Prostatectomie radicale robot-assistée par abord extrapéritonéal (10 ans d expérience)

Objectifs : Décrire les résultats de 1000 prostatectomies radicales robot-assistées (PRRA) par voie extrapéritonéale. Méthodes : De 2001 à 2011,1019 patients ont été opérés par PRRA pour un cancer de la prostate localisé. Le suivi moyen était de 24.6 mois. Les données démographiques, chirurgicales et post-opératoires étaient collectées dans une base de données prospective. Résultats : L âge moyen était de 62.7 ans, le PSA pré-opératoire moyen de 9,27 et le score de Gleason pré-opératoire moyen de 6,4 (Gleason 6 : 59,8% ; Gleason 7 : 33,1%). La durée opératoire et les pertes sanguines moyennes étaient respectivement de 129 minutes et 514 mL. La durée moyenne de séjour et de sondage urinaire était respectivement de 4 et 7,9 jours. Le taux de complication était de 15,6%. Le taux de préservation nerveuse unilatérale et bilatérale était respectivement de 9,2% et 70,3%. Il y avait 31,7% pT3a et 10,4% pT3b-pT4 (25,2% de bas risques et 59,4% de risques intermédiaires selon D Amico). Le taux de marges chirurgicales positives était de 19,8% dans les cancers pT2, 42.4% dans les pT3a et 62.8% dans les pT3b et pT4 pour un taux moyen de marge de 31,8%. La continence était de 75% à 12 mois et la puissance sexuelle de 52,2%. Le taux de progression à 5 ans est de 21,5% et 7% des patients ont eu d un traitement complémentaire. Conclusions : En 10 ans la PRRA s'est imposée comme une alternative aux traitements de référence avec des résultats oncologiques et fonctionnels comparables associés à certains avantages spécifiques. La sélection des patients et de la technique opératoire reste le principal enjeu afin de réduire le taux de marge en conservant des résultats fonctionnels satisfaisantsPARIS12-CRETEIL BU Médecine (940282101) / SudocSudocFranceF

Methotrexate efficacy and tolerance in plaque psoriasis. A prospective real-life multicentre study in France

International audienc

Clinical trial protocol for P-NeLoP: a randomized controlled trial comparing the feasibility and outcomes of robot-assisted partial nephrectomy with low insufflation pressure using AirSeal versus standard insufflation pressure (UroCCR no. 85 study)

Abstract Robot-assisted partial nephrectomy (RAPN) is the standard of care for small, localized kidney tumors. This surgery is conducted within a short hospital stay and can even be performed as outpatient surgery in selected patients. In order to allow early rehabilitation of patients, an optimal control of postoperative pain is necessary. High-pressure pneumoperitoneum during surgery seems to be the source of significant pain during the first hours postoperatively. Our study is a prospective, randomized, multicenter, controlled study which aims to compare post-operative pain at 24 h between patients undergoing RAPN at low insufflation pressure (7 mmHg) and those operated on at standard pressure (12 mmHg) using the AirSeal system. This trial is registered in the US National Library of Medicine Trial Registry (NCT number: NCT05404685)

The Impact of Histological Variants on Oncological Outcomes After Surgical Resection of a Nonmetastatic Renal Cell Carcinoma with Tumor Thrombus: A Multi-institutional Study

International audienceBackgroundThere is no definitive evidence of the prognosis impact of histological variants (HVs) in patients who undergo surgical resection of a nonmetastatic renal cell carcinoma (nm-RCC) with venous tumor thrombus (TT).ObjectiveTo investigate the impact of HVs on the prognosis of patients with nm-RCC with TT after radical surgery.Design, setting, and participantsPatients who underwent radical nephrectomy with the removal of the venous TT for an nm-RCC were included in a retrospective study.Outcome measurements and statistical analysisThree groups were identified: clear cell (ccRCC), papillary (pRCC), and chromophobe (chRCC) RCC. The primary outcome measures (disease-free and overall survival [OS]) were assessed using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate Cox proportional hazard models were used to study the impact of HVs on survival.Results and limitationsA total of 873 patients were included. The histological subtypes were distributed as follows: ccRCC in 780 cases, pRCC in 58 cases, and chRCC in 35 cases. At the time of data analysis, 612 patients were recurrence free and 228 had died. A survival analysis revealed significant differences in both OS and recurrence-free survival across histological subtypes, with the poorest outcomes observed in pRCC patients (p < 0.05). In a multivariable analysis, pRCC was independently associated with worse disease-free survival and OS (hazard ratio [HR]: 1.71; p = 0.01 and HR: 1.24; p = 0.04), while chRCC was associated with more favorable outcomes than ccRCC (HR: 0.05; p < 0.001 and HR: 0.02; p < 0.001). A limitation of the study is its retrospective nature.ConclusionsIn this multicentric series, HVs appeared to impact the medium-term oncological prognosis of kidney cancer with TT

Real-World Effectiveness and Safety of Apremilast in Older Patients with Psoriasis

