C S Martinez-Cisneros

A Fernandez

C Antonelli

B Levenfeld

A Varez

K Vezzù

V Di Noto

J.-Y Sanchez

Opening the door to liquid-free polymer electrolytes for calcium batteries

Keywords: Calcium electrolytes, calcium batteries, polymer electrolytes, energy storage, poly(oxyethylene), (POE, PEO)

ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction

The market for batteries, which approached 50 billion $ in 2012 [START_REF] Pillot | Lithium ion battery raw material supply & demand 2016-2025[END_REF], is expected to grow by more than 60% by 2020; such a growth is expected to reach 100% in the case of lithium batteries (LiBs). Long-time confined to portable electronics, the growth of the market for LiBs is driven by those developments achieved in Battery Electric Vehicles (BEVs) and Plug-in-Hybrid Electric Vehicles (PHEVs). The latter are expected to play a crucial role to curtail both greenhouse gas emissions and urban pollution. Indeed, as concerns the automotive market, the Federal Council of Germany voted to ban internal combustion engines (ICEs) by 2030 [START_REF] Gitlin | Germany's Bundesrat votes to ban the internal combustion engine by 2030[END_REF], while in France the ban on ICEs has been placed by 2040 [START_REF] Chrisafis | France to ban sales of petrol and diesel cars by 2040[END_REF]. These decisions are yielding a huge impact on the development strategies of car manufacturers, greatly promoting the diffusion of BEVs and PHEVs. Besides BEV and PHEV, non-mobile grid-levelling applications typically require large-scale energy storage systems to buffer the intermittency of the demand and, in the case of renewable energies such as solar and wind, of the supply of electricity. However, the high cost of LiBs bottlenecks their application as large-scale energy storage systems for the power grid [START_REF] Clercq | French renewables power grid pilot shows limits of batteries in Europe, Reuters[END_REF]. Hence, the end users require cheaper, safer and more efficient batteries for both electric vehicles and stationary energy storage applications. Such criteria often contradict one another. More efficient: if the electrode materials were changed from Li4Ti5O12/LiFePO4 to C/LiCoO2, the battery energy density would increase from 70 to 200 Wh•kg -1 ; however, at the same time, the cyclability of the device would be reduced [START_REF] Opitz | Can Li-Ion batteries be the panacea for automotive applications?[END_REF]. Safer: regarding safety, the combustion of a 18650 Li-ion cells releases twice the energy of a TNT grenade by summing the cell energy ca. 0.93 J⋅g -1 and the combustion energy of organic components i.e. solvents, separator and binders [START_REF] Barsukov | Battery Power Management for Portable Devices[END_REF]. Cheaper: even if the cost of battery packs is constantly decreasing [START_REF] Lambert | Electric vehicle battery cost dropped 80% in 6 years down to $227/kWh[END_REF], the target of 150 $•kWh -1 has not been reached yet owing to the material costs and to the processing cost of LiBs [8, [START_REF] Wood | Prospects for reducing the processing cost of lithium ion batteries[END_REF].

Another handicap suffered by LiBs in the medium term is the shortage of lithium ores, triggered by the huge demand for this energy storage technology. Thus, it is mandatory to devise new batteries where Li is replaced by cheaper elements that are more abundant in Earth's crust, e.g., Na, K, Mg and Ca, whose properties are compared in Table 1.

The ideal solution to devise high-energy density batteries remains based on the implementation of metals at the negative electrode. This approach yields important advantages, as it raises the capacity, the voltage and the energy density of the battery; concurrently, the processing of the battery is simplified and the ohmic losses are reduced.

It should be highlighted that calcium and lithium exhibit the same volumetric capacity. Furthermore, calcium is characterized by a very low reduction potential, -2.87 V vs. SHE, close to lithium one (-3.05 V vs. SHE). In addition, calcium exhibits the highest electrical conductivity among the metals listed in Table 1. On the other hand, one relevant parameter for the battery safety is the melting temperature of the alkaline/alkaline-earth metal anode. Calcium melts at 842°C; this is the highest melting temperature among all the metals listed in Table 1. Hence, it is inferred that a battery based on a calcium metal negative, Ca 0 , would provide high capacity and high safety as compared to a graphite electrode, which barely exhibits a reversible capacity of 85 mAhg over 200 cycles and co-intercalates solvent molecules as DMAC [START_REF] Park | Stable and high-power calcium-ion batteries enabled by calcium intercalation into Graphite[END_REF]. Based on all these pieces of information, a Ca 0 -based calcium battery, CaB, would be a perfect post-lithium alternative. A non-rechargeable CaB, was early proposed by Peled et al. [11[12[13], who claimed similar performances than LiB ones and improved safety, but did not succeed in cycling Ca 0 . More recently, a 600 mAh/g practical capacity was reported for a Ca 0 /S primary CaB [START_REF] See | A high capacity calcium primary cell based on the Ca-S system[END_REF]. Regarding the cycling issue of Ca 0 , Aurbach et al. [START_REF] Aurbach | The Electrochemical Behavior of Calcium Electrodes in a Few Organic Electrolytes[END_REF] reported the first general study concerning Ca 0 behavior in aprotic organic liquid electrolytes based on Ca(ClO4)2 where, contrary to Li 0 , Ca 2+ deposition onto Ca 0 did not occur. Post-mortem analyses of the Ca 0 surface revealed the presence of passivation films of Ca(CO3)2 and Ca(OH)2, which prevent further diffusion of Ca 2+ and its deposition on Ca 0 . For a long time, the deposition of Ca 2+ onto Ca 0 , only occurred at very high temperatures [16[17].

