Evaluation of perioperative complications in open and laparoscopic surgery for renal cell cancer with tumor thrombus involvement using the Clavien-Dindo classification.

OBJECTIVE: To identify risk factors for perioperative complications and morbidity in renal cell cancer (RCC) surgery with tumor thrombus invasion (TTI). PATIENTS AND METHODS: Retrospective single-center analysis of 128 patients who underwent open (n = 97) or laparoscopic (n = 31) radical nephrectomy (NT) for RCC between 1999 and 2010. TTI was at Mayo-Level 0, I, II, III, IV in 88, 7, 10, 4, and 19 cases, respectively. Cavotomy was performed in 27, liver mobilisation in 20, and cardiovascular bypass in 17 patients. RESULTS: The rate of any early postoperative complication (PC) by Clavien-Dindo classification was 58.6%, while the severe early PC rate was 29.7%. There was a statistically significant difference in multivariate analysis in the incidence of any early PC and of severe early PC by Charlson score (OR:1.584 (95%CI:1.141-2.199), p = 0.006; OR:3.065 (95%CI:1.218-7.714), p = 0.017) and by tumor thrombus level TNM-UICC 2010 T3a/T3c (OR:10.668 (95%CI:1.266-89.871), p = 0.029; OR:10.502 (95%CI:2.981-36.992), p < 0.001). In pT3a cases open NT was associated with a higher early (57.9% vs. 25.8%) and severe (24.6% vs. 9.7%) PC rate compared to laparoscopic NT. The 30-day mortality rate was 0%. The 90-day mortality rate was 6.3% but 100% cancer-related. In Cox regression analysis tumor thrombus level was not predictive for overall survival. CONCLUSIONS: The strongest risk factor for early and severe PC in patients with TTI is a supradiaphragmatic tumor thrombus. In cases with severe PC, this fact persists when comparing Mayo-Levels II-III and Level IV. In pT3a cases open NT shows a 2-fold higher early PC rate compared to laparoscopic NT.

Tumour shrinkage measured with first treatment evaluation under VEGF-targeted therapy as prognostic marker in metastatic renal cell carcinoma (mRCC).

BACKGROUND: The aim of our analysis is to further characterise the prognostic relevance of early tumour shrinkage (TS) during VEGF-targeted therapy in mRCC, in order to explore whether this could define a group of patients with long-term survivorship. METHODS: A hundred patients were stratified into five subgroups according to their change of tumour size with first treatment evaluation: -100% to -60%; -59% to -30% and -29% to 0% TS or gain of tumour size from 1% to 19% and ≤20% or occurrence of new lesions (i.e., progressive disease). RESULTS: The median PFS and OS were 10.4 months and 28.2 months, respectively. The median OS stratified according to the subgroups as described above was 77.4, 33.5, 26.9, 30.0 and 14.3 months, respectively. Multivariate analysis revealed early TS as a prognostic marker (P=0.021; HR 1.624). CONCLUSION: The extent of TS defines a small proportion of patients with an excellent prognosis. Larger studies are warranted to define the relationship of long-term survivorship and extent of TS with targeted therapies.

[Significance of the sinus x-ray prior to septoplasty]. / Stellenwert der präoperativen Röntgendiagnostik der Nasennebenhöhlen vor Septumplastik.

