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Background: To report the long-term results of adjuvant treatment with one cycle of modified bleomycin, etoposide, and cisplatin (BEP) in patients with clinical stage I (CS I) nonseminomatous germ-cell tumors (NSGCT) at high risk of relapse., Patients and Methods: In a single-arm, phase II clinical trial, 40 patients with CS I NSGCT with vascular invasion and/or >50% embryonal cell carcinoma in the orchiectomy specimen received one cycle of adjuvant BEP (20 mg/m(2) bleomycin as a continuous infusion over 24 h, 120 mg/m(2) etoposide and 40 mg/m(2) cisplatin each on days 1-3). Primary end point was the relapse rate., Results: Median follow-up was 186 months. One patient (2.5%) had a pulmonary relapse 13 months after one BEP and died after three additional cycles of BEP chemotherapy. Three patients (7.5%) presented with a contralateral metachronous testicular tumor, and three (7.5%) developed a secondary malignancy. Three patients (7.5%) reported intermittent tinnitus and one had grade 2 peripheral polyneuropathy (2.5%)., Conclusions: Adjuvant chemotherapy with one cycle of modified-BEP is a feasible and safe treatment of patients with CS I NSGCT at high risk of relapse. In these patients, it appears to be an alternative to two cycles of BEP and to have a lower relapse rate than retroperitoneal lymph node dissection. If confirmed by other centers, 1 cycle of adjuvant BEP chemotherapy should become a first-line treatment option for this group of patients., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Central nervous system involvement is a rare and serious complication of Behçet's disease (BD). Herein, we describe a patient with an atypical central lesion, who experienced progressive hypesthesia of the right arm and sensory loss of the trigeminal nerve together with intense headache. A repeated biopsy was necessary to conclusively establish the diagnosis of BD. Therapy with infusions of infliximab led to a remarkable full remission. TNFα-blocking therapy was successfully replaced by azathioprine. The present well-illustrated case demonstrates the difficulty of establishing the diagnosis of BD with central nervous system involvement, the dramatic benefit of short given TNF-α-blocking agent, and the long-term remission with azathioprin.

Purpose: Vocational rehabilitation (VR) programs aim to facilitate work participation. However, there is no universal framework to describe the functioning of individuals who participate in VR. The objective of this paper is to report on the Core Set for VR based on the International Classification of Functioning, Disability and Health (ICF) by the World Health Organization (WHO)., Methods: A formal decision-making and consensus-based process was conducted based on the evidence from four preparatory studies. Twenty-three international experts chosen by WHO Region and expertise in VR attended the consensus conference., Results: Ninety ICF categories were included in the comprehensive Core Set (activities and participation = 40, environmental factors = 33, body functions = 17), while the brief Core Set included 13 second-level categories (activities and participation = 6, environmental factors = 4, body functions = 3)., Conclusions: The expert opinion and evidence-based Core Set could serve as an international standard for what to measure and report concerning functioning of individuals in VR. The Core Set could also provide a common language among clinicians, researchers, insurers, and policymakers in the implementation of successful VR. Further testing and validation studies are encouraged.

Background: Polymer as carrier substance for drugeluting stents (DES) has been accused of inducing inflammation and hypersensitivity reactions leading to restenosis and stent thrombosis. Thus, a new paclitaxel-eluting stent (PES) with aminoparylene as a carrier substance is tested in the present study., Methods: In 10 pigs, stents were implanted in the epicardial coronary arteries: 1) bare-metal stents (BMS, control stent); 2) cobalt-chromium stents (CCS); and 3) PES. Stent length was 15 mm, and diameter was 3 mm. The animals were restudied after 6 weeks. Quantitative coronary angiography was performed at baseline and follow up. Minimum luminal diameter (MLD) and late loss were calculated in all animals. Histologic vessel lumen, intimal proliferation and restenosis were determined by morphometry. Disruption of the lamina elastica interna (LEI) and inflammatory reactions were assessed by histology., Results: The MLD at baseline was 2.83 +/- 0.28 mm, and at follow up it was 2.29 +/- 0.44 (p < 0.05; n = 30). Late loss and angiographic restenosis were smallest in the CCS and largest in the PES (ns). Neointimal proliferation was similar for all 3 stents, ranging between 1.38 and 1.64 mm(2) (ns). There was a significant correlation between disruption of the LEI and inflammatory reactions., Conclusions: PTs with aminoparylene as a carrier substance show similar late loss and angiographic restenosis to that of BM and CCS. The incidence of inflammatory reactions (35% of all histologic sections) is similar in all stents, but highest in PES. The mechanism of this reaction is unclear, but may be either due to the drug itself, the disruption of the LEI or to a hypersensitivity reaction.

Purpose: In male patients with ileal bladder substitute we ascertained the likelihood of spontaneous voiding failure, the corrective procedures required and the eventual outcomes., Materials and Methods: Following cystectomy and ileal bladder substitution for urothelial cancer between April 1985 and September 2002 male patients were identified and analyzed from the prospective departmental database. Four patients underwent ileum conduit conversion following urethral recurrence or pouch necrosis and were excluded from study. Funnel-shaped outlets were avoided during bladder substitute surgery after the first 4 patients with this configuration experienced voiding failure and required corrective procedures. Only patients with a minimum 5-year followup were assessed for voiding failure, corrective procedures and final outcomes., Results: Of 354 patients with a median age of 65 years (range 36 to 84) treated with bladder substitute 180 (51%) were alive at 5 years. All 180 of these patients spontaneously voided within 3 months of surgery. During this 5-year observation period 22 (12%) patients experienced voiding problems requiring de-obstructive procedures. Following intervention 177 (98%) patients were spontaneously voiding by 5 years. Of 237 patients 77 (32%) were alive at 10 years. Of these 77 patients followed for another 5 years 10 (13%) had similar voiding problems requiring de-obstructive procedures. Subsequently 74 (96%) were voiding spontaneously by 10 years., Conclusions: Patients often fail to void spontaneously after ileal bladder substitution. However, if a funnel-shaped outlet is avoided and de-obstructive surgery is appropriately implemented, excellent long-term results are seen with spontaneous voiding and clean intermittent catheterization can be avoided.

