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The aim of the present study was to evaluate the clinical significance of the concentration of serum amyloid A (SAA) in patients with renal cell carcinoma (RCC). SAA protein was determined with enzyme-linked immunosorbent assay in serum samples of 55 healthy controls and 98 RCC patients subdivided into groups with localized tumor (N0M0, n=40), with lymph node metastases (N1M0, n=13), and distant metastases (M1, n=45). SAA concentrations in controls and N0M0 group of RCC were not different while SAA concentrations were significantly elevated in M1 patients compared to the N1M0 and N0M0 patients. In this respect, SAA provided an accurate detection of distant metastases with the area under the ROC curve of 0.86. SAA was identified as a significant independent factor of survival in RCC patients using the multivariate Cox proportional hazards regression model. SAA could be a useful analyte in predicting the survival outcome of RCC patients.

Living donor kidney transplantation (LD-KTX) is increasing worldwide. With the prevalence of urolithiasis ranging between 4% and 15%, the number of donors with current nephrolithiasis or a history of the disease will increase as well. A questionnaire was sent to all German centers with LD-KTX programs (urologists and general surgeons). Answers were compared for differences between urological and surgical kidney transplant centers. Response rate was 74%. Nephrolithiasis at the time of KTX is an exclusion criterion at 36% of the German centers (58% urological/19% surgical, chi(2) = 4.65, p = 0.03, Fishers exact p = 0.05), 96% of the centers accept kidney donors with a history of nephrolithiasis. The length of the stone-free episode is regarded as relevant by 42% of all centers (58% urological vs. 32% surgical centers, p = ns). Stone composition is a criterion for 54% of centers (66% vs. 44%, p = ns). More than half of the centers accept a history of cystine stones, almost all centers of struvite and urate stones. Donors with current nephrolithiasis were less commonly accepted by urologists than by general surgeons. For almost all centers history of nephrolithiasis does not preclude living kidney donation. Stone composition proved to be of little relevance for decision making.

Objectives This study assessed the usefulness of serial measurements of bone turnover markers in men with metastatic prostate cancer treated with zoledronic acid to detect disease progression. Methods Serum measurements of total alkaline phosphatase (tALP), bone-specific alkaline phosphatase (bALP), cross-linked N-terminal (NTx) and cross-linked C-terminal (CTx) telopeptides of type I collagen, amino-terminal procollagen propeptides of type I collagen (PINP), C-terminal telopeptides of type I collagen (ICTP), and prostate-specific antigen (PSA) were performed in 77 prostate cancer patients suffering from bone metastases and treated with zoledronic acid up to 15 mo. Fifty patients were with and 27 patients without objective evidence of metastatic bone progression during the administration of zoledronic acid. Results The baseline bone marker concentrations were not significantly different between the groups. After administration of zoledronic acid all bone markers except of ICTP decreased compared with baseline. CTx showed the greatest decrease. In patients with metastatic bone progression PINP, tALP, bALP, and ICTP were significantly higher at weeks 24, 36, 48, and 60 after starting treatment with zoledronic acid compared with patients without progression. In addition to the information of prostate-specific antigen as a monitoring parameter, the bone formation marker showed a better distinction between patients with and without disease progression. Conclusions Selected bone turnover markers provide valuable information regarding progression of bone metastasis in men with metastatic prostate cancer under bisphosphonate therapy. The clinical impact should be confirmed in prospective randomised studies.

Worldwide, specific pediatric allocation schemes successfully try to minimize waiting time for children with end-stage renal disease (ESRD). The article is a review of current issues in pediatric kidney transplantation. The procedure is the treatment of choice for children and adolescents with ESRD, with 1- and 3-year graft survival rates of 95% and 90% and recipient survival after 5 and 10 years of 95% and 90%. Preoperative surgery is often necessary to minimize negative effects of congenital anomalies. No minimum age exists for pediatric transplantation, but most often the recipient body weight is ideally above 10 to 15 kg. Technical concepts should include extravesical anastomosis, stenting of the ureter, and potentially intraperitoneal placement of the graft. Immunosuppression has constantly improved. The aim is a tailored regimen to reduce side effects and improve compliance, which necessitates intense counseling of the child and the parents prior to, during, and after transplantation as many adolescents lose their graft due to noncompliance. Intense follow-up must also exclude infections, especially with herpes and polyoma viruses. For the future, age matching may be only one promising concept to improve results. As only a small number of children require the procedure in each country, multinational studies should be initiated to optimize outcomes in children and adolescents.

OBJECTIVE To show the effect of different results for total prostate specific antigen (tPSA) and percentage free/total PSA (%fPSA) obtained with different assays for differentiating between benign and malignant prostate diseases. PATIENTS AND METHODS Data were used for tPSA and fPSA levels from 596 patients with prostate cancer (314) or no evidence of cancer (282) within the PSA range 0.5–10 ng/mL, analysed with assays from Abbott (AxSYM), Beckman Coulter (Access), DPC (Immulite 2000), and Roche (Elecsys 2010), and with tPSA and complexed PSA (cPSA) assays from Bayer (ADVIA Centaur), as already reported. Receiver operating characteristics (ROC), specificities at assay-dependent and fixed thresholds, and the percentages of correct classification rates of patients were calculated. RESULTS Whereas the areas under the ROC curves were no different among all tPSA assays, the assay-specific thresholds at 90% sensitivity were 2.5–3.1 ng/mL. When using fixed 2.5 or 4 ng/mL tPSA thresholds there was a wide sensitivity range, with significant differences among almost all assays, resulting in significantly different classification rates of patients. These differences were even larger when using fixed %fPSA thresholds. CONCLUSIONS The current situation of differences among PSA values measured with different assays do not allow the recommendation of uniform PSA limits as biopsy criteria. For that purpose, better harmonization of PSA values between the different PSA test systems must be realized.

To evaluate diagnostic and prognostic significance of plasma osteopontin (OPN) in patients with renal cell carcinoma (RCC).The retrospective study included 80 patients with RCC (pN0M0, n = 32; pN1M0, n = 11; M1, and n = 37), and 52 healthy controls (27 females and 25 males). OPN, the bone marker bone-specific alkaline phosphatase (bALP) and carboxyterminal telopetide of type-I collagen (ICTP), and the enzymes alanine aminotransferase (ALAT), and gamma-glutamyltransferase (GGT) were evaluated together with Memorial Sloan-Kettering Cancer Center (MSKCC) laboratory parameters. Data were analyzed by receiver-operating characteristics (ROC), survival analysis, and Cox proportional hazards regression model.OPN and ICTP levels in RCC patients with distant metastases were significantly elevated (medians 115 and 4.7 microg/l, P0.001) compared to those without metastases (31.1 and 2.5 microg/l) and controls (28.9 and 2.1 microg/l) but did not differ between patients with bone or non-bone metastases. Both bALP and ALAT were not different between all study groups, while GGT was only increased in patients with non-bone metastases. In ROC analysis, OPN showed the best discrimination between patients with and without metastases (area under the curve: 0.888). High OPN values were associated with poor survival (Kaplan-Meier analysis, log-rank test, P = 0.002). Multivariate Cox regression with forward and backward stepwise elimination confirmed plasma OPN as independent predictive survival factor in RCC patients.Our results show that high plasma OPN levels are associated with distant metastases and poor survival in RCC patients. The use of OPN as potential marker to monitor new treatment strategies in patients with advanced RCC should be evaluated in prospective studies.

Objectives Minimally invasive radical nephrectomy has gained widespread acceptance in the urological community. Both the laparoscopic and retroperitoneoscopic approach have been established and advocated for radical surgery. Our experience and the advantages and indications for each procedure are analyzed in this article. Methods Data from two clinics that routinely perform either laparoscopic or retroperitoneoscopic nephrectomy for localized tumours are compared. At the Charite Urology Clinic, Campus Mitte, the transperitoneal laparoscopic approach is the preferred technique for T1 and selected T2 tumours. At the Basel University Hospital, the preferred technique for patients with clinical T1 renal tumours is retroperitoneoscopy. Results During a period of 5 yr, 163 patients underwent minimally invasive nephrectomy using either the laparoscopic ( n =125) or the retroperitoneoscopic ( n =38) approach. There were no major intraoperative complications with either technique. Intra- and postoperative data were comparable and oncological outcome was similar for both techniques, at a mean follow-up of 25 mo. Conclusions Both retro- and transperitoneal approaches of minimally invasive radical nephrectomy are safe procedures that achieve the same standard and duplicate oncological principles established for open surgery.

