MRI in active surveillance: a critical review

INTRODUCTION: Recent technological advancements and the introduction of modern anatomical and functional sequences have led to a growing role for multiparametric magnetic resonance imaging (mpMRI) in the detection, risk assessment and monitoring of early prostate cancer. This includes men who have been diagnosed with lower-risk prostate cancer and are looking at the option of active surveillance (AS). The purpose of this paper is to review the recent evidence supporting the use of mpMRI at different time points in AS, as well as to discuss some of its potential pitfalls. METHODS: A combination of electronic and manual searching methods were used to identify recent, important papers investigating the role of mpMRI in AS. RESULTS: The high negative predictive value of mpMRI can be exploited for the selection of AS candidates. In addition, mpMRI can be efficiently used to detect higher risk disease in patients already on surveillance. CONCLUSION: Although there is an ongoing debate regarding the precise nature of its optimal implementation, mpMRI is a promising risk stratification tool and should be considered for men on AS

The FGF2‐induced tanycyte proliferation involves a connexin 43 hemichannel/purinergic‐dependent pathway

In the adult hypothalamus, the neuronal precursor role is attributed to the radial glia-like cells that line the third-ventricle (3V) wall called tanycytes. Under nutritional cues, including hypercaloric diets, tanycytes proliferate and differentiate into mature neurons that moderate body weight, suggesting that hypothalamic neurogenesis is an adaptive mechanism in response to metabolic changes. Previous studies have shown that the tanycyte glucosensing mechanism depends on connexin-43 hemichannels (Cx43 HCs), purine release, and increased intracellular free calcium ion concentration [(Ca2+)i] mediated by purinergic P2Y receptors. Since, Fibroblast Growth Factor 2 (FGF2) causes similar purinergic events in other cell types, we hypothesize that this pathway can be also activated by FGF2 in tanycytes to promote their proliferation. Here, we used bromodeoxyuridine (BrdU) incorporation to evaluate if FGF2-induced tanycyte cell division is sensitive to Cx43 HC inhibition in vitro and in vivo. Immunocytochemical analyses showed that cultured tanycytes maintain the expression of in situ markers. After FGF2 exposure, tanycytic Cx43 HCs opened, enabling release of ATP to the extracellular milieu. Moreover, application of external ATP was enough to induce their cell division, which could be suppressed by Cx43 HC or P2Y1-receptor inhibitors. Similarly, in vivo experiments performed on rats by continuous infusion of FGF2 and a Cx43 HC inhibitor into the 3V, demonstrated that FGF2-induced β-tanycyte proliferation is sensitive to Cx43 HC blockade. Thus, FGF2 induced Cx43 HC opening, triggered purinergic signaling, and increased β-tanycytes proliferation, highlighting some of the molecular mechanisms involved in the cell division response of tanycyte

Role of multiparametric magnetic resonance imaging for patients under active surveillance for prostate cancer : a systematic review with diagnostic meta-analysis

Background: The use of multiparametric magnetic resonance imaging (mpMRI) in the setting of patients under active surveillance (AS) is promising. In this systematic-review we aimed to analyse the role of mpMRI in patients under AS. Methods: A comprehensive literature research for English-language original and review articles, recently published, was carried out using Medline, Scopus and Web of sciences databases until 30 October 2017. The following MeSH terms were used: 'active surveillance', 'prostate cancer', 'multiparametric magnetic resonance imaging'. A diagnostic meta-analysis was performed for 3.0 T mpMRI in predicting disease re-classification. Results: In total, 226 studies were selected after research and after removal of duplicates. After analysis on inclusion criteria, 43 studies were identified as eligible for this systematic review with a total of 6,605 patients. The timing of MRI during follow-up of AS differed from all studies like criteria for inclusion in the AS protocol. Overall, there was a low risk of bias across all studies. The diagnostic meta-analysis for 1.5 tesla showed a sensitivity of 0.60, negative predictive value (NPV) of 0.75 and a hierarchical summary receiving operating curve (HSROC) of 0.74 while for 3.0 tesla mpMRI a sensitivity of 0.81, a NPV of 0.78 and a HSROC of 0.83. Conclusions: Overall, the available evidence suggests that both 1.5 or 3.0 Tesla mpMRI are a valid tool to monitor progression during AS follow-up, showing good accuracy capabilities in detecting PCa re-classification. However, the modality to better define what means 'disease progression' on mpMRI must be further evaluated