INTRODUCTION: There is still disagreement concerning the significance of sinus x-ray prior to septoplasty: according to the previous guidelines for Diagnostic and Therapy of the German Society for Oto-Rhino-Laryngology and head and neck surgery in 1996, a sinus x-ray prior to septoplasty was seen as "necessary." According to the guidelines from 2010, a suitable radiology imaging is just "optional." In the present study, we analyzed the significance of a sinus x-ray to exclude a chronic sinusitis prior to septoplasty. PATIENTS AND METHODS: A total of 96 patients were included in this study. All were admitted to the hospital by an ENT specialist for septoplasty with conchotomy. The preoperatively performed sinus x-ray was evaluated with regard to an already existing sinusitis. These results were correlated with the patients' anamnesis and the nasal endoscopic view. RESULTS: A sinus x-ray (occipitomental) was obtained in all 96 patients. No pathological result was observed in 82 patients, while 14 patients showed pathology in the paranasal sinus. After a detailed appraisal of the sinus x-ray with pathology, 7 patients with pathological findings in the paranasal sinus remained. In the other 7 patients, the statement was false positive. In only 3 patients was a CT image obtained, which resulted in modification of the surgical procedure. CONCLUSION: Our findings show that a routinely performed sinus x-ray is not necessary prior to septoplasty. If there is reasonable suspicion for pathology in the paranasal sinus, radiological imaging is necessary, whereby a CT scan should be performed.

Functional characterization of isolated, perfused outermedullary descending human vasa recta.

AIM: The renal medulla plays an important role in the control of water and salt balance by the kidney. Outer medullary descending vasa recta (OMDVR) are microscopic vessels providing blood flow to the renal medulla. Data on the physiology of human vasa recta are scarce. Therefore, we established an experimental model of human single isolated, perfused OMDVR and characterized their vasoactivity in response to angiotensin II and to pressure changes. METHODS: Human non-malignant renal tissue was obtained from patients undergoing nephrectomy due to renal cell carcinoma. OMDVR were dissected under magnification and perfused using concentric microscopic pipettes. The response of OMDVR to angiotensin II and pressure changes was quantified in serial pictures. All patients signed a consent form prior to surgery. RESULTS: Outer medullary descending vasa recta constricted significantly after bolus applications of angiotensin II. OMDVR constriction to angiotensin II was also concentration dependent. Response to luminal pressure changes was different according to the diameter of vessels, with larger OMDVR constricting after pressure increase, while smaller ones did not. CONCLUSION: Outer medullary descending vasa recta constrict in response to angiotensin II and pressure increases. Our results show that OMDVR may take part in the regulation of medullary blood flow in humans. Our model may be suitable for investigating disturbances of renal medullary circulation in human subjects.

Treatment of everolimus-resistant metastatic renal cell carcinoma with VEGF-targeted therapies.

BACKGROUND: Treatment of everolimus-resistant disease remains largely undefined in metastatic renal cell carcinoma (mRCC). We report on 40 patients (pts) who receive systemic treatment after failure of everolimus. PATIENTS AND METHODS: Forty pts received sunitinib (n=19), sorafenib (n=8), dovitinib (n=10) or bevacizumab/interferon (n=3) after failure of everolimus. Median progression-free survival (PFS), overall survival (OS) and best tumour response (according to Response Evaluation Criteria In Solid Tumors) were analysed retrospectively. Kaplan-Meier, log-rank test and Cox regression analyses were used to estimate or predict OS and PFS. RESULTS: Treatment of everolimus-resistant disease was associated with a PFS of 5.5 months. (range 0.4-22.3) and an objective partial remission (PR) in 4 pts (10%) and stable disease (SD) in 22 pts (55%). In univariate analyses, first-line treatment with sorafenib was the only variable to correlate with a prolonged PFS of treatment in everolimus-resistant disease (P=0.036). However, its significance as a predictive marker for subsequent therapy could not be verified in multivariate analyses. CONCLUSIONS: Vascular endothelial growth factor targeted therapy shows promising activity in everolimus-resistant metastatic renal cancer and warrants further studies.

[Introduction of interdisciplinary prostate cancer centers based on the recommendations of the German Cancer Society. A cost-benefit analysis 3 years after accreditation]. / Etablierung von interdisziplinären Prostatakrebszentren nach den Empfehlungen der DKG. Eine Kosten-Nutzen-Analyse 3 Jahre nach Zertifizierung.

