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Objectives: To assess the prognostic implication of urinary collecting system invasion (CSI) in renal cell cancer (RCC)., Methods: Surveying a mean follow-up of 85 months, we investigated a cohort of 834 patients after radical (n = 710) or partial (n = 124) nephrectomy. At the time of surgery, 63 patients (7.6%) suffered from metastatic RCC. Various histopathologic parameters were analysed, and cancer specific survival (CSS) curves were individualized for each parameter. Furthermore, multivariate analysis was accomplished., Results: Collecting system invasion was independently associated with a significant decline in CSS and was associated with simultaneous metastatic spread at the time of surgery and multilocular (involvement of at least two different organ systems) dissemination., Conclusions: The prognostic implication of CSI in RCC appears to be more complex than expected. Therefore, pathologists should report on CSI to enable selection of patients to be investigated in prospective studies which are needed to clarify the prognostic role of CSI in RCC.

Purpose: Sunitinib has demonstrated antitumor activity in metastatic renal cell carcinoma (mRCC) when given at 50 mg/d on a 4-weeks-on 2-weeks-off regimen. Herein, we report results of an open-label, multicenter phase II mRCC study of sunitinib administered on a continuous once-daily dosing regimen., Patients and Methods: Eligibility criteria included histologically proven mRCC with measurable disease, failure of one prior cytokine regimen, and good performance status. Patients were randomly assigned to a sunitinib starting dose of 37.5 mg/d in the morning (AM) or evening (PM). RECIST-defined objective response rate (ORR) was the primary end point. Secondary end points included progression-free survival (PFS), overall survival (OS), adverse events (AEs), and quality-of-life measures., Results: One hundred seven patients were randomly assigned to AM (n = 54) or PM (n = 53) dosing and on study for a median 8.3 months. Eighty-three patients discontinued, 65 due to disease progression and 16 because of AEs; two patients withdrew consent. Dosing was reduced to 25 mg/d in 46 patients (43%) due to grade 3/4 AEs. The most common grade 3 treatment-related AEs were asthenia/fatigue (16%), diarrhea (11%), hypertension (11%), hand-foot syndrome (9%), and anorexia (8%). ORR was 20% with a 7.2-month median response duration. Median PFS and OS were 8.2 and 19.8 months, respectively, at median follow-up of 26.4 months. Efficacy, tolerability, and quality-of-life results were similar between patients dosed in the AM or PM., Conclusion: Sunitinib 37.5 mg, administered on a continuous once-daily dosing regimen, has a manageable safety profile as second-line mRCC therapy, providing flexible dosing, which can be explored in combination studies.

Currently, there is no widespread use of percutaneous renal artery embolisation (PRAE) as a pre-operative treatment in the management of renal cell carcinoma (RCC). There is also a scarcity of studies concerning the potential benefits of this procedure. All patients with RCC who underwent pre-operative PRAE before nephrectomy (n = 227) and all patients solely undergoing surgery (n = 607) at our institution from 1992 to 2006 were included. Information on techniques used, perioperative transfusion requirements, pathological and clinical variables, acute toxicity and complications were obtained from a retrospective review of medical records. Propensity modelling techniques were used to compare cancer-specific survival (CSS) and overall survival (OS) in both groups. Propensity scores were calculated from a logistic matching model including age, gender, clinical tumour size, grading, pN stage, cM stage, pT stage, histology and microvascular invasion. This resulted in 189 matches. The mean follow-up of the entire group of matched patients was 81 months. The 5-year actuarial CSS and OS for the total group of matched patients was 80.8% and 73.9%, respectively. CSS and OS did not show any significant differences between the matched treatment groups. There were no statistical differences in surgical complications between all patients treated with pre-operative PRAE (n = 227) and all patients without PRAE (n = 607), except for blood transfusion (61% vs 24%; p<0.01). Symptoms of post-embolization syndrome, including lumbar pain, fever, nausea, hypertension and macroscopic haematuria, were reported by 202 patients (89%), in most cases being mild and self-limited. There is no conclusive evidence that pre-operative PRAE provides survival benefits in the management of surgically resected RCC.

The treatment of metastatic renal cell carcinoma (mRCC) has been changed by the introduction of targeted agents. Consideration of individual patient factors, such as previous treatment and prognostic risk, e.g. according to the Memorial Sloan-Kettering Cancer Center (MSKCC) risk criteria), can assist in ensuring that patients receive appropriate targeted therapies. Available clinical evidence shows sunitinib to be the reference standard of care for the first-line treatment of mRCC in patients at favourable or intermediate prognostic risk according to MSKCC criteria. Combined treatment with bevacizumab plus interferon-alpha can also be considered for the first-line treatment of mRCC in this setting. For the first-line treatment of poor-risk patients, temsirolimus has shown benefit in a phase III study, while sunitinib can also be considered. For second-line treatment in cytokine-refractory patients, sorafenib is recommended based on phase III trial results; sunitinib has also shown activity after failure of cytokine therapy or targeted agents. As well as antitumour activity, the tolerability of targeted agents should be evaluated in the context of individual patients, considering factors such as comorbidities and age. As our understanding of the activity of targeted agents for mRCC increases, we should ensure that these agents are used appropriately to provide patients with optimal treatment benefits.

Objectives: To determine the value of microvascular invasion, tumor size, and Fuhrman grade to predict the survival of patients with surgically resected renal cell carcinoma (RCC)., Methods: A total of 771 consecutive patients (T1-4, Nx, M0) were retrospectively reviewed. For each patient with RCC, the prognostic Sao Paulo score (SPS) was calculated using the following variables: tumor size (>7 cm vs

Background: Discontinuation of treatment with tyrosine kinase inhibitors (TKIs) and readministration in case of recurrence could improve quality of life (QoL) and reduce treatment costs for patients with metastatic renal cell carcinoma (mRCC) in which a complete remission (CR) is achieved by medical treatment alone or with additional resection of residual metastases., Objective: To evaluate whether TKIs can be discontinued in these selected patients with mRCC., Design, Setting, and Participants: A retrospective analysis of medical records and imaging studies was performed on all patients with mRCC treated with TKIs (n=266) in five institutions. Patients with a CR under TKI treatment alone or with additional metastasectomy of residual disease following a partial response (PR), in which TKIs were discontinued, were included in the analysis. Outcome criteria analysed were time to recurrence of previous metastases, occurrence of new metastases, symptomatic progression, improvement of adverse events, and response to reexposure to TKIs., Interventions: Sunitinib 50mg/day for 4 wk on and 2 wk off, sorafenib 800mg/day., Measurements: Response according to Response Evaluation Criteria in Solid Tumours (RECIST)., Results and Limitations: We identified 12 cases: 5 CRs with sunitinib, 1 CR with sorafenib, and 6 surgical CRs with sunitinib followed by residual metastasectomy. Side-effects subsided in all patients off treatment. At a median follow-up of 8.5 mo (range: 4-25) from TKI discontinuation, 7 of 12 patients remained without recurrence and 5 had recurrent disease, with new metastases in 3 cases. Median time to progression was 6 mo (range: 3-8). Readministration of TKI was effective in all cases. The study is limited by small numbers and retrospective design., Conclusions: Discontinuation of TKI in patients with mRCC and CR carries the risk of progression with new metastases and potential complications. Further investigation in a larger cohort of patients is warranted before such an approach can be regarded as safe.

