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Objectives: Radical perineal prostatectomy (RPP) is an alternative to the retropubic, laparoscopic or robotic prostatectomy approaches. This study reports the experience with RPP of a single surgeon at a single institution; the technical aspects, oncological outcome, and complications, such as urinary incontinence and erectile dysfunction, were investigated., Methods: A total of 212 consecutive patients with a mean age of 63 (range 45-74) years and clinically localised prostate cancer were monitored. Between January 2001 and December 2010, all patients underwent RPP that was performed by a single experienced surgeon at one institution. All data were introduced into a database focussing on the intra-operative and post-operative complications, continence rate, potency and oncological outcome., Results: The mean follow-up was 48 (6-117) months. Intra-operative complications, both early and late, occurred in 19% of the patients. The average length of in-hospital stay was 9 (3-45) days, and the mean period of time spent with a urethral catheter in place was 9 (4-45) days. The continence rate was 81%, and the potency rate, without any pharmacological aid, was 27%. The overall PSA-free survival rate was 86%. There was one cancer-specific death., Conclusion: On the basis of our prospective data, we conclude that RPP provides satisfactory oncological results with an acceptable outcome in terms of quality of life. RPP can be considered to be mini-invasive and achieves results that are equivalent to those of the alternative surgical approaches., (Copyright © 2011 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

Objectives: To evaluate the rate and duration of prostate-specific antigen (PSA) response to high-dose bicalutamide (150 mg) in nonmetastatic castration-resistant prostate cancer patients and its impact on metastasis-free survival., Methods: This single center, prospective study included 38 prostate cancer patients surgically or medically castrated who had PSA increases above their nadir after previous antiandrogen manipulation and in absence of bone metastases. Patients were given daily dose of bicalutamide 150 mg. Clinical evaluations and serum PSA testing were performed every 3 months. Response was defined according to PSA decline from baseline as if ≥ 50% or ≥ 85%. The duration of response was the time from entering into study until PSA increased ≥ 25% or ≥ 2 ng/ml from the nadir. Bone scintigraphy was repeated at PSA increase or at symptom appearance., Results: The mean follow-up was 34.5 months (range, 3-75.2). A PSA decline was observed in 17 of 38 patients (44.7%): 7 (18.4%) ≥ 85% and 10 (26.3%) ≥ 50 but < 85% responders. The median duration of response was 18.5 months for partial and 37.4 months for complete responders. The median time to metastasis was 52.5 months for responders and 15.7 months for nonresponders (Log-Rank test 9.3, P = .002)., Conclusions: High-dose bicalutamide can induce a second response in almost half of castration-resistant prostate cancer patients without metastasis. The duration of response is more than 1.5 years on average and responders have prolonged metastasis-free survival., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objective: To investigate the role of (18) F-fluorodeoxyglusose positron-emission tomography (FDG-PET), combined with computed tomography (CT) and forced diuresis, in the staging and follow-up of urothelial carcinoma (UC)., Patients and Methods: We recruited 44 patients with muscle-invasive urothelial bladder cancer (UBC) before radical cystectomy (RC), 19 under follow-up after RC and seven after systemic chemotherapy. For those who had RC, histopathology was used as the reference standard to compare the sensitivity and specificity of FDG-PET/CT and standard CT in detecting UBC and pelvic lymph node metastasis. Furthermore, 36 patients with ≥ 6 months of follow-up imaging were considered to describe the progression of UC and extrapelvic positive FDG-PET/CT images., Results: For the detection of primary UBC, FDG-PET/CT was slightly more sensitive than CT (85% vs 77%) but less specific (25% vs 50%). For the detection of pelvic node metastasis FDG-PET/CT was more sensitive than CT (57% vs 33%) with a specificity of 100% for both imaging techniques. In 20 patients, extrapelvic FDG-PET/CT images showed suspected disease at the first evaluation. UC progressed in nine of the 10 patients who had synchronous multiple PET-positive retroperitoneal or mediastinal lymph nodes, and in only two of the nine with unique hyperactive lesions in the lung. FDG-PET/CT also detected a pT1G3 UC of the renal pelvis and all bone metastases detected by bone scintigraphy., Conclusions: FDG-PET/CT could replace standard CT and bone scintigraphy in the presurgical staging and monitoring of patients with UC after surgery or chemotherapy., (© 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.)

Objectives: The aim of this study was to evaluate sex- and age-related variations of the nutritional status in the aged population of central Sardinia, a geographical area with a high frequency of long-lived people, particularly men., Design: The sample consisted of 200 subjects over 70 years of age (men: N= 100, age= 81.0 +/- 7.0 years; women: N= 100, age= 81.5 +/- 7.3 years)., Setting: Orroli (central Sardinia, Italy)., Measurements: Mini nutritional assessment (MNA) and bioelectrical impedance vector analysis (BIVA) were used to evaluate nutritional status and body composition., Results: The indicators revealed a generally good nutritional status. The MNA results (men: 24.6 +/- 2.2; women: 23.4 +/- 2.5) showed that 64.1% of the subjects had a normal nutritional status and only a small proportion (1.2%) could be classified as malnourished. BIVA showed that most subjects (74.2%) were normal, while the prevalence of low body cell mass was 10.7% and that of dehydration 11.2%. According to the MNA, the nutritional status was significantly better in the men. Almost three-quarters of the men (73.1%) were well nourished vs. half of the women (50.6%). A worsening of the nutritional status with age was observed. The proportion of malnourished individuals, as assessed by MNA, increased from 0% to 9.1% from 70-79 to > 90 years., Conclusions: With respect to their contemporaries from other regions, the elderly of Orroli presented a better nutritional status, a similar worsening with age and generally higher sexual dimorphism.

