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Sandra Steffens,
Andreas Al Ghazal,
Julie Steinestel,
Rieke Lehmann,
Gerd Wegener,
Thomas J Schnoeller,
Marcus V Cronauer, Florian Jentzmik,
Mark Schrader,
Markus A Kuczyk,
Andres J Schrader
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ABSTRACT: BACKGROUND: High levels of circulating C-reactive protein (CRP) have recently been linked to poor clinical outcome in various malignancies. The aim of this study was to evaluate the prognostic significance of the preoperative serum CRP level in patients with squamous cell carcinoma (SCC) of the penis. METHODS: This retrospective analysis included 79 penile cancer patients with information about their serum CRP value prior to surgery who underwent either radical or partial penectomy at two German high-volume centers (Ulm University Medical Center and Hannover Medical School) between 1990 and 2010. They had a median (mean) follow-up of 23 (32) months. RESULTS: A significantly elevated CRP level (>15 vs. <= 15 mg/l) was found more often in patients with an advanced tumor stage (>=pT2) (38.9 vs. 11.6%, p=0.007) and in those with nodal disease at diagnosis (50.0 vs. 14.6%, p=0.007). However, high CRP levels were not associated with tumor differentiation (p=0.53). The Kaplan-Meier 5-year cancer-specific survival (CSS) rate was 38.9% for patients with preoperative CRP levels above 15 mg/l and 84.3% for those with lower levels (p=0.001). Applying multivariate analysis and focusing on the subgroup of patients without metastasis at the time of penile surgery, both advanced local tumor stage (>=pT2; HR 8.8, p=0.041) and an elevated CRP value (>15 mg/l; HR 3.3, p=0.043) were identified as independent predictors of poor clinical outcome in patients with penile cancer. CONCLUSIONS: A high preoperative serum CRP level was associated with poor survival in patients with penile cancer. If larger patient populations confirm its prognostic value, its routine use could enable better risk stratification and risk-adjusted follow-up of patients with SCC of the penis.
BMC Cancer 05/2013; 13(1):223. · 3.01 Impact Factor
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ABSTRACT: PURPOSE: To evaluate the clinical value of the pre-treatment calculated free testosterone (fT), total testosterone (tT), sexual hormone-binding globulin (SHBG) and estradiol (E2) levels as potential predictors of pathological stage and grade in patients with clinically localized prostate cancer. METHODS: Preoperative sex hormone serum levels were prospectively measured in 137 patients who underwent radical prostatectomy at the University Hospital Ulm from February 2011 to February 2012. We related sex hormone levels to clinicopathologic data including tumour stage, Gleason score and prostate specific antigen (PSA). (Non)parametric statistical tests and receiver operating characteristics (ROC) analyses were performed. RESULTS: Preoperative serum fT levels were significantly associated with advanced disease (pT3-4 and/or pN+; p = 0.047) and lymph node involvement (pN+) (p = 0.027). Patients with low (<0.047 μg/l) vs. normal fT values (≥0.047 μg/l) were associated with higher tumour stage (p = 0.049), positive lymph node status (pN+ , p = 0.038) and advance disease (p = 0.016). Moreover, low tT values (≤0.193 μg/l; p = 0.018) and elevated SHBG levels (>48.4 nmol/l, p = 0.043) correlated with a higher Gleason score. Conversely, E2 levels were not associated with tumour stage or grade. Applying multivariate analysis, unlike tT, SHBG, and E2 levels, low fT levels were a significant independent predictor of advanced disease (relative hazard ratio 3.05, p = 0.028). CONCLUSIONS: Low pre-treatment fT levels were significantly associated with tumour stage and extraprostatic tumour spread and might-in addition or combination with PSA-serve as a useful prognostic parameter for prostate cancer patients prior to radical prostatectomy.
World Journal of Urology 07/2012; · 2.41 Impact Factor
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ABSTRACT: A recently identified mechanism allowing prostate cancer (PCa) cells to grow in the absence of androgens is the expression of constitutively active, C-terminally truncated androgen receptor (AR) variants lacking vast parts of the ligand-binding domain. These AR variants termed ARΔLBD are either products of alternative splicing, point mutations leading to premature stop codons or proteolytic cleavage of the AR. Some controversies exist about the requirement of additional full-length AR for the full transcriptional activity of the ARΔLBD. On basis of a mutated, C-terminally truncated AR termed Q640X, we developed an experimental model for the study of ARΔLBD in PCa cells.
Activation of AR-dependent promoters was analyzed by reporter gene assays. Dimerization studies were conducted using a mammalian two-hybrid system.
Although Q640X/Q640X homodimers were able to induce the expression of certain AR target genes, Q640X/AR heterodimers were necessary to activate the full panel of androgen-dependent genes under androgen-deprived conditions.
