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Skin fibrosis is one central hallmark of the heterogeneous autoimmune disease systemic sclerosis. So far, there are hardly any standardized and effective treatment options. Pathogenic mechanisms underlying fibrosis comprise excessive and uncontrolled myofibroblast differentiation, increased extracellular matrix protein (ECM) synthesis and an intensification of the forces exerted by the cytoskeleton. A deeper understanding of fibroblast transformation could help to prevent or reverse fibrosis by specifically interfering with abnormally regulated signaling pathways. The transcription factor NF-κB has been implicated in the progression of fibrotic processes. However, the cellular processes regulated by NF-κB in fibrosis as well as the NF-κB isoforms preferentially involved are still completely unknown. In an in vitro model of fibrosis, we consistently observed the induction of the c-Rel subunit of NF-κB. Functional abrogation of c-Rel by siRNA resulted in diminished cell contractility of dermal fibroblasts in relaxed, but not in stressed 3D collagen matrices. Furthermore, directed migration was reduced after c-Rel silencing and total N-cadherin expression level was diminished, possibly mediating the observed cellular defects. Therefore, NF-кB c-Rel impacts central cellular adhesion markers and processes which negatively regulate fibrotic progression in SSc pathophysiology., (© 2021. The Author(s).)

Introduction and Objectives: Bladder cancer is characterized by gender-dependent disparities. To further address this issue, we analysed a prospective, multicentre cystectomy registry., Methods: An online database was developed that included patient demographics, intra/perioperative data, surgical data and in-house complications., Results: Four hundred fifty-eight patients (112 [24.5%] women and 346 [75.5%] men) were analysed. Men and women were comparable regarding age (mean 68 years), body mass index (mean 26.5) and the mean Charlson score (4.8). Women had more advanced tumour-stages (pT3/pT4; women: 57.1%; men: 48.1%). The rate of incontinent urinary diversion was higher in women (83.1%) than in men (60.2%) and in a multivariate analysis, the strongest predictors were M+ status (OR 11.2), female gender (OR 6.9) and age (OR 6.5). Women had a higher intraoperative blood transfusion rate. The overall rate of in-house complications was similar in both genders (men: 32.0%, women: 32.6%). Severe (Clavien-Dindo grade >2) medical (women: 6.3%; men: 5.2%) and surgical (women: 21.5%; men: 14.4%) in-house complications, however, were more frequent in women., Conclusions: This multicentre registry demonstrates several gender-related differences in patients undergoing radical cystectomy. The higher transfusion rate, the rare use of orthotopic bladder substitutes and the higher in-house complication rate underline the higher complexity of this procedure in women., (© 2017 S. Karger AG, Basel.)

Introduction: With increasing life expectancy, curative treatment of octogenarians with urothelial carcinoma of the bladder (UCB) becomes more important., Materials and Methods: The treatment modalities of 276 octogenarians with UCB who were treated at the University Hospital of Erlangen between 1982 and 2011 were assessed retrospectively., Results: One hundred forty-six patients had non-muscle invasive bladder cancer (NMIBC) while 71 had muscle invasive bladder cancer (MIBC). No data was available for 59 patients. Eighty-five (58.2%) of the 146 patients with NMIBC received transurethral resection of the bladder tumor (TURBT) only, another 38 patients (26%) underwent additional intravesical therapy; and 8.9% were treated with radiochemotherapy (RCT), 4.1% with radiotherapy (RT), 1.4% with systemic chemotherapy and 1.4% with radical cystectomy (RC). Of the 71 patients suffering from MIBC, 39 (54.9%) received TURBT alone. A potentially curative therapy was performed on 31 of the 71 patients with MIBC (43.7%). Of these, 16 patients (51.6%) received RCT, 9 patients (29.0%) RT and 6 patients (19.4%) RC. In Kaplan-Meier analysis, patients with MIBC had better median overall survival with curative treatment compared to TURBT alone (28 vs. 9 months; p < 0.001, log-rank test)., Conclusions: By offering a wide range of treatment options, over 43% of octogenarians with MIBC received a curative therapy at a maximum care hospital., (© 2016 S. Karger AG, Basel.)

