Clinical and pathological nodal staging score for urothelial carcinoma of the bladder: an external validation.

PURPOSE: Radical cystectomy (RC) and pelvic lymph node dissection (LND) are standard treatments for muscle-invasive urothelial carcinoma of the bladder. Lymph node staging is a prerequisite for clinical decision-making regarding adjuvant chemotherapy and follow-up regimens. Recently, the clinical and pathological nodal staging scores (cNSS and pNSS) were developed. Prior to RC, cNSS determines the minimum number of lymph nodes required to be dissected; pNSS quantifies the accuracy of negative nodal staging based on pT stage and dissected LNs. cNSS and pNSS have not been externally validated, and their relevance for prediction of cancer-specific mortality (CSM) has not been assessed. METHODS: In this retrospective study of 2,483 RC patients from eight German centers, we externally validated cNSS and pNSS and determined their prediction of CSM. All patients underwent RC and LND. Median follow-up was 44 months. cNSS and pNSS sensitivities were evaluated using the original beta-binominal models. Adjusted proportional hazards models were calculated for pN0 patients to assess the predictive value of cNSS and pNSS for CSM. RESULTS: cNSS and pNSS both pass external validation. Adjusted for other clinical parameters, cNSS can predict outcome after RC. pNSS has no independent impact on prediction of CSM. The retrospective design is the major limitation of the study. CONCLUSIONS: In the present external validation, we confirm the validity of both cNSS and pNSS. cNSS is an independent predictor of CSM, thus rendering it useful as a tool for planning the extent of LND.

Endogenous BTG2 expression stimulates migration of bladder cancer cells and correlates with poor clinical prognosis for bladder cancer patients.

BACKGROUND: The B-cell translocation gene 2 (BTG2) is considered to act as a tumour-suppressor gene because of its antiproliferative and antimigratory activities. Higher levels of BTG2 expression in tumour cells have been linked to a better clinical outcome for several cancer entities. Here, we investigated the expression and function of BTG2 in bladder cancer. METHODS: The expression of BTG2 in bladder cancer cells was silenced by RNA interference. Cell motility was investigated by wound healing and Boyden chamber assays. The protein expression of BTG2 in bladder cancer was studied by immunohistochemistry. RESULTS: We observed that targeted suppression of BTG2 by RNA interference did not result in growth stimulation but led to a substantial inhibition of bladder cancer cell motility. Tissue microarray analyses of bladder cancer cystectomy specimens revealed that higher BTG2 expression levels within the tumours correlated strongly with a decreased cancer-specific survival for bladder cancer patients. CONCLUSION: These results indicate that endogenous BTG2 expression contributes to the migratory potential of bladder cancer cells. Moreover, high levels of BTG2 in bladder cancers are linked to decreased cancer-specific survival. These findings question the conception that BTG2 generally acts as a tumour suppressor and typically represents a favourable clinical marker for cancer patients.

Conservative management of rectal perforation after nerve sparing endoscopic extraperitoneal radical prostatectomy (nsEERPE) in a patient with a past history of polypectomy.

INTRODUCTION: Rectal polypectomy causes thinning (or even perforation) of the rectal wall in addition to thermic injury at the polypectomy site. CASE REPORT: We present a rare case of spontaneous rectal perforation after uncomplicated nerve sparing endoscopic extraperitoneal radical prostatectomy in a patient with a previous history of rectal polypectomy at the perforation site. The patient could be treated conservatively. There was complete healing of the fistula without any effect on functional results. This Conservative therapy for such rectal perforations is indicated if the patient's general condition remains stable without any signs of infection. CONCLUSIONS: Polypectomy is an important risk factor for rectal perforation during nsEERPE. Adequate time interval should be given to allow healing and avoid adding further thermal wall damage which may obscure healing leading to complications like fistula. Conservative therapy for small missed rectal perforations constitutes an attractive, feasible and non invasive treatment entity. Following this principle we have not faced this complication in following similar cases.

MR imaging of the prostate at 3.0T with external phased array coil - preliminary results.

