Rubin H. Flocks and colloidal gold treatments for prostate cancer.

In the early 1950s, Rubin H. Flocks of the University of Iowa began to treat prostate cancer patients with colloidal gold (Au(198)) therapy, evolving his technique over nearly 25 years in 1515 patients. We reviewed the long-term outcomes of Flocks' prostate cancer patients as compared to those patients treated by other methods at the University of Iowa before Flocks' chairmanship. We reviewed archived patient records, Flocks' published data, and long-term survival data from the Iowa Tumor Registry to determine short- and long-term outcomes of Flocks' work with colloidal gold. We also reviewed the literature of Flocks' time to compare his outcomes against those of his contemporaries. The use of colloidal gold, either as primary or adjunctive therapy, provided short- and long-term survival benefit for the majority of Flocks' patients as compared to historical treatment options (p < 0.001). Flocks' use of colloidal gold for the treatment of locally advanced prostate cancer offered short- and long-term survival benefits compared to other contemporary treatments.

High expression of KLK14 in prostatic adenocarcinoma is associated with elevated risk of prostate-specific antigen relapse.

OBJECTIVE: Reliable prognostic tools for prostate cancer are still needed and KLK14, a young member of the growing family of human kallikrein-related peptidases, has been estimated to become a new significant marker. It is the aim of this study to analyze the clinical value of immunohistochemical expression of KLK14 in prostate cancer tissue samples. METHODS: Protein expression of KLK14 was assessed immunohistochemically in 186 tissue samples from radical prostatectomies. Areas of normal prostatic tissue, of prostatic epithelial neoplasia and of prostatic adenocarcinoma were checked in relation to clinicopathological parameters of the patients. Expression of KLK14 mRNA was quantified in 25 matches of normal and cancerous prostatic tissue, collected by laser capture microdissection. Real-time reverse transcriptase polymerase chain reaction analysis was used to supplement the immunohistochemical data. RESULTS: Expression of the KLK14 protein correlated with the pathological tumor status in prostate cancer and was associated with disease progression defined by prostate-specific antigen relapse in univariate Kaplan-Meier analysis. The multivariate Cox proportional hazards regression model proved KLK14 to be an independent prognostic factor in prostate cancer. CONCLUSION: In conclusion, we consider KLK14 to be a suitable prognostic marker for the detection of cases at risk of disease progression after radical prostatectomy.

Body mass index (BMI) and mutations of tumor suppressor gene p53 (TP53) in patients with urinary bladder cancer.

OBJECTIVE: Obesity is estimated to account for up to 20% of all cancer deaths. Mutations of TP53 are frequently correlated with tumor development and progression. We evaluated the effect of body mass index (BMI) and mutation status of tumor suppressor gene p53 (TP53) on patients with urinary bladder cancer. MATERIALS AND METHODS: Clinical samples were used from 75 patients with tumors of the urinary bladder. Mutation status in TP53 exons 5, 6, 7, and 8 was analyzed by temperature gradient gel electrophoresis of exon-specific PCR products and by sequence analysis. Statistical analysis included Pearson's correlation. RESULTS: For noninvasive bladder cancer, the mutation frequency in TP53 was 44.6%, while for invasive bladder cancer the mutation frequency in TP53 was 84.2%. Normal weight, overweight, and patients with obesity had a TP53 mutation frequency of 68.4%, 44.8%, and 25%, respectively (P < 0.05). CONCLUSIONS: TP53 mutation frequently occurs in higher stages of bladder tumors. Body mass index is not associated with a higher TP53 mutation frequency in our study, but BMI should be included for collecting data of bladder cancer risk profile.

Attitude to nephrolithiasis in the potential living kidney donor: a survey of the German kidney transplant centers and review of the literature.

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.

TP53 gene mutations as an independent marker for urinary bladder cancer progression.

This study evaluates the influence of the TP53 genetic status on tumour recurrence and progression with a highly effective electrophoretic technique. DNA from tissue of 75 non-invasive urinary bladder cancers was PCR amplified in the TP53 exons 5-8 and run on horizontal polyacrylamide gels under defined temperature conditions to yield specific gel shifts. Kaplan-Meier and Cox-Regression analysis were performed with tumour progression. The overall tumour recurrence in our patient population was 76.0% (57/75). Tumour recurrence frequency was 69.4% (34/49) in patients with TP53 wild-type, and 88.5% (23/26) in patients with TP53 mutation. There was no statistically significant difference with regard to recurrence frequency and time to recurrence. The progression-free survival was significantly shorter in patients with TP53 mutations, and the frequency of tumour progression was significantly higher in mutated as compared to wild-type tumours. Cox-Regression analysis showed a significant and independent influence of TP53 mutation on tumour progression in comparison with tumour grade, stage and history of prior bladder cancer. If segregated by exons, mutations in the DNA binding region of exon 8 seem to have a particular high influence on tumour progression. We conclude that genetic analysis of TP53 can select patients at high risk of bladder tumour progression that should be followed closely and may benefit from early radical surgical procedures.