The introduction of prostate cancer treatment centers according to the criteria of the German Cancer Society ("Deutsche Krebsgesellschaft", DKG) aims at improving the quality of care for patients with prostate cancer. Systematic analyses of the effects and costs are lacking as yet. Three years after certification of the Interdisciplinary Prostate Cancer Center at the Charité Hospital Berlin we observed a decrease in the rate of positive surgical margins (tumor stage pT2), but other parameters of treatment quality including patient satisfaction remained unchanged. A survey among urologists of the region showed a high acceptance of prostate cancer centers in general. The majority of participating urologists appreciated the work of the Charité center, in particular the treatment recommendations given by the center were mostly followed and the majority of urologists regularly use educational activities of the center. However, only 30% of the participating urologists confirmed short-term improvements in the quality of patient care. Yearly additional costs for the Charité prostate cancer center are estimated at 205,000 euro (precertification phase and certification) and 138,000 euro (monitoring phase), despite the initial drop in mean treatment costs per case (radical prostatectomy). The introduction of prostate cancer treatment centers certified by the DKG is cost intensive, increases in treatment efficiency notwithstanding. Short-term improvements in quality of care cannot be unequivocally demonstrated. Prostate cancer centers serve an important role in counseling and medical education and may thus help disseminate evidence-based treatment strategies.

Outcome of treatment discontinuation in patients with metastatic renal cell carcinoma and no evidence of disease following targeted therapy with or without metastasectomy.

BACKGROUND: It is unknown if discontinuation of targeted therapy (TT) and readministration in case of recurrence is feasible in patients with metastatic renal cell carcinoma (mRCC) in which complete response (CR) is achieved by TT alone or no evidence of disease (NED) with additional resection of residual metastases. PATIENTS AND METHODS: Patients in whom TT was discontinued after CR to TT alone or NED after additional metastasectomy were included in this retrospective analysis. Outcome criteria evaluated were time off TT, recurrence of metastases and response to re-exposure to TT. Univariate and multivariate analyses were carried out to identify variables potentially predictive of outcome. RESULTS: In 36 patients with CR or NED under TT with sunitinib (22), sorafenib (11), bevacizumab/interferon (2) and temsirolimus (1), TT was discontinued. Recurrence was observed in 24 patients (66.7%). Re-exposure to TT was effective in 86.9% of these cases. Twelve patients (33.3%) remained recurrence free at a median follow-up of 12 months (range 3-31). Median time off TT was 7 months (range 1-31). Factors that correlate with outcome could not be identified. CONCLUSIONS: In the majority of patients with mRCC and CR or NED, discontinuation of TT was followed by recurrence, but re-exposure to TT was effective.

Treatment of otosclerosis with a superelastic nitinol piston: first results.

Stapedotomy with implantation of an alloplastic prosthesis is a well-established therapy for the treatment of otosclerosis. Since the middle of 2008, a new Nitinol prosthesis with memory function and superelastic properties has been available which is expected to make fixation on the long process of the incus much easier. The advantage of this prosthesis is that heat-induced wire crimping is no longer necessary and damage to the incus caused by heat is avoided. Since May 2008, laser-assisted stapedotomy with implantation of a Nitinol prosthesis was performed in 21 patients suffering from otosclerosis. The prostheses used for all patients had a size of 4.5 mm × 0.4 mm. The patient collective consisted of 14 women and 7 men with a mean age of 53.4 years. Pre- and postoperatively, an ENT examination was carried out followed by an audiological evaluation of the hearing result. In addition, the properties of the prosthesis ("proper fitt", "handling", and "overall rating") were evaluated intraoperatively by means of a test protocol. The Nitinol prosthesis was implanted successfully in all 21 patients. The mean air-bone gap for the frequencies from 0.5 to 4 kHz was 9.83 dB postoperatively. Intraoperatively, the fit of the prosthesis was rated as "good to very good", the handling as "good" and the overall rating of the system was "good to very good". Our patient collective showed good postoperative hearing results. Due to simple intraoperative handling, especially placing the Nitinol prosthesis in position, the critical work step of crimping is no longer necessary.

