[Oxygenation-sensitive cardiac magnetic resonance imaging]. / Sauerstoffsensitive kardiale Magnetresonanztomographie.

BACKGROUND: Oxygenation-sensitive cardiac magnetic resonance imaging (OS-CMR) is an evolving cardiac imaging technique offering new perspectives to understand, predict, and diagnose cardiac pathologies. OBJECTIVES: To provide an overview of the basic principles of OS-CMR, the current diagnostic applications and how it may aid in future diagnostic challenges. MATERIALS AND METHODS: Description, analysis, and interpretation of the current literature on basic research and applicational studies in both humans and animals assessing OS-CMR. RESULTS: OS-CMR is based on the paramagnetic properties of deoxygenated hemoglobin, which is visualized by a T2*-sensitive sequence. The measured signal correlates with the oxygenation of the myocardium and can analyze vascular function during pharmacological vasodilation or vasoactive breathing exercises (hyperventilation, apnea). The herewith triggered changes in myocardial oxygenation and oxygenation reserve can be used to identify relevant stenoses in coronary artery disease. Other areas of application involve myocardial hypertrophy, microvascular dysfunction, and pulmonary hypertension. CONCLUSION: A broad number of applications for the clinical use of OS-CMR exist so far, especially in combination with breathing exercises. OS-CMR can be conducted medication- and needle-free. Limitations involve the current lack of clinically approved, automated evaluation tools and the unavailability of vendor- and site-independent normal values.

The diagnostic accuracy of truncated cardiovascular MR protocols for detecting non-ischemic cardiomyopathies.

Cardiovascular magnetic resonance imaging is one of the most important diagnostic modalities in the evaluation of cardiomyopathies. However, significant limitations are the complex and time-consuming workflows and the need of contrast agents. The aim of this multi-center retrospective study was to assess workflows and diagnostic value of a short, contrast agent-free cardiac magnetic resonance protocol. 160 patients from Heidelberg, Germany and 119 patients from Montreal, Canada with suspected cardiomyopathy and 20 healthy volunteers have been enrolled. Scans were performed at a 1.5Tesla or 3Tesla scanner in Heidelberg and at a 3Tesla scanner in Montreal. We used single-slice T1 map only. A stepwise analysis of images has been performed. The possible differential diagnosis after each step has been defined. T1-values and color-encoded T1 maps significantly contributed to the differential diagnosis in 54% of the cases (161/299); the final diagnosis has been done without late gadolinium enhancement images in 83% of healthy individuals, in 99% of patients with dilated cardiomyopathy, in 93% of amyloidosis patients, in 94% of patients with hypertrophic cardiomyopathy and in 85% of patients with hypertensive heart disease, respectively. Comparing the scan time with (48 ± 7 min) vs. without contrast agent (23 ± 5 min), significant time saving could be reached by the short protocol. Subgroup analysis showed the most additional diagnostic value of T1 maps in amyloidosis and hypertrophic cardiomyopathy or in confirmation of normal findings. In patients with unclear left ventricular hypertrophy, a short, non-contrast protocol can be used for diagnostic decision-making, if the quality of the T1 map is diagnostic, even if only one slice is available.

Modifications of Surgical Suction Tip Geometry for Flow Optimisation: Influence on Suction-Induced Noise Pollution.

