Nicolas Barry Delongchamps

Multiparametric magnetic resonance imaging for the detection and localization of prostate cancer: combination of T2-weighted, dynamic contrast-enhanced and diffusion-weighted imaging.

Study Type – Diagnostic (exploratory cohort) 
Level of Evidence 2b

Prebiopsy Magnetic Resonance Imaging and Prostate Cancer Detection: Comparison of Random and Targeted Biopsies

PURPOSE We compared the accuracy of visual targeted biopsies vs computerized transrectal ultrasound-magnetic resonance imaging registration using a rigid (Esaote®, nondeformable) or elastic (Koelis®, deformable) approach. MATERIALS AND METHODS A total of 391 consecutive patients with suspected localized prostate cancer were prospectively included in analysis. All patients underwent prostate magnetic resonance imaging, followed by 10 to 12-core random prostate biopsies. When magnetic resonance imaging detected suspicious findings, targeted biopsy was performed, including visual, rigid system and elastic system targeted biopsies in the first 127 patients, the next 131 and the last 133, respectively. Cancer detection rates were assessed by conditional logistic regression. Targeted biopsies alone and random biopsies were further compared for the amount of tissue sampled and microfocal cancer detection, the latter defined as a single core with 5 mm or less of Gleason 6 cancer. RESULTS Patient characteristics and random biopsy detection rates were similar among the groups. Magnetic resonance imaging detected at least 1 suspicious area in 54 (42%), 78 (59%) and 82 patients (62%) in groups 1, 2 and 3, respectively. The cancer detection rates of rigid and elastic system targeted biopsies were significantly higher than the random biopsy rate (p = 0.0065 and 0.0016, respectively). Visual targeted biopsy did not perform better than random biopsy (p = 0.66). Rigid and elastic system targeted biopsies allowed for decreasing the number of cores and the detection of microfocal cancer, while increasing the detection of high grade cancer. CONCLUSIONS When performed with computerized magnetic resonance imaging-transrectal ultrasound image registration, targeted biopsy alone improved cancer detection over random biopsies, decreased the detection rate of microfocal cancer and increased the detection rate of cancer with a Gleason score of greater than 6.

Early T Cell Signalling Is Reversibly Altered in PD-1+ T Lymphocytes Infiltrating Human Tumors

To improve cancer immunotherapy, a better understanding of the weak efficiency of tumor-infiltrating T lymphocytes (TIL) is necessary. We have analyzed the functional state of human TIL immediately after resection of three types of tumors (NSCLC, melanoma and RCC). Several signalling pathways (calcium, phosphorylation of ERK and Akt) and cytokine secretion are affected to different extents in TIL, and show a partial spontaneous recovery within a few hours in culture. The global result is an anergy that is quite distinct from clonal anergy induced in vitro, and closer to adaptive tolerance in mice. PD-1 (programmed death -1) is systematically expressed by TIL and may contribute to their anergy by its mere expression, and not only when it interacts with its ligands PD-L1 or PD-L2, which are not expressed by every tumor. Indeed, the TCR-induced calcium and ERK responses were reduced in peripheral blood T cells transfected with PD-1. Inhibition by sodium stibogluconate of the SHP-1 and SHP-2 phosphatases that associate with several inhibitory receptors including PD-1, relieves part of the anergy apparent in TIL or in PD-1-transfected T cells. This work highlights some of the molecular modifications contributing to functional defects of human TIL.

Saturation biopsies on autopsied prostates for detecting and characterizing prostate cancer

To evaluate a 36‐core saturation biopsy scheme on autopsied prostate glands to estimate the detection rate based on the true cancer prevalence, and to compare the cancer features on biopsy with whole‐mount pathological analysis, as saturation biopsies have been proposed as a tool to increase the prostate cancer detection rate, and as a staging tool to identify potentially insignificant cancers before surgery.

Detection of significant prostate cancer with magnetic resonance targeted biopsies--should transrectal ultrasound-magnetic resonance imaging fusion guided biopsies alone be a standard of care?

PURPOSE Magnetic resonance imaging-transrectal ultrasound fusion targeted prostate biopsies were suggested to detect significant cancer with more accuracy than systematic biopsies. In this study we evaluate the pathological characteristics of multiparametric magnetic resonance imaging detected and undetected tumor foci on radical prostatectomy specimens. MATERIALS AND METHODS We selected 125 consecutive patients treated with radical prostatectomy for clinically localized prostate cancer diagnosed on magnetic resonance imaging-transrectal ultrasound targeted biopsy and/or systematic biopsy. On multiparametric magnetic resonance imaging each suspicious area was graded according to the PI-RADS score. On radical prostatectomy specimen, tumor foci with a Gleason score greater than 3+3 and/or tumor volume greater than 0.5 ml were considered significant. A correlation analysis between multiparametric magnetic resonance imaging and pathological findings was performed. RESULTS Pathological analysis of radical prostatectomy specimens detected 230 tumor foci. Of these, 137 were considered significant (Gleason score greater than 3+3 in 112) and were observed in 111 (89%) glands. A total of 95 individual tumor foci, including 14 significant foci, were missed with multiparametric magnetic resonance imaging. All of them were located in glands where another focus was detected with multiparametric magnetic resonance imaging. An additional 9 individual tumor foci, including 7 significant, were detected on multiparametric magnetic resonance imaging but missed with targeted biopsy, resulting in 5 (4%) significant cancers undetected with magnetic resonance imaging-transrectal ultrasound fusion targeted biopsy. The magnetic resonance imaging target largest diameter was associated with high volume (greater than 0.5 cc) foci detection, while PI-RADS score and cancer involvement on targeted biopsy were associated with significant foci detection. CONCLUSIONS In these series of men with suspicious prostate multiparametric magnetic resonance imaging findings, magnetic resonance imaging-transrectal ultrasound fusion guided targeted biopsy alone strategy would have resulted in the under detection of only 4% significant cancers.

