983267, located at region 3 of chromosome 8q24, with this type of cancer. Methods: Samples of total blood from 86 patients with histologically confirmed prostate cancer and 99 healthy individuals were genotyped using real time polymerase chain reaction (PCR). Tumor-node-metastasis (TNM) stage, Gleason score and levels of prostate-specific antigen (PSA) at diagnosis were included in the analysis. Results: A highly significant association (odds ratio2.84 and p-value0.002) was found between rs6983267 and prostate cancer in the Greek population. The sensitivity, specificity, negative and positive predictive values of the presence of G allele for the discrimination between patients and controls were 81.40, 39.4, 53.9 and 70.9, respectively. A lower proportion of homozygotes was found in patients with PSA level

This paper reports on an experiment that investigates the predictability of software project size from software product size. The predictability research problem is analyzed at the stage of early requirements by accounting the size of functional requirements as well as the size of non-functional requirements. The experiment was carried out with 55 graduate students in Computer Science from Concordia University in Canada. In the experiment, a functional size measure and a project size measure were used in building estimation models for sets of web application development projects. The results show that project size is predictable from product size. Further replications of the experiment are, however, planed to obtain more results to confirm or disconfirm our claim.

We present an extremely infrequent Urologic entity of asymptomatic. double-blind ureteral duplication in an 8-year-old girl. Contemporary imaging modalities provided major assistance in the diagnosis. Surgical management is advocated because of the potential for future complications, such as lithiasis, obstruction of the collecting system, and renal failure. UROLOGY 73: 210.e1-210.e2, 2009. (C) 2009 Elsevier Inc.

Normal function of Insulin-like Growth Factor II Receptor (IGF2R) gene has been associated with negative control of tumor growth in vivo and in vitro. Rare alleles at a 3′ UTR short tandem repeat polymorphism of IGF2R are known to decrease transcript stability. One such allele (A2/B2) increases significantly the risk of oral squamous cell carcinoma and non-small cell lung carcinoma (NSCLC) in Caucasians. To determine potential association(s) between A2/B2 presence and development and/or progression of disease, we examined in 103 NSCLC patients, free of IGF2R allelic imbalance aberrations, the 3′ UTR allelic status in relation to tumor kinetic parameters (proliferation index-PI and apoptotic index-AI) and clinicopathological data. PCR and automated sequence analyses were employed to genotype the IGF2R 3′ UTR polymorphism. Given that, oncogenic mitogens, which escape degradation by IGF2R, can also activate p53 through a DNA damage response, the patterns between p53 status and IGF2R genetic constitution were also evaluated in relation to the above parameters. The A2/B2 variant was significantly more common (p = 0.005, χ2-test) in lung cancer patients (25% vs 15%). Its presence was accompanied by high cellular proliferation (p = 0.028, t-test) along with increased tumor cell growth (GI = PI/AI) (p = 0.022, t-test) and it was significantly found in advanced stages. Also, patients carrying the A2/B2 in their genetic constitution that exhibit aberrant p53 expression have faster growing tumors and progress more rapidly to advanced stages. In conclusion, the IGF2R-A2/B2 variant probably provides a selective advantage for NSCLC progression through increased tumor growth. © 2007 Elsevier Ireland Ltd. All rights reserved.

OBJECTIVE: To investigate the tissue distribution of ischaemia in human detrusor in patients with bladder outlet obstruction (BOO) and to correlate the results with clinical variables, as clinical BOO is a common problem in ageing men and ischaemia might be important in detrusor dysfunction. PATIENTS AND METHODS: From September 2004 to October 2006, 70 patients were recruited, comprising 60 scheduled for surgery to treat benign prostatic hyperplasia (the study group) and 10 as controls. Detrusor tissue was retrieved and stained for hypoxia-inducible factor (HIF)-1α, a cellular marker of hypoxia. RESULTS: The mean (sd) total number of cells immunoreactive to HIF-1α in the study group was 93.3 (48.09), and in the specimens from the control group only few rare cells showed weak immunoreactivity to HIF-1α (0-2). Positive cells were in different proportions between muscle bundles and submucosa, expressed mainly in stromal cells. The urothelium and detrusor muscle showed no immunoreactivity to HIF-1α. There was strong immunoreactivity in patients with prolonged BOO (

