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Die radikale Tumornephrektomie ist die traditionelle Standardoperation zur Behandlung des Nierenzellkarzinoms. Es werden jedoch zunehmend kleinere, inzidentelle Nierentumoren diagnostiziert. Haufig sind gerade auch altere Patienten mit erheblichen Komorbiditaten davon betroffen. Diese Situation lasst die Durchfuhrung einer radikalen Operation mit Verlust der Niere als Standardtherapieverfahren nicht mehr gerechtfertigt erscheinen. Die offene Nierenteilresektion gilt als ein technisch komplexer Eingriff mit hoherem Schwierigkeitsgrad und einer Komplikationsrate von bis zu 20%, der mit den Kriterien einer minimalen Invasivitat nicht vereinbar ist. Dies offnet den Raum fur innovative minimal-invasive therapeutische Verfahren. Die laparoskopische Nierenteilresektion ist eine sehr attraktive, jedoch technisch anspruchsvolle Methode zur definitiven operativen Behandlung kleiner renaler Raumforderungen. Im Vergleich zur offenen Nierenteilresektion weist die laparoskopische Technik eine hohere Rate an Komplikationen und Reeingriffen auf. Daher ist diese Methode derzeit nicht als Standard akzeptiert und sollte laparoskopisch versierten Zentren vorbehalten bleiben. Energieablative Verfahren, wie die Kryotherapie und die Radiofrequenztherapie, gewinnen zunehmend an klinischer Bedeutung und scheinen ebenfalls effektive Behandlungsmethoden darzustellen. Den neuen Therapieverfahren ist jedoch der Mangel an Langzeitdaten zur Tumorkontrolle und zum Uberleben der Patienten gemein. Daher sollten diese Verfahren derzeit nur in klinischen Studien oder als alternative Behandlungsmethode bei ausgewahlten Patienten zur Anwendung kommen, bei denen ein kurativer operativer Ansatz nicht in Frage kommt. Ein weiterer alternativer Ansatz besteht in der aktiven Uberwachung (Surveillance) von kleinen renalen Raumforderungen. Nach aktuellen Erkenntnissen betragt die durchschnittliche Wachstumsgeschwindigkeit kleiner Nierentumoren nur wenige Millimeter pro Jahr. Bei Hochrisikopatienten erscheint auf der Basis dieser Beobachtungen ein initial abwartendes Verhalten durchaus gerechtfertigt.

In der vorliegenden randomisierten Studie wurde das Anasthesiemodul des klinischen Behandlungspfades „laparoskopische Prostatektomie“ exemplarisch fur zeitintensive minimal-invasive Operationen untersucht. Hierzu wurden 40 Patienten fur die beiden Narkoseverfahren total-intravenose Anasthesie (TIVA) mit Propofol und Remifentanil vs. balancierte „Minimal-flow-Anasthesie“ mit Desfluran und Remifentanil randomisiert. In der modularen Verlaufsbeobachtung wurden Qualitatsindikatoren, wie Vigilanz, Schmerzen, Ubelkeit und Erbrechen (PONV) sowie Mobilisation gemessen. Im „Bottom-up-Verfahren“ wurden die Kosten evaluiert und analysiert. Es gab keine anasthesiebedingten Abweichungen vom Behandlungspfad. Beide Narkoseformen waren sehr gut steuerbar. Hinsichtlich des Kreislaufverhaltens wurden beide Narkoseformen gleich gut vertragen. Keinen signifikanten Unterschied gab es hinsichtlich PONV (16 von 40 Patienten). Die Patienten der Desflurangruppe zeigten postnarkotisch einen schnelleren Eintritt der Vigilanz (p=0,037) und des Schmerzempfindens. Der Schmerzmittelbedarf war direkt nach Narkoseende und im Aufwachraum signifikant hoher als in der Propofolgruppe (p=0,017). Der Anasthesieminutenpreis fur die laparoskopische Prostatektomie in der Propofolgruppe betrug im Median EUR 2,79 (minimaler Preis EUR 2,41, maximal EUR 3,21), in der Desflurangruppe EUR 2,68 (minimal EUR 2,45, maximal EUR 3,39). Die Gesamtanasthesiekosten beider Verfahren lagen innerhalb des durch die Erlosmatrix der „diagnosis related groups“ (DRG) vorgegebenen Rahmens; die Medikamentenkosten lagen in der Kostenartenanalyse leicht oberhalb der DRG-Erlosmatrix. Beide Narkoseformen eignen sich auch unter „German-refined-diagnosis-related-groups- (G-DRG-)Bedingungen, um zeitintensive operative Eingriffe kosteneffektiv durchfuhren zu konnen. Die anasthesiologischen Prozessablaufe mussen sich an der Narkoseform orientieren, die prophylaktische Gabe von Analgetika muss beispielsweise nach Desfluran-Remifentanil-Narkosen schneller und hoher dosiert erfolgen als nach Propofol-Remifentanil-Narkosen. Nach lang dauernden laparoskopischen Eingriffen ist die prophylaktische Gabe von Antiemetika indiziert. Die Optimierung anasthesiologischer Prozesse kann zur kontinuierlichen Qualitatsverbesserung klinischer Behandlungspfade beitragen.