A case of primary malignant melanoma of the urethra in a 60-year-old male is presented. Despite multiple adverse prognostic factors and against expectations, after a follow-up of 5.5 years he is still alive.

Background: Few data are available in comparing different incontinent urinary diversions (ICUD)., Objective: To compare early, short-term, and long-term complications in three different forms of ICUD., Design, Setting, and Participants: 130 high-risk patients undergoing radical cystectomy and ICUD were prospectively enrolled at one institution. The patients were divided into three groups: ileal conduit (IC), colon conduit (CC), and ureteroureterocutaneostomy (UUCS)., Intervention: All patients underwent radical cystectomy and one form of ICUD., Measurements: The complications observed were prospectively listed and subsequently compared. Statistical analysis was performed using the Pearson's chi-square test. A p-value < or = 0.05 was considered statistically significant., Results and Limitations: 130 patients with a median age of 71.0 yr (range 46-81) underwent radical cystoprostatectomy (RCP): n=95 (73%) or anterior pelvic exenteration (APE) n=35 (27%) with lymphadenectomy. An IC was performed in 55, a CC in 34, and a UUCS in 41 patients, respectively. A high comorbidity, mainly diabetes, arteriosclerosis, pulmonary insufficiency, and borderline renal function (creatinine>1.5mg%) was found in 12.7% of group 1, in 35.2% of group 2, and in 48.9% of group 3. Overall median follow-up was 16 mo (range 5-84). Perioperative mortality occurred in 1.5%. The overall perioperative diversion-unrelated complication rate was 23.6%. IC showed the lowest rate with 18.1%, followed by CC with 26.4%, and UUCS with 32%, respectively. In contrast, major diversion-related complications occurred in 18.1% of IC, in 5.8% of CC, and none in UUCS. The same was true for late surgical reintervention, with 20% for IC, 5.8% for CC, and 2.4% for UUCS., Conclusions: Complications are closely related to the method selected. The IC had the highest rate of severe complications as well as surgical reinterventions and late complications in the intestinal tract.

Purpose of Review: To review the most recent publications focusing on the use of genetic markers (DNA, RNA and nucleosides) in urine and serum and provide an opinion on their potential utility for screening, diagnosis and prognosis of urothelial carcinoma., Recent Findings: Several studies have shown the diagnostic utility of urine tests based on improved microsatellite analysis of loss-of-heterozygosity, detection of fibroblast growth factor receptor 3 mutations, detection of single RNA and multiple gene signatures as well as nucleoside profiles. Although of interest, all these studies lack appropriate controls and validation before being considered as serious candidate clinical biomarkers. The presence of fibroblast growth factor receptor 3 mutations in tumors was identified as a hallmark of tumors of low malignant potential. Serum DNA analysis of hypermethylation of a set of genes shows promise as an indicator of cancer progression and mortality. Finally, a case-control study of 775 patients and 397 controls showed that DNA hypomethylation of blood cells combined with smoking habits can provide stratification of cancer risk that may be very helpful in conceiving bladder cancer screening studies., Summary: The challenge is not so much to identify better markers or methods but rather to commit to implementing them into clinical practice by stimulating and funding the clinical trials required.

Aim: To evaluate the clinical outcome of high-risk prostate cancer (PC) treated by radical prostatectomy (RP) according to risk factors., Methods: Patients with stage cT1-T3 PC were stratified in high and low/intermediate risk groups using D'Amico's criteria: PSA>or=20 ng/ml or Gleason score>or=8 or clinical stage>or=T2c. The Kaplan Meier and Log rank test were used to generate estimates of biochemical free-survival (BFS) and PC specific mortality (PCSM)., Results: We analysed 1,109 patients with a median age of 64.1 years, a mean PSA of 12.8 and a median follow-up of 8.18 years (max. 17.5 years). Overall PSA failures (PSAF) were observed in 23.4%, mortality by all causes in 11.4% and PCSM in 2.9%. The 10-year BFS of the 290 high-risk was 45 versus 75.5% for low/intermediate risk patients and the 10-year PCSM was 10.3 versus 1.4%, respectively. Of the 290 high-risk PC, 25% had organ-confined disease at surgery with 28% PSAF compared to 55% PSAF for non-organ-confined PC irrespective of nodal status. High-risk patients with 1 or>or=2 high risk criteria had 2.6 and 3.86 times increased risk of PSAF compared to low/intermediate risk. Ten-year PCSM for PC individual risk criteria was 4.5% for PSA>or=20, 9.2% for stage>or=T2c and 18.2% for Gleason>or=8., Conclusion: Patients with high-risk PC treated by RP by experienced surgeons can have a favourable long-term survival. Further substratification should take into account the variable prognostic implication of the different individual risk factors.

Background: The clinical picture of Alzheimer's disease includes anthropometric and body composition variations. Somatotyping is a practical non-invasive method to assess body type., Objective: The objective of this study was to describe the somatotype of a sample of Alzheimer's patients., Methods: The sample consisted of 55 Alzheimer disease individuals in the mild-moderate stage (17 men, mean age = 76.9 +/- 7.2 years; 38 women, mean age = 79.6 +/- 6.4 years). The pathological subjects were compared with a control group consisting of 280 healthy individuals (134 men, mean age = 74.2 +/- 7.3 years; 146 women, mean age = 74.9 +/- 7.4 years). The Heath-Carter somatotype was applied., Results: The Alzheimer patients (mean somatotype: 6.1-5.5-0.8 in men, 7.0-5.3-0.7 in women) are less mesomorphic and more ectomorphic than the controls (mean somatotype: 6.1-6.3-0.6 in men, 7.7-6.3-0.4 in women), the differences being significant in women (mesomorphy, p = 0.000; ectomorphy, p = 0.012)., Conclusion: Alzheimer patients show peculiar somatometric characteristics. The somatotype technique could represent a suitable tool for the study and monitoring of physical variations., (Copyright 2007 S. Karger AG, Basel.)

