Kidney transplantation in children and adolescents.

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.

Morbidity and quality of life during thermotherapy using magnetic nanoparticles in locally recurrent prostate cancer: results of a prospective phase I trial.

PURPOSE: To investigate the treatment-related morbidity and quality of life (QoL) during thermotherapy using superparamagnetic nanoparticles in patients with locally recurrent prostate cancer. MATERIALS AND METHODS: Ten patients with biopsy-proven locally recurrent prostate cancer following primary therapy with curative intent and no detectable metastases were entered on a prospective phase I trial. Endpoints were feasibility, toxicity and QoL. Following intraprostatic injection of a nanoparticle dispersion, six thermal therapy sessions of 60 min duration were delivered at weekly intervals using an alternating magnetic field. National Cancer Institute (NCI) common toxicity criteria (CTC) and the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-PR25 questionnaires were used to evaluate toxicity and QoL, respectively. In addition, prostate specific antigen (PSA) measurements were carried out. RESULTS: Maximum temperatures up to 55 degrees C were achieved in the prostates at 25-30% of the available magnetic field strength. Nanoparticle deposits were detectable in the prostates one year after thermal therapy. At a median follow-up of 17.5 months (3-24), no systemic toxicity was observed. Acute urinary retention occurred in four patients with previous history of urethral stricture. Treatment-related morbidity was moderate and QoL was only temporarily impaired. Prostate-specific antigen (PSA) declines were observed in eight patients. CONCLUSIONS: Interstitial heating using magnetic nanoparticles was feasible and well tolerated in patients with locally recurrent prostate cancer. Deposition of nanoparticles in the prostate was highly durable. Further refinement of the technique is necessary to allow application of higher magnetic field strengths.

[Cytokine-based and targeted therapy of metastatic renal cell carcinoma--a current analysis]. / Zytokinbasierte und molekulare Therapie des metastasierten Nierenzellkarzinoms--eine aktuelle Analyse.

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.

Fast-track surgery in laparoscopic radical prostatectomy: basic principles.

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.

[Management of trauma to the male external genitalia]. / Externes Genitaltrauma beim Mann.

Male genital injury, although rarely life-threatening, demands prompt, appropriate management to prevent long-term sexual and psychological damage. However, because of the rarity and disparity of severe genital injuries, there is still no universal therapeutic strategy. Urethral injury, although rare, may be associated with substantial long-term morbidity such as fistulas and strictures. Injuries to the scrotum and its contents may cause impaired fertility, chronic pain, hypogonadism, and altered self-image. Penile injury may lead to pain, curvature, and erectile dysfunction. This article concentrates on reviewing the major etiologies and mechanisms of urethral and genital injuries in men and summarizes principles and strategies of treatment based on the guidelines of the European Association of Urology.

[Kidney transplantation in childhood and adolescence]. / Nierentransplantation im Kindes- und Jugendalter.

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.

[Ten years of laparoscopic living kidney donation. From an extravagant to a routine procedure]. / 10 Jahre laparoskopische Lebendnierenspende. Von Rarität zu Routine.

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.

Loss of the tissue-specific proapoptotic BH3-only protein Nbk/Bik is a unifying feature of renal cell carcinoma.

We report for the first time inactivation of a tissue-specific Bcl-2 homology domain 3 (BH3)-only protein as a common aspect in human cancer. In detail, we show that loss of the BH3-only protein natural born killer (Nbk)/Bcl-2-interacting killer (Bik) is a common feature of clear-cell renal cell carcinoma (RCC). While strong Nbk expression is found in the renal tubuli and the epithelial lining of the glomerula, a consistent loss of Nbk expression was observed in primary RCC tissue and RCC cell lines. Mutation of Nbk is, however, rare, whereas deletion of the Nbk gene at 22q13.2 is frequent. In addition to loss of heterozygosity (LOH), DNA methylation mediates transcriptional silencing of the Nbk gene. The conditional restoration of Nbk/Bik expression led to apoptotic death of RCC but not of nonmalignant renal epithelia. A broader expression analysis of RCC cell lines for BH3-only proteins revealed that loss of Nbk coincides with failure to express Bim, whereas Puma, Bid and BNIP3 are readily detectable and, in case of Puma, inducible by p53. These data delineate a role for defects in BH3-only proteins as tumor suppressors in RCC and may explain at the same time the impressive clinical apoptosis resistance of RCC.

[Urological evaluation and follow-up of the kidney transplant patient]. / Urologische Betreuung von Patienten vor und nach Nierentransplantation.

Patients with end-stage renal disease awaiting kidney transplantation require regular urological evaluation. The urologist's main task is early diagnosis and treatment of genitourinary malignancies and evaluation of the lower urinary tract. Furthermore, urologists are often confronted with the question of whether or not to perform pretransplant urological surgery, i.e., native nephrectomy for polycystic kidney disease. Urological care after kidney transplantation involves diagnosis and treatment of ureteral complications, malignancies, lower urinary tract symptoms, and last but not least erectile dysfunction, which has a prevalence of 20-50% among kidney transplant recipients. For the evaluation and follow-up of the living kidney donor, international guidelines have been developed in recent years to also help the urologist to perform a correct evaluation and follow-up of the kidney donor.

Clinical hyperthermia of prostate cancer using magnetic nanoparticles: presentation of a new interstitial technique.