INTRODUCTION: Suction devices for clearing the surgical field are among the most commonly used tools of every surgeon because a better view of the surgical field is essential. Forced suction may produce disturbingly loud noise, which acts as a nonnegligible stressor. Especially, in emergency situations with heavy bleeding, this loud noise has been described as an impeding factor in the medical decision-making process. In addition, there are reports of inner ear damage in patients due to suction noises during operations in the head area. These problems have not been solved yet. The purpose of this study was to analyse flow-dependent suction noise effects of different surgical suction tips. Furthermore, we developed design improvements to these devices. METHODS: We compared five different geometries of suction tips using an in vitro standardised setup. Two commercially available standard suction tips were compared to three adapted new devices regarding their flow-dependent (10-2000 mL/min) noise emission (dB, weighting filter (A), distance 10 cm) and acoustic quality of resulting noises (Hamilton fast Fourier analysis) during active suction at the liquid-air boundary. Noise maps at different flow rates were created for all five suction devices, and the proportion of extracted air was measured. The geometries of the three custom-made suction tips (new models 1, 2, and 3) were designed considering the insights after determining the key characteristics of the two standard suction models. RESULTS: The geometry of a suction device tip has significant impact on its noise emission. For the standard models, the frequency spectrum at higher flow rates significantly changes to high-frequency noise patterns (>3 kHz). A number of small side holes designed to prevent tissue adhesion lead to increased levels of high-frequency noise. Due to modifications of the tip geometry in our new models, we are able to achieve a highly significant reduction of noise level at low flow rates (new model 2 vs. standard models p < 0.001) and also the acoustic quality improved. Additionally, we attain a highly significant reduction of secondary air intake (new model 2 vs. the other models p < 0.001). CONCLUSION: Improving flow-relevant features of the geometry of suction heads is a suitable way to reduce noise emissions. Optimized suction tips are significantly quieter. This may help us to reduce noise-induced hearing damage in patients as well as stress of medical staff during surgery and should lead to quieter operation theatres overall. Furthermore, the turbulence reduction and reduced secondary air intake during the suction process are expected to result in protective effects on the collected blood and thus could improve the quality of autologous blood retransfusions. We are on the way to evaluate potential benefits.

Guidelines for training in cardiovascular magnetic resonance (CMR).

These "Guidelines for training in Cardiovascular Magnetic Resonance" were developed by the Certification Committee of the Society for Cardiovascular Magnetic Resonance (SCMR) and approved by the SCMR Board of Trustees.

Age and gender effects on the extent of myocardial involvement in acute myocarditis: a cardiovascular magnetic resonance study.

OBJECTIVE: Based upon epidemiological studies, male gender and younger age are risk factors for developing fatal myocarditis. The impact of age and gender on myocardial injury pattern in acute myocarditis, however, is not well understood. In patients with clinically acute myocarditis, this study sought to characterise the relation between patient age and gender and the extent of myocardial involvement using cardiovascular magnetic resonance (CMR) imaging. CMR markers for oedema, inflammation and fibrosis defined myocardial involvement. DESIGN, SETTING AND PATIENTS: 65 patients (42 years old (SD 15), 41 male) with clinically acute myocarditis were assessed. Using standard methods, T2-weighted and contrast-enhanced T1-weighted (early and late enhancement) CMR images were acquired. T2 images were visually and quantitatively assessed for oedema. Early enhancement images were quantified for inflammation, as was regional fibrosis in late enhancement images. Data were analysed for groups of age (>40, <40 years) and gender. RESULTS: 62% of all patients had evidence of regional oedema, which was more prevalent in patients below 40 years of age (80.7% vs 51.3%, p<0.05), as was myocardial fibrosis (76.9% vs 48.7%, p<0.05). However, early enhancement was more frequently found in patients above 40 years (84.2% vs 61.5%, p<0.05). Men were twice as likely as women to demonstrate myocardial fibrosis (73.2 vs 37.5%, p<0.01). CONCLUSION: In patients with clinically acute myocarditis, myocardial fibrosis was more frequent in men and in patients younger than 40 years. Injury sustained in younger patients appears to be more regional and more severe, as indicated by a higher incidence of irreversible injury.

[Comparison of the effectiveness between long-term instillation of mitomycin C and short-term prophylaxis with MMC or bacille Calmette-Guérin. Study of patients with non-muscle-invasive urothelial cancer of the urinary bladder]. / Vergleich der Effektivität der Langzeitinstillation mit Mitomycin C gegen Kurzzeitprophylaxen mit MMC oder Bacillus Calmette-Guerin. Untersuchung bei Patienten mit nicht muskelinvasivem Urothelkarzinom der Harnblase.