Aim: To establish independent prognostic factors on a chromosomal basis in superficial bladder cancer, using a multicolour fluorescence in situ hybridisation (FISH) probe mix., Patients and Methods: In 2002, voided urine from 75 consecutive patients (mean age 71.7, range 52-93) years under follow-up for superficial urothelial cancer was studied prospectively. The patients were observed for a mean (standard deviation (SD)) period of 39.3 (6.8) months (range 27-58) until July 2005. A multicolour FISH on liquid-based voided urinary cytology was carried out on all patients. Univariate analysis, using a log rank test, was used to determine the prognostic relevance of a low-risk pattern and a high-risk pattern. Progression-free survival time was calculated from the date of first diagnosis to first recurrence or progression according to the Kaplan-Meier product-limit method., Results: One patient was lost to follow-up. 27 of the 74 remaining (36.8%) patients showed recurrent disease. In 9 (33.3%) patients with a low-risk pattern disease recurred after a mean (SD) observation time of 29.7 (1.9) months (range 8.3-52.3, median 30.8 (12.4)). 18 (66.7%) patients with a high-risk pattern developed recurrence within a mean (SD) of 17.6 (2.0) months (range 4-38.8, median 16.7 (11.6)). The Kaplan-Meier curve for progression-free survival showed marked differences between the low-risk and the high-risk groups., Conclusion: Patients with a high-risk chromosomal pattern have a markedly shorter disease-free survival time and higher progression rate than patients with a low-risk pattern. High-risk patients can therefore be treated more aggressively to prevent tumour spreading.

Background: On the basis of a multicolor-FISH test we aimed at verifying whether there is any molecular biological background for the different behavior of Gleason Score 7 prostate cancer (PCa)., Patients and Methods: Biopsies of 44 patients with histological verified PCa, 20 with Gleason score 3 + 4 (group A) and 24 with 4 + 3 (group B), were analyzed using FISH., Results: In group A, FISH detected a unique gain of 8q24 in 2 patients (10.0%) and a unique loss of 8p22 in 9 patients (45.0%). No concurrent loss and gain of both sites were found in this group. Of group B (4 + 3) a unique loss of 8p22 was observed in 14 patients (58.3%) and a concurrent loss of 8p22 and gain of 8q24 in 6 patients (25.0%)., Conclusion: Different molecular genetic patterns could explain the different biological behavior of the 2 groups. The analysis of chromosomal aberrations could therefore influence the clinical decision process in the future., (Copyright 2006 Wiley-Liss, Inc.)

Objectives: To assess the utility of ImmunoCyt/uCyt+ in combination with cytology to reduce the number and cost of cystoscopies in the follow-up of patients with urothelial cancer of the bladder., Methods: A total of 216 patients under follow-up after transurethral resection of the bladder for urothelial cancer were enrolled in the present study. The mean follow-up time was 26 months (range 3 to 96). Patients were tested for bladder cancer with ImmunoCyt/uCyt+, urinary cytology, and cystoscopy every 3 months. All patients with positive cystoscopy results for recurrence or suspect areas underwent transurethral resection of the bladder. Cystoscopy was considered the reference standard to establish the bladder tumor diagnosis. The patients were divided into low, intermediate, and high risk groups for progression according to the European Association of Urology criteria., Results: A total of 195 patients were suitable for evaluation. The urine samples from 21 patients were considered not evaluable for ImmunoCyt/uCyt+, and those patients were excluded from the study. Of all the control patients, 69.7% had negative cystoscopy findings. In the low-risk group, 84 patients underwent 131 cystoscopies, which diagnosed 30 Stage pTaG1 recurrences but no progression. Cytology and ImmunoCyt/uCyt+ together had a sensitivity of 86.6% and a negative predictive value of 95.2%., Conclusions: Of the cystoscopies performed during the 26 months of follow-up, 69.7% were negative. In the low-risk group, 30 Stage pTaG1 tumors and no progression was detected at a total cost of 14,672 Euros (USD 17,606). ImmunoCyt/uCyt+ and cytology every 6 months combined with annual cystoscopy reduced the morbidity and cost of follow-up in this group.