INTRODUCTION: Among all imaging modalities, MRI of the prostate has the highest sensitivity to predict extracapsular tumor spread, seems to have added value for the preoperative treatment planning. It is an adjunct tool in patients with high suspicion of prostate cancer and so far negative TRUS-guided biopsies. Due to the higher intrinsic signal, it is expected that 3.0T enables to image the prostate without endorectal coil. Aim of this study was to evaluate the diagnostic accuracy of phased array coil 3.0T MRI in patients with suspicion of prostate cancer. MATERIAL AND METHODS: A high spatial resolution T2-w 3.0T pulse sequence (0.47 x 0.47 x 3mm voxel size) was performed in 26 patients prior to US-guided biopsy. Qualitative analysis comprised visual signal to noise, tissue contrasts and motion artifacts. MR diagnoses were correlated with histology. Diagnostic indices for the detection of prostate cancer in the peripheral zone were calculated. RESULTS: Histopathologic examination revealed pro?state cancer in 12 and benign prostate disorders in 14 patients. Motion artifacts due to peristalsis were rated moderate. Mean visual signal to noise was high. Contrast between peripheral and central zone of the prostate was excellent. MRI had 4 false negative and 2 false positive diagnoses (sensitivity 66.7 %, specificity 86.7 % diagnostic accuracy 76.9%). CONCLUSION: At 3.0T, diagnostic indices for cancer detection seem to be comparable to data reported about endorectal 1.5T MRI. Thus 3.0 T offers new options for MR imaging of the prostate in selected patients who cannot or are not willing to be examined with the endorectal coil.

[Management of urethral strictures]. / Management von Harnröhrenstrikturen.

Urethral strictures represent a relevant problem, particularly among urological patients, since they can also develop in conjunction with endourological instrumentation. After functional and radiological diagnostics, the choice of an individualized treatment concept is foremost while taking into consideration minimally invasive endourological procedures and techniques of surgical reconstruction. The best long-term results for this disorder, which has a considerable tendency to recur, are achieved with open reconstructive methods whereas urethrotomy pursues a curative approach only in cases of short-segment bulbar urethral strictures without spongiofibrosis.

[Qualitative and quantitative analysis of urolithiasis with the Rietveld method (x-ray diffraction)]. / Genaue qualitative und quantitative Harnsteinanalyse mit Hilfe der Rietveld-Methode (Röntgendiffraktion).

BACKGROUND: The Rietveld method is one of the most innovative and most important applications in x-ray diffraction and has now, for the first time, been applied to standard-free precise quantitative crystallographic analysis of urinary stones. MATERIAL AND METHODS: The capability of the Rietveld method was demonstrated by analysis of a synthetic mixture of five typical urinary stones: whewellite, hydroxylapatite, brushite, struvite, and uric acid, with 20 weight % for each pure component. RESULTS: The quantitative phase analysis (Rietveld method) yielded a mean absolute error of only 1.6% for the weight fractions of the single urinary stone components. The largest error in weight fraction, 2.3%, occurred with hydroxylapatite, caused by the typical insufficient crystallinity. CONCLUSION: Crystallographic analysis of complex urinary stones with the aid of x-ray diffraction, in combination with a Rietveld structure refinement, is the method of first choice for qualitative and quantitative phase analysis. With this tool, significant changes in weight fractions for recurrent urinary stones can be precisely detected, with therapeutic consequences.

[CpG island hypermethylation of the DNA. Perspectives of a molecular biomarker for prostate cancer]. / CpG-Insel-Hypermethylierung der DNA. Perspektiven eines molekularen Biomarkers für das Prostatakarzinom.

The exact classification of clinically significant versus insignificant prostate cancer displays one of major problems in current urological practice. Using novel molecular biomarkers, we are trying to decrease overdiagnosis of insignificant cancer. CpG island hypermethylation as a common epigenetic event is a well-recognized phenomenon during carcinogenesis. We have shown that hypermethylation at several gene loci distinguishes between benign and malignant forms of prostatic disorders. Furthermore using tests in cancer tissue and serum samples, one can draw prognostic conclusions and predict biochemical failure following radical prostatectomy with curative intent.

[Prostate cancer research. Biomarkers as promising options for optimized diagnosis and treatment]. / Prostatakarzinomforschung. Biomarker als Hoffnung für optimierte Diagnostik und Therapie.

A better understanding of signal transduction and gene regulation during prostate carcinogenesis will allow the development of novel diagnostic and prognostic biomarkers and a better prediction of the individual course of prostate cancer disease. It will also enhance the design and development of specific small molecular components aiming for specific therapies. The research groups in Bonn succeeded in the competition for an endowed professorship supported by the Rudolf Becker Stiftung (German Science Endowment Fund) settled in the"Centrum für integrierte Onkologie" funded by the German Cancer Aid. This should be the perfect breeding ground for future research in the field of prostate cancer.

[Pediatric renal cell carcinoma. A rare differential diagnosis of Wilms' tumor]. / Das Nierenzellkarzinom beim Kind. Eine seltene Differenzialdiagnose zum Wilms-Tumor.

