Safety of meglumine gadoterate (Gd-DOTA)-enhanced MRI compared to unenhanced MRI in patients with chronic kidney disease (RESCUE study)

OBJECTIVE: To prospectively compare the renal safety of meglumine gadoterate (Gd-DOTA)-enhanced magnetic resonance imaging (MRI) to a control group (unenhanced MRI) in high-risk patients. METHODS: Patients with chronic kidney disease (CKD) scheduled for MRI procedures were screened. The primary endpoint was the percentage of patients with an elevation of serum creatinine levels, measured 72 ± 24 h after the MRI procedure, by at least 25 % or 44.2 μmol/l (0.5 mg/dl) from baseline. A non-inferiority margin of the between-group difference was set at −15 % for statistical analysis of the primary endpoint. Main secondary endpoints were the variation in serum creatinine and eGFR values between baseline and 72 ± 24 h after MRI and the percentage of patients with a decrease in eGFR of at least 25 % from baseline. Patients were screened for signs of nephrogenic systemic fibrosis (NSF) at 3-month follow-up. RESULTS: Among the 114 evaluable patients, one (1.4 %) in the Gd-DOTA-MRI group and none in the control group met the criteria of the primary endpoint [Δ = −1.4 %, 95%CI = (−7.9 %; 6.7 %)]. Non-inferiority was therefore demonstrated (P = 0.001). No clinically significant differences were observed between groups for the secondary endpoints. No serious safety events (including NSF) were noted. CONCLUSION: Meglumine gadoterate did not affect renal function and was a safe contrast agent in patients with CKD. KEY POINTS: • Contrast-induced nephropathy (CIN) is a potential problem following gadolinium administration for MRI. • Meglumine gadoterate (Gd-DOTA) appears safe, even in patients with chronic kidney disease. • Gd-DOTA only caused a temporary creatinine level increase in 1/70 such patients. • No case or sign of NSF was detected at 3-month follow-up

ESUR prostate MR guidelines 2012

The aim was to develop clinical guidelines for multi-parametric MRI of the prostate by a group of prostate MRI experts from the European Society of Urogenital Radiology (ESUR), based on literature evidence and consensus expert opinion. True evidence-based guidelines could not be formulated, but a compromise, reflected by “minimal” and “optimal” requirements has been made. The scope of these ESUR guidelines is to promulgate high quality MRI in acquisition and evaluation with the correct indications for prostate cancer across the whole of Europe and eventually outside Europe. The guidelines for the optimal technique and three protocols for “detection”, “staging” and “node and bone” are presented. The use of endorectal coil vs. pelvic phased array coil and 1.5 vs. 3 T is discussed. Clinical indications and a PI-RADS classification for structured reporting are presented

Evaluation de l'IRM dynamique pour le diagnostic du cancer de prostate (à propos de 46 corrélations imagerie-anatomopathologie)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Traitement endovasculaire des sténoses veineuses juxta-anastomotiques des fistules radio-radiales pour l'hémodialyse (suivi à long terme et facteurs pronostiques)

LYON1-BU Santé (693882101) / SudocSudocFranceF

Elastographie par résonance magnétique du rein (étude de faisabilité sur dix volontaires sains)

LYON1-BU Santé (693882101) / SudocSudocFranceF

Atteintes rénales de la sclérose tubéreuse de Bourneville, revue bibliographiqe et enquête sur la qualité de prise en charge auprès de 257 patients

LYON1-BU Santé (693882101) / SudocSudocFranceF

Apport de l'imagerie au traitement du cancer de prostate par ultrasons focalises de haute intensité

Nous avons tenté, dans ce travail, d'améliorer l'évaluation radiologique des patients traités par HIFU transrectaux pour cancer de prostate dans 4 directions différentes. 1. Meilleure définition de la cible : l'IRM dynamique après injection de gadolinium semble une technique prometteuse de localisation du cancer à l'intérieur de la glande. Dans un premier temps, nous avons obtenu les courbes de rehaussement du cancer de prostate et des tissus sains avoisinants et nous avons cherché à en déduire la meilleure fenêtre d'imagerie. Nous avons ensuite appliqué cette technique aux patients présentant une récidive après traitement radiothérapique et prouvé que, dans ce sous groupe, l'imagerie dynamique permettait une meilleure visualisation du cancer que l'IRM T2 classique. 2. Appréciation de la zone traitée : nous avons montré que l'IRM permettait une évaluation fiable des limites de la zone traitée par les HIFU; en revanche, elle ne permet pas d'apprécier la qualité de la nécrose. Une étude de faisabilité a montré que l'élastographie échographique pouvait aussi montrer les limites de la zone de nécrose induite par les HIFU. 3. Recherche de facteurs pronostiques : nous avons montré que la perfusion prostatique (appréciée par Doppler couleur) n'influait pas sur la qualité de la nécrose induite par les HIFU et que le Doppler ne pouvait donc pas prédire les résultats du traitement. 4.Suivi post-thérapeutique : le Doppler couleur peut détecter les foyers tumoraux résiduels après traitement HIFU mais notre évaluation a montré que ses performances ne permettaient pas de se passer des biopsies systématiques de contrôleLYON1-BU.Sciences (692662101) / SudocSudocFranceF

Mid-term results demonstrate salvage high-intensity focused ultrasound (HIFU) as an effective and acceptably morbid salvage treatment option for locally radiorecurrent prostate cancer.