CD146 protein in prostate cancer: revisited with two different antibodies.

AIMS: CD146 is a potentially metastasis promoting cell adhesion molecule and its expression has been described in various solid tumours. We aimed to evaluate the expression of CD146 in prostate cancer by immunohistochemistry in a clinically characterised study cohort to evaluate its prognostic properties. METHODS: We evaluated the CD146 protein expression using a polyclonal and a monoclonal antibody on 169 clinico-pathologically characterised cases. Statistical analyses were applied to test for correlations and diagnostic and prognostic associations. RESULTS: CD146 detection with the polyclonal antibody revealed marked differential expression between tumour and normal tissue and was also a significant marker for shortened PSA relapse free survival. The monoclonal CD146 antibody demonstrated a weaker epithelial signal, which was significantly correlated with that of the polyclonal antibody, but revealed no prognostic value. However, the Western blot of the polyclonal antibody displayed a clearly reduced specificity. CONCLUSIONS: Evaluation of protein expression can be highly dependent on the primary antibody employed. A credible evaluation of antibody specificity is crucial to prove the validity of protein expression studies. The immunoreactivity of the polyclonal CD146 antibody (Abcam, ab28360) is prognostic of PSA-relapse in prostate cancer patients, although its immunoreactivity is possibly not restricted to CD146 associated epitopes.

Elevated plasma osteopontin as marker for distant metastases and poor survival in patients with renal cell carcinoma.

PURPOSE: To evaluate diagnostic and prognostic significance of plasma osteopontin (OPN) in patients with renal cell carcinoma (RCC). METHODS: 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. RESULTS: OPN and ICTP levels in RCC patients with distant metastases were significantly elevated (medians 115 and 4.7 microg/l, P < 0.001) 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. CONCLUSIONS: 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.

Enhanced inhibitory effect of the matrix metalloproteinase inhibitor Ro 28-2653 in combination with estramustine and etoposide on the prostate carcinoma in the rat Dunning orthotopic tumor model.

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.

Serum (-5, -7) proPSA for distinguishing stage and grade of prostate cancer.

BACKGROUND: ProPSA has been suggested for the detection of preferentially aggressive prostate cancer (PCa). We report on the use of proPSA and free PSA to enhance preoperative staging and grading. PATIENTS AND METHODS: Serum samples from 376 PCa patients within the PSA range 1-25 microg/l who underwent radical prostatectomy were analysed for PSA, free PSA (fPSA) and (-5, -7) proPSA. RESULTS: ProPSA was only significantly different between pT2 and pT3 PCa (p = 0.02) in the subgroup of patients with % fPSA < 10%. The ratio proPSA/% fPSA differed between G2 and G3 (p = 0.004), Gleason < 7 and Gleason > or =7 (p = 0.001), and pT2 and pT3 tumors (p < 0.0001) at PSA 1-25 microg/l. However, % fPSA improved differentiation only between Gleason < 7 and Gleason > or = 7 tumors, not between pT2 and pT3 or G2 and G3 tumors. CONCLUSION: ProPSA as a single parameter did not improve the detection of non-organ confined or aggressive PCa whereas proPSA/% fPSA further improved staging and grading within all analysed PSA ranges.

Transrectal broadband-Doppler sonography with intravenous contrast medium administration for prostate imaging and biopsy in men with an elevated PSA value and previous negative biopsies.

