Update on the ICUD-SIU consultation on multi-parametric magnetic resonance imaging in localised prostate cancer

Introduction: Prostate cancer (PCa) imaging is a rapidly evolving field. Dramatic improvements in prostate MRI during the last decade will probably change the accuracy of diagnosis. This chapter reviews recent current evidence about MRI diagnostic performance and impact on PCa management. Materials and methods: The International Consultation on Urological Diseases nominated a committee to review the literature on prostate MRI. A search of the PubMed database was conducted to identify articles focussed on MP-MRI detection and staging protocols, reporting and scoring systems, the role of MP-MRI in diagnosing PCa prior to biopsy, in active surveillance, in focal therapy and in detecting local recurrence after treatment. Results: Differences in opinion were reported in the use of the strength of magnets [1.5 Tesla (T) vs. 3T] and coils. More agreement was found regarding the choice of pulse sequences; diffusion-weighted MRI (DW-MRI), dynamic contrast-enhanced MRI (DCE MRI), and/or MR spectroscopy imaging (MRSI) are recommended in addition to conventional T2-weighted anatomical sequences. In 2015, the Prostate Imaging Reporting and Data System (PI-RADS version 2) was described to standardize image acquisition and interpretation. MP-MRI improves detection of clinically significant PCa (csPCa) in the repeat biopsy setting or before the confirmatory biopsy in patients considering active surveillance. It is useful to guide focal treatment and to detect local recurrences after treatment. Its role in biopsy-naive patients or during the course of active surveillance remains debated. Conclusion: MP-MRI is increasingly used to improve detection of csPCa and for the selection of a suitable therapeutic approach

Chemical analysis and aqueous solution properties of Charged Amphiphilic Block Copolymers PBA-b-PAA synthesized by MADIX

We have linked the structural and dynamic properties in aqueous solution of amphiphilic charged diblock copolymers poly(butyl acrylate)-b-poly(acrylic acid), PBA-b-PAA, synthesized by controlled radical polymerization, with the physico-chemical characteristics of the samples. Despite product imperfections, the samples self-assemble in melt and aqueous solutions as predicted by monodisperse microphase separation theory. However, the PBA core are abnormally large; the swelling of PBA cores is not due to AA (the Flory parameter chiPBA/PAA, determined at 0.25, means strong segregation), but to h-PBA homopolymers (content determined by Liquid Chromatography at the Point of Exclusion and Adsorption Transition LC-PEAT). Beside the dominant population of micelles detected by scattering experiments, capillary electrophoresis CE analysis permitted detection of two other populations, one of h-PAA, and the other of free PBA-b-PAA chains, that have very short PBA blocks and never self-assemble. Despite the presence of these free unimers, the self-assembly in solution was found out of equilibrium: the aggregation state is history dependant and no unimer exchange between micelles occurs over months (time-evolution SANS). The high PBA/water interfacial tension, measured at 20 mN/m, prohibits unimer exchange between micelles. PBA-b-PAA solution systems are neither at thermal equilibrium nor completely frozen systems: internal fractionation of individual aggregates can occur.Comment: 32 pages, 16 figures and 4 tables submitted to Journal of Interface and Colloidal Scienc

Replacement of the essential Dictyostelium Arp2 gene by its Entamoeba homologue using parasexual genetics

Background: Cell motility is an essential feature of the pathogenesis and morbidity of amoebiasis caused by Entamoeba histolytica. As motility depends on cytoskeletal organisation and regulation, a study of the molecular components involved is key to a better understanding of amoebic pathogenesis. However, little is known about the physiological roles, interactions and regulation of the proteins of the Entamoeba cytoskeleton. Results: We have established a genetic strategy that uses parasexual genetics to allow essential Dictyostelium discoideum genes to be manipulated and replaced with modified or tagged homologues. Our results show that actin related protein 2 (Arp2) is essential for survival, but that the Dictyostelium protein can be complemented by E. histolytica Arp2, despite the presence of an insertion of 16 amino acids in an otherwise highly conserved protein. Replacement of endogenous Arp2 with myc-tagged Entamoeba or Dictyostelium Arp2 has no obvious effects on growth and the protein incorporates effectively into the Arp2/3 complex. Conclusion: We have established an effective two-step method for replacing genes that are required for survival. Our protocol will allow such genes to be studied far more easily, and also allows an unambiguous demonstration that particular genes are truly essential. In addition, cells in which the Dictyostelium Arp2 has been replaced by the Entamoeba protein are potential targets for drug screens