Objective: To determine the value of particular clinical variables for the preoperative prognostic Cindolo formula (PPCF) to predict disease-free survival (DFS) of patients with surgically treated renal cell carcinoma (RCC)., Patients and Methods: In all, 771 consecutive patients (T1-4NxM0) who had radical or partial nephrectomy were reviewed retrospectively. For each patient with RCC, PPCF was constructed according to clinical size and clinical presentation. On the basis of PPCF, patients were divided into Cindolo good prognosis (CGP) and Cindolo poor prognosis (CPP) groups. We also analysed further clinical variables (Eastern Cooperative Oncology Group score, American Society of Anesthesiologists score, body mass index, hepatic dysfunction, night sweat, fever, value of blood platelets, leukocytes, haemoglobin level, gender, age and location). DFS was estimated using the Kaplan-Meier method. Univariable and multivariable Cox proportional hazard regression models were fitted to determine associations between the PPCF, measured clinical features, and DFS., Results: Four of the variables emerged as statistically significant for DFS from the univariable analysis (P < 0.001), i.e. clinical presentation, clinical tumour size, haemoglobin level and blood platelet count. In the multivariable analysis, only clinical tumour size and blood platelet count remained significant for DFS. By contrast, clinical presentation, used in the PPCF, had no significant influence. According to the PPCF we developed the preoperative Amissah Prognosis Score (PAPS) calculated as (0.19 x clinical size) + (0.492 x platelet count (400/nL = 1) with a threshold between the two resulting prognosis groups at 1.76. The multivariable hazard ratio (95% confidence interval, CI) for the PAPS was 2.98 (2.15-4.12) (P < 0.001) compared to a hazard ratio for the PPCF of 1.36 (0.99-1.87) (P = 0.061). Furthermore, the predictive ability was greater when using the PAPS (area under the curve 0.721; 95% CI, 0.680-0.763; P

Introduction: Prostate carcinoma ranges among the most common cancers in German men. One of its standard treatments is radical prostatectomy (RP). Postoperative comorbidities of RP include erectile dysfunctions, which may impact patients' relationship quality. Little is known, to date, about patients' and their partners' psychosocial resources that might reduce the risk of damage to relationship outcomes. Such resources include spousal social support interactions., Aim: We investigated cross-sectional and prospective relations of patient-reported and partner-reported received and provided spousal support, and patients' indicators of erectile functions and relationship satisfaction prior to and 1 year following laparoscopic radical prostatectomy., Main Outcome Measures: Patient-reported relationship satisfaction (Relationship Questionnaire; Fragebogen zur Partnerschaftsdiagnostik) and erectile functions (International Index of Erectile Function) were investigated as main outcomes., Methods: One hundred thirty-nine patients and their heterosexual partners provided data prior to and 12 months after the operation. Main outcomes were patient-reported relationship satisfaction and erectile functions. In addition to several covariates, central predictors were patients' and partners' accounts of received and provided spousal support. Data were assessed using questionnaires., Results: Erectile functions were associated with patients' relationship satisfaction presurgery, but not 12 months postsurgery. Patient-reported received and provided support was positively associated with relationship satisfaction at all times. Patient-reported provision of support was also related with better erectile functions prior to and postsurgery. Some of these associations could be replicated using partner accounts of respective support indicators., Conclusions: Regarding patients' relationship satisfaction and sexual functions, findings associate more consistent benefit with patients' own provision of supports when compared with their own support receipt.

From a proactive agentic perspective, social support is not just seen as a protective cushion against environmental demands. Rather, support may facilitate an individual's self-regulation by enhancing perceived self-efficacy (i.e., enabling hypothesis). In the present study, patient-reported indicators of mobilized and received spousal support as predictors of their own and their spouses' self-efficacy beliefs were investigated within 1 year following radical prostatectomy. During this time frame, postoperative sequelae such as urinary incontinence and erectile dysfunctions are still likely to interfere with couples' everyday activities. Seventy-two patients receiving radical prostatectomy and their spouses participated. Patients' and spouses' self-efficacy beliefs and patients' received and mobilized spousal support were assessed prior to and 12 months following surgery. Additional patient-reported covariates at 1 year post-surgery were degree of bother by urinary incontinence, overall sexual satisfaction, and relationship satisfaction. Results indicated that patients' received spousal support was associated with higher levels of patients' self-efficacy only cross-sectionally, but not longitudinally. Support mobilized by the patient prior to and 1 year after surgery, however, positively predicted spouses' levels and changes in self-efficacy. Results, thus, did not fully confirm predictions by the enabling hypothesis of social support; rather, associated aspects, such as the degree of being mobilized as a provider of support or being needed, seem to enhance agency beliefs in spouses.

Objective: To determine the value of clinical and pathological parameters defining the Störkel score in order to predict outcomes of patients with surgically treated renal cell carcinoma (RCC)., Material and Methods: A total of 834 consecutive patients having radical or partial nephrectomy were retrospectively reviewed. For each patient with RCC, the prognostic Störkel score was calculated according to the following variables: Robson stage, Thoenes nuclear grading, histological type, pattern of growth, and age. Based on the Störkel score, patients were divided into groups: those with good prognosis (GP), intermediate prognosis (IP), and poor prognosis (PP). Cancer-specific survival (CSS) and overall survival (OS) were estimated using the Kaplan-Meier method. The accuracy of prediction of CSS and OS with the Störkel score was analyzed using Kaplan-Meier analysis, proportional hazards regression, and graphic representation [(Kaplan-Meier curves, area under the curve (AUC)]. In 564 patients who were still alive, the median follow-up was 79 months (mean 84.8 months)., Results: In the GP, IP, and PP groups, CSS after 8 years was 86.7%, 75.6%, and 13.7%, respectively (p<0.001). In the multiple analysis, only the Robson stage and Thoenes nuclear grading independently predicted CSS. Accordingly, the prognostic accuracy of the Störkel score (CSS prediction: AUC=0.744, 95% CI=0.70-0.79) was not better than with a reduced model that included the Robson stage and grading only (CSS prediction: AUC=0.765, 95%CI=0.72-0.81)., Conclusions: Of all parameters included in the Störkel score, only the Robson stage and nuclear grading are significant prognostic factors. Hence, we recommend an accordant modification of the score with additional variables.

Radical prostatectomy has a negative impact on prostate cancer patients' health-related quality of life (HRQoL). Social support may help patients adjust to their situation after surgery. We investigated patients' accounts of received social support as well as their spouses' accounts of provided social support as predictors of patients' HRQoL 6 months after surgery. Moreover, we tested whether patients with lower HRQoL at 2 weeks after surgery had the most benefit from spousal support. A total of 77 patients (M = 61.57 years, SD = 6.03) and their spouses (M = 58.46 years, SD = 7.52) completed questionnaires at 2 weeks and 6 months after laparoscopic radical prostatectomy. Received social support, spousal provided social support, and HRQoL were assessed 2 weeks after surgery, and HRQoL was assessed again 6 months later. Patients with lower HRQoL at 2 weeks after surgery benefited more from the receipt and their partners' provision of support in terms of HRQoL 6 months later than patients with a higher HRQoL at the beginning. Assessing patients' HRQoL might be one method to identify those individuals who are in special need of support from their spouses.

Background: Fast-track surgery describes perioperative treatment concepts ensuring a faster postoperative convalescence phase. By using a multimodal fast-track concept in patients undergoing laparoscopic radical prostatectomy, we aimed to investigate the feasibility of this procedure after elective surgery and a possible discharge 3 days postoperatively., Patients and Methods: Twenty-five patients per group were randomized for conventional or fast-track treatment, respectively. Perioperative data, early complications, possible hospital discharge, and readmission rate were analyzed. Before hospital discharge, all patients were interviewed about their evaluation of the received regimen and their overall satisfaction perioperatively., Results: The mean postoperative hospital stay was 3.6 days in the fast-track group vs. 6.7 days in the conventional group (p<0.01). Overall complications were low but were significant between the two groups, with the fast-track procedure being more favorable. Readmission rate was also low but was not significant. Overall satisfaction was significantly higher in the fast-track group, whereas the subjective evaluation did not differ between the two regimens., Conclusions: Fast-track concepts are well transferable in laparoscopic radical prostatectomy settings. Patients receiving this procedure, as well as clinics offering it, may benefit from a suitable fast-track concept.

With cross-over living donor kidney transplantation, immunologic incompatibilities within the original donor/recipient pair can be overcome. As minimal invasive techniques for organ recovery are increasingly applied, this should also be performed in a cross-over kidney transplantation. We present the first report of a successful simultaneous laparoscopic kidney recovery for cross-over kidney transplantation as well as a review of the international practice of cross-over kidney transplantation in the context of national laws. Cross-over kidney transplantation should be encouraged. A databank on pairs willing to participate in organ exchange programs should be created.

