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INTRODUCTION: Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) is increasingly used in the setting of malignant gastric outlet obstruction (GOO). However, little is known about the role of primary EUS-GE. The aim of the present study is to compare the outcomes of EUS-GE by using the freehand technique as a first- and second-line approach after enteral stenting (ES). METHODS: This is an observational single-center study using a prospectively collected database. All consecutive patients who underwent an EUS-GE using the freehand technique due to malignant GOO were included. Patients with previous gastric surgery, a wire-guided EUS-GE technique, or those presenting without GOO were excluded. The primary outcome was the clinical success, defined as a solid oral intake at 1 week after the procedure (GOO Score, GOOSS ≥ 2). The secondary outcomes were technical success and adverse event (AE) rates. The impact on nutritional parameters was also assessed. RESULTS: Forty-five patients underwent an EUS-GE for all indications. Finally, 28 patients (mean age: 63 ± 17.2 years, 57.1% male) with (n = 13, 46.4%) and without (n = 15, 53.6%) a previous ES were included. The technical success was achieved in 25 cases (89.3%), with no differences between the two groups (92.3% vs. 86.7%, p = 1). The median limb diameter and procedure time were 27 mm (range:15-48) and 37 min. Overall, clinical success was achieved in 22 cases (88%), with three failures due to AEs (n = 2) or peritoneal carcinomatosis (n = 1). The diet progression was quicker in patients with a previous ES (GOOSS at 48 h, 2 vs. 1, p = 0.023), but the GOOSS at 1 week (p = 0.299), albumin gain (p = 0.366), and BMI gain (0.257) were comparable in the two groups. The AE rate was 7.1%. CONCLUSIONS: EUS-GE achieves a high technical and clinical success in patients with GOO regardless of the presence of a previous ES. Patients with previous ES may have a quicker progression of their diet, but the GOOSS and nutritional status in the long term at 1 week or 1 month are comparable. Primary EUS-GE might require fewer procedures and less discontinuation of chemotherapy to achieve a comparable result. ispartof: CANCERS vol:14 issue:22 ispartof: location:Switzerland status: published

Molecular switches are chemical compounds exhibiting the possibility of reversible transformations between their different forms accompanied by a modification in their properties. Among these, switching of multi-addressable Benzazolo-OXazolidines (BOXs) from a closed form to an open form results in drastic modifications in their linear and nonlinear optical properties. Here, we target molecules containing two identical BOX units (DiBOX) connected by different π-conjugated linkers, and we combine synthesis, UV/visible absorption, and hyper-Rayleigh scattering (HRS) measurements, together with density functional theory (DFT) calculations. Three derivatives have been considered, which differ by the linker: (i) a bithiophene moiety (Bt), (ii) two 3,4-ethylenedioxythiopene (EDOT) units, and (iii) a triad composed of an EDOT-thiophene-EDOT sequence (TtO). As a matter of fact, these systems can adopt three states (CF-CF, POF-POF, and CF-POF) depending on the closed form (CF) or the protonated open form (POF) of each BOX unit. Despite chemical equivalence, stepwise switching of such systems under the addition of a chemical acid or an oxidant has been experimentally evidenced for two of them (DiBOX-Bt and DiBOX-TtO). Then, DFT calculations show that the first BOX opening leads to the formation of a push-pull π-conjugated segment, exhibiting a huge increase in the first hyperpolarizability (β) and a bathochromic shift with respect to the fully closed form. On the contrary, the second BOX opening induces not only a slight bathochromic shift but also a reduction in their β values conferring the great and uncommon abilities to modulate their linear and nonlinear properties over three discrete levels. Among these results, those on DiBOX-Bt agree with the experimental data obtained by HRS measurements and further shed light on their structure-property relationship.

The elaboration of multichromophoric system which can undergo a reversible transformation over more than two different states can be easily performed by the covalent assembly of several identical switching subunits around a central node. However, the selective addressability of each of them still represents a challenging task. This study reports on the elaboration of multichromophoric systems incorporating three identical indolino-oxazolidine (BOX) moieties as multimodal addressable units. Depending of the open/closed oxazolidine ring status of each of them, these systems can be interconverted between four different states in stepwise manner by using indifferently acid addition or electrochemical stimulation. More important, we have demonstrated by using a dissymmetric triarylamine node that the classical statistical BOX opening is broken then reaching a regioselective addressability. The switching of the three identical BOX units differentiated by their π conjugated junction to the central core follows a preferential order leading to the preponderant and successive formation of only four forms over the eight theoretically and equally expected. To provide limitations and outlooks for such strategy, their switching capacities have been rationalized by DFT calculations.