Probing the exchange field of a quantum-dot spin valve by a superconducting lead

Electrons in a quantum-dot spin valve, consisting of a single-level quantum dot coupled to two ferromagnetic leads with magnetizations pointing in arbitrary directions, experience an exchange field that is induced on the dot by the interplay of Coulomb interaction and quantum fluctuations. We show that a third, superconducting lead with large superconducting gap attached to the dot probes this exchange field very sensitively. In particular, we find striking signatures of the exchange field in the symmetric component of the supercurrent with respect to the bias voltage applied between the ferromagnets already for small values of the ferromagnets' spin polarization.Comment: published version, 10 pages, 7 figure

Pitfalls in Interpreting mp-MRI of the Prostate: A Pictorial Review with Pathologic Correlation

Objectives: The purpose of this pictorial review is to present a wide spectrum of prostate multiparametric MRI (mp-MRI) pitfalls that may occur in clinical practice, with radiological and pathological correlation. Methods: All examinations were performed according to ESUR Guidelines protocols. Results and Conclusion: mp-MRI imaging of the prostate often leads to interpreting doubts and misdiagnosis due to the many interpretative pitfalls that a tissue, whether healthy or treated, may cause. These “false-positive” findings may occur in each stage of the disease history, from the primary diagnosis and staging, to the post-treatment stage, and whether they are caused by the tissue itself or are iatrogenic, their recognition is critical for proper treatment and management. Knowledge of these known pitfalls and their interpretation in the anatomical-radiological context can help radiologists avoid misdiagnosis and consequently mistreatment. Main Messages: • Some physiological changes in the peripheral and central zone may simulate prostate cancer. • Technical errors, such as mispositioned endorectal coils, can affect the mp-MRI interpretation. • Physiological changes post-treatment can simulate recurrenc

Evidence of volcanic ash at a K-T boundary section: Ocean drilling program hole 690 C, Maud Rise, Weddell Sea off East Antarctica

Rare vitric volcanogenic ash but more abundant clay minerals considered volcanogenic in origin are associated with an expanded and essentially complete K-T boundary sequence from Ocean Drilling Project (ODP) Hole 690 C on Maud Rise in the Weddell Sea off East Antarctica. Results at this writing are preliminary and are still based to some extent on shipboard descriptions. Further shore-based studies are in progress. It would appear, however, that the presence of volcanic ash and altered ash in the Danian section beginning at the biostratigraphically and paleomagnetically determined K-T boundary on Maud Rise can be cited as evidence of significant volcanic activity within the South Atlantic-Indian Ocean sector of the Southern Ocean coincident with the time of biotic crises at the end of the Maestrichtian. This is a postulated time of tectonic and volcanic activity within this Southern Hemisphere region, including possible initiation of the Reunion hot spot and a peak in explosive volcanism on Walvis Ridge (1) among other events. A causal relationship with the biotic crisis is possible and volcanism should be given serious consideration as a testable working hypothesis to explain these extinctions

The role of magnetic resonance imaging (MRI) in focal therapy for prostate cancer: recommendations from a consensus panel

OBJECTIVE: To establish a consensus on the utility of multiparametric magnetic resonance imaging (mpMRI) to identify patients for focal therapy. METHODS: Urological surgeons, radiologists, and basic researchers, from Europe and North America participated in a consensus meeting about the use of mpMRI in focal therapy of prostate cancer. The consensus process was face-to-face and specific clinical issues were raised and discussed with agreement sought when possible. All participants are listed among the authors. Topics specifically did not include staging of prostate cancer, but rather identifying the optimal requirements for performing MRI, and the current status of optimally performed mpMRI to (i) determine focality of prostate cancer (e.g. localising small target lesions of \u3e/=0.5 mL), (ii) to monitor and assess the outcome of focal ablation therapies, and (iii) to identify the diagnostic advantages of new MRI methods. In addition, the need for transperineal template saturation biopsies in selecting patients for focal therapy was discussed, if a high quality mpMRI is available. In other words, can mpMRI replace the role of transperineal saturation biopsies in patient selection for focal therapy? RESULTS: Consensus was reached on most key aspects of the meeting; however, on definition of the optimal requirements for mpMRI, there was one dissenting voice. mpMRI is the optimum approach to achieve the objectives needed for focal therapy, if made on a high quality machine (3T with/without endorectal coil or 1.5T with endorectal coil) and judged by an experienced radiologist. Structured and standardised reporting of prostate MRI is paramount. State of the art mpMRI is capable of localising small tumours for focal therapy. State of the art mpMRI is the technique of choice for follow-up of focal ablation. CONCLUSIONS: The present evidence for MRI in focal therapy is limited. mpMRI is not accurate enough to consistently grade tumour aggressiveness. Template-guided saturation biopsies are no longer necessary when a high quality state of the art mpMRI is available; however, suspicious lesions should always be confirmed by (targeted) biopsy