BACKGROUND: Adjuvant instillation therapy with chemo- or immunotherapeutic agents is an integral component in the treatment of non-muscle-invasive bladder cancer. There is, however, no general consensus on the choice of medication and the optimal duration of therapy. This multicenter trial compared a long-term treatment regimen with mitomycin C (MMC) with two short-term treatment approaches with MMC or bacille Calmette-Guérin (BCG) for intermediate-/high-risk bladder tumor after transurethral resection. In patients with low-risk bladder tumors, the effectiveness of six weekly MMC instillations was determined and compared with the results of patients not receiving adjuvant treatment. MATERIAL AND METHODS: A total of 495 patients with intermediate-/high-risk bladder tumor (recurrent and/or multifocal pTaG1, pTaG2-3, or pT1G1-3) were randomly administered either BCG-RIVM 2x108 CFU in six weekly instillations, MMC 20 mg in six weekly instillations, or MMC 20 mg in six weekly instillations with subsequent monthly instillations for 3 years. A total of 132 low-risk patients (first diagnosis of a unifocal pTaG1 bladder tumor) were randomly allocated to two treatment arms. In the first arm, 20 mg MMC were instilled weekly six times. In the control arm, the patients received no adjuvant therapy. RESULTS: The 3-year recurrence-free rate in the patients of the intermediate-/high-risk group was 65.5% (95% CI: 55.9-73.5%) in the BCG arm and 68.6% (95% CI: 59.9-75.7%) in the MMC short-term arm. In the MMC long-term arm, the 3-year recurrence-free rate was significantly higher at 86.1% (95% CI: 77.9-91.4%, log-rank test: p=0.001). There was no increased toxicity observed with long-term administration of MMC. In the low-risk group, the 3-year recurrence-free rate after adjuvant therapy was 74% (95% CI: 60.0-83.8%) and in the patients receiving no adjuvant treatment 63% (95% CI: 46.6-75.5%, corresponding to a hazard ratio of 0.58 (95% CI: 0.28-1.18%). The difference between the treatment arms was not significant. CONCLUSION: Long-term prophylaxis with MMC results in a significantly reduced recurrence rate in intermediate-/high-risk bladder cancer with a comparable toxicity profile in comparison to short-term MMC or short-term BCG. Our study showed no significant decrease of the recurrence rate in low-risk tumors with six adjuvant MMC instillations. This treatment approach thus does not represent an alternative to early instillation.

[One molecule, two faces. Epithelial loss of cell adhesion molecule CEACAM1 activates angiogenesis in bladder and prostate cancer]. / Ein Molekül, zwei Gesichter. Epithelialer Verlust des Zelladhäsionsmoleküls CEACAM1 aktiviert Angiogenese beim Harnblasen- und Prostatakarzinom.

BACKGROUND: Angiogenesis is a prerequisite for tumor growth and metastasis in which CEACAM1 plays an essential role. PATIENTS AND METHODS: The role of CEACAM1 in vascularization and invasion of prostate and bladder cancer was studied. RESULTS: Our analyses demonstrate an epithelial downregulation of CEACAM1 in superficial bladder tumors and in PIN of the prostate. Concurrently, CEACAM1 is upregulated in endothelial cells of tumor blood vessels. CEACAM1 knockdown in tumor cell lines of the prostate and urinary bladder via siRNA results in an increase of tumor vascularization while CEACAM1 overexpression in these cells suppresses it. CONCLUSIONS: CEACAM1-induced signaling mechanisms play a role in induction of angiogenesis in superficial tumors of the prostate and bladder. Strategies to either conserve the epithelial CEACAM1 or to target endothelial CEACAM1 might be useful for an antiangiogenic therapy of bladder and prostate cancer.

[DNA methylation on urinalysis and as a prognostic marker in urothelial cancer of the bladder]. / DNA-Methylierung in der Urindiagnostik und als Prognosemarker beim Urothelkarzinom der Harnblase.