Objectives Laparoscopic partial nephrectomy (LPN) is emerging as an attractive, minimally invasive, nephron-sparing technique for selected renal tumors. We report our technique and outcome involving the experience of three different surgeons. Patients and methods Between March 2001 and June 2005, 80 patients underwent transperitoneal LPN for exophytic tumors. Mean age was 58 yr (range: 30–79). Median tumor size was 2.6cm (range: 0.5–8.5). In 64 cases the renal artery was clamped with endoscopic bulldog clamps. Hemostasis was achieved by application of FloSeal; lesions of the collecting system were closed with Lahodny sutures in 33 cases (31%). Frozen sections were obtained in all cases to document margin status. Results All 80 procedures were successful with no intraoperative complications. Mean surgical time was 203min (range: 110–355); clamping time was 20min (range: 6–75) in 64 cases. In 33 cases the collecting system was opened and required laparoscopic suturing. Margins were negative in 72 cases, in 6 cases secondary resection was necessary to achieve negative margin status, and in 2 cases radical nephrectomy was performed. In 2 cases relaparoscopy was performed for infected hematoma and suspected bleeding. Prolonged extravasation of the collecting system was treated conservatively with a double-J stent in 2 cases. At a mean follow-up of 28 mo (range: 7–62), no recurrence was observed. Conclusions LPN using FloSeal is a feasible and safe method for treatment of small renal masses. The technique is reproducible by surgeons accustomed to complex laparoscopic procedures. Patient outcome was comparable with data published for open standard procedures.

Objectives To assess the diagnostic performance of the major electrophoretic subforms of free prostate-specific antigen (PSA), named F2 and F3, for differentiating between benign and malignant prostatic disease in men with total PSA (tPSA) concentrations up to 10 μg/L. Methods In sera from 50 patients with prostate cancer (PCa) and 44 men without evidence of malignancy (NPCa), F2 and F3 were quantified by two-dimensional electrophoresis and Western blotting. The F2/F3 ratios were compared with the conventional parameter tPSA and percentage fPSA/tPSA ratio (%fPSA) in univariate and multivariate analyses using receiver operating characteristic analysis. Results F2 was lower in the NPCa group (median 17%) than in the PCa group (55%), and F3 was greater in the NPCa group (62%) than in the PCa group (45%), resulting in a significantly lower F2/F3 ratio in the NPCa group than in the PCa group (0.32 versus 1.21). The F2/F3 ratio correlated with the %fPSA and prostate volume but not Gleason score, tumor stage, age, or tPSA. The F2/F3 ratio and F2-F3/%fPSA ratio had greater areas under the receiver operating characteristic curves than did tPSA or %fPSA, especially in the subgroup of %fPSA greater than 15%. Models of binary logistic regression confirmed the improvement of diagnostic accuracy using the F2/F3 ratio as an independent variable. Conclusions Compared with tPSA and %fPSA, the fPSA subforms F2 and F3, assessed as F2/F3 or F2-F3/%fPSA ratios, enhanced the differentiation between men with and without PCa for tPSA levels up to 10 μg/L. Additional characterization of these forms should be performed to develop a feasible assay.

Fast-track surgery describes innovative treatment concepts ensuring a faster convalescence phase. The aim of this study was to allow hospital discharge 3 days after surgery without additional complications in patients receiving LRPE for localized prostate cancer. Twenty-five patients each were randomized in the study groups to verify if a fast-track regimen could be transferred into clinical routine. The perioperative data, early complications, hospital stay as well as readmission rate were analyzed. The mean postoperative stay was 3.6 days in the fast-track group versus 6.7 days in the conventional group. The overall complications were significantly less in the fast-track procedure. The readmission rate was low and not significant. Patients receiving an LRPE benefit from a suitable fast-track concept. The postoperative hospital stay could be shortened nearly by half with a significantly decreased overall complication rate. Thus, fast-track concepts might contribute to saving resources in the long term. However, more evidence based on larger prospective trials is needed to achieve optimal quality of life for patients perioperatively.

Objectives We report on ureteral and surgical complications in our first 110 consecutive recipients of kidneys procured with laparoscopic living donor nephrectomy (LLDN). Methods The records of all living donor transplants with LLDN performed between February 1999 and December 2004, including 10 pediatric transplants, were reviewed retrospectively. Three urologists performed LLDN using a pure laparoscopic non–hand-assisted transperitoneal technique. Kidney transplantation was performed in a standard fashion. For ureteroneocystostomy, the intravesical Politano-Leadbetter (P-L) technique was used. Results Two-year patient and graft survival was 99% and 98%, respectively. Serum creatinine at 12 months was 1.36±0.1mg/dl in adult and 0.99±0.23mg/dl in pediatric recipients. Nineteen right donor kidneys were transplanted into adult recipients. Surgical complications included three symptomatic lymphoceles, one peritransplant haematoma and one kinking of a lower pole artery. All five (4.5%) ureteral complications occurred in adult recipients with a mean age of 33.2±2.8 years. The incidence of ureteral complications was not clustered around the early phase of our LLDN experience. Of the three (2.7%) patients diagnosed with ureteral obstruction, two required ureteral reimplantation, and one was managed conservatively. Another two patients (1.8%) with a urinary leak received a double J stent and a cystostomy catheter for 3 and 5 months, respectively. Of the five patients with a ureteral complication, three had received a donor kidney with more than one renal artery. Conclusions LLDN combined with the intravesical (P-L) ureteral implantation technique provides excellent graft outcomes with low recipient morbidity. Renal artery multiplicity may increase the risk of ureteral complications.

Purpose: Therapeutic efficacy of the novel matrix metalloproteinase (MMP) inhibitor Ro 28-2653 has been shown in various models of different tumor entities. We hypothesized that the inhibitor effect of Ro 28-2653 on the tumor growth could be improved by combination with chemotherapeutic drugs and examined therefore the effect of Ro 28-2653 alone and in combination with etoposide or estramustine in the MatLyLu Dunning R-3327 rat tumor model characteristic for the androgen-independent prostate cancer (PCa). Methods: In vitro effects were estimated measuring the proliferation of MatLyLu cells incubated with the three agents alone or in combination using the XTT test. The in vivo effects of the agents alone or in combination were examined by measuring the tumor weight 18 days after tumor cell injection. Results: The proliferation rate was only inhibited by etoposide while that effect was increased in combination with Ro 28-2653 and estramustine. Ro 28-2653 reduced the tumor weight by 86%. That effect was significantly increased in combination with etoposide to 92%. Conclusions: The inhibitory effect of the MMP inhibitor Ro 28-2653 on the tumor growth in the Dunning PCa model is enhanced by the standard chemotherapeutic drug etoposide. A combined application of both agents could be considered as potential tool to improve the therapy of patients with advanced PCa after failure of hormonal treatment.

Housekeeping genes as endogenous references are generally used for the relative quantification of target genes in gene profiling studies. To date that issue has not been sufficiently investigated in bladder cancer. From a panel of 9 potential candidates we selected the most stable housekeeping genes for gene normalization in bladder cancer tissue.Expression profiles of the 9 genes ACTB, ALAS1, G6PD, GAPD, HMBS, HPRT1, K-ALPHA-1, SDHA and TBP were established in matched malignant and nonmalignant tissue specimens from 14 patients with bladder cancer. Quality assessment of isolated RNA was performed with a 2100 Bioanalyzer (Agilent Technologies, Palo Alto, California) and real-time reverse transcriptase-polymerase chain reaction was performed with LightCycler. The software geNorm and NormFinder (Aarhus University, Aarhus, Denmark) were used to identify the most suitable reference genes.RNA was isolated with high purity and integrity. Candidate reference genes showed a broad range of between 20 and 34 polymerase chain reaction cycles. Expression did not depend on patient sex or tumor stage. GAPD, G6PD and HMBS showed significant differences in expression between malignant and nonmalignant pairs (at least p0.04). Expression of the remaining genes did not differ between the matched pairs. SDHA and TBP were the most stably expressed genes, covering higher and lower expression levels.For normalization purposes in gene profiling studies of bladder cancer the genes SDH and TBP are recommended as single reference genes depending on the expression level of the target gene or more favorably in combination.