Purpose of this study was to evaluate prognostic impact of rare variants of urothelial bladder cancer (BC) after treatment with combined radiochemotherapy (RCT). To this end tumour tissue of 238 patients with urothelial carcinoma (UC) treated with transurethral resection of the bladder (TUR-B) and RCT with curative intent was collected. Histomorphological analysis included re-evaluation and semi-quantitative assessment of rare UC subtypes. Additionally, human epidermal growth factor receptor 2 (HER2) chromogenic in situ hybridisation (CISH) was performed in tumours with a micropapillary component exceeding 30 %. Long-term follow-up was available for 200 patients (range 3-282 months). Variant UC histology was found in 45 of 238 tumours, most frequently micropapillary UC (N = 17) including cases with a small fraction of tumour with micropapillary morphology. The mere presence of micropapillary morphology did not affect prognosis. In tumours with extensive (≥30 %) micropapillary morphology (N = 8) Kaplan-Meier analysis revealed significantly worse cancer specific survival (CSS) (P = 0.002) compared to conventional UC (mean survival times 97 months and 229 months, respectively). Univariate Cox regression analysis of cases with ≥30 % micropapillary morphology revealed a hazard ratio of 4.726 (95 % CI 1.629-13.714) for CSS (P = 0.004). CISH revealed HER2 gene amplification in 3/10 tumours with ≥30 % micropapillary component. In conclusion, for BC treated with TUR-B and RCT, the presence of micropapillary morphology in more than 30 % of the tumour is an adverse prognostic factor. Further studies are needed to evaluate a potential benefit of different, especially multimodal treatment strategies for micropapillary UC and also other subtypes of UC. Her2 represents a promising therapeutic target in a subset of micropapillary UC.

The standard treatment for invasive bladder cancer is radical cystectomy. In selected patients, bladder-sparing therapy can be performed by transurethral resection (TURBT) and radio-chemotherapy (RCT) or radiotherapy (RT). Our published in vitro data suggest that the Neuropilin-2 (NRP2)/VEGF-C axis plays a role in therapy resistance. Therefore, we studied the prognostic impact of NRP2 and VEGF-C in 247 bladder cancer patients (cN0M0) treated with TURBT and RCT (n = 198) or RT (n = 49) and a follow-up time up to 15 years. A tissue microarray was analyzed by immunohistochemistry. NRP2 expression emerged as a prognostic factor in overall survival (OS; HR: 3.42; 95% CI: 1.48 - 7.86; p = 0.004) and was associated with a 3.85-fold increased risk of an early cancer specific death (95% CI: 0.91 - 16.24; p = 0.066) in multivariate analyses. Cancer specific survival (CSS) dropped from 166 months to 85 months when NRP2 was highly expressed (p = 0.037). Patients with high VEGF-C expression have a 2.29-fold increased risk of shorter CSS (95% CI: 1.03-5.35; p = 0.043) in univariate analysis. CSS dropped from 170 months to 88 months in the case of high VEGF-C expression (p = 0.041). Additionally, NRP2 and VEGF-C coexpression is a prognostic marker for OS in multivariate models (HR: 7.54; 95% CI: 1.57-36.23; p = 0.012). Stratification for muscle invasiveness (T1 vs. T2-T4) confirmed the prognostic role of NRP2 and NRP2/VEGF-C co-expression in patients with T2-T4 but also with high risk T1 disease. In conclusion, immunohistochemistry for NRP2 and VEGF-C has been determined to predict therapy outcome in bladder cancer patients prior to TURBT and RCT., (© 2014 UICC.)

Objectives: To evaluate the efficacy of flexible ureterscopy (fURS) and extracorporal shockwave lithotripsy (SWL) in the treatment of urolithiasis, complemented by a subgroup analysis of lower pole calyx., Methods: Retrospective analysis of patients treated by fURS or SWL was performed by independent variables such as gender, age, nephrolith size, double-J stent (DJ stent) and stone localisation., Results: Out of 326 patients, 165 were treated by SWL and 161 by fURS. Complete stone removal was achieved by fURS in 83.2% and by SWL in 43.0% (p < 0.001). Asymptomatic behaviour (88-89%) and complication rate (10-11%) were nearly the same in both methods. A higher retreatment rate for SWL was necessary; otherwise, an auxillary DJ stent was performed more often preoperative before fURS. The subgroup analysis of lower pole calyx confirmed these evaluations., Conclusions: Complete stone-free removal was almost 8 times higher after fURS compared to SWL. The efficacy of fURS in treatment of urolithiasis is substantially higher than the efficacy of SWL., (© 2015 S. Karger AG, Basel.)