The contribution of Ponrouch et al. [START_REF] Ponrouch | Towards a calcium-based rechargeable battery[END_REF] shows promise results, as it demonstrates the deposition at temperatures in the range of 75-100 °C of Ca 2+ onto Ca 0 from a liquid electrolyte based on cyclic carbonates. However, this deposition process, observed from cyclic voltammetry measurements, was characterized by a high overpotential and a low capacity. In view of the observed passivation of Ca 0 by Ca (CO3)2 [START_REF] Aurbach | The Electrochemical Behavior of Calcium Electrodes in a Few Organic Electrolytes[END_REF], the selected cyclic carbonates are probably not the most suitable solvents for this application. P.G. Bruce et al. [START_REF] Wang | Plating and stripping calcium in an organic electrolyte[END_REF] recently reported improved calcium deposition/stripping, discarding cyclic and acyclic carbonates but using, as electrolyte, a THF solution of Ca(BH4)2. In this case, deposition/stripping was observed at room temperature, over 50 cycles with a much lower polarization and a better plating/stripping than those reported by Ponrouch [START_REF] Ponrouch | Towards a calcium-based rechargeable battery[END_REF]. The formation of CaH2, with derives from the dehydrogenation of THF into 2, 3-dihydrofuran, was observed on Ca 0 . As stated by the authors and pointed out by Ponrouch [20], the electrolyte used in this work exhibits too low anodic stability to be used with a highpotential cathode and the THF solvent undergoes a significant degradation. Therefore, neither carbonates nor THF could allow cycling efficiently calcium batteries. Besides, the review of Muldoon et al. [START_REF] Muldoon | Quest for nonaqueous multivalent secondary batteries: Magnesium and beyond[END_REF] ascribed the lack of interest for CaB to the lack of suitable electrolytes. Can calcium polymer electrolytes, CAPE, become an alternative to liquid ones? First results evidenced fairly high conductivities of Ca salts hosted by solvent-free commercial poly(oxyethylene) POE or PEO homopolymer and POE-based amorphous networks [START_REF] Martinez-Cisneros | From lithium to post-lithium batteries: Na & Ca conducting solvent-free polymer electrolytes[END_REF]. It has been recently reported that highly concentrated polymeric solution of calcium nitrate in poly(oxyethylene) and poly(oxytetramethylene) networks, both obtained by UV insolation [23[24] can provide at high temperature (110ºC) conductivities in excess of 0.1 mS/cm. Regarding CAPE, high conductivity is a necessary but not sufficient condition: it is indeed essential to form stable macromolecular solutions of Ca salts in a wide range of salt concentrations. As a matter of fact, polypropylene oxide, PPO, long time used as an amorphous alternative to POE regarding Infra-Red and Raman studies, was found, a decade later, to undergo microphase separation with several POP/Li salts electrolytes [START_REF] Vachon | Prud'homme, Microphase Separation and Conductivity Behavior of Poly(propylene oxide)-Lithium Salt Electrolytes[END_REF]. In this work, we aim at investigating solvent-free polymer electrolytes to pave the way towards the development of sustainable and cheaper batteries with improved safety. As a first approach, we study the features of polymer electrolytes based on a "reference" host polymer, i.e., poly(oxyethylene), POE or PEO, hosting different Ca salts.

Experimental

Materials

Analytical-grade reagents were supplied by Sigma-Aldrich. Poly(oxyethylene) (POE) (Mw 3•10 5 g•mol -1 ) was used as the host polymer. In a first approach, calcium trifluoromethane sulfonate, Ca(CF3SO3)2, was used to prepare polymer electrolytes at different O/Ca ratios [START_REF] Nykvist | Rapidly falling costs of battery packs for electric vehicles[END_REF][START_REF] Kim | Thermodynamic properties of calcium-Bismuth alloys determined by emf measurements[END_REF]20,[START_REF] Lipkowski | The electrochemistry of novel materials[END_REF][START_REF] Vezzù | Effect of subcritical CO2 on ionic conductivity of {Al[O(CH2CH2O)8.7]ρ (LiClO4)z}n hybrid inorganicorganic networks[END_REF]. For comparison purposes, calcium polymer electrolytes based on calcium iodide, CaI2, and calcium bis(trifluoromethanesulfonyl)imide, Ca(TFSI)2 were also prepared at two O/Ca ratios (30 and 40).