Background and Purpose: Spontaneous perforation of the upper ureter is a rare condition that poses diagnostic and therapeutic problems. We report on five cases from three institutions and discuss the literature. Patients and Methods: Five patients presented with renal colic and the imaging modalities used to assess them showed extravasation of urine. Results: The cause of spontaneous perforation of the ureter was a ureteral stone in one case and was unknown in four cases. In all cases, a Double-J ureteral stent was inserted under fluoroscopy. Urinoma was percutaneously drained in only one patient. Repeat imaging showed normal renal function and morphology in all patients. Conclusion: Spontaneous perforation of the ureter should be suspected after renal colic. Endourologic treatment offers excellent results, even for the management of acute complications. © 2008 Mary Ann Liebert, Inc.

The aim of this study was to investigate the patterns of renal function recovery during partial nephrectomy (PN) on an experimental solitary kidney rabbit model and establish the upper tolerable time limits of applied ischemia. Forty-eight New Zealand rabbits underwent an open right nephrectomy and after 30 days, the animals were clustered into five groups (A, B, C, D, E). The first four groups received an open left PN, under different types of ischemia. Groups A (n = 8) and B (n = 10) were subjected to 90 and 60 min of warm ischemia (WI), respectively, while groups C (n = 10) and D (n = 10) received 90 and 120 min of cold ischemia (0) with ice-slush cooling. Group E (n = 10) served as sham group. Serum determinations of creatinine (SCr) and BUN were recorded preoperatively and on postoperative days (POD) 1, 3, 6 and 15. The animals were euthanized and the remaining kidneys were harvested and evaluated microscopically. The type and duration of ischemia were statistically significant parameters (P < 0.001). Groups B, C and D exhibited a similar pattern of recovery from trial initiation to the 15th POD (P = 0.788 and P = 0.068, respectively). Group A was extremely differentiated, with 100% mortality caused by uremia. The microscopic findings were consistent to the serum biochemistry. In our solitary kidney rabbit model, the upper limits of tolerable WI seem to be set on 60 min. Cl can safely preserve the model’s renal function - even up to 120 min.

Purpose: To evaluate the efficacy of doxazosin in inducing spontaneous passage of stones in the distal ureter and to compare its efficacy according to the size of the stone. Patients and Methods: Seventy-three patients with a mean age of 46.38 +/- 10.17 years who presented with a distal-ureteral stone were divided into four groups according to stone size and drug treatment

Purpose: To report the safety and efficacy of percutaneous nephrostomy and primary antegrade recanalization for treatment of iatrogenic ureteral strictures after gynecologic surgery. Patients and Methods: Ten women had symptoms suggestive of ureteral obstruction during the immediate postoperative period (5 days-1 week after surgery). Under analgesia and conscious sedation, standard percutaneous nephrostomy was performed, and a long 7F sheath was placed in the upper ureter. The obstructions were traversed with the aid of a 0.0035-inch Glidewire and a 5F angled Glide catheter (Terumo, Japan). Subsequently, the areas were dilated with angioplasty balloons to a maximum diameter of 7 mm. Finally, an 8F percutaneous internal/external nephroureteral drainage stent was inserted to secure ureteral patency. Follow-up was carried out by serial nephrostomography until removal of the stent and by renal ultrasonography thereafter. Results: Twelve obstructions with a mean length of 1.4 cm (range 0.4-1.9 cm) were managed. The technical success rate was 100%. No major complications occurred, and normal renal function was restored. The mean follow-up was 12 months. In 60% of the patients, a patent ureter was depicted at 1 week, whereas in four patients, repeat dilation of the obstructed segment was required. The stents were removed after a mean period of 4.8 weeks. Conclusion: Percutaneous nephrostomy and primary antegrade ureteral balloon dilation is safe and efficacious for treating ureteral injury after pelvic surgery and obviates open surgical manipulations.

