[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.

[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.

[Utilizing optical coherence tomography (OCT) for visualization of urothelial diseases of the urinary bladder]. / Anwendung der optischen Kohärenztomographie (OCT) bei der Darstellung von Urothelerkrankungen der Harnblase.

PURPOSE: The technique of optical coherence tomography (OCT) has significantly improved over the last few years. This new diagnostic procedure allows imaging of tissue structure of the bladder wall during cystoscopy with high resolution. MATERIALS AND METHODS: The penetration depth of OCT is limited to 2.5 mm. The resolution is approximately 15 microm. Fifty patients with different clinical conditions of the bladder were examined. Altogether 488 OCT images were generated. RESULTS: OCT of normal bladder mucosa clearly shows a differentiation between urothelium, lamina propria, and smooth muscle. Cystitis and metaplasia are characterized by blurring of the laminated structure and thickening of the epithelial layer. In malignant areas there is complete loss of the regular layered tissue structure. CONCLUSION: OCT improves the diagnosis of flat lesions of the urothelium. It has the potential for facilitating intraoperative staging of malignant areas in the bladder.

[The impact of ALA (5-aminolevulinic acid)-fluorescence detection on the prognosis of superficial bladder cancer]. / Der Stellenwert der ALA-(5-Amino-Lävulinsäure)-Fluoreszenzdetektion für die Prognose des oberflächlichen Blasenkarzinoms. Eine 1-Jahres-Uberlebensanalyse.

PURPOSE: Throughout the past years, several studies have shown that fluorescence cystoscopy with ALA (5-aminolevulinic acid) improves the detection rate of superficial bladder tumors by approximately 20 % compared to standard white light cystoscopy. These results suggest a reduced rate of residual/recurrent tumors with the routine use of ALA fluorescence technique prior to bladder tumor resection. The present prospectively randomized study was performed to verify this hypothesis. MATERIALS AND METHODS: A total of 115 bladder tumor patients were randomized for initial resection under white light or ALA fluorescence. After 6 to 8 weeks, a second-look resection was performed in all patients guided by ALA fluorescence. Additional white light cystoscopies were performed after 3, 6 and 12 months. RESULTS: The second-look resection did not find a tumor in 31 of 51 (59 %) patients initially resected under white light guidance compared to 43 of 51 (84 %) patients in the fluorescence group. This difference was statistically significant (p = 0.005). At 12 months, a tumor was not found in 17 of 48 patients from the white light group vs. 25 of 47 patients from the fluorescence group (p = 0.03). Seven patients were lost to follow-up. CONCLUSIONS: By reducing otherwise inevitable re-operations, fluorescence cystoscopy decreases morbidity and lowers treatment costs.

[Taxanes in the chemotherapy of hormone-refractory prostate carcinoma]. / Taxane in der Chemotherapie des hormonrefraktären Prostatakarzinoms.

Prostate cancer represents one of the most prevalent malignancies in men. Standard therapy of metastatic prostate cancer consists of androgen deprivation, which is a palliative therapy yielding a clinical response of limited duration. In hormone-refractory prostate cancer (HRPC), response to chemotherapy with regimens available until about ten years ago has been disappointing. Nowadays, due to increasing life expectancy and earlier diagnosis and therapy of prostate cancer, more patients with hormone-refractory disease are still in relatively good overall condition. With the taxanes, much more effective cytostatic substances for chemotherapy of HRPC are available today. Using modern taxane-based chemotherapy, effective palliation of pain can be achieved in 50-70% of patients with HRPC, while retaining an acceptable quality of life. There is also evidence for improved overall survival after taxane-based chemotherapy, although this remains to be proven by ongoing studies. This article presents an overview of current studies investigating the outcome after taxane-based chemotherapy, as well as new therapeutic approaches in combination with docetaxel.

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.

[An artificial neural network as a tool in risk evaluation of prostate cancer. Indication for biopsy with the PSA range of 2-20 microg/l]. / Nutzung von artifiziellen neuronalen Netzwerken zur Risikoabschätzung eines Prostatakarzinoms. Biopsieindikationen im PSA-Bereich von 2-20 microg/l.

In this prospective study covering 5.5 years we evaluated the diagnostic power of an artificial neural network (ANN) based on PSA, %fPSA, and clinical data in the PSA range 2-20 microg/l as prostate biopsy indicator. A total of 944 patients with prostate cancer or benign hyperplasia (BPH) were analyzed. The calculation of the individual patient's risk before prostate biopsy was performed at the 90% and 95% specificity and sensitivity levels within the PSA ranges 2-4, 4.1-10, and 10.1-20 microg/l. For the low PSA range 2-4 microg/l, we recommend a first time biopsy at an ANN specificity level of 95%. For PSA range 4.1-10 microg/l, we recommend a first time biopsy at an ANN sensitivity level of 95%. A rebiopsy at the PSA range 10.1-20 micro g/l should be performed based on a 95% sensitivity level. The use of an ANN at PSA 2-20 microg/l enhances the specificity and sensitivity of %fPSA by 9-39%. The application of an ANN based on %fPSA and clinical data improves the diagnostic performance compared to %fPSA only.

Tumor type M2 pyruvate kinase expression in metastatic renal cell carcinoma.

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.

[MRI of prostate cancer using three different coil systems: image quality, tumor detection, and staging]. / MRT des Prostatakarzinoms mit drei verschiedenen Spulensystemen: Abbildungsqualität des Tumors und Staging.

