[Show abstract][Hide abstract] ABSTRACT: Uro-oncological neoplasms have both a high incidence and mortality rate and are therefore a major public health problem. The aim of this study was to evaluate research activity in uro-oncology over the last decade.
We searched MEDLINE and ClinicalTrials.gov systematically for studies on prostatic, urinary bladder, kidney, and testicular neoplasms. The increase in newly published reports per year was analyzed using linear regression. The results are presented with 95% confidence intervals, and a p value <0.05 was considered statistically significant.
The number of new publications per year increased significantly for prostatic, kidney and urinary bladder neoplasms (all <0.0001). We identified 1,885 randomized controlled trials (RCTs); also for RCTs, the number of newly published reports increased significantly for prostatic (p = 0.001) and kidney cancer (p = 0.005), but not for bladder (p = 0.09) or testicular (p = 0.44) neoplasms. We identified 3,114 registered uro-oncological studies in ClinicalTrials.gov. However, 85% of these studies are focusing on prostatic (45%) and kidney neoplasms (40%), whereas only 11% were registered for bladder cancers.
While the number of publications on uro-oncologic research rises yearly for prostatic and kidney neoplasms, urothelial carcinomas of the bladder seem to be neglected despite their important clinical role. Clinical research on neoplasms of the urothelial bladder must be explicitly addressed and supported.
[Show abstract][Hide abstract] ABSTRACT: PURPOSE: Cancers complicating organ allografts are a major cause of morbidity and mortality after renal transplantation. Different registries have described an overall three to eightfold increase in cancer risk compared with the general population. This retrospective study investigated the incidence and outcome of de novo malignancies following kidney transplantation in a single German kidney transplantation center. MATERIALS AND METHODS: Between 1966 and 2005, 1882 patients underwent kidney transplantation at the Erlangen-Nuremberg kidney transplantation center. The incidence and types of post-transplant malignancies were retrospectively analyzed according to the patients' records and the database of the local cancer registry. RESULTS: We identified 257 malignancies in 231 patients, an overall incidence of 13.7%. The mean follow-up time was 9.9 yr (range, 0.4-25.5 yr). The observed incidence data corresponded to a 12.1-fold increase in the overall risk of developing a malignant nonskin tumor compared with the nontransplanted population. Urinary tract malignancies represented the most frequent malignancies among the nonskin tumors (32.1%), followed by gastrointestinal tract (30.7%) and gynecological (14%) cancers. When we considered the duration from renal transplantation to tumor detection and tumor-specific survival, there was no difference between patients treated with or without a cyclosporine A-based regimen. CONCLUSIONS: In our study, the overall risk of developing a post-transplant nonskin malignancy was 12.1-fold higher compared with the age-matched general population. Development of solid organ malignancies is one of the most frequent causes of morbidity and mortality in renal transplant recipients; thus, close tumor screening in patients after kidney transplantations is warranted.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES: To introduce a simplified technique for MRI-guided core biopsies (MRGB) of the prostate in the supine position using large-bore magnet systems. METHODS: Fifty men with a history of negative transrectal ultrasound-guided biopsies underwent MRGB in either a 1.5-T (13/50) or 3.0-T (37/50) wide-bore MRI unit. MRGBs were conducted with the patients in a supine position using a dedicated MR-compatible biopsy device. RESULTS: We developed a dedicated positioning device for the supine position. Using this device, the biopsies were performed successfully in all patients. Apart from minor rectal bleeding, only one patient developed a major side effect (urosepsis). Histology revealed prostate cancer in 25/50 (50 %) patients. CONCLUSIONS: The new technique appears feasible. Its major advantage is the more comfortable and patient-friendly supine position during the biopsy without the need to modify the MRI system's patient table. KEY POINTS : • A novel positioning device for MRI-guided prostate biopsies has been developed. • Biopsies can be performed in the patient-friendly supine position. • The positioning device can be utilised without modifying the MRI's patient table.