Aims: To analyse tumour characteristics and the prognostic significance of prostatic cancers with extranodal extension of lymph node metastases (ENE) in 102 node-positive, hormone treatment-naive patients undergoing radical prostatectomy and extended lymphadenectomy., Methods and Results: The median number of nodes examined per patient was 21 (range 9-68), and the median follow-up time was 92 months (range 12-191). ENE was observed in 71 patients (70%). They had significantly more, larger and less differentiated nodal metastases, paralleled by significantly larger primary tumours at more advanced stages and with higher Gleason scores than patients without ENE. ENE defined a subgroup with significantly decreased biochemical recurrence-free (P = 0.038) and overall survival (P = 0.037). In multivariate analyses the diameter of the largest metastasis and Gleason score of the primary tumour were independent predictors of survival., Conclusions: ENE in prostatic cancer is an indicator lesion for advanced/aggressive tumours with poor outcome. However, the strong correlation with larger metastases suggests that ENE may result from their size, which was the only independent risk factor in the metastasizing component. Consequently, histopathological reports should specify the true indicator of poor survival in the lymphadenectomy specimens, which is the size of the largest metastasis in each patient.

Background and Purpose: Anti-inflammatory drugs are used in the treatment of acute renal colic. The aim of this study was to investigate the effects of selective COX-2 inhibitors and the non-selective COX inhibitor diclofenac on contractility of human and porcine ureters in vitro and in vivo, respectively. COX-1 and COX-2 receptors were identified in human ureter and kidney., Experimental Approach: Human ureter samples were used alongside an in vivo pig model with or without partial ureteral obstruction. COX-1 and COX-2 receptors were located in human ureters by immunohistochemistry., Key Results: Diclofenac and valdecoxib significantly decreased the amplitude of electrically-stimulated contractions in human ureters in vitro, the maximal effect (Vmax) being 120 and 14%, respectively. Valdecoxib was more potent in proximal specimens of human ureter (EC50=7.3 x 10(-11) M) than in distal specimens (EC50=7.4 x 10(-10) M), and the Vmax was more marked in distal specimens (22.5%) than in proximal specimens (8.0%) in vitro. In the in vivo pig model, parecoxib, when compared to the effect of its solvent, significantly decreased the maximal amplitude of contractions (Amax) in non-obstructed ureters but not in obstructed ureters. Diclofenac had no effect on spontaneous contractions of porcine ureter in vivo. COX-1 and COX-2 receptors were found to be expressed in proximal and distal human ureter and in tubulus epithelia of the kidney., Conclusions and Implications: Selective COX-2 inhibitors decrease the contractility of non-obstructed, but not obstructed, ureters of the pig in vivo, but have a minimal effect on electrically-induced contractions of human ureters in vitro.

Skeletal tuberculosis is now uncommon in developed countries. In immunocompromised patients--particularly in the HIV-infected--who present with subacute or chronic joint pain refractory to conventional treatment, osteoarticular tuberculosis should still be included in the differential diagnosis. We report on a lethal case of disseminated tuberculosis in an HIV-infected subject. Dissemination may have resulted from the implantation of an articular prosthesis in a knee joint with unsuspected osteoarticular tuberculosis. The diagnosis was established months later when the patient presented with far-advanced tuberculous meningitis, miliary tuberculosis of the lungs, femoral osteomyelitis and extended cold abscesses along the femoral shaft. Failure to respond to a conventional four-drug regimen is explained by the resistance pattern of his multi-drug resistant strain of Mycobacterium tuberculosis, which was only reported after the patient's death. This case illustrates the diagnostic challenges of osteoarticular tuberculosis and the consequences of a diagnostic delay in an HIV-infected individual.

Urinary diversion after cystectomy have evolved from simple diversion and protection of the upper tracts to functional and anatomic restoration as close as possible to the natural preoperative state. Over the past 15 years, orthotopic reconstruction has evolved from "experimental surgery" to the "preferred method of urinary diversion" in both sexes. Urologist that perform this technique should have an appropriate experience with pelvic surgery and be able to perform a nerve sparing radical cystectomy. Nevertheless, the postoperative management of these patients is more important than the surgical construction if good longterm results are to be achieved. For this reason, a great knowledge about the neobladder's physiology, postoperative complications and their treatment are needed. We review the most important aspects in the postoperative management of patients with ileal neobladder. We also resume the long term outcomes concerning to continence, sexual function, renal impairment, oncologic safety and quality of life.

Case studies, based on actual patients' situations, provide a method of clinical decision making to foster critical thinking in nurses. This paper describes the method and process of group case studies applied in continuous education settings. This method bases on Balints' case supervision and was further developed and combined with the nursing diagnostic process. A case study contains different phases: Pre-phase, selection phase, case delineation and case work. The case provider narratively tells the situation of a patient. This allows the group to analyze and cluster signs and symptoms, to state nursing diagnoses and to derive nursing interventions. Results of the case study are validated by applying the theoretical background and critical appraisal of the case provider. Learning effects of the case studies were evaluated by means of qualitative questionnaires and analyzed according to Mayring. Findings revealed the following categories: a) Patients' problems are perceived in a patient centred way, accurate nursing diagnoses are stated and effective nursing interventions implemented. b) Professional nursing tasks are more purposefully perceived and named more precise. c) Professional nursing relationship, communication and respectful behaviour with patients were perceived in differentiated ways. The theoretical framework is described in the paper "Clinical decision making and critical thinking in the nursing diagnostic process". (Müller-Staub, 2006).

