[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.

Antioxidant enzymes in malignant prostate cell lines and in primary cultured prostatic cells.

The antioxidant enzymes catalase, glutathione reductase (GR), glutathione S-transferase (GST), glutathione peroxidase (GPx), and superoxide dismutase (SOD) were determined in the androgen-response LNCaP and androgen-nonresponsive PC-3 and DU 145 cells as well as in prostatic epithelial cell cultures of benign and malignant human prostatic tissue. There were no differences between the enzyme activities of the human primary cell cultures from cancerous tissue and their normal counterparts. The enzyme activities of the three permanent cell lines were either higher (SOD, catalase, GR) or lower (GST, GPx) than in the primary cell cultures. In LNCaP cells catalase and GR were significantly higher, GST, in contrast, was significantly lower than in PC-3 and DU 145 cells. GST in PC-3 and DU 145 cells, and SOD in all the three cell lines showed no significant differences. Catalase, GPx and GR values were significantly different in the three permanent cell lines. The different enzymatic equipment of the prostate cancer cell lines provides the basis for experimental testing of new concepts of cancer treatment with the help of systematic modulations of the antioxidant defence systems in prostate cancer.

Molecular forms of prostate-specific antigen and human kallikrein 2 as promising tools for early diagnosis of prostate cancer.

Prostate-specific antigen (PSA) is the most useful marker in the early detection of prostate cancer and for the monitoring of patients with this diagnosis. Molecular forms of PSA and also human kallikrein 2 have been used to discriminate between benign prostatic hyperplasia and prostate cancer as well as for the detection of prostate cancer within the gray zone of PSA. In this respect, a literature survey on the diagnostic validity of free PSA (fPSA) related to total PSA (tPSA), PSA bound to alpha1-antichymotrypsin (ACT-PSA), and complexed PSA is given together with our results. The ratio of fPSA:tPSA has been shown to improve the specificity of prostate cancer diagnosis on the basis of tPSA measurements. Unnecessary biopsies can be reduced by about 19-64% in the total PSA range of 4-10 microg/liter while only missing 5-10% of cancers. Furthermore, carcinomas in patients with PSA values <4 microg/liter can be detected, indicating an improved sensitivity because of the percent fPSA at low PSA values. ACT-PSA or complexed PSA alone and the calculated derivatives are not superior in their discriminatory power compared with the percent fPSA. The diagnostic significance of the other molecular PSA forms and human kallikrein 2 needs to be evaluated in more extensive clinical trials.

Soluble CD44 molecules in serum of patients with prostate cancer and benign prostatic hyperplasia.

Recent studies suggest that expression of CD44 splice variants are of prognostic significance for a variety of neoplasias. It was the aim of this study to investigate whether any correlation exists between the concentration of soluble CD44 molecules in serum (CD44 standard form and CD44 splice variants v5 and v6) and the prostate cancer stage. Serum levels of these soluble CD44 isoforms were measured by ELISA tests specific for these proteins in controls (n = 30), patients with benign prostatic hyperplasia (BPH; n = 30), with prostate cancer without metastasis (T1,2,3pN0M0; n = 30) and with locally advanced prostate cancer and/or metastatic disease (T3,4pN1,2M1; n = 19). sCD44std and sCD44v6 concentrations were not significantly different among the four groups studied, with few patients' levels outside the central 95% reference intervals. The mean sCD44v5 concentrations of both prostate cancer and BPH patients were significantly lower than those of the controls. There was no significant difference between the soluble CD44 concentrations of the two groups of prostate cancer patients studied. In contrast to results observed in other carcinomas, the determination of soluble CD44 proteins in serum is not suitable for providing additional prognostic information on patients with prostate cancer.

Cathepsins B, H, L and cysteine protease inhibitors in malignant prostate cell lines, primary cultured prostatic cells and prostatic tissue.

