Tahir Durmus

Prostate cancer detection on transrectal ultrasonography-guided random biopsy despite negative real-time magnetic resonance imaging/ultrasonography fusion-guided targeted biopsy: reasons for targeted biopsy failure

To examine the value of additional transrectal ultrasonography (TRUS)‐guided random biopsy (RB) in patients with negative magnetic resonance imaging (MRI)/ultrasonography (US) fusion‐guided targeted biopsy (TB) and to identify possible reasons for TB failure.

Evaluation of the prostate imaging reporting and data system for the detection of prostate cancer by the results of targeted biopsy of the prostate.

PurposeThe purpose of this study was to evaluate the magnetic resonance prostate imaging reporting and data system (PI-RADS) for the detection of prostate cancer by the results of magnetic resonance imaging (MRI)–guided biopsy of the prostate as a reference standard. Patients and MethodsIn 55 patients who had undergone MRI-guided biopsy of the prostate, we retrospectively matched every biopsy core with the corresponding lesion in previously acquired endorectal multiparametric MRI including T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and dynamic contrast-enhanced MRI (DCE-MRI) at 1.5 T. Two readers blinded to the results of the biopsy evaluated each biopsied lesion according to the PI-RADS scoring system. The results of the targeted biopsy were used as a reference standard. Receiver operating characteristic analysis was performed for statistical analysis. ResultsA total of 113 lesions in the 55 patients were evaluated; 30 lesions were malignant. When evaluated according to the criteria of the PI-RADS scoring system, DCE-MRI revealed a lower area under the receiver operating characteristic curve (AUC) (0.76) compared with T2WI (0.88; P = 0.06) and DWI (0.93; P = 0.004). A sum score combining T2WI, DWI, and DCE-MRI yielded an AUC of 0.93, whereas a sum score combining only T2WI and DWI yielded an AUC of 0.95. In central gland lesions, T2WI showed a numerically higher AUC compared with DWI (0.98 and 0.95), whereas, in peripheral zone lesions, DWI was superior (AUC of 0.93 and 0.73; P = 0.04). An approach assigning a PI-RADS score for T2WI to central gland lesions and for DWI to peripheral zone lesions yielded an AUC of 0.96 and was numerically superior compared with any sequence alone and sum scores combining T2WI and DWI as well as T2WI, DWI, and DCE-MRI. ConclusionsThe PI-RADS scoring system shows a good diagnostic performance for the detection of prostate cancer when using a sum score. However, DCE-MRI does not seem to add significant value when evaluated according to the recommended criteria. Assigning a score for T2WI to central gland lesions and for DWI to peripheral zone lesions might be sufficient for stratification of patients for further diagnostic workup.

Survivin minigene DNA vaccination is effective against neuroblastoma.

The inhibitor of apoptosis protein survivin is highly expressed in neuroblastoma (NB) and survivin‐specific T cells were identified in Stage 4 patients. Therefore, we generated a novel survivin minigene DNA vaccine (pUS‐high) encoding exclusively for survivin‐derived peptides with superior MHC class I (H2‐Kk) binding affinities and tested its efficacy to suppress tumor growth and metastases in a syngeneic NB mouse model. Vaccination was performed by oral gavage of attenuated Salmonella typhimurium SL7207 carrying pUS‐high. Mice receiving the pUS‐high in the prophylactic setting presented a 48–52% reduction in s.c. tumor volume, weight and liver metastasis level in contrast to empty vector controls. This response was as effective as a survivin full‐length vaccine and was associated with an increased target cell lysis, increased presence of CD8+ T‐cells at the primary tumor site and enhanced production of proinflammatory cytokines by systemic CD8+ T cells. Furthermore, depletion of CD8+ but not CD4+ T‐cells completely abrogated the pUS‐high mediated primary tumor growth suppression, demonstrating a CD8+ T‐cell mediated effect. Therapeutic vaccination with pUS‐high led to complete NB eradication in over 50% of immunized mice and surviving mice showed an over 80% reduction in primary tumor growth upon rechallenge in contrast to controls. In summary, survivin‐based DNA vaccination is effective against NB and the rational minigene design provides a promising approach to circumvent potentially hazardous effects of using full length antiapoptotic genes as DNA vaccines.