Purpose: Integration of high-risk papillomavirus DNA has been considered an important step in oncogenic progression to cervical carcinoma. Disruption of the human papillomavirus (HPV) genome within the E2 gene is frequently a consequence. This study investigated the influence of episomal viral DNA on outcome in patients with advanced cervical cancer treated with primary radiotherapy., Methods and Materials: Paraffin-embedded biopsies of 82 women with locally advanced cervical cancer could be analyzed for HPV infection by multiplex polymerase chain reaction (PCR) by use of SPF1/2 primers. E2-gene intactness of HPV-16-positive samples was analyzed in 3 separate amplification reactions by use of the E2A, E2B, E2C primers. Statistical analyses (Kaplan-Meier method; log-rank test) were performed for overall survival (OS), disease-free survival (DFS), local progression-free survival (LPFS), and distant metastases-free survival (DMFS)., Results: Sixty-one (75%) of 82 carcinomas were HPV positive, 44 of them for HPV-16 (72%). Seventeen of the 44 HPV-16-positive tumors (39%) had an intact E2 gene. Patients with a HPV-16-positive tumor and an intact E2 gene showed a trend for a better DFS (58% vs. 38%, p = 0.06) compared with those with a disrupted E2 gene. A nonsignificant difference occurred regarding OS (87% vs. 66%, p = 0.16) and DMFS (57% vs. 48%, p = 0.15)., Conclusion: E2-gene status may be a promising new target, but more studies are required to elucidate the effect of the viral E2 gene on outcome after radiotherapy in HPV-positive tumors.

Background and Purpose: Little is known about the incidence and treatment of ureteropelvic junction (UPJ) obstruction of renal grafts. We report on three cases treated by endopyelotomy., Patients and Methods: Graft function declined in three patients 98, 135, and 144 days after kidney transplantation. Acute rejection was excluded by renal biopsy. Ultrasonography revealed a dilated collecting system, and a percutaneous nephrostomy tube was placed. An antegrade nephrostogram showed UPJ obstruction. Percutaneous antegrade endopyelotomy was performed with the cold-knife technique, and the area was stented for 6 weeks using a 14F/8.2F Smith endopyelotomy stent., Results: No intraoperative or postoperative complications occurred. The endopyelotomies were successful, and the creatinine clearances returned to normal., Conclusion: Antegrade endopyelotomy in patients with UPJ obstruction of a renal graft is feasible and effective. Normal kidney function was restored after correction of the obstruction.

Open radical prostatectomy represents one possible therapeutic option for treating patients with clinically localized prostate cancer Patient selection and the surgical management have undergone important changes during the last years, resulting in lower morbidity and probably in a better tumor control due to a better standardisation of the surgical technique. Long-term functional outcome regarding continence and potency are of increasing importance and influence mainly the quality of life in these patients. Open radical retropubic prostatectomy remains the gold standard in patients with localized prostate cancer, due to its low morbidity and excellent oncological and functional results. The value of laparoscopic and robotic radical prostatectomy is still discussed controversially. Due to the relative high morbidity during the so-called learning curve and the lack of long-term oncological and functional results, these techniques seem to show less favourable results.

Benign Prostatic Hyperplasia is a common entity among the aging male population. Its prevalence is increasing with age and is around 80% in the over 80-years old. The androgen-estrogen ratio changes in favor of the estrogens, which leads to a growth of prostatic tissue, presenting histologically as hyperplasia. BPH can cause irritative or obstructive symptoms or both. Nowadays we speak of bladder storage or bladder voiding symptoms, summarised as LUTS (Lower Urinary Tract Symptoms). LUTS has a structural and a functional component, the structural being caused by the size of the adenoma itself the functional depending on the muscle tone of the bladder neck and the prostatic urethra. To investigate LUTS, we use validated symptom scores, sonography for residual urine and eventually a urodynamic evaluation. There are 3 grades of BPH. The indication for an interventional therapy is relative in BPH II, and absolute in BPH III. Prior to treatment, other diseases mimicking the same symptoms, have to be ruled out and adequatly treated. Electro-resection of the prostate (TUR-P) remains the standard therapy and the benchmark any new technology has to compete with. TUR-P has good short- and longterm results, but can be associated with a considerable perioperative morbidity, and the learning curve for the operator is long. The most promising of the newer techniques is the Holmium-Laser-Enucleation of the prostate (Laser-TUR-P), showing at least identical short- and median-term results, but a lower perioperative morbidity than TUR-P For several minimally-invasive techniques, indications are limited. TUMT TUNA, WIT and laser-coagulation all produce a coagulation necrosis of the prostatic tissue by thermic damage with secondary tissue shrinking. Urodynamic results however, are not comparable to TUR-P or Laser-TUR-P, and significantly more secondary interventions within 2 to 5 years are required. Minimal-invasive techniques present a favorable alternative for younger patients without complications of BPH, and for older patients with relevant comorbidities, and can usually be performed under local anaesthesia. The morbidity is low and further therapies remain possible later, if necessary.