International audience; Combining different molecular switching functions in a single molecule is a simple strategy to develop commutable molecules featuring more than two commutation states. The present study reports on two molecular systems consisting of two indolino-oxazolidine (Box) moieties connected to an aromatic bridge (phenyl or bithiophene) by ethylenic junctions. Such systems, referenced as BiBox, are expected to show up multiaddressable and multiresponsive behaviors. On one hand, the oxazolidine ring opening/closure of Box moieties can be addressed by chemical stimuli, and on the other hand, the trans-to-cis isomerization of the ethylenic junctions is induced by visible light irradiation (with a thermal back conversion). NMR and UV−visible spectroscopies allowed to characterize up to nine out of the ten theoretically expected commutation states as well as to measure the kinetics of the interconversions. Also, steady state fluorescence spectroscopy measurements highlighted the strong influence of the open/closed states of the Box moieties on their emission properties.

Over the past decade many efforts have been focused on the synthesis, modification and application of multi-responsive molecular systems. Up to now, two main strategies have been conducted to elaborate such systems: either by connecting different molecular switches through covalent links or by mixing them within supramolecular assemblies to obtain multiresponsiveness through the combination of various stimulations (i.e., photon, electron, proton, etc…). In thisthesis, we report a different approach based on the employment of identical indolinooxazolidine (BOX) unit as multi-modal switch. Indeed, the opening of the oxazolidine ring can be reversibly and selectively achieved either under UV irradiation, electrochemical stimulation or acidity changes. According to our first strategy, two BOX units were connected around a simple linear aromatic plate forms, such as bithiophene and EDOT-Thiophene-EDOT unit as spacer. Interestingly, these systems are able to commute between 3 different metastable states in a stepwise manner with all kinds of stimulations. Going further, in order to promote the metastable states, it was possible to increase the number of BOX by connecting three of them on more elaborated pi systems which are potentially able to exhibit up to four discriminate metastable states. Complementary to that, a second strategy was to synthesize various nitrogen ligands functionalized by at least one BOX unit and their coordination chemistry with zinc and ruthenium metals. The response of the ligands as well as their corresponding complexes under photo, electro and acidic stimulation were also investigated and fully characterized., Au cours des dernières décennies, de nombreux efforts se sont focalisés sur la synthèse, la modification et l’utilisation de systèmes moléculaires multi-adressables. Afin d’élaborer de tels systèmes capables de répondre à des stimulations de différentes natures (par exemple : photon, électron, proton, etc…) les deux principales stratégies consistaient à ce jour à connecter différents types d’unités stimulables soit par liaison covalente soit par dispersion au sein d’assemblages supramoléculaires. Au cours de cette thèse, nous nous sommes attachés à développer une nouvelle approche basée sur l’utilisation d’un unique switch multi-mode : les indolino-oxazolidine (BOX). En effet, cette unité est capable de commuter entre deux états métastables (ouvert et fermé) et ce de façon indifférenciée par application d’une stimulation lumineuse, électrochimique ou encore par variation du pH. En suivant une première stratégie, deux unités BOX ont été connectées via l’utilisation d’un simple système conjugué linéaire tels qu’une unité bithiophène et un enchainement EDOT-Thiophène-EDOT (ETE) comme espaceur. Nous avons démontré que ces systèmes multi-stimulables sont capables de commuter de façon pas à pas entre 3 états métastables différents et ce quel que soit la nature du stimulus. Afin de démontrer les nombreuses possibilités de cette approche et augmenter le nombre d’états métastables, 3 unités BOX ont été connectés par l’utilisation de systèmes conjugués plus élaborés permettant ainsi de conduire à des interrupteurs moléculaires capables de présenter jusqu’à 4 états différents. En complément de cette approche purement organique, une seconde stratégie a consisté à fonctionnaliser différents ligands azotés par au moins une entité BOX afin d’élaborer des systèmes plus complexes par chimie de coordination avec des ions métalliques de zinc et de ruthénium. Les ligands préparés ainsi que les complexes correspondants ont été pleinement caractérisés et leur addressabilité sous stimulation chimique, électrique et lumineuse étudiée.