Minimally invasive versus open distal pancreatectomy for resectable pancreatic cancer (DIPLOMA):an international randomised non-inferiority trial

Background: The oncological safety of minimally invasive surgery has been questioned for several abdominal cancers. Concerns also exist regarding the use of minimally invasive distal pancreatectomy (MIDP) in patients with resectable pancreatic cancer as randomised trials are lacking. Methods: In this international randomised non-inferiority trial, we recruited adults with resectable pancreatic cancer from 35 centres in 12 countries. Patients were randomly assigned to either MIDP (laparoscopic or robotic) or open distal pancreatectomy (ODP). Both patients and pathologists were blinded to the assigned approach. Primary endpoint was radical resection (R0, ≥1 mm free margin) in patients who had ultimately undergone resection. Analyses for the primary endpoint were by modified intention-to-treat, excluding patients with missing data on primary endpoint. The pre-defined non-inferiority margin of −7% was compared with the lower limit of the two-sided 90% confidence interval (CI) of absolute difference in the primary endpoint. This trial is registered with the ISRCTN registry (ISRCTN44897265). Findings: Between May 8, 2018 and May 7, 2021, 258 patients were randomly assigned to MIDP (131 patients) or ODP (127 patients). Modified intention-to-treat analysis included 114 patients in the MIDP group and 110 patients in the ODP group. An R0 resection occurred in 83 (73%) patients in the MIDP group and in 76 (69%) patients in the ODP group (difference 3.7%, 90% CI −6.2 to 13.6%; pnon-inferiority = 0.039). Median lymph node yield was comparable (22.0 [16.0–30.0] vs 23.0 [14.0–32.0] nodes, p = 0.86), as was the rate of intraperitoneal recurrence (41% vs 38%, p = 0.45). Median follow-up was 23.5 (interquartile range 17.0–30.0) months. Other postoperative outcomes were comparable, including median time to functional recovery (5 [95% CI 4.5–5.5] vs 5 [95% CI 4.7–5.3] days; p = 0.22) and overall survival (HR 0.99, 95% CI 0.67–1.46, p = 0.94). Serious adverse events were reported in 23 (18%) of 131 patients in the MIDP group vs 28 (22%) of 127 patients in the ODP group. Interpretation: This trial provides evidence on the non-inferiority of MIDP compared to ODP regarding radical resection rates in patients with resectable pancreatic cancer. The present findings support the applicability of minimally invasive surgery in patients with resectable left-sided pancreatic cancer. Funding: Medtronic Covidien AG, Johnson &amp; Johnson Medical Limited, Dutch Gastroenterology Society.</p

Minimally invasive versus open distal pancreatectomy for resectable pancreatic cancer (DIPLOMA):an international randomised non-inferiority trial

Background: The oncological safety of minimally invasive surgery has been questioned for several abdominal cancers. Concerns also exist regarding the use of minimally invasive distal pancreatectomy (MIDP) in patients with resectable pancreatic cancer as randomised trials are lacking. Methods: In this international randomised non-inferiority trial, we recruited adults with resectable pancreatic cancer from 35 centres in 12 countries. Patients were randomly assigned to either MIDP (laparoscopic or robotic) or open distal pancreatectomy (ODP). Both patients and pathologists were blinded to the assigned approach. Primary endpoint was radical resection (R0, ≥1 mm free margin) in patients who had ultimately undergone resection. Analyses for the primary endpoint were by modified intention-to-treat, excluding patients with missing data on primary endpoint. The pre-defined non-inferiority margin of −7% was compared with the lower limit of the two-sided 90% confidence interval (CI) of absolute difference in the primary endpoint. This trial is registered with the ISRCTN registry (ISRCTN44897265). Findings: Between May 8, 2018 and May 7, 2021, 258 patients were randomly assigned to MIDP (131 patients) or ODP (127 patients). Modified intention-to-treat analysis included 114 patients in the MIDP group and 110 patients in the ODP group. An R0 resection occurred in 83 (73%) patients in the MIDP group and in 76 (69%) patients in the ODP group (difference 3.7%, 90% CI −6.2 to 13.6%; pnon-inferiority = 0.039). Median lymph node yield was comparable (22.0 [16.0–30.0] vs 23.0 [14.0–32.0] nodes, p = 0.86), as was the rate of intraperitoneal recurrence (41% vs 38%, p = 0.45). Median follow-up was 23.5 (interquartile range 17.0–30.0) months. Other postoperative outcomes were comparable, including median time to functional recovery (5 [95% CI 4.5–5.5] vs 5 [95% CI 4.7–5.3] days; p = 0.22) and overall survival (HR 0.99, 95% CI 0.67–1.46, p = 0.94). Serious adverse events were reported in 23 (18%) of 131 patients in the MIDP group vs 28 (22%) of 127 patients in the ODP group. Interpretation: This trial provides evidence on the non-inferiority of MIDP compared to ODP regarding radical resection rates in patients with resectable pancreatic cancer. The present findings support the applicability of minimally invasive surgery in patients with resectable left-sided pancreatic cancer. Funding: Medtronic Covidien AG, Johnson &amp; Johnson Medical Limited, Dutch Gastroenterology Society.</p