Long-term follow-up studies have demonstrated that effective local tumor control and long-term tumor-free progression rates can be achieved by nephron-sparing surgery. However, hemostasis is a major issue and the lack of effective means of hemostasis has limited a wider use of the laparoscopic approach to nephron-sparing surgery. Between January 2001 and August 2002, a total of 36 patients with renal cell carcinomas were treated by partial nephrectomies using a two-component tissue sealant (FloSeal). The median age was 55.2 years (range: 34-71 years). Follow-up time was 1-18 months (median: 5.5 months). The tumor diameter ranged from 2 to 5 cm (median: 2.9 cm). Open retroperitoneal surgery was performed in 17 cases and laparoscopic partial nephrectomy in 19 cases. The two-component tissue sealant (consisting of a gelatin matrix with granular and thrombin components) was applied after resection of the tumor and before perfusion of the kidney. The following parameters were recorded: (1) time until complete hemostasis was achieved, (2) decrease in postoperative hemoglobin level, (3) postoperative bleeding, and (4) presence or absence of a perirenal hematoma 24 h and 10 days postoperatively by ultrasound. After application of the tissue sealant for 1-2 min to the moist resection site, hemostasis was immediate in all cases. During the laparoscopic partial nephrectomies, a laparoscopic applicator was used that avoided wasting the tissue sealant within the dead space of the instrument. When reperfusion of the kidney was established, hemostasis was maintained. The decrease in postoperative hemoglobin level ranged from 0.3 to 1.2 points (median: 0.8 points). None of the patients required blood transfusions. There were no cases of postoperative bleeding. An ultrasound examination 24 h and 10 days postoperatively demonstrated the absence of a significant perirenal hematoma. The two-component tissue sealant FloSeal provided immediate and durable hemostasis in open and laparoscopic partial nephrectomies. The tissue sealant may provide a tool to expand the possibilities of laparoscopic nephron-sparing surgery.

Because of the minimal invasiveness of the laparoscopic approach, we introduced the laparoscopic dismembered pyeloplasty in our treatment modalities for patients with primary UPJ obstruction. We report on our technique and the results after a median follow-up of more than 2 years. Between August 1997 and September 2002, 52 patients underwent a laparoscopic dismembered pyeloplasty at our institution. All patients had a symptomatic primary PJ obstruction. We prefer the transperitoneal route with laterocolic exposure of the kidney. After preparation and exposure of the ureter and the renal pelvis, we performed in each case the dismembered Anderson-Hynes pyeloplasty with resection of the pelvis and reanastomosis between the ureter and renal pelvis. Intracorporeal suturing and knotting techniques were used exclusively. All procedures could be performed successfully. In no case was conversion to open surgery necessary. The mean operative time was 180 min. Crossing vessels were present in 57% of patients. The mean postoperative hospital stay was 4 days. The first patient had an anastomosis insufficiency, which required laparoscopic repair. The same patient failed in the follow-up. He developed a late recurrence of the stenosis and needed an open repair. In all other patients the obstruction was resolved or significantly improved. The long-term success rate is 98% with a follow-up of 25 months. Our results with laparoscopic dismembered pyeloplasties compare favorably with those achieved by open pyeloplasties with less perioperative morbidity and discomfort. We do believe that laparoscopic dismembered pyeloplasty will be the method of choice in the treatment of UPJ obstruction.

The antimicrotubule drug estramustine phosphate (EMP) has been shown to sensitize prostate carcinoma cells to radiation via synchronization at the G2/M phase of the cell cycle. This synchronization may also render cells more sensitive to hyperthermia, providing a rationale for multimodal treatment approaches. We have investigated the effects of EMP and hyperthermia, as well as the regulation of heat shock proteins (HSP) in the PC-3 prostatic carcinoma cell line. Cells were incubated with four doses of EMP for 48 h followed by a 1-h hyperthermia treatment ranging from 41 degrees C to 44 degrees C. Cell cycle distribution at the end of the EMP incubation was investigated by flow cytometry. Cytotoxicity was assessed by colony formation assays. HSP accumulation was investigated by Western immunoblotting. Doses of 1, 5, 10 and 15 microM EMP synchronized 27, 28, 46, and 68% of PC-3 cells at G2/M. With 5, 10 and 15 microM, a sensitizing effect of EMP was assessed at hyperthermic temperatures of 42, 43 and 44 degrees C. EMP did not alter the expression of HSP72, but substantially induced the synthesis of HSP27 in PC-3 cells. Our data show that EMP sensitizes PC-3 cells to hyperthermia induced cytotoxicity. This observation supports the rationale for multimodal treatment approaches in locally advanced prostate cancer.