Background: The authors provide an update on the clinical value and role of the uCyt+/ImmunoCyt test as a noninvasive tool for the detection of recurrent urothelial carcinoma., Methods: Between January 2002 and October 2004, 942 patients (mean age, 72.6 yrs; range, 32-87 yrs) were enrolled in this prospective study. These patients mostly had been followed for superficial urothelial carcinoma (UC) confined to the mucosa and lamina propria (pathologic tumor [pT] classification pTa, pT1, and pTis [carcinoma in situ]) for a mean of 15.62 months (range, 4-28 mos). Voided urinary cytology and the uCyt+/ImmunoCyt test for all patients were performed on liquid-based cytology slides. Patients underwent subsequent cystoscopy when cytology or uCyt+/ImmunoCyt results were positive and when they underwent biopsy evaluation of any suspicious lesion. Altogether, 1991 uCyt+/ImmunoCyt analyses were performed., Results: Two hundred ninety-eight patients who had adequate samples available were diagnosed with histologically proven UC. The sensitivity of cytology increased from 8.3% for Grade 1 tumors to 75.3% for Grade 3 tumors; whereas, with the uCyt+/ImmunoCyt, the sensitivity was 79.3% for Grade 1 tumors, 84.1% for Grade 2 tumors, and 92.1% for Grade 3 tumors. For cytology and uCyt+/ImmunoCyt combined, the sensitivity was 79.3% for Grade 1 tumors, 90.9% for Grade 2 tumors, and 98.9% for Grade 3 tumors., Conclusions: The current data confirmed the clinical usefulness of the uCyt+/ImmunoCyt test in the follow-up of patients with recurrent UC. Used as a noninvasive tool, cytology escorted by uCyt+/ImmunoCyt may reduce the morbidity and cost of follow-up for patients who have a low risk of recurrence while avoiding superfluous cystoscopic examinations. However, additional studies will be necessary to establish and compare the morbidity and cost of each method., ((c) 2006 American Cancer Society.)

Background and Objectives: Oxidative stress can induce cell mutations or proliferation which then can progress to carcinogenesis or remodeling. The same oxidative stress-mediated mechanism could participate in prostate cell proliferation and remodeling present in benign prostatic hyperplasia (BPH). Doxazosin induces prostate epithelial and stromal cell apoptosis through production of transforming growth factor-beta (TGF-beta), but cellular mechanisms are not completely clarified. In 10 prostate samples from BPH untreated patients who underwent TUR, we have assessed the gene and protein expression of: p22(phox) (subunit of NAD(P)H oxidase essential for O(2)(-) production); heme oxygenase-1 (HO-1) (induced by oxidative stress and antiapoptotic); TGF-beta (inhibitor of prostatic epithelial and stromal cell growth); the in vitro effect of doxazosin on expression of these markers., Methods: RT-PCR and Western blot with specific primers and antibodies. p22(phox), HO-1 and TGF-beta were quantified by the ratio between their PCR and Western blot products and GAPDH., Results: Doxazosin significantly reduced p22(phox) gene and protein expression (0.61 +/- 0.04 vs. 0.36 +/- 0.04 d.u., p < 0.0002; 0.85 +/- 0.03 vs. 0.47 +/- 0.03, p < 0.0001, respectively). Doxazosin concentration dependently reduced HO-1 gene and protein expression (0.57 +/- 0.07 vs. 0.49 +/- 0.06 d.u. (1 microM) p < 0.04, vs. 0.22 +/- 0.08 (10 microM) p < 0.0001; 0.78 +/- 0.04 vs. 0.44 +/- 0.1 (10 microM) p < 0.003 respectively) and increased TGF-beta protein expression (0.58 +/- 0.05 vs. 0.74 +/- 0.16 (1 microM) n.s. vs. 0.81 +/- 0.07 (10 microM) p < 0.01)., Conclusions: Induction of oxidative stress-related proteins seems to be involved in the prostate cell proliferation and remodeling present in BPH. Doxazosin may reduce oxidative stress through reduction of p22(phox). Surprisingly, HO-1, which is induced and protected by oxidative stress, is also reduced by doxazosin. HO-1 is a potent antiapoptotic factor and downregulator of TGF-beta. From the results of this preliminary study it could be proposed that the proapoptotic effect of doxazosin could be mediated, at least in part, through the contemporary inhibition of HO-1., (Copyright (c) 2006 S. Karger AG, Basel.)

Background: Urine bound tests, which have been developed for the early detection of urothelial cancer (UC), do not seem to match cytology in the detection of carcinoma in situ (CIS) as their sensitivity in the case of CIS is poor. ImmunoCyt/uCyt+ in CIS seems promising, but the number of analysed CIS is still small. The aim of the present study was to assess the value of this test in the detection and follow-up of carcinoma in situ of the urinary bladder., Patients and Methods: Thirty-five patients, with histologically verified CIS of the urinary bladder, were included in the study. At the first diagnosis, patients underwent cytology, cystoscopy, bioptical bladder mapping and ImmunoCyt/uCyt+. All patients underwent BCG instillation therapy. The patients were followed with cytology, ImmunoCyt/uCyt+, cystoscopy and bladder mapping after every BCG cycle and then every 3 months., Results: At the first CIS diagnosis, the sensitivity of cytology and ImmunoCyt/uCyt+ was 100%. At the first control after therapy, cytology detected 81.8% of recurrences and ImmunoCyt/uCyt+ detected 90.9%. At the second control, both tests each detected 50% of recurrences. At every control, the combination of both the tests together gave a sensitivity of 100%. The specificity of cytology after therapy improved from 88.2% at the first control up to 100% at the third control. The specificity of ImmunoCyt/uCyt+ after BCG initially decreased from 70.6% to 55.5% and finally increased to 88.9%., Conclusion: ImmunoCyt/uCyt+ is as sensitive as cytology in the first diagnosis of CIS. In the follow-up, even if it is less sensitive, its combination with cytology leads to detection of 100% of the recurrences. Despite decreasing specificity after therapy, the value remains acceptable and increases during maintenance therapy. The ImmunoCyt/uCyt+ test could play an important role in controlling the response of patients to instillation therapies or in the modification of their application schedules.