Hybrid Design Optimization of High Voltage Pulse Transformers for Klystron Modulators

This paper presents a hybrid optimization methodology for the design of high voltage pulse transformers used in klystron modulators. The optimization process is using simplified 2D FEA design models of the 3D transformer structure. Each intermediate optimal solution is evaluated by 3D FEA and correction coefficients of the 2D FEA models are derived. A new optimization process using 2D FEA models is then performed. The convergence of this hybrid optimal design methodology is obtained with a limited number of time consuming 3D FEA simulations. The method is applied to the optimal design of a monolithic high voltage pulse transformer for the CLIC klystron modulator

HV Pulse Transformer Generalized Equivalent Circuit Identification Based on Detailed Mechanical Structure

A modelling methodology of High Voltage pulse transformers based on High Order Generalized Equivalent Circuits (HOGEC) identified from 3D FEA is applied to a prototype and experimental validation tests are performed. The identified High Order Generalized Equivalent Circuit of the prototype is used to investigate the influence of the detailed mechanical structure and the local winding configuration on pulse transformer operation performance

Design of a Solid-State Fast Voltage Compensator for klystron modulators requiring constant AC power consumption

This paper proposes a novel topological solution for klystron modulators integrating a Fast Voltage Compensator which allows an operation at constant power consumption from the utility grid. This kind of solution is mandatory for the CLIC project under study, which requires several hundreds of synchronously operated klystron modulators for a total pulsed power of 39 GW. The topology is optimized for the challenging CLIC specifications, which require a very precise output voltage flat-top as well as fast rise and fall times (3µs). The Fast Voltage Compensator is integrated in the modulator such that it only has to manage the capacitor charger current and a fraction of the charging voltage. Consequently, its dimensioning power and cost is minimized

Definition d'un actionneur a aimants permanents et electronique integree pour l'automobile

SIGLEAvailable from INIST (FR), Document Supply Service, under shelf-number : TD 83517 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

deconvPDAC : a quantifier of PDAC tumor cellular heterogeneity

International audiencePancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and invasive tumoral lesion affecting the pancreas. Molecular analysis and classification based on gene expression landscapes is complicated by the intrinsic heterogeneity of PDAC tumors. Like all solid cancer, PDAC are made up of the ‘tumoral mass’ (predominantly epithelial cells) which is surrounded by a microenvironment composed of stromal (fibroblasts, pericytes, endothelial) and immune cells, giving support, nutrients and sometimes resistance/metastatic potential to neoplastic cells. Precise quantification of this tumor heterogeneity is of utmost importance, as these multiple components are key factors in explaining tumor progression and response to therapy.A promising approach to accurately quantify cell type heterogeneity in PDAC relies on the recent emergence of bulk deconvolution algorithms based on single-cell reference profiles [1]. One of the main limitations of these approaches is the accuracy of the single-cell based profiles, which can strongly impair the quantification and the biological interpretation of the inferred tumor composition [2]. To overcome these difficulties, we built an integrative set of PDAC cell-type specific gene markers, based on a dedicated pre-established gene markers curation and subsequent analysis of PDAC recent single-cell RNA-seq datasets. After several steps of quality control, filtration, annotation and data integration, we launched a systemic identification of integrative cell-types specific gene markers. We then intend to use these markers to revise our current understanding of cell-type heterogeneity in PDAC using single-cell based bulk deconvolution approaches. We also have a goal to build an R package dedicatedto the deconvolution of PDACs, leveraging the robust cell-type specific gene markers and integrated references we have been able to establish over the last few years.References[1] Francisco Avila Cobos, Mohammad Javad Najaf Panah, Jessica Epps, et al. Effective methods for bulkRNA-seq deconvolution using scnRNA-seq transcriptomes. Genome Biology, 24(1):177, August 2023.[2] Geng Chen, Baitang Ning, and Tieliu Shi. Single-Cell RNA-Seq Technologies and Related ComputationalData Analysis. Frontiers in Genetics, 10, 2019. Publisher: Frontiers

Evaluation of Insulation Systems for the Optimal Design of High Voltage Pulse Transformers

This paper presents a study for the design of the insulation systems of high voltage pulse transformer based on experimental tests and numerical simulations. Data of high voltage tests on solid and liquid insulation materials are presented and discussed. The understanding of each part of the insulation is supported by electrostatic fields simulations