Background: The comparability of total and free prostate-specific antigen (tPSA and fPSA) results among commercial PSA assays has been suggested to be improved by calibration to WHO PSA reference materials and the development of equimolar-response assays. To characterize the current situation, we assessed 5 frequently used commercial assay combinations for tPSA and fPSA regarding the interchangeability of the PSA values and the ratio of fPSA to tPSA (%fPSA), equimolar characteristics, and diagnostic accuracy. Methods: Sera from 314 patients with prostate cancer (PCa) and 282 men with no evidence of prostate cancer (NPCa) were measured with tPSA and fPSA assays from Abbott (AxSYM), Beckman Coulter (Access), Diagnostic Products Corporation (Immulite 2000), and Roche (Elecsys 2010) and with tPSA and complexed PSA (cPSA) assays from Bayer (ADVIA Centaur). Results: Method comparisons (Passing and Bablok regressions; Bland–Altman plots) showed assay-dependent results for tPSA, fPSA, and %fPSA. With the Access tPSA values taken as 100%, tPSA concentrations varied from 87% (AxSYM and ADVIA Centaur) to 115% (Immulite), leading to different numbers of patients classified according to the commonly recommended tPSA cutoffs for performing a biopsy. Different %fPSA values also led to assay-dependent ROC analysis results, a finding that shows the importance for the diagnostic accuracy. Conclusion: Interchangeability of tPSA, fPSA, and %fPSA values obtained by commercial PSA assays remains inadequate, but attention to this issue may minimize the misinterpretation of PSA results obtained by different assays.

Die Ursachen der terminalen Niereninsuffizienz im Kindesalter unterscheiden sich deutlich von denen des Erwachsenenalters. Die Therapie der Wahl besteht in der Nierentransplantation. In Deutschland wurden im Jahre 2003 117 Kinder und Jugendliche nierentransplantiert. Spezifische Probleme bestehen in der Immunsuppression und den daraus resultierenden Komorbiditaten im Kindesalter. Der vorliegende Beitrag gibt eine Ubersicht uber die Moglichkeiten und Probleme der Vorbereitung, der Transplantation und des weiteren Verlaufs von Nierentransplantationen im Kindesalter.

The determination of pro prostate specific antigen (proPSA) forms has been suggested to be promising in prostate cancer diagnosis. In this multicenter trial we evaluated the diagnostic usefulness of (-5, -7) proPSA.A total of 2,055 white men, including 1,046 with and 1,009 without prostate cancer, with total PSA (tPSA) between 0.28 and 81 ng/ml were retrospectively analyzed. Of these men 2,026 and 1,727 had tPSA less than 20 and less than 10 ng/ml, respectively. All subjects were untreated for prostatic disease and underwent multisector needle biopsy of the prostate. An Elecsys 2010 analyzer was used to determine tPSA, free PSA (fPSA) and (-5, -7) proPSA in the 2,055 serum samples. ROC analyses were performed to discriminate men with biopsy positive and negative results in the entire and in select tPSA ranges.In the select tPSA range 2 to 4 ng/ml the area under the ROC curve for proPSA (0.53) and proPSA/fPSA (0.59) was not significantly larger than that for tPSA (0.60) or the fPSA/tPSA (f/tPSA) ratio (0.64). In the tPSA range 4 to 10 ng/ml the area under the curve for the ratio proPSA/fPSA (0.67) was larger than for tPSA (0.53) but not larger than for f/tPSA (0.69). The f/tPSA ratio demonstrated the best discriminatory power in this tPSA range of 4 to 10 ng/ml.In this multicenter study no improvement in diagnostic accuracy was shown when comparing (-5, -7) proPSA and the corresponding ratios with tPSA or f/tPSA. Further studies using other proPSA forms or tumor associated proteins should be done.

As shown in various studies 5-aminolevulinic acid (ALA) induces fluorescence of malignant and dysplastic bladder tissue and increases tumor detection rates by about 20%. However, data on the long-term benefits are sparse. Thus, the 5-year outcome data of a prospective randomized trial comparing patients who initially underwent bladder tumor resection (TUR) under standard white light or with ALA induced fluorescence were evaluated.A total of 115 patients with suspected superficial bladder cancer were randomized to undergo standard or ALA assisted TUR. After the second look TUR at 6 weeks patients were followed for a median of 39 (standard) and 42 (ALA) months.Median time to first recurrence was 5 months in the standard and 12 months in the ALA group. Recurrence-free survival was 25% in the standard and 41% in the ALA group. The recurrence rate at 2, 12, 36 and 60 months after initial TUR was 41%, 61%, 73% and 75%, and 16%, 43%, 59% and 59% in the white light and ALA groups, respectively. The total number of recurrences was 82 in the standard and 61 in the ALA group. Tumor progression occurred in 9 patients in the standard and 4 in the ALA group. Cost analysis suggests a considerable economical advantage of ALA fluorescence assisted TUR compared to the standard procedure.The initial advantage of improved tumor detection and decreased recurrence rates by ALA fluorescence assisted TUR is maintained for years, and effectively reduces morbidity and costs in patients with superficial bladder tumors.

Using quantitative reverse transcription-polymerase chain reaction (RT-PCR), reference genes are utilized as endogenous controls for relative quantification of target genes in gene profiling studies. The suitability of housekeeping genes for that purpose in prostate cancer tissue has not been sufficiently investigated so far. The objective of this study was to select from a panel of 16 potential candidate reference genes the most stable genes for gene normalization. Expression of mRNA encoding ACTB, ALAS1, ALB, B2M, G6PD, GAPD, HMBS, HPRT1, K-ALPHA-1, POLR2A, PPIA, RPL13A, SDHA, TBP, UBC, and YWHAZ was examined in matched, microdissected malignant and nonmalignant tissue specimens obtained from 17 nontreated prostate carcinomas after radical prostatectomy by real-time RT-PCR. The genes studied displayed a wide expression range with cycle threshold values between 16 and 37. The expression was not different between samples from pT2 and pT3 tumors or between samples with Gleason scores7 andor=7 (P0.05). ACTB, RPL13A, and HMBS showed significant differences (P0.02 at least) in expressions between malignant and nonmalignant pairs. All other genes did not differ between the matched pairs, and the software programs geNorm and NormFinder were used to ascertain the most suitable reference genes from these candidates. HPRT1, ALAS1, and K-ALPHA-1 were calculated by both programs to be the most stable genes covering a broad range of expression. The expression of the target gene RECK normalized with HRPT1 alone and with the normalization factors generated by the combination of these three reference genes as well as with the unstable genes ACTB or RPL13A is given. That example shows the significance of using suitable reference genes to avoid erroneous normalizations in gene profiling studies for prostate cancer. The use of HPRT1 alone as a reference gene shown in our study was sufficient, but the normalization factors generated from two (HRPT1, ALAS1) or all three genes (HRPT1, ALAS1, K-ALPHA-1) should be considered for an improved reliability of normalization in gene profiling studies of prostate cancer.