A round table meeting was held to discuss the role of hormonal therapy in localised prostate cancer. The findings of the group were that immediate hormonal therapy does not provide an overall survival advantage in localised and locally advanced prostate cancer. Bicalutamide can prolong disease free survival in patients with locally advanced prostate cancer, however it is important to underline that at this time it has not been shown to influence disease specific nor overall survival. It remains also unproven that early treatment is superior to treatment at progression. However, a trend towards decreased survival with bicalutamide was observed in low risk patients such as those with localised disease. In patients receiving bicalutamide, there were increased cardiovascular side-effects, in addition to the high incidence of gynaecomastia. Early hormonal therapy has to be balanced against such side-effects and the inevitable appearance of hormone refractory disease in patients who progress after hormonal therapy. Consequently, patients with localised, low risk disease are not considered appropriate candidates for hormonal therapy used either as mono-therapy or in the adjuvant setting.

In clinically Localized prostate cancers, the interest of pelvic Lymphadenectomy is debated. Nevertheless, this intervention provides important information on disease prognosis (number of positive lymph nodes, tumoural volume, and extracapsular perforation of the affected ganglions); information that previously no other technique could provide. However, no consensus exists concerning patients who should benefit from pelvic Lymphadenectomy and on the extent of this intervention. For most surgeons, decision making regarding ganglion curage is based on nomograms. According to these nomograms, patients with a level of prostate specific antigen (PSA) <10 ng/mL and a Gleason score <7 have a very low risk for ganglionic metastases; this is the reason why the benefit of pelvic Lymphadenectomy remains controversial. Besides, most of these nomograms are based upon the results of standard Lymphadenectomy (iliac vein and obturator fossa) with, subsequently, a related risk of imprecision. In addition, potential therapeutic benefit may be expected from extended ganglion curage, despite the fact that this is not clearly documented yet, due to the benign course of the disease. In other tumoural diseases (stomach cancer, breast cancer, colorectal cancer, blade cancer), on the contrary, survival and stage identification depend on the number of removed ganglions, thus on the extent of Lymphadenectomy.

Lymph node dissection remains the only reliable method for exact staging to date. Extended lymphadenectomy including tissue along the external iliac vein, the obturator fossa, and along the internal iliac vessels should be performed in all patients undergoing radical prostatectomy. There is an increasing amount of data suggesting that removal of all diseased nodes, which contain minimal metastatic disease, may have a positive impact on disease-free and, perhaps, on overall survival. Due to the relatively benign course of the disease, longer follow-up periods are still necessary to make a definitive statement.

The most frequently encountered urologic emergencies in daily practice include obstructive pyelonephritis, acute scrotal pain, acute urinary retention, urinary lithiasis and priapism. This article gives an overview on the pathogenesis, clinical presentation, diagnostic assessment and treatment strategies for each of these emergencies.

Integrins are cell-surface receptors, which mediate cell-to-cell and cell-to-extracellular matrix adhesion. Besides playing an important role in tumour angiogenesis, beta3-integrin is also expressed in several types of epithelial cancer cells. It was the purpose of the present study to evaluate the prognostic value of beta3-integrin expression in patients with cervical cancer. Biopsies were taken from 82 patients with squamous cell or adenocarcinomas of the uterine cervix who had undergone external-beam radiotherapy with or without brachytherapy. These tissue samples were analysed immunohistochemically for the expression of beta3-integrin. The impact of immunoreactivity for beta3-integrin on survival end points was assessed by univariate and multivariate analyses, and its correlation with clinicopathological characteristics evaluated by crosstabulations. beta3-integrin was expressed in 61% (50 of 82) of the patients. Kaplan-Meier curves revealed local progression-free survival, distant metastasis-free survival and cause-specific survival to be significantly shorter (P-values according to the log-rank test: 0.002, 0.04 and 0.01, respectively) in patients with beta3-integrin expression. The prognostic impact of this parameter was even higher than for other well-known prognostic parameters and remained statistically significant in the multivariate analyses. beta3-integrin, which is expressed in the majority of patients with advanced cervical cancer, has a significant prognostic impact on outcome according to univariate and multivariate analyses.

Orthotopic ileal bladder substitution (Studer pouch) has gained much popularity during the last decade, offering the best form of urinary diversion in appropriately selected patients. The superiority of this procedure is well known, with a low complication and high success rate. In the present study the most important details in patient selection, surgical technique, perioperative management with short- and long-term postoperative follow-up are described. Adequate preoperative assessment results in a proper indication for surgery and appropriate patient selection. The cystectomy should be performed with atraumatic dissection and preservation of the urethral autonomic innervation and sphincter apparatus. The bladder substitute is constructed from a terminal ileal segment of proper length formed into a spherical shape. Implantation of the ureters into the reservoir should not be performed using an anti- reflux technique to avoid a high stricture rate. Anastomosis of the bladder substitute to the urethra must be flat and wide open, avoiding a funnel-shaped outlet. In the immediate postoperative period, careful monitoring is necessary to minimize metabolic complications of acidosis and salt loss. To achieve successful voiding rehabilitation, with complete reservoir emptying, good functional reservoir capacity and satisfactory continence, it is necessary to educate the patients as to the physiological functioning of the bladder substitute. Careful lifelong follow up is essential for the successful outcome. Respecting strict patient selection criteria and proper surgical technique are of utmost importance for the successful outcome of the procedure, but only if combined with regular follow-up.