The effect of prenatal hypoxia on the development of the β-adrenoceptor during the ontogenesis of rats was investigated. It was shown that the offspring from hypoxic dams, in comparison with normoxic control animals, exhibited alterations of the density (Bmax) of the myocardial β-receptors and of the catecholamine levels in heart tissue during development. The results suggest that the β-adrenoceptor changes might be involved in the phenomenon of enhanced sensitivity of prenatal hypoxic animals to catecholamines in adult age.

In this study, the effect of prenatal hypoxia on the catecholamine sensitivity of the offspring of pregnant rats was investigated. The offspring from hypoxic animals showed after treatment with isoproterenol in adult age a distinctly more pronounced decrease of protein content and enzyme activities in heart tissue as well as a significantly higher elevation of enzyme activities in blood plasma as compared with the offspring from normoxic rats. These results suggest a long-lasting enhancement of catecholamine sensitivity after prenatal oxygen deficiency.

Beliefs in one's ability to perform a task or behaviour successfully are described as self-efficacy beliefs (Bandura, 1977). Since individuals have to deal with differing demands during a behaviour-change process, they form phase-specific self-efficacy beliefs directed at these respective challenges. The present study, based on the Health Action Process Approach (Schwarzer, 2001), examines the theoretical differentiation, relative importance, and differential effects of four phase-specific self-efficacy beliefs, including task self-efficacy, preactional self-efficacy, maintenance self-efficacy, and recovery self-efficacy.In a prospective longitudinal study, 112 prostatectomy-patients received questionnaires at 2 days, 2 weeks, 1 month, and 6 months post-surgery.Participants provided data on phase-specific self-efficacies as well as phase indicators of health-behaviour change, that is, intentions, planning, and pelvic-floor exercise. Hierarchical regression analyses were conducted to test the study hypotheses.Task self-efficacy was not uniquely associated with intentions. Preactional self-efficacy was related to action planning. Maintenance self-efficacy did not predict behaviour. Recovery self-efficacy was associated with re-uptake of pelvic-floor exercise after relapses only.Findings underline the importance of differentiating between task self-efficacy and preactional self-efficacy during early phases of behaviour change as well as of considering the occurrence of relapses as a moderator of potential effects of recovery self-efficacy on the maintenance of behaviour change. Advanced knowledge on distinct, phase-specific self-efficacy beliefs may facilitate the design of effective tailored interventions for behaviour change.

Pre-cystectomy nomograms with a high predictive ability for locally advanced urothelial carcinomas of the bladder would enhance individual treatment tailoring and patient counselling. To date, there are two currently not externally validated nomograms for prediction of the tumour stages pT3-4 or lymph node involvement.Data from a German multicentre cystectomy series comprising 2,477 patients with urothelial carcinoma of the bladder were applied for the validation of two US nomograms, which were originally based on the data of 726 patients (nomogram 1: prediction of pT3-4 tumours, nomogram 2: prediction of lymph node involvement). Multivariate regression models assessed the value of clinical parameters integrated in both nomograms, i.e. age, gender, cT stage, TURB grade and associated Tis. Discriminative abilities of both nomograms were assessed by ROC analyses; calibration facilitated a comparison of the predicted probability and the actual incidence of locally advanced tumour stages.Of the patients, 44.5 and 25.8% demonstrated tumour stages pT3-4 and pN+, respectively. If only one case of a previously not known locally advanced carcinoma (pT3-4 and/or pN+) is considered as a staging error, the rate of understaging was 48.9% (n=1211). The predictive accuracies of the validated nomograms were 67.5 and 54.5%, respectively. The mean probabilities of pT3-4 tumours and lymph node involvement predicted by application of these nomograms were 36.7% (actual frequency 44.5%) and 20.2% (actual frequency 25.8%), respectively. Both nomograms underestimated the real incidence of locally advanced tumours.The present study demonstrates that prediction of locally advanced urothelial carcinomas of the bladder by both validated nomograms is not conferrable to patients of the present German cystectomy series. Hence, there is still a need for statistical models with enhanced predictive accuracy.