Preparation of POE-based electrolytes

The green approach previously described [START_REF] Martinez-Cisneros | Development of sodium-conducting polymer electrolytes: Comparison between film-casting and films obtained via green processes[END_REF] Films obtained are further dried under vacuum at 50°C for 12 h and stored in a glove box (M. Braun, GmbH, Germany) filled with argon, in which moisture was lower than 1 ppm to prevent any water absorption.

X-Ray diffraction

X-Ray diffraction (XRD) measurements were carried out using a Philips X'PERT MPD diffractometer (Cu Kα radiation) operating at 40 kV and 40 mA. The XRD patterns were recorded over a 2θ range of 5-80° using a step scan of 0.02° and a counting time of 1 sec per step.

Scanning Electron Microscopy (SEM)

The distribution of calcium in the electrolytes was studied by using the FEI Teneo Scanning Electron Microscope. For this purpose, X-ray mapping involving the creation of multiple elemental maps was performed at 6 kV and 0.8 nA using the EDAX TEAM™ EDS Analysis System for samples based on Ca(CF3SO3)2, CaI2 and Ca(TFSI)2, all at O/Ca=30.

Thermal and thermomechanical analyses

The thermogravimetric analysis (TGA) of samples (∼8.5 mg) was performed using a Pyris 1 TGA (Perkin Elmer, USA) thermogravimetric analyzer. Samples were heated in a platinum crucible from 30°C to 650°C (at 10°C•min -1 ) under a nitrogen atmosphere. The onset temperature (Tonset) was established as the intersection point between the tangent drawn at the point of highest slope with the extrapolated baseline. Differential scanning calorimetry (DSC) was conducted using a DSC822e (Mettler Toledo, Switzerland) under a 50 mL•min -1 constant flow of nitrogen. The melting temperature (Tm) and the enthalpy of fusion (ΔHm) were estimated between -90°C and 150°C (scan rate: 10°C•min -1 ). DSC measurements were collected during the second heating scan; the first heating scan removes the thermal history of the samples. The relative percentage of crystallinity (Xc)

was directly related to the area under the 1 st melting peak by using equation 1 [START_REF] Bhattacharya | Effect of sodium-mixed anion doping in PEO-based polymer electrolytes[END_REF]:

= ∆ ∆ ⁄ × 100% (eq. 1)
where ΔHm is the melting enthalpy estimated experimentally and ΔH 0 m is the melting enthalpy for 100% crystalline POE (213.7 J•g -1 [START_REF] Noor | Solid polymeric electrolyte of poly ( ethylene ) oxide-50 % epoxidized natural rubber-lithium triflate[END_REF]). Dynamic Mechanical Thermal Analyses (DMTA) were carried out using a DMA Q800 machine (TA Instruments, USA)

working in tensile mode at 1 Hz and at an oscillation amplitude of 15 µm. DMTA samples were rectangular (2.5 mm x 7.5 mm), with a thickness ranging between 100 and 150 µm.

DMTA measurements were performed by heating samples from -100°C to +120°C at a heating rate of 5°C•min -1 in air atmosphere.

Ionic conductivity measurements

Conductivity measurements are collected by Impedance Spectroscopy (IS) using an Impedance/Gain-Phase Analyzer SI1260 (Solartron, UK) and applying a 100 mV amplitude signal in the 1 Hz -10 MHz frequency range. The measurements were carried out upon heating, at temperatures between 20 and 90°C with a step of 10°C. The samples are sandwiched between stainless steel blocking electrodes (Ø = 11 mm) embedded in a Swagelok-Nylon cell. A dwell time of 30 minutes between measurements was found to be enough for the system to reach a stable temperature.

Results and Discussion

Since high molecular weight POEs undergo dramatic chain breaking even as its solutions are mildly sheared [START_REF] Bossard | Influence of dispersion procedure on rheological properties of aqueous solutions of high molecular weight PEO[END_REF], we chose the commercial grade having a molecular weight of 300,000 g•mol -1 . Among the calcium salts previously used in liquid electrolytes can be quoted Ca(ClO4)2 [START_REF] Aurbach | The Electrochemical Behavior of Calcium Electrodes in a Few Organic Electrolytes[END_REF], Ca(CF3SO3)2, Ca(BF4)2 [18][19]. We discarded Ca(ClO4)2 for safety reasons and Ca(BH4)2 because both its limited anodic stability and its expected too low conductivities in non-polar CAPE. As for Ca(BF4)2 we feared the possible disproportionation of the tetrafluoroborate anion into BF3 and F -leading to a highly resistive SEI made of CaF2. For the same reasons we didn't pay attention to PF6 -and FSI [(F-SO2)2] -anions still more likely than BF4 -to generate CaF2. Even though C-F bonds can be broken in contact with highly reductive metals as alkaline ones via metal-halogen exchange, we assumed that this reaction would be more limited in aprotic solvent-free polyether and selected calcium triflate and calcium trifluoromethane sulfