[Diagnostics and treatment of prostate cancer after kidney transplantation]. / Diagnostik und Therapie des Prostatakarzinoms nach Nierentransplantation.

The number of patients with prostate cancer and end-stage renal disease or prostate cancer following kidney transplantation has continuously increased in industrialized countries. According to the data generated by Penn et al. a higher incidence of prostate cancer following kidney transplantation can be seen but is probably due to a more intense screening of the recipients. It is rather a common opinion that no elevated risk of prostate cancer following kidney transplantation exists. In patients with strictly localized prostate cancer curative treatment should be the aim also after kidney transplantation. Kidney transplantation does not interfere with surgical access to the prostate gland (retropubic or perineal). Nonlocal tumors of the prostate should also be treated following the general recommendations regarding prostate cancer. Looking at the current literature, a reduction or change of immunosuppression seems reasonable. It is necessary to establish a nationwide (or even European) cancer register, especially for patients before and after transplantation.

Interleukin-2- and interferon alfa-2a-based immunochemotherapy in advanced renal cell carcinoma: a Prospectively Randomized Trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN).

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.

[Prostate biopsy: Procedure in the clinical routine]. / Prostatabiopsie : Durchführung im klinischen Alltag.

Over the last decade there has been a 25% decrease in the mortality rates for prostate cancer. The reasons for this significant decrease are most likely associated with the application of urological screening tests. The main tools for early detection are currently increased public awareness of the disease, prostate-specific antigen (PSA) tests and transrectal ultrasound (TRUS) guided topographically assignable biopsy sampling. Together with the histopathological results these features provide essential information for risk stratification, diagnostics and therapy decisions. The evolution of prostate biopsy techniques as well as the use of PSA testing has led to an increased identification of asymptomatic men, where further clarification is necessary. Significant efforts and increased clinical research focus on determining the appropriate indications for a prostate biopsy and the optimal technique to achieve better detection rates. The most widely used imaging modality for the prostate is TRUS; however, there are no clearly defined standards for the clinical approach for each individual biopsy procedure, dealing with continuous technical optimization and in particular the developments in imaging. In this review the current principles, techniques, new approaches and instrumentation of prostate biopsy imaging control are presented within the framework of the structured educational approach.

Differential diagnostic use of interleukin patterns in patients being monitored after transplantation.

BACKGROUND AND AIM: We investigated how far the determination of selected interleukins in bodily fluids of patients who had received kidney allografts can help to confirm the diagnosis of complications after transplantations. MATERIALS AND METHODS: Levels of soluble interleukin-2-receptor, interleukin 6 and interleukin 8 were determined in serum and urine of 79 patients. According to the type of diagnosis obtained with histological, serological and microbiological methods and to the clinical course, the groups "stable graft function without complication", "allograft rejection", "cytomegalovirus infection", "systemic extrarenal bacterial infection", "urinary tract infection" and "pyelonephritis" were created. RESULTS AND CONCLUSIONS: The activation of the immune system in different ways depending on the trigger substance (alloantigen, virus, bacterium) and the possibility to differentiate systemic and local processes cause typical patterns of interleukin levels in serum and urine in conjunction with the above mentioned complications after kidney transplantation. Cytomegalovirus infections and systemic extrarenal bacterial infections differ from rejection by the unchanged urine interleukins IL 6 and IL 8, the local urinary tract infections differ from rejection by the unchanged serum interleukins. Acute pyelonephritis differs from rejection by the significantly higher serum IL 6 level. During our daily clinical work, the practical interleukin determinations were proven to be an important tool for early and differential diagnosis of complications after kidney transplantation.

Endopeptidase 24.11/CD10 is down-regulated in renal cell cancer.