Objective: Morbidity and postoperative pain after extraperitoneal (E-LRPE) and transperitoneal (T-LRPE) laparoscopic radical prostatectomy was compared to open extraperitoneal radical prostatectomy (O-RPE)., Material and Methods: Between January 2002 and October 2003, we evaluated 41 E-LRPE, 39 T-LRPE and 41 O-RPE prospectively. All operations were performed as standard procedures by the same group of surgeons and perioperative results and complications were evaluated. Pain management was performed with tramadol 50-100 mg on demand, and no other form of anaesthesia was given. Postoperative pain was assessed daily in all patients quantifying analgesic requirement and evaluation of Visual Analogue Scale (VAS). All patients had at least a 12 month follow-up., Results: Mean age, prostate volume, PSA and Gleason score were comparable between all three groups (p>0.05). Mean blood loss was lower with laparoscopy (189+/-140 and 290+/-254 ml), as compared to 385+/-410 ml for O-RPE (p=0.002). However, mean operating times were significantly longer in L-TRPE (279+/-70 min) as compared to E-LRPE (217+/-51 min) and O-RPE (195+/-72 min) (p<0.001), but E-LRPE and O-RPE showed no statistical difference (p=0.1143). Average VAS score on the 1st and 5th postoperative day for E-LRPE versus T-LRPE versus O-RPE was 4.9+/-1.0 versus 7.8+/-1.5 versus 5.8+/-1.9 and 1.6+/-0.9 versus 2.3+/-1.2 versus 2.3+/-0.9 respectively, which was significant lower (p=0.02) between E-LRPE versus T-LRPE (p<0.001) and O-RPE (p=0.008), but equal (p=0.655) between T-LRPE and O-RPE since postoperative day 3. Mean tramadol analgesic consumption within the first postoperative week was 290 versus 490 versus 300 mg respectively, which was statistical different between E-LRPE and T-LRPE (p<0.001), O-RPE and T-LRPE (p<0.001), but not between E-LRPE and O-RPE (p=0.550). Statistical analysis revealed a strong correlation of urinary leakage with increased postoperative pain (p=0.029) in all groups, especially for T-LRPE (p=0.007). Likewise, increased operating times (>240 min) were associated with increased post-operative pain (p=0.049). Full continence defined as no pads at one year was achieved in 36/41 (88%, E-LRPE) versus 33/39 (85%, T-LRPE) versus 33/41 (81%, O-RPE), respectively (p=0.2)., Conclusion: E-LRPE resulted in a significant subjective (VAS Score, p<0.001) and objective (analgetic consumption, p<0.001) pain reduction compared to T-LRPE, but only in VAS Score compared to O-RPE (p=0.008). Analgetic consumption during first postoperative week was equal in E-LRPE (290 mg) and O-RPE (300 mg) (p=0.550). Shorter operating times, lower urinary leakage rates, lower stricture rates and lower blood loss in E-LRPE compared to T-LRPE are mainly explained due to the long learning curve in LRPE, which we did not overcome yet, and not due to the approach (extraperitoneal versus transperitoneal).

Objectives: To evaluate the bladder preservation strategy in invasive bladder cancer particularly relapse, progression and complications., Materials and Methods: From January 2000 to May 2004 a total of 24 patients (mean age of 81 years; range 68-92) with muscle invasive bladder cancer who had refused or were not eligible for cystectomy were followed up for a period of up to four years., Results: 24 (21 M/3 F) patients were followed up for a mean time of 680 (182-1253) days. All patients complained of frequency, urgency and severe nocturia. The second most frequent complication was bleeding which required a salvage cystectomy in 7 cases. Other major complications were intestinal occlusion in three cases, an enterovesical fistula, brain metastasis requiring neurosurgical intervention and radiation therapy of the brain, bone metastasis in the cervical spinal column and chronic renal failure. The mean re-admission rate was 8 per patient and the mean time spent at the hospital was 109 (range 13-253) days., Conclusion: In our series the bladder preserving strategy does not confirm the optimistic results of other authors. The complications forced us to carry out a salvage cystectomy in nearly half of the cases. The other half of the patients complained of other severe complications reducing the quality of life of the remaining life span.

Unlabelled: The tubularized-incised plate urethroplasty has traditionally been used in children for repairing hypospadias. As shown here, it can also be used successfully in adults, with very good results. The rate of wound healing, infection and complications is the same as in children, as are the cosmetic and functional outcomes., Objectives: To evaluate the outcome of uretero-ureterocutaneostomy (UUC) wrapped by omentum for palliative cystectomy in symptomatic elderly high-risk patients with high-stage bladder cancer., Patients and Methods: The study included 15 patients (14 men and one woman, aged 72-87 years, American Society of Anesthesiology score 3) with symptomatic recurrent bleeding bladder cancer (T2/T3) who were treated with palliative cystectomy. UUC was performed by mobilizing the right pre-vesical divided ureter up to the pelvi-ureteric junction and a high retroperitoneal crossover to the divided left ureter. A stoma was created with a circular 2-cm skin excision and resecting the fatty subcutaneous tissue. Wrapped by the omentum, both well-vascularized ureteric stumps were pulled through a cross-like fascia incision up to skin level. Spatulated and everted, the 'butterfly' flaps were fixed to the skin and underlying omentum. Soft splints were inserted for 21 days and a Karaya ring placed., Results: The postoperative course and stoma healing was normal in 14 of the 15 patients; the sigmoid was resected because of sigmoid diverticulitis in one. The median (range) follow-up was 15 (6-24) months. There was pyelonephritis in one patient, and the dilatation of the upper tract (grade 3) in two returned to grade 2, with new asymptomatic grade 1 dilatation in one other. All patients were without stents and stoma care was provided at home., Conclusions: This modified UUC by omental wrapping in 15 high-risk patients after palliative cystectomy was simple and safe, and their recovery was uneventful. To date the few patients with stomal obstruction were managed by J catheters, changed every 4-6 months.