2-Ketoisocaproate (KIC) is used as a therapeutic agent, and a KIC-producing organism may serve as a platform for products deriving from this 2-keto acid. We engineered Corynebacterium glutamicum for the production of KIC from glucose by deletion of ltbR and ilvE, encoding the transcriptional repressor LtbR and transaminase B, respectively, and additional overexpression of ilvBNCD, encoding acetohydroxyacid synthase, acetohydroxyacid isomeroreductase, and dihydroxyacid dehydratase. The KIC-producing strain was improved by deletion of the methylcitrate synthase genes and by decreasing citrate synthase activity by exchange of the native promoter of the citrate synthase gene. In shake-flask fermentations under L-leucine limitation, the newly constructed strain C. glutamicum VB (pJC4ilvBNCD) produced 31 ± 2 mM (4.0 ± 0.3 g l(-1)) KIC and showed a product yield of about 0.26 ± 0.02 mol per mole (0.19 ± 0.01 g per gram) of glucose. As by-product, the strain formed about 33 mM 2-ketoisovalerate, which is a precursor of KIC. KIC production was further improved by additional expression of an isopropylmalate synthase allele (leuA (EC-G462D)), encoding an enzyme resistant towards L-leucine inhibition, and by addition of acetate as additional substrate. With glucose and acetate, the newly constructed strain produced 71 ± 3.2 mM (9.2 ± 0.4 g l(-1)) KIC with a yield of 0.24 ± 0.01 mol C (KIC) per mole C (in both substrates) and with nearly no 2-ketoisovalerate by-product formation (<2 mM). Investigating the activities and regulation of the native isopropylmalate synthase and dehydratase of C. glutamicum, we observed competitive and noncompetitive inhibition, respectively, by KIC.

Purpose: To evaluate sex as a possible prognostic factor in bladder cancer patients treated with transurethral resection (TURBT) and radio- (RT) or radiochemotherapy (RCT)., Methods: Kaplan-Meier analyses and multiple Cox proportional hazards regression analyses were performed to analyze sex as a possible prognostic factor on the overall (OS) and cancer-specific (CSS) survival of 386 male and 105 female patients who underwent TURBT and RCT or RT with curative intent between 1982 and 2007., Results: After a follow-up of 5 years, female sex demonstrated a hazard ratio (HR) of 1.79 (95 % CI 1.24-2.57) for OS; for CSS, the HR was 2.4 (95 % CI 1.52-3.80). Sex was an adverse prognosticator of both OS and CSS independent from age at diagnosis, cT stage, grading, concurrent cis, LVI, focality, therapy response, resection status and therapy mode. Kaplan-Meier analysis showed significantly reduced OS of women compared with men, with a median survival of 2.3 years for female patients and 5.1 years for male patients (p = 0.045, log-rank test). The estimated median CSS was 7.1 years for female patients and 12.7 years for male patients (p = 0.11, log-rank test)., Conclusions: Female sex is an independent prognostic factor for reduced OS and CSS in bladder cancer patients treated by TURBT and RT or RCT. These data are in agreement with those reported for OS after radical cystectomy in muscle-invasive bladder cancers. Therefore, further studies are strongly warranted to obtain more information about molecular differences regarding sex-specific carcinogenesis in bladder cancer and about possible therapeutic considerations.

Unlabelled: 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., Objective: 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., Patients and Methods: 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., Results: 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%., Conclusions: 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., (© 2012 THE AUTHORS. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL.)

Aim: 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., Patients and Methods: Ninety-six men with suspected prostate cancer underwent MRI-guided prostate biopsies under real-time imaging control in supine position., Results: 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%)., Conclusion: 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.

