Exosomes released by EBV-infected nasopharyngeal carcinoma cells convey the viral Latent Membrane Protein 1 and the immunomodulatory protein galectin 9

BACKGROUND: Nasopharyngeal carcinomas (NPC) are consistently associated with the Epstein-Barr virus (EBV). Their malignant epithelial cells contain the viral genome and express several antigenic viral proteins. However, the mechanisms of immune escape in NPCs are still poorly understood. EBV-transformed B-cells have been reported to release exosomes carrying the EBV-encoded latent membrane protein 1 (LMP1) which has T-cell inhibitory activity. Although this report suggested that NPC cells could also produce exosomes carrying immunosuppressive proteins, this hypothesis has remained so far untested. METHODS: Malignant epithelial cells derived from NPC xenografts – LMP1-positive (C15) or negative (C17) – were used to prepare conditioned culture medium. Various microparticles and vesicles released in the culture medium were collected and fractionated by differential centrifugation. Exosomes collected in the last centrifugation step were further purified by immunomagnetic capture on beads carrying antibody directed to HLA class II molecules. Purified exosomes were visualized by electron microscopy and analysed by western blotting. The T-cell inhibitory activities of recombinant LMP1 and galectin 9 were assessed on peripheral blood mononuclear cells activated by CD3/CD28 cross-linking. RESULTS: HLA-class II-positive exosomes purified from C15 and C17 cell supernatants were containing either LMP1 and galectin 9 (C15) or galectin 9 only (C17). Recombinant LMP1 induced a strong inhibition of T-cell proliferation (IC50 = 0.17 nM). In contrast recombinant galectin 9 had a weaker inhibitory effect (IC50 = 46 nM) with no synergy with LMP1. CONCLUSION: This study provides the proof of concept that NPC cells can release HLA class-II positive exosomes containing galectin 9 and/or LMP1. It confirms that the LMP1 molecule has intrinsic T-cell inhibitory activity. These findings will encourage investigations of tumor exosomes in the blood of NPC patients and assessment of their effects on various types of target cells

Endoscopic submucosal dissection techniques and technology: European Society of Gastrointestinal Endoscopy (ESGE) Technical Review

ESGE suggests conventional endoscopic submucosal dissection (ESD; marking and mucosal incision followed by circumferential incision and stepwise submucosal dissection) for most esophageal and gastric lesions. ESGE suggests tunneling ESD for esophageal lesions involving more than two-thirds of the esophageal circumference. ESGE recommends the pocket-creation method for colorectal ESD, at least if traction devices are not used. The use of dedicated ESD knives with size adequate to the location/thickness of the gastrointestinal wall is recommended. It is suggested that isotonic saline or viscous solutions can be used for submucosal injection. ESGE recommends traction methods in esophageal and colorectal ESD and in selected gastric lesions. After gastric ESD, coagulation of visible vessels is recommended, and post-procedural high dose proton pump inhibitor (PPI) (or vonoprazan). ESGE recommends against routine closure of the ESD defect, except in duodenal ESD. ESGE recommends corticosteroids after resection of  > 50 % of the esophageal circumference. The use of carbon dioxide when performing ESD is recommended. ESGE recommends against the performance of second-look endoscopy after ESD. ESGE recommends endoscopy/colonoscopy in the case of significant bleeding (hemodynamic instability, drop in hemoglobin > 2 g/dL, severe ongoing bleeding) to perform endoscopic hemostasis with thermal methods or clipping; hemostatic powders represent rescue therapies. ESGE recommends closure of immediate perforations with clips (through-the-scope or cap-mounted, depending on the size and shape of the perforation), as soon as possible but ideally after securing a good plane for further dissection

Hyponamétrie et hémorragie sous-arachnoïdienne anévrysmale, existe-t-il une perte en sel?

INTRODUCTION : Le syndrome de perte en sel d’origine cérébrale (anglais, CSW) est une des deux causes principales d’hyponatrémie (hNa) compliquant les hémorragies sous-arachnoïdiennes anévrysmales (anglais, aSAH). Les évaluations permettant de le différencier d’un syndrome d’antidiurèse inappropriée (anglais, SIADH) sont difficiles et la prise en charge de ces deux syndromes est opposée. OBJECTIFS : L’objectif principal de l’étude était la mesure de la perte en sel chez les patients présentant une hNa secondaire à une aSAH et d’estimer la fréquence du CSW. Les objectifs secondaires comprenaient l’évaluation de la mortalité à 1 an, du handicap neurologique à 3 mois et des complications neurologiques chez les patients présentant une hNa avec ou sans perte en sel. Les effets des traitements minéralocorticoïdes dans l’hNa étaient aussi analysés. MÉTHODES : Il s’agit d’une étude rétrospective monocentrique incluant les patients admis en réanimation pour une aSAH entre le 1/11/2012 et le 1/05/2020. Les patients présentant une hNa à l’admission, une insuffisance rénale sévère ou une endocrinopathie décompensée étaient exclus. La perte en sel était définie par une perte en sel urinaire supérieure aux apports mesurés entre l’admission et le diagnostic de l’hNa et était nécessaire au diagnostic de CSW. RÉSULTATS : Trois cents trente-six patients ont été inclus. Parmi les 102 patients (30%) qui ont présenté une hyponatrémie, 17 (17%) avaient une perte en sel (16,0g ± 11,6) et seulement 5 (5%) étaient compatibles avec un CSW. Ce syndrome était pourtant suspecté et traité par les cliniciens dans 88% des hNa (90/102). Parmi les 102 patients, les apports sodés étaient en moyenne de 105,2 ± 79,6g et la perte urinaire de 83,3 ± 64,4g. La mortalité à 1 an (19% vs 16%, p = 0,68), le score GOS à 3 mois (4 [3 ;5] vs 4 [3 ;5], p = 0,80), la natrémie à J4, la natriurèse à J4 et le taux de vasospasme étaient semblables dans le groupe traité par minéralocorticoïdes ou non. CONCLUSION : La perte en sel permet d’expliquer la physiopathologie de l’hyponatrémie dans l’HSA anévrysmale dans moins de 5% des cas. Le traitement anti-natriurétique par minéralocorticoïdes n’a pas montré de bénéfice sur la correction de la natrémie, la survie et le handicap neurologique. Ces données suggèrent que le CSW devrait être considéré comme un diagnostic d’exception

An unusual malignant main bile duct stricture: a biliary metastasis of endometrial adenocarcinoma.

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A collaborative application for characterizing colorectal lesions could improve quality of tumor resection

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Hybrid peroral endoscopic myotomy for large Zenker’s diverticulum

International audienceIn this one‐year prospective study, Parkinson's disease (PD) patients with or without mania following STN‐DBS were compared to investigate risk and etiological factors, clinical management and consequences. Eighteen (16.2%) out of 111 consecutive PD patients developed mania, of whom 17 were males. No preoperative risk factor was identified. Postoperative mania was related to ventral limbic subthalamic stimulation in 15 (83%) patients, and resolved as stimulation was relocated to the sensorimotor STN, besides discontinuation or reduction of dopamine agonists and use of low‐dose clozapine in 12 patients, while motor and nonmotor outcomes were similar. These findings underpin the prominent role of limbic subthalamic stimulation in postoperative mania. ANN NEUROL 2022;92:411–41

Endoscopic mucosal resection with a magnetic traction system: a new strategy to facilitate complete resection

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Endoscopic submucosal dissection with early multitraction placed before circumferential incision allows excellent exposure but with a risk of catching the muscularis propria

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