The androgen receptor co-activator CREB (cAMP-response element binding protein)-binding protein (CBP) enhances androgen receptor activity after stimulation by androgenic hormones and androgen receptor antagonists. The aim of the present study was to investigate the regulation of CBP expression by steroid and peptide hormones in prostate cancer. For this purpose, LNCaP cells were treated with the synthetic androgen methyltrienolone (R1881), epidermal growth factor, insulin-like growth factor-I or interleukin-6 (IL-6). CBP protein and mRNA expression were studied by western blotting and real-time PCR, respectively. CBP expression was also investigated in tissue specimens obtained from 26 patients with therapy-resistant carcinoma of the prostate. In LNCaP cells, CBP protein was down-regulated by R1881 or IL-6. The non-steroidal anti-androgen bicalutamide antagonized the effects of R1881 and the Janus kinase inhibitor AG 490 reversed the effects of IL-6. In contrast, neither R1881 nor IL-6 caused any effect on CBP expression in the PC-3 cell line. In LNCaP cells, the inhibition of CBP expression by R1881 or IL-6 was also observed at the mRNA level. CBP protein was detected in all 26 specimens by immunohistochemistry. The results suggest that up-regulation of CBP during androgen ablation may be relevant to the failure of endocrine therapy in patients with prostate carcinoma.

Objectives: To assess the influence of intravesical instillation of epirubicin or bacille Calmette-Guérin (BCG) in patients with bladder cancer on the clinical performance of the uCyt+ test, which traces the three monoclonal antibodies M344, LDQ 10, and 19A211 in urothelial cells., Methods: A total of 267 patients with a mean age of 70.5 years (range 35 to 87) were included in this prospective study. All patients were being followed up after complete transurethral resection of superficial urothelial cancer. All patients received a single instillation of 80 mg epirubicin within 24 hours of transurethral resection and 163 underwent subsequent cycles of chemotherapy with epirubicin or immunotherapy with BCG. This was because of multifocality, high-recurrence, or high-grade urothelial cancer. At the next control, all patients underwent urinary cytology, with the uCyt+ test performed on liquid-based cytology (ThinPrep), subsequent cystoscopy, and evaluation of any suspicious lesion by biopsy. Patients who underwent intravesical BCG therapy underwent random bladder cold biopsy after every instillation series., Results: Of the 267 patients, 8 could not be evaluated by uCyt+ because of insufficient cells. Of the remaining 259 patients under assessment, 86 had proven urothelial cancer. In the 101 patients under assessment with only a single intravesical instillation of epirubicin (group 1), the overall sensitivity for cytology and the uCyt+ test was 44.7% and 76.6%, respectively. Cytology had a specificity of 90.7% and uCyt+ of 64.8%. The negative predictive value for cytology and uCyt+ was 65.3% and 76.1%, respectively. Of the 158 patients under evaluation who were treated with long-term intravesical therapy (group 2), the overall sensitivity and specificity for cytology and the uCyt+ test was 37.8% and 84.6% and 94.9% and 70.6%, respectively. The negative predictive value for cytology and the uCyt+ test was 83.1% and 93.3%, respectively. Statistical analysis showed no statistically significant difference between the overall sensitivity (P = 0.512) and specificity (P = 0.558) for the uCyt+ test in the two groups of patients., Conclusions: The sensitivity and specificity of the uCyt+ test are not significantly affected by intravesical long-term treatment with epirubicin or BCG.

Objectives: To perform a biologic characterization of the urothelial neoplasms of patients in the intermediate-risk group using multicolor-fluorescence in situ hybridization (FISH). A general consensus has not been reached with regard to the optimal therapy and follow-up of patients with urothelial neoplasms at intermediate risk of progression. On the basis of the chromosomal pattern, we developed a new follow-up algorithm for this group and report our preliminary results., Methods: Voided urine samples of 51 consecutive patients (mean age 72.2 years, range 52 to 93) under follow-up after complete transurethral resection of intermediate-risk urothelial carcinoma were evaluated by liquid-based cytology (ThinPrep) and uCyt+. From the residual material, Multicolor-FISH (Urovysion) was performed. Any cystoscopically suspicious lesion was biopsied or removed transurethrally. The mean follow-up time was 14.2 months (range 6 to 30, SD 5.5)., Results: Two of the 51 patients were not evaluated because of the presence of intense granulocytosis and insufficient urothelial cells. Of the 49 remaining patients, the results of the Multicolor-FISH analysis were negative (diploid chromosomal pattern) in 14; 20 patients showed the loss of one or both alleles of p16 and/or an aneuploidy of chromosome 3, and 15 patients had aneuploidy of chromosome 7 and/or 17. Of the 14 FISH-negative patients, 2 (14.3%) had histologically verified recurrence, and 3 (15.0%) of the 20 p16/3-positive patients had recurrence and 9 (60.0%) of the 15 7/17-positive patients had either recurrence or progression., Conclusions: Using the Urovysion test, it is possible to predict the biologic behavior of urothelial cancer with a significant impact on the follow-up of patients. The intermediate-risk group of urothelial cancer can be eliminated in the routine workup by classifying these patients according to their chromosomal pattern and defining those patients who can follow the low-risk scheme and those who must be monitored according to the guidelines for high-risk superficial lesions.