Elevated activities of cysteine proteinases, the cathepsins B, H, L (CB, CH, CL) and diminished cysteine protease inhibitors (CPI) have been demonstrated in a variety of tumours and have been suggested to contribute to invasion and metastasis. The situation for prostate cancer is still unknown. In this study, using fluorimetric assays, the catalytic activities of CB, CH, CL were measured in prostatic tissue samples after radical prostatectomy, adenomectomy, transurethral resection of the prostate, in cell cultures grown from cancerous and non-cancerous parts of human prostate after prostatectomy and in the cell lines LNCaP, DU 145 and PC 3. CPIs were determined using heat activation before testing their inhibitory activity against purified CB. Comparing matched pairs of normal and cancerous tissue samples from the prostate, significantly decreased levels of CB, CL in malignant parts of the prostate were found. In contrast, primary cell cultures from cancerous samples showed elevated levels of CB, CH, CL and increased ratios of cathepsins to CPI compared with cell cultures from normal prostate. Established cell lines showed a similar distribution pattern of each cathepsin, DU 145 containing the highest levels, followed by LNCaP and PC 3. Our results suggest that elevated cathepsin levels and consequently increased ratios of cathepsins to CPI in primary cell cultures from cancerous versus non-cancerous parts of the prostate may be indicative of a cellular proteolytic imbalance in prostatic cancer cells. In this respect, primary cell culture experiments should be preferred to determinations in tissue samples.

High-dose rate interstitial with external beam irradiation for localized prostate cancer--results of a prospective trial.

PURPOSE: A prospective phase II trial was carried out to test the feasibility and effectiveness of a combined interstitial with external beam radiotherapy approach for localized prostate cancer. MATERIALS AND METHODS: Between October 1992 and December 1994, 82 evaluable patients were treated. T2 and T3 tumours, according to the AJCC classification system of 1992, were found in 21 and 61 cases, respectively. The median follow-up was 24 months; three patients were lost during follow-up. All of the patients were pathologically proven to be node-negative by laparoscopic node dissection of the fossa obturatoria region. A dose of 9 Gy a week was prescribed during the first and second weeks of treatment (10 Gy each week from October 1992 to December 1993) interstitially with high-dose rate Iridium-192 brachytherapy to the prostate and tumour extension beyond the capsule. External beam four-field box irradiation was then given to the prostate to a dose of 45 Gy/25 fractions (40 Gy/20 fractions from October 1992 to December 1993). RESULTS: Before starting treatment, a PSA value of > or =10 ng/ml was found in 64.6% (53/82) of patients with a median PSA of 14.0 ng/ml. The median PSA 3, 12 and 24 months after completion of therapy was 1.20, 0.78 and 0.70 ng/ml, respectively. The PSA value was < 1.0 ng/ ml in 52.9% of patients at 2 years. Negative punch biopsies 12 and 24 months after therapy were observed in 69.8% (44/63) and 73. 1% (38/ 52) of patients, respectively. A positive biopsy combined with a PSA value of > 1.0 ng/ml was considered as local failure. The local tumour control rate was 79.5% at 2 years. Acute side-effects were not increased relative to external beam irradiation alone. Severe side-effects were observed in three patients (two of the three patients had additional risk factors (colitis ulcerosa and diabetes mellitus)); they developed rectourethral fistulae requiring colostomy after biopsies from the anterior rectal wall. CONCLUSION: The described method is feasible and well tolerable. The three complications observed were not caused by irradiation alone. Biopsies from the anterior rectal wall after definitive high-dose radiotherapy for prostate cancer have to be seen as obsolete. The rate of negative prostate biopsies of 73.1% after 24 months represents an encouraging result.

Rapid detection of elevated prostate-specific antigen levels in blood: performance of various membrane strip tests compared.