Germ cell tumour is the most frequent malignant tumour type in young men with a 100% rise in the incidence every 20 years. Despite this, the high sensitivity of germ cell tumours to platinum-based chemotherapy, together with radiation and surgical measures, leads to the high cure rate of > or = 99% in early stages and 90%, 75-80% and 50% in advanced disease with 'good', 'intermediate' and 'poor' prognostic criteria (IGCCCG classification), respectively. The high cure rate in patients with limited metastatic disease allows the reduction of overall treatment load, and therefore less acute and long-term toxicity, e.g. organ sparing surgery for specific cases, reduced dose and treatment volume of irradiation or substitution of node dissection by surveillance or adjuvant chemotherapy according to the presence or absence of vascular invasion. Thus, different treatment options according to prognostic factors including histology, stage and patient factors and possibilities of the treating centre as well may be used to define the treatment strategy which is definitively chosen for an individual patient. However, this strategy of reduction of treatment load as well as the treatment itself require very high expertise of the treating physician with careful management and follow-up and thorough cooperation by the patient as well to maintain the high rate for cure. Treatment decisions must be based on the available evidence which has been the basis for this consensus guideline delivering a clear proposal for diagnostic and treatment measures in each stage of gonadal and extragonadal germ cell tumour and individual clinical situations. Since this guideline is based on the highest evidence level available today, a deviation from these proposals should be a rare and justified exception.

The surgical technique described here is not more complex than that of an ileal conduit but has significant advantages. The aboral end of an isolated portion of the distal ileum is formed into a low pressure, high capacity bladder substitute that combines Goodwin's 'cup-patch' technique and Couvelaire's ileo-urethral anastomosis. Although the neobladder is constructed from only about 40 cm of ileum, it achieves a capacity of 500 ml within a few weeks, simultaneously with rapid improvement of urinary incontinence. The procedure described is easy to perform and its long-term functional results have passed the test of time. Aside from the surgical technique per se, success with this method of bladder substitution is mainly ascribed to meticulous postoperative care and follow-up.

The aim of radical cystectomy with subsequent urinary diversion is to combine a safe oncological outcome with a satisfactory lower urinary tract function. Recent findings on the anatomy, physiology and nerve supply of the pelvis have resulted in a modified nerve-sparing cystectomy technique. A number of studies have shown that the oncological outcome is not compromised by such a technique; in particular the rate of local recurrences is not enhanced. Nerve-sparing cystectomy is of importance for the lower urinary tract function, including continence status after orthotopic bladder substitution and erectile function. Prerequisites for a nerve-sparing technique are a profound knowledge on the nerve supply of the pelvic organs and a subtle surgical technique. Recent surgical developments, for example in prostate and seminal vesicle sparing cystectomy techniques, indicate that it will be feasible to restore lower urinary tract and also sexual function after radical cystectomy and orthotopic bladder substitution.

Anaplastic seminomas account for 5-10% of all seminomas. Their metastatic pattern is similar to the classic form of seminoma. We report on an oligophrenic patient with seminoma pT1 who developed a metastasis to the corpus spongiosum and penile urethra, which was successfully treated by local external radiotherapy resulting in long-term tumor remission over a 4-year follow-up period.

Purpose: In the early stages of cervical cancer treated with surgery alone, hypoxia-inducible factor-1alpha (hif-1alpha) expression is prognostic for overall survival. Because hypoxia plays an important role in radiation resistance, we investigated hif-1alpha expression in cervical cancer treated with local radical radiotherapy (RT)., Methods and Materials: Between 1990 and 1998, 91 patients with squamous cell or adenocarcinoma of the uterine cervix were treated with external beam RT with and without brachytherapy. Biopsies from 78 patients were available for immunohistochemistry. The impact of the immunoreactivity of hif-1alpha in regard to survival end points was determined by univariate and multivariate analyses. Correlations with clinicopathologic characteristics were determined by cross-tabulations., Results: Hif-1alpha was expressed in 73 (94%) of 78 patients. It was closely linked to the pretreatment hemoglobin level (p = 0.04, r = -0.22, Spearman correlation test). The Kaplan-Meier curves showed a significantly shorter local progression-free survival (p = 0.04, log-rank) and overall survival (p = 0.01, log-rank) and a trend for shorter disease-free survival (p = 0.15) for patients with increased hif-1alpha expression. The multivariate analyses revealed hif-1alpha expression to be an independent factor for overall survival (p = 0.02)., Conclusion: Hif-1alpha is expressed in the vast majority of patients with advanced cervical cancer and had a prognostic significance. A weak but significant correlation was noted with pretreatment hemoglobin level.

Objective: To evaluate the prognostic significance of serially measured tissue polypeptide-specific antigen (TPS) levels in patients with metastatic prostatic carcinoma treated with intermittent maximal androgen blockade (MAB). To determine its value with respect to predicting response to treatment and time to clinical progression. Finally to compare TPS with prostate-specific antigen (PSA) measurements in terms of prognostic impact in patients with metastatic prostatic carcinoma., Methods and Patients: TPS and PSA measurements were performed before start of and monthly during intermittent MAB in 68 patients participating in EORTC protocol 30954. Both TPS and PSA were measured in serum. Fifty-six patients from eight centers were included in the final analysis because at least three TPS values were available. TPS and PSA values were correlated with clinical course of the disease. Median follow-up was 21.3 months. Three patient groups were defined on clinical grounds: (a) clinically progressive disease (n=18); (b) clinically stable disease (n=33); and (c) patients who did not reach a predefined nadir PSA value following 9 months of treatment (n=5)., Results: Pretreatment TPS was significantly higher in the clinically progressive patients than in the other patient groups (p=0.0041). When grouping patients according to their pretreatment TPS values (cut-off value of 100 U/l) the pretreatment TPS value (>100 U/l) proved to be a statistically significant prognostic factor with respect to time to progression: elevated TPS was associated with a 3.8 increased risk for progressive disease (p=0.0055). Pretreatment PSA (>100 ng/ml) was of no prognostic value for time to progression. In five patients increase of TPS coincided with or preceded clinical progression during treatment, whereas PSA remained normal., Conclusion: Additional value of pretreatment TPS measurements in metastatic prostate cancer patients is found in defining the patients with rapid clinical progression. Following MAB an increase in TPS signifies clinical progression even if PSA is found to remain normal.