Introduction. Biopsy-related vascular injuries in renal transplants are rare, but they can lead to dramatic clinical symptoms prompting immediate treatment. Transcatheter embolization is a minimally invasive technique used to treat some forms of arterial bleeding. This study evaluated the efficacy of this technique in iatrogenic biopsy-related vascular lesions in renal allografts. Materials and methods. Over the last eight years, six patients with severe renal hemorrhage were admitted to the angiography department of our hospital for evaluation and possible further treatment. All of them had a history of previous biopsy of a transplanted kidney. They all presented with clinical signs of hemodynamic instability. Angiographic investigation of the kidneys preceded further intervention in all cases. All underwent hyperselective embolization of the specific bleeding vessel with the use of microcoils and/or gelfoam particles. Results. Successful embolization of the feeding artery could be performed in all patients. Superselective segmental renal artery embolization had a successful outcome concerning a steady renal function and a stable clinical course. No complications occurred. Conclusion. Transcatheter embolization is a safe and efficient endovascular technique to treat biopsy-related vascular injuries in renal transplants. Immediate clinical success and significant benefit in renal function can be obtained, and the longevity of the allograft after successful embolization mainly depends on the natural outcome.

Purpose. Radical surgery represents the treatment of choice for carcinoma of the upper urinary tract. Nevertheless, approximately 50% of patients with stage T greater than or equal to 3 or lymph node involvement die from their disease, mainly as a result of the development of distant metastases. Therefore, there is a need for effective adjuvant systemic treatment. We prospectively studied a cohort of patients who underwent surgery for high-risk carcinoma of the upper urinary tract to assess the feasibility of the combination of paclitaxel and carboplatin as adjuvant treatment. Patients and Methods. Thirty-six patients with tumor stage greater than or equal to 3 or lymph node involvement were treated with four cycles of paclitaxel at 175 mg/m(2) and carboplatin (area under the curve 5, Calvert Formula) every 3 weeks following surgery. Results. Median follow-up was 40.6 months. Chemotherapy was well tolerated with 32 patients (89%) receiving full carboplatin and paclitaxel doses without delays. The most frequent grade 3/4 toxicity was neutropenia (39%) which was complicated with fever in only one case (3%). Nonhematologic grade 3 or 4 toxicities were reported in only one case. Five-year survival was 62% (95% Cl, 35% to 69%), while 5-year disease-free survival was 40.2% (95% Cl, 15.8% to 64.6%). Local failure rate was 30%, as opposed to 17% of patients who developed distant metastases. No patients with grade 2 tumors relapsed during follow-up, as opposed to 60% of patients with grade 3 tumors, Conclusion. Adjuvant chemotherapy with paclitaxel and carboplatin is feasible and may reduce the risk of distant metastases in high-risk upper urinary tract carcinoma. (C) 2004 by American Society of Clinical Oncology.

OBJECTIVES To assess the effect of bladder instillations of hyaluronic acid (HA) on the rate of recurrence of urinary tract infection (UTI). PATIENTS AND METHODS Forty women (mean age 35 years) with a history of recurrent UTI received intravesical instillations of HA (40 mg in 50 mL phosphate-buffered saline) once weekly for 4 weeks then once monthly for 4 months. The UTI status was assessed over a prospective follow-up of 12.4 months and compared with the rates of UTI before instillation, determined by a retrospective review of patient charts covering 15.8 months. RESULTS After HA treatment no patients had a UTI during the 5-month treatment phase and 28 (70%) were recurrence-free at the end of the follow-up. The mean (SD) rate of UTI per patient-year was 4.3 (1.55) before treatment and 0.3 (0.55) afterward (P < 0.001). The median time to recurrence after HA treatment was 498 days, compared with 96 days beforehand (P < 0.001). The tolerability was excellent, as side-effects were limited to nine patients who reported mild bladder irritation; no patient interrupted the treatment. CONCLUSIONS In this preliminary study, bladder instillations of HA had a significant effect on the rate of UTI in women with a history of recurrent UTIs. The bladder instillation of HA is an acceptable and promising therapeutic alternative in patients with recurrent UTI. Expanded placebo controlled clinical trials examining this application of HA are currently underway.

Background. Renal transplantation is an effective treatment for end-stage renal disease. Ureteral stenosis is the most frequent urologic complication. We report our long-term follow-up results concerning endourologic treatment of ureteral obstruction after renal transplantation. Methods. Between May 1997 and September 2000, 15 patients with renal transplant obstructive uropathy were managed with percutaneous nephrostomy and prolonged ureteral stenting. Results. Petcutaneous nephrostomies were performed successfully in all 15 kidneys. In 13 patients, antegrade ureteral stenting was attempted, which was successful in 11 patients (85%). After prolonged ureteral stenting (mean duration 15 months), the stent was removed in all patients, 90% of whom had no recurrence. During follow-up (36 to 71 months; mean 51), urea, creatinine, sodium, and potassium determinations and ultrasound scans were performed. Success was defined as a reduction in hydronephrosis. No major complications were observed. Conclusions. Modern endourologic procedures have replaced open reconstructive surgery in most patients with ureteral obstruction after renal transplantation, because they may offer a definitive treatment with low morbidity.