OBJECTIVE: Owing to the widespread use of abdominal imaging studies the detection rate of solid renal masses has increased, and an accurate characterisation of imaging features of renal masses has become more essential for case management. METHOD AND RESULTS: MR imaging (MRI) and computed tomography (CT) are frequently used modalities for detection and differentiation of renal masses. This article gives a review of imaging characteristics of benign and malignant renal masses, discussing their appearance in CT and MR imaging. Advanced MR techniques like diffusion-weighted imaging and apparent diffusion coefficient (ADC) mapping, which have shown promising results in the differentiation between benign and malignant renal lesions, will be introduced. CONCLUSION: MRI and CT are useful in the characterisation and estimation of the prognosis for renal masses.

Objective: To evaluate 15-year experience with patients treated with transurethral resection (TUR) of a bladder tumor (TURBT) followed by radiochemotherapy (RCT) or radiation (RT) and to describe the association of different parameters with clinical outcome., Patients and Methods: Bladder cancer patients (473) who underwent TURBT and RCT or RT with curative intent between 1982 and 2007 in our clinic were evaluated. The clinical course, operative and pathological characteristics and the long-term clinical outcome were assessed., Results: Complete remission (CR) was achieved in 70.4% of the patients. The 5-, 10- and 15-year overall survival rates were 49%, 30% and 19%, respectively. Long-term results were significantly affected by pT stage, lymphatic vessel invasion, residual tumor status, lymph node metastasis, kind of therapy (RCT vs. RT), and the response as confirmed by restaging TUR after RCT/RT., Conclusion: Organ-preservation therapy in patients with bladder cancer is a valid option compared to radical cystectomy in selected patients, ideally with early-stage bladder cancer, in whom a complete transurethral resection of the tumor can be accomplished and radiochemotherapy is superior to radiation for favorable long-term outcome.

2-Ketoisovalerate is used as a therapeutic agent, and a 2-ketoisovalerate-producing organism may serve as a platform for products deriving from this 2-keto acid. We engineered the wild type of Corynebacterium glutamicum for the growth-decoupled production of 2-ketoisovalerate from glucose by deletion of the aceE gene encoding the E1p subunit of the pyruvate dehydrogenase complex, deletion of the transaminase B gene ilvE, and additional overexpression of the ilvBNCD genes, encoding the l-valine biosynthetic enzymes acetohydroxyacid synthase (AHAS), acetohydroxyacid isomeroreductase, and dihydroxyacid dehydratase. 2-Ketoisovalerate production was further improved by deletion of the pyruvate:quinone oxidoreductase gene pqo. In fed-batch fermentations at high cell densities, the newly constructed strains produced up to 188 ± 28 mM (21.8 ± 3.2 g liter(-1)) 2-ketoisovalerate and showed a product yield of about 0.47 ± 0.05 mol per mol (0.3 ± 0.03 g per g) of glucose and a volumetric productivity of about 4.6 ± 0.6 mM (0.53 ± 0.07 g liter(-1)) 2-ketoisovalerate per h in the overall production phase. In studying the influence of the three branched-chain 2-keto acids 2-ketoisovalerate, 2-ketoisocaproate, and 2-keto-3-methylvalerate on the AHAS activity, we observed a competitive inhibition of the AHAS enzyme by 2-ketoisovalerate.

Corynebacterium glutamicum efficiently utilizes maltose as a substrate. We show here that the presence of maltose increases glucose utilization by raising the expression of ptsG, which encodes the glucose-specific EII permease of the phosphotransferase system. Consequently, the L-valine productivity of a pyruvate dehydrogenase complex-deficient C. glutamicum strain was improved by the presence of maltose.

To date, the current literature does not report on oncological surgery in bilateral renal cell cancer and coincidental simultaneous prostate cancer. We present the case of a 66-year-old patient presenting as a challenge due to this oncological-surgical constellation. Based on the present case study and the postoperative follow-up, we discuss possible surgical strategies and demonstrate that, even in the case of multiple tumour locations, a satisfying oncological and functional long-term result is achievable., (Georg Thieme Verlag Stuttgart * New York.)