OBJECTIVES: To compare the ability of four commercially available membrane strip tests to detect increased (4 microg/L or more) concentrations of prostate-specific antigen (PSA) in blood. METHODS: Serum samples with PSA concentrations less than 4 microg/L (n = 67) and from greater than 4 microg/L to 20 microg/L (n = 32) were independently examined by two observers using the PSA membrane strip tests from Chembio, Medpro, Seratec, and Syntron. The positive and negative results of each membrane strip test were classified as either true positive or negative and false negative or positive by comparing them with the quantitative PSA assay of Immulite DPC using the conventional threshold value of 4 microg/L. RESULTS: The interobserver variations of the tests were between 93% and 97%. The color stability of the Seratec and Chembio tests did not show significant differences between test results read within 10 to 20 minutes of the reaction time; however, the results of the other two tests were especially affected by variations in the reading time. The sensitivity and specificity of the tests in relation to the threshold of 4 microg/L were 67% to 93% and 87% to 97%, respectively. CONCLUSIONS: The Syntron test and, within certain limitations, the Seratec test fulfill the concept of a rapid and convenient PSA determination to detect PSA concentrations greater than 4 microg/L. Methodologic optimization of the tests by a grading of the PSA measuring ranges (eg, between 0 and 2, 3 and 4, 4 and 6, and 7 and 10 microg/L) should be taken into account for future development.

Analytical aspects regarding the measurement of metalloproteinases and their inhibitors in blood.

OBJECTIVE: Both in vitro and in vivo investigations have shown that the balance between matrix metalloproteinases (MMP) and the tissue inhibitors of metalloproteinases (TIMP) seems to be important in physiological and pathological processes which involve tissue remodeling and repair. DESIGN AND METHODS: In order to investigate the analytical reliability of new commercial ELISA tests. BIOTRAK test kits (Amersham Int.) were used for the determination of metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinase-1 (TIMP-1), and the MMP-1/TIMP-1 complex in blood. RESULTS: The detection limits and the precision data were in the usual ranges of ELISA tests so that concentrations found in blood could be determined reliably. Since all three analytes were lower in heparin plasma than in serum or EDTA plasma, heparin plasma was selected as the specimen of choice. Measurement of diluted samples gave higher values than those of undiluted native plasma samples because the inhibitory effects of specific/unspecific inhibitors or other matrix components were apparently reduced. To obtain comparable data from different laboratories, the predilution of samples must be defined. We recommend to use diluted plasma samples of 1:5, 1:21, and 1:11 for the determination of MMP-1, TIMP-1, and the complex MMP-1/TIMP1, respectively. The preliminary upper 95% reference limits measured under these conditions in healthy subjects (40 females: 40 males) were 14.4 micrograms/L for MMP-1 in females, 20 micrograms/L for MMP-1 in males. 1668 micrograms/L for TIMP-1 and 116 micrograms/L for the complex MMP-1/TIMP-1. CONCLUSION: The study has shown that the BIOTRAK test combinations for MMP-1, TIMP-1, and MMP-1/TIMP-1 complex allow a reliable measurement of the analyte concentrations in heparin plasma. In order to avoid preanalytical misinterpretations only heparin plasma samples in defined dilutions should be used.

Urinary markers of malignancy.

Transitional cell carcinoma (TCC) is the second most common malignancy in the genitourinary tract. The majority of urothelial tumors are superficial when the patient first presents, but despite adequate resection of the primary lesion the recurrence rate is particularly high. In a small but significant group of patients the tumor is primary invasive or subsequently can progress and leads to death. Voided urine can be easily obtained and therefore diagnostic urine tests would be ideal for screening or follow up of TCC. Although many urinary markers have been described, none of them is used routinely in clinical practice. Promising tumor markers still need to be evaluated in multi-center clinical studies. Larger prospective trials are necessary in order to identify prognostic indicators that would help to predict disease progression or response to different treatment modalities (BCG, chemo-, radiotherapy, etc.). Hopefully, new diagnostic urine tests will allow to identify patients who will most benefit from early cystectomy with or without adjuvant treatment, bladder sparing protocols or systemic treatment. In this paper we have reviewed the literature and discuss, from the clinician's point of view, the current status of various diagnostic tests for urinary markers. [Lee SJ, Lee WE, Chang SG, Lee CH, Kim JI. A comparative study of telomerase, Lewis X, BTA, NMP22 and urinary cytology in bladder tumor. J Urol 1999;161(suppl):152.]

Ratio of alpha 1-antichymotrypsin--prostate specific antigen to total prostate specific antigen in prostate cancer diagnosis.