[Show abstract][Hide abstract] ABSTRACT: Introduction: Renal cell carcinoma (RCC) is characterized by intense angiogenesis with hyperexpression of proangiogenic factors. This study explored the potential of dynamic tissue perfusion measurement (DTPM) to detect differences in tissue perfusion between kidneys with RCC and corresponding healthy kidneys. Patients and Methods: 30 patients with unilateral, histologically confirmed RCC underwent DTPM by color Doppler ultrasound. Before scheduled surgery, Doppler ultrasound data were acquired from four transverse areas of the affected kidney and the contralateral healthy kidney. Doppler ultrasound data were recorded over a 10-second period and characteristic tissue perfusion parameters were determined. Results: The kidneys with RCC displayed characteristic changes in perfusion parameters. A significant increase in signal intensity and a significant decrease in flow resistance were noted. A combination of several DTPM parameters was used to distinguish correctly between kidneys bearing RCC or healthy kidneys with up to 75% accuracy. There was no association between the perfusion parameters and the pathological characteristics of the respective tumors. Conclusions: DTPM is a promising tool for the evaluation of whole-organ tissue perfusion. This study demonstrates the feasibility of performing DTPM measurements in kidneys bearing RCC lesions. In tumors that are characterized by extensive neovascularization, this method has the potential to be a valuable diagnostic tool.
Urologia Internationalis 11/2012; · 1.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recent studies have underlined the role of nuclear receptors in the involvement of prostate cancer signalling pathways.
A total of 84 benign prostate hyperplasia (BPH), 84 low risk prostate cancer (LPC) and 64 advanced disease (APC) cases were sampled on a tissue microarray (TMA) and stained for retinoic acid receptor (RAR)-α, retionoid X receptor (RXR)-α, liver X receptor (LXR)-α, farnesoid X receptor (FXR) and proliferate-activated receptor gamma (PPAR)-γ and the (pro)-inflammatory molecules cyclooxygenase 2 (COX2), tumor necrosis factor (TNF)-α and inducible Nitric oxide synthase (iNOS) immunohistochemically.
PPAR-γ expression in APC tissues was found to be significantly higher than that in LPC and BPH specimens (p<0.001). In contrast, RXR-a expression was significantly lower (p<0.001). COX2 staining demonstrated a trend towards overexpression in APC (p=0.025). No significant differences were found for RAR-α, iNOS and TNF-α expression. Staining of FXR and LXR was seen diffusely in the cytoplasm as well as in the nucleus, preventing sufficient evaluation by definition.
This study provides the basis for applying PPAR-γ ligands clinically in treatment of APC.
Anticancer research 08/2012; 32(8):3479-83. · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: PURPOSE: To overcome the difficulties in the interpretation of postoperative tumor obtaining biopsy cores for patients who treated their prostate cancer with high-intensity focussed ultrasound (HIFU) therapy. METHODS: The H&E slides of 58 patients with residual prostate cancer after HIFU treatment were systematically reviewed. Correlation between the pathologist's findings and immunohistochemical expression of MIB-1, alpha-Methyl-Co-Racemase and 34βE-12 staining was analyzed. RESULTS: Mean time from treatment to biopsy was 40.2 (8-208) weeks. The expert review of the H&E slides identified 40 patients with viable carcinoma in the post-HIFU biopsy cores. 18 patients were revised to necrosis-only-tumors. These biopsies were performed not later than 16 weeks after HIFU treatment (median 10.9 weeks, range 8-14). Both MIB-1 and AMACR staining displayed significant differential expression in viable carcinoma (p < 0.001) compared to necrosis tumors. Referring to viable carcinoma tissue, AMACR staining index was significantly rising, the longer treatment dated back from biopsy (p < 0.002). In this context, 34-β-E12 stained negative through all tumor areas and positive in the majority (85%) of the surrounding non-neoplastic epithelium. CONCLUSIONS: AMACR and MIB-1 reliably differentiate viable carcinoma from a process of ongoing irreversible necrosis in early post-HIFU prostate biopsy cores and therefore proposed-in addition with 34 beta-E12-as useful markers exposing suspicious tumor foci in difficult cases.
World Journal of Urology 02/2012; · 2.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To explore the potential of transrectal magnetic resonance image- (MRI-) guided biopsies of the prostate in a patient cohort with prior negative ultrasound guided biopsies.
Ninety-six men with suspected prostate cancer underwent MRI-guided prostate biopsies under real-time imaging control in supine position.
Adenocarcinoma of the prostate was detected in 39 of 96 patients. For individual core biopsies, MRI yielded a sensitivity of 93.0% and a specificity of 94.4%. When stratifying patients according to the free-to-total prostate-specific antigen (PSA) ratio, the prostate cancer discovery rate was significantly higher in the group with ratios less than 0.15 (57.1%).
MRI-guided biopsy of the prostate is a diagnostic option for patients with suspected prostate cancer and a history of repeatedly negative transrectal ultrasound-guided biopsies. Combined with the free-to-total PSA ratio, it is a highly effective method for detecting prostate cancer.