The therapeutic gold standard of muscle-invasive tumour stages is radical cystectomy (RC), but there are still conflicting reports about associated morbidity and mortality and the oncologic benefit of RC in elderly patients. The aim of the present study was the comparison of overall (OS) and cancer-specific survival (CSS) in patients75 and75 years of age (median follow-up was 42 months).Clinical and histopathological data of 2,483 patients with urothelial carcinoma and consecutive RC were collated. The study group was dichotomized by the age of 75 years at RC. Statistical analyses comprising an assessment of postoperative mortality within 90 days, OS and CSS were assessed. Multivariate logistic regression and survival analyses were performed.The 402 patients (16.2%) with an age of ≥75 years at RC showed a significantly higher local tumour stage (pT3/4 and/or pN+) (58 vs 51%; p=0.01), higher tumour grade (73 vs 65%; p=0.003) and higher rates of upstaging in the RC specimen (55 vs 48%; p=0.032). Elderly patients received significantly less often adjuvant chemotherapy (8 vs 15%; p0.001). The 90-day mortality was significantly higher in patients ≥75 years (6.2 vs 3.7%; p=0.026). When adjusted for different variables (gender, tumour stage, adjuvant chemotherapy, time period of RC), only in male patients and locally advanced tumour stages was an association with 90-day mortality noticed. The multivariate analysis showed that patients ≥75 years of age have a significantly worse OS (HR=1.42; p0.001) and CSS (HR=1.27; p=0.018).An age of ≥75 years at RC is associated with a worse outcome. Prospective analyses including an assessment of the role of comorbidity and possibly age-dependent tumour biology are warranted.

Few and partially contradictory data are available regarding the prognostic signature of downstaging of muscle-invasive clinical tumour stages in patients treated with radical cystectomy.Clinicopathological parameters of 1,643 patients (study group, SG) treated with radical cystectomy due to muscle-invasive urothelial bladder cancer were summarized in a multi-institutional database. Patients of the SG fulfilled the following conditions: clinical tumour stage T2 N0 M0 and no administration of neoadjuvant radiation or chemotherapy. Cancer-specific survival (CSS) rates were calculated referring to pathological tumour stages in cystectomy specimens (pT2, pT2,pT2) (mean follow-up: 51 months). Furthermore, a multivariable model integrating clinical information was developed in order to predict the probability of downstaging.A total of 173 patients (10.5%) of the SG presented with downstaging in pathological tumour stages (pT0: 4.8%, pTa: 0.4%, pTis: 1.3%, pT1: 4.1%); 12 of these patients had positive lymph nodes (7%, in comparison with 21% pN+ of pT2 tumours and 43% ofpT2 tumours). Patients with tumour stagespT2, pT2 andpT2 had CSS rates after 5 years of 89, 69 and 46%, respectively (p0.001). In a multivariable Cox model the presence of pathological downstaging resulted in a significant reduction of cancer-specific mortality (HR 0.30; 95% CI 0.18-0.50). By logistic regression analysis the date of TURB (benefit for more recent operations) was identified as the only independent predictor for downstaging of muscle-invasive clinical tumour stages. Age, gender, grading and associated Tis in the TURB did not reveal any significant influence.Patients with muscle-invasive clinical tumour stages and downstaging in cystectomy specimens represent a subgroup with significantly enhanced CSS rates. Further trials that integrate the parameters tumour size, stages cT2a vs cT2b and focality are required in order to define the independent prognostic signature of downstaging of tumour stages more precisely.

Due to an insufficient mean agreement between the Gleason score (GS) revealed from multibiopsy and definitive histology after radical prostatectomy (RP) of merely about 45 %, a modification of the GS including an elimination of GS 2-4 was -accomplished in 2005. The aim of the present study was to evaluate the concordance of GS and WHO grading in biopsy and definitive histology and to -determine parameters influencing the diagnostic accuracy of the biopsy and the prognosis.Within a 10-year-period before modification of the GS, radical prostatectomy was performed in 856 patients (study group, SG; mean age 64.2 years). The grade of agreement between GS and WHO grading in biopsy and definitive histology was calculated by kappa statistics (kappa) (for the complete and single time -periods). Furthermore, we assessed the univariable and multivariable influence of different preoperatively available parameters on disease-free survival (DFS). The mean follow-up period was 39 months (range: 10-139 months).Undergrading of GS and WHO grading decreased continuously within the three time -periods in favour of a higher agreement regarding the histological results revealed from biopsy and definitive histology. However, we found only a poor to moderate agreement in the complete time period (kappa values of 0.354 for GS and 0.404 for WHO grading) that - with regard to both parameters - was improved by an increased number of biopsy cores taken. PSA value, clinical -tumour stage, number of positive cores (dichotomised at 34 %), annual RP case load (dichotomised at 75), and GS revealed an independent significant influence on DFS. Patients with GS 2-4 in the biopsy exhibited an upgrade to GSor = 7 in only 5.7 %, and -showed, -independent of the definitive histology, a significantly better prognosis in comparison with patients presenting with a higher GS.The results of the present study again suggest the independent prognostic impact of the GS revealed from biopsy. However, the concordance with the GS in the definitive histology remains deficient and is improvable by taking a higher number of biopsy cores. Although the elimination of GS 2-4 might be comprehensible for the pathologist's purpose, it results in a considerable loss of pretherapeutic prognostic information.