Objective: The determination of further prognostic factors is essential for the establishment of risk groups for patients with surgically treated renal cell carcinoma (RCC). The objective of this study was to validate the prognostic value of macroscopic tumour necrosis, concerning postoperative survival., Material and Methods: A total of 607 patients (387 men, 220 women), who had undergone surgical treatment for RCC, was retrospectively reviewed. Necrotic areas in the tumour were identified macroscopically followed by microscopic confirmation. Cancer-specific survival (CSS) and overall survival (OS) were estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards regression models were fitted to determine associations between tumour necrosis, clinical and pathological features, and survival. In 447 patients who were still alive at the end of the study, median follow-up was 66 months (mean 71.2 months)., Results: Tumour necrosis was identified in 25.5% of patients (n=155). After 5 years, CSS and OS in the group of patients with tumour necrosis amounted to 77.0% and 64.4%, respectively, compared with 89.8%and 81.9% in the group of patients without tumour necrosis (in each case p<0.001). Patients with tumour necrosis significantly more often showed a metastatic stage, lymph-node involvement, a higher pathological tumour stage, a higher grading and a larger tumour size. In addition, a more frequent appearance of microvascular invasion and thrombocytosis could be proven in patients with tumour necrosis in comparison to patients without these histopathological findings. On multivariate regression analysis, only metastatic stage, lymph-node involvement, platelet count >400/nl and tumour necrosis remained significant for survival (CSS, OS)., Conclusions: According to the results, tumour necrosis may be a useful factor in the prognostic assessment of patients with RCC. The integration of this parameter in prognostic models for postoperative survival is recommended.

Signalling by erythropoietin (EPO) is increasingly recognised as a relevant mechanism in tumour biology, potentially leading to enhanced proliferation, angiogenesis and therapy resistance. Paraneoplastic polycythemia by cancerous overproduction of EPO is a rare event, but most frequently seen in patients with renal cell carcinoma (RCC). The majority of clear cell RCC displays a strong activation of the transcription factor regulating EPO, the Hypoxia-inducible Factor (HIF). Therefore, it is unclear why only a small minority of patients develop polycythemia. We studied 70 RCC for EPO gene and HIFalpha isoform expression. 34% of all RCC showed expression of EPO mRNA in RNase protection assays, which were almost exclusively of the clear cell type. Only 1 patient presented with polycythemia. In situ hybridisation revealed that expression of EPO was in the tumour cells. Expression of EPO mRNA was always associated with activation of HIF, which could involve HIF-1alpha and/or HIF-2alpha. The frequency of EPO gene expression in RCC is therefore much higher than the prevalence of polycythemia. Furthermore, activation of HIF appears necessary for EPO gene expression in RCC, but is clearly not the only determinant. Further to the reported expression of EPO receptors in tumour tissues, the finding of widespread expression of EPO in RCC supports the recent notion of an involvement of this system in paracrine or autocrine effects of tumour cells., ((c) 2007 Wiley-Liss, Inc.)

Worldwide, specific pediatric allocation schemes successfully try to minimize waiting time for children with end-stage renal disease (ESRD). The article is a review of current issues in pediatric kidney transplantation. The procedure is the treatment of choice for children and adolescents with ESRD, with 1- and 3-year graft survival rates of 95% and 90% and recipient survival after 5 and 10 years of 95% and 90%. Preoperative surgery is often necessary to minimize negative effects of congenital anomalies. No minimum age exists for pediatric transplantation, but most often the recipient body weight is ideally above 10 to 15 kg. Technical concepts should include extravesical anastomosis, stenting of the ureter, and potentially intraperitoneal placement of the graft. Immunosuppression has constantly improved. The aim is a tailored regimen to reduce side effects and improve compliance, which necessitates intense counseling of the child and the parents prior to, during, and after transplantation as many adolescents lose their graft due to noncompliance. Intense follow-up must also exclude infections, especially with herpes and polyoma viruses. For the future, age matching may be only one promising concept to improve results. As only a small number of children require the procedure in each country, multinational studies should be initiated to optimize outcomes in children and adolescents.

Background: Housekeeping genes are commonly used as endogenous reference genes for the relative quantification of target genes in gene expression studies. No conclusive systematic study comparing the suitability of different candidate reference genes in clear cell renal cell carcinoma has been published to date. To remedy this situation, 10 housekeeping genes for normalizing purposes of RT-PCR measurements already recommended in various studies were examined with regard to their usefulness as reference genes., Results: The expression of the potential reference genes was examined in matched malignant and non-malignant tissue specimens from 25 patients with clear cell renal cell carcinoma. Quality assessment of isolated RNA performed with a 2100 Agilent Bioanalyzer showed a mean RNA integrity number of 8.7 for all samples. The between-run variations related to the crossing points of PCR reactions of a control material ranged from 0.17% to 0.38%. The expression of all genes did not depend on age, sex, and tumour stage. Except the genes TATA box binding protein (TBP) and peptidylprolyl isomerase A (PPIA), all genes showed significant differences in expression between malignant and non-malignant pairs. The expression stability of the candidate reference genes was additionally controlled using the software programs geNorm and NormFinder. TBP and PPIA were validated as suitable reference genes by normalizing the target gene ADAM9 using these two most stably expressed genes in comparison with up- and down-regulated housekeeping genes of the panel., Conclusion: Our study demonstrated the suitability of the two housekeeping genes PPIA and TBP as endogenous reference genes when comparing malignant tissue samples with adjacent normal tissue samples from clear cell renal cell carcinoma. Both genes are recommended as reference genes for relative gene quantification in gene profiling studies either as single gene or preferably in combination.

Fast-track surgery describes innovative treatment concepts ensuring a faster convalescence phase. The aim of this study was to allow hospital discharge 3 days after surgery without additional complications in patients receiving LRPE for localized prostate cancer. Twenty-five patients each were randomized in the study groups to verify if a fast-track regimen could be transferred into clinical routine. The perioperative data, early complications, hospital stay as well as readmission rate were analyzed. The mean postoperative stay was 3.6 days in the fast-track group versus 6.7 days in the conventional group. The overall complications were significantly less in the fast-track procedure. The readmission rate was low and not significant. Patients receiving an LRPE benefit from a suitable fast-track concept. The postoperative hospital stay could be shortened nearly by half with a significantly decreased overall complication rate. Thus, fast-track concepts might contribute to saving resources in the long term. However, more evidence based on larger prospective trials is needed to achieve optimal quality of life for patients perioperatively.

Close relationships are usually the most important source of social support. But even in close relationships, symptoms of distress in one or both partners may undermine support processes. Seventy-seven patients receiving laparoscopic radical prostatectomy (44-73 years) and their spouses (38-72 years) provided data 1 day prior to surgery as well as 2 days and 2 weeks post-surgery. Our assumption that the commonly found support-eroding potential of receivers' depressive symptoms would not be evident during early stages of an acute crisis situation, such as major tumor surgery, tended to be supported by the data. However, depressive symptoms and degree of patient-reported post-operative pain were associated with a delayed decrease in spousal instrumental support provision 2 weeks after surgery. Spousal depression was largely unrelated to the provision of support. The present findings hint at the limits of a loved-one's capacity to assist in times of need., (Copyright (c) 2006 John Wiley & Sons, Ltd.)

Background: A 16-year-old white male with a history of obstructive uropathy presented to a pediatric outpatient clinic with a first syncope. At presentation, he had a hemoglobin level of 220 g/l, a serum erythropoietin level of 27.4 U/l and a serum creatinine level of 200.7 micromol/l (2.27 mg/dl)., Investigations: Physical examination, serum laboratory analysis, renal ultrasound, MRI, and 99mTc-MAG3 scintigraphy of the kidneys., Diagnosis: Chronic renal insufficiency caused by obstructive hydronephrosis and accompanied by increased erythropoietin levels of renal origin and polycythemia., Management: Serial phlebotomies and laparoscopic removal of the right hydronephrotic kidney.

