INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with poor prognosis and limited treatment options. Electroporation-based therapies, such as electrochemotherapy (ECT) and irreversible electroporation (IRE), could be promising alternatives. ECT combines reversible electroporation with chemotherapy, enhancing intracellular drug uptake, while IRE leads to nonthermal tumor ablation. Both have been suggested as immunotherapy potentiators (electroimmunotherapy) in some tumor locations. We conducted a systematic review to evaluate the efficiency and safety of ECT, IRE, and immunoelectroporation in PDAC treatment. METHODS: We searched Medline, Embase, Cochrane, and Google-Scholar for ECT, IRE, and electroimmunotherapy following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. For ECT and electroimmunotherapy, regarding the scarcity of the data, we described independently each study protocol and results. For IRE, we collected protocol, efficiency, and safety data to provide a global analysis. RESULTS: Fifteen studies described the effects of ECT for PDAC treatment: Safety and efficiency were promising in both preclinical and human models. Thirty-eight clinical studies including 2,245 patients were analyzed for IRE, with patients mostly treated for locally advanced pancreatic cancer and a median overall survival of 17.2 months at the expanse of a 36% adverse event rate, half of which severe. Seven (preclinical and clinical) studies investigated electroimmunotherapy suggesting significant potentiation of immunotherapy in both preclinical and human models. DISCUSSION: In the largest systematic review to date regarding electroporation in PDAC treatment, analysis of study results plead against the use of IRE but highlight the potential benefits of ECT and electroimmunotherapy.
Postpartum anal incontinence is common. After a first delivery (D1) with perineal trauma, follow-up is advised to reduce the risk of anal incontinence. Endoanal sonography (EAS) may be considered to evaluate the sphincter and in case of sphincter lesions to discuss cesarean section for the second delivery (D2). Our objective was to study the risk factors for anal continence impairment following D2. Women with a history of traumatic D1 were followed before and 6 months after D2. Continence was measured using the Vaizey score. An increase ≥2 points after D2 defined a significant deterioration. A total of 312 women were followed and 67 (21%) had worse anal continence after D2. The main risk factors for this deterioration were the presence of urinary incontinence and the combined use of instruments and episiotomy during D2 (OR 5.12, 95% CI 1.22–21.5). After D1, 192 women (61.5%) had a sphincter rupture revealed by EAS, whereas it was diagnosed clinically in only 48 (15.7%). However, neither clinically undiagnosed ruptures nor severe ruptures were associated with an increased risk of continence deterioration after D2, and cesarean section did not protect against it. One woman out of five in this population had anal continence impairment after D2. The main risk factor was instrumental delivery. Caesarean section was not protective. Although EAS enabled the diagnosis of clinically-missed sphincter ruptures, these were not associated with continence impairment. Anal incontinence should be systematically screened in patients presenting urinary incontinence after D2 as they are frequently associated.
Endoscopy is a major producer of hospital waste. Liquid waste collected during endoscopic procedures represents a third of endoscopy waste and is often managed as regulated medical waste (RMW), costing more and emitting more greenhouse gases (GHGs) than regular landfill waste. We assessed the carbon footprint and financial impact of alternative processing methods to RMW. After 1 month of prospectively weighing endoscopic liquid waste, costs (€) and GHG emissions (kgCO2e) were calculated using the Carebone tool to compare the following processing methods to standard RMW: (a) solidification – aspiration canister contents are made less prone to leakage by including a jellifying additive and can be disposed of in landfill waste bags instead of RMW; (b) urban sewer disposal (USD) – fluids are eliminated into sewers by using a dedicated system instead of aspiration canisters. Costs and GHG emissions were modelled according to the different scenarios. Mean procedure-related waste was 1.56 kg per patient, one-third of which was liquid waste. Compared with RMW (assuming 0.5 L of waste per endoscopic procedure), a center treating 4000 patients / year would save 923 € and avoid 1440 kgCO2e in GHG emissions with solidification, while USD would cost 105 898 € more and avoid only 96.5 kgCO2e. Different caseload and volume assumptions are discussed. Endoscopic procedure-related liquid waste represents a third of the waste emitted per patient in an endoscopy unit. Solidification allows fluids to be safely reallocated to landfill waste and may reduce processing costs and environmental impact. USD appears to be neither environmentally nor economically beneficial for endoscopy units.
Electroporation (EPN) is the process by which cell membranes become transiently or permanently permeable upon exposure to pulsed electric fields of suitable intensity and duration. Depending on the pulse parameters, permeabilization can be reversible or irreversible, enabling a wide range of biomedical applications. To improve our understanding of EPN effects on tissues and select efficient treatments and parameters, relevant in vitro tumour models are required. Three-dimensional (3D) cell spheroids have emerged as valuable systems, as they more accurately replicate tumour microenvironment and cell-to-cell interactions than conventional 2D cultures. In this work, we present a new microdevice designed for the culture and gradual electroporation of a population of several hundred uniformly sized spheroids, allowing the systematic study of electroporation over a wide range of electric field intensities within a single experiment. Gradual permeabilization of HT-29 colorectal cancer cell spheroids was performed using a standard electrochemotherapy protocol, and electroporation efficiency was assessed by analysing propidium iodide (PI) uptake. Spheroids were treated with electric fields ranging from 800 V cm−1 to 3400 V cm−1. In toto analysis of PI distribution within spheroids by confocal microscopy revealed highly heterogeneous permeabilization patterns throughout the spheroid volume, for all intensities investigated, even at the highest one of 3400 V cm−1. This study introduces a robust 3D in vitro assay for the systematic evaluation of electroporation-based treatments, providing new insights into the influence of electric field heterogeneity, electrical protocol, and estimation of molecular uptake in the spheroid volume.
Benign biliary strictures (BBS) are commonly managed by progressive calibration using plastic or metallic stents. Although fully-covered metallic stents (FC-SEMS) enable immediate calibration to a larger diameter compared with plastic stents, they remain prone to migration and use is limited in intrahepatic and peri-hilar strictures. We report on using uncovered expandable bioresorbable stents (BRES) in a series of selected BBS patients. This retrospective monocentric case series included all consecutive patients treated between 2023 and 2024. Patients were highly selected for uncommon situations for which usual stents were not well suited and followed for at least 12 months after the procedure. Technical success, clinical success, and adverse events (AEs) were systematically recorded. Five procedures were performed in five patients with implantation of a total of eight UNITY-B stents. Three patients underwent internalization of an internal-external drainage across a bilio-digestive anastomotic stricture. One patient was treated with retrograde extra-anatomical endoscopic drainage for an anastomotic stricture. One patient underwent calibration of an intrahepatic stricture following radiofrequency of an IPMN-B. Technical success was achieved in all cases (100%), with clinical success observed in 80% of patients. No AEs were observed. Use of bioresorbable UNITY-B stents appears feasible and safe for selected benign biliary strictures, including in intrahepatic locations. Further studies are needed to confirm these preliminary findings.