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).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).In the GP, IP, and PP groups, CSS after 8 years was 86.7%, 75.6%, and 13.7%, respectively (p0.001). 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).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.

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.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.The mean postoperative hospital stay was 3.6 days in the fast-track group vs. 6.7 days in the conventional group (p0.01). 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.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.

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.

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.

Die radikale Tumornephrektomie ist die traditionelle Standardoperation zur Behandlung des Nierenzellkarzinoms. Es werden jedoch zunehmend kleinere (

Long-term follow-up studies have demonstrated that effective local tumor control and long-term tumor-free progression rates can be achieved by nephron-sparing surgery. However, hemostasis is a major issue and the lack of effective means of hemostasis has limited a wider use of the laparoscopic approach to nephron-sparing surgery. Between January 2001 and August 2002, a total of 36 patients with renal cell carcinomas were treated by partial nephrectomies using a two-component tissue sealant (FloSeal). The median age was 55.2 years (range: 34-71 years). Follow-up time was 1-18 months (median: 5.5 months). The tumor diameter ranged from 2 to 5 cm (median: 2.9 cm). Open retroperitoneal surgery was performed in 17 cases and laparoscopic partial nephrectomy in 19 cases. The two-component tissue sealant (consisting of a gelatin matrix with granular and thrombin components) was applied after resection of the tumor and before perfusion of the kidney. The following parameters were recorded: (1) time until complete hemostasis was achieved, (2) decrease in postoperative hemoglobin level, (3) postoperative bleeding, and (4) presence or absence of a perirenal hematoma 24 h and 10 days postoperatively by ultrasound. After application of the tissue sealant for 1-2 min to the moist resection site, hemostasis was immediate in all cases. During the laparoscopic partial nephrectomies, a laparoscopic applicator was used that avoided wasting the tissue sealant within the dead space of the instrument. When reperfusion of the kidney was established, hemostasis was maintained. The decrease in postoperative hemoglobin level ranged from 0.3 to 1.2 points (median: 0.8 points). None of the patients required blood transfusions. There were no cases of postoperative bleeding. An ultrasound examination 24 h and 10 days postoperatively demonstrated the absence of a significant perirenal hematoma. The two-component tissue sealant FloSeal provided immediate and durable hemostasis in open and laparoscopic partial nephrectomies. The tissue sealant may provide a tool to expand the possibilities of laparoscopic nephron-sparing surgery.

Due to the increasing waiting time for transplantation of a cadaveric kidney, living donor kidney transplantation is an increasingly oncoming issue. Laparoscopic donor nephrectomies (LDN) have been performed since 1995 and presently more than 100 transplant centers offer this minimally invasive surgical approach. The advantages for the donor of less pain, shorter hospital stay, earlier return to work, better cosmetic results in combination with an organ function equal to open donor nephrectomy are the reasons for an enormous increase in LDN. Since up to 30% of the donor kidneys have multiple vessels for blood supply, an increase of these organs for LDN can be expected. We performed a retrospective study of LDN at our center and compared donors with multiple vs single vessel supply. From February 1999 to September 2002, 63 LDN were performed at the department of Urology, Charité University Hospital, Berlin. A comparison between 18 donor kidneys with multiple vessel supply and 45 donor organs with single vessels showed no difference for the time of laparoscopic explantation (207 vs 201 min, p=0.4) or the warm (166 vs 148 s, p=0.2) and cold ischemic times (117 vs 103 min, p=0.66). As could be expected, the mixed ischemic time, i.e., the time for anastomosis of the kidney with the recipient's vessels, showed a significant difference (53 vs 46 min, p=0.02). Intra- and postoperative complication rates for donors and recipients were not different in both groups. Laparoscopic donor nephrectomy for kidneys with multiple vessels is feasible and safe for donor and recipient.