Background: This study investigated whether the therapeutic efficacy and morbidity of three minimally invasive techniques for varicocele correction--laparoscopic varicocelectomy (LV), antegrade sclerotherapy (AS), and retrograde embolization (RE)--differed between children and adults., Methods: During a 10-year period, 356 procedures for varicocele correction, including 122 cases of LV, 108 cases of AS, and 126 cases of RE, were performed for 314 patients at our institution. Of these patients, 223 were 19 years of age or younger (group 1), and 133 were older than 19 years (group 2). Diagnosis and postoperative results were established clinically and with the use of Doppler ultrasonography. The failure rates and complications for each procedure were retrospectively evaluated and compared between the two age groups., Results: The median follow-up period was 69 months (range, 6-122 months). For 25 patients (19.8%), RE was not feasible for technical reasons. In both groups, LV had a lower failure rate than AS or RE, but the difference between LV and AS was not significant in group 1 (7.7(% vs 11.9%; p > 0.5). Also in group 1, AS was associated with fewer complications than LV 1 (4.5% vs 15.4%; p < 0.05). In group 2, LV was significantly more effective in correcting varicoceles than the other two techniques (p < 0.01). In this group, the complication rates for all three procedures did not differ significantly (p > 0.05)., Conclusions: In our experience, LV was more effective than AS or RE in correcting varicoceles. For children and adolescents, AS may be more indicated because of the slightly lower complication rate and similar recurrence rates, as compared with LV, for this age group. The higher incidence of postoperative hydrocele formation after LV warrants more refined techniques such as the lymphatic-sparing approach.

The systemic treatment of renal cell cancer represents a challenge for uro-oncologists. Although no internationally recognised treatment regime has been defined, cytokine therapy has been the standard of care for metastatic disease. The growing understanding of the relevant mechanisms in the molecular biology of renal cell carcinoma has led to the development of targeted therapies. Novel tyrosine kinase and angiogenesis inhibitors have had a beneficial effect on progression-free and overall survival in patients with advanced renal cell cancer and represented a significant progress. Even though several important aspects regarding treatments and combinations of these drugs with each other as well as with cytokines still remain unclear, cytokine therapy will probably become less important as a first-line treatment. With increasing therapeutic options becoming available as potential new standards and with the old standards being poorly defined, a critical analysis of the role of different systemic therapies for renal cell carcinoma is warranted. A better knowledge of molecular markers and their prognostic relevance could allow the rational use of different targeted therapies in individual patients in the future. Until such therapies become available, the systemic treatment options should be selected carefully in individual patients.

Objectives: Laparoscopic transperitoneal radical prostatectomy (LRP) is an alternative to open radical prostatectomy, but data based on large populations are not frequently available. This study was initiated to evaluate LRP with regard to complications, urinary continence, and oncologic outcome., Methods: We retrospectively reviewed 1000 consecutive patients with a mean age of 62 yr (SD+/-6 yr) and clinically localized prostate cancer. Between May 1999 and October 2004, all 1000 patients underwent LRP performed by eight urologists at one institution (Charité Hospital Berlin, Campus Mitte). The review procedure was based on complete patient documents (hospital stay, n=1000) and an interview by one physician. Histopathologic results, intraoperative and early and late complications, continence rate, and time to first PSA increase (n=952) were recorded. Erectile function was not part of this review. Twenty-two patients received neoadjuvant treatment for >2 mo., Results: The median follow-up was 28.8 mo (range: 7.2 to 69.7). Intraoperative and early complications occurred in 11.8% of patients. In 77.6% the urethrovesical anastomosis tested by cystography at day 5 or 6 after LRP was intact; 76% used none or not more than one pad per 24h. The overall PSA-free survival was more than 90% for pT2, 80.3% for pT3a, and 72.4% for pT3b until July 2005. The mortality rate was 0.3%., Conclusions: In the present series of 1000 patients, a specific disadvantage of LRP compared with the open approach, as reported in the literature, could not be shown. On the basis of short-term follow-up data, our retrospective evaluation confirms that LRP provides satisfactory results. We believe that laparoscopic radical prostatectomy can be the technique of choice in the future.

Human parvovirus B19 is a common cause of benign erythema infectiosum (fifth disease) in otherwise healthy children. Immunocompromized patients are at risk of developing chronic infections leading to chronic hyporegenerative anemia. We report the case of a nine-year-old boy who presented five days after renal transplantation with seizures and signs of encephalitis on MRI. The clinical course was characterized by anemia and seroconversion for parvovirus B19 accompanied by a high viral load (>10(9) copies per milliliter). A transfusion of red blood cells that the patient required after transplantation was found to be negative for parvovirus B19, leaving the donated organ as the most likely source of infection. Reduction of the immunosuppressive regimen led to complete recovery of the patient with a stable RBC count upon discharge. Parvovirus B19 infections should be considered in the differential diagnosis of seizures after solid organ transplantation.

Allogeneic stem cell transplantation and donor lymphocyte infusions are currently under clinical investigation as an innovative therapeutic option for patients with metastatic renal cell carcinoma. A variety of trials have proven the clinical efficacy of allogeneic stem cell transplantation using reduced-intensity conditioning protocols and donor lymphocyte infusions, as demonstrated by the induction of objective remissions in metastatic renal cell carcinoma patients. However, despite clinical remissions, reduced-intensity conditioning protocols and donor lymphocyte infusions were associated with a high treatment-related mortality rate of approximately 17%. The disproportion between clinical efficacy and treatment-related mortality may mainly be caused by the selection of patients that had often been heavily pretreated, with a large tumor burden and rapidly progressing tumors. The improvement of efficacy with the preservation of a powerful graft-versus-tumor effect while reducing the toxicity, is the major experimental and clinical challenge of allogeneic stem cell transplantation in the treatment of metastatic renal cancer and other solid tumors. Recently, there has been a revolutionary development of molecular-targeted agents in metastatic renal cancer. These inhibitors of angiogenesis and signal-transduction pathways have demonstrated clinical efficacy and significant survival prolongation in the first- and second-line settings, while causing moderate toxicity. Some of these agents have already been approved by the US FDA and will probably replace standard cytokines, such as interferon-alpha2 and interleukin-2, in metastatic renal cancer. In the context of these innovative clinical developments, allogeneic stem cell transplantation clearly has to be regarded an investigational clinical treatment approach. Therefore, patients should only be treated at centers that are experienced in clinical trials, and patient selection remains a critical factor for a successful transplant procedure.

Purpose: We assessed the diagnostic accuracy of bone markers in the serum of patients with renal cell carcinoma to detect bone metastases and evaluate the prognostic potential concerning renal cell carcinoma caused mortality., Materials and Methods: The bone formation markers total and bone specific alkaline phosphatase, the bone resorption markers cross-linked N-terminal and tartrate-resistant acid phosphatase isoenzyme 5b, and the osteoclastogenesis markers osteoprotegerin and ligand of the receptor activator of nuclear factor-kappaB, were measured in the serum of 72 patients with renal cell carcinoma, including 28 with pN0M0, 8 with pN1M0 and 36 with M1, and in 32 female and 36 male controls by enzyme-linked immunosorbent assay techniques. Data were evaluated by receiver operating characteristics and survival analysis., Results: Bone specific alkaline phosphatase, tartrate-resistant acid phosphatase isoenzyme 5b and ligand of the receptor activator of nuclear factor-kappaB did not significantly differ between patients with renal cell carcinoma and controls. Compared with controls tartrate-resistant acid phosphatase isoenzyme 5b, cross-linked N-terminal and osteoprotegerin showed increased concentrations in patients with nonbone metastases but not in those with bone metastases. No bone turnover marker led to differentiation between patients with nonbone and bone metastases. Increased osteoprotegerin above the upper 95% cutoff limit, tumor stage and distant metastatic spread were associated with renal cell carcinoma related survival on Kaplan-Meier analyses. A multivariate Cox proportional hazards regression model revealed that these 3 variables were independent prognostic factors for cancer related death., Conclusions: Bone turnover markers are hardly useful to diagnose bone metastases in patients with renal cell carcinoma. However, osteoprotegerin together with clinicopathological characteristics may be helpful as prognosticator of cancer specific death.