OBJECTIVE: To evaluate the analytical performance and diagnostic utility of prostate specific antigen (PSA) bound to alpha 1-antichymotrypsin (ACT) in serum to improve the differentiation between benign prostatic hyperplasia (BPH) and prostate cancer (PCa). METHODS: A total of 351 white men 21 to 88 years old were analysed. Serum concentration of tPSA, free PSA (fPSA) and ACT-PSA were measured in 163 untreated PCa patients (median age 66 years), 94 patients with histologically or clinically confirmed BPH (median age 65 years) and 94 men without prostate disease considered as controls (median age 54 years). The Elecsys system 2010 (Roche Diagnostics, Germany) was used for the determinations of tPSA and fPSA. The ACT-PSA assay is a new developed prototype on the ES system (Roche Diagnostics, Germany). RESULTS: The ACT-PSA assay showed reliable data of analytical performance in comparison to established assays for tPSA and fPSA. The median concentrations of tPSA (PCa: 9.22 micrograms/L, BPH: 2.28 micrograms/L, controls: 0.99 microgram/L) and ACT-PSA (7.99 micrograms/L vs. 1.63 micrograms/L vs. 0.58 microgram/L) were significantly different, respectively. The median ratios of fPSA/tPSA (PCa: 12.3%, BPH: 25.4%), ACT-PSA/tPSA (90.5% vs. 66.6%) and fPSA/ACT-PSA (14.0% vs. 38.6%) were significantly different between PCa and BPH patients. Significant differences of ratios between BPH and controls were not observed. Receiver operating characteristics analysis (tPSA up to 20 micrograms/L) for discrimination between PCa and BPH showed that the ratios fPSA/tPSA (area under the curve: 0.861) and fPSA/ACT-PSA (0.847) were significantly different from tPSA (0.663), but ACT-PSA (0.733) alone and also the ratio of ACT-PSA/tPSA (0.780) were not significantly different from tPSA (0.663). CONCLUSION: The ratio fPSA/tPSA showed the best discrimination between BPH and PCa. The single or additional determination of ACT-PSA to tPSA does not improve the differentiation between the two groups of patients.

Comparison between equimolar- and skewed-response assays of prostate specific antigen: is there an influence on the clinical significance when measuring total serum prostate specific antigen?

Using the Tandem-E, Axsym and LIA-mat assays, prostate specific antigen (PSA) was measured in pure PSA solutions of known concentrations of free and complexed PSA and in serum of patients with prostate cancer (n = 31), benign prostate hyperplasia (n = 32) and in healthy controls (n = 27). Measurements of pure PSA solutions showed that the AxSym assay exemplified typical properties of the skewed-response assay reacting more to free PSA than to the complexed PSA forms whereas the other two assays showed an equimolar-response. When PSA was measured in the serum of the tree groups, the AxSym test and Tandem-E gave similar PSA values whereas the LIA-mat test yielded significantly lower values. These results were not related to the amount of free PSA in the samples and proved that discordant PSA values between PSA assays were not mainly caused by the use of skewed- or equimolar assays. Despite these differences, receiver-operation characteristic analysis confirmed that the clinical validity of all three PSA tests did not differ.

[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.

[MRI of the prostate after combined radiotherapy (afterloading and percutaneous): histopathologic correlation]. / MRT der Prostata nach kombinierter Radiotherapie (Afterloading und perkutan): Histopathologische Korrelation.

AIM: To identify the MRI changes of the prostate after combined (high-dose rate interstitial with external beam) radiotherapy for, localized prostate cancer and to correlate the findings with histology in order to determine the value of MR imaging in the follow-up of these patients. MATERIAL AND METHODS: Twenty-three patients underwent MR imaging at 1.5 T between 6 and 24 months after completion of combined radiotherapy. The prostate was imaged with axial and coronal T2-weighted sequences and axial T1-weighted sequences before and after intravenous administration of Gd-DTPA. Quadrant or sextant biopsy was performed in all cases and three patients with proven persistence of the tumor underwent salvage prostatectomy. The MRI findings were compared with the biopsy results or the large-area sections. RESULTS: On T2-weighted images the fibrotically changed peripheral zone was hypointense while persistent tumor tissue showed hyperintensity. Solid tumors were depicted when they had a diameter of 1 cm or more. Persistent tumors of the diffuse multifocal type escaped detection. Contrast-enhanced T1-weighted imaging yielded no additional information. The accuracy in detecting persistent tumor was 74%. CONCLUSIONS: Histopathologic changes seen after combined radiotherapy correlate with the findings on T2-weighted MR images. MR imaging cannot replace follow-up by routine biopsy. Its only role is assessing local operability in cases found to have increasing PSA levels during follow-up. Further studies are needed to determine the role of MR imaging in this patient population.