Renal cell carcinoma is likely to become one of the most important indications for laparoscopic surgery worldwide. The laparoscopic technique combines the benefits of the minimally invasive approach with established surgical principles. In our institution the laparoscopic transperitoneal approach with intact specimen extraction has become the standard technique for radical nephrectomies. We report the indications, techniques, and oncological outcome in a single center experience in 100 cases. The mean tumor size was 5.9 cm (range: 2-11 cm), the blood loss was 220 ml, and the mean surgical time was 211 min, including the learning curves of five surgeons. Histological findings were pT1 in 66 (66%), pT2 in 11 (11%), and pT3 in 19 (19%) patients with an increasing tumor size according to the experience of the surgeons. In four cases (4%) histology did not prove malignant disease. Positive lymph nodes were detected in three cases (3%) and surgical margins were negative for tumor in all patients. To date 61 patients were available for follow-up; patients with primary metastatic disease were excluded from this analysis. Follow-up was between 1 and 30 months with an average of 12.9 months. Progressive disease occurred in two cases in patients with pT3G3 tumors. No cases of local recurrence or port metastasis occurred during observation. Laparoscopic radical nephrectomy is a routine, effective treatment for patients with renal cell carcinoma. Our follow-up data up to 30 months confirm the effectiveness of laparoscopic radical nephrectomy in terms of surgical principles and oncological outcome.

Objectives Long-term follow-up studies have demonstrated that effective local tumor control and long-term tumor-free progression rates can be achieved by nephron-sparing surgery. However, hemostasis is a major issue, and the lack of effective means of hemostasis has limited the wider use of the laparoscopic approach to nephron-sparing surgery. Methods Between January 2001 and April 2002, 25 patients with renal cell carcinoma were treated with partial nephrectomy using a two-component tissue sealant (FloSeal). The median age was 54 years (range 42 to 71). The follow-up time was 1 to 12 months (median 3.5). The tumor diameter ranged from 2 to 5 cm (median 2.8). Fifteen cases were performed by open retroperitoneal surgery, and 10 cases were performed laparoscopically. The two-component tissue sealant (consisting of a gelatin matrix granula component and a thrombin component) was applied after resection of the tumor and before perfusion of the kidney. The following parameters were recorded: time until complete hemostasis was achieved; decrease in postoperative hemoglobin level; postoperative bleeding; and presence or absence of a perirenal hematoma 24 hours and 10 days postoperatively by ultrasonography. Results After application of the tissue sealant for 1 to 2 minutes to the moist resection site, hemostasis was immediate in all cases. During the laparoscopically performed partial nephrectomies, a laparoscopic applicator was used to avoid wasting the tissue sealant within the dead space of the instrument. When reperfusion of the kidney was established, hemostasis was maintained. The decrease in postoperative hemoglobin level ranged from 0.3 to 1.2 points (median 0.7). None of the patients required blood transfusions. No postoperative bleeding occurred. The ultrasound examination 24 hours and 10 days postoperatively demonstrated the absence of a significant perirenal hematoma. Conclusions The two-component tissue sealant FloSeal provided immediate and durable hemostasis in open and laparoscopically performed partial nephrectomies. The tissue sealant may provide a tool to expand the possibilities of laparoscopic nephron-sparing surgery.

The Annual Report on the status of cancer in the USA 1973–1997 revealed that prostate cancer was the number one cancer site in men for each of the race/ethnic groups in the country. However, the rates showed a fourfold variation, from 49.6 per 100,000 for American Indian/Alaska Native men to 225.0 for Black men. Four trends in the incidence rates were identified: a steady increase from 1973 to 1988, an acceleration in the increase from 1988 to 1992, a substantial decline from 1992 to 1995, and approximately level rates thereafter. Over 50% of all cancer cases and cancer deaths were caused by cancers of the breast, prostate, lung and bronchus, and colon/rectum [63]. The increases seen in rate of incidence were clearly linked to the initiation of screening by means of prostate-specific antigen (PSA). The augmented incidence of prostate cancer was thus principally accounted for by earlier diagnosis, which in turn led to a stage migration to lower stages [43, 67].

Within the last 10 years, immunotherapy has progressively become an established treatment for patients with metastatic renal cell carcinoma. The cytokines interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) are the substances that have shown the greatest effects. Both have been approved for the treatment of patients with metastatic renal cell carcinoma in Germany. Subcutaneous application of these frequently combined cytokines is the schedule of immunotherapy used most often in Germany. Combined cytokine therapy (IL-2 and IFN-alpha) achieves response rates comparable to more aggressive immunotherapies. The retrospective analysis of treatment results from 66 patients with a follow-up of at least 5 years after the start of combined s.c. IL-2 and s.c. IFN-alpha +/- 5-fluorouracil (response classification: CR: 7, PR: 11, SD: 20, PD: 28) shows that the classification of the treatment results according to WHO criteria is the strongest predictor for survival compared with basic factors such as TNM status, grading, or number of metastatic sites. The combination of cytokine treatment with other treatment modalities (for example, surgical intervention) leads to a differentiated treatment according to the tumor status of the patient with metastatic renal cell carcinoma. Specific immunotherapies are still experimental. No approval has been granted for any of these treatments. Only standardization of these protocols can lead to a supplemental form of immunotherapy. Although several aspects of cytokine-based immunotherapy need further scientific evaluation, it is the treatment of choice for patients with metastatic renal cell carcinoma. However, for further progress in this field, prospective evaluation of immunotherapy for metastatic renal cell carcinoma is still needed. The German society for immunotherapy serves as a platform for this research.