Objectives: We report on ureteral and surgical complications in our first 110 consecutive recipients of kidneys procured with laparoscopic living donor nephrectomy (LLDN)., Methods: The records of all living donor transplants with LLDN performed between February 1999 and December 2004, including 10 pediatric transplants, were reviewed retrospectively. Three urologists performed LLDN using a pure laparoscopic non-hand-assisted transperitoneal technique. Kidney transplantation was performed in a standard fashion. For ureteroneocystostomy, the intravesical Politano-Leadbetter (P-L) technique was used., Results: Two-year patient and graft survival was 99% and 98%, respectively. Serum creatinine at 12 months was 1.36+/-0.1mg/dl in adult and 0.99+/-0.23 mg/dl in pediatric recipients. Nineteen right donor kidneys were transplanted into adult recipients. Surgical complications included three symptomatic lymphoceles, one peritransplant haematoma and one kinking of a lower pole artery. All five (4.5%) ureteral complications occurred in adult recipients with a mean age of 33.2+/-2.8 years. The incidence of ureteral complications was not clustered around the early phase of our LLDN experience. Of the three (2.7%) patients diagnosed with ureteral obstruction, two required ureteral reimplantation, and one was managed conservatively. Another two patients (1.8%) with a urinary leak received a double J stent and a cystostomy catheter for 3 and 5 months, respectively. Of the five patients with a ureteral complication, three had received a donor kidney with more than one renal artery., Conclusions: LLDN combined with the intravesical (P-L) ureteral implantation technique provides excellent graft outcomes with low recipient morbidity. Renal artery multiplicity may increase the risk of ureteral complications.

We performed a prospectively randomised clinical trial to compare the efficacy of four subcutaneous interleukin-2-(sc-IL-2) and sc interferon-alpha2a (sc-IFN-alpha2a)-based outpatient regimens in 379 patients with progressive metastatic renal cell carcinoma. Patients with lung metastases, an erythrocyte sedimentation rate < or =70 mm h(-1) and neutrophil counts < or =6000 microl(-1) (group I) were randomised to arm A: sc-IL-2, sc-IFN-alpha2a, peroral 13-cis-retinoic acid (po-13cRA) (n=78), or arm B: arm A plus inhaled-IL-2 (n=65). All others (group II) were randomised to arm C: arm A plus intravenous 5-fluorouracil (iv-5-FU) (n=116), or arm D: arm A plus po-Capecitabine (n=120). Median overall survival (OS) was 22 months (arm A; 3-year OS: 29.7%) and 18 months (arm B; 3-year OS: 29.2%) in group I, and 18 months (arm C; 3-year OS: 25.7%) and 16 months (arm D; 3-year OS: 32.6%) in group II. There were no statistically significant differences in OS, progression-free survival, and objective response between arms A and B, and between arms C and D, respectively. Given the known therapeutic efficacy of sc-IL-2/sc-INF-alpha2a/po-13cRA-based outpatient chemoimmunotherapies, our results did not establish survival advantages in favour of po-Capecitabine vs iv-5-FU, and in favour of short-term inhaled-IL-2 in patients with advanced renal cell carcinoma receiving systemic cytokines.

Objectives: With increasing surgical skills and novel methods of hemostasis laparoscopic Partial nephrectomy has become an attractive treatment option for selected renal tumors. We report techniques, perioperative data and oncological outcome in a single center experience with three different surgeons., Patients and Methods: Between March 2001 and October 2004, 44 patients underwent laparoscopic transperitoneal partial nephrectomy for exophytic tumors. Median tumor size was 3 cm (1-5 cm). In 25 cases the renal artery was clamped using endoscopic bulldog clamps and tumor resection was performed with scissors or the harmonic scalpel. Hemostasis was achieved by application of FloSeal only; closure of the collecting system with Lahodny sutures was performed, if necessary. Frozen sections were obtained in all cases., Results: All procedures were successful with no intraoperative complications. Mean surgical time was 210 min (115-355 min); clamping time was 21 min (7-41 min) in 25 cases. In 8 cases suturing of the collecting system was required. Margins were negative in 37 cases, in five cases secondary resection was necessary to achieve negative margin status; in two cases radical nephrectomy was performed. There were no significant differences between surgeons in terms of patient data and results. At a mean follow-up of 15 months (6-37 months) no recurrence was observed., Conclusions: Laparoscopic partial nephrectomy using FloSeal is a feasible and safe method for treatment of small renal masses. The technique is reproducible by surgeons who are used to complex laparoscopic procedures like expected in high volume laparoscopic centers.

Objective: Both laparoscopic surgery and antegrade sclerotherapy are effective treatment options in the management of varicoceles. However, very limited data comparing these two approaches are available in the literature. We present our experience regarding outcome and complications with each treatment modality., Patients and Methods: During a 10-year period, 122 cases of laparoscopic varicocelectomy (LV) and 108 cases of antegrade sclerotherapy (AS) were performed in our institution. Diagnosis and postoperative results were established clinically and using Doppler ultrasonography. Data regarding failure rate, complications, operative time and length of hospital stay of each procedure were retrospectively evaluated., Results: Median follow-up was 59 months (5-130). Failure rates for LV and AS were 4.9% and 15.7%, respectively (p < 0.01). Complications occurred in 13.1% after LV, including 13 cases (10.7%) of hydrocele formation, and 4.6% after AS. Hydroceles following LV were significantly more frequent in patients with compared to patients without previous inguinal surgery (27.8% vs. 8.5%; p < 0.05). There was no significant difference between LV and AS regarding operative time (36 vs. 34 min, p > 0.05) and hospital stay (2.2 vs. 2.1 days, p > 0.5)., Conclusions: In our experience, LV was more effective than AS in correcting varicoceles. Complications other than hydroceles were higher after AS. The higher incidence of postoperative hydrocele formation following LV warrants strategies such as the lymphatic sparing approach, especially in patients with previous inguinal surgery.

Ten years ago the first laparoscopic living donor nephrectomy (LDN) was performed. Today, LDN is a routine operation in many US-American transplantation centers and an increasing number of centers in Europe are practicing LDN. In this article the different aspects of LDN for donor, kidney, recipient and operating surgeon are evaluated. We performed a literature research concerning LDN and the different aspects. Our own experience, as the largest LDN center in Germany, is part of the evaluation. Laparoscopic extraction of a kidney from a living donor is as safe for the donor as the open approach. At the same time, LDN offers multiple advantages like reduced pain and shorter convalescence. For the donated kidney and the recipient no disadvantages occur from the laparoscopic technique, as long as special intra- and perioperative demands are met. For the operating surgeon multiple developments have expanded the technical armentarium. LDN is safe for donor, recipient and kidney. Central issue of an optimal LDN is sufficient experience with laparoscopic urological techniques.

Objective: The literature regarding the constitutional type of children and adolescents with varicocele is inconsistent. The aim of this investigation was to examine a possible influence of weight, height and body mass index (BMI) on the formation of varicoceles during childhood and adolescence., Material and Methods: In a retrospective data analysis, 193 Caucasian children and adolescents aged 9-19 years (mean age 14.7 years) with left-sided varicocele grade 2-3 were studied. The weight, height and BMI of the subjects were compared with the age-correlated normal values currently accepted in Germany. Additionally, the familial disposition for varicocele and the occurrence of relevant concurrent diseases were considered., Results: In the group of patients examined, the mean percentiles of weight (57th) and height (58th) were significantly above and the mean BMI percentile (42th) was significantly below the age-correlated 50th percentile for the normal population (p=0.019, 0.005 and 0.002). In our case material, 12.2% of all brothers of the patients had varicoceles., Conclusions: The results of this investigation suggest a correlation between physical appearance and the formation of a varicocele during childhood or adolescence. We were able to demonstrate that patients with varicocele were heavier and taller than an age-correlated normal population, but had a distinctly lower BMI. Further studies are needed to verify whether this rather athletic habitus, together with the postulated difference in muscle:fat ratio, represents an important etiologic factor for varicocele formation.