Therapeutic efficacy of the novel matrix metalloproteinase (MMP) inhibitor, Ro 28-2653 (5-biphenyl-4-yl-5-[4-(-nitro-phenyl)-piperazin-1-yl]-pyrimidine-2,4,6-trione), has been shown in various models of different tumor entities. The tumor growth-reducing effect has been demonstrated in the orthotopic rat prostate Dunning model (subline MatLyLu). Based on these results we investigated Ro 28-2653 in combination with estramustine on the G subline of the Dunning tumor. This subline is characterized by a low metastatic ability and androgen sensitivity. Efficacy was determined by recording tumor growth in vivo by magnetic resonance imaging (MRI). Tumor cells were injected into the prostates of 81 Copenhagen rats. MRI was performed at day 100 and at day 126 after tumor cell injection. The duration of therapy was 17 days with daily oral application of Ro 28-2653 (100 mg/kg) and four i.p. injections of estramustine (7.5 mg/kg). Histological evaluations were conducted to provide further information about the effects on tumor morphology. Orthotopic tumor induction was successful in 100% of the animals. Tumor volume calculations with MRI showed a significant difference between the control groups, the animals treated with Ro 28-2653, and the animals treated with the combination of Ro 28-2653 and estramustine. The new MMP inhibitor Ro 28-2653 reduces tumor growth and provides a compatible therapeutic alternative for patients with prostate cancer.

Objective: We investigated the efficacy and toxicity of a first-line combination chemotherapy using weekly paclitaxel and carboplatin in patients with metastatic transitional cell cancer (TCC). Patients and methods: Thirty-three patients with advanced measurable TCC of the urothelium were entered onto this trial. Patients were treated once weekly with a combination therapy of paclitaxel (100mg/m 2 ) and carboplatin (AUC 2, according to the Calvert formula). Therapy courses were administered for six consecutive weeks. After two cycles, a re-staging was carried out to evaluate response. Results: Objective response rate was 57.6% with 6 complete (18.2%) and 13 partial remissions (39.4%). Seven patients had stable disease (21.2%) and 7 patients had progressed at the first evaluation of response (21.2%). Median progression-free interval and median survival was 6.5 (1–35) and 12 (2.5–58) months, respectively. Toxicity was moderate and manageable with grade 3 and 4 neutropenia in 8 patients (24%), but no case of neutropenic fever. Other hematological grade 3 toxicities occurred in 9 patients (27%) and grade 3 peripheral neuropathy in 2 patients (6%). There was no treatment-related death. Dose reduction or short delay of treatment was necessary in 3 patients. Conclusions: Combination therapy using weekly paclitaxel and carboplatin was active in patients with advanced TCC and adverse prognostic features. The weekly dosing used in this trial warrants further investigation as an alternative first-line approach in patients with poor renal reserve and/or performance status or as a second-line management of advanced TCC.

Objectives: To evaluate the outcome of high dose rate (HDR) brachytherapy with iridium 192 (Ir 192 ) and 3D conformal external beam radiotherapy in patients with localized prostate cancer. Methods: A total of 442 patients with localized prostate cancer underwent combined radiotherapy with interstitial brachytherapy with Ir 192 and 3D conformal external beam radiotherapy between December 1992 and March 2001. Patients underwent laparoscopic pelvic lymph node dissection to exclude patients with lymphatic involvement. Iridium 192 was delivered twice with a one-week interval in afterloading technique. 247 patients (56%) had clinical T3 disease and 128 patients (29%) had an initial PSA of more than 20ng/ml. Progression was defined as biochemical failure according to ASTRO criteria. Patients were diveded according to pretreatment variables that independently affected prostate-specific antigen (PSA) relapse-free survival in three risk groups. Low risk was defined as cT1c–cT2 and G1–G2 and PSA n =94). Intermediate risk included patients with cT1c–cT2 and G1–G2 and PSA between 10 and 20ng/ml ( n =53). High risk group patients were cT3 or G3 or PSA>20ng/ml ( n =295). Results: Median follow-up was 5 years. Late grade 3–4 complications according to RTOG/EORTC criteria occurred in 50 patients (11%).The initial PSA value decreased from median 11.8ng/ml to 0.98ng/ml 12 months after treatment, to 0.3ng/ml after 60 months and to 0.1ng/ml 10 years after therapy. 53% of the patients ( n =235) reached a PSA nadir of 0.5ng/ml. 66 patients (15%) had a local recurrence, 54 (12%) developed systemic disease and 12 (3%) had both local and systemic failure. The progression free survival rate was 65% at 5-year follow-up. Five-year progression free survival was 81% in the low risk group, 65% in the intermediate risk group and 59% in the high risk group. Five-year overall survival was 87% and 5-year disease specific survival 94%. Initial PSA value, risk group and age were significantly related to progression free survival. Conclusions: Combined HDR brachytherapy with Iridium 192 is an alternative treatment option for patients with localized prostate cancer. Initial PSA value, risk group, and age are important prognostic factors for progression free survival.

Laparoscopic live donor nephrectomy (LDN) has removed disincentives of potential donors and may bear the potential to increase kidney donation. Multiple modifications have been made to abbreviate the learning curve while at the same time guarantee the highest possible level of medical quality for donor and recipient. We reviewed the literature for the evolution of the different LDN techniques and their impact on donor, graft and operating surgeon, including the subtleties of different surgical accesses, vessel handling and organ extraction. We performed a literature search (PubMed, DIMDI, medline) to evaluate the development of the LDN techniques from 1995 to 2003. Today more than 200 centres worldwide perform LDN. Hand-assistance has led to a spread of LDN. Studies comparing open and hand-assisted LDN show a reduction of operating and warm ischaemia times for the hand-assisted LDN. Different surgical access sites (trans- or retroperitoneal), different vessel dissection approaches, donor organ delivery techniques, delivery sites and variations of hand-assistance techniques reflect the evolution of LDN. Proper techniques and their combination for the consecutive surgical steps minimize both warm ischaemia time and operating time while offering the donor a safe minimally invasive laparoscopic procedure. LDN has breathed new life into the moribund field of living kidney donation. Within a few years LDN could become the standard approach in living kidney donation. Surgeons working in this field must be trained thoroughly and well acquainted with the subtleties of the different LDN techniques and their respective advantages and disadvantages.

Introduction: Until now, there has been no gold standard for monitoring delirium in intensive care unit (ICU) patients. In this prospective cohort study, a new score, the Delirium Detection Score (DDS), for severity of delirium in the ICU was evaluated. Methods: After ethical approval and written informed consent, intensive care doctors and nurses assessed 1073 consecutive patients in surgical ICUs using the DDS together with the Ramsay Sedation Scale (RSS). The DDS is composed of eight criteria (orientation, hallucination, agitation, anxiety, seizures, tremor, paroxysmal sweating, and altered sleepwake rhythm). Additionally, intensive care doctors had to document the Sedation-Agitation Scale (SAS) combined with a defined clinical assessment. For interrater reliability, pair of evaluators assessed patients in a blinded fashion at the same time. Results: RSS1 (9%) was associated with a significantly (p

Seven out of 29 patients with metastatic renal cell carcinoma (RCC) considered eligible for allogeneic stem cell transplantation underwent nonmyeloablative stem cell transplantation (NST) from HLA-identical donors. Conditioning comprised cyclophosphamide, fludarabine and antithymocyte globulin. Prolonged mixed chimerism (MC) after engraftment converted to complete donor chimerism (CC) after infusion of donor lymphocytes and/or graft-versus-host disease (GvHD) in six patients. Five patients developed severe GvHD. Two of seven patients had a delayed tumor response after conversion to CC. After a median follow-up of 10 months (4-24 months), 5/7 patients are alive, one in very good partial remission (PR), one with stable and three with progressive disease. One of the seven patients died from sepsis in PR and 1/7 died from rapid tumor progression after sustained MC. None of the 22 nontransplanted patients responded to further therapies. Survival after 1 year was 59% in transplanted and 66% in nontransplanted patients (n.s.). A pooled data analysis from the literature suggests a graft-versus-tumor effect after transplant in patients with metastatic RCC, which becomes effective after chimerism conversion. Available data demonstrate high nonrelapse mortality in these patients. NST in RCC still has to be regarded as an investigational approach requiring careful patients' selection and longer follow-up within clinical studies.