According to the National Institutes of Health classification system, chronic non-bacterial prostatitis/chronic pelvic pain syndrome (CPPS) is subdivided into an inflammatory (category IIIa) and a non-inflammatory (category IIIb) form. The difference is based on the presence or absence of white blood cells in expressed prostatic secretions, urine after prostatic massage, or semen. This is the only criterion which allows a differentiation between the IIIa and IIIb forms. The symptoms, i.e. pain and urinary complaints of various degrees, are thought to be similar in both forms. These symptoms can be assessed with the Chronic Prostatitis Symptom Index (CPSI) and the International Prostate Symptom Score (IPSS), which are both available in a validated German translation. One hundred and six patients with CPPS were evaluated with CPSI and IPSS. Urinary symptoms troubled all patients. Men with category IIIa had significantly more urinary symptoms when compared to men with category IIIb. There was no difference between the two groups regarding pain and impact on the quality of life. Although pain is thought to be the hallmark of CPPS, the contribution of urinary troubles to the symptoms must not be underestimated.

Objective: To evaluate the perioperative gene-specific primed nested reverse transcription-polymerase chain reaction (RT-PCR) for prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) for staging patients undergoing radical prostatectomy and predicting biochemical recurrence., Patients and Methods: In 80 consecutive patients undergoing radical prostatectomy for prostate cancer, blood samples were drawn before, during and 1 and 7 days after removing the prostate. After buffy coat and mRNA extraction, gene-specific primed nested RT-PCR was performed for PSA, PSMA and glyceraldehyde-3-phosphate dehydrogenase mRNA, and Southern blot analysis of the PCR reaction., Results: The sensitivity of gene-specific RT-PCR to detect tumour cells was comparable with random primed RT-PCR. In the 80 patients the stage distribution was pT1 in two (2.5%), pT2 in 30 (37.5%) and > or = pT3 in 48 (60%); the nodal status was pN0 in 57 (71%), pN1 in 11 (14%) and pN2 in 12 (15%). The gene-specific RT-PCR reaction for PSA and PSMA was positive in no patients with pT1, 11 (37%) with pT2 and 23 (48%) with stage > or = pT3 disease. The result for PSA was positive in 12 (52%) and for PSMA in 11 (48%) of those with positive nodal status. Neither gene-specific RT-PCR for PSA or PSMA was able to predict organ-confined disease (P > 0.5). After a median (range) follow-up of 37 (11-67) months a biochemical recurrence was predicted in 65% of patients by preoperative RT-PCR for both PSA and PSMA, with a sensitivity, specificity, positive and negative predictive value of 58%, 80%, 87% and 47%, respectively; the assay after surgery predicted a recurrence in 73%, with respective values of 68%, 84%, 84% and 57%., Conclusions: Gene-specific primed nested RT-PCR for PSA and PSMA is a sensitive and simple assay; it might add substantial information for tumour staging in individual patients. RT-PCR before surgery allows the prediction of recurrence in 65% of cases and after surgery in 73%.

Background: The origin of extragonadal retroperitoneal germ cell tumors remains controversial. Whether they develop primarily in the retroperitoneum or whether they are metastases of a primary testicular tumor has long been debated., Patients and Methods: We retrospectively analyzed 26 patients treated as having primary extragonadal retroperitoneal germ cell tumors based upon the findings of testicular palpation by the referring physician. Testicular evaluation was then extended with ultrasonographical and histological examinations., Results: Biopsy of the extragonadal tumor was performed in 25 patients, confirming diagnosis of extragonadal retroperitoneal germ cell tumor. Prior to treatment patients were clinically evaluated by several physicians and the testes were not considered suspicious for testicular cancer. At urological workup, testes were found to be atrophic and/or indurated in 14 (54%) patients, enlarged in one (4%) and unremarkable in 11 (42%). Ultrasound examination of the testes in 20 patients showed pathological findings in all of them. Histology of the testis was available in 25 of 26 patients and revealed active tumor in three, intratubular germ cell neoplasia in four, scar tissue in 12, sclerosis in three, sclerosis and fibrosis in one, and fibrosis alone in two., Conclusions: So-called primary extragonadal germ cell tumors in the retroperitoneum are very likely a rare or non-existing entity and should be considered as metastases of a viable or burned-out testicular cancer until proven otherwise. All of our patients with histologically examined testes had pathological finding, 76% of which were either viable tumor or scars.

Purpose: Continence after radical prostatectomy is thought to depend completely on the striated urethral sphincter. However, some patients complain only of occasional post-void dribbling. Therefore, we determined whether urethral dysfunction may be another cause of incontinence., Materials and Methods: The sensory threshold of electric stimulation was measured by double ring electrodes in the membranous urethra and 2.5 cm. distal in 29 men before and in 29 after radical retropubic prostatectomy. In addition, voiding cystourethrography was performed in 66 patients before and in 49 after surgery to determine complete post-void urethral emptying or milking., Results: The mean sensory threshold of the membranous urethra was 15 +/- 3 mA. preoperatively versus 38 +/- 17 postoperatively (p <0.0001). The sensory threshold 2.5 cm. further distal was 12 +/- 5 mA. before and 10 +/- 4 after radical prostatectomy, which was not statistically significant. Postoperatively in completely continent patients and in those with dribbling the mean threshold was 32 +/- 12 and 43 +/- 18 mA. in the membranous urethra (p = 0.09), and 11 +/- 4 and 9 +/- 4 mA. in the bulbar urethra, respectively, which was not statistically significant. Of the 66 patients 36 (55%) showed post-void urethral milking before surgery but only 8 of 49 (16%) showed it postoperatively (chi-square test p <0.0001), including 7 who were completely continent and 1 who complained of occasional post-void dribbling., Conclusions: After radical prostatectomy sensitivity of the membranous but not of the bulbar urethra is affected, correlating with postoperative continence. In addition, post-void dribbling seems to be associated with the loss of urethral milking. We conclude that preserving urethral function is another important continence factor after radical prostatectomy.