Determinants of postnatal spleen tissue regeneration and organogenesis

Abstract The spleen is an organ that filters the blood and is responsible for generating blood-borne immune responses. It is also an organ with a remarkable capacity to regenerate. Techniques for splenic auto-transplantation have emerged to take advantage of this characteristic and rebuild spleen tissue in individuals undergoing splenectomy. While this procedure has been performed for decades, the underlying mechanisms controlling spleen regeneration have remained elusive. Insights into secondary lymphoid organogenesis and the roles of stromal organiser cells and lymphotoxin signalling in lymph node development have helped reveal similar requirements for spleen regeneration. These factors are now considered in the regulation of embryonic and postnatal spleen formation, and in the establishment of mature white pulp and marginal zone compartments which are essential for spleen-mediated immunity. A greater understanding of the cellular and molecular mechanisms which control spleen development will assist in the design of more precise and efficient tissue grafting methods for spleen regeneration on demand. Regeneration of organs which harbour functional white pulp tissue will also offer novel opportunities for effective immunotherapy against cancer as well as infectious diseases

Utilization of multiparametric prostate magnetic resonance imaging in clinical practice and focal therapy: report from a Delphi consensus project

To codify the use of multiparametric magnetic resonance imaging (mpMRI) for the interrogation of prostate neoplasia (PCa) in clinical practice and focal therapy (FT). An international collaborative consensus project was undertaken using the Delphi method among experts in the field of PCa. An online questionnaire was presented in three consecutive rounds and modified each round based on the comments provided by the experts. Subsequently, a face-to-face meeting was held to discuss and finalize the consensus results. mpMRI should be performed in patients with prior negative biopsies if clinical suspicion remains, but not instead of the PSA test, nor as a stand-alone diagnostic tool or mpMRI-targeted biopsies only. It is not recommended to use a 1.5 Tesla MRI scanner without an endorectal or pelvic phased-array coil. mpMRI should be performed following standard biopsy-based PCa diagnosis in both the planning and follow-up of FT. If a lesion is seen, MRI-TRUS fusion biopsies should be performed for FT planning. Systematic biopsies are still required for FT planning in biopsy-naïve patients and for patients with residual PCa after FT. Standard repeat biopsies should be taken during the follow-up of FT. The final decision to perform FT should be based on histopathology. However, these consensus statements may differ for expert centers versus non-expert centers. The mpMRI is an important tool for characterizing and targeting PCa in clinical practice and FT. Standardization of acquisition and reading should be the main priority to guarantee consistent mpMRI quality throughout the urological communit

Prostate cancer, treatment modalities and complications: an evaluation of the scientific literature

Prostate (PR) cancer (CA) is one of the most common malignant neoplasms in men all over the world. In general, if prostate cancer (PC) is detected early, treatment usually involves either surgical removal of the prostate or radiotherapy (RT). Hormone Therapy (HT) or chemotherapy (CH) is the preferred treatment for more advanced cases of PC or if CA spreads beyond the PT. A number of complications, such as urinary incontinence (IU) or erectile dysfunction (ED), can be associated with some modalities of treatment of the PC. The aim of this work is to evaluate, in PubMed, the number of publications related with prostate cancer and the main modalities of treatment, as well as some clinical complications. The searches were performed in PubMed (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi) in the period 1950 to 2008 using the words: (i) CA, (ii) CA and PR or penis or testis, (iii) CA and PR and RT, CA and PR and surgery (SU), CA and PR and CH and, CA and PR and HT and (iv) CA and PR and RT and IU or ED, CA and PR and SU and IU or ED, CA and PR and CH and IU or ED and, CA and PR and HT and CH and IU or ED, and (V) PC and the same modalities of treatment. The data was obtained on July 20th, 2008. PC, as expected has been cited extensively and surgery has been identified as the most widely referenced modality of treatment. Furthermore, urinary incontinence and erectile dysfunction are important complications that have attracted significant scientific interest. In conclusion, these findings have shown the relevance of the PubMed to analyze quantitatively the publications in cancer and this information could be worthwhile in aiding the comprehension of some clinical aspects related with PC, as well as the development of preventative actions. The analysis of the scientific interest, considering the number of publications in the PubMed, reveals research trends in the field and demonstrates the importance of the surgical procedures in the treatment of the prostate cancer. Moreover, this finding is relevant due to the fact that surgery is the treatment of choice when early detection of PC is achieved. However, it is important to consider clinical complications related to such procedures, such as urinary incontinence and erectile dysfunctions that can reduce the quality of life of the patient