Tumor target volume for focal therapy of prostate cancer-does multiparametric magnetic resonance imaging allow for a reliable estimation?

PURPOSE We determined whether endorectal multiparametric magnetic resonance imaging at 1.5 Tesla could predict tumor target volume in the perspective of focal therapy of prostate cancer. MATERIALS AND METHODS A total of 84 consecutive patients underwent multiparametric magnetic resonance imaging before radical prostatectomy. The volume of each suspicious area detected on magnetic resonance imaging and of all surgical histological foci was determined by planimetry. We first used each magnetic resonance imaging sequence (T2-weighted, diffusion weighted and dynamic contrast enhanced) and then the sequence showing the largest tumor area (multiparametric volume). Finally, the largest area of any sequence was used to calculate a target volume according to the volume of a cylinder. Agreement between magnetic resonance imaging and pathological findings was assessed by linear regression and residual analysis. RESULTS Histology revealed 99 significant tumors with a volume of greater than 0.2 cc and/or a Gleason score of greater than 6. Of the tumors 16 (16.2%) were undetected by multiparametric magnetic resonance imaging. Linear regression analysis showed that tumor volume estimated by T2-weighted or diffusion weighted imaging correlated significantly with pathological volume (r(2) = 0.82 and 0.83, respectively). Residuals from diffusion weighted imaging volume estimations did not significantly differ from 0. Nevertheless, diffusion weighted imaging underestimated pathological volume in 43 of 87 cases (49%) by a mean of 0.56 cc (range 0.005 to 2.84). Multiparametric and target volumes significantly overestimated pathological volume by a mean of 16% and 44% with underestimation in 28 (32%) and 15 cases (17%), respectively. Volume underestimation was significantly higher for tumor foci less than 0.5 cc. The percent of Gleason grade 4 did not influence tumor volume estimation. CONCLUSIONS Magnetic resonance imaging can detect most significant tumors. However, delineating a target volume may require further adjustment before planning magnetic resonance imaging targeted focal treatment.

Thrombospondin-1 Triggers Cell Migration and Development of Advanced Prostate Tumors

The antitumor effects of pharmacologic inhibitors of angiogenesis are hampered in patients by the rapid development of tumor resistance, notably through increased invasiveness and accelerated metastasis. Here, we reevaluated the role of the endogenous antiangiogenic thrombospondin 1 (TSP1) in prostate carcinomas in which angiogenesis is an active process. In xenografted tumors, we observed that TSP1 altogether inhibited angiogenesis and fostered tumor development. Our results show that TSP1 is a potent stimulator of prostate tumor cell migration. This effect required CD36, which also mediates TSP1 antiangiogenic activity, and was mimicked by an antiangiogenic TSP1-derived peptide. As suspected for pharmacologic inhibitors of angiogenesis, the TSP1 capacities to increase hypoxia and to trigger cell migration are thus inherently linked. Importantly, although antiangiogenic TSP1 increases hypoxia in vivo, our data show that, in turn, hypoxia induced TSP1, thus generating a vicious circle in prostate tumors. In radical prostatectomy specimens, we found TSP1 expression significantly associated with invasive tumors and with tumors which eventually recurred. TSP1 may thus help select patients at risk of prostate-specific antigen relapse. Together, the data suggest that intratumor disruption of the hypoxic cycle through TSP1 silencing will limit tumor invasion.

Saturation biopsies for prostate cancer: current uses and future prospects

Since its introduction, ultrasound-guided prostate biopsy has undergone significant evolution. Because of the low sensitivity of ultrasonography in detecting prostate cancer, tissue is sampled randomly within the gland. In an attempt to enhance cancer detection and characterization, the trend has been to increase the number of biopsy cores taken. Saturation biopsies of the prostate gland were first evaluated as a diagnostic tool. When performed as an initial procedure, saturation biopsies do not seem to improve cancer detection when compared to standard biopsy. However, saturation biopsies might be of clinical value in patients with previous negative standard biopsies but persistently rising PSA levels. As a staging tool, the use of saturation biopsies was proposed mainly to avoid overtreatment of clinically insignificant cancers. Results from clinical and autopsy studies have suggested that saturation biopsies are more accurate than standard biopsies in histological characterization of prostate cancer. Improving cancer characterization might require an increase in the number of cores taken, but knowing their precise location is paramount. Strict template guidance and three-dimensional techniques offer a more comprehensive approach than current ultrasound-guided approaches, and the advantage of precisely recording every core location. New imaging techniques, such as diffusion-weighted and spectroscopic MRI might also help in targeting prostate biopsies.

Hybrid tumour ‘oncocytoma‐chromophobe renal cell carcinoma’ of the kidney: a report of seven sporadic cases

To determine whether renal hybrid tumours (HT) appear as a specific clinical and radiological entity, as HT are characterized by the association of both oncocytes and chromophobe cells within the same tumour, and have been described in patients with oncocytosis and Birt‐Hogg‐Dube syndrome.

Bladder recurrence after radical nephroureterectomy: predictors and impact on oncological outcomes.

To identify predictive factors of bladder recurrence after radical nephroureterectomy and to evaluate the impact of this event on oncological outcomes.