Introduction: Apremilast is a drug recently developed for psoriasis. Few data are available on its use in the elderly. We evaluated the tolerance and effectiveness of apremilast used in daily practice for psoriasis treatment in older patients. Methods: We performed a multicenter, retrospective study involving patients aged ≥ 65 years who had received apremilast as a psoriasis treatment. Demographic data and details regarding psoriasis and adverse events (AEs) were collected from patient medical records. Results: 135 patients were included (mean age: 73.5 years). Treatment was stopped in 74 patients (54.8%) for AEs (n = 43, 56.6%), primary failures (n = 18, 23.4%), and relapses (n = 7, 9.2%). When patients were stratified by age at treatment initiation, the main cause of discontinuation in patients ≥ 75 years was AEs, whereas in patients aged 65–74 years it was primary failures (28.3%). Sixty-one patients reported AEs, mainly digestive (n = 49). Regarding effectiveness, 45.2% of patients reached PGA 0/1 between 3 and 6 months after treatment initiation. One-year apremilast continuation rates were better in the 65–74 and 75–84 years subgroups than in the > 85 years subgroup (p = 0.01). Conclusion: Apremilast seems to be an effective and safe therapeutic option for psoriasis in the elderly. The main AEs reported by patients did not seem to differ from those reported previously in younger populations. However, AEs were more frequent in patients > 75 years old leading to more frequent discontinuation of apremilast compared with younger patients, suggesting a higher level of vigilance is needed in the elderly

Effectiveness and safety of anti-interleukin-17 therapies in elderly patients with psoriasis

Anti-interleukin-17 agents have recently been develo-ped for the treatment of psoriasis. This study evaluated the tolerance and effectiveness of anti-interleukin-17 agents for psoriasis in elderly patients in daily practi-ce. A multicentre, retrospective study was performed, involving psoriatic patients aged ≥65 years who had received an anti-interleukin-17 agent, including se-cukinumab, ixekizumab or brodalumab. A total of 114 patients were included: 72 received secukinumab, 35 ixekizumab, and 7 brodalumab. Treatment was stop-ped in 32 patients (28.9%), because of relapses in 14 patients (41.2%), primary failures in 11 patients (32.4%), or adverse events in 7 patients (20.6%). The 3 most frequently reported adverse events were injec-tion site reactions (n = 4), oral candidiasis (n = 3), and influenza-like illness (n = 3). Regarding effectiveness, 80 patients (70%) reached a Physician Global Assessment score of 0/1, 6 months after treatment initiation. In conclusion, anti-interleukin-17 therapy appears to be an effective and safe therapeutic option for psoriasis treatment in patients aged ≥ 65 years

Immune checkpoints are predominantly co-expressed by clonally expanded CD4+FoxP3+ intratumoral T-cells in primary human cancers

Abstract Background In addition to anti-PD(L)1, anti-CTLA-4 and anti-LAG-3, novel immune checkpoint proteins (ICP)-targeted antibodies have recently failed to demonstrate significant efficacy in clinical trials. In these trials, patients were enrolled without screening for drug target expression. Although these novel ICP-targeted antibodies were expected to stimulate anti-tumor CD8 + T-cells, the rationale for their target expression in human tumors relied on pre-clinical IHC stainings and transcriptomic data, which are poorly sensitive and specific techniques for assessing membrane protein expression on immune cell subsets. Our aim was to describe ICP expression on intratumoral T-cells from primary solid tumors to better design upcoming neoadjuvant cancer immunotherapy trials. Methods We prospectively performed multiparameter flow cytometry and single-cell RNA sequencing (scRNA-Seq) paired with TCR sequencing on freshly resected human primary tumors of various histological types to precisely determine ICP expression levels within T-cell subsets. Results Within a given tumor type, we found high inter-individual variability for tumor infiltrating CD45 + cells and for T-cells subsets. The proportions of CD8+ T-cells (~ 40%), CD4+ FoxP3- T-cells (~ 40%) and CD4+ FoxP3+ T-cells (~ 10%) were consistent across patients and indications. Intriguingly, both stimulatory (CD25, CD28, 4-1BB, ICOS, OX40) and inhibitory (PD-1, CTLA-4, PD-L1, CD39 and TIGIT) checkpoint proteins were predominantly co-expressed by intratumoral CD4+FoxP3+ T-cells. ScRNA-Seq paired with TCR sequencing revealed that T-cells with high clonality and high ICP expressions comprised over 80% of FoxP3+ cells among CD4+ T-cells. Unsupervised clustering of flow cytometry and scRNAseq data identified subsets of CD8+ T-cells and of CD4+ FoxP3- T-cells expressing certain checkpoints, though these expressions were generally lower than in CD4+ FoxP3+ T-cell subsets, both in terms of proportions among total T-cells and ICP expression levels. Conclusions Tumor histology alone does not reveal the complete picture of the tumor immune contexture. In clinical trials, assumptions regarding target expression should rely on more sensitive and specific techniques than conventional IHC or transcriptomics. Flow cytometry and scRNAseq accurately characterize ICP expression within immune cell subsets. Much like in hematology, flow cytometry can better describe the immune contexture of solid tumors, offering the opportunity to guide patient treatment according to drug target expression rather than tumor histological type