Tolerability and diagnostic value of gadoteric acid in the general population and in patients with risk factors: Results in more than 84,000 patients

PURPOSE To review the tolerability and diagnostic effectiveness of gadoteric acid under daily practice conditions in the general population and at-risk patients. MATERIALS AND METHODS A total of 84,621 patients (45.4% men, 54.6% women, mean age 52.0 ± 16.9 years) were studied in 129 German centers. Patients underwent contrast-enhanced magnetic resonance imaging (MRI) using gadoteric acid (Gd-DOTA, Dotarem(®), Guerbet, Roissy CdG, France) as IV contrast medium (mean volume, 16.4 ml). 22.9% of the patients had at least one risk factor (e.g., allergies, previous allergic reaction to a contrast medium, and renal impairment). 554 patients received pretreatment before contrast medium administration (0.7%). Adverse events were documented and image quality was assessed. RESULTS A diagnosis was possible in 99.7% of all cases. Image quality was rated good or excellent in 97.1%. Adverse events (e.g., nausea, vomiting, and urticaria) were observed in 0.34% of the examinations and were mostly rated as minor. There were 8 patients with serious adverse events. The adverse event rate was significantly higher in patients with a history of allergies (0.62%; p<0.001) and in patients with a previous allergic reaction to contrast medium (1.23%; p<0.001). There was no elevated incidence of adverse events in patients with renal impairment. CONCLUSION Gadoteric acid is a well-tolerated MRI contrast medium in patients with and without risk factors that is associated with a low rate of adverse events and good or excellent image quality in most patients.

Salmonella SL7207 application is the most effective DNA vaccine delivery method for successful tumor eradication in a murine model for neuroblastoma

Attenuated Salmonella is an approved oral life vaccine that is currently entering pre-clinical cancer vaccination studies as a promising DNA carrier. In a syngeneic mouse model for neuroblastoma, oral gavage of Salmonella typhimurium (SL7207) carrying recent generated survivin DNA vaccines induced a stronger cellular anti-NB immune response than gene gun application or injection of lentivirally transduced bone marrow-derived DCs. The level of Salmonella-associated side effects was not significant as indicated by unaffected survivin-mediated hematopoiesis and wound healing. We believe that our findings provide an important baseline to translate Salmonella-based DNA vaccination into a clinical application for neuroblastoma.

Detektion des Prostatakarzinoms durch Echtzeit-MRT/US-Fusionsbiopsie: 3T MRT und moderne Ultraschalltechnik

PURPOSE Multiparametric MRI of the prostate is a noninvasive diagnostic method with high sensitivity and specificity for prostate cancer. The aim of this study is to evaluate whether prostate cancer detection rates of transrectal ultrasound (TRUS)-guided biopsy may be improved by an image fusion of state-of-the-art ultrasound (CEUS, elastography) and MR (T2w, DWI) imaging. MATERIALS AND METHODS 32 consecutive patients with a history of elevated PSA levels and at least one negative TRUS-guided biopsy with clinical indication for a systematic re-biopsy underwent multiparametric 3 T MRI without endorectal coil. MR data (T2w) were uploaded to a modern sonography system and image fusion was performed in real-time mode during biopsy. B-mode, Doppler, elastography and CEUS imaging were applied to characterize suspicious lesions detected by MRI. Targeted biopsies were performed in MR/US fusion mode followed by a systematic standard TRUS-guided biopsy. Detection rates for both methods were calculated and compared using the Chi²-test. RESULTS Patient age was not significantly different in patients with and without histologically confirmed prostate cancer (65.2 ± 8.0 and 64.1 ± 7.3 age [p = 0.93]). The PSA value was significantly higher in patients with prostate cancer (15.5 ± 9.3 ng/ml) compared to patients without cancer (PSA 10.4 ± 9.6 ng/ml; p = 0.02). The proportion of histologically confirmed cancers in the study group (n = 32) of the MR/US fusion biopsy (11/12; 34.4 %) was significantly higher (p = 0.01) in comparison to the TRUS systematic biopsy (6/12; 18.8 %). CONCLUSION Real-time MR/US image fusion may enhance cancer detection rates of TRUS-guided biopsies and should therefore be studied in further larger studies.