Introduction: In regard to therapy and prognosis of urological tumors, specific tumor markers are lacking especially in renal and urinary bladder carcinoma. Our study examines the relevance of serum serotonin levels to urinary bladder, prostate, renal, and testicular carcinoma when it comes to prognosis and occurrence of these oncological conditions., Materials and Methods: Serotonin levels were obtained in 109 patients presenting with urothelial carcinoma to the urinary bladder, adenocarcinoma of the prostate and renal cell carcinoma, as well as presenting with seminomatous and non-seminomatous testicular tumors. All of these conditions varied in grades and metastases. Serum levels were drawn between 7 and 8 a.m. exclusively in order to avoid circadian changes., Results: Serotonin levels in urothelial carcinoma appeared within pathological range in correlation with tumor stage, life expectancy, and statistical significant with distant metastases. In prostate carcinoma, serotonin levels showed a tendency with organ exceeding growth, Grading/Gleason Score, PSA values >100 ng/ml, and the presence of distant metastases. In renal cell carcinoma, serotonin levels were decreased in patients with lymph node and distant metastases; there was no significant correlation with extent of infiltration. In regard to testicular carcinoma, decreased serotonin levels were merely noted in mixed tumors and the one extragonadal seminoma. Otherwise there was no correlation observed with stage and grade as well as with common tumor markers (AFP/betaHCG)., Conclusion: Serotonin levels are suitable for prognostic evaluation of urothelial carcinoma in the urinary bladder, adenocarcinoma of the prostate, and renal cell carcinoma, especially taking into account the lab cost of 25 per test.

Purpose: 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., Patients and Methods: 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., Results: 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)., Conclusion: 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.

The primary Merkel cell carcinoma, a neuroendocrine tumor, mostly appears on skin areas exposed to light. Complete excision with a safety margin plus local lymphadenectomy is the basic therapy. In cases of relapse or metastasis, surgical treatment is also the first choice. Chemotherapy or radiotherapy are used only for a palliative purpose. To date, in no case of metastasis has healing occurred. Lymphogenic and hematogenic metastasizing to the urinary bladder is rare, however infiltrating tumor growth into the urinary bladder occurs more frequently. In urology, the Merkel cell tumor has been detected only sporadically, while infiltration of the bladder has been described in three cases worldwide. We report the case of a patient with a single metastasis of a Merkel cell tumor in the urinary bladder, after excision of the femoral primary cancer two years earlier.

Purpose: 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., Methods and Materials: 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., Results: 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., Conclusion: 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.

Background: Prostate cancer is the second leading cause of death among men in Western countries. Genetic alterations of the estrogen receptor gene are known to be indicative of a higher risk of this disease. The estrogen receptor gene is found as two subtypes, alpha and beta. In this study the estrogen receptor alpha and beta genes were tested in 2 human prostate cancer cell lines: the hormone-sensitive PC-EW and the hormone-independent PC-OR., Materials and Methods: Genomic DNA was isolated from 2 cell lines from metastatic prostate adenocarcinoma in hetero-transplanted male athymic nude (nu/nu) Balb/c mice. Mutation screening was performed by sequencing of exons 1-8 and intron 1 of the human estrogen receptor gene alpha, and exons 1-9 of estrogen receptor gene beta., Results: No point mutations were detected in the ER gene subtypes of either cell line. Polymorphisms were found of ER-alpha in exon 1, intron 1, exon 3, 4, 5, intron 6 and exon 8 and of ER-beta in intron 2 and exon 9., Conclusion: Point mutations of ER-alpha and -beta are not necessary for metastatic prostate cancer, alterations in different areas of the ER genes are more often found. These polymorphisms are a part of many genetic influences that accumulate to contribute to men's overall risk for developing prostate cancer.

Background: 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., Materials and Methods: 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., Results: 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., Conclusion: 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.

The occurrence of primary non-Hodgkin's lymphomas of the testes is described in just a few studies in the urological literature. The clinical symptomatology and especially the treatment concept for this relatively rare tumor entity are hardly discussed. Imaging diagnostics, e.g., with CT or MRI, play a decisive role in determining the diagnosis and whether a primary testicular disease is involved or a generalized systemic disease. In cases of primary B-cell lymphomas of the testes, a high inguinal orchiectomy should be performed for diagnostic and therapeutic purposes. The standard chemotherapy for aggressive non-Hodgkin's lymphomas is the CHOP regimen consisting of cyclophosphamide, doxorubicin, vincristine, and prednisone. This article presents two adults aged 67 and 75 years with histologically proven B-cell lymphoma of the testes and discusses the characteristics of this relatively rare clinical picture as well as treatment and prognosis.