Systematic development of laparoscopy during the last decade has led to establishing laparoscopic radical prostatectomy (LRP) as a surgical procedure. On the basis of extensive experience at our center, the advantages of the minimally invasive method are described as well as the problems still in existence. Reduced trauma caused by laparoscopic access in combination with clearly reduced blood loss has resulted in less morbidity after laparoscopic procedures. This is reflected in a shorter postoperative stay in hospital and faster convalescence. LRP as an ambitious and complex procedure has an average complication rate of 12%, which shows that the method has surpassed the stage of experimental surgery. By direct comparison, the costs of LRP are higher than for the open surgical procedure, but on the whole this is economically balanced by the lower morbidity, shorter hospital stay, and faster convalescence. The progress in technology to be expected in the field of laparoscopy will further increase quality, precision, and safety of LRP and thus contribute to the establishment of laparoscopic radical prostatectomy as a surgical method of choice.

Several experimental data are available regarding the efficacy of the combination of interstitial hyperthermia and conformal radiation therapy. We planned a phase II trial as a member of the special hyperthermia research group of the Deutsche Forschungsgemeinschaft (German Research Society) to determine the efficacy of thermoradiotherapy using interstitial cobalt-palladium thermoseeds in the treatment of patients with localized prostate cancer. Forty-one patients with localized prostate cancer were enrolled in the study between July 1997 and April 2000. The interstitial hyperthermia induced in a magnetic field was applied in six sessions once a week. Conformal three-dimensional radiation therapy was given simultaneously in daily fractions of 1.8 Gy with a total dose of 68.4 Gy. We measured intraprostatic temperatures between 42 degrees and 46 degrees C. No major side effects were observed during the hyperthermia session. The median level of prostate-specific antigen (PSA) decreased from 11.25 ng/ml to 0.88 ng/ml 3 months after treatment and to 0.38 ng/ml 12 months after treatment with a median follow-up of 10 months. The mean prostate volume decreased from 32.6 ml to 26 ml after 3 months of treatment and to 18.5 ml after 12 months. Interstitial hyperthermia is a feasible, well-tolerated procedure in prostate cancer therapy. A significant PSA decrease was observed. Longer follow-up is necessary to determine the efficacy.

Brachytherapy of prostate cancer has become attractive in recent years in Germany. There are several radioactive sources available, which are physically different. Some of them are used as permanent or temporary implants. The permanent sources most frequently used are iodine 125, palladium 103, and gold 198. Iridium is a temporary implant. The techniques used in Germany are low-dose rate (LDR) and high-dose rate brachytherapy, which differ in dose distribution and patient population. The success of prostate cancer brachytherapy depends on patient selection and choosing the right source for the technique used. Best suited for LDR monotherapy is the low-risk patient with a prostate-specific antigen (PSA) level below 10 ng/ml, maximal tumor stage T2b, and a Gleason score of less than 7.

Encouraged by the groups in Paris, we performed 145 laparoscopic radical prostatectomies between June 1999 and the end of November 2000. The indication for laparoscopic prostatectomy is the same as for open surgery: an organ-confined cancer. Previous abdominal surgery, transurethral resection, and/or relative adiposity are not considered to be contraindications for this laparoscopic procedure. The mean operating time was 255 min; the last 60 procedures took an average of 200 min. In no case was it necessary to convert to open surgery. Worthy of note was the low blood loss of 185 ml on average so that in 98% of the patients no blood transfusion was required. After completing the learning curve, the average indwelling catheter time was only 5.5 days. The postoperative complication rate was 11.7%, consisting mainly of minor complications. Also with regard to continence and potency, the results were representative. Postoperatively, 75%, 86%, 92%, and 93% of the patients were continent after 3, 6, 9, and 12 months, respectively. In our opinion, laparoscopic radical prostatectomy is an alternative to open prostatectomy, offering a number of advantages for the patient and surgeon as well.