INTRODUCTION AND OBJECTIVES: Detection of promoter hypermethylation has been proposed as a promising tool for cancer diagnosis and as a prognostic marker in various cancers. We studied the versatility of DNA methylation for noninvasive diagnosis and as a prognostic marker for non-muscle-invasive bladder carcinoma. METHODS: Tumor specimens were microdissected and DNA was extracted from 105 paraffin-embedded paraffin specimens from patients undergoing transurethral resection for non-muscle-invasive bladder carcinoma. Urine specimens were collected from patients undergoing cystectomy for bladder cancer and from healthy volunteers. Methylation status was assessed with the real-time quantitative methylation-sensitive PCR (MethyLight). We checked a panel of 20 cancer-associated genes (p14ARF, p16 CDKN2A, STAT-1, SOCS-1, DR-3, DR-6, PIG-7, BCL-2, H-TERT, BAX, EDNRB, DAPK, RASSF-1A, FADD, TMS-1, E-CADHERIN, ICAM-1, TIMP-3, MLH-1, COX-2) for DNA methylation. RESULTS: Follow-up data were available in 95 of 105 patients (91.4%). A tumor recurrence was observed in 26 patients (27.3%). We could identify six genes (SOCS-1, STAT-1, BCL-2, DAPK, TIMP-3, E-cadherin), where methylation was associated with tumor recurrence. In Kaplan-Meier analysis, TIMP-3 showed a significant association with recurrence-free survival. Methylation of TIMP-3 predicted prolonged disease-free interval. Regarding urinalysis we could identify a pattern of methylation markers including DAPK, BCL-2, and H-TERT that yielded a sensitivity of 81.1% with a specificity of 100% in a cancer-free control population CONCLUSIONS: We present data on the clinical usefulness of methylation analysis in bladder carcinoma. Our data confirm that methylation analysis is a promising tool for bladder cancer diagnosis and prognosis.

[Technical aspects of nerve sparing during retropubic prostatectomy]. / Aspects techniques de la préservation nerveuse au cours de la prostatectomie rétropubienne.

Retropubic radical prostatectomy is the most commonly used therapeutic option for the treatment of clinically localized prostate cancer. An ongoing stage migration towards organ-confined cancers allows performing a nerve-sparing procedure in a growing number of patients. Key elements for achieving convincing functional results are a sphincter preserving Ligation of the distal part of Santorini's plexus and the subtle preparation of the neurovascular bundle. This article gives a detailed description of the operative technique. Furthermore, a strategy for patient selection and tumour selection for the indication of nerve-sparing radical prostatectomy (NSRP) is suggested.

CCS/CAR/CANM/CNCS/CanSCMR joint position statement on advanced noninvasive cardiac imaging using positron emission tomography, magnetic resonance imaging and multidetector computed tomographic angiography in the diagnosis and evaluation of ischemic heart disease--executive summary.

BACKGROUND: Over the past few decades, advanced imaging modalities with excellent diagnostic capabilities have emerged. The aim of the present position statement was to systematically review existing literature to define Canadian recommendations for their clinical use. METHODS: A systematic literature review to 2005 was conducted for positron emission tomography (PET), multidetector computed tomographic angiography and magnetic resonance imaging (MRI) in ischemic heart disease. Papers that met the criteria were reviewed for accuracy, prognosis data and study quality. Recommendations were presented to primary and secondary panels of experts, and consensus was achieved. RESULTS: Indications for PET include detection of coronary artery disease (CAD) with perfusion imaging, and defining viability using fluorodeoxyglucose to determine left ventricular function recovery and/or prognosis after revascularization (class I). Detection of CAD in patients, vessel segments and grafts using computed tomographic angiography was considered class IIa at the time of the literature review. Dobutamine MRI is class I for CAD detection and, along with late gadolinium enhancement MRI, class I for viability detection to predict left ventricular function recovery. Imaging must be performed at institutions and interpreted by physicians with adequate experience and training. CONCLUSIONS: Cardiac imaging using advanced modalities (PET, multidetector computed tomographic angiography and MRI) is useful for CAD detection, viability definition and, in some cases, prognosis. These modalities complement the more widespread single photon emission computed tomography and echocardiography. Given the rapid evolution of technology, initial guidelines for clinical use will require regular updates. Evaluation of their integration in clinical practice should be ongoing; optimal use will require proper training. A joint effort among specialties is recommended to achieve these goals.

CEA-related cell adhesion molecule-1 is involved in angiogenic switch in prostate cancer.