The reasons for end-stage renal disease in pediatric patients differ from adults. The therapy of choice is renal transplantation. A total of 117 children and adolescents were treated with renal transplantation in 2003 in Germany. Immunosuppressive therapy and related comorbidities are the main problems in pediatric patients. The following article provides a summary of transplantation in children, preparation, and follow-up.

Methods: In this study we investigated the anesthesiological module of a clinical pathway. We chose the pathway of "laparoscopic prostatectomy" as an example for time-consuming minimally invasive surgery and 40 patients were randomly assigned to 2 groups receiving either total intravenous anesthesia (TIVA) using propofol/ remifentanil or balanced minimal flow anesthesia using desflurane/ remifentanil. During this module the indicators of quality such as vigilance, pain, postoperative nausea and vomiting (PONV) and mobilization were measured. Costs were evaluated and analyzed by a bottom-up procedure., Results: There were no anesthesia-related deviations from clinical pathways and both forms of anesthesia management were equally well tolerated by the patients. No significant difference was observed regarding hemodynamic measurements or PONV. The patients in the desflurane/ remifentanil group recovered more rapidly (p=0.037) and had more pain. The amount of analgesic agents given immediately following anesthesia was significantly higher than in the TIVA group (p=0.017). The median anesthesia costs per minute for laparoscopic prostatectomy in the propofol group were 2.79 EUR (minimum cost 2.41 EUR, maximum cost 3.21 EUR) and in the desflurane group 2.68 EUR (minimum cost 2.45 EUR, maximum cost 3.39 EUR). The total anesthesia costs for both groups were within the proceeds matrix range for diagnosis-related groups (DRG). However, the cost analysis for medication was slightly higher than the proceeds matrix range for DRGs., Conclusion: Both forms of anesthesia can be implemented for time-consuming surgical procedures and allow a cost-effective anesthesia management. Anesthesiological procedures must go hand-in-hand with the type of anesthesia selected. The prophylactic use of analgetics for desflurane/ remifentanil anesthesia should be given earlier and in higher doses than in propofol/ remifentanil anesthesia. The prophylactic use of antiemetics following laparoscopic procedures of long duration is indicated. Optimizing anesthesiological procedures could lead to a continuous improvement in the quality of therapeutic pathways.

Today, laparoscopic donor nephrectomy (LDN) in many centers features the standard approach for kidney retrieval in living donors. More than 60% of the centers in the USA currently perform LDN and numbers are rising in Europe as well. Today's variety of laparoscopic approaches reflects the evolution in the field of LDN. Multiple modifications have been made for the laparoscopic approach, with consequences for intraoperative handling of the kidney, operating and ischemic times and with impact on donor, organ, and recipient. We reviewed the literature from 1995 to 2004 and critically evaluated the different technical modifications, their specific advantages and disadvantages and their impact for the operation. The article aims to help the surgeon choose the technique he feels most safe with for performing laparoscopic kidney retrieval safely and with good results for donor and recipient.

The urokinase-type plasminogen activator (uPA) system plays a central role in extracellular matrix degradation, cell migration, and invasion. uPA belongs to the family of serine proteases. It has been shown that its proteolytic activity is involved in the metastatic process by activation and binding to its receptor (uPAR). Previous studies in several organ systems have elucidated a higher uPA expression in malignant tissue in comparison to normal tissue. In this study uPA and uPAR gene expression were investigated in 18 human renal cell carcinoma (RCC) specimens in comparison with adjacent non-malignant renal tissues. mRNA in situ hybridisation and immunohistochemical staining were performed. mRNA of uPA and uPAR was significantly higher expressed in 56% (10/18) and 72% (13/18) of the RCC specimens in comparison to the adjacent non-malignant renal tissue (p<0.0001), respectively. uPA-mRNA and uPAR-mRNA were expressed predominantly in malignant renal cells and in very few surrounding stromal cells. The elevated expression of uPAR-protein in RCC reached statistical significance compared to adjacent normal tissue (p=0.007). uPAR genes were higher expressed in comparison to uPA alone. There was a statistical trend that higher expression of uPA and uPAR corresponded with TNM tumour stage and grade in RCC. Further investigations need to be done with larger sample sizes to prove a correlation of expression between uPA and uPAR to a more aggressive phenotype. We conclude that uPA- and uPAR are overexpressed in RCC and could function as tumour markers.

Objective: We investigated the efficacy and toxicity of a first-line combination chemotherapy using weekly paclitaxel and carboplatin in patients with metastatic transitional cell cancer (TCC)., Patients and Methods: Thirty-three patients with advanced measurable TCC of the urothelium were entered onto this trial. Patients were treated once weekly with a combination therapy of paclitaxel (100mg/m(2)) and carboplatin (AUC 2, according to the Calvert formula). Therapy courses were administered for six consecutive weeks. After two cycles, a re-staging was carried out to evaluate response., Results: Objective response rate was 57.6% with 6 complete (18.2%) and 13 partial remissions (39.4%). Seven patients had stable disease (21.2%) and 7 patients had progressed at the first evaluation of response (21.2%). Median progression-free interval and median survival was 6.5 (1-35) and 12 (2.5-58) months, respectively. Toxicity was moderate and manageable with grade 3 and 4 neutropenia in 8 patients (24%), but no case of neutropenic fever. Other hematological grade 3 toxicities occurred in 9 patients (27%) and grade 3 peripheral neuropathy in 2 patients (6%). There was no treatment-related death. Dose reduction or short delay of treatment was necessary in 3 patients., Conclusions: Combination therapy using weekly paclitaxel and carboplatin was active in patients with advanced TCC and adverse prognostic features. The weekly dosing used in this trial warrants further investigation as an alternative first-line approach in patients with poor renal reserve and/or performance status or as a second-line management of advanced TCC.

Nonmyeloablative stem cell transplantation (NST) and donor lymphocyte infusions (DLI) are currently under clinical investigation as an innovative therapeutic option for patients with metastatic renal cell carcinoma (RCC). The underlying concept, adopted from patients with hematologic malignancies, aims at a reduction of conditioning toxicity and exploits the graft versus malignancy effect of donor T-lymphocytes after transplantation. Clinical data from more than 100 patients treated worldwide have been published so far. The data provide evidence that NST is feasible with a very low rate of engraftment failure. Objective remissions in these heterogenous studies were observed in 23% of the patients overall. Remissions after NST developed only after complete engraftment of donor lymphoid cells had occurred. Objective responses were almost always accompanied by graft versus host disease (GvHD) after withdrawal of immunosuppression and/or DLI. GvHD and infections were the main contributors to a substantial transplant related morbidity and mortality, the major drawback of allogeneic stem cell transplantation. Therefore, clinical studies are necessary to further investigate and improve the selection of patients with metastatic RCC or other solid tumors for NST and to reduce post-transplant complications. This article reviews the results, side effects and potential future developments of NST in the treatment of solid tumors.