Our aim was to assess the diagnostic accuracy of bone markers in serum of patients with prostate cancer (PCa) for early detection of bone metastases and their usefulness as predictors of PCa-caused mortality. In sera of 117 PCa patients (pN0M0, n = 39; pN1M0, n = 34; M1, n = 44), 35 healthy men and 35 patients with benign prostatic hyperplasia, bone formation markers [total and bone-specific alkaline phosphatase (tALP, bALP), amino-terminal procollagen propeptides of type I collagen (P1NP), osteocalcin (OC)], bone resorption markers [bone sialoprotein (BSP), cross-linked C-terminal (CTX) and cross-linked N-terminal (NTX) telopeptides of type I collagen, tartrate-resistant acid phosphatase isoenzyme 5b (TRAP)] and osteoclastogenesis markers [osteoprotegerin (OPG), receptor activator of nuclear factor kappaB ligand (RANKL)] were measured. tALP, bALP, BSP, P1NP, TRAP, NTX and OPG were significantly increased in PCa patients with bone metastases compared to patients without metastases. OPG showed the best discriminatory power to differentiate between these patients. Logistic regression analysis resulted in a model with OPG and TRAP as variables that predicted bone metastasis with an overall correct classification of 93%. Patients with concentrations of OPG, P1NP, tALP, bALP, BSP, NTX, TRAP and CTX above cut-off levels showed significantly shorter survival than patients with low marker concentrations. Multivariate Cox proportional hazards regression revealed that only OPG and BSP were independent prognostic factors for PCa-related death. Thus, the importance of serum OPG in detecting bone metastatic spread, alone or in combination with other bone markers, and predicting survival in PCa patients has been clearly demonstrated.

In spite of increasing knowledge about the tumor biology of prostate cancer (PC), molecular events involved in tumor progression are not well characterized. There is evidence that a number of genetic alterations play a role in tumor progression and in addition, angiogenesis also contributes. In this study, comparative genomic hybridization (CGH), a sensitive method for detecting regional DNA copy number abnormalities, and microsatellite analysis was used to identify frequent genome changes in PC. Correlation of these data with microvessel density (MVD) and clinical follow-up data was performed to determine genetic alterations that are associated with angiogenesis and subsequent tumor progression.Fifty-seven paraffin embedded radical prostatectomy (RP) specimens were microdissected. DNA from the microdissected PC tissue was amplified by degenerate oligonucleoitide primed (DOP)-polymerase chain reaction (PCR), and CGH was performed on the PCR product. Quantitative analyses of the CGH profiles were performed using a t-statistic. Additionally, a microsatellite analysis of chromosome 13q was performed on a subgroup of 31 of the tumors. Using a polyclonal antibody against factor VIII, MVD was determined for all RP specimens. The results of CGH and microsatellite analysis were correlated with the clinical data of the patients and with MVD.Forty-two of the tumors (75%) showed one or more gains while 39 (70%) showed one or more losses per tumor. The most frequent DNA copy number gains were on chromosome 3, 4, 7, 8, 10, 11, 12, 13, and X. The most frequent losses were on chromosomes 2, 5, 6, 8, 10, 13, 15, and 16. Cancer recurrence occurred in 15 patients. The total number of DNA copy number losses was significantly higher in patients with this progression (86%) than without (52%) (P0.001). There was no significant difference in the number of gains in patients with or without progression. Contingency table analysis showed a significant correlation between progression and losses in regions of chromosomes 6q and 13q and a gain of chromosome 7q. In multivariate analysis, only loss of chromosome 6 was independently prognostic. The gains that correlated most closely with MVD35 were on chromosomes 2q, 7q, and Xq, while the losses most closely associated with MVD35 were on chromosomes 8q, 10q, and 13q. However, only the association between loss of chromosome 13q and MVD35 was statistically significant. Microsatellite analysis revealed a statistically significant correlation between MVD and instability of locus 171.This study indicates that the frequency of genetic alterations in PC as detected by CGH correlates with clinical outcome, and that losses of DNA from chromosomes 6q and 13q are important events that correlate with tumor progression, with loss of 13q, especially instability of locus 171, also associated with angiogenesis.

Objectives: Renal cell carcinoma is likely to become one of the most important indication for laparoscopic surgery. The laparoscopic technique combines the benefits of minimal invasive approach with established surgical principles. In our institution the laparoscopic transperitoneal approach with intact specimen removal has become the standard technique for radical nephrectomies. We report the indications, techniques and oncological outcome in a single center experience. Patients and Methods: Between July 1999 and March 2003 we performed laparoscopic radical nephrectomies for renal cell cancer in 125 patients. Their initial staging, complications, and postoperative course were evaluated. During this period a total of about 1800 laparoscopic cases were performed. To date 82 patients were available for follow up data and have been analyzed for oncological outcome. Patients with primary metastatic disease were excluded from this analysis. Results: 123 procedures out of 125 were successful. In two cases (1.6%) conversion to open surgery was necessary due to bleeding (1 case) or bowel injury (1 case). In additional 3 cases (2.4%) intraoperative complications could be managed laparoscopically. In two cases (1.6%) postoperative bleeding lead to open revision for hemostasis. The mean tumor size was 5.1cm (range 2–14cm); median blood loss was 210ml (range 50–900ml). The mean surgical time was 200min (range 90–435), including the learning curves of five surgeons. Histological findings were pT1 in 78 (62.4%), pT2 in 12 (9.6%) and pT3 in 28 (22.4%) patients. In 7 cases (5.6%) histology did not confirm malignant disease. Positive lymph nodes were detected in 3 cases (2.4%); surgical margins were negative for tumor in all patients. Follow-up was between 3 and 50 months with an average of 23.5 months. Disease progression was observed in 3 cases after 6, 11 and 12 months. No cases of local recurrence or port metastasis occurred during observation. Conclusions: Laparoscopic radical nephrectomy is a routine, effective treatment for patients with pT1–2N0M0 renal cell carcinoma. With more experience a tumor up to 10–12cm in size can be managed safely offering all the benefits of minimal surgery to the patients. Although no long-term follow-up is available our follow-up data up to 50 months confirm the effectiveness of laparoscopic radical nephrectomy in terms of surgical principles and oncological outcome.

Other cDNA microarray studies have shown that hepsin is one of the highly over expressed genes in prostate cancer tissue compared with nonmalignant and benign prostatic hyperplasia tissue. We quantitatively analyzed hepsin gene expression with real-time polymerase chain reaction and calculated its relationships with clinicopathological parameters in a large cohort of samples.Matched prostate tissue samples from the cancerous and noncancerous parts of the same prostates were obtained from 90 patients with prostate cancer who underwent radical prostatectomy. Quantitative reverse transcriptase-polymerase chain reaction was performed using LightCycler Fast Start DNA Master SYBR Green I on a LightCycler (Roche Diagnostics GmbH, Mannheim, Germany) system. The ratio of hepsin-to-beta-actin (a housekeeping gene) was used to normalize data.Hepsin over expression in cancerous compared with noncancerous tissue was found in 81 of the 90 patient samples (90%, p0.001). In 48 patients (53%) hepsin over expression was more than 10-fold in cancerous tissue. The ratio of cancerous-to-noncancerous hepsin expression was significantly higher in the 39 patients with grade 3 tumors compared with the 51 with grade 2 tumors (median 15.5 vs 9.6, p = 0.031). For the prognosis a cutoff at the 75th percentile provided a significant difference between patients at lower risk (pT2, G2 and Gleason score less than 7) and higher risk (pT3/4, G3 and Gleason score 7 or greater) for relapse.This report of the quantitative analysis of hepsin expression, which is the first to our knowledge, shows strong and significant over expression in prostate cancer tissue. Hepsin expression may be a new prognostic marker that could be used for assessing prostate cancer aggressiveness.