Tumor cell metabolism is characterized by a high rate of aerobic glycolysis. The metabolic differences require changes in glycolytic enzyme activities and isoenzyme patterns. The inactive form of the M2 pyruvate kinase (Tu M2-PK) is specifically expressed in tumor cells and has been detected immunohistochemically in tumor tissue but also in peripheral blood of patients with different malignant tumors. In this study, Tu M2-PK in the plasma of patients with renal cell carcinoma (RCC) was compared with healthy volunteers. Tu M2-PK was quantified with a commercially available enzyme linked immunosorbent assay (ELISA) kit. Using the ELISA kit, plasma probes of 57 healthy individuals were compared to 63 patients with RCC (51 patients with non-metastatic RCC, 12 patients with metastatic RCC). Statistical analysis was performed with the non-parametric ANOVA test according to Kruskal-Wallis. In patients with renal cell carcinoma, Tu M2-PK was significantly higher than in healthy volunteers. For organ-defined, non-metastatic tumors, sensitivity was only 27.5%, if the 95% reference values of the control group were used for discrimination. The differences were more pronounced in patients with metastatic disease. Tu M2-PK was significantly enhanced compared to healthy controls, but also to the group with non-metastatic disease, the sensitivity was 66.7%. Our data show that Tu M2-PK has no impact as an unspecific marker for the diagnosis of renal cell carcinoma. This is especially relevant to organ-defined, non-metastatic RCC. In advanced metastatic disease, a potential importance as a parameter for treatment control in palliative therapeutic approaches can be assumed, and warrants further investigations.

We report about the successful laparoscopic removal of ureteral stones. Since July 1993, 21 patients with large ureteral calculi have undergone laparoscopic ureterolithotomy. In 19 of 21 patients, laparoscopic ureterolithotomy was successful. The mean operating time was 90 minutes. The postoperative inhospital stay was 1 to 4 days. Laparoscopic ureterolithotomy offers an alternative to open surgery in patients with large ureteral stones or when less invasive measures fail.

Hyperthermia can enhance the clinical response of chemotherapeutic agents in prostate cancer, but optimal sequencing of this combination therapy needs to be developed. Given the role of heat shock proteins (HSPs) in the development of resistance (thermotolerance) to subsequent hyperthermic stresses as well as to certain chemotherapeutics, the study of HSP regulation is important in the establishment of effective schedules in multimodal treatment strategies.In this study we evaluated the effects of the chemotherapeutic agents cisplatin, 5-fluorouracil, and adriamycin in combination with hyperthermia. (43 degrees C, 1 h) on clonogenic survival and inducible HSP70 regulation in Dunning rat adenocarcinoma of the prostate. HSP70 was analyzed by Western blot and by measuring beta-galactosidase produced by cells stably transfected with a gene construct containing the E. coli beta-galactosidase gene driven by the Drosophila HSP70 promoter.Colony formation assays revealed a sensitizing effect of hyperthermia when simultaneously combined with each chemotherapeutic agent, resulting in a potentiated cytotoxicity compared to subsequenced treatments. Thermotolerant cells showed a significantly better survival when treated with adriamycin alone, but also when each chemotherapeutic agent was combined with hyperthermia. This enhanced survival was correlated with inducible HSP70 accumulation. The chemotherapeutics modified the HSP70 promoter activation induced by hyperthermia, suggesting changes in the development of cellular thermotolerance.Our data reveal synergistic cytotoxic effects of the synchronous application of chemotherapeutic agents and hyperthermia on this model of prostate cancer. Furthermore, they demonstrate that the induction of HSPs in thermotolerant cells, as measured by HSP70 induction, results in a modulation the chemotherapeutic-mediated cytotoxicity. Therefore, HSP70 is a useful marker of cellular resistance in multimodal approaches combining hyperthermia and chemotherapeutic agents in the treatment of locally advanced prostate carcinoma.

Development of afterloading techniques in combination with external radiotherapy allows for curative therapy modality for stage C prostate cancer. Between 10/92 and 12/95 128 patients were treated. Stage B and C tumors were found in 36 and 89 cases, respectively. All patients were pathologically proven to be node-negative by laparoscopic node dissection of the fossa obturatoria region. 9 Gy a week was applied during the first and second weeks of treatment (10/92-12/93: 10 Gy each week) interstitially with high-dose rate iridium192 brachytherapy to the prostate. After this, a four-field box of external beam radiation therapy was given to the prostate to a dose of 45 Gy/25 fractions (10/92-12/93: 40 Gy/20 fractions). Before starting treatment median PSA was 13.8 ng/ml. The median PSA 3, 12, and 24 months after completion of therapy was 1.2, 0.78, and 0.75 ng/ml, respectively. Negative biopsies 12 and 24 months after therapy were observed in 56% (49/87) and 72% (31/43), respectively.