UNLABELLED: THE AIM of this study was to determine the prostate cancer detection rate of targeted biopsy using contrast-enhanced ultrasound (US) in patients with elevated prostate specific antigen (PSA) levels and previous negative biopsy. PATIENTS AND METHODS: A total of 114 patients initially underwent ultrasonography using transrectal ultrasound (TRUS) and power Doppler. All the patients had at least one previous biopsy series negative for prostate carcinoma. Ninety-five of the patients were examined with a new broadband Doppler technique, advanced dynamic flow (ADF), after i.v. injection of the echo enhancer (2.4 ml, SonoVue). The systematic biopsies were also obtained supplemented by removal of two targeted tissue cores in all the patients with a suspicious area in the inflow phase or late phase. RESULTS: Histology confirmed prostate cancer in 30 of the 95 patients. Sensitivity for the detection of prostate cancer by contrast-enhanced US was 100% and specificity was 48%. Suspicious areas were identified in 48 cases including 40 hypervascularized areas and 14 hypoechoic areas after 60 sec. Targeted biopsy identified 24 of the 30 carcinomas. Randomized octant biopsy identified only 8 of the 30 carcinomas. All 65 patients with negative histology were prostate cancer free at 12-month follow-up. The ADF US scans were degraded by fewer artifacts than the power Doppler images. CONCLUSION: Contrast-enhanced ADF Doppler allows reliable differentiation of prostate cancer and normal prostate tissue with a high sensitivity in patients with previous negative biopsy and fewer artifacts than power Doppler images, thus providing a good basis for targeted prostate biopsy instead of systematic biopsy.

[Thermal therapy of prostate cancer using magnetic nanoparticles]. / Termoterapia en cáncer de próstata mediante el uso de nanopartículas magnéticas.

A novel method of interstitial heating using magnetic nanoparticles and a direct injection technique has been evaluated in human cancers in recent clinical trials. In prostate cancer, this approach was investigated in two separate phase-I-studies, employing magnetic nanoparticle thermotherapy alone and in combination with permanent seed brachytherapy. The feasibility and good tolerability was shown in both trials, using the first prototype of a magnetic field applicator. As with any other heating technique, this novel approach requires specific tools for planning, quality control and thermal monitoring, based on appropriate imaging and modelling techniques. In these first clinical trials, a newly developed method for planning and non-invasive calculations of the 3-dimensional temperature distribution based on computed tomography could be validated. Limiting factors of this approach at present are patient discomfort at high magnetic field strengths and suboptimal intratumoral distribution of nanoparticles. Until these limitations will be overcome and thermal ablation can safely be applied as a monotherapy, this treatment modality is being evaluated in combination with irradiation in patients with localized prostate cancer.

In situ gene expression and localization of metalloproteinases MMP1, MMP2, MMP3, MMP9, and their inhibitors TIMP1 and TIMP2 in human renal cell carcinoma.

Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) play a major role in the maintenance of extracellular matrix homeostasis. Alterations of MMP and TIMP expressions have been found in several malignant tumour entities. In this study the expression pattern of MMP1, MMP2, MMP3, MMP9, and their inhibitors TIMP1, and TIMP2 were investigated at mRNA and protein levels in human renal cell carcinoma (RCC). Formalin fixed paraffin embedded tumour samples of 10 patients and adjacent non-malignant controls were analysed by radioactive labelled riboprobe in situ hybridisation (isH) and immunohistochemistry. The slides were evaluated semiquantitatively. MMP1-antigen was strongly expressed in tumour epithelium with moderate stroma expression in one case. The gelatinases MMP2 and MMP9 showed moderate to strong signals in tumour epithelial cells at the mRNA and protein level, while the expression in tumour stroma was moderate. MMP3-mRNA and -antigen were expressed moderately to strong in tumour epithelium and focally in stroma cells. mRNA or TIMP1- and TIMP2-mRNA and -antigen were also predominantly expressed in tumour epithelium; only few samples showed positive expression in stroma cells. mRNA expression could be generally correlated to the protein expression in our study group, except for MMP1 (mRNA expression was only expressed in two cases). We found a pronounced expression for the gelatinases MMP2 and MMP9 and for MMP3 in RCC at the mRNA and protein level. The expression of TIMP1 and TIMP2 appears also to be relevant in RCC. Due to the small sample size further investigations need to be done to prove a statistical significant correlation between the MMP/TIMP expression and clinicopathological parameters.

Gene expression studies in prostate cancer tissue: which reference gene should be selected for normalization?

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 scores <7 and >or=7 (P>0.05). ACTB, RPL13A, and HMBS showed significant differences (P<0.02 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.

Combined determination of plasma MMP2, MMP9, and TIMP1 improves the non-invasive detection of transitional cell carcinoma of the bladder.