[Incarcerated hernia after laparoscopic drainage of a lymphocele]. / Inkarzerierte Hernie nach laparoskopischer Lymphozelenfensterung.

Laparoscopic lymphocele drainage is considered the gold standard for the treatment of lymphoceles after kidney transplantation. We report on a female patient who developed a symptomatic posttransplant lymphocele. After laparoscopic lymphocele drainage the patient presented with acute pain in the left lower abdomen. A CT scan showed a hernia into the peritoneal window. This is a rare but potentially severe complication after intraperitoneal lymphocele drainage. CT imaging and swift reoperation with enlargement of the peritoneal window are critical to avoid serious complications. To avoid bowel incarceration, the peritoneal window should be as large as possible.

[What is most important is what comes across : Urological guidelines from the target group's point of view]. / Entscheidend ist, was ankommt : Urologische Leitlinien aus Sicht der Zielgruppe.

BACKGROUND: Guidelines are developed to improve the quality of patient care. The effect of German urologic guidelines has not been evaluated so far. Therefore, we aimed to systematically investigate the acceptance, use, and quality of the published guidelines from a user's perspective. METHODS: A link to an online questionnaire concerning use and barriers to the application of guidelines was distributed via e-mail by the German Society of Urology (DGU). German urologists' opinions on differences in national guideline quality were evaluated regarding prostate cancer (PCA), bladder cancer, germ cell tumors (GCT), renal cell carcinomas, and erectile dysfunction. RESULTS: Four hundred sixty-seven German urologists participated. More than 90% of the participants considered guidelines to be helpful. The Internet as the main tool for guideline distribution was favored by 28.4%, followed by publication in Urologe A. The main barrier to guideline usage was attributed to the lack of up-to date clinical data. Guidelines for GCT scored best in all quality categories and reached the highest level of use (65.8%), and 40.5% of participating urologists considered the additional establishment of comprehensive care centers for GCT as more effective for quality improvement than guideline development alone. For the other urologic tumors, especially PCA, guideline development was favored as a tool for quality improvement. CONCLUSION: More than 90% of participating urologists accept clinical guidelines as useful instruments in clinical practice and for therapeutic decisions. Our results should be integrated into guideline dissemination and implementation strategies in order to achieve a higher degree of treatment conformation to guidelines.

[Postoperative and adjuvant intravesical therapy of superficial bladder tumours. Clinical practice and applied therapeutic agents]. / Intravesikale Instillationstherapie beim oberflächlichen Harnblasenkarzinom, Leitlinien und Wirklichkeit: Versorgungsstudie.

BACKGROUND: The aim of this questionnaire was to obtain an impression of the practice and applied therapeutic agents in postoperative and adjuvant intravesical therapy of superficial bladder tumours. PATIENTS AND METHODS: Standardised questionnaires answered by urologists about instillation therapy in 351 patients were analysed. RESULTS: Results showed a discrepancy between the clinical practice and the guidelines in respect of the postoperative instillations and the use of BCG immunotherapy, respectively. CONCLUSION: It does not seem to be standard practice to treat every patient with one immediate post-operative instillation. Only a minority of high-risk patients received intravesical BCG instillations. Substances mainly used for instillation therapy were mitomycin C and doxorubicin.

[Histiocytosis of Langerhans cells. Simultaneous manifestation in both mastoid cavities]. / Langerhans-Zell-Histiozytose. Simultane Manifestation in beiden Mastoidhöhlen.

Histiocytosis X (Langerhans cells) is a rare disease with different forms of manifestation in the head and neck, which mostly occurs in children. We report the case of a 52-year-old male patient from Saudi Arabia who presented in the out-patient department of the University Hospital Charité Berlin with therapy-resistant otitis externa. ENT examination additionally showed nasal polyps. A paranasal computed tomography scan revealed as an incidental finding a mass forming tumor in both mastoids with osseous destruction of the posterior cranial fossa. Histological evaluation of the suspected tissue revealed histiocytosis X in both mastoids. After exclusion of a systemic disease local low-dose radiotherapy with 9 Gy (3x3 Gy) of the mastoid cavities was administered.