The regulatory mechanisms responsible for malignant transformation, tumor progression and metastasis in renal cell cancer (RCC) are still unclear, but there is some evidence that biologically active peptides might have regulatory effects on the behavior of this malignancy. Tumor cells can change local concentrations of active peptides by modulating their cell-surface enzymes. Using immunohistochemistry and enzyme-histochemistry, the expression of various membrane peptidases was examined in RCC and adjacent noninvaded renal parenchyma (n = 44). We describe the down-regulation of neutral endopeptidase 24.11 (NEP) protein expression in RCC of the clear cell/chromophilic type when compared with renal parenchyma, and show for the first time the lack of enzyme activity of NEP in RCC. The strongest expression could be found for dipeptidyl peptidase IV (DPIV) which is only decreased in RCC of the chromophobe cell type and is even present in oncocytoma. Aminopeptidase N (APN) and aminopeptidase A (APA) show attenuated expression in up to one third of clear cell/ chromophilic RCC. Chromophobe RCC and oncocytomas do not express APN, APA, NEP and gamma-glutamyltranspeptidase.

Efficacy and safety of inhaled recombinant interleukin-2 in high-risk renal cell cancer patients compared with systemic interleukin-2: an outcome study.

Systemic IL-2 is an effective treatment for low to intermediate risk mRCC patients, its efficacy is marginal in high-risk cases. Therefore, other treatment approaches are required for this population. Ninety-four high-risk patients with RCC and pulmonary metastases were treated with inhaled plus concomitant low-dose subcutaneous rhIL-2. Clinical response, survival and safety were compared with those from IL-2 given systemically at the registered dose and schedule in 103 comparable historical controls. In the rhIL-2 INH group, treatment consisted of 6.5 MIU rhIL-2 nebulized 5x/day and 3.3 MIU rhIL-2 SC once daily. The rhIL-2 SYS group received treatment which consisted of intravenous infusion of 18.0 MIU/m2/day rhIL-2 or SC injection of 3.6-18.0 MIU rhIL-2. Some patients in both groups also received IFNalpha. Mean treatment durations were 43 weeks rhIL-2 INH and 15 weeks rhIL-2 SYS. Significantly longer overall survival and progression-free survival durations were observed in the rhIL-2 INH group. The probability of survival at 5 years was 21% for the rhIL-2 INH group. No patients survived 5 years in the rhIL-2 SYS group. A multivariate analysis of overall survival adjusting for differences in baseline characteristics between the two treatment groups resulted in a risk ratio of 0.43 (95% CI 0.30-0.63; P < 0.0001). The data suggested an association between the response (SD or better) and survival, especially in the rhIL-2 INH group. The inhalation regimen was well tolerated. This outcome study suggests that administration of rhIL-2 by inhalation is efficacious and safe in high-risk mRCC patients with pulmonary metastases, who have no other treatment option available.

[New techniques in uro-sonography]. / Neue Techniken der Urosonographie.

New sonographic techniques in urology, together with their principles of operation, will be presented. Together with the utilization of broadband ultrasound scanners and digital beam formers, leading to better spatial resolution and increased line density in ultrasound imaging, panorama sonography enables the outline of wide lateral regions independent of the width of the scanner. Spatial compound sonography achieves a comparatively better visualization of details in the b-mode image than has yet been available. The continuously improved 3-D, now leading to 4-D, techniques, which means real time capabilities, make the visualization of unrestricted imaging planes, which are not seen in conventional 2-D techniques, possible. The second harmonic imaging technique, including the special applications tissue harmonic imaging (THI) and contrast harmonic imaging (CHI), uses special ultrasound signal processing procedures for capturing and evaluating tissue hemoperfusion-here in combination with ultrasound contrast agents (UCA). Furthermore, microvascular imaging (MVI) enables the visualization of perfusion in tissues reaching the microcirculation regions. This leads to new possibilities for the assessment of pathological perfusion patterns, e.g. in andrology (perfusion of testicles) and uro-oncology (hyperperfusion of malignant regions).

[Transrectal ultrasound of the prostate. Current status and prospects]. / Transrektale Sonographie der Prostata. Aktueller Stand und Perspektiven.

In recent years the role of ultrasound in the diagnosis of prostate carcinoma has increased in importance. In view of the increasing incidence of prostate cancer, which is the most frequent malignant neoplasm in men, TRUS (transrectal ultrasound) is an important imaging method in the diagnosis of various prostate diseases. This paper provides a basic overview of physical and technical bases of TRUS investigation of the prostate. It concerns technical developments and modern techniques designed to improve its value in diagnosis. Impressive innovations in ultrasound equipment, particularly in the area of colour-coded Doppler sonography in association with microbubble-enhanced colour Doppler ultrasound, have given rise to justifiable hope of improvements in the early diagnosis of prostate cancer.