We demonstrate here that epithelial carcinoembryonic antigen (CEA)-related cell adhesion molecule-1 (CEACAM1) downregulation in prostate intraepithelial neoplasia (PIN) is inversely correlated with its upregulation in adjacent blood vessels. CEACAM1 silencing in prostate cancer cell line DU-145 via small interfering ribonucleic acid (siRNA) increased but its overexpression suppressed the expression of angiogenic/lymphangiogenic factors such as vascular endothelial growth factor (VEGF)-A, -C and -D, and angiogenic inhibitor collagen 18/endostatin. Furthermore, CEACAM1 overexpression in DU-145 cells increased but CEACAM1 silencing reduced angiopoietin-1 expression. Inverse relation was found for angiopoietin-2. Supernatant of CEACAM1-overexpressing DU-145 suppressed but that of CEACAM1-silenced increased the VEGF-induced endothelial tubes. Electron microscopically the majority of PIN-associated blood vessels was structurally destabilized exhibiting endothelial fenestration, trans- and inter-endothelial gaps. In some PIN areas, invasion of single tumor cells into the destabilized blood vessels was observed. These data show that disappearance of epithelial CEACAM1 in PIN is accompanied by its upregulation in adjacent vasculature which apparently correlates with vascular destabilization and increased vascularization of prostate cancer. Strategies to either conserve the epithelial CEACAM1 or to target endothelial CEACAM1 might be useful for an anti-angiogenic therapy of prostate cancer.

[Success rates of two-layer, microsurgical vasovasostomy. Results from a patient questionnaire and comparison with one-layer technique]. / Erfolgsraten der zweischichtigen mikrochirurgischen Vasovasostomie. Ergebnisse einer Patientenbefragung und Vergleich mit der einschichtigen Technik.

UNLABELLED: Vasovasostomy is the most commonly performed procedures in the therapy for occlusive azoospermia after vasectomy. In our clinic the two-layer microsurgical technique (DL VVST) is considered to be the gold standard. We have examined the results of DL VVST by means of a questionnaire and compared them with those of the monolayer technique (ML VVST). MATERIALS AND METHOD: In the period from 1996 to 2001, a microsurgical DL VVST with 10 x 0 Prolene sutures under the operation microscope was performed in 141 patient. Aspects of the operation, social aspects and postoperative results (results of spermiogram, birth rates) were assessed by means of a questionnaire. The results were compared with those of a historical patient collective who had undergone a modified monolayer VVST with 7 x 0 Prolene (n = 64). RESULTS: The questionnaire could be sent to 90/141 patients, the response rate was 63/90 (70 %). The time interval between vasectomy and VVST was on average 9.5 years. The patency rate was 86 %, the birth rate 24 %. Severe or moderately sever complications did not occur. In the historical patient collective, the average occlusion interval was 6.9 years. The patency rate in these patients in whom the VVST was performed merely under the loupe and in a monolayer technique was 87 %, the pregnancy rate 48 %. CONCLUSION: The highly positive results of VVST with pregnancy rates > 80 % from earlier publications could not be reproduced. According to our results, the two-layer VVST does not afford better results than the monolayer technique.

Myocardial first-pass perfusion magnetic resonance imaging: a multicenter dose-ranging study.

BACKGROUND: MRI can identify patients with obstructive coronary artery disease by imaging the left ventricular myocardium during a first-pass contrast bolus in the presence and absence of pharmacologically induced myocardial hyperemia. The purpose of this multicenter dose-ranging study was to determine the minimally efficacious dose of gadopentetate dimeglumine injection (Magnevist Injection; Berlex Laboratories) for detecting obstructive coronary artery disease. METHOD AND RESULTS: A total of 99 patients scheduled for coronary artery catheterization as part of their clinical evaluation were enrolled in this study. Patients were randomized to 1 of 3 doses of gadopentate dimeglumine: 0.05, 0.10, or 0.15 mmol/kg. First-pass perfusion imaging was performed during hyperemia (induced by a 4-minute infusion of adenosine at a rate of 140 microg x kg(-1) x min(-1)) and then again in the absence of adenosine with otherwise identical imaging parameters and the same contrast dose. Perfusion defects were evaluated subjectively by 4 blinded reviewers. Receiver-operating curve analysis showed that the areas under the receiver-operating curve were 0.90, 0.72, and 0.83 for the low-, medium-, and high-contrast doses, respectively, compared with quantitative coronary angiography (diameter stenosis > or =70%). For the low-dose group, mean sensitivity was 93+/-0%, mean specificity was 75+/-7%, and mean accuracy was 85+/-3%. CONCLUSIONS: First-pass perfusion MRI is a safe and accurate test for identifying patients with obstructive coronary artery disease. A low dose of 0.05 mmol/kg gadopentetate dimeglumine is at least as efficacious as higher doses.