Transitional cell carcinoma of the renal pelvis is relatively uncommon, and only 5% of all urothelial carcinomas occur in the renal collecting system. Invasive tumors are often aggressive in their biological behavior and show a high tendency for systemic progression. Conservative therapy should only be considered an option in patients with imperative indications (solitary functioning kidney, bilateral tumor, renal insufficiency). In some cases, organ-sparing techniques such as open resection or endourological treatment (percutaneous or by ureteroscopy) can be performed. However, nephroureterectomy with excision of a bladder cuff is considered to be the standard treatment and should be performed whenever possible.

Bladder substitution in women with transitional cell carcinoma (TCC) is not a universally accepted procedure. There are many concerns, one of which is the potential risk of metachronous and synchronous urethral transitional cell carcinoma involvement. Another concern is that voiding dysfunction may be more frequent than in male patients. The numbers of female patients who have had this procedure are still small, and follow-up data are relatively brief. Thus, the true role for orthotopic bladder substitution in the female is still being evaluated. This paper reviews the data on this type of surgery in women, with emphasis on urethral TCC risk and on voiding dysfunction. Early results from a number of institutions are encouraging, particularly in correctly selected patients. Based on more than 15 years experience in an albeit small number of patients, we believe that if there is a functional external sphincter and tumor margins can be safely cleared, this form of surgery offers patients the best opportunity to preserve quality of life following cystectomy.

Purpose: We evaluated the influence of stent size in 2 consecutive series of unselected patients in whom primary ureteropelvic junction obstruction was managed by antegrade endopyelotomy and stenting with a 14 or 27Fr stent at the level of the incision., Materials and Methods: Antegrade endopyelotomy was performed in 132 patients with primary ureteropelvic junction obstruction. The endopyelotomy was stented for 6 weeks. In 77 patients (group 1) a 14/8.2Fr percutaneous endopyelotomy (Smith) catheter was used. In 55 patients (group 2) a modified 14/8.2Fr Smith catheter was over pulled with a 27Fr wound drain. The wound drain was removed after 2 to 3 weeks and the standard 14/8.2Fr stent remained in place for another 3 to 4 weeks. Success at 6 to 8 weeks, and 6 and 24 months postoperatively was based on clinical evaluation, and excretory urography and/or diuretic renography. Thereafter clinical and ultrasound followup was performed every 2 to 3 years., Results: Preoperatively data on the risk factors of large pyelocaliceal volume and impaired renal function were similar in the 2 groups. The overall success rate was 70% in group 1 at a median followup of 67 months (range 2 to 118) and 94% in group 2 at a median followup of 23 months (range 2 to 52). The early success rate after 6 to 8 weeks in groups 1 and 2 was 83% and 94%, respectively. The long-term success rate after 2 years was 71% and 93%, respectively. Perioperatively and postoperatively the incidence of complications was 16% in group 1 and 24% in group 2. When group 2 complications due to a lack of experience with the new stent were excluded from analysis, the remaining 15% complication rate was comparable to that in group 1. Mean pyelocaliceal volume decreased significantly in each group and remained stable. Split renal function did not change preoperatively to postoperatively with no significant difference in the 2 groups., Conclusions: Stenting an antegrade endopyelotomy with a modified 27Fr instead of a 14Fr catheter seems to increase the early and, even more impressively, the long-term success rate to a level similar to that of open pyeloplasty.

Purpose: We searched for compounds that are pharmacologically active on ureteral motility for treating ureteral colic to ease retrograde access into the ureter and improve the clearance of stones or stone particles from the ureter. The effects of the alpha1-adrenergic receptor agonist phenylephrine, the nonselective beta and beta2-adrenergic receptor agonists isoproterenol and fenoterol, and the phosphodiesterase inhibitors papaverine (nonspecific) and rolipram (type IV) on the frequency and amplitude of ureteral contractions when administered intravenously or topically were investigated in pigs., Materials and Methods: A total of 52 pigs were anesthetized. A double lumen 6Fr catheter was inserted through each renal pelvis and into the ureter, allowing perfusion of saline or drug solution into the renal pelvis and the recording of contractions from the mid portion of the ureter., Results: The alpha1 and beta-adrenergic receptors of the ureter are not tonically activated by endogenous epinephrine or norepinephrine. Phenylephrine administered intravenously at a dose of 0.01 to 3 mg./kg. and topically at 0.1 to 3 mg./ml. per minute increased contraction frequency 10 and 4-fold, respectively, and contraction amplitude 2-fold each in a dose dependent manner. Arterial blood pressure increased markedly during intravenous administration of phenylephrine but was minimally affected during topical application. The phenylephrine effects were reversed by the antagonist prazosin. Isoproterenol administered intravenously at a dose of 0.01 to 10 mg./kg. and topically at 0.1 to 200 microg./ml. per minute decreased contraction frequency to 13% and 31% of controls, respectively. Contraction amplitude was not affected by intravenous administration but decreased to 59% of controls when applied topically. These effects were also observed with a slight delay in the saline perfused contralateral ureter. The heart rate also increased, suggesting absorption of the drug by the urothelium. The isoproterenol effects were blocked by the antagonist propranolol. Fenoterol administered intravenously at a dose of 0.1 to 30 microg./kg. and topically at 0.003 to 1 mg./ml. per minute decreased contraction frequency to 14% and 10% of controls, and contraction amplitude to 84% and 65%, respectively. These effects on the drug perfused ureter were also observed on the contralateral saline perfused ureter but to a lesser extent. The fenoterol effects were blocked by the antagonist propranolol. Papaverine administered intravenously at a dose of 0.001 to 3 mg./kg. decreased contraction frequency to 33% of controls. Topically administered papaverine as well as intravenous and topically administered rolipram had no relevant effect on ureteral motility., Conclusions: Intravenous phenylephrine increases, and isoproterenol and fenoterol decrease the frequency and amplitude of ureteral contractions in the pig. The same effects are observed with the topical administration of phenylephrine, which causes a significant local but not systemic side effect. Topical administration of isoproterenol and fenoterol produced local as well as systemic effects, suggesting absorption by the urothelium. However, to our knowledge a drug that relaxes ureteral peristalsis in pigs without causing systemic side effects has not yet been identified.