[Determination of acoustic parameters from ultrasound raw and HF data--a comparison]. / Bestimmung von akustischen Parametern aus Ultraschall roh- und HF-Daten--ein Vergleich.

Different methods for determination of acoustical tissue parameters based on rf data acquisition as well as the analysis of B-mode image data are well established. Because of limitations of the dynamic range and the restricted control of the tgc and focus settings the analysis of image data is not achievable in clinical practice. On the other side rf data are not available in most of the clinical scanners. So the analysis of raw data can be used as an compromise. Raw- and rf-data of complete B-mode scans obtained form a set of test phantoms by a clinical ultrasound device (HDI 5000, Philips) in connection with the applied gain settings were analyzed. For different system settings the estimated parameters showed a good agreement with the acoustical properties of the phantoms.

[19th annual conference of the working group on kidney transplantation of the academy of german urologists : mainz, 10-12 november 2011]. / 19. Jahrestagung des Arbeitskreises Nierentransplantation der Akademie der Deutschen Urologen : Mainz 10. bis 12. November 2011.

The 19th Annual Conference of the Working Group on Kidney Transplantation (KTX) of the Academy of German Urologists took place on 10-12 November 2011 in Mainz. The main topics at the meeting were surgical and technical aspects, immunosuppressive therapy, transplant rejection, pregnancy, sexuality, and psychological conflicts of kidney transplant recipients. The speakers documented the pertinence of interdisciplinarity for KTX and were not only from the field of urology but also from anesthesiology, gynecology, surgery, dermatology, nephrology, radiology, and psychosomatic medicine. The Bernd Schönberger Prize was awarded at the end of the event.

Prospective, nonrandomized comparison between right- and left-sided hand-assisted laparoscopic donor nephrectomy.

BACKGROUND: Despite technical improvements, laparoscopic living donor right nephrectomy can be associated with difficulties to obtain a sufficient lengths of right renal vessels. We report our experience with right-sided, hand-assisted, laparoscopic donor nephrectomy (HALDN). PATIENTS AND METHODS: During a 7-year period (2003-2010), right HALDN was performed on 51 and left HALDN on 40 living kidney donors. We prospectively collected perioperative outcome data in donors and recipients including graft function and calculated 1-year graft survival according to the Kaplan-Meier-method. RESULTS: There were no conversions. The mean procedure time was 123 minutes versus 135 minutes for left HALDN (P = .09). Mean blood loss was 92 mL versus 101 mL in left HALDN (P = .09). There was no renal artery or vein thrombosis. The mean warm ischemia time was 47 seconds versus 41 seconds in left HALDN (P = .21). Hospital discharge was on an average at 3.4 days postoperatively. Delayed graft function occurred in two recipients: one in the left group and the other in the right group. Further, no significant difference in serum creatinine values was seen between the groups at 1 year after the transplantation. One-year graft survival rate was 97.5% in the left versus 98.1% in the right group. CONCLUSION: Right HALDN is as safe and feasible as left HALDN. Hand-assistance results in a convenient length of right renal vessels without an increased incidence of vascular thrombosis.

[Obesity as a risk factor for prostate cancer: role for adipocytokines and involvement of tyrosine kinase pathway]. / Ubergewicht als Risikofaktor für das Prostatakarzinom: Rolle der Adipozytokine und Beteiligung der Tyrosinkinasen1.