[Cystectomy for indications other than bladder cancer]. / Die Zystektomie aus anderer Indikation als dem Blasenkarzinom.

A cystectomy for indications other than transitional cell cancer of the bladder or general bladder cancer is frequently performed in cooperation with other surgical specialties such as general surgery or gynecology. In these cases the urological procedure as well as the oncological and surgical concepts of other specialties have to be combined. We studied our cystectomy patients who had undergone such a combined procedure for a non-urothelial indication concerning perioperative and postoperative complications.A total of 204 cystectomies were performed by the Department of Urology at the University of Hamburg, Germany between 1995 and 2003. Bladder cancer was the indication for cystectomy in 162 patients, but 42 patients had a non-urothelial indication for this procedure. These patients included 12 cases of advanced rectal cancer, 9 cases of advanced cervical cancer, 6 cases of advanced sigmoid cancer, 4 cases of advanced prostate cancer, 1 case of prostate sarcoma, 5 cases of complex vesicointestinal fistulae, 2 cases of urachal cancer, 1 leiomyosarcoma, 1 rhabdomyoma, and 1 rhabdomyosarcoma, respectively. Perioperative and postoperative complications of those patients were compared to patients who underwent cystectomy for transitional cell cancer of the bladder.Those 42 patients who underwent cystectomy for non-urothelial indications included 14 male and 28 female patients. The mean age was 58.2 years with a range of 3-78 years. For urinary diversion 30 ileum conduits, 4 sigma conduits, and 8 ileum neobladders were used. The mean operative time was 6.25 h. The mean blood loss was 2200 ml. An average of four red blood cell concentrates (RBC) had to be given. Postoperative hydronephrosis had to be treated in three (7%) patients unilaterally and in two (5%) patients bilaterally with a temporary nephrostomy. Postoperative urinary leakage lasting more than 30 days was found in two (5%) patients. A deep vein thrombosis as well as an ileus was found in five (12%) patients each, respectively. There was no perioperative mortality in this study. When comparing the complications of those patients with the 162 patients who underwent cystectomy for bladder cancer, the only significant difference ( p=0.033, chi-square test) was a higher ileus rate in the patients with cystectomy for a non-urothelial indication. Complications with cystectomy for non-urothelial indications are in large comparable to those for transitional cell carcinoma of the bladder. The higher ileus rate in non-urothelial patients can be explained by the more radical procedures in this group of patients. Even though the group of patients undergoing cystectomy for indications other than bladder cancer was small in this trial, the procedure is standardized in combination with other specialties. Larger patient numbers and a longer follow-up will lead to more data in this special group of patients.

Comparison of multitarget fluorescence in situ hybridization in urine with other noninvasive tests for detecting bladder cancer.

OBJECTIVES: To present a single-centre study investigating aneuploidy at chromosomes 3, 7, 17 and 9p21 (e.g. loss at 9p21) using a multitarget fluorescence in situ hybridization (FISH) system, as identifying genetic alterations in urine specimens is a promising approach for the noninvasive detection of bladder cancer. PATIENTS AND METHODS: Urine samples from 103 patients were evaluated, including those from 46 with histologically confirmed urothelial carcinoma, two with other urological malignancies, and 55 who acted as controls. The urine samples were taken before any manipulation. The validity of FISH (Urovision, Vysis, Downers Grove, Ill, USA) was compared with other noninvasive urine tests, including the BTA-Stat test, the nuclear matrix protein (NMP)-22 test, and immunocytology against 486p3/12 and LewisX. Those evaluating the tests were unaware of the clinical and histopathological data. FISH was considered positive if five or more urinary cells had gains of two or more chromosomes. The threshold for the urine tests were 10 U/mL (NMP-22), 30% positive cells (486p3/12), or 5% positive cells, respectively (LewisX). RESULTS: The sensitivity was 69% (FISH), 67% (BTA-Stat), 69% (486p3/12), 96% (LewisX) and 71% (NMP22), respectively; the respective specificity was 89%, 78%, 76%, 33% and 66%. CONCLUSION: Multitarget FISH had a better specificity than the other urine markers but because of its inadequate sensitivity it does not seem to be powerful enough to replace endoscopy. Optimizing the marker panel could provide a higher sensitivity.