Background: The meta-analysis of maximal androgen blockade (MAB) concluded that there is no survival advantage of MAB over castration alone. However, the results from the largest trials yield conflicting results., Methods: The design and results of three trials were examined., Results: Most studies were planned to detect an over-optimistic difference in survival and immature data were published. The survival curves show that statistical assumptions are not fulfilled. Excluding from the meta-analysis all trials where a negative impact of disease flare on survival could not be excluded resulted in no difference in survival between MAB and castration., Conclusions: Trials of MAB should be planned to detect differences of no more than 5-10% in median survival. The analyses should only be carried out on mature data and should take into account the possibility of a negative impact on survival due to disease flare if no anti-androgen has been given initially with an LH-RH agonist., (Copyright 2001 Wiley-Liss, Inc.)

Purpose: After cystectomy and ileal bladder substitution, sensitivity in the membranous urethra correlates with postoperative urinary continence. We determine whether sensitivity is decreased only in the most proximal part of the urethra or also more distally in the bulbar urethra, which would give some indication as to which nerves may be injured during radical cystoprostatectomy., Materials and Methods: The sensory threshold for electrical stimulation was measured with double ring electrodes in the membranous urethra, and 2.5 cm. distally to it in 41 men after cystectomy and ileal bladder substitution, and in a control group of 29 men., Results: The mean sensory threshold plus or minus standard deviation of the membranous urethra was 9 +/- 2 mA. in the control group compared to 26 +/- 11 mA. in the postoperative group (p <0.001). Mean sensory threshold 2.5 cm. distal to the membranous urethra was 8 +/- 3 versus 9 +/- 3 mA. in the control and postoperative groups, respectively (not significant). Patients with daytime continence had a mean threshold of 22 +/- 8 mA. in the membranous urethra compared to 38 +/- 11 mA. in those who were incontinent (p <0.004) and a threshold of 8 +/- 3 mA. 2.5 cm. distal to the membranous urethra compared to 8 +/- 2 mA. in those who were incontinent (not significant)., Conclusions: After cystectomy and ileal bladder substitution, urethral sensitivity 2.5 cm. distal to the membranous urethra is unaffected by surgery and does not correlate with postoperative continence. In contrast, a decreased sensitivity in the membranous urethra correlates with an increased risk of postoperative incontinence. Preservation of sensitivity in the membranous urethra seems to be an important factor for achieving continence after cystectomy and ileal bladder substitution, and does not seem to be dependent on the extrapelvic portion of the pudendal nerve.

Objective: To determine whether the sensitivity of the membranous urethra is an important factor to obtain continence after ileal bladder replacement., Material and Method: The sensitivity threshold after electrical stimulation of the membranous urethra by a ring electrode placed on a urethral catheter was measured in 47 men after ileal bladder replacement (postoperative group). The control group consisted of 35 men before radical prostatectomy or cystoprostatectomy., Results: The mean sensitivity threshold of the membranous urethra was 9 +/- 2 mA in the control group and 27 +/- 11 mA in the postoperative group (p < 0.001). The sensitivity threshold of daytime continent and incontinent patients was 24 +/- 9 and 39 +/- 10 mA, respectively (p < 0.001)., Conclusion: The sensitivity of the membranous urethra decreases in patients after cystoprostatectomy and ileal bladder replacement. The sensitivity of the membranous urethra is better in continent patients than in incontinent patients and therefore appears to be an important factor for continence after ileal bladder replacement.

Purpose: We investigate fertility and sexual function in patients following orchiectomy and adjuvant cisplatin based chemotherapy for high risk, stage I nonseminomatous germ cell tumor of the testis., Materials and Methods: Between 1985 and 1994, 59 patients with stage I nonseminomatous germ cell tumor and poor prognostic factors were treated with 2 cycles of cisplatin, vinblastine and bleomycin, or bleomycin, etoposide and cisplatin after orchiectomy. At least 32 months following treatment all patients were contacted and asked to complete a questionnaire regarding fertility and sexual activity, and to volunteer for a semen and hormonal analysis., Results: Of the 59 patients 49 (83%) completed the questionnaire. Before chemotherapy 18 (37%) patients had fathered children, 6 (12%) were involuntarily childless and none had a major sexual dysfunction. After treatment 11 (22%) patients fathered children, and 5 (10%) were involuntarily childless, with 4 involuntarily childless before chemotherapy. There were no significant alterations in sexual function. Semen analysis in 27 patients was normal in 23, and revealed mild oligospermia in 2 and azoospermia in 2. In 18 patients with hormone analysis median values for luteinizing hormone and free testosterone were normal but median value for follicle-stimulating hormone was slightly increased., Conclusions: Two cycles of cisplatin based adjuvant chemotherapy do not seem to affect adversely fertility or sexual activity.