Objectives: To evaluate the feasibility and safety of transurethral en bloc resection of bladder tumors using a flat loop. Transurethral en bloc resection of bladder tumors facilitates pathologic evaluation., Methods: A total of 37 patients with papillary transitional cell carcinoma of the bladder underwent transurethral en bloc resection with the use of a flat loop electrode., Results: In 37 patients, 62 lesions were removed using a flat loop to perform the en bloc technique. This method is safe to perform in the case of papillary tumors with a diameter of up to 25 mm and that are found in specific areas of the bladder., Conclusions: It is both safe and feasible to perform en bloc resection with a flat loop electrode but attention must be paid to the limitations of this technique. Excellent pathologic evaluation of the grade and stage of the removed specimen is possible.

The aim of the study was to assess the value of liquid-based urinary cytology as a tool to perform uCyt+ and Multicolour-FISH in patients under follow-up after urothelial cancer. Therefore, standard cytology was compared to liquid-based cytology with the addition of the uCyt+ test, which traces the three monoclonal antibodies M344, LDQ10 and 19A211 in exfoliated urothelial cells; and Multicolour-FISH (including centromere-specific probes for chromosomes 3, 7, 17 and a locus-specific probe for 9p21/p16) performed on thin-layer specimens. UCyt+ showed an overall sensitivity of 86.2% and cytology of 45.0%. Overall sensitivity of both the tests combined was 90%. Sensitivity of Multicolour-FISH was 96.4%. All conventional cytology diagnoses were confirmed by liquid-based cytology. Liquid-based cytology is a valid tool for the performance of adjunctive analyses, such as uCyt+ and Multicolour-FISH, on residual cellular material.

Introduction: Laparoscopic 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., Patients and Methods: Between 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., Results: In 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., Conclusion: Improved 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.

Objectives: To report on our 2-year experience in teaching transurethral resection (TUR) of bladder tumors to five trainees. We analyzed their problems, as well as those of the teachers, and present our solutions., Methods: Between April 2000 and March 2002, five residents and three members of the staff took part in a training program to teach TUR of the bladder. From a total of 692 patients with bladder tumors admitted for treatment to our department, 417 were selected for the study. These 417 had papillary tumors of small to medium size (maximum 25 mm in diameter). The mean patient age was 61 years (range 32 to 92) for men (n = 322; 77%) and 68.4 years (range 48 to 91) for women (n = 95; 33%)., Results: A total of 417 teaching TURs were performed during a 24-month period. A total of 65 complications (16%) occurred and were analyzed from the database. The most common complication was postoperative bleeding, occurring in 33 cases (8%), followed by extraperitoneal perforation, which occurred in 16 cases (4%)., Conclusions: Despite careful patient selection and the use of video-assisted equipment and permanent supervision by an experienced resectionist, a significant number of complications occurred. The question: "How to teach the teacher to teach TUR of the bladder?" remains open.

Objective: The aim of this retrospective study was to evaluate treatment protocols and results of upper tract stone treatment in patients with clotting disorders., Methods: In a 6-year period, 6,827 stone interventions (ESWL or endourologic procedures) were performed in 5,739 patients. Thirty-five (0.61%) patients suffered from a variety of systemic clotting disorders or were anti-coagulated. Clotting disorders were corrected by specific therapy prior to any intervention. A total of 76 interventions were performed consisting of ESWL, ureteroscopy (URS), percutaneous nephrolithotomy (PNL), ureteric stenting or percutaneous nephrostomy., Results: All patients became stone-free within 3 months or had clinically insignificant residual fragments. Severe complications were observed in 10/76 (13.1%) interventions. ESWL was successful in 88.9% (16/18) of patients, but associated with a 33.3% (6/18) complication rate; 27.8% (5/18) of patients required auxiliary procedures. URS and PNL were successful in all cases and complications occurred in 0% (0/7) and 33% (1/3) of patients, respectively. Time to complete stone clearance after ESWL was 32.0+/-49.3 days compared with a mean of 19.4+/-28.6 days in a non-coagulopathy control group; no difference was observed for endourologic procedures. Average costs of treatment in patients undergoing ureteroscopy was higher in patients with coagulopathy (4,611 versus 2,342); however, the difference was less pronounced compared with ESWL (6,070 versus 1,731)., Conclusion: Patients with coagulopathy have a higher rate of complications despite apparently normal clotting parameters during treatment and hospitalisation was prolonged. The efficacy of ESWL was lower in patients with coagulopathy and we currently favour endoscopic procedures for stone removal in this patient group.

Objectives: To test the clinical value and role of uCyt+ as a noninvasive tool for the detection and surveillance of urothelial carcinoma., Methods: Included in this prospective study were 235 patients (mean age 71.5 years, range 32 to 86). Of these, 98 patients had signs and symptoms suggestive of bladder cancer and 137 patients were being followed up after complete transurethral resection of superficial urothelial cancer (UC). All patients underwent urinary cytology and the uCyt+ test performed on ThinPrep (thin layer). All underwent subsequent cystoscopy and evaluation of any suspicious lesion by biopsy., Results: A total of 102 patients had histologically proven UC. In the group of patients with signs and symptoms suspicious of UC, the sensitivity of cytology increased from 5% for G1 to 84.6% for G3 tumors; for uCyt+, it was 85% for G1, 100% for G2, and 92.3% for G3 tumors. Combining cytology and uCyt+, the sensitivity was 85% for G1 and 100% for G2 and G3. In the group of follow-up patients, the sensitivity of cytology increased from 4.3% for G1 to 94.4% for G3 tumors; for uCyt+, it was 78.2% for G1, 70% for G2, and 94.4% for G3 tumors. Combining both tests, the sensitivity was 78.2% for G1, 90% for G2, and 100% for G3., Conclusions: The uCyt+ is a valid test in the detection of UC of all grades and stages. It improves the sensitivity of cytology in low-grade tumors. The two tests combined may be a highly sensitive method to detect UC early in detection and surveillance.