The following study supports the hypothesis that castration-resistant prostate cancer (CRPC) cells are able to activate specific androgen-dependent genes by selective modulation of the ratio between ARΔLBD and their putative dimerization partners like the full-length AR or other ARΔLBD in the absence of androgens. The present data suggest that AR-mutant Q640X is a powerful experimental tool for the functional analysis of ARΔLBD in CRPC.
World Journal of Urology 02/2012; 30(3):333-9. · 2.41 Impact Factor
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ABSTRACT: PURPOSE: To assess long-term clinical and oncological outcome in women undergoing radical cystectomy and ileal neobladder reconstruction for invasive bladder cancer. METHODS: From 1995 to 2010, a total of 121 women with clinically organ-confined urothelial carcinoma underwent radical cystectomy with an orthotopic ileal neobladder. Median follow-up was 56 months. Clinical course, functional, pathological, and oncological outcome of these women were analyzed. RESULTS: Seventy-six patients (62.8%) experienced a complication of some type within 90 days of the procedure. 56 patients (46.3%) experienced minor complications, whereas 20 patients (16.5%) experienced major complications. Pathological subgroups included 70 patients (57.9%) with organ confined, lymph node-negative tumors, 24 (19.8%) with extravesical, lymph node-negative disease and 27 (22.3%) patients with lymph node-positive disease. The 5-year overall survival rate in patients with organ-confined (≤pT2, pN0), locally advanced (≥pT3, pN0), and metastatic disease was 80.2%, 81.9%, and 45.1%, respectively. 4 women (3.3%) experienced a local (pelvic) recurrence. One patient presented with a urethral recurrence (0.8%). Daytime and nighttime urinary continence (0-1 pad) was reported by 82.4 and 76.5%, respectively. Clean intermittent self-catheterization was required by 58.0%. The retrospective study design was the major limitation of the study. CONCLUSIONS: Despite a considerable complication rate, radical cystectomy with orthotopic diversion in female patients with bladder cancer may be considered a standard therapeutic option for selected patients with excellent oncological outcome including a low incidence of local and urethral recurrence.
World Journal of Urology 02/2012; · 2.41 Impact Factor
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ABSTRACT: Objective. To evaluate and compare noncontinent and continent urinary diversion after radical cystectomy in patients with bladder cancer. Methods. A total of 301 patients submitted to radical cystectomy at the Charité-University Hospital Berlin from 1993 to 2007 including 146 with an ileal conduit and 115 with an ileal neobladder. Clinical and pathological data as well as oncological outcome were retrospectively analyzed and compared. Quality of life was analyzed using the EORTC QLQ-C30 and BLM30 questionnaires. Results. 69.1% and 69.6% of all patients who received an ileal conduit and ileal neobladder, respectively, developed early complications. The two groups differed significantly concerning the occurrence of postoperative ileus (P = 0.02) favoring patients who received an ileal conduit but not with regard to any other early-onset complication evaluated. Patients with ileal neobladder had a significantly better global health status and quality of life (P = 0.02), better physical functioning (P = 0.02), but also a higher rate of diarrhoea (P = 0.004). Conclusion. Cystectomy with any type of diversion remains a complication-prone surgery. Even if the patient groups are not homogeneous in all respects, there are many arguments in favor of the ileal neobladder as the urinary diversion of choice.
ISRN urology. 01/2012; 2012:342796.
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ABSTRACT: Objective. To evaluate functional outcome of the retrourethral transobturator sling suspension (RTS) in the treatment of stress urinary incontinence (SUI) caused by prior prostate surgery. Methods. The RTS (AdVance male sling) was implanted in 32 patients who suffered from mild to severe postsurgical-treatment incontinence at the University Hospital Ulm from September 2010 to September 2011 including 10 patients with prior radiation therapy. Functional data (uroflowmetry, daily pad use, and postvoid residual urine) as well as quality of life with impact of urinary problems (ICIQ-UI SF) were prospectively assessed at baseline and during followup. Results. After a median followup of 9 months (range, 3-14) the incontinence cure rate (no pad usage) was 56.2% and the improvement rate (1-2 pads/day or ≥50% reduction) was 21.9%. No improvement was observed in 21.9%. Daily pad use and ICIQ-UI SF score improved significantly. No major perioperative complications occurred. Postoperatively, 15.6% of the patients exhibited transient acute urinary retention which resolved without further treatment after a maximum of 3 weeks. One patient underwent sling explantation due to dislocation and persistent perineal pain. Conclusions. The implantation of the RTS is a safe and effective procedure in selected patients with SUI resulting from prostate surgery.
ISRN urology. 01/2012; 2012:304205.
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ABSTRACT: The risk of local recurrence after radical prostatectomy (RP) is considerably dependent on local tumor stage. To improve local staging, the aim of this study was to assess the feasibility of quantitative methylation-specific PCR (Q-MSP) for the identification of promoter hypermethylation of the detoxifying glutathione-S-transferase P1 gene (GSTP1) to detect occult prostate cancer (PCa) cells in the prostatic fossa after RP.