The Scientific World Journal 01/2012; 2012:975971. · 1.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Reporting guidelines aim to ensure adequate and complete reporting of clinical studies and are an indispensable tool to translate scientific results into clinical practice. The extent to which reporting guidelines are incorporated into the author instructions of journals publishing in the field of urology remained unclear.
We assessed the author instructions of uro-nephrological journals indexed in 'Journal Citation Reports 2009'. Two authors independently assessed the author guidelines. We evaluated additional information including whether a journal was published by or in association with a medical association. Discrepancies were resolved by re-checking the respective author instructions and by discussion with a third author.
The recommendations of the International Committee of Journal Editors were endorsed by 32 journals (58.2%) but were mentioned in 12 (37.5%) only to give general advice about manuscript preparation. Fourteen journals (25.5%) mentioned at least one reporting guideline, with CONSORT the most frequently cited. Journals with high impact factors were more likely to endorse CONSORT (p < 0.009). Other reporting guidelines were mentioned by <6% of the journals.
All key stakeholders involved in the publication process should more frequently promote the awareness and use of reporting guidelines.
Urologia Internationalis 11/2011; 88(1):54-9. · 1.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We present a case of high-flow priapism due to perineal trauma and subsequent arteriocavernosal fistula, which was diagnosed by sonography. Selective arterial embolization led to complete detumescence without compromising the patient's erectile function. Color Doppler sonography is an appropriate diagnostic tool to diagnose arteriocavernosal fistula. Selective arterial embolization is a safe and effective therapeutic option.
Journal of Clinical Ultrasound 09/2011; 40(1):60-2. · 0.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Standard treatment for superficial bladder cancer is transurethral resection of the bladder tumor (TURBT) followed by intravesical therapy. Little is known about the biologic behavior and treatment response of superficial disease within an irradiated bladder. We specifically analyzed patients who developed superficial recurrence after TURBT and radiotherapy or radiochemotherapy.
Between 1982 and 2006, a total of 531 consecutive patients with invasive bladder cancer were treated by using various bladder-sparing protocols at our institution. Of these, 389 (76%) achieved a complete response after TURBT and radiotherapy/radiochemotherapy. During follow-up, 68 of 389 patients (17%) developed a superficial local relapse (< or = T1) and form the subject of this study.
Sixty-four of 68 patients underwent conservative TURBT with or without intravesical treatment (4 patients underwent immediate cystectomy): 31 of 64 patients (48%) had no further bladder recurrence, 21 (33%) experienced additional superficial recurrences, and 12 (19%) ultimately progressed to muscle-invasive disease. Disease-specific survival rates were 87% and 72% at 5 and 10 years, respectively. Compared with 255 patients without local bladder relapse after primary treatment, no significant difference was found for disease-specific survival rates (72% after superficial vs. 79% without local relapse at 10 years, p = 0.78). However, significantly fewer patients with a superficial relapse survived with their native bladder (50% after superficial vs. 76% without local relapse at 10 years, p < 0.001).
A further bladder-sparing approach with TURBT and intravesical therapy is reasonable for patients with superficial relapse after combined-modality treatment without compromising survival. However, these patients are at greater risk of requiring late cystectomy.
International Journal of Radiation OncologyBiologyPhysics 04/2008; 70(5):1502-6. · 4.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The inhibitor of apoptosis protein survivin is of critical importance for regulation of cellular division and survival. Published data point to a restricted function of survivin in embryonic development and cancer; thus survivin has been broadly proposed as an ideal molecular target for specific anti-cancer therapy. In contrast to this paradigm, we report here broad expression of survivin in adult differentiated tissues, as demonstrated at the mRNA and protein levels. Focusing on the kidney, survivin is strongly expressed in proximal tubuli, particularly at the apical membrane, which can be verified in rat, mouse, and human kidneys. In the latter, survivin expression seems to be even stronger in proximal tubuli than in adjacent cancerous tissue. Primary and immortalized human renal tubular cells also showed high levels of survivin protein expression, and RNA interference resulted in a partial G(2)/M arrest of the cell cycle and increased rate of apoptosis. In conclusion, survivin may be of importance for renal pathophysiology and pathology. The predominant apical expression of survivin may indicate a further, yet unknown, function. Interventional strategies to inhibit survivin's function in malignancy need to be carefully (re)evaluated for renal side effects, as well as for other possible organ dysfunctions.
