Multiparametric Magnetic Resonance Imaging of the Prostate for Tumour Detection and Local Staging: Imaging in 1.5T and Histopathologic Correlation.

PURPOSE: The study sought to prospectively evaluate which technique among T2-weighted images, dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI), diffusion-weighted (DW) MRI, or a combination of the 2, is best suited for prostate cancer detection and local staging. METHODS: Twenty-seven consecutive patients with biopsy-proven adenocarcinoma of the prostate underwent MRI on a 1.5T scanner with a surface phased-array coil prior radical prostatectomy. Combined anatomical and functional imaging was performed with the use of T2-weighted sequences, DCE MRI, and DW MRI. We compared the imaging results with whole mount histopathology. RESULTS: For the multiparametric approach, significantly higher sensitivity values, that is, 53% (95% confidence interval [CI]: 41.0-64.1) were obtained as compared with each modality alone or any combination of the 3 modalities (P < .05). The specificity for this multiparametric approach, being 90.3% (95% CI: 86.3-93.3) was not significantly higher (P < .05) as compared with the values of the combination of T2+DCE MRI, DW+DCE MRI, or DCE MRI alone. Among the 3 techniques, DCE had the best performance for tumour detection in both the peripheral and the transition zone. High negative predictive value rates (>86%) were obtained for both tumour detection and local staging. CONCLUSIONS: The combination of T2-weighted sequences, DCE MRI, and DW MRI yields higher diagnostic performance for tumour detection and local staging than can any of these techniques alone or even any combination of them.

Outcomes of European Basic Laparoscopic Urological Skills (EBLUS) Examinations: Results from European School of Urology (ESU) and EAU Section of Uro-Technology (ESUT) over 6 Years (2013-2018).

BACKGROUND: The European School of Urology (ESU) and EAU Section of Uro-Technology (ESUT) started hands-on-training (HOT) sessions in 2007 along with structured European Basic Laparoscopic Urological Skills (EBLUS) examinations in 2013. EBLUS includes an online theoretical course, HOT by expert tutors on a set of dry-lab exercises, and finally a standardised examination for skill assessment and certification. OBJECTIVE: To analyse the results and predictors of success from the EBLUS examinations that were conducted during the European Urology Residents Education Programme (EUREP) and other international and national dedicated ESU events. DESIGN, SETTING, AND PARTICIPANTS: ESU has been delivering EBLUS courses and examinations over the past 6 yr (2013-2018) in more than 40 countries worldwide. Trainees were asked about their laparoscopic background (procedures assisted/performed) and about the availability of HOT or simulator/box trainer in their facility. Apart from the online theoretical course, 4 HOT tasks [(1) peg transfer, (2) pattern cutting, (3) single knot tying, and (4) clip and cut] with its quality assessment of depth perception, bimanual dexterity, and efficiency were a part of the assessment and were considered critical to pass the EBLUS examination. RESULTS AND LIMITATIONS: A total of 875 EBLUS examinations were delivered (EUREP, n=385; other ESU events, n=490), with complete data available for 533 (61%) participants among which 295 (55%) passed the examinations. Pass rate increased on a yearly basis from 35% to 70% (p<0.001) and was similar between EUREP (56%) and other ESU/ESUT events (55%). The significant predictors of success were passing tasks 1 [odds ratio (OR): 869.9, 95% confidence interval (CI): 89.6-8449.0, p<0.001] and 2 (OR: 3045.0, 95% CI: 99.2-93 516.2, p<0.001) of the examinations. A limitation of EBLUS was its inability to provide more advanced training such as wet-lab or cadaveric training. CONCLUSIONS: Over the past few years more trainees have passed the European Basic Laparoscopic Urological Skills (EBLUS) examinations. Trainees who spend more time on laparoscopic procedures demonstrated a better performance and pass rate. We found almost no difference between the EBLUS results collected from EUREP and other ESU/ESUT events, which confirms the robustness of the training and examinations conducted worldwide. PATIENT SUMMARY: Training in laparoscopy helps trainees pass the European Basic Laparoscopic Urological Skills (EBLUS) examinations, reflected by an increase in the pass rate over the past 6 yr. Our results also confirm the robustness of EBLUS training and examinations worldwide.

Cartilage Tissue Engineering by the 3D Bioprinting of iPS Cells in a Nanocellulose/Alginate Bioink.

