[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: Plasmacytoid urothelial carcinoma of the bladder represents a rare and aggressive variant of urothelial carcinoma, which is usually diagnosed at an advanced pathologic stage. Until now, no reports exist on this rare tumor type in the upper urinary tract. Herein, we present the first report on the clinical course of a metastatic plasmacytoid urothelial carcinoma of the renal pelvis and show its unfavorable outcome despite multimodal therapy.
Urologia Internationalis 02/2012; 89(1):120-2. · 1.07 Impact Factor
[show abstract][hide abstract] ABSTRACT: Transurethral resection of bladder tumour (TURBT) is the 'gold standard' in the diagnosis and therapy of non-muscle-invasive bladder cancer. To improve the quality of this technique an additional TUR (after 4-6 weeks) or a simultaneous photodynamic diagnosis is often offered. The present study shows different variables that influence, to a greater or lesser extent, the accuracy of the TUR diagnosis and the success of the operation. This is very important for the further management of bladder cancer, be it in tumour follow-up or in preparation for more invasive therapies.
To analyse the impact of a standardised extended transurethral resection of bladder tumour (TURBT) protocol on the determination of the residual tumour status at initial TURBT session and recurrence rate in the primary resection area. Despite, the fact that there is a clear consensus on the aims of TURBT, there is little agreement on how to perform TURBT to achieve that goal.
We retrospectively evaluated 221 consecutive patients, who underwent 305 TURBT sessions for bladder cancer, including patients with recurrent tumours. All the TURBTs were extended by taking additional deep and marginal specimens, according to a standardised protocol. Clinical and histopathological data were retrieved from the patients' records.
Across all tumour stages, residual tumour (pR1) was found in 38% of the additionally taken specimens. There was a significant association of pR1 status with tumour stage, grade, and size. Also in the group of non-muscle-invading tumours, the rate of R1 resection was rather high at 22%. There was no association with focality and the training status of the surgeon. At follow-up, of all the patients with a unifocal primary tumour there was recurrence in the same area as the primary in 5.1%.
Extended TURBT provides detailed information about the horizontal and vertical extent of the bladder tumour. The implementation of standardised TURBT procedures, such as our protocol of an extended TURBT, is greatly needed to improve local tumour control. Whether a diagnostic re-TUR may be restricted to those cases with positive margins or ground specimens remains to be studied.
BJU International 02/2012; 110(2 Pt 2):E76-9. · 3.05 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: 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 investigate whether the addition of chemotherapy to radiotherapy (RT) is beneficial particularly in bladder tumors that possess the capacity for rapid proliferation.
The Ki-67 index was evaluated by immunohistochemistry on pretreatment biopsies from 136 patients treated by transurethral tumor resection (TURBT) and RT (n=50) or platin-based radiochemotherapy (RCT; n=86). Ki-67 expression was correlated with response to RT/RCT and long-term local control rates. The median follow-up was 43 months.
The percentage of Ki-67-positive cells ranged from 1.5% to 89%. Complete response (CR) was observed in 100/131 patients (76%, five without restaging TURBT). A statistically significant association between high Ki-67 index (>or= median) and CR was noted for patients receiving RCT (93% vs. 66% for Ki-67 < median; p=0.001), but not for patients treated with RT alone (p=0.12). Long-term local control was 39% for patients treated with RT, and 44% for patients after RCT (p=0.49). Patients with high Ki-67 index did significantly better when subjected to combined RCT (55% vs. 33% with low Ki-67 index; p=0.006), whereas no difference between high and low Ki-67 status was observed in the RT group (39% each; p=0.57). On multivariate analysis, Ki-67 status was an independent predictor for local failure in the RCT group (risk ratio, 0.43; p=0.007). Disease-specific survival was significantly better after RCT (62%) as compared with RT (42%; p=0.03), however, the Ki-67 index was not related to this endpoint.
Rapid proliferation is associated with improved local control, if patients are treated with concurrent RCT. The cytostatic effect of concurrent chemotherapy may effectively inhibit repopulation during fractionated RT.
Strahlentherapie und Onkologie 10/2007; 183(10):552-6. · 4.16 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: For high-risk T1 bladder cancer, the most important issue is how to restrict radical cystectomy to selective patients with a high likelihood of tumor progression and to choose an initial bladder-sparing approach in others without affecting survival. Radiotherapy or radiochemotherapy (RT/RCT) may help to strike a balance between intravesical treatment and early cystectomy.
Between 1982 and 2004, 141 patients with high-risk T1 bladder cancer (84 patients with T1 grade 3 [T1G3]; others with T1G1/2 and associated carcinoma-in-situ, multifocality, tumor diameter > 5 cm, or multiple recurrences) were treated with RT (n = 28) or platinum-based RCT (n = 113) after transurethral resection of bladder tumor (TURBT). Six weeks after RT/RCT, response was evaluated by restaging TURBT. Salvage cystectomy was recommended for patients with persistent disease and for tumor progression after initial complete response (CR). Median follow-up was 62 months; 65 patients have been observed for 5 years or more.
CR was achieved in 121 of 137 patients (88%; four patients without restaging TURBT). Tumor progression for the entire group of 141 patients was 19% and 30% at 5 and 10 years, respectively (for 121 patients with CR, 15% and 29%; for 84 patients with T1G3, 13% and 29%, respectively). Disease-specific survival rates were 82% and 73% at 5 and 10 years (CR, 89% and 79%; T1G3, 80% and 71%, respectively). More than 80% of survivors preserved their bladder; 70.4% were "delighted" or "pleased" with their urinary function.
RT/RCT after TURBT with selective bladder preservation is a reasonable alternative to intravesical treatment or early cystectomy for high-risk T1 bladder cancer.
Journal of Clinical Oncology 06/2006; 24(15):2318-24. · 18.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: Thirty-seven consecutive patients with elevated PSA levels and negative tumor prostate biopsies underwent a MR-guided prostate biopsy in a 1.5-T scanner in the supine position. After localization of suspected tumor areas using an endorectal coil and two body-phased array coils, the biopsy device was positioned without any repositioning of the patient. The biopsy device consisted of a mount, a ball joint, a positioning stage and an insertion stage with a needle guide, which was filled with a MR-visible fluid to control positioning of the needle using a balanced steady-state free precession sequence (TrueFISP) and a high-resolution turbo spin echo (T2-TSE) sequence. Core biopsies were taken manually in the magnet. The biopsy needle could be correctly positioned in all cases. Suspected lesions with a diameter > or =10 mm could be successfully punctured. Four to nine (mean = 6) biopsies were taken per patient. In 14 patients, prostate cancer was confirmed at histology. Twenty-four biopsies positive for cancer were performed in 14 patients. A correct correlation was found between the site of biopsy and histology. MR-guided prostate biopsy can be effective in increasing primary positive tumor biopsy results in patients with a history of negative tumor TRUS-guided prostate biopsies.
European Radiology 06/2006; 16(6):1237-43. · 3.55 Impact Factor