BACKGROUND The prognostic impact of tumor grading and staging is markedly reduced in organ confined or moderately differentiated prostate cancer, which underscores the importance of new prognostic markers. Evaluating public expression data of prostate cancer, we found an upregulation of the candidate gene CD24. METHODS We examined immunohistochemically the expression of CD24 protein in 31 nodal metastases and 102 adenocarcinomas of the prostate and correlated our findings to clinicopathological parameters. RESULTS CD24 expression was found in 48% of primary prostate cancer cases and in 68% of lymph node metastases. Kaplan Meier curves and Cox regression analysis showed that CD24 expression was strongly linked to significantly earlier disease progression (relative risk = 3.2), which was especially pronounced in organ confined, or moderately differentiated primary prostate tumors. CONCLUSIONS We conclude that CD24 is an important prognostic tissue marker for prostate cancer which could help to define patients of low or high risk of recurrence. © 2003 Wiley-Liss, Inc.

The determination of complexed prostate specific antigen (cPSA) has been suggested to be promising for prostate cancer (PCa) diagnosis. In a multicenter trial we evaluate the diagnostic use of PSA forms in the low total PSA (tPSA) range.A total of 283 white men with and 417 without PCa and tPSA concentrations between 0 and 6 ng/ml were retrospectively analyzed. All 700 untreated subjects underwent a multisector needle biopsy of the prostate. The Elecsys analyser 1010 (Roche Diagnostics, Mannheim, Germany) was used for determination of tPSA and free PSA. Determination of cPSA and tPSA was performed using immunoassays of the Bayer Immuno 1 system (Bayer Diagnostics, Tarrytown, New York).Receiver operating characteristics analyses for discrimination between cases with and without PCa were performed. The areas under the curves (AUC) for cPSA, tPSA and free-to-total PSA (f/tPSA) showed no significant differences in the tPSA ranges of 0 to 6 (700 cases), 0 to 4 (510) and 0.5 to 2.5 ng/ml (253). Within the tPSA range of 2.5 to 4 ng/ml (230 cases) the AUC for cPSA (0.61) was significantly larger than that for tPSA (Roche 0.51, Bayer 0.54) but did not differ from the AUC of f/tPSA (Roche). On the basis of the cutoffs for 95% specificity or sensitivity, no significant increase in corresponding sensitivity or specificity was found between tPSA with cPSA.In the tPSA range of less than 4 ng/ml no improvement in diagnostic accuracy was shown between cPSA with tPSA or the ratio of f/tPSA. The search for a useful marker in the low PSA range must continue.

In einer prospektiven Studie uber 5 1/2 Jahre wurde die diagnostische Wertigkeit eines artifiziellen neuronalen Netzwerkes (ANN) mit den 5 Eingangsvariablen PSA, %fPSA, Prostatavolumen, rektaler Tastbefund und Patientenalter im PSA-Bereich von 2–20 µg/l als Prostatabiopsieindikator evaluiert. Daten von 944 Prostatakarzinom- und BPH-Patienten wurden in einem ANN ausgewertet. Die Ermittlung der Biopsieindikationen erfolgte in den verschiedenen PSA-Bereichen 2,0–4,0; 4,1–10,0 und 10,1–20,0 µg/l an den jeweiligen 90%- und 95%-Spezifitats- oder Sensitivitatsgrenzwerten.

Although laparoscopic radical prostatectomy (LRP) is accomplished within 2 to 3 hours by experienced surgeons, less is known about the operating times (OTs) for recently trained surgeons or the influence of additional factors. As of November 2001 at our institution, two senior surgeons had each performed more than 100 cases of LRP and two junior surgeons had each performed fewer than 30. We prospectively studied the next 100 consecutive LRPs to assess the factors influencing the OT.Transperitoneal LRPs were performed by two senior (n = 62) and two junior surgeons (n = 38) with random case assignment. We assessed body mass index, prostate size, prior abdominal surgery, androgen deprivation, surgeon experience, procedures in addition to LRP, lymph node dissection, nerve sparing, and sural nerve grafting as potential predictors of the OT.Prostate weight, androgen deprivation, and prior abdominal surgery did not significantly affect the OT, but grade 1 obesity increased the OT by an average of 38 minutes. The mean OT by surgeon experience was 214 minutes for seniors and 347 minutes for juniors (P0.001). By procedure type, the OT ranged from 180 minutes for LRP only by seniors to 459 minutes for LRP plus lymph node dissection plus sural nerve grafting by juniors. Lymph node dissection and sural nerve grafting significantly increased the OT by 46 and 101 minutes, respectively, and nerve sparing did not. For each combination of procedures, seniors averaged significantly shorter times than did juniors. A multiple regression model with stepwise selection showed that prostate weight, sural nerve grafting, pelvic lymph node dissection, use of a surgical robot, and surgeon experience significantly affected the OT.The results of this prospective study of 100 cases of LRP showed that the OT for senior surgeons averaged 2 to 3 hours, but less experienced surgeons, and additional procedures, add significantly to the OT.

Background: A new assay measures prostate-specific antigen (PSA) not complexed to α1-antichymotrypsin (nACT-PSA) after removing PSA complexed to ACT by use of anti-ACT antibodies. We evaluated nACT-PSA and its ratio to total PSA (tPSA) as alternatives to free PSA (fPSA) and its ratio to tPSA in differentiating prostate cancer (PCa) and benign prostatic hyperplasia (BPH) in patients with tPSA of 2–20 μg/L. Methods: PSA in serum of 183 untreated patients with PCa and 132 patients with BPH was measured retrospectively on the chemiluminescence immunoassay analyzer LIAISON® (Byk-Sangtec Diagnostica) with the LIAISON tPSA and LIAISON fPSA assays. The nACT-PSA fraction was determined with a prototype assay measuring the residual PSA after precipitation of ACT-PSA with an ACT-precipitating reagent. Results:nACT-PSA was higher than fPSA in samples with fPSA concentrations 1 μg/L fPSA. The median ratios of fPSA/tPSA and of nACT-PSA/tPSA were significantly different between patients with BPH and PCa (19.4% vs 12.2% and 17.4% vs 13.0%, respectively). Within the tPSA ranges tested (2–20, 2–10, and 4–10 μg/L), areas under the ROC curves for the fPSA/tPSA ratios were significantly larger than those for nACT-PSA/tPSA. In the tPSA ranges Conclusions: nACT-PSA and its ratio to tPSA provide lower diagnostic sensitivity and specificity than fPSA/tPSA. The fPSA/tPSA ratio represents the state-of-the-art method for differentiating between PCa and BPH.

Living donor kidney transplantation is one possibility to meet the growing demand for organs in patients with chronic renal failure. In 1995 the first laparoscopic living donor nephrectomy (LDN) was performed in the United States. More than 100 transplant centers worldwide perform LDN. The expectations of a larger number of willing organ donors were fulfilled due to the less traumatic operation. Meanwhile, several techniques exist to retrieve a kidney laparoscopically, including the trans- or retroperitoneal, strictly laparoscopic, or hand-assisted approach. From February 1999 to September 2002, 63 strictly laparoscopic, transperitoneal LDNs were performed at the Department of Urology of the Charite University Hospital, Berlin. Warm ischemic time was 148 s (105-360) and operating time was 203 min (110-305). Intraoperative complications were due to insufficient closure of the vessels in four patients. Mean postoperative hospital stay was 5.7 days (3-9). One year after LDN, renal function as well as creatinine levels of the recipient showed no difference compared to the organs harvested via the approach at our department prior to implementation of LDN. Strictly laparoscopic transperitoneal donor nephrectomy is a safe method for kidney retrieval and ensures excellent graft function.