Cyclooxygenase-2 promotes angiogenesis in pTa/T1 urothelial bladder carcinoma but does not predict recurrence.

OBJECTIVE: To investigate the effect of cyclooxygenase-2 (COX-2) on microvessel density (MVD) and on the clinical prognosis in patients with non-muscle invasive urothelial carcinoma of the bladder, as COX-2 expression is significantly greater in epithelial tumours and there is increasing evidence that COX-2 might contribute to tumour neovascularization. PATIENTS AND METHODS: We assessed tumour samples from 110 patients undergoing transurethral resection for primary pTa/pT1 bladder carcinoma (pTa, 84; pT1, 26; grade 1, 22; grade 2, 81; grade 3, seven). Paraffin sections were assessed immunohistochemically using antibodies against COX-2, CD34 (endothelial cells) and CD105 (proliferating vessels). COX-2 expression was quantified by the number of stained cells (negative, +, ++) and the MVD calculated as vessels per field. RESULTS: Of the 110 tumours, 45 (41%) had no immunostaining for COX-2, 40 had faint staining with at least isolated positive cells (+) and 25 stained ++. COX-2 positive tumours had significantly greater vascularization for proliferating vessels. In COX-2 negative tumours the MVD was 22.1, identified by CD34 immunostaining, and 3.4 for proliferating vessels (CD105), whereas COX-2 positive tumours had a MVD of 18.3 (CD34), and of 5.8, respectively (CD105). Complete follow-up data were available in 91 patients; after a mean follow-up of 25 months, 18 (20%) had tumour recurrences. There was no significant difference in the recurrence rates or disease-free survival between COX-2-positive (19%, 25.6 months) or -negative patients (21%, 25.2 months). CONCLUSION: These results confirm the involvement of COX-2 in angiogenesis in bladder cancer, as COX-2 promoted blood vessel proliferation in the tumour zone, and indicate the usefulness of COX-2-inhibiting drugs in preventing and treating superficial bladder cancer.

[Non-invasive urine tests in diagnosis and as prognostic markers for urinary bladder carcinoma. Comparison of the BTAstat and NMP 22 tests with immunocytology using monoclonal antibodies against Lewis X and 486p3/12]. / Nichtinvasive Urintests in der Diagnostik und als Prognosemarker beim Harnblasenkarzinom.

INTRODUCTION AND OBJECTIVES: The non-invasive detection of urothelial carcinoma remains challenging. The aim of this study was the prospective evaluation of urine markers for bladder carcinoma. We compared the NMP 22 and BTAstat tests with immunocytology (IC) using monoclonal antibodies against the Lewis X antigen and against 486p3/12. METHODS: NMP 22 and BTAstat were performed on urine samples, and IC with 486p3/12 and Lewis X staining was performed on urine samples as well as bladder wash specimens ( n=146) in patients ( n=115) undergoing transurethral resection on suspicion of bladder cancer (70 specimens) or follow up cystoscopy because of a history of bladder cancer (76 specimens). Bladder cancer was detected in 54 patients (pTa: n=25, pT1: n=20, pT2: n=8, CiS: n=1). Cut-off levels were 10 U/ml for the NMP 22, 30% positive cells for 486p3/12, and 5% positive cells for the Lewis X test. RESULTS: The BTAstat test was positive in 65 (44.5%) cases, the NMP 22 in 69 (47.3%) cases, IC with 486p3/12 and the Lewis X was positive in 52 (35.6%) and 109 (74.7%) cases, respectively. Sensitivity was 70.3% (BTAstat), 68.5% (NMP 22), 94.4% (Lewis X), and 68.5% (486p3/12), respectively. The specificity was 70.6% (BTAstat), 65.2% (NMP 22), 36.9% (Lewis X), and 83.6% (486p3/12), respectively. Among the patients with a false positive test 2/22 (9.0%) patients (BTAstat), 2/25 (8%) patients (NMP 22 test), 4/43 (9.3%) patients (Lewis X), and 3/11 (27%) patients (486p3/12), respectively, suffered from tumor recurrence. In contrast, among the patients with a correct negative test 2/39 (2.0%) (BTAstat), 2/36 (0.5%) (NMP 22), 0/18 (0%) (Lewis X), and 1/50 (2.0%) (486p3/12), respectively, suffered from tumor recurrence. CONCLUSIONS: IC with the Lewis X revealed a higher sensitivity than all of the tested, commercially available methods. Because of its high sensitivity and its high negative predictive value, the Lewis X test may be useful for screening a high-risk population. Patients with a false positive 486p3/12 test have an increased risk of tumor recurrence when compared with patients with a correct negative test.