[Testicular cancer - explanatory models for high cisplatin chemosensibility and new therapeutic options]. / Testikuläre Keimzelltumoren - Erklärungsmodelle für die hohe Ansprechrate auf Cisplatin-basierte Chemotherapien und neue Therapieoptionen.

This article offers a review about the current facts of chemotherapy in testicular cancer. Besides a short presentation of the guideline-standard therapy the authors deal with the question as to why testicular cancer shows an extraordinarily high chemosensibility compared to other tumours. Furthermore, the current data on alternative chemotherapies as well as of molecular, molecular-genetic and pharmacogenetic therapeutic concepts are explored. Data were obtained from researches in Medline of the Pubmed database.

[Expression levels of the IAP antagonists XAF1, Smac/DIABLO and HtrA2 in testicular germ cell tumours]. / Expression der pro-apoptotischen Apoptoseinhibitor-(IAP)Antagonisten XAF1, Smac/DIABLO und HtrA2 in Keimzelltumoren des Hodens.

PURPOSE: Down-regulation of the IAP antagonistis XAF1, Smac/DIABLO and HtrA2, has been related to the onset and progression of various malignancies. We examined the mRNA-expression of these pro-apoptotic parameters in testicular germ cell tumors (TGCT) and normal testicular tissue and correlated their expression levels to clinicopathological tumour features. MATERIAL AND METHODS: Real-time RT-PCR was used to quantify the mRNA-expression of XAF1, Smac/DIABLO and HtrA2 in normal testicular tissue (n = 18), carcinoma in situ (n = 4), seminomas (n = 64), and non-seminomatous germ cell tumors (n = 35). RESULTS: Compared to normal testicular tissue, the expression levels of XAF1 were increased in TGCT (p < 0.001), whereas those of Smac/DIABLO and HtrA2 were decreased (p < 0.001 and p < 0.001). Smac/DIABLO expression levels showed a significant trend towards a gradual decrease from normal testicular tissue to CIS and seminomas and finally to NSGCT (p < 0.001). Moreover, XAF1 and HtrA2 expression levels gradually increased with progression of clinical tumour stage in seminoma patients (p = 0.001 and p = 0.018), their expression levels being strongly intercorrelated (Spearman rho correlation coefficient: 0.674; p < 0.001). CONCLUSION: These data suggest that a down-regulation of Smac/DIABLO and HtrA2 is implicated in the development and progression of TGCT, whereas overexpression of XAF1 in TGCT might contribute to their extraordinary sensitivity to chemotherapy. Regarding the additional correlation of XAF1 and HtrA2 expression with clinical tumour stage in seminoma patients, it appears reasonable to further evaluate these three IAP antagonists as molecular parameters for the prediction of treatment response and prognosis of TGCT patients.

Expression parameters of the polycomb group proteins BMI1, SUZ12, RING1 and CBX7 in urothelial carcinoma of the bladder and their prognostic relevance.