Gastrin releasing peptide (GRP) is a neuropeptide that has been suggested to play a role in the development of some malignancies. Our aim was: (1) to identify the expression of GRP in cancerous prostate glands, and (2) to correlate its expression to various pathological parameters and to the patient’s clinical outcome. Using standard immunohistochemistry, we evaluated GRP expression in both biopsy and radical prostatectomy specimens from 30 patients with prostatic adenocarcinomas. GRP was expressed in 18 radical prostatectomy specimens (60%) and in 15 biopsies (50%). There was an association between positive immunoexpression of GRP, relapse (P=0.029) and advanced tumor stages (i.e. pT3, pT4) (P=0.049). In the respective biopsies, GRP immunostatus was similar to that observed in the subsequent radical prostatectomy specimens. GRP immunoexpression may be of some value as a diagnostic and prognostic marker. Patients whose pathology specimens demonstrate GRP immunopositivity should be closely monitored, since they appear to be at higher risk of disease progression and relapse.

Prostate cancer is one of the main causes of morbidity and mortality among men. Several oncogenes and growth factors have been studied in an attempt to explain the molecular basis of carcinogenesis and progress of this carcinoma. In this study we correlated the immunohistochemical expression of antioncogene nm-23 H1 and transforming growth factor beta 1 (TGF-beta 1) with the clinical stage, PSA values, Gleason score and survival in prostate cancer.Fifty nine patients with prostate cancer were evaluated. PSA measurement, Gleason score determination and clinical staging were recorded for all the patients by the time of initial diagnosis and prior to any treatment. Follow-up ranged from 12 to 40 months. Tissue sections from representative areas of the tumors were immunohistochemically stained for nm-23 H1 and TGF-beta 1. The expression of these markers was correlated with stage, PSA values, Gleason score and survival.There was a negative correlation between nm-23 H1 staining and tumor stage and grade. High grade (Gleason score 8-10) and stage D tumors showed weaker staining than low stage and grade tumors. There was a positive correlation between TGF-beta 1 staining, tumor stage and serum PSA levels. Additionally, TGF-beta 1 proved to be a negative predicting factor for patient survival. In tumors expressing both markers, TGF-beta 1 was the one to determine the aggressiveness of the carcinoma.nm-23 H1 appears to be a tumor suppressor gene in prostate cancer, while TGF-beta 1 may act as a stimulating agent provoking aggressive behavior and metastasis. Their immunohistochemical staining may constitute complementary information in the evaluation of prostate cancer patients.

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 mi. for NMP22 and 12 mug./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 law grade tumors, and the higher specificity. The contribution of these tests for detection of bladder cancer should still be considered adjunctive to cystoscopy.

Matrix metalloproteinases (MMPs) are proteolytic enzymes important at several points during multistep neoplastic progression. Although MMP-1 and MMP-3 have been implicated in the progression of various human cancers, their expression in bladder cancer has not been addressed. Immunohistochemistry (Strept-ABC-HRP method) and in situ hybridization were performed to detect MMP-1 protein, MMP-3 protein, and MMP-3 mRNA, respectively, in 59 transitional cell bladder carcinomas. To assess the role of these MMPs in bladder cancer, their expression was evaluated in relation to known clinicopathologic parameters and patients’ disease-free and overall survival. Immunoreactivity for MMP-1 and MMP-3 proteins was observed in the cytoplasm of cancer cells in 30.5% and 24% of samples, respectively. Transcripts for MMP-3 mRNA were localized in stromal cells in 71.2% of cases and in cancer cells in 49% of cases. MMP-1 immunoreactivity demonstrated a statistically significant association with deeply invasive and grade III tumors versus superficial and lower grade tumors. MMP-3 protein immunoreactivity and MMP-3 mRNA immunolocalization did not associate with the parameters studied. However, MMP-3 mRNA localization in stromal cells demonstrated a borderline association with poor patients’ disease-free and overall survival. In conclusion, the authors’ results demonstrate a differential expression between MMP-1 and MMP-3 in bladder cancer; MMP-1 appears to participate in invasiveness and possibly in loss of differentiation in urothelial carcinomas in contrast to MMP-3.