The aim of this pilot study was to evaluate whether the technique of magnetic fluid hyperthermia can be used for minimally invasive treatment of prostate cancer. This paper presents the first clinical application of interstitial hyperthermia using magnetic nanoparticles in locally recurrent prostate cancer. Treatment planning was carried out using computerized tomography (CT) of the prostate. Based on the individual anatomy of the prostate and the estimated specific absorption rate (SAR) of magnetic fluids in prostatic tissue, the number and position of magnetic fluid depots required for sufficient heat deposition was calculated while rectum and urethra were spared. Nanoparticle suspensions were injected transperineally into the prostate under transrectal ultrasound and flouroscopy guidance. Treatments were delivered in the first magnetic field applicator for use in humans, using an alternating current magnetic field with a frequency of 100 kHz and variable field strength (0-18 kA m(-1)). Invasive thermometry of the prostate was carried out in the first and last of six weekly hyperthermia sessions of 60 min duration. CT-scans of the prostate were repeated following the first and last hyperthermia treatment to document magnetic nanoparticle distribution and the position of the thermometry probes in the prostate. Nanoparticles were retained in the prostate during the treatment interval of 6 weeks. Using appropriate software (AMIRA), a non-invasive estimation of temperature values in the prostate, based on intra-tumoural distribution of magnetic nanoparticles, can be performed and correlated with invasively measured intra-prostatic temperatures. Using a specially designed cooling device, treatment was well tolerated without anaesthesia. In the first patient treated, maximum and minimum intra-prostatic temperatures measured at a field strength of 4.0-5.0 kA m(-1) were 48.5 degrees C and 40.0 degrees C during the 1st treatment and 42.5 degrees C and 39.4 degrees C during the 6th treatment, respectively. These first clinical experiences prompted us to initiate a phase I study to evaluate feasibility, toxicity and quality of life during hyperthermia using magnetic nanoparticles in patients with biopsy-proven local recurrence of prostate cancer following radiotherapy with curative intent. To the authors' knowledge, this is the first report on clinical application of interstitial hyperthermia using magnetic nanoparticles in the treatment of human cancer.

[Relevance of intraoperative frozen section diagnostics in urological surgery]. / Stellenwert der intraoperativen Schnellschnittdiagnostik in der Urologie.

Intraoperative frozen section diagnosis (FSD) plays an important role in urological surgery. The surgeon obtains information on suspicious tissue and can adapt his strategy for the operation, thus sparing the patient from a second intervention. Most important for a successful FSD is close co-operation between the urologist and an experienced pathologist. A very reliable assessment of urological tissues can be made with the help of FSD. The same applies for the margin status of tumours, which is most important for example in renal tumour enucleation to achieve the same oncological result as with a radical tumour nephrectomy. For the diagnosis of lymph nodes the indication for FSD depends on the urological primary lesion. Especially for prostate cancers some authors rather recommend the evaluation of the nodal status according to nomograms. FSD for "sentinel nodes" is promising but has not yet found its way into routine diagnostics.

Laparoscopic versus open donor nephrectomy in Germany: impact on donor health-related quality of life and willingness to donate.

INTRODUCTION: Laparoscopic living donor nephrectomy (LDN) offers multiple advantages to the donor. Since 1999 LDN has become the only surgical approach for living kidney donation in our department. To our knowledge a donor health-related quality of life (QoL) has not yet been performed with standardized and validated questionnaires to compare laparoscopic with open nephrectomy. We therefore performed a study with two questionnaires (SF-36/GBB-24) and one set of open questions for all donors in our department. METHODS: Questionnaires were sent out to all donors between 1983 and 2001 with at least a 1-year follow-up. To exclude a bias a maximum response rate was sought; donors who did not answer were recontacted as well as their recipients or their physicians to motivate them for participation. RESULTS: The response rate was (89.8%). Except for less limb pain in the laparoscopy group, no difference could be detected for donors QoL with respect to the surgical method. Willingness to donate again was not affected by the surgical method. Nevertheless if asked again today, most donors want laparoscopic kidney retrieval. CONCLUSIONS: Donors health-related QoL is not affected by the surgical method when queried retrospectively. Nevertheless, most donors today would favor laparoscopy, if they could chose again. How laparoscopy affects a reluctant donor to step forward must be determined in a prospective study.

Laparoscopic donor nephrectomy.

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.

Repression of thermotolerance in Dunning R3327 prostate carcinoma cells by 2-deoxy-glucose.

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.

Quality of life of living kidney donors in Germany: a survey with the Validated Short Form-36 and Giessen Subjective Complaints List-24 questionnaires.

BACKGROUND: Most studies evaluating the impact of kidney donation on donors' quality of life (QOL) have limitations such as small cohort size, unmatched references, use of nonstandardized and nonvalidated questionnaires, or low response rates. METHODS: We performed a study on donors' QOL that was designed to avoid these limitations. All available living renal donors in our department in the last 18 years were included in the study. QOL was assessed with two validated, standardized questionnaires (Short Form-36, Giessen Subjective Complaints List [Giessener Beschwerdebogen]-24) and compared with gender- and age-matched references. In addition, specific questions relating to kidney donation were asked. RESULTS: The response rate (89.8%) is one of the highest reported for studies on QOL of living kidney donors. Most donors had an equal or better QOL than the healthy population. Donors' willingness to donate again (93.4%) or recommend living-donor kidney transplantation (92.4%) was high, irrespective of complications. A small number of donors experienced financial drawbacks or occupational disadvantages. Donors aged 31 to 40 years were found to be at risk of QOL deterioration after organ donation. Donor and recipient complications had a significant impact on donors' QOL. One third of the donors found that the psychologic care preceding and after kidney donation was insufficient. CONCLUSIONS: Our findings support the practice of living-donor kidney transplantation as a good means to meet the persisting organ shortage. Further effort must be put into minimizing donor and recipient complications. The specific demands of younger donors should be further elucidated. In addition to medical follow-up, living kidney donors should also be offered lifelong psychologic counseling.