The newly discovered human kallikrein 15 gene KLK15 has been shown in preliminary analysis to be associated with more aggressive types of prostate cancer. We quantitatively measured and compared gene expression of KLK15 in malignant and benign prostate tissues.Matched prostate tissue samples from the cancerous and noncancerous parts of the same prostates were obtained from 90 patients who underwent radical prostatectomy. Quantitative reverse transcriptase-polymerase chain reaction using SYBR Green I and the LightCycler system (Roche Applied Science, Mannheim, Germany) was performed. Associations of KLK15 expression with clinicopathological parameters were analyzed.KLK15 over expression in cancerous versus noncancerous tissue was found in 76 of the 90 patient samples (84.4%, p0.001). The ratio of cancerous-to-noncancerous KLK15 expression tended to be higher in patients with stage pT3/4 versus pT2 tumors (p = 0.1). KLK15 expression tended to be higher in grade 3 than in grade 2 tumors and in Gleason score 7 or greater than in Gleason score less than 7 tumors (p = 0.18 and 0.23, respectively). A 1.7 cutoff at the 40th percentile provided a significant difference in stages pT2 and pT3/4 tumors (p = 0.029).On quantitative real-time polymerase chain reaction KLK15 expression was significantly higher in cancerous than in noncancerous tissue. Up-regulation of the KLK15 gene in advanced and more aggressive tumors may indicate a possible role for KLK15 protein as future serum marker for prostate cancer and for distinguishing tumor aggressiveness.

Background Matrix metalloproteinases (MMPs) play an important role in invasion and metastatic spread of cancer cells. The objective of this study was to assess MMPs in plasma of Dunning tumor rats as indicators of the progression of prostate cancer and follow-up parameters after treatment. Methods Prostate cancer was induced in male Copenhagen rats by either subcutaneous or orthotopic implantation of R3327-MatLyLu cells. During the development of the tumor, plasma MMP-2, and MMP-9 were measured by gelatin-substrate zymography and Western blot technique with densitometry in untreated animals, rats treated with laser-induced hyperthermia, or with the new synthetic MMP inhibitor RO 28-2653. Results Normal prostatic tissue of the Copenhagen rats predominantly expressed proMMP-2 but not proMMP-9 whereas MMP-9 was only found in cancerous tissue. Elevated plasma MMP-9 values were demonstrated in rats with subcutaneous or orthotopic tumors. Animals with tumors and treated with the MMP inhibitor RO 28-2653 had both a lower tumor volume and a lower plasma MMP-9 concentration compared with controls. Conclusions The determination of plasma MMP-9 in Dunning tumor rats is a useful tool to monitor the progression of prostate cancer and to assess the efficacy of drugs like MMP inhibitors or other treatment protocols. Prostate 54: 206–211, 2003. © 2002 Wiley-Liss, Inc.

BACKGROUND Activated leukocyte cell adhesion molecule (ALCAM, CD166) is expressed in various tissues, including malignant melanoma, prostate cancer cell lines, and prostate cancer. We aimed to clarify the expression patterns of ALCAM in normal and malignant prostate tissue. METHODS RNA from 54 matched pairs of microdissected prostate tissue (tumor and normal) was hybridized to a custom built 4K GeneChip. Frozen section immunohistochemistry was used to confirm the ALCAM expression. RESULTS Chip-based transcript analysis revealed an up-regulation of ALCAM in prostate cancer in 22% of cases. Immunohistochemistry showed a focally raised ALCAM expression in 81% and a decreased expression in 19% of cases. These expression patterns correlated significantly with Gleason tumor grade: ALCAM up-regulation was found in most low-grade tumors (Gleason grade 1–3), whereas down-regulation occurred preferentially in high-grade tumors (Gleason grade 4 and 5), although up-regulation of ALCAM expression was preserved in two Gleason grade 5 tumors. CONCLUSION ALCAM expression is commonly disturbed in prostate cancer, which might indicate a role of ALCAM in the progression of this disease. Prostate 54: 34–43, 2003. © 2002 Wiley-Liss, Inc.

Objective : To determine the technical feasibility of sural nerve grafting for restoration of cavernous nerve continuity after radical retropubic prostatectomy by the laparoscopic approach. Materials and methods : 15 potent men (mean age: 56±4 years) underwent laparoscopic radical prostatectomy with deliberate wide uni- or bilateral neurovascular bundle resection. After prostatectomy, but before the vesicourethral anastomosis, an autologous sural nerve graft was interposed between the divided end of the cavernous nerves using a laparoscopic approach. Results : All 15 procedures could be completed laparoscopically. Visual cooptation between the nerve graft and the cut ends of the neurovascular bundles was possible in all 15 cases. Surgical time for the entire procedure ranged between 210 to 275 min with 30 to 60 min of this time required for the nerve harvest and graft. Conclusion : This experience demonstrates that sural nerve graft replacement is technically feasible by the laparoscopic approach. The magnified optics, bloodless surgical field, and improved instrumentation create an optimal environment for sural nerve grafting to the cut ends of the neurovascular bundles. Quality of life survey data at 12 to 18 month follow-up will be needed to assess functional return.

Objectives. Cathepsin B, H, and L (CB, CH, CL) are lysosomal proteolytic enzymes that belong to the group of cysteine proteinases. The imbalance between proteinases and their inhibitors is believed to correlate with tumor progression and shortened patient survival. In transitional cell carcinoma (TCC) only limited data have been published. Methods. Using spectrofluorometric assays, catalytic activities of CB, CH, and CL in urine were measured to evaluate the potential diagnostic and prognostic value for patients with TCC of the bladder. Second morning urine was collected and used for measurements. CB, CH, and CL activities were determined for groups of patients with superficial disease (Ta-1, n = 43) and muscle-invasive tumors (T2, n = 18; or greater than T2, n = 9), as well as for different tumor grades (G1, n = 12; G2, n = 26; and G3, n = 31). For comparison, 14 urine samples from patients with bladder inflammation and 43 samples from a control group were also included. Results. Compared with the control group, patients with superficial Stage Ta-T1 disease and muscle-invasive Stage T2 or greater disease, as well as patients with G3 tumors, revealed significantly higher urinary CL activity. CB and CH did not show any tumor-related activity increase. CB was significantly lower in patients with nonrecurrent tumors. Conclusions. These results suggest that elevated levels of CL in urine might be indicative of a cellular proteolytic imbalance in TCC of the bladder and may have a prognostic and/or diagnostic value.

We present our experience with the first 5 patients who underwent radical cystectomy with bilateral pelvic lymphadenectomy and continent urinary diversion (rectal sigmoid pouch) performed with an intracorporeal laparoscopic technique at our center.There were 3 males and 2 females 59 to 65 years old with organ confined, muscle invasive transitional cell carcinoma of the bladder who underwent surgery. The procedure included pelvic lymph node dissection, radical cystectomy with prostate or uterus and tubal structures, creation of the rectal sigmoid pouch and bilateral stented antireflux implantation of the ureters into the pouch. Freehand laparoscopic suturing and in situ knot tying techniques were used exclusively. The mobilized specimens were removed in an endoscopy bag via the rectum or vagina. Laparotomy was not required.Operating time was 6.9 to 7.9 hours (median 7.4) and blood loss was 190 to 300 ml. (median 245). None of the 5 patients none needed blood transfusion. Oral intake was started on hospital day 3, ureteral stents were removed on day 8 and the pouch catheter was removed on day 9. The hospital stay was 10 days for all cases. Histopathological examination of the specimens revealed stage pT1 G3 urothelial carcinoma in case 1, pT2b G2 in cases 2 and 3, pT3a G2 in case 4 and pT3aG3 in case 5. The lymph nodes and resection margins were tumor-free. No intraoperative or postoperative complications were observed.To our knowledge, this is the first series of laparoscopic radical cystectomy with intracorporeal continent urinary diversion (rectal sigmoid pouch), and our results are promising. With more experience and improvement of the surgical technique, laparoscopic radical cystectomy with continent urinary diversion may become an alternative surgical method for treating select patients with localized muscle invasive bladder cancer.

