Comparison of real-time elastography and multiparametric MRI for prostate cancer detection: A whole-mount step-section analysis

OBJECTIVE. The purpose of this study was to compare prostate cancer detection rate of real-time elastography (RTE) with that of multiparametric MRI to evaluate the advantages and disadvantages of the two methods. SUBJECTS AND METHODS. Thirty-nine patients with biopsy-proven prostate cancer underwent both RTE and multiparametric MRI to localize prostate cancer before radical prostatectomy. RTE was performed to assess prostate tissue elasticity, and hard lesions were considered suspicious for prostate cancer. Multiparametric MRI included T2-weighted MRI, diffusion-weighted MRI (DWI), and contrast-enhanced MRI (CE-MRI) with an endorectal coil at 1.5 T. After radical prostatectomy, whole-mount step sections of the prostate were generated, and the prostate cancer detection rates with both modalities were analyzed for cancer lesions measuring 0.2 cm 3 or larger. RESULTS. Histopathologic examination revealed 61 cancer lesions. RTE depicted 39 of 50 cancer lesions (78.0%) in the peripheral zone and 2 of 11 (18.2%) in the transitional zone. Multiparametric MRI depicted 45 of 50 cancer lesions (90.0%) in the peripheral zone and 8 of 11 (72.7%) in the transitional zone. Significant differences between the two modalities were found for the transitional zone and anterior part in prostates with volumes greater than 40 cm3 (p \u3c 0.05). Detection rates for high-risk prostate cancer (Gleason score ≥ 4 and 3) and cancer lesions with volumes greater than 0.5 cm3 were high for both methods (93.8% and 80.5% for RTE, 87.5% and 92.7% for multiparametric MRI). Volumetric measurements of prostate cancer were more reliable with T2-weighted MRI than with RTE (Spearman rank correlation, 0.72 and 0.46). CONCLUSION. RTE and multiparametric MRI depicted high-risk prostate cancer with high sensitivity. However, multiparametric MRI seems to have advantages in tumor volume assessment and for the detection of prostate cancer in the transitional zone and anterior part within prostates larger than 40 cm3. American Roentgen Ray Society

Potentials and limitations of real-time elastography for prostate cancer detection: a whole-mount step section analysis.

OBJECTIVES: To evaluate prostate cancer (PCa) detection rates of real-time elastography (RTE) in dependence of tumor size, tumor volume, localization and histological type. MATERIALS AND METHODS: Thirdy-nine patients with biopsy proven PCa underwent RTE before radical prostatectomy (RPE) to assess prostate tissue elasticity, and hard lesions were considered suspicious for PCa. After RPE, the prostates were prepared as whole-mount step sections and were compared with imaging findings for analyzing PCa detection rates. RESULTS: RTE detected 6/62 cancer lesions with a maximum diameter of 0-5 mm (9.7%), 10/37 with a maximum diameter of 6-10 mm (27%), 24/34 with a maximum diameter of 11-20 20 mm (70.6%), 14/14 with a maximum diameter of \u3e20 mm (100%) and 40/48 with a volume ≥0.2 cm(3) (83.3%). Regarding cancer lesions with a volume ≥ 0.2 cm³ there was a significant difference in PCa detection rates between Gleason scores with predominant Gleason pattern 3 compared to those with predominant Gleason pattern 4 or 5 (75% versus 100%; P = 0.028). CONCLUSIONS: RTE is able to detect PCa of significant tumor volume and of predominant Gleason pattern 4 or 5 with high confidence, but is of limited value in the detection of small cancer lesions

Safe and Effective Cynomolgus Monkey GLP—Tox Study with Repetitive Intrathecal Application of a TGFBR2 Targeting LNA-Gapmer Antisense Oligonucleotide as Treatment Candidate for Neurodegenerative Disorders

The capability of the adult central nervous system to self-repair/regenerate was demonstrated repeatedly throughout the last decades but remains in debate. Reduced neurogenic niche activity paralleled by a profound neuronal loss represents fundamental hallmarks in the disease course of neurodegenerative disorders. We and others have demonstrated the endogenous TGFβ system to represent a potential pathogenic participant in disease progression, of amyotrophic lateral sclerosis (ALS) in particular, by generating and promoting a disequilibrium of neurodegenerative and neuroregenerative processes. The novel human/primate specific LNA Gapmer Antisense Oligonucleotide “NVP-13”, targeting TGFBR2, effectively reduced its expression and lowered TGFβ signal transduction in vitro and in vivo, paralleled by boosting neurogenic niche activity in human neuronal progenitor cells and nonhuman primate central nervous system. Here, we investigated NVP-13 in vivo pharmacology, safety, and tolerability following repeated intrathecal injections in nonhuman primate cynomolgus monkeys for 13 weeks in a GLP-toxicology study approach. NVP-13 was administered intrathecally with 1, 2, or 4 mg NVP-13/animal within 3 months on days 1, 15, 29, 43, 57, 71, and 85 in the initial 13 weeks. We were able to demonstrate an excellent local and systemic tolerability, and no adverse events in physiological, hematological, clinical chemistry, and microscopic findings in female and male Cynomolgus Monkeys. Under the conditions of this study, the no observed adverse effect level (NOAEL) is at least 4 mg/animal NVP-13

The Role of lncRNAs TAPIR-1 and -2 as Diagnostic Markers and Potential Therapeutic Targets in Prostate Cancer

In search of new biomarkers suitable for the diagnosis and treatment of prostate cancer, genome-wide transcriptome sequencing was carried out with tissue specimens from 40 prostate cancer (PCa) and 8 benign prostate hyperplasia patients. We identified two intergenic long non-coding transcripts, located in close genomic proximity, which are highly expressed in PCa. Microarray studies on a larger cohort comprising 155 patients showed a profound diagnostic potential of these transcripts (AUC~0.94), which we designated as tumor associated prostate cancer increased lncRNA (TAPIR-1 and -2). To test their therapeutic potential, knockdown experiments with siRNA were carried out. The knockdown caused an increase in the p53/TP53 tumor suppressor protein level followed by downregulation of a large number of cell cycle- and DNA-damage repair key regulators. Furthermore, in radiation therapy resistant tumor cells, the knockdown leads to a renewed sensitization of these cells to radiation treatment. Accordingly, in a preclinical PCa xenograft model in mice, the systemic application of nanoparticles loaded with siRNA targeting TAPIR-1 significantly reduced tumor growth. These findings point to a crucial role of TAPIR-1 and -2 in PCa