[Suprarenal leiomyoma of the vena cava. A rare differential adrenal gland tumor diagnosis]. / Suprarenales Leiomyom der Vena cava. Eine seltene Differenzialdiagnose eines Nebennierentumors.

Leiomyomas are benign tumors that can arise in the smooth muscle and can appear practically everywhere; hence, they must be taken into consideration as a rare possibility in the differential diagnosis of numerous tumors. While leiomyomas of the peripheral vessels are a relatively common finding, they are rarely found in the central vessels. Only a few cases of leiomyomas in the vena cava are known. In contrast to malignant leiomyosarcomas, leiomyomas usually grow towards the lumen. We report on the rare case of a leiomyoma in the inferior vena cava that appeared in the image to be located in the adrenal gland. Therefore, transperitoneal extirpation of the site was undertaken. It was only during surgery that a tumor emanating from the vessel wall became apparent. Thus, after an initial laparoscopic approach it became necessary to change to open resection of the tumor with cavotomy and resection of the vessel wall. The histopathological work-up revealed a benign leiomyoma and further imaging diagnostics gave no indication for the presence of metastases.

Frequent p16/MTS1 inactivation in early stages of urothelial carcinoma of the bladder is not associated with tumor recurrence.

OBJECTIVE: p16, located at chromosome 9p21, is a negative regulator of G1 cell checkpoint and functions as tumor suppressor gene. Only few data are available on the frequency and clinical relevance of p16 alterations in Ta, T1 transitional cell carcinoma (TCC) of the bladder. We investigated 40 patients with Ta, T1 TCC of the bladder for p16 alterations (mutations, homozygote deletions, allelic loss) or reduced p16 immunoreaction. PATIENTS AND METHODS: DNA was prepared from microdissected tumor tissue from 40 patients with pTa, pT1 TCC of the bladder (pTa: 18 patients; pT1: 22 patients; grade 1: 7 patients; grade 2: 28 patients; grade 3: 5 patients). Mutation screening was performed using polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP) and direct sequencing at exon 1 and exon 2. Detection of homozygote deletions was performed using multiplex PCR. Immunohistochemistry (IHC) was performed using an anti-human monoclonal antibody (p16, Pharmingen). Allelic loss was detected by PCR using three different microsatellite markers (D9S161, D9S171, D9S319). RESULTS: SSCP and direct sequencing revealed 3 cases of base substitution which turned out to be natural polymorphisms. Homozygote deletions were not detected in any case. p16 IHC revealed reduced p16 expression (<5% positive nuclei) in 10 patients; 30 patients had a positive reaction (> or =5% positive nuclei) and 10 patients a strong positive reaction (> or =50% positive nuclei). Thirteen of 37 informative cases revealed loss of heterozygosity (LOH) with at least one marker. After a median follow-up of 23 months, 15 patients suffered from disease recurrence. Statistical analysis using Kaplan-Meier analysis and the log-rank test did not reveal significant association of recurrence-free interval and detection of LOH (p = 0.34) or p16 IHC (p = 0.9). CONCLUSIONS: We present a comprehensive evaluation of chromosome 9p21 alterations including p16 analysis and clinical follow-up data. Although p16 mutations and homozygote deletions are rarely detectable in Ta, T1 TCC, the reduction of p16 expression and the frequent hemizygote deletions at 9p21 suggest an early involvement of chromosome 9p and p16 in superficial TCC.