Renal cell carcinoma (RCC) is a very rare pediatric disease and should be treated as an entity of its own because of differences in symptoms, therapy, and prognosis from the adult form of the disease. Our objective is to discuss the difficulties in clinical diagnosis, prognosis, and therapy of this very rare disease in children and to provide a review of the current literature.

[Functional retrourethral sling. A change of paradigm in the treatment of stress incontinence after radical prostatectomy]. / Die funktionelle retrourethrale Schlinge. Ein Paradigmenwechsel in der Therapie der Belastungsinkontinenz nach radikaler Prostatektomie.

The ever rising number of radical prostatectomies entails an increasing number of patients suffering from postoperative stress incontinence. Several minimally invasive techniques exist as surgical intervention options. All these procedures are based on an obstruction of the urethra. The functional retrourethral sling is a new and innovative sling suspension, which offers for the first time a non-obstructive functional therapeutic approach. The sling adjusts the changed anatomy after radical prostatectomy and exerts its effect by repositioning the lax and descended supporting structures of the sphincter in the former preoperative position. Thus continence can be achieved again. The success rate of this new technique is very good, yielding good results regarding both improving incontinence and continence rate. This new technique is secure and the results are reproducible.

[Results of the evaluation of 85,337 urinary stone analyses]. / Ergebnisse der Harnsteinanalyse von uber 85337 Harnsteinen.

In this work 85337 urinary stones were analysed by X-ray diffraction in regard of their qualitative and quantitative composition. Urological practitioners and hospitals from all areas of the former FRG sent urinary stones to the Institute of Mineralogy in Bonn and to the Urology Department of the St Josef-Hospital in Troisdorf up to December 31st, 1994. The evaluations were carried out with special regard to the frequency of occurrence and to the quantity portions. The frequency of occurrence of one component describes the percentage of the urinary stones which contain this component. The quantity portion describes the average amount of one component in regard to all urinary stones which contain this component as well. The frequency of occurrence of whewellite was 75.77% and of wheddellite 46.41%. 34.25% of all calculi were monomineralic and 55.3% were bimineralic.

Prostate cancer tissue is masked by bicalutamide: a case report.

Prostate cancer is the most common malignant tumor in men. Recently, a slightly decreased frequency of margin positivity following neoadjuvant bicalutamide treatment due to tumor shrinkage was reported. Trials investigating other anti-androgens in the past also reported lower frequencies of surgical margin positivity, but patients outcome has not improved. In this case, local recurrence was confirmed by needle biopsy in a patient five years following radical prostatectomy for prostate adenocarcinoma. After therapy with 50 mg bicalutamide for a month, the tumour was resected. Despite of detailed histological work-up and immunohistochemistry cancer suspicious lesions were not found. We think that bicalutamide may be capable of masking prostate cancer cells.

[Aggressive course of a malignant alveolar soft tissue sarcoma]. / Aggressive Verlaufsform eines malignen alveolären Weichteilsarkoms.

Alveolar soft part sarcoma is a rare soft tissue tumor. Most patients who are affected by this sarcoma are between 15 and 35 years old. The tumor is characterized by its uncommon location of metastasis. Publications concerning this sarcoma subform are rare and the best therapeutic procedure is not yet clear. Surgical excision, radiation and chemotherapy are performed, whereas complete surgical excision achieves the best results in long-term follow-up. We report a patient's history who rapidly died of his sickness despite the low initial tumor stage.

Is there evidence for a close connection between side of intravesical tumor location and ipsilateral lymphatic spread in lymph node-positive bladder cancer patients at radical cystectomy? Results of the PROMETRICS 2011 database.

PURPOSE: To evaluate the possible association between bladder tumor location and the laterality of positive lymph nodes (LN) in a prospectively collected multi-institutional radical cystectomy (RC) series. METHODS: The study population included 148 node-positive bladder cancer (BC) patients undergoing RC and pelvic lymph node dissection in 2011 without neoadjuvant chemotherapy and without distant metastasis. Tumor location was classified as right, left or bilateral and compared to the laterality of positive pelvic LN. A logistic regression model was used to identify predictors of ipsilaterality of lymphatic spread. Using multivariate Cox regression analyses (median follow-up: 25 months), the effect of the laterality of positive LN on cancer-specific mortality (CSM) was estimated. RESULTS: Overall, median 18.5 LN [interquartile range (IQR), 11-27] were removed and 3 LN (IQR 1-5) were positive. There was concordance of tumor location and laterality of positive LN in 82% [95% confidence interval (CI), 76-89]. Patients with unilateral tumors (n = 78) harbored exclusively ipsilateral positive LN in 67% (95% CI 56-77). No criteria were found to predict ipsilateral positive LN in patients with unilateral tumors. CSM after 3 years in patients with ipsilateral, contralateral, and bilateral LN metastasis was 41, 67, and 100%, respectively (p = 0.042). However, no significant effect of the laterality of positive pelvic LN on CSM could be confirmed in multivariate analyses. CONCLUSIONS: Our prospective cohort showed a concordance of tumor location and laterality of LN metastasis in BC at RC without any predictive criteria and without any influence on CSM. It is debatable, whether these findings may contribute to a more individualized patient management.

