Long-term follow-up after endoscopic resection for superficial esophageal squamous cell carcinoma: a multicenter Western studyAbstract

Background Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are the first-line treatments for superficial esophageal squamous cell carcinoma (SCC). This study aimed to compare long-term clinical outcome and oncological clearance between EMR and ESD for the treatment of superficial esophageal SCC. Methods We conducted a retrospective multicenter study in five French tertiary care hospitals. Patients treated by EMR or ESD for histologically proven superficial esophageal SCC were included consecutively. Results Resection was performed for 148 tumors (80 EMR, 68 ESD) in 132 patients. The curative resection rate was 21.3 % in the EMR group and 73.5 % in the ESD group (P < 0.001). The recurrence rate was 23.7 % in the EMR group and 2.9 % in the ESD group (P = 0.002). The 5-year recurrence-free survival rate was 73.4 % in the EMR group and 95.2 % in the ESD group (P = 0.002). Independent factors for cancer recurrence were resection by EMR (hazard ratio [HR] 16.89, P = 0.01), tumor infiltration depth ≥ m3 (HR 3.28, P = 0.02), no complementary treatment by chemoradiotherapy (HR 7.04, P = 0.04), and no curative resection (HR 11.75, P = 0.01). Risk of metastasis strongly increased in patients with tumor infiltration depth ≥ m3, and without complementary chemoradiotherapy (P = 0.02). Conclusion Endoscopic resection of superficial esophageal SCC was safe and efficient. Because it was associated with an increased recurrence-free survival rate, ESD should be preferred over EMR. For tumors with infiltration depths ≥ m3, chemoradiotherapy reduced the risk of nodal or distal metastasis

Fluoxetine targets an allosteric site in the enterovirus 2C AAA+ ATPase and stabilizes a ring-shaped hexameric complex

Enteroviruses are globally prevalent human pathogens responsible for many diseases. The nonstructural protein 2C is a AAA+ helicase and plays a key role in enterovirus replication. Drug repurposing screens identified 2C-targeting compounds such as fluoxetine and dibucaine, but how they inhibit 2C is unknown. Here, we present a crystal structure of the soluble and monomeric fragment of coxsackievirus B3 2C protein in complex with (S)-fluoxetine (SFX), revealing an allosteric binding site. To study the functional consequences of SFX binding, we engineered an adenosine triphosphatase (ATPase)-competent, hexameric 2C protein. Using this system, we show that SFX, dibucaine, HBB [2-(α-hydroxybenzyl)-benzimidazole], and guanidine hydrochloride inhibit 2C ATPase activity. Moreover, cryo-electron microscopy analysis demonstrated that SFX and dibucaine lock 2C in a defined hexameric state, rationalizing their mode of inhibition. Collectively, these results provide important insights into 2C inhibition and a robust engineering strategy for structural, functional, and drug-screening analysis of 2C proteins

Gastric submucosal dissection with water-jet knife (« Flush knife ») on a porcine experimental model under spontaneous ventilation

Du 18 au 26 mai 2007, a été effectuée, chez dix porcs anesthésiés en ventilation spontanée, une dissection sous-muqueuse gastrique étendue de 6 cm2 avec un dissecteur à jet d’eau de type «Flush knife» afin d’apprécier l’efficacité et l’innocuité de cette nouvelle méthode de dissection au regard des complications possibles (perforation, hémorragie, immédiate ou tardive). Le modèle expérimental porcin anesthésié en ventilation spontanée a été jugé intéressant pour l’apprentissage de la dissection sousmuqueuse car simple à manipuler du point de vue anesthésique, avec des doses totales de 2 à 3 mL de Zoletil 100® en injections à la demande par paliers de 0,2 à 0,3 mL. La dissection sous-muqueuse au « Flush knife» est de réalisation simple et a été effectuée dans cette étude par des endoscopistes pratiquant moins de 10 dissections par an avec un temps moyen de 10 mn par cm2, cela sans complication immédiate ou tardive

Fluoxetine targets an allosteric site in the enterovirus 2C AAA+ ATPase and stabilizes a ring-shaped hexameric complex

International audienceEnteroviruses are globally prevalent human pathogens responsible for many diseases. The nonstructural protein 2C is a AAA+ helicase and plays a key role in enterovirus replication. Drug repurposing screens identified 2C-targeting compounds such as fluoxetine and dibucaine, but how they inhibit 2C is unknown. Here, we present a crystal structure of the soluble and monomeric fragment of coxsackievirus B3 2C protein in complex with (S)-fluoxetine (SFX), revealing an allosteric binding site. To study the functional consequences of SFX binding, we engineered an adenosine triphosphatase (ATPase)-competent, hexameric 2C protein. Using this system, we show that SFX, dibucaine, HBB [2-(-hydroxybenzyl)-benzimidazole], and guanidine hydrochloride inhibit 2C ATPase activity. Moreover, cryo-electron microscopy analysis demonstrated that SFX and dibucaine lock 2C in a defined hexameric state, rationalizing their mode of inhibition. Collectively, these results provide important insights into 2C inhibition and a robust engineering strategy for structural, functional, and drug-screening analysis of 2C proteins