A total of 39 consecutive patients with clinically organ-confined PCa underwent RP. After gland excision, biopsies were obtained from eight defined areas of the prostatic fossa and bisected for both histopathological and molecular analyses. Results were related to clinicopathological data including tumor stage, Gleason score, prostate-specific antigen (PSA), and biochemical recurrence.
Of 39 patients, 11 with PCa had at least one positive molecular margin status indicated by GSTP1 methylation. These included 5 of 17 (29.4%) with organ-confined and 6 of 22 (27.3%) with advanced (≥pT3 and/or pN+) PCa. GSTP1 methylation in surgical margins strongly correlated with histopathological R-status (P = 0.022) and preoperative PSA (P = 0.01) whereas no association with tumor stage (pT2 vs pT3), grade (Gleason score <7 vs ≥7), and lymph node status was found. No patient experienced biochemical relapse.
GSTP1 hypermethylation detected by Q-MSP in prostatic fossa biopsies after RP is well suited for the detection of occult tumor cells in surgical margins. However, the limited number of patients and the short-term follow-up does not allow definite conclusions on the prognostic value of GSTP1 in surgical margins.
World Journal of Urology 09/2011; 30(4):541-6. · 2.41 Impact Factor
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ABSTRACT: Sarcosine in prostate cancer tissue samples was recently reported to be increased during prostate cancer progression to metastasis and suggested to be a key metabolite of cancer cell invasion and aggressiveness. We reevaluated sarcosine in prostate cancer tissue samples as a potential indicator of tumor aggressiveness, and as a predictor of recurrence-free survival.
Sarcosine in matched samples of malignant and nonmalignant tissue from 92 patients with prostate cancer after radical prostatectomy was measured in the framework of a global metabolite profiling study of prostate cancer by gas chromatography/mass spectrometry. We related results to age, prostate volume, tumor stage, Gleason score, preoperative prostate specific antigen and biochemical recurrence, defined as a persistent prostate specific antigen increase of greater than 0.2 ng/ml. Nonparametric statistical tests, ROC curves and Kaplan-Meier analyses were done.
Median sarcosine content in tissue was about 7% higher in matched malignant vs nonmalignant samples, which was significantly. Sarcosine values were not associated with tumor stage (pT2 vs pT3), tumor grade (Gleason score less than 7 vs 7 or greater) or biochemical recurrence. The lack of metastatic tissue samples was a study limitation.
Sarcosine in prostate cancer tissue samples cannot be considered a suitable predictor of tumor aggressiveness or biochemical recurrence.
The Journal of urology 02/2011; 185(2):706-11. · 4.02 Impact Factor
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ABSTRACT: Whenever technically feasible and oncologically justified, nephron-sparing surgery is the current standard of care for localized renal cell carcinomas (RCC). The main complications of partial nephrectomy, especially for large and centrally located tumors, are urinary leakage and parenchymal bleeding. We prospectively evaluated the pros and cons of using porcine small intestinal submucosa (SIS, Surgisis®) to close the renal defect after nephron-sparing surgery.
We used Surgisis® (Cook medical, Bloomington, IN, USA) to secure and compress the capsular defect after tumor resection in 123 patients submitted to 129 partial nephrectomies between August 2003 and February 2011.
The median tumor size was 3.7 cm (range 1.1-13.0 cm). Procedures were performed with cold ischemia in 24 cases (18.2%), with warm ischemia in 46 (35.6%), and without ischemia in 59 cases (44.8%). In the total group of patients, 4 (3.1%) developed urinary fistula, and only 2 (1.6%) required postoperative transfusions due to hemorrhage after the application of the small intestinal submucosa membrane.
Small intestinal submucosa is an easy-to-use biomaterial for preventing complications such as postoperative bleeding and urinary fistula in nephron-sparing surgery, especially in cases where tumor excision causes significant renal capsular and/or renal pelvic defects.
World Journal of Surgical Oncology 01/2011; 9:126. · 1.12 Impact Factor
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European urology 12/2010; 59(4):e17-8; author reply e19. · 7.67 Impact Factor
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European urology 08/2010; · 7.67 Impact Factor
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ABSTRACT: Sarcosine in urine was recently suggested to be a promising tool in prostate cancer (PCa) diagnostics.
To reevaluate sarcosine as a potential biomarker for early PCa detection and for prediction of tumour aggressiveness.
Sarcosine was measured in urine samples from 106 PCa patients and 33 patients with no evidence of malignancy (NEM), confirmed by 8-12 core prostate biopsies, after standardised digital rectal examination, as well as from 12 healthy men and women. The results were related to the clinicopathologic data on prostate volume, tumour stage, Gleason score, and prostate specific antigen (PSA).