BACKGROUND: Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) play a major role in the maintenance of extracellular matrix homeostasis and are involved in the process of tumour invasion and metastasis in several malignant tumour entities. The goal of this study is to evaluate the diagnostic value of various circulating MMPs and TIMPs in blood plasma for a non-invasive detection of transitional cell carcinoma of the bladder (TCC). METHODS: In this study the concentrations of MMP1, MMP2, MMP3, MMP9, their inhibitors TIMP1, TIMP2, and the MMP1/TIMP1-complex (MTC1) were quantified in blood plasma with the sandwich enzyme-linked immunosorbent assay (ELISA). Blood plasma samples were investigated from 68 patients (non-metastasized, n = 57 and metastasized, n = 11) with TCC of the bladder and from 79 healthy controls. The mROC program was used to calculate the best two- and three- marker combinations. The diagnostic values for all single markers and the marker combinations were estimated both by the overall diagnostic performance index area under the ROC curve (AUC) and the sensitivity and specificity at cutoff limits with the highest diagnostic accuracy and at the 90% and 95% limits of sensitivity and specificity, respectively. RESULTS: The median MMP2 concentration was elevated in blood plasma in all patient groups with TCC in comparison to the controls (p < 0.001). The concentrations of TIMP1, TIMP2, and MTC1 in plasma probes were significantly lower from patients with non-metastasized TCC compared to the controls. MMP2 tested alone reached the highest sensitivity and specificity at 75%, respectively. The sensitivity and specificity increased when tested in combination with MMP9 and TIMP1 (97%, 94%, respectively). The combination of MMP9 and TIMP1 also showed an improved sensitivity (80%) and specificity (99%) than tested alone. CONCLUSION: MMP2 is a statistically significant marker in blood plasma for bladder cancer detection with an increased diagnostic value in combination with MMP9 and TIMP1. This study showed that the highest sensitivities and specificities are not obtained by testing each marker alone. As shown by the best two-marker combination, which includes MMP9 and TIMP1, the optimized combination does not always include the best single markers.

Differential gene expression of urokinase-type plasminogen activator and its receptor in human renal cell carcinoma.

The urokinase-type plasminogen activator (uPA) system plays a central role in extracellular matrix degradation, cell migration, and invasion. uPA belongs to the family of serine proteases. It has been shown that its proteolytic activity is involved in the metastatic process by activation and binding to its receptor (uPAR). Previous studies in several organ systems have elucidated a higher uPA expression in malignant tissue in comparison to normal tissue. In this study uPA and uPAR gene expression were investigated in 18 human renal cell carcinoma (RCC) specimens in comparison with adjacent non-malignant renal tissues. mRNA in situ hybridisation and immunohistochemical staining were performed. mRNA of uPA and uPAR was significantly higher expressed in 56% (10/18) and 72% (13/18) of the RCC specimens in comparison to the adjacent non-malignant renal tissue (p<0.0001), respectively. uPA-mRNA and uPAR-mRNA were expressed predominantly in malignant renal cells and in very few surrounding stromal cells. The elevated expression of uPAR-protein in RCC reached statistical significance compared to adjacent normal tissue (p=0.007). uPAR genes were higher expressed in comparison to uPA alone. There was a statistical trend that higher expression of uPA and uPAR corresponded with TNM tumour stage and grade in RCC. Further investigations need to be done with larger sample sizes to prove a correlation of expression between uPA and uPAR to a more aggressive phenotype. We conclude that uPA- and uPAR are overexpressed in RCC and could function as tumour markers.

Four tumour markers for urinary bladder cancer--tissue polypeptide antigen (TPA), HER-2/neu (ERB B2), urokinase-type plasminogen activator receptor (uPAR) and TP53 mutation.