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.

Purpose: 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., Patients and Methods: 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., Results: 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., Conclusion: RT/RCT after TURBT with selective bladder preservation is a reasonable alternative to intravesical treatment or early cystectomy for high-risk T1 bladder cancer.

Aim: Conservative therapy using deep transurethral resection (TUR) followed by radiochemotherapy is a novel treatment strategy in stage TI grade 3 (TIG3) transitional cell carcinoma (TCC) of the bladder. The aim of this study was to present our long-term results of radiochemotherapy in T1G3 TCC patients., Materials and Methods: A total of 64 patients with TIG3 TCC of the bladder underwent a TUR and a subsequent radiochemotherapy protocol at our institution. Following TUR, a median dose of 55.8 (range; 45-69.4) Gy radiation therapy was applied to the bladder, and simultaneous chemotherapy was initiated using cisplatin, carboplatin and/or 5-fluorouracil. After completion of the protocol, response was evaluated by repeat TUR, and check cystoscopies were performed at regular intervals. Median patient age was 66 (range; 30-82) years and median follow-up was 43.2 (range; 6-127) months., Results: Complete response was achieved in 55 (90.2%) patients. Of the complete responders, 7 patients experienced a superficial (Ta, T1) recurrence and 8 patients had progression. In 8 patients with refractory superficial and invasive relapses, a salvage cystectomy was mandated. The overall progression rate was 14%. The overall and disease-free survival rates were 76% and 93%, respectively at 5 years. During followup, 4 patients suffered from reduced bladder capacity, and 2 patients underwent cystectomy due to shrinking bladder., Conclusion: Combined multimodality therapy is a safe and curative treatment option for patients with T1G3 TCC of the bladder in the hands of dedicated multimodality teams. Therefore, it is reasonable to justify radiochemotherapy combined with TUR in the first-line treatment of T1G3 tumors.

Background: 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., Materials and Methods: 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., Results: 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., Conclusion: Only the stemline-interpretation of Fu after DNA cytophotometry is efficient for diagnosis of prostate cancer, and allows prognostic statements of the disease.

Background: The effect of the distance to normal renal parenchyma (DTNRP) on survival after nephron-sparing surgery (NSS) for renal cell cancer (RCC) was analyzed. Additionally, the role of T-classification, tumor diameter and tumor grading was considered., Patients and Methods: NSS was performed on 126 patients with RCC between 1988 and 2000. Eighty-six patients were submitted to annual follow-up. These 86 patients were sub-classified into statistical groups according to the distance to normal renal parenchyma (< or = 2mm; > 2mm - < or = 5mm; >5 mm), T-classification, tumor diameter (< or = 20mm; > 20mm - < or = 30 mm; >30 mm - < or = 50mm; > 50mm) and tumor grading. The effect of belonging to one of these groups on survival was analyzed using the Log-Rank-Test (SPSS; version 11.0) and the Kaplan and Meier survival data. The level of significance was set at p < 0.05., Results: During the follow-up period, 4 patients died related to RCC and 15 patients died from other causes. The tumor-specific survival was 95.4%. At the end of 2002, the mean follow-up time was 5.5 years (range 0.1 - 14.7). None of the variables which had been analyzed in our statistical groups had an effect on the overall survival., Conclusion: The distance to normal renal parenchyma does not influence survival, suggesting an additional resection to be unnecessary even in cases where the DTNRP is reported by frozen section to be less than 2 mm. RCC up to 5 cn in tumor diameter can be safely removed by NSS, even in the presence of a functional intact contralateral kidney.

Background: 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., Materials and Methods: 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., Results: 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., Conclusion: 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.