The value of ADC, T2 signal intensity, and a combination of both parameters to assess Gleason score and primary Gleason grades in patients with known prostate cancer

Background The ability to non-invasively analyze tumor aggressiveness is an important predictor for individual treatment stratification and patient outcome in prostate cancer (PCA). Purpose To evaluate: (i) whether apparent diffusion coefficient (ADC), the T2 signal intensity (SI), and a combination of both parameters allow for an improved discrimination of Gleason Score (GS) ≥7 (intermediate and high risk) and GS <7 (low risk) in PCA; and (ii) whether ADC may distinguish between 3 + 4 and 4 + 3 PCA (primary Gleason grades [pGG]). Material and Methods Prostatectomy specimens of 66 patients (mean age, 63 ± 5.6 years; 104 PCA foci) with a preceding multiparametric 1.5 T endorectal coil magnetic resonance imaging (MRI) were included. ADC (b values = 0, 100, 400, 800 s/mm2), standardized T2 (T2s), and the ADC/T2s ratio were tested for correlation with GS applying multivariate analysis. ADC cutoff values were calculated for prediction of GS and pGG, and logarithm of the odds (LOGIT) was used to express the probability for GS and pGG. Diagnostic accuracy was assessed by ROC analysis. Results We found an almost linear negative relationship of ADC for GS ≥7 (P = 0.002). The effect of ADC for GS ≥7 (adjusted odds ratio = 0.995) was almost identical for peripheral and transition zone PCA (P = 0.013 and P < 0.001, respectively). ADC showed an AUC of 78.9% for discrimination between GS <7 and GS ≥7. An ADC cutoff of <1.005 × 10−3 mm2/s indicated a GS ≥7 (90.5% sensitivity, 62.5% specificity). Within the group of GS = 7 PCA, an ADC > 0.762 × 10−3 mm2/s indicated a pGG of 3 (AUC = 69.6%). Conclusion T2s and the ADC/T2s ratio do not provide additional information regarding prediction of GS. ADC values have a good discriminatory power to distinguish tumors with GS ≥7 from GS <7 and to predict pGG in GS = 7 PCA.

A study in three European IBD cohorts confirms that the ATG16L1 c.898A > G (p.Thr300Ala) variant is a susceptibility factor for Crohn’s disease

BACKGROUND AND AIMS A recent study reported that a nonsynonymous SNP rs2241880 (c.898A>G, p.Thr300Ala) within ATG16L1 confers susceptibility to Crohns disease (CD). We analyzed ATG16L1 c.898A>G in three independent European inflammatory bowel disease (IBD) cohorts from Germany, Hungary and the Netherlands. METHODS In total, we included 910 European IBD patients and compared the ATG16L1 c.898A>G genotype frequency with 707 ethnically matched healthy controls. We included patients from 3 populations originating from Germany (CD n=310; ulcerative colitis [UC] n=179), Hungary (CD n=147; UC n=117), and the Netherlands (CD n=157). Subtyping analysis was performed in respect to CARD15 alterations and clinical characteristics. RESULTS We found a highly significant association of c.898A>G to CD. The association was significant (p=0.0005) for the total CD cohort but also for the individual populations from Germany (p=0.02) and Netherlands (p=0.02) whereas in the Hungarian CD patients a clear trend was observed (p=0.19; OR 1.227, 95% CI 0.910; 1.654). No association was found between c.898A>G and UC. No statistical interactions were observed between ATG16L1 c.898A>G and CARD15 variants. Furthermore no association to a CD subphenotype was detected. CONCLUSIONS We confirm that ATG16L1 variant c898A>G confers a risk variant for CD but is not associated with a distinct CD phenotype.