The survival impact of neoadjuvant hormonal therapy before radical prostatectomy for treatment of high-risk prostate cancer.

BACKGROUND: Several randomized controlled trials assessed the outcomes of patients treated with neoadjuvant hormonal therapy (NHT) before radical prostatectomy (RP). The majority of them included mainly low and intermediate risk prostate cancer (PCa) without specifically assessing PCa-related death (PCRD). Thus, there is a lack of knowledge regarding a possible effect of NHT on PCRD in the high-risk PCa population. We aimed to analyze the effect of NHT on PCRD in a multicenter high-risk PCa population treated with RP, using a propensity-score adjustment. METHODS: This is a retrospective multi-institutional study including patients with high-risk PCa defined as: clinical stage T3-4, PSA >20 ng ml-1 or biopsy Gleason score 8-10. We compared PCRD between RP and NHT+RP using competing risks analysis. Correction for group differences was performed by propensity-score adjustment. RESULTS: After application of the inclusion/exclusion criteria, 1573 patients remained for analysis; 1170 patients received RP and 403 NHT+RP. Median follow-up was 56 months (interquartile range 29-88). Eighty-six patients died of PCa and 106 of other causes. NHT decreased the risk of PCRD (hazard ratio (HR) 0.5; 95% confidence interval (CI) 0.32-0.80; P=0.0014). An interaction effect between NHT and radiotherapy (RT) was observed (HR 0.3; 95% CI 0.21-0.43; P<0.0008). More specifically, of patients who received adjuvant RT, those who underwent NHT+RP had decreased PCRD rates (2.3% at 5 year) compared to RP (7.5% at 5 year). The retrospective design and lack of specific information about NHT are possible limitations. CONCLUSIONS: In this propensity-score adjusted analysis from a large high-risk PCa population, NHT before surgery significantly decreased PCRD. This effect appeared to be mainly driven by the early addition of RT post-surgery. The specific sequence of NHT+RP and adjuvant RT merits further study in the high-risk PCa population.

[MR techniques for noninvasive diagnosis of prostate cancer]. / MR-Techniken zur nicht-invasiven Diagnostik des Prostatakarzinoms.

The diagnosis of prostate cancer is suggested on the basis of an elevated PSA level, abnormal digital exam, and abnormal transrectal ultrasound. US-guided biopsy is used to confirm the diagnosis, but up to 30% of prostate cancer may be missed with this approach. Meanwhile MR imaging and proton MR spectroscopy have emerged as the most sensitive additional tools for the noninvasive evaluation of prostate cancer. This article reviews the clinical indications for MRI of the prostate and summarizes new techniques such as high field strength (3 tesla) and dynamic contrast-enhanced MRI.

Surgical outcome following radical nephrectomy in cases with inferior vena cava tumour thrombus extension.

AIM: To report our experience with extensive surgery in patients with and without metastatic renal cell carcinoma and gross venous tumour thrombus. MATERIAL AND METHODS: Twenty-seven patients with unilateral renal cell carcinoma and tumour thrombus into the vena cava underwent radical nephrectomy and thrombectomy. Eight patients presented with metastatic disease at the time of surgery. Mean follow-up was 17 months (1-54 months, median 9 months). Follow-up was available for 26 patients (96%). RESULTS: Thirteen patients were alive at the time of the study; 11 without evidence of disease with a mean follow-up of 25 months and two (one with and one without metastasis at surgery) with distant metastasis at 16 and 36 months. Eleven patients have died of progressive disease. Mean survival in patients (19 patients) without metastatic disease at time of surgery was 15.2 months; patients (seven patients) with metastatic disease at surgery had a mean survival of 6.7 months. CONCLUSION: Radical nephrectomy and vena caval tumour thrombectomy can be performed in selected patients with an acceptable complication rate. Patients without metastatic disease have a better prognosis than patients with metastatic disease.

GSTP1 hypermethylation as a molecular marker in the diagnosis of prostatic cancer: is there a correlation with clinical stage, Gleason grade, PSA value or age?