PURPOSE: Obesity is considered to be a risk factor for prostate cancer. Mitogenic actions of leptin, an adipocyte-derived hormone in a variety of cancer cell types have been identified. We have investigated the proliferative effects of leptin on human prostate cancer cells and assessed the role of tyrosine kinase signalling in mediating these actions. MATERIALS AND METHODS: Two human androgen-resistant prostate cancer cell lines and one androgen-sensitive human prostate adenocarcinoma cell line were treated with leptin (5-100 ng / mL) for up to 48 hours. Under serum-free conditions, cell proliferation was measured using an enzyme-linked colorimetric assay. Furthermore, phosphorylation of a downstream component of MAPK (ERK1 / 2) was detected by Western blotting and a specific inhibitor of MAPK (PD98059; 40 microM) was used to evaluate the role of this signalling pathway. RESULTS: Leptin dose-dependently increased the cell number in both androgen-resistant cell lines after 24 h and 48 h of incubation (percent of control: DU145 = 194.6 +/- 5.9 %, PC-3 = 177.9 +/- 6.8 %; 100 ng / mL leptin; 48 h; p < 0.001). Conversely, leptin's proliferative effect on the androgen-sensitive cell line was less pronounced (percent of control: LNCaP = 112.3 +/- 6.1 %; 100 ng / mL leptin; 48 h). Leptin also caused dose-dependent ERK1 / 2 phosphorylation in both androgen-resistant cell lines. In addition, pre-treatment with PD98059 inhibited these responses and attenuated leptin's mitogenic action. CONCLUSIONS: Data from this in vitro study suggest an association between obesity-associated hyperleptinemia and an increased risk for prostate cancer. Further investigations are necessary to clarify whether these data have clinical relevance regarding the use as a prognostic marker for predicting the timing of the occurrence of androgen resistency.

[Malignant neoplasms and kidney transplantation]. / Maligne Neoplasien und Nierentransplantation.

Together with cardiovascular disorders and metabolic changes, malignant diseases are considered as great challenges in clinical transplantation. As far as long-term function of transplanted organs is concerned, an impact of malignancies is obvious. However, it is important to distinguish between neoplastic disease originating from preexisting lesions in the transplanted organs and de novo graft tumors. Further, there is also a high risk of developing malignant disease during the dialysis, likely due to potential harmful metabolic changes associated with this procedure. After curative management of tumors in such patients, an interval of 2 years for surveillance should be adhered to before patients are put back on the waiting list. The overall risk of transmission of a malignant disease with the transplanted graft has been considered to be as low as <0.2%. In this context, and considering the continual shortage of donated organs, there is an international consensus about the use of kidney grafts with a history of small tumors (<2 cm in diameter und low-grade, i.e., G1). However, the lesions should have been removed with subsequent histopathologic characterization before the acceptance of the organ for transplantation. Early diagnosis and management of de novo malignant disease in transplant patients is crucial for the prognosis of graft function and patient survival. Genitourinary malignancies are frequent among de novo malignancies in transplanted patients. Thus, there is a need for clearly structured concepts for screening of transplant patients in order to detect early malignancies. The incidence of malignant disease correlates directly with the extent of immunosuppression in patients with end-stage renal disease (ESRD) on dialysis, as well as after transplantation with life-long immunosuppressant therapy. In addition, also geographic factors seem to play a role in the differential incidence of tumors among different populations. For instance, the highest incidence of malignancies among immunosuppressed patients has been observed in Australia followed by the USA and Europe. This might be due to the high incidence of de novo skin cancer, which has been linked to the extent of UV exposure.

[Current aspects in the diagnosis of renal cell cancer]. / Aktuelle Aspekte zur Diagnostik des Nierenzellkarzinoms.

The sonography represents a central role in the diagnosis of suspect processes of the kidney, specially of renal cell cancers and it is quasi the most used method between all radiologic techniques for the early diagnosis of this tumor. The increasing incidence in the last years of renal cell cancers, above all in the european industrialized nations, requires a practical and rapid diagnostic method like sonography, which, if precosiouly done, allows to perform a nephron-sparing operation with a good prognosis according to curative purpose.

[Current aspects in the therapy of renal cell cancer]. / Aktuelle Aspekte zur Therapie des Nierenzellkarzinoms.

The nephron-sparing partial nephrectomy has become the gold standard in the surgical therapy of small renal tumors (4-7 cm). In metastased renal cell cancers it is reasonable to perform a nephrectomy or a partial nephrectomy in combination with cytokine-therapy (clear cell type) and/or a targeted therapy with Angiogenesis-Inhibition, in presence of a Karnofsky-Index > 70%. A surgical standard procedure for organ-confined renal cell cancers and an immunological standard therapy for metastased renal cell cancers are no more proper; in fact nowadays exists a spectrum of different efficient therapies. Surgery in metastased diseases is indicated if it can improve the quality of life of the patient.