Sarcosine in urine was determined by gas chromatography-mass spectrometry using a commercial amino acid assay and was normalised to urine creatinine. Nonparametric statistical tests and receiver operating characteristics (ROC) analyses were performed to assess the diagnostic performance.
The median sarcosine-creatinine ratio in urine was 13% lower in PCa than in NEM patients. Sarcosine values were not associated with tumour stage (pT2 vs pT3) or grade (Gleason score <7 vs > or = 7). ROC analyses proved that the discrimination between PCa and NEM patients was not improved by sarcosine in comparison with total PSA, but it was significantly worse than the percent free PSA. The higher proportion of PCa than NEM patients can be considered a limitation of this study.
Sarcosine in urine after rectal digital examination cannot be considered as a suitable marker to differentiate between patients with and without PCa.
European urology 07/2010; 58(1):12-8; discussion 20-1. · 7.67 Impact Factor
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European urology 05/2010; · 7.67 Impact Factor
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European urology 03/2010; · 7.67 Impact Factor
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ABSTRACT: Transperitoneal radical cystectomy with intraperitoneal ileal neobladder is the standard surgical treatment for muscle-invasive bladder cancer. To reduce morbidity, we established in 2002 an extraperitoneal approach including extraperitonealization of the ileal neobladder. This retrospective study compares the results of the two procedures with a focus on the peri- and postoperative course.
Ninety-five male patients with invasive urothelial cancer who underwent radical cystectomy with ileal neobladder at our hospital from January 1998 to May 2007 were analyzed. Forty-seven patients underwent transperitoneal radical cystectomy with intraperitoneal ileal neobladder. The remaining 48 were submitted to the extraperitoneal technique with extraperitonealization of the neobladder. We compared both methods regarding operating time, intraoperative blood loss, complications and oncological outcome.
The incidence of postoperative ileus was significantly lower after the extraperitoneal than after the transperitoneal approach (2/48 vs. 10/47 cases; p = 0.012). However, pelvic lymphoceles were more frequent (6 vs. 0 cases; p = 0.014). The two techniques did not differ with regard to the other major and minor complications, the operating time (mean 377.4 vs. 405.4 min) or the intraoperative blood loss (mean 363 vs. 412 ml). Oncological outcome disclosed no difference between both techniques.
The extraperitoneal technique with extraperitonealization of the ileal neobladder is comparable in safety and reliability to the transperitoneal surgical approach and yields good peri- and postoperative results with regard to the parameters we examined. Noteworthy are the significant reduction of postoperative ileus and the higher incidence of lymphoceles. Both may be caused by the separate extraperitoneal regional healing processes.
World Journal of Urology 09/2009; 28(4):457-63. · 2.41 Impact Factor
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ABSTRACT: This study aimed to investigate the microRNA (miRNA) profile in prostate carcinoma tissue by microarray analysis and RT-qPCR, to clarify associations of miRNA expression with clinicopathologic data and to evaluate the potential of miRNAs as diagnostic and prognostic markers. Matched tumor and adjacent normal tissues were obtained from 76 radical prostatectomy specimens. Twenty-four tissue pairs were analyzed using human miRNA microarrays for 470 human miRNAs. Differentially expressed miRNAs were validated by TaqMan RT-qPCR using all 76 tissue pairs. The diagnostic potential of miRNAs was calculated by receiver operating characteristics analyses. The prognostic value was assessed in terms of biochemical recurrence using Kaplan-Meier and Cox regression analyses. Fifteen differentially expressed miRNAs were identified with concordant fold-changes by microarray and RT-qPCR analyses. Ten microRNAs (hsa-miR-16, hsa-miR-31, hsa-miR-125b, hsa-miR-145, hsa-miR-149, hsa-miR-181b, hsa-miR-184, hsa-miR-205, hsa-miR-221, hsa-miR-222) were downregulated and 5 miRNAs (hsa-miR-96, hsa-miR-182, hsa-miR-182, hsa-miR-183, hsa-375) were upregulated. Expression of 5 miRNAs correlated with Gleason score or pathological tumor stage. Already 2 microRNAs classified up to 84% of malignant and nonmalignant samples correctly. Expression of hsa-miR-96 was associated with cancer recurrence after radical prostatectomy and that prognostic information was confirmed by an independent tumor sample set from 79 patients. That was shown with hsa-miR-96 and the Gleason score as final variables in the Cox models build in the 2 patient sets investigated. Thus, differential miRNAs in prostate cancer are useful diagnostic and prognostic indicators. This study provides a solid basis for further functional analyses of miRNAs in prostate cancer.
International Journal of Cancer 09/2009; 126(5):1166-76. · 5.44 Impact Factor
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International Journal of Cancer, v.126, 1166-1176 (2010).