Purpose: The laparoscopic access for radical prostatectomy offeres an alternative to the open surgical procedure with less morbidity. We report on our experience with 125 laparoscop

BACKGROUND The aim was to evaluate the clinical performance of alpha1-antichymotrypsin prostate-specific antigen (PSA-ACT) for early diagnosis of prostate cancer (PCa) in a multicenter trial. METHODS Three hundred sixty-seven white men with PCa and 290 with benign prostatic hyperplasia (BPH) with tPSA concentrations between 2 and 20 μg/L were analyzed. The Elecsys system 2010 (Roche Diagnostics, Germany) was used for determination of total PSA (tPSA) and free PSA (fPSA). The PSA-ACT test was a prototype assay used on the ES system (Roche Diagnostics). RESULTS The median concentrations of tPSA (PCa: 8.43 μg/L vs. BPH: 6.60 μg/L) and PSA-ACT (8.30 μg/L vs. 6.46 μg/L) were significantly different, respectively. The median ratios of fPSA/tPSA (PCa: 12% vs. BPH: 16%) and PSA-ACT/tPSA (98% vs. 95%) were significantly different. Receiver operating characteristics (ROC) analysis for discrimination between PCa and BPH (tPSA between 2 and 20 μg/L) was performed with 252 matched pairs and showed that the area under the curve (AUC) of the ratio fPSA/tPSA (0.66) was significantly different from tPSA (0.50) and PSA-ACT (0.52). PSA-ACT alone or the ratio PSA-ACT/tPSA (0.56) were not significantly different from tPSA. For tPSA between 4 and 10 μg/L (n = 145 pairs), the AUC of the ratio fPSA/tPSA (0.65) was significantly higher than tPSA (0.50) and PSA-ACT (0.54). Significant differences between tPSA and PSA-ACT or PSA-ACT/tPSA (0.56) were not found. CONCLUSIONS The determination of PSA-ACT as well as the PSA-ACT/tPSA ratio did not improve the diagnostic impact in patients undergoing evaluation for PCa compared to fPSA/tPSA ratio. Prostate 47:77–84, 2001. © 2001 Wiley-Liss, Inc.

Magnetic fluid hyperthermia (MFH) selectively heats up tissue by coupling alternating current (AC) magnetic fields to targeted magnetic fluids, so that boundaries of different conductive tissues do not interfere with power absorption. In this paper, a new AC magnetic field therapy system for clinical application of MFH is described. With optimized magnetic nanoparticle preparations it will be used for target-specific glioblastoma and prostate carcinoma therapy.

Objective: To evaluate the diagnostic utility of free prostate specific antigen (fPSA), alpha–1– antichymotrypsin–bound PSA (PSA–ACT), complexed PSA (cPSA), and including their associated ratios to total PSA (tPSA) in serum for discrimination between prostate cancer (PCa) and benign prostatic hyperplasia (BPH). Methods: A total of 166 white men (age: 65–88 years) with a tPSA between 2 and 20 µg/l were retrospectively analysed. Serum concentrations of tPSA, fPSA, PSA–ACT and cPSA were measured in 118 untreated PCa patients and 48 patients with BPH. The tPSA and cPSA concentrations were measured with the Bayer Immuno 1 system (Bayer Diagnostics, Tarrytown, USA). The Elecsys system 2010 (Roche Diagnostics, Mannheim, Germany) was used for determination of tPSA and fPSA. The PSA–ACT assay is a newly, developed prototype assay on the ES system (Roche Diagnostics, Mannheim, Germany). Results: For statistical analysis only patients with tPSA between 2 and 20 µg/l were enrolled. The median concentrations of tPSA (Bayer: PCa 7.36 µg/l, BPH 4.03 µg/l; Roche: PCa 7.75, BPH 4.13), PSA–ACT (PCa 6.98, BPH 3.18) and cPSA (PCa 6.46, BPH 3.20) were significantly different. The median ratios of fPSA/tPSA (PCa 12.8 vs. BPH 22.4%), PSA–ACT/tPSA (PCa 89.8 vs. BPH 76.1%) and cPSA/tPSA (PCa 90.5 vs. BPH 81.7%) were significantly different between PCa and BPH patients. Using the areas under the curves, receiver operating characteristics analysis (tPSA: 2–20 µg/l) for discrimination between PCa and BPH showed that the ratios fPSA/tPSA (area under the curve: 0.77), PSA–ACT/tPSA (0.72) and cPSA/tPSA (0.78) were significantly different from tPSA (Bayer: 0.53; Roche: 0.55). PSA–ACT (0.64) and cPSA (0.59) alone were not significantly different from tPSA. The calculated ratios fPSA/tPSA, PSA–ACT/tPSA and cPSA/tPSA were not significantly different. Conclusion: The determination of PSA–ACT or cPSA and the associated ratios do not improve the diagnostic impact to discriminate between PCa and BPH compared to fPSA/tPSA ratio. The ratios PSA–ACT/tPSA or cPSA/tPSA can be considered to be alternative tools of fPSA/tPSA.

Objectives. To investigate the importance of the site of tumor implantation on the treatment response to laser-induced hyperthermia (LIH) of rat prostate cancer (PCa), because interventional manipulations of PCa have been reported to increase metastatic dissemination. Methods. Seven to nine days after either subcutaneous or orthotopic implantation of MatLyLu cells, LIH (46.5°C) was induced using pulsed irradiations of a neodymium:yttrium-aluminum-garnet laser. Both local control and distant metastases were evaluated. Plasma metalloproteinase 9 (MMP-9) was tested as a possible marker of PCa progression and LIH response. Results. Twelve days after LIH treatment of subcutaneous tumors, the volumes were reduced by 64% after 8 minutes of irradiation, 73% after 10 minutes, 81% after 15 minutes, and 91.1% after 20 minutes. In the orthotopic model, the corresponding tumor reductions were 44% after 10 minutes, 61% after 20 minutes, and 65% after 30 minutes. Lung metastases were observed in only 1 animal with subcutaneous tumors. In contrast, 86% of the orthotopic tumor-bearing animals treated for 30 minutes had lung metastases compared with 23% of the untreated tumor-bearing rats. MMP-9 expression was detected in both orthotopic and subcutaneous tumor tissue and in the plasma of tumor-bearing rats. The prostate tissue of healthy rats and subcutaneous tumor-bearing rats was devoid of MMP-9. The plasma levels of MMP-9 showed a trend toward direct correlation with local tumor control but no correlation with the incidence of metastasis. Conclusions. These data emphasize the importance of the site of tumor implantation for evaluation of the efficacy of therapeutic interventions and may warrant further studies before widespread clinical application of LIH as monotherapy.

Matrix-metalloproteinases (MMPs) are associated with invasive and metastatic behavior of several human malignant tumors. We have determined MMP-2 and MMP-9 and tissue inhibitors of MMPs (TIMP-1 and TIMP-2) in blood plasma and in renal tissue samples of patients with renal cell carcinoma (RCC) from cancerous and non-cancerous parts of the same kidney. In tumor tissue, MMP-9 and TIMP-1 were significantly higher than in normal counterparts. MMP-2 was not different between tumor tissue and normal counterparts. TIMP-2 values could not be measured. In plasma, MMP-9 concentrations were significantly higher in RCC patients than in healthy controls, MMP-2 and TIMP-2 concentrations were higher in healthy controls and TIMP-1 concentrations were not different.

Die perineale Prostatektomie stellt in Verbindung mit der LPLA eine logische Alternative bei der kurativen Behandlung von Patienten mit einem lokal begrenzten Prostatakarzinom dar.

Background: The aim of this study was to compare the diagnostic utility of a new assay that measures all forms of prostate-specific antigen complexed (cPSA) to serum proteins except α2-macroglobulin with the assay of free PSA (fPSA) and the corresponding ratios to total PSA (tPSA) to improve the differentiation between benign prostatic hyperplasia (BPH) and prostate cancer (PCa). Methods: Serum samples were collected from 91 men without prostate disease and with normal digital rectal examination (controls), 144 untreated patients with PCa, and 89 patients with BPH. tPSA and cPSA were measured using the Bayer Immuno 1 system; fPSA and the additional tPSA were measured with the Roche Elecsys system. Results: The median cPSA/tPSA, fPSA/tPSA, and fPSA/cPSA ratios were significantly different between patients with BPH and PCa (78.7% vs 90.7%, 25.5% vs 12.1%, and 36.8% vs 14.3%, respectively; P Conclusions: Compared with tPSA, the fPSA/tPSA and cPSA/tPSA ratios both improve the differentiation between BPH and PCa comparably and are similarly effective in reducing the rate of unnecessary biopsies, whereas cPSA alone does not have any effect.