BACKGROUND: The polycomb group (PCG) proteins are epigenetic transcriptional repressors involved in the control of cellular proliferation and oncogenesis. This study aimed at examining whether mRNA tumor levels of the PCG family members BMI1, SUZ12, RING1, and CBX7 relate to histopathological parameters in urothelial carcinomas of the bladder and whether they may provide prognostic information following tumor resection. METHODS: The relative gene expression of BMI1, SUZ12, RING1, and CBX7 was analyzed by real-time RT-PCR in tumor tissue obtained from 93 patients with urothelial carcinoma of the bladder undergoing surgical treatment. Expression data was correlated with pathological variables and outcome. RESULTS: PCG family members BMI1, SUZ12, RING1, and CBX7 are commonly expressed in urothelial carcinomas of the bladder. The relative CBX7 mRNA expression levels gradually decreased from superficial (pTa) to invasive (pT1) and finally to muscle-invasive (> or =pT2) tumors (p = 0.008). Furthermore, CBX7 expression was statistically significantly correlated with tumor grade (p = 0.04). No correlation of mRNA levels with histopathological tumor features or tumor recurrence was observed for the other PCG components investigated. CONCLUSION: Expression levels of CBX7 inversely correlate with the progression of tumor stage and grade in urothelial carcinomas of the bladder, suggesting that downregulation of CBX7 indicates aggressive urothelial carcinoma phenotype.

Low-frequency distortion product otoacoustic emission test compared to ECoG in diagnosing endolymphatic hydrops.

Previous studies assumed that specific audiometric measures like low-frequency biasing were noninvasive and inexpensive techniques for diagnosing endolymphatic hydrops (EH). The aim of this study was to compare the results of low-frequency DPOAE (LF-DPOAE) with those of transtympanic electrocochleography (ECoG) in patients with Menière's disease (MD). The prospective study included 50 patients, 22 to 72 years old, who were diagnosed with Menière's disease according to the criteria laid down by the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) in 1995. LF-DPOAE and ECoG were performed on the same day after standard audiometry. Enlarged amplitude of summation potential to action potential ratio was used as the diagnostic criterion for EH. The results were compared to those of LF-DPOAE. In this audiometric examination we used the modulation index (MI) to detect EH if MI < 0.5. ECoG yielded a result in 46 of the 50 patients examined. An enlarged SP/AP ratio was found in 23 patients (50%). The results of 33 patients could be compared, i.e. assessable results in both tests. The two tests yielded the same results in 13 patients and different ones in 20 patients. ROC analysis and Mann-Whitney statistics showed no significant correlation between the two tests. With ECoG as the gold standard for verifying EH, we found that LF-DPOAE is not yet a suitable method for diagnosing EH.

EZH2 polycomb transcriptional repressor expression correlates with methylation of the APAF-1 gene in superficial transitional cell carcinoma of the bladder.

The EZH2 gene controls methylation of various EZH2 target promoters. The APAF-1, DAPK-1 und IGFBP-3 genes are frequently methylated in bladder cancer, and methylation of these genes is found in more aggressive tumor types. The aim of our study was to investigate a potential link between EZH2 mRNA expression and the extent of APAF-1, DAPK-1 and IGFBP-3 methylation in urothelial transitional cell carcinoma (TCC) and to correlate the data with histopathological parameters and follow-up data. EZH2 mRNA expression was measured by real-time reverse transcription polymerase chain reaction, and the methylation analysis was performed using methylation-specific real-time polymerase chain reaction. Tissue specimens were obtained from 35 patients with TCC. EZH2 mRNA expression was detected in all tumor specimens investigated. The EZH2 expression levels correlated well with the differentiation grade of the tumor specimens (p = 0.03), and the APAF-1 methylation correlated with tumor stage (p = 0.0001) and grade (p = 0.004). Matched pair analysis demonstrated a statistically significant correlation between elevated EZH2 mRNA expression and higher methylation levels of APAF-1 in superficial (p = 0.024) and well- differentiated (p = 0.04) TCC. In patients with recurrent TCC, APAF-1 and IGFBP-3 methylation levels were significantly higher (p = 0.03 and p = 0.01, respectively), which was not observed when EZH2 mRNA expression or DAPK-1 methylation levels were related to the clinical outcome. In conclusion, our data show that EZH2 expression and APAF-1 methylation are related to tumor progression and invasiveness. Moreover, these data present first evidence that APAF-1 methylation is related to transcriptional activity of EZH2 expression in early-stage tumor disease of the bladder.