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 Do 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 mi. and mean post-void residual was 30 mi. 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.

Aims-The nuclear enzyme DNA topoisomerase II has been shown to be required for chromatin condensation and chromosomal segregation during mitosis; its isoform topo II alpha is linked with active cell proliferation in mammalian cells. The aim of this study was to examine the relation of the expression of topo II alpha to the biological behaviour of conventional urinary bladder cancer. Methods-Formalin fixed, paraffin wax embedded tissue from 94 specimens of bladder urothelial cancer were immunohistochemically stained for topo II alpha. For each case, a topo II alpha index was determined. A similar index had been determined for Ki-67, a known cell proliferation marker. Each case had also been graded, staged, and evaluated for DNA ploidy as well as for p53 and bcl-2 immunoreactivity. Results-Raised topo II alpha expression tin greater than or equal to 10% of malignant nuclei) correlated with two adverse prognosticators-high grade (p = 0.027) and invasion of the muscularis propria (p = 0.013), but with no other evaluated parameter. By multivariate survival analysis using Cox’s proportional hazard model, high expression of topo II alpha was found to be predictive for worse survival (p = 0.0047). Patients’ age, tumour stage, and grade were also retained as independent prognostic factors (p = 0.0349, p = 0.00005, and p = 0.0130, respectively). The negative influence of increased topo II alpha immunopositivity on patients’ survival was also seen in the subgroup of patients with non-muscle invasive carcinomas (p = 0.0004), in patients with a bcl-2 negative phenotype (p = 0.0330), and in those with low Ki-67 indices (p = 0.0341). Conclusions-Because topo II alpha and Ki-67 failed to demonstrate a significant interrelation, they appear to be different molecules that both function at separate phases in the complex process of cellular proliferation. The assessment of increased topo II alpha immunoreactivity in specimens from urothelial carcinomas might help to select patients (particularly among those with superficial tumours) in the worse prognostic categories for new therapeutic strategies.

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. UROLOGY 55: 871-875, 2000. (C) 2000, Elsevier Science Inc.

Purpose: We determined and compared the presence and frequency of interferon-alpha 2b receptors in urothelial neoplasms and normal urothelium, since the biological activity of interferons becomes apparent only after they bind to specific receptors. Materials and Methods: With our method detection of interferon-alpha 2b receptors required a large number of cells, that is more than 1 x 10(6) cells per ml. We studied 14 patients with relatively large tumors of all stages and grades. Three patients had grade I, 4 grade II and 7 grade III disease. As controls we used biopsies of normal urothelium from 14 patients who underwent transvesical prostatectomy. Interferon-alpha 2b receptors were detected quantitatively through the binding of radiolabeled (125)iodine human recombinant interferon-alpha 2b in normal and malignant urothelial tissue samples. The interferon-alpha 2b receptors are expressed as receptor sites per cell, and the results were evaluated with Scatchard analysis. Results: The number of interferon-alpha 2b receptor sites per cell ranged from 43 to 100 (mean plus or minus standard deviation 62 +/- 18) in normal urothelium and from 110 to 210 (mean 174 +/- 25) in malignant epithelium. This difference was statistically significant (p < 0.001, Student’s t test 13.75). The difference in the number of interferon-alpha 2b receptors in grades I plus II and grade III tumors is suggestive but not statistically significant (p < 0.10, Student’s t test 2.075). High grade tumors expressed greater numbers of interferon-alpha 2b receptors than low grade tumors. Conclusions: The method used needs refining so that it will require fewer cells to determine interferon-alpha 2b receptors. Interferon-alpha 2b receptors are detected in bladder urothelium and are abundant in malignant tissue with increasing frequency as tumor grade increases. If we can establish, in the future, a correlation of the number of interferon-alpha 2b receptors with the potential response of patients to intravesical instillation therapy with interferon, we might have an important prognostic method for selecting subgroups of patients with transitional cell carcinomas who will benefit from interferon-alpha 2b instillation.