[The staging of bladder tumors in MRT: the value of the intravesical application of an iron oxide-containing contrast medium in combination with high-resolution T2-weighted imaging]. / Staging von Harnblasentumoren in der MRT: Wertigkeit der intravesikalen Applikation von eisenoxidhaltigem Kontrastmittel in Kombination mit hochaufgelöster T2-gewichteter Bildgebung.

AIM: To investigate superparamagnetic iron oxide (SPIO) particles as intravesically applied contrast material in combination with high-resolution T2-weighted MR imaging for the diagnostic assessment of urinary bladder tumors. METHODS: A prospective study was performed in 40 patients with suspected urinary bladder tumors who underwent MR imaging with a body phased-array coil at 1.5 T. Prior to imaging, a SPIO-containing solution (179.2 mg Fe/l) was instilled into the bladder. All patients were examined with T2-weighted, half-fourier acquired single shot turbo spin echo sequences and T1-weighted fast low angle shot sequences in 3 planes as well as a T2-weighted turbo spin echo sequence (TSE) using a 512 matrix. An additional gadolinium-enhanced dynamic study was performed in 33 patients. All patients underwent transurethral resection of the bladder or cystectomy. RESULTS: The combination of intravesically applied SPIO particles and a high-resolution T2-weighted TSE sequence depicted intravesical tumors as small as 4 mm. A reliable identification of the different layers of the bladder wall was possible in 5 cases only. The T2-weighted TSE sequence allowed the correct determination of the depth of infiltration in 29 of 36 patients with urothelial cancer by assessing the inner and outer boundary of the urinary bladder wall. This sequence had a diagnostic accuracy of 81% compared to 84% for the dynamic study (26/31). CONCLUSION: Even small tumors could be identified with the T2-weighted TSE sequence after intravesical administration of SPIO particles but it was not possible to reliably differentiate the layers of the bladder wall. The results suggest that a dynamic MR imaging study cannot be dispensed with in patients with urinary bladder cancer.

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.

[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.

[Molecular forms of prostate-specific antigen and human kallikrein 2 as possible indicators in prostatic carcinoma diagnosis]. / Molekulare Formen des prostataspezifischen Antigens und des humanen Kallikreins 2 als mögliche Indikatoren in der Prostatakarzinomdiagnostik.

Prostate-specific antigen (PSA) is the most useful marker in the early detection of prostate cancer and in the monitoring of patients with this diagnosis. Molecular forms of PSA and human kallikrein 2 (hK2) have been used to discriminate between benign prostatic hyperplasia and prostate cancer, as well as for the detection of prostate cancer within the gray zone of PSA. In this respect, a literature survey on the diagnostic validity of free PSA (fPSA) related to total PSA (tPSA), PSA bound to alpha 1-antichymotrypsin (ACT-PSA), and complexed PSA (cPSA) is given together with our own results. The ratio of fPSA/tPSA has been shown to improve both sensitivity and specificity of prostate cancer diagnosis based on tPSA measurements. The number of biopsies can be reduced in the total PSA range of 4-10 micrograms/l. Furthermore, carcinomas can be detected in patients with PSA values less than 4 micrograms/l. ACT-PSA or cPSA alone and the calculated derivatives are not superior in their discriminatory power compared with tPSA and the fPSA% value. The other molecular PSA forms and hK2 are still objects of research and their diagnostic significance needs to be evaluated in more extensive clinical trials.

[Tumor M2 pyruvate kinase in renal cell carcinoma. Studies of plasma in patients]. / Tumor-M2-Pyruvatkinase beim Nierenzellkarzinom. Untersuchungen im Plasma von Patienten.

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.

[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.