Added Value of Multiparametric Ultrasonography in Magnetic Resonance Imaging and Ultrasonography Fusion–guided Biopsy of the Prostate in Patients With Suspicion for Prostate Cancer

OBJECTIVE To analyze whether magnetic resonance imaging-ultrasonography (MRI-US) fusion-guided biopsy detects more and clinical significant prostate cancer (PCa) in comparison to conventional transrectal US-guided prostate biopsy (PBX) and to investigate if multiparametric (mp) US during MRI-US fusion can further characterize mpMRI-suspected lesions according to the prostate MRI reporting and data system (PI-RADS). METHODS From January 2012 to January 2014, 169 patients with a median of 2 negative conventional PBX and/or initially or consistently elevated prostate-specific antigen levels were prospectively included and underwent 3 T mpMRI. Real-time MRI-US fusion scan was used to biopsy the mpMRI-targeted lesions (n = 316). Scanning by mpUS, including B-mode, power Doppler, strain elastography, and contrast-enhanced US was performed to further characterize those lesions and to score by US modalities resulting in an mpUS score. Afterward, a conventional 10-core PBX was performed. PCa detection based on the results of targeted and conventional PBX was estimated. Performances of single US modalities were analyzed. The mpUS score was also investigated for PCa and PI-RADS score prediction. RESULTS Among 169 patients, 71 PCa (42%) were detected. From these 71 cases, clinically significant PCa (Gleason score ≥7) were detected exclusively by MRI-US fusion in 31 from 46 cases (67.4%). The highest sensitivity was observed in contrast-enhanced US (85%) and elastography (80%). The mpUS score predicts PCa and PI-RADS score with an overall accuracy of 86% and 80%, respectively. CONCLUSION MRI-US fusion-guided PBX detects more clinically significant PCa compared with conventional TRUS. The mpUS score correlates with PI-RADS in PCa prediction.

Assessment of Mitral Valve Stenosis by Helical MDCT: Comparison With Transthoracic Doppler Echocardiography and Cardiac Catheterization

OBJECTIVE We evaluated the precision of helical MDCT for the quantification of mitral valve stenosis (MVS) compared with transthoracic echocardiography (TTE) and cardiac catheterization. MATERIALS AND METHODS A total of 28 patients with MVS of differing severity underwent an ECG-gated contrast-enhanced MDCT scan. The mitral valve area (MVA) was determined planimetrically by MDCT and was compared with Doppler TTE using the pressure half-time method and with cardiac catheterization using the Gorlin formula. RESULTS Planimetry of the MVA with MDCT was feasible in all cases. The MVA on MDCT (1.88 ± 0.76 cm(2)) was significantly larger than that seen with TTE (1.74 ± 0.75 cm(2); p = 0.039) or cardiac catheterization (1.72 ± 0.67 cm(2); p = 0.037). The correlation between MDCT and TTE (r = 0.90; p < 0.001; limits of agreement, ± 0.65 cm(2)) and that between MDCT and cardiac catheterization (r = 0.86; p < 0.001; limits of agreement, ± 0.76 cm(2)) were good and similar to the correlation between TTE and cardiac catheterization (r = 0.88; p < 0.001; limits of agreement, ± 0.71 cm(2)). The best cutoff level for detecting moderate-to-severe stenosis at MDCT was an MVA of 1.70 cm(2), resulting in a sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 73%, 88%, 82%, 80%, and 83%, respectively, with two false-positive and three false-negative results. CONCLUSION The MVA planimetrically determined by MDCT is systematically larger than those calculated by Doppler TTE and cardiac catheterization. However, because of a good correlation between methods and adjustment for the systematic bias, MDCT may allow reliable quantification of MVS and effectual discrimination among severity grades, although discrepancies between methods remain in individual cases.