OBJECTIVES: Epigenetic events such as promoter hypermethylation have been implicated in prostate carcinogenesis. We present a real-time, methylation specific protocol to detect hypermethylation in the promoter region of the GSTP1 gene in benign hyperplasia and adenocarcinoma of the prostate. METHODS: In our preliminary study, 31 prostate cancer and 5 benign prostatic hyperplasia (BPH) tissue samples were analyzed. Genomic DNA was isolated from formalin-fixed and paraffin-embedded specimens and subjected to sodium bisulfite modification, followed by real-time, methylation specific PCR. Patients with prostatic cancer were also subdivided according to their Gleason score, PSA, age and TNM Staging. Prostate cancer cell lines (LNCaP, DU145, PC3) and a BPH cell line (BPH-1) were also tested as controls. RESULTS: GSTP1 promotor hypermethylation was detected in 28 of the 31 prostate cancer cases (90.3%) and none of the five (0%) BPH cases. Statistical analysis did not reveal a significant correlation between GSTP1 hypermethylation and Gleason score, PSA, age or TNM staging. All prostate cancer cell lines were testes positive for GSTP1 promotor hypermethylation, whereas the BPH cell line (BPH-1) was tested negative. CONCLUSION: GSTP1 promotor hypermethylation occurs during carcinogenesis and is considered to be a major event of prostate carcinogenesis. Our data support this thesis and shows that GSTP1 hypermethylation reliably distinguishes between prostate cancer and BPH . Although it is not yet clear at what time during carcinogenesis hypermethylation of the GSTP1 promotor occurs it seems to provide valuable information for prostate cancer screening and diagnosis. Larger studies are underway to determine the potential role for GSTP1 hypermethylation in clinical settings.

[Outpatient extracorporeal shock wave lithotripsy. Prospective evaluation of 2937 cases]. / Ambulante extrakorporale Stosswellenlithotripsie (ESWL). Evaluation der Behandlungsergebnisse von 2937 Fällen.

PURPOSE: Extracorporeal shock wave lithotripsy (ESWL) is mainly performed on inpatient basis in Germany. It has yet to be considered if outpatient treatment in Germany is indicated when sufficient urological care is guaranteed. MATERIALS AND METHODS: Between September 1989 and December 2002, a total of 10,505 patients with urolithiasis were treated at the Institut zur Steinzertrümmerung in Troisdorf, Germany with the Siemens Lithostar plus. Of these patients, 2937 (43%) were treated on an outpatient basis. The data were collected prospectively from September 1989. Patient satisfaction was evaluated with a self-developed, non-validated questionnaire. RESULTS: The overall success rate was 81.8%. The complication rate after ESWL was 40.2%, whereas 4.9% of the patients had to be admitted to a hospital; 73.5% did not need auxiliary treatment before and 78.6% after ESWL, respectively. More than 90% of the patients were satisfied with the result of outpatient treatment. CONCLUSIONS: Outpatient ESWL can be safely performed as minimally invasive treatment after thorough patient selection in Germany. The success and quality of treatment was not altered because of outpatient treatment. A network of ESWL center and post-interventional care center has to be established to guarantee 24-h service for auxiliary necessities.

[GSTP1 CpG island hypermethylation as a molecular marker of prostate cancer]. / Die GSTP1-CpG-Insel-Hypermethylierung als molekularer Marker des Prostatakarzinoms.

BACKGROUND: Prostate cancer is the most commonly diagnosed cancer in men in Europe and North America. Despite its high prevalence, the molecular mechanism of its underlying development and progression is poorly understood. Many studies have revealed multiple molecular alterations during prostate cancer carcinogenesis. GSTP1 CpG island hypermethylation is one of the molecular changes that occur during carcinogenesis. METHODS: We evaluated the role of GSTP1 CpG island hypermethylation in prostatic cancers and discussed its possible role as a molecular biomarker of prostate cancer. RESULTS: Studies haven shown that GSTP1 CpG island hypermethylation is present in about 90% of prostatic carcinomas. The DNA alteration was also detectable in body fluids such as blood, urine, ejaculate, or prostatic secretions. One study showed hypermethylation in histologically unsuspicious lymph nodes in surgical specimens in patients with biochemical PSA (prostate-specific antigen) recurrence. Additionally, it is possible to distinguish between normal prostatic tissue, benign prostatic hyperplasia, and prostate cancer. CONCLUSIONS: The detection of GSTP1 CpG island hypermethylation serves as a molecular marker in prostate cancer screening, detection, and diagnosis. It may even provide information on prostate cancer prognosis. However, prospective trials to evaluate its predictive value are necessary.