Objectives: Allograft stones are an uncommon clinical problem and management is mainly based on anecdotal experience, rather than analysis of larger series., Methods: In an 8-year period, 19 patients were treated for 19 renal and 3 ureteral stones. In 9 patients, stones were transplanted and 10 formed de novo stones within a mean of 28 months (range 13 to 48) after transplantation. In 4 patients, stones were removed during transplantation. Seven patients were treated with extracorporeal shock wave lithotripsy (ESWL), 3 patients had stones removed percutaneously, 1 by antegrade ureteroscopy, and 1 at the time of ureteral reimplantation. Three patients passed stones spontaneously., Results: In 3 of 4 patients with stones detected before transplantation, the procedure was completed successfully after endoscopic stone removal. Three of 5 patients with transplanted stones required emergency nephrostomy; 1 patient had permanent renal impairment. Three (42.9%) of 7 patients treated with ESWL needed transient nephrostomy; ultimately, all became stone free within a mean 15 days (range 10 to 40). Endoscopic stone removal always resulted in complete clearance without renal impairment. All patients were stone free during a follow-up of 29 months (range 13 to 48)., Conclusions: Nine (47%) of 19 stones were actually transplanted. Therefore, intraoperative screening by ultrasonography with subsequent endoscopic removal is advisable. Small stones (4 mm or less) may be closely followed up, because they can pass spontaneously. ESWL is the treatment of choice for caliceal stones sized 5 to 15 mm. However, for stones greater than 15 mm or for ureteral stones, antegrade endoscopic procedures seem to be more favorable.

Objectives: To 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., Methods: Thirty-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., Results: Sixteen 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., Conclusions: The 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.

Objectives: To compare the diagnostic value of two rapid tests, the bladder tumor antigen (BTA stat) test and the newly developed urinary bladder cancer (UBC) Rapid test, in patients having symptoms suggestive of urothelial cell carcinoma (UCC) and patients being followed up after transurethral resection., Methods: One hundred eighty patients with a mean age of 65.8 years (range 22 to 92) were included in the present study. The tests were performed on voided urine samples. Fifty-seven patients had symptoms suggestive of UCC and 123 patients were being followed up after complete transurethral resection of UCC. The voided urine was evaluated by the BTA stat and UBC Rapid test, which detects cytokeratins 8 and 18. All patients underwent subsequent cystoscopic evaluation and biopsy of any suspicious lesion., Results: In 53 patients with histologically proved UCC, the BTA stat had a sensitivity of 52.8% and the UBC Rapid test of 66%. According to the histologic stage, the sensitivity of the BTA stat was 42.8% in pTa tumors, 61.5% in pT1, and 70% in pT2 or higher tumors. The sensitivity of the UBC test was 60.7% in pTa, 69. 2% in pT1, and 80% in pT2 or higher tumors. For histologic grades 1 to 3, the sensitivity was 38.8%, 52.6%, and 68.7% for the BTA stat and 44.4%, 78.9%, and 75% for the UBC Rapid test, respectively. The specificity was 70% and 90% for the BTA stat and UBC Rapid test, respectively., Conclusions: The UBC Rapid test was superior to the BTA stat in both sensitivity and specificity. Both assays are simple office procedures and require no special knowledge. However, they cannot replace, but only lower, the number of cystoscopies during the follow-up of patients with previous UCC of the bladder.

Objectives: To compare the diagnostic value of two enzyme-linked immunosorbent assay (ELISA) tests, the nuclear matrix protein 22 (NMP22) test and a newly developed urinary bladder cancer (UBC) test, in patients having symptoms suggestive of urothelial cell carcinoma (UCC) and patients under follow-up after transurethral resection (TUR)., Methods: Two hundred forty patients with a mean age of 65.8 years (range 22 to 92) were included in this retrospective study. The tests were performed on previously frozen urine samples. Eighty-one patients had symptoms suggestive of bladder cancer and 159 patients were being followed up after complete TUR of UCC. Voided urine was evaluated by the NMP22 test and the monoclonal UBC-ELISA test, which traces cytokeratins 8 and 18. All patients underwent subsequent cystoscopy and biopsy evaluation of any suspicious lesion. The cutoff levels for bladder cancer positivity were 10 U/mL for the NMP22 test and 12 microg/L for the UBC test., Results: In the 54 patients with histologically proved UCC, the NMP22 test had a sensitivity of 55.5% and the UBC test a sensitivity of 64.8%. According to the histologic stages, the sensitivity of NMP22 was 51.7% in pTa tumors, 46.1% in pT1, and 70% in pT2 or higher tumors; the sensitivity of UBC was 62.1% in pTa, 53.8% in pT1, and 80% in pT2 or higher tumors. For histologic grades 1 to 3, the sensitivity was 50%, 50%, and 68.7% for NMP22 and 66.6%, 60%, and 68.7% for UBC, respectively. The specificity was 79% and 92% for NMP22 and UBC, respectively., Conclusions: The monoclonal UBC-ELISA test is superior to the NMP22 test in both sensitivity and specificity. Nevertheless, neither test can replace cystoscopy.

Purpose: The 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., Materials and Methods: Participating 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., Results: Histologically 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., Conclusions: Immunocyt 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.