Objectives: To evaluate the outcome of high dose rate (HDR) brachytherapy with iridium 192 (Ir(192)) and 3D conformal external beam radiotherapy in patients with localized prostate cancer., Methods: A total of 442 patients with localized prostate cancer underwent combined radiotherapy with interstitial brachytherapy with Ir(192) and 3D conformal external beam radiotherapy between December 1992 and March 2001. Patients underwent laparoscopic pelvic lymph node dissection to exclude patients with lymphatic involvement. Iridium 192 was delivered twice with a one-week interval in afterloading technique. 247 patients (56%) had clinical T3 disease and 128 patients (29%) had an initial PSA of more than 20 ng/ml. Progression was defined as biochemical failure according to ASTRO criteria. Patients were divided according to pretreatment variables that independently affected prostate-specific antigen (PSA) relapse-free survival in three risk groups. Low risk was defined as cT1c-cT2 and G1-G2 and PSA<10 ng/ml (n=94). Intermediate risk included patients with cT1c-cT2 and G1-G2 and PSA between 10 and 20 ng/ml (n=53). High risk group patients were cT3 or G3 or PSA>20 ng/ml (n=295)., Results: Median follow-up was 5 years. Late grade 3-4 complications according to RTOG/EORTC criteria occurred in 50 patients (11%). The initial PSA value decreased from median 11.8 ng/ml to 0.98 ng/ml 12 months after treatment, to 0.3 ng/ml after 60 months and to 0.1 ng/ml 10 years after therapy. 53% of the patients (n=235) reached a PSA nadir of 0.5 ng/ml. 66 patients (15%) had a local recurrence, 54 (12%) developed systemic disease and 12 (3%) had both local and systemic failure. The progression free survival rate was 65% at 5-year follow-up. Five-year progression free survival was 81% in the low risk group, 65% in the intermediate risk group and 59% in the high risk group. Five-year overall survival was 87% and 5-year disease specific survival 94%. Initial PSA value, risk group and age were significantly related to progression free survival., Conclusions: Combined HDR brachytherapy with Iridium 192 is an alternative treatment option for patients with localized prostate cancer. Initial PSA value, risk group, and age are important prognostic factors for progression free survival.

Laparoscopic live donor nephrectomy (LDN) has removed disincentives of potential donors and may bear the potential to increase kidney donation. Multiple modifications have been made to abbreviate the learning curve while at the same time guarantee the highest possible level of medical quality for donor and recipient. We reviewed the literature for the evolution of the different LDN techniques and their impact on donor, graft and operating surgeon, including the subtleties of different surgical accesses, vessel handling and organ extraction. We performed a literature search (PubMed, DIMDI, medline) to evaluate the development of the LDN techniques from 1995 to 2003. Today more than 200 centres worldwide perform LDN. Hand-assistance has led to a spread of LDN. Studies comparing open and hand-assisted LDN show a reduction of operating and warm ischaemia times for the hand-assisted LDN. Different surgical access sites (trans- or retroperitoneal), different vessel dissection approaches, donor organ delivery techniques, delivery sites and variations of hand-assistance techniques reflect the evolution of LDN. Proper techniques and their combination for the consecutive surgical steps minimize both warm ischaemia time and operating time while offering the donor a safe minimally invasive laparoscopic procedure. LDN has breathed new life into the moribund field of living kidney donation. Within a few years LDN could become the standard approach in living kidney donation. Surgeons working in this field must be trained thoroughly and well acquainted with the subtleties of the different LDN techniques and their respective advantages and disadvantages.

Purpose: ADAMs (a disintegrin and metalloproteinases) as cell surface proteins with adhesion and protease activity, and hepsin as a transmembrane protease have important roles in many biological processes. We assessed the expression of various ADAMs and of hepsin in human renal cell carcinoma (RCC), and correlated expression with clinicopathological data., Materials and Methods: mRNA expression of ADAM-8, 17, 19, 28, TS1 and TS2, and of hepsin was investigated in paired tissue samples from cancerous and noncancerous parts of the kidneys of 27 patients with RCC who underwent tumor nephrectomy. Measurements were performed by quantitative real-time reverse transcriptase-polymerase chain reaction on a LightCycler instrument (Roche Applied Science, Mannheim, Germany). The data were related to housekeeping gene porphobilinogen deaminase mRNA., Results: All ADAMs except ADAM-TS1 were significantly higher but hepsin was less expressed (at least p <0.05) in cancerous vs matched noncancerous tissue. Expression was differentially related to tumor stage. ADAM-8 and ADAM-TS2 over expression as well as decreased hepsin expression were associated with shorter patient survival. The Cox proportional hazards regression model revealed that ADAM-TS2 was an independent prognostic factor for cancer related death. ADAM-8 was the best predictor of distant metastases., Conclusions: The differential expression of hepsin and ADAMs suggests early and late involvement of membrane proteases in the development of RCC. Their association with the clinical outcome illustrates their potential usefulness as biomarkers for RCC.

Objectives: To present our experience with the first series of rectosigmoid pouch creation performed completely laparoscopically for continent urinary diversion after radical cystectomy to treat transitional cell carcinoma of the bladder. We evaluated the intermediate functional and oncologic outcomes., Methods: Between April 2000 and January 2004, 20 patients underwent laparoscopic radical cystectomy with urinary diversion for transitional cell carcinoma at the Department of Urology, Charite Hospital, Campus Mitte. Of the 20 patients, 12 received a rectosigmoid pouch for urinary diversion. The procedures were performed completely laparoscopically, including free-hand laparoscopic suturing and in situ knot tying techniques. The mobilized specimens were removed in an endoscopy bag by way of the rectum or vagina., Results: All operations were completed laparoscopically by two surgeons without conversion to open surgery. The median operating time was 485 minutes. One patient needed a blood transfusion of 2 U. All specimens had negative surgical margins. Two patients required reoperation. The median follow-up was 33 months. All patients were continent during the day, and 11 patients were continent at night. One patient developed unilateral hydronephrosis with loss of kidney function. No patient developed local recurrence, but 3 patients had systemic progression. Two of the three died of metastatic disease., Conclusions: This is the first series of laparoscopic radical cystectomy using an intracorporeal rectosigmoid pouch. Our functional data for continence and upper urinary tract obstruction were comparable with those of open rectosigmoid pouch studies. We were able to demonstrate an oncologic outcome similar to that achieved by the open surgical approach.

The transient addition of the cytosolic energy depletor 2-deoxy-glucose to cultures of rat prostate carcinoma cells blunted the induction of Hsp70 protein following exposure to elevated temperatures in a manner that appeared to parallel its effects on energy metabolism. While the reduction in stress-induced heat-shock protein expression by treatment with 2-deoxy-glucose had no effects on the acute loss of cellular viability after exposure to heat, the acquisition of thermotolerance in response to a conditioning stimulus was specifically repressed. Therefore, 2-deoxy-glucose will be a useful tool in the investigation of mechanisms that mediate immediate versus chronic responses to cellular stress, including the specific roles played by members of the heat-shock protein family of proteins. These results might have important implications in the design of protocols for the hyperthermic treatment of tumours.

Seven out of 29 patients with metastatic renal cell carcinoma (RCC) considered eligible for allogeneic stem cell transplantation underwent nonmyeloablative stem cell transplantation (NST) from HLA-identical donors. Conditioning comprised cyclophosphamide, fludarabine and antithymocyte globulin. Prolonged mixed chimerism (MC) after engraftment converted to complete donor chimerism (CC) after infusion of donor lymphocytes and/or graft-versus-host disease (GvHD) in six patients. Five patients developed severe GvHD. Two of seven patients had a delayed tumor response after conversion to CC. After a median follow-up of 10 months (4-24 months), 5/7 patients are alive, one in very good partial remission (PR), one with stable and three with progressive disease. One of the seven patients died from sepsis in PR and 1/7 died from rapid tumor progression after sustained MC. None of the 22 nontransplanted patients responded to further therapies. Survival after 1 year was 59% in transplanted and 66% in nontransplanted patients (n.s.). A pooled data analysis from the literature suggests a graft-versus-tumor effect after transplant in patients with metastatic RCC, which becomes effective after chimerism conversion. Available data demonstrate high nonrelapse mortality in these patients. NST in RCC still has to be regarded as an investigational approach requiring careful patients' selection and longer follow-up within clinical studies.