The employment of DNA flow or image cytometry for oncological diagnostic procedures is favored because of its high correlation to tumor biological behavior. Prognostic statements and therapeutic strategies therefore are based on the high validity of DNA cytometric measurements. Using 151 bladder washings from patients suspected of bladder cancer for this study, we examined the clinical value of various common methods of DNA single cell (SCI) and stemline interpretations (SLI). Comparing the specificity and sensitivity of DNA image cytometry in detection of bladder tumors, we found 81 and 52%, respectively, for SCI of Boecking, 84 and 45% for SLI of Boecking, 61 and 58% for SLI of Fu, and 82 and 40% for conventional stemline interpretation. To improve diagnostic and prognostic validity of DNA image cytometry, we designed our own method of interpretation. In consequence, we identified six single DNA parameters out of all recorded measurements that correlated most to histopathological grading (G1-G3). Creating reference values at random and rating by points, we used a cytometric grading system for ranking. In detection of bladder cancer specificity and sensitivity ultimately arrived at almost 70% in application of our method. Thus, by this study, we were able to show that sensitivity of DNA examination can be increased by combining various DNA parameters. Apart from our own scheme, the discrepancy in interpretation of DNA image cytometry does not allow us to recommend this procedure as the only diagnostic in detection of bladder cancer. However, in regard to prognostic statements, particularly tumor biological behavior, DNA image cytometry appears to be useful.

Development and progression of tumours is generally driven by an accumulation of genetic alterations. In this study we correlated chromosome 17 aneuploidy to invasiveness of bladder cancer by the method of fluorescence in situ hybridisation (FISH) in urinary cytospins. We investigated the value of FISH compared to DNA cytophotometry in the diagnosis of bladder cancer. 39 patients with or suspicious for bladder tumour were analyzed. 19 patients had a bladder tumor at the time of diagnosis, 14 superficial (Ta-T1) and 5 invasive (T2-3). The remaining 20 patients had no tumour at the time of diagnosis, however 9 of them had one in prehistory (Ta-T2). For FISH we used the DNA probe of HER-2/neu located on chromosome 17. DNA image cytometry was performed according to single cell interpretation of Böcking. Our results showed a correlation between HER-2/neu CEP 17 alterations and invasive bladder cancer to the extent of 10-70% aberrant cells for patients with current invasive bladder tumour as well as for patients who had been cured but with as invasive bladder cancer in prehistory. On the other hand, the percentage of aneuploid cells for negative biopsy and superficial tumour was 0-2%. The DNA cytophotometry brought an uniform aneuploidy only for present invasive tumours: negative biopsies, superficial cancer and invasive tumour just in prehistory, showed mixed diploid-aneuploid DNA patterns. Our results showed that for the detection of aberrant tumour cells the method of FISH is more sensitive than DNA cytometry. FISH could provide important information in the prognosis of bladder cancer.

Bladder cancer is clinically characterized by a high recurrence rate for superficial tumours up to 70% and by the invasiveness of advanced bladder cancer. To learn more about the biological behaviour of an individual bladder cancer different tumour markers have been investigated. The aim of our study was to compare the potential of aggression of both superficial and invasive bladder tumours by means of the proliferation marker Ki67, the tumour suppressor gene p53, the non metastasizing protein nm23 and the evaluation of DNA ploidy. We examined 36 patients, 28 with a bladder tumour (Ta-T4) and 8 without as a control group. For immunohistochemistry (Ki67, p53, nm23) we took paraffin sections and scored semiquantitatively under a microscope. The DNA cytophotometry was done on bladder washings by evaluating the DNA ploidy of single cells. The results showed that benign tissues were negative for Ki67 and p53 but positive for nm23. The DNA diagnosis was diploid for all benign samples. The superficial bladder cancer (Ta, T1) showed, in comparison to the invasive tumours, significantly lower numbers of aneuploid cells and a higher rate of p53 mutations. On the other hand the invasive tumours (T2-4) were correlated to significantly higher proliferation rates and higher potencies for metastasizing. The combination of the investigated tumour markers allowed a graduation of the biological behavior of an individual bladder cancer. Especially a high p53 mutation rate and a non aneuploid DNA diagnosis were indicators for the recurrence of superficial bladder tumours. Invasive growth of bladder cancer was characterized by high Ki67 proliferation and low nm23 protein binding.