PURPOSE: Tissue polypeptide antigen (TPA) is present in the proteolytic fragments of cytokeratins 8, 18 and 19 as a component of the cytoskeleton of nonsquamous epithelia. HER-2/neu protein is a transmembrane tyrosine kinase cell surface growth factor receptor that is expressed on normal epithelial and some cancer cells. The urokinase-type plasminogen activator receptor (uPAR) is a GPI-linked single-chain glycoprotein. Mutations of the tumour suppressor gene P53 (TP53) are frequently correlated with tumour development and progression. We compared TPA, HER-2/neu and uPAR, and TP53 mutation in tumour-free and bladder cancer patients. MATERIALS AND METHODS: Clinical samples were used from 60 patients with tumours of the urinary bladder and from 9 patients with benign urological diseases. TPA was analyzed by the immunoluminometric assay LIA-mat TPA-MProlifigen. HER-2/neu was measured using the Bayer Oncoprotein test. uPAR was measured with the IMUBIND Total uPAR ELISA Kit. Mutation status in TP53 exons 5, 6, 7 and 8 was analyzed by temperature gradient gel electrophoresis of exon-specific PCR products and by sequence analysis. Statistical analysis included ROC, Mann-Whitney U-test and Pearson's correlation. RESULTS: Pathological concentrations of TPA, HER-2/neu and uPAR are detectable in the serum and in urine of bladder cancer patients. The calculated diagnostic sensitivity for TPA in serum was 68.37%, for TPA in urine 33.3%, for HER-2/neu 86.7% and for uPAR 79.5%. Pathological levels of TPA in serum (p=0.001) and HER-2/neu (p =0.001) were significantly higher in patients with bladder cancer in comparison to the control group. For superficial bladder cancer, the mutation frequency in TP53 was 50%, while for invasive bladder cancer the mutation frequency in TP53 was 100%. Elevated TPA, HER-2/neu and uPAR levels were associated with all grades and stages of bladder cancer. CONCLUSION: TPA, HER-2/neu or uPAR can differ between bladder cancer patients and the control group, but not between superficial and invasive bladder cancer. TP53 mutation frequently occurs in higher stages of bladder tumours.

Gadolinium-enhanced three-dimensional magnetic resonance angiography versus conventional digital subtraction angiography: which modality is superior in evaluating living kidney donors?

This study evaluates the correlation of magnetic resonance angiography (MRA) and digital subtraction angiography (DSA) with the operative vessel findings in living kidney donors. The intraoperative vessel findings of 52 living renal donors were compared with the preoperative diagnoses of each imaging technique. Sixty-seven arteries were found during explantation. Forty kidneys showed a single arterial blood supply, and 12 kidneys showed a multiple arterial blood supply. No advantage of either imaging method was found for arterial imaging. There were 55 veins identified during organ harvesting. MRA could not determine the venous system in one donor (1.9%) and failed to detect one small pole vein in another. DSA did not yield a venous diagnosis in seven patients (13.5%) and yielded misdiagnoses in four patients. The correct diagnosis of renal donor veins differed significantly in favor of MRA (kappa 0.79 vs. 0.45; P=0.008). MRA is superior to DSA in assessing the renal vasculature in living kidney donors.

Increased cell-free DNA in plasma of patients with metastatic spread in prostate cancer.

We compared the plasma DNA concentrations in patients with different prostate cancer (PCa) stages and with benign prostate hyperplasia (BPH) and in healthy persons. Patients with localized cancer had DNA plasma within the reference interval. Increased plasma DNA was found in patients with lymph node and distant metastases and also in BPH. The association between plasma DNA and the survival time was similarly strong as with prostate-specific antigen. It can be concluded that plasma DNA has a limited validity as metastatic marker in PCa patients but follow-up studies combined with the investigation of tumor-related characteristics of plasma DNA would be reasonable.

Sural nerve graft during laparoscopic radical prostatectomy. Initial experience.

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.

In situ gene expression of urokinase-type plasminogen activator and its receptor in transitional cell carcinoma of the human bladder.

The urokinase-type plasminogen activator (uPA) system plays a central role in the blood clot dissolution and tissue plasticity. uPA is a serine protease that is also involved in the metastatic process upon activation and binding to its receptor (uPAR). Studies have shown that levels of uPA in malignant tumors are higher than in the corresponding normal tissue or in benign tumors of the same tissue. We investigated uPA and uPAR gene expression in 20 human transitional cell carcinomas (TCC) of the bladder (n=19) and the renal pelvis (n=1) in comparison with adjacent non-malignant tissues. We performed mRNA in situ hybridization (isH) and immunohistochemical staining. uPA-mRNA and uPAR-mRNA were present in 95% (19/20) and 85% (17/20) of the TCC samples, respectively and significantly higher expressed than in the adjacent normal tissue. uPA-mRNA was expressed only in malignant urothelial cells, whereas uPAR-mRNA was localized in malignant urothelial cells as well as in surrounding stromal cells. There was a statistically significant lower expression of uPA/uPAR-protein in adjacent normal tissue. Strong uPAR-protein signal intensity was related to a marked protein expression as semi-quantitatively determined by immunohistochemistry. For uPA-protein this observation was less frequent. There was a statistical trend that higher expression of uPA and uPAR corresponded with tumor stage and grade of TCC. Statistical significance was reached for uPAR-antigen compared to tumor stage (p=0.025). We conclude that higher expression of uPA and uPAR could indicate a more aggressive phenotype of TCC.