American Journal Of Pathology 12/2007; 171(5):1483-98. · 4.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To give an update on the long-term outcome of an intensified protocol of combined radiochemotherapy (RCT) with 5-fluorouracil (5-FU) and cisplatin after initial transurethral resection of bladder tumor (TURBT) with selective organ preservation in bladder cancer.
One hundred twelve patients with muscle-invading or high-risk T1 (G3, associated Tis, multifocality, diameter >5 cm) bladder cancer were enrolled in a protocol of TURBT followed by concurrent cisplatin (20 mg/m(2)/day as 30-min infusion) and 5-FU (600 mg/m(2)/day as 120-h continuous infusion), administered on Days 1-5 and 29-33 of radiotherapy. Response to treatment was evaluated by restaging TURBT 4-6 weeks after RCT. In case of invasive residual tumor or recurrence, salvage cystectomy was recommended.
Ninety-nine patients (88.4%) had no detectable tumor at restaging TURBT; 71 patients (72%) have been continuously free from local recurrence or distant metastasis. Superficial relapse occurred in 13 patients and muscle-invasive recurrence in 11 patients. Overall and cause-specific survival rates for all patients were 74% and 82% at 5 years, respectively. Of all surviving patients, 82% maintained their own bladder, 79% of whom were delighted or pleased with their urinary condition. Hematologic Grade 3/4 toxicity occurred in 23%/6% and Grade 3 diarrhea in 21% of patients. One patient required salvage cystectomy due to a shrinking bladder.
Concurrent RCT with 5-FU/cisplatin has been associated with acceptable acute and long-term toxicity. Overall and cause-specific survival rates are encouraging. More than 80% of patients preserved their well-functioning bladder.
International Journal of Radiation OncologyBiologyPhysics 08/2007; 68(4):1072-80. · 4.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Non-invasive methods for detecting genetic alterations of bladder cancer are increasingly becoming the focus of attention as diagnostic tools. The fluorescence in situ hybridization we performed to detect genetic alterations of chromosomes 3, 7, 9p21, and 17 (UroVysion Test) showed very high sensitivity, higher even than cytology, in detecting bladder tumors of varying differentiation (pTa-pT4). The use of this test in everyday clinical urology can be a very useful decision aid in treating problem cases. A pT1G3 bladder carcinoma in the presence of multichromosomal alterations should be treated as a muscle-invasive pT2 tumor. Other superficial bladder tumors (pTaGI-III, pT1GI-II) with negative histopathology in follow-up and positive FISH analysis with the UroVysion Test should have bladder mapping performed again. Although FISH analysis is currently the most sensitive marker for bladder tumors, the elaborate handling, the cost of the DNA probes and the laboratory equipment required, limit the use of this method in the urologist's everyday routine.
World Journal of Urology 10/2006; 24(4):418-22. · 2.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In invasive bladder cancer, several groups have reported the value of organ preservation by a combined-treatment approach, including transurethral resection (TUR-BT) and radiochemotherapy (RCT). As more experience is acquired with this organ- sparing treatment, patient selection needs to be optimized. Clinical factors are limited in their potential to identify patients most likely to respond to RCT, thus, additional molecular markers for predicting treatment response of individual lesions are sorely needed.
The apoptotic index (AI) and Ki-67 index were evaluated by immunohistochemistry on pretreatment biopsies of 134 patients treated for bladder cancer by TUR-BT and RCT. Expression of each marker as well as clinicopathologic factors were then correlated with initial response, local control and cancer-specific survival with preserved bladder in univariate and multivariate analysis.
The median AI for all patients was 1.5% (range 0.2-7.4%). The percentage of Ki-67-positive cells in the tumors ranged from 0.2% to 85% with a median of 14.2%. A significant correlation was found for AI and tumor differentiation (G1/2: AI = 1.3% vs. G3/4: AI = 1.6%; p = 0.01). A complete response at restaging TUR-BT was achieved in 76% of patients. Factors predictive of complete response included T-category (p < 0.0001), resection status (p = 0.02), lymphovascular invasion (p = 0.01), and Ki-67 index (p = 0.02). For local control, AI (p = 0.04) and Ki-67 index (p = 0.05) as well as T-category (p = 0.005), R-status (p = 0.05), and lymphatic vessel invasion (p = 0.05) reached statistical significance. Out of the molecular markers only high Ki-67 levels were associated to cause-specific survival with preserved bladder. On multivariate analysis, T-category was the strongest independent factor for initial response, local control and cancer-specific survival with preserved bladder.