Cartilage lesions can progress into secondary osteoarthritis and cause severe clinical problems in numerous patients. As a prospective treatment of such lesions, human-derived induced pluripotent stem cells (iPSCs) were shown to be 3D bioprinted into cartilage mimics using a nanofibrillated cellulose (NFC) composite bioink when co-printed with irradiated human chondrocytes. Two bioinks were investigated: NFC with alginate (NFC/A) or hyaluronic acid (NFC/HA). Low proliferation and phenotypic changes away from pluripotency were seen in the case of NFC/HA. However, in the case of the 3D-bioprinted NFC/A (60/40, dry weight % ratio) constructs, pluripotency was initially maintained, and after five weeks, hyaline-like cartilaginous tissue with collagen type II expression and lacking tumorigenic Oct4 expression was observed in 3D -bioprinted NFC/A (60/40, dry weight % relation) constructs. Moreover, a marked increase in cell number within the cartilaginous tissue was detected by 2-photon fluorescence microscopy, indicating the importance of high cell densities in the pursuit of achieving good survival after printing. We conclude that NFC/A bioink is suitable for bioprinting iPSCs to support cartilage production in co-cultures with irradiated chondrocytes.

Enhanced growth of neural networks on conductive cellulose-derived nanofibrous scaffolds.

The problem of recovery from neurodegeneration needs new effective solutions. Tissue engineering is viewed as a prospective approach for solving this problem since it can help to develop healthy neural tissue using supportive scaffolds. This study presents effective and sustainable tissue engineering methods for creating biomaterials from cellulose that can be used either as scaffolds for the growth of neural tissue in vitro or as drug screening models. To reach this goal, nanofibrous electrospun cellulose mats were made conductive via two different procedures: carbonization and addition of multi-walled carbon nanotubes. The resulting scaffolds were much more conductive than untreated cellulose material and were used to support growth and differentiation of SH-SY5Y neuroblastoma cells. The cells were evaluated by scanning electron microscopy and confocal microscopy methods over a period of 15 days at different time points. The results showed that the cellulose-derived conductive scaffolds can provide support for good cell attachment, growth and differentiation. The formation of a neural network occurred within 10 days of differentiation, which is a promising length of time for SH-SY5Y neuroblastoma cells.

The Role of Virtual Cystoscopy, after Multidetector Computed Tomography Imaging Reconstruction without the Use of Contrast Medium, in the Diagnosis and Evaluations of Bladder Tumors: Preliminary Study.

Introduction. Although conventional cystoscopy is considered to be the gold standard for diagnosis and follow-up of bladder tumors, it remains an invasive and costly procedure. With the advent of the multidetector CT (MDCT) scanners supported by specialized software virtual cystoscopy (VC) is possible. We assess the role of VC in diagnosing and evaluating bladder lesions. Materials and Methods. Between September 2010 and October 2011, 25 consecutive patients with cystoscopically confirmed bladder tumor underwent VC. The radiologists involved in this prospective study were blinded to the exact findings. After draining any residual urine with a catheter, the bladder was retrogradely insufflated with 200-600 cc of air. No intravenous or intravesical contrast was used. MDCT scan was performed in supine and prone positions and three-dimensional reconstruction of the urinary bladder was performed. Results. The examination was well tolerated by all patients with no complications. In total, 43 lesions were detected both with conventional cystoscopy and VC. Tumor size measured by CT ranged from 3 to 80 mm in diameter. The pathological report revealed noninvasive transitional cell carcinomas in all cases. Conclusion. VC has promising results in detecting exophytic bladder lesions. In the future it could be part of the diagnostic algorithm for bladder tumors.

Osteoprotegerin expression during the micro- and macrometastatic phases of the osteoblastic metastasis in prostate cancer: therapeutic implications.

INTRODUCTION: Osteoprotegerin (OPG) acts as a soluble decoy receptor for the bone marrow stroma cell-derived and osteoblast-derived receptor activator of nuclear factor-kB ligand (RANKL), thus regulating the RANK-mediated osteoclastogenesis and osteoclast-mediated bone resorption at the metastatic niche of cancer in skeleton. AREAS COVERED: This article discusses the 'key' role of OPG expression during the early events of cancer cell invasion into the bone matrix and the subsequent events underlying the formation of osteoblastic metastasis, a unique event observed in human prostate cancer biology. EXPERT OPINION: Understanding the cellular and molecular events implicated in bone metastasis can facilitate designing new therapeutic strategies for targeting early and/or late events in the metastasis processes. The RANKL/RANK/OPG pathway is a key regulator of pathological bone metabolism in metastatic sites. Targeted manipulation of these molecules may provide sustainable antitumor responses.