Purpose: To examine the feasibility and potential of magnetic fluid hyperthermia (MFH) as a minimally invasive method for hyperthermia treatment of prostate cancer., Materials and Methods: Orthotopic Dunning R3327 prostate tumors were induced in 20 male Copenhagen rats. The animals either received MFH treatment following intratumoral administration of magnetic fluids or were used as either tumor growth controls for determination of iron distribution in selected organs or as histologic controls without MFH treatment. The MFH treatments were carried out at 45 degrees C or 50 degrees C using an AC magnetic field applicator system designed for small animals., Results: Sequential treatments with MFH were possible following a single intratumoral injection of magnetic fluid. Intratumoral temperatures of 50 degrees C and more were obtained and were monitored online using fluoro-optic thermometry. Four days after MFH treatments, 79% of the injected dose of ferrites was still present in the prostate., Conclusions: The successful intraprostatic nanoparticle infiltration and stable steady-state intratumoral treatment temperatures demonstrate the feasibility of MFH in a prostate cancer model. Efficacy and survival benefit must be confirmed in further experiments.

Objective: Thermoradiotherapy in the treatment of prostate cancer is based on a variety of experimental and clinical phase I data which have proven the synergistic effects of this combination. We report on a phase II trial in a special hyperthermia research group (SFB 273) of the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) to determine feasibility, acute toxicity and efficacy of this combination for prostate cancer., Methods: 57 patients with localized prostate cancer were treated with interstitial hyperthermia using cobalt-palladium thermoseeds and conformal radiation between July 1997 and December 2000. Thermoseeds were placed into the prostate homogeneously. Hyperthermia was created using a magnetic field and was delivered in six sessions once weekly for one hour. 3D-conformal radiotherapy of 68.4Gy was given simultaneously in daily fractions of 1.8Gy., Results: Intraprostatic temperatures were between 42 and 46 degrees C. No major side effects were observed during hyperthermia. Median follow-up was 36 months (range 3-72 months). Median PSA value decreased from 11.6ng/ml to 2.4ng/ml 3 months after treatment, to 1.3ng/ml 12 months after treatment and to 0.55ng/ml 2 years after therapy., Conclusion: Interstitial hyperthermia is feasible, well tolerated and led to a steep decrease of PSA values. Combining effective interstitial hyperthermia with conformal radiotherapy may be an exciting innovative treatment option for prostate cancer.

Purpose: We conducted a prospectively randomized clinical trial to compare the efficacy of three outpatient therapy regimens in 341 patients with progressive metastatic renal cell carcinoma., Patients and Methods: Patients were stratified according to known clinical predictors and were subsequently randomly assigned. Treatment arms were: arm A (n = 132), subcutaneous interferon alfa-2a (sc-IFN-alpha-2a), subcutaneous interleukin-2 (sc-IL-2), and intravenous (IV) fluorouracil; arm B (n = 146): arm A treatment combined with per oral 13-cis-retinoic acid; and arm C (n = 63), sc-IFN-alpha-2a and IV vinblastine., Results: Treatment (according to the standard 8-week Hannover Atzpodien regimen) arms A, B, and C yielded objective response rates of 31%, 26%, and 20%, respectively. Arm B, but not arm A, showed a significantly improved progression-free survival (PFS) compared with arm C (P =.0248). Both arm A (median overall survival, 25 months; P =.0440) and arm B (median overall survival, 27 months; P =.0227) led to significantly improved overall survival (OS) compared with arm C (median OS, 16 months). All three sc-IFN-alpha-2a-based therapies were moderately or well tolerated., Conclusion: Our results established the safety and improved long-term therapeutic efficacy of sc-IL-2 plus sc-INF-alpha-2a-based outpatient immunochemotherapies, compared with sc-INF-alpha-2a/IV vinblastine.

Objectives: Renal cell carcinoma is likely to become one of the most important indication for laparoscopic surgery. The laparoscopic technique combines the benefits of minimal invasive approach with established surgical principles. In our institution the laparoscopic transperitoneal approach with intact specimen removal has become the standard technique for radical nephrectomies. We report the indications, techniques and oncological outcome in a single center experience., Patients and Methods: Between July 1999 and March 2003 we performed laparoscopic radical nephrectomies for renal cell cancer in 125 patients. Their initial staging, complications, and postoperative course were evaluated. During this period a total of about 1800 laparoscopic cases were performed. To date 82 patients were available for follow up data and have been analyzed for oncological outcome. Patients with primary metastatic disease were excluded from this analysis., Results: 123 procedures out of 125 were successful. In two cases (1.6%) conversion to open surgery was necessary due to bleeding (1 case) or bowel injury (1 case). In additional 3 cases (2.4%) intraoperative complications could be managed laparoscopically. In two cases (1.6%) postoperative bleeding lead to open revision for hemostasis. The mean tumor size was 5.1cm (range 2-14 cm); median blood loss was 210 ml (range 50-900 ml). The mean surgical time was 200 min (range 90-435), including the learning curves of five surgeons. Histological findings were pT1 in 78 (62.4%), pT2 in 12 (9.6%) and pT3 in 28 (22.4%) patients. In 7 cases (5.6%) histology did not confirm malignant disease. Positive lymph nodes were detected in 3 cases (2.4%); surgical margins were negative for tumor in all patients. Follow-up was between 3 and 50 months with an average of 23.5 months. Disease progression was observed in 3 cases after 6, 11 and 12 months. No cases of local recurrence or port metastasis occurred during observation., Conclusions: Laparoscopic radical nephrectomy is a routine, effective treatment for patients with pT1-2N0M0 renal cell carcinoma. With more experience a tumor up to 10-12 m in size can be managed safely offering all the benefits of minimal surgery to the patients. Although no long-term follow-up is available our follow-up data up to 50 months confirm the effectiveness of laparoscopic radical nephrectomy in terms of surgical principles and oncological outcome.

ADAMs (a disintegrin and metalloproteinase) are cell-surface proteins with adhesion and protease activity which play important roles in many biological processes. Little is known about their role in cancer. The aim of the study was to assess the quantitative expression of the ADAMs in human renal cell carcinoma (RCC) and to associate expression levels with clinicopathological data. We investigated the mRNA expression of ADAM-8, -17, -19, -28, ADAM-TS1, and ADAM-TS2 in paired tissue samples from cancerous and non-cancerous parts of the kidneys of 27 patients with RCC who underwent tumour nephrectomy. Measurements were performed by means of the quantitative real-time RT-PCR on a LightCycler instrument. ADAM-8, -17, and -19 were significantly higher expressed (p<0.05 at least) in cancerous compared with the matched non-cancerous tissue in pT1 and > or =pT2 tumours, ADAM-28 and ADAM-TS2 only in pT1 tumours, and ADAM-TS1 was not differently expressed. All ADAMs except ADAM-TS1 showed an increase of expression in the non-cancerous tissue with rising pT stage suggesting an early involvement of ADAMs in the development of RCC. The expression of ADAM-8 was related to a shorter survival of patients and was the best predictor of distant metastases. Our results indicate a potential role for ADAMs in RCC and that the overexpression might be a useful predictive tool.

The M2 isoenzyme of pyruvate kinase (M2-PK) is specifically expressed in tumor cells (TuM2-PK) and has been detected in the peripheral blood of patients with renal cell carcinoma (RCC). TuM2-PK is not useful as a biological marker in localized RCC. We analysed TuM2-PK in 68 patients with metastatic RCC after initial surgery and prior to or during chemoimmunotherapy of metastases. In 50 patients, the levels of TuM2-PK were measured during chemoimmunotherapy with interleukin-2, interferon-alpha2a and 5-fluorouracil for up to 8 months and were correlated to response as assessed by radiological imaging techniques. TuM2-PK was quantified with a commercially available enzyme linked immunosorbent assay kit using a cut off of 15 kU/l. In 48 of 68 patients (71%), TuM2-PK was elevated above the cut-off. TuM2-PK was significantly higher in G3 tumors than in G2 tumors. In 34 of 50 patients (68%) undergoing chemoimmunotherapy, a positive correlation between TuM2-PK values and response to treatment was observed. Based on these data, we would not recommend the routine clinical use of TuM2-PK in metastatic RCC at this point.