The indices of pretreatment apoptosis and Ki-67 predict a favorable outcome in bladder cancer patients treated with TUR-BT and RCT. Molecular markers may help to select patients for an organ-sparing approach.
Strahlentherapie und Onkologie 04/2005; 181(4):213-22. · 4.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The incidence and mortality rate of prostate cancer has been steadily increasing in most countries worldwide. A potential implication of the progesterone receptor has been reported in prostatic carcinogenesis. In this study, an allele of human progesterone receptor gene (PROGINS), which was demonstrated to be associated with an increased risk of sporadic ovarian cancer, was tested in two human prostate cancer cell lines, PC-EW and PC-OR.
Genomic DNA was isolated from the cell lines in athymic nude mice. The polymorphisms in exon 4 and exon 5 and the insertion in intron G (PROGINS) were identified by sequencing and gel electrophoresis.
The PROGINS allele and the polymorphisms in exon 4 and exon 5 were found heterozygous in the PC-OR cell line but not in the PC-EW cell line.
We described the polymorphisms of exon 4, exon 5 and PROGINS in prostate cancer. Mutation screening of the PGR gene may provide information for risk assessment of developing prostate cancer.
Anticancer research 01/2005; 25(3A):1607-9. · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Prostate cancer is the leading tumor of the male in Western societies. Genetic alterations of the androgen receptor gene are known in the advanced metastatic disease. In this study, the androgen receptor gene was tested in two human prostate cancer cell lines, the androgen-sensitive PC-EW and the androgen-independent PC-OR.
Genomic DNA was isolated from two cell lines from metastatic prostate adenocarcinoma in heterotransplanted male athymic nude (nu/nu) Balb/c mice. Mutation screening was performed by sequencing of exons 1-8 of the human androgen receptor gene.
Despite two polymorphisms found in the transactivation domain of hAR exon 1, no point mutations were detected in the hAR gene of both cell lines.
Point mutations of hAR are not necessary for metastatic prostate cancer, while alterations in the solyglutamine and polyglycine repeat region in exon 1 of the MR gene are more often found. These repeats are two of many genetic influences that contribute to the overall risk of developing prostate cancer.
Anticancer research 01/2005; 25(3A):1611-4. · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The heterogeneity in prostate cancer is the reason for the difficult diagnosis and prognosis of this tumor. In this study, we looked for a correlation between prostate specific antigen (PSA), tumor staging and DNA cytophotometry.
Twenty-two prostates (pT1-T4) from patients with prostate cancer, who underwent radical prostatectomy, were examined. Preoperative PSA and postoperative DNA image cytometry, after 2-8 needle biopsies out of each organ, were evaluated.
The prostate cancer tissues showed, in DNA stemline-interpretation according to Fu, in homogenous diploid tumors an average PSA level of 3.8 ng/ml, and, in homogenous aneuploid tumors, a level of 14.0 ng/ml. Tumors with heterogeneous DNA patterns with a majority of aneuploidy had an average PSA level of 85.6 ng/ml, and heterogeneous tissues with a majority of diploidy a level of 10.9 ng/ml.
Only the stemline-interpretation of Fu after DNA cytophotometry is efficient for diagnosis of prostate cancer, and allows prognostic statements of the disease.
Anticancer research 01/2005; 25(3A):1783-5. · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to evaluate the suitability of MR Spectroscopy in screening for prostate cancer in comparison to T2-weighted MR imaging.
Forty-six patients with biopsy confirmed prostate cancer underwent combined endorectal-body-phased-array MRI at 1.5T (Tesla). Twelve patients were additionally examined with 3D-spectroscopy sequence. The results of the spectroscopy were compared with the findings of T2-weighted MR imaging and the histological examination of radical prostatectomy specimens.
With 3D-spectroscopy, a choline+creatine/citrate-ratio of 0.45 for healthy tissue and a ratio of 1.90 for tumor tissue were found and a significant difference between the groups was demonstrated. In 6 cases diagnosis of tumor localization was improved with spectroscopy in comparison with T2-weighted imaging alone.
3D-spectroscopy is a suitable technique for improving MR imaging of prostate cancer. This method can improve the diagnostic accuracy of T2-weighted imaging alone. At present, 3D-CSI spectroscopy alone can not be recommended with sufficient validity.
Anticancer research 27(1B):687-93. · 1.71 Impact Factor