Frequent epigenetic inactivation of p53 target genes in seminomatous and nonseminomatous germ cell tumors.

Hypermethylation of tumor-suppressor genes has been implicated in the pathogenesis of human cancers. This study was designed to examine the methylation profiles of a selected group of p53 target genes (APAF-1, CASP-8, DAPK-1, IGFBP-3) and to correlate the findings with the histopathological characterization of testicular germ cell tumors (TGCT). Promoter methylation status was analysed by highly sensitive real-time methylation-specific PCR in 46 primary TGCTs (26 seminomas and 20 nonseminomas) and 15 normal testicular tissue samples. APAF-1 methylation was detected in all of the seminomatous and nonseminomatous TGCTs as well as in 60% of normal testicular tissue. Methylation of DAPK-1 was frequent in seminomas (50%) and nonseminomas (20%), but not in normal testicular tissue (6%). The degree of DAPK-1 methylation correlated with the clinical stage of the disease (P=0.05) and was useful in differentiating seminomatous from nonseminomatous, and malignant from nonmalignant testicular tissue (P=0.04 and 0.02, respectively). The APAF-1 methylation index achieved a highly significant differentiation between seminomatous or nonseminomatous tissue and nonmalignant testicular tissue (P=0.0001). In testicular tumorigenesis, promoter methylation of specific p53 target genes occurs at early stage but to varying degrees. Methylation also occurs in normal testicular tissue, which is in contrast to findings in other urogenital malignancies. Further studies will be necessary to determine whether the methylation level may be used as marker for risk estimation, especially in clinical stage I disease.

Methylation of tumour suppressor genes APAF-1 and DAPK-1 and in vitro effects of demethylating agents in bladder and kidney cancer.

To examine the significance of the methylation level of the p53 target and tumour suppressor genes apoptotic protease activating factor-1 (APAF-1) and death-associated protein kinase-1 (DAPK-1) in 80 microdissected tumour samples from transitional cell carcinoma (TCC) of the bladder and 80 tumour samples from clear-cell renal cell carcinoma (RCC) as well as from non-tumourous bladder and kidney tissue. Growth-inhibitory effects of the demethylating agents 5-Aza-2'-deoxycytidine (5-Aza-CdR) and zebularine were investigated in TCC and RCC cell lines. The methylation frequency of APAF-1 (DAPK-1) was 100% (77%) in TCC and 100% (33%) in RCC. The methylation levels of APAF-1 could differentiate between the individual tumour stages in TCC as well as in RCC. The APAF-1 methylation levels in RCC were significantly higher in tumours larger than 4 cm and in high-grade tumours. The methylation frequencies in normal tissue for APAF-1 (DAPK-1) were 11% (8%) in bladder tissue and 9% (5%) in kidney tissue. The growth-inhibitory effect of the demethylating agents in TCC (RT4, T24) and RCC (A498, ClearCa-5) cell lines resulted in a 17-132% prolongation of the doubling time (DT). In RCC cell lines, zebularine was superior to 5-Aza-CdR in achieving a DT prolongation. Quantitative real time RT-PCR detected a re-expression of mRNA transcripts of APAF-1 or DAPK-1. In conclusion, demethylating agents effectively retard growth of TCC and RCC cell lines. Methylation level analysis of specific genes has the potential for further tumour characterisation in TCC and RCC.

[Rectal perforation as a late complication of ProACT implantation]. / Rektumperforation als Spätkomplikation einer ProACT-Implantation.

Operative approaches to solve severe urinary incontinence following radical prostatectomy include artificial urinary sphincters, bulking agents, urethral sling procedures, and the ProACT device (Uromedica Inc.). Previously reported complications of the ProACT procedure comprise ruptures and dislocations of balloons as well as erosions and perforations of the bladder or urethra. We report the case of a rectal perforation as a late complication of the ProACT procedure after prostatectomy and adjuvant radiotherapy. To the best of our knowledge this complication has not been described before.