Study of genetic and epigenetic alterations in urine samples as diagnostic markers for prostate cancer.

BACKGROUND: Early diagnosis of prostate cancer and identification of new prognostic factors remain main issues in prostate cancer research. In this study, we sought to test a panel of cancer-specific markers in urine samples as an aid for early cancer diagnosis. MATERIALS AND METHODS: Sedimented urine samples of 66 candidates for needle biopsy were tested. Real time-polymerase chain reaction (RT-PCR) was applied to detect the expression of transmembrane protease serine-2 and Ets-related gene fusion (TMPRSS2-ERG), Ets-related gene (ERG), prostate cancer antigen-3 (PCA3), and serine peptidase inhibitor kazal type-1 (SPINK1) transcripts. For testing of the methylation status of Glutahione S-tranferase P (GSTP1) and Ras association domain family member-1(RASSF1A) promoter region, methylation-specific PCR (MSP-PCR) was applied. RESULTS: Among the tested parameters, the presence of TMPRSS2-ERG (OR=9.044, 95% CI=2.207-37.066, p=0.002), as well as a positive test result for PCA3 (OR=7.549, 95% CI=1,858-30,672, p=0.005) were associated with the subsequent diagnosis of prostate cancer. A multivariable logistic regression including all the significantly associated variables [prostate-specific antigen (PSA), digital rectal examination (DRE), TMPRSS2-ERG and PCA3], yielded a model with area under the receiver-operating characteristic curve (AUC) =0.894 (95% CI=0.772-1.00). CONCLUSION: A multiplexed quantitative PCR analysis on sedimented urine, in conjunction with the results of serum PSA levels and DRE, has the potential to accurately foresee subsequent needle biopsy outcomes. On the basis of the above, algorithms may be designed to guide decisions for needle biopsy.

Feasibility and radiation induced toxicity regarding the first application of transperineal implementation of biocompatible balloon for high dose radiotherapy in patients with prostate carcinoma.

OBJECTIVE: To evaluate the feasibility of the transperineal implementation of biocompatible balloon (Prospace) and the acute toxicity of high dose 3DCRT in patients with localized low risk prostate cancer. MATERIALS AND METHODS: Between December 2011 and April 2012, fifteen patients were treated with external 3DCRT consisted of 76-78 Gy in 38-39 daily fractions (2.0 Gy/ fraction). Before 3DCRT, we placed the Prospace though the perineum by a minimally invasive procedure in the intermediate space between the rectum and the prostate. The primary study endpoint was the evaluation of acute toxicity according to the EORTC/RTOG radiation toxicity scale. Erectile function was evaluated with the IIEF-5 questionnaire. Rectosigmoidoscopy was performed at baseline, at the end of 3DCRT and 3 months thereafter in order to assess also the rectal toxicity according to Subjective-RectoSigmoid (S-RS) scale. The evaluation of pain related to Prospace implementation was done with the visual analogue score (VAS). RESULTS: The acute toxicities were as follows: grade I GI toxicity in two patients and for GU toxicity, three patients with grade I of nocturia, four patients with grade I of frequency, two patients with grade I and two patients with grade II of dysouria. The mean score of rectal toxicity according to S-RS score was 1.8(±0.6). The mean VAS score related to Prospace was 1.4(±0.5). Erectile function was unchanged. The Prospace device was found stable in sequential CTs during irradiation. CONCLUSIONS: The implementation of PROSPACE was feasible, while the acute radiation toxicity was low and comparable with IMRT techniques.

US Imaging in Peyronie's Disease.

The aim of this study is to assess the role of ultrasound (US) in Peyronie's Disease (PD). PD is a psychologically and physically devastating disorder that manifests in middle-aged men. Fibrous inelastic plaques in the tunica albuginea, result in palpable penile scar in the flaccid condition and cause painful erections and penile deformity, including penile curvature, hinging, narrowing, and shortening of penis. Penile deformity is the most common (52%) first symptom of PD and is present in 94% of affected men. US is the primary imaging modality of choice due to its easy availability, low risk, and ability to image and quantify both calcified and soft tissue elements of PD. US provides identification of smaller and non-palpable lesions and shows the extent of fibrosis. Detection of calcifications within the plaque suggests stabilization of the disease and provides information useful to select patients for appropriate treatment.