BACKGROUND: Local occurrence of prostate cancer (PCa) after external beam radiation (EBRT) may benefit from definitive local therapy. OBJECTIVE: To evaluate the safety and efficacy of salvage high-intensity focal ultrasound (HIFU) in local PCa recurrence after EBRT and to determine prognostic factors for optimal patient selection. DESIGN, SETTING, AND PARTICIPANTS: Between 1995 and 2006, patients with a local PCa recurrence after EBRT were retrospectively included. INTERVENTION: All patients received salvage HIFU with the Ablatherm device. MEASUREMENTS: Prognostic factors (pre-EBRT risk group, androgen-deprivation [AD] use, pre-HIFU prostate-specific antigen [PSA], Gleason score and positive biopsy percentage) were studied in univariate and multivariate analyses. Progression was defined as positive biopsy and/or last PSA > nadir + 2 ng/ml and/or adjuvant therapy introduction. All complications were recorded. RESULTS AND LIMITATIONS: Some 194 HIFU sessions for 167 patients were performed. Local cancer control was achieved with negative biopsy results in 122 (73%) patients. The median PSA nadir was 0.19 ng/ml. The mean follow-up period was 18.1 mo (range: 3-121 mo). Seventy-four patients required no hormone therapy. The actuarial 5-yr overall survival rate was 84%. The actuarial 3-yr progression-free survival rate was significantly lower in three circumstances: (1) worsening of the pre-EBRT stage with 53%, 42%, and 25% for low-, intermediate-, and high-risk patients, respectively, (2) increase in the pre-HIFU PSA, and (3) use of AD during PCa management. In multivariate analyses, the risk ratio for intermediate- and high-risk patients were 1.32 and 1.96, respectively. The risk ratio was 2.8 if patients had received AD. No rectal complications were observed. Urinary incontinence accounted for 49.5% of the urinary sphincter implantations required in 11% of patients. This is a retrospective study in which the role of the PSA doubling time and the time until recurrence was not evaluated. CONCLUSIONS: Salvage HIFU is a curative treatment option for local relapse after EBRT with acceptable morbidity. Careful patient selection is imperative depending upon the aforementioned prognostic factors

The current role of prostate multiparametric magnetic resonance imaging

Prostate multi-parametric magnetic resonance imaging (mpMRI) has shown excellent sensitivity for Gleason ≥7 cancers, especially when their volume is ≥0.5 mL. As a result, performing an mpMRI before prostate biopsy could improve the detection of clinically significant prostate cancer (csPCa) by adding targeted biopsies to systematic biopsies. Currently, there is a consensus that targeted biopsies improve the detection of csPCa in the repeat biopsy setting and at confirmatory biopsy in patients considering active surveillance. Several prospective multicentric controlled trials recently showed that targeted biopsy also improved csPCa detection in biopsy-naïve patients. The role of mpMRI and targeted biopsy during the follow-up of active surveillance remains unclear. Whether systematic biopsy could be omitted in case of negative mpMRI is also a matter of controversy. mpMRI did show excellent negative predictive values (NPV) in the literature, however, since NPV depends on the prevalence of the disease, negative mpMRI findings should be interpreted in the light of a priori risk for csPCa of the patient. Nomograms combining mpMRI findings and classical risk predictors (age, prostate-specific antigen density, digital rectal examination, etc.) will probably be developed in the future to decide whether a prostate biopsy should be obtained. mpMRI has a good specificity for detecting T3 stage cancers, but its sensitivity is low. It should therefore not be used routinely for staging purposes in low-risk patients. Nomograms combining mpMRI findings and other clinical and biochemical data will also probably be used in the future to better assess the risk of T3 stage disease. Keywords: Prostate cancer, Magnetic resonance imaging, Prostate biopsy, Active surveillance, Nomogram

Emergence of Single- versus Multi-State Allostery

Several physical mechanisms have been proposed to explain allostery in proteins. They differ by the number of internal states that they assume a protein to occupy, leaving open the question of what controls the emergence of these distinct physical forms of allostery. Here, we analyze a simplified model of protein allostery under a range of physical and evolutionary constraints. We find that a continuum of mechanisms between two archetypes emerges through evolution. In one limit, a single-state mechanism exists where ligand binding induces a displacement along a single normal mode, and in the other limit, a multi-state mechanism exists where ligand binding induces a switch across an energy barrier to a different stable state. Importantly, whenever the two mechanisms are possible, the multi-state mechanism confers a stronger allosteric effect and thus a selective advantage. This work defines the essential constraints that distinguish single- and multi-state allostery and sets the stage for a physical theory of its evolutionary origins