PURPOSE: To compare three MRI coil systems in terms of image quality, delineation of prostate cancer, and tumor staging. MATERIALS AND METHODS: 49 patients with prostate cancer underwent MRI at 1.5 Tesla using a combination of an endorectal coil with a phased-array body coil (combination coil) prior to radical prostatectomy. Images were reconstructed from the data sets acquired with the endorectal coil alone and from those acquired with the combined coil. In addition, 19 patients of the study patients were examined with the body phased-array coil alone without the endorectal coil. The prostate was imaged at a slice thickness of 3 mm using axial and coronal T 2 -weighted sequences and an axial T 1 -weighted sequence. Preoperative analysis of all images acquired was done to determine the accuracy of MRI in local staging of prostate cancer. An additional retrospective analysis served to compare the different coil systems in terms of overall image quality, delineation and localization of the tumor, and criteria for local staging of prostate cancer. RESULTS: Preoperative analysis showed MRI to have an accuracy of 59 % in local tumor staging. Retrospective coil-by-coil analysis demonstrated image quality and tumor delineation to be best for the combination coil and the endorectal coil. Regarding the staging criteria for transcapsular tumor extension and infiltration of adjacent organs, a significant advantage of the combination coil compared to the endorectal coil was identified only for the criterion of smooth bulging. In addition, the endorectal coil and the combination coil were found to be superior to the body phased-array coil in assessing 15 of 17 criteria for local tumor staging but the differences were not significant. CONCLUSION: In view of the achieved superior image quality, the combination coil or the endorectal coil is the preferred method for staging prostate cancer.

[Improvement of hemostasis in laparoscopic and open partial nephrectomy with gelatin thrombin matrix (FloSeal)]. / Verbesserung der Hämostase bei laparoskopischen und offenen Teilnephrektomien durch Gelatine-Thrombin-Matrix (FloSeal).

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.

[Laparoscopic radical nephrectomy: indications, techniques, and oncological outcome]. / Die laparoskopische transperitoneale Tumornephrektomie. Indikation, Technik und onkologisches Outcome.

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.

[Renal carcinoma with invasion of the suprahepatic vena cava (Staehler stage III and IV): surgical treatment and results]. / Nierenzellkarzinom mit suprahepatischem V.-cava-Befall (Stadium III und IV nach Staehler). Operative Therapie und Ergebnisse.

The operative treatment of patients with renal cell carcinoma (RCC) and suprahepatic infradiaphragmatic or supradiaphragmatic vena cava invasion (Staehler stage III and IV) is still an interdisciplinary challenge. The potential high complication rate and the enormous operative-technical efforts have to be brought into line with the individual benefit for the patient. In this study, we have retrospectively analyzed the operative results of 24 patients. We have further compared the patients during follow-up and immunotherapy due to metastasis with a control group of 75 patients without vena cava invasion. Perioperative mortality in the 24 patients was 4%. Four patients had metastasis at presentation and 14 further patients developed metastatic disease during median follow-up of 23.5 months. Median survival was 45 months with a 1-, 3-, and 5-year survival rate of 92, 57, and 33%, respectively. In a multivariate analysis, only the presence of metastasis (p=0.002) and marginal immunotherapy (p=0.1), but not vena cava invasion (p=0.259) or a positive lymph node status (p=0.624) were significant predictors of a poor survival. For patients with RCC and suprahepatic infradiaphragmatic or supradiaphragmatic vena cava invasion (Staehler stage III and IV), the combination of an aggressive surgical treatment combined with subsequent immunotherapy in the presence of metastatic disease offers a realistic therapeutic option with reasonable survival rates.

[Clinical significance of macroscopic 5-aminolevulinic acid (ALA)-inducer fluorescence in transurethral resection of non-invasive bladder cancer]. / Klinicheskoe znachenie vizual'noi fliuorestsentsii indutsirovannoi 5-aminolevulinovoi kislotoi (ALA) pri transuretral'noi rezektsii neinvasivnogo raka mochevogo puzyria.

Macroscopic fluorescence which is induced with aminolevulinic acid (ALA) allows visualizing of small flat tumors, carcinoma in situ, true neoplasm margins and dysplasias of the bladder. Following ALA instillation, cystoscopy was performed under both standard and blue light illumination. In a prospective randomized multicenter study, 102 patients underwent TUR of bladder tumor(s) either with white light or ALA-fluorescence. Significant reduction in the number of residual tumours was detected in 59% (p = 0.005) after 8 weeks, 3 months--in 58% (p = 0.002) and 6 months in 38% (p = 0.01) respectively.

The novel synthetic inhibitor of matrix metalloproteinases Ro 28-2653 induces apoptosis in Dunning tumor cells.

The effect of synthetic inhibitors of matrix metalloproteinases (MMP) has been shown against a variety of tumors in preclinical models. Ro 28-2653, a novel synthetic MMP inhibitor, is able to reduce tumor growth in orthotopic prostatic cancer in rats (R3327 Dunning tumor). However, at present this inhibitory mechanism in tumor inhibition in vivo can only be partly explained by the inhibition of the catalytic activity of MMPs overexpressed in cancereous tissue. Using the flow cytometric method, we have investigated the effect of various concentrations of Ro 28-2653 on the Dunning tumor cells with regard to the staining of F-actin and DNA as markers of apoptosis. In combination with fluorescence microscopy we detected the loss of F-actin and the degradation of internucleosomal DNA. This effect of Ro 28-2653 on apoptosis was dose- and time-dependent increasing with concentration between 10 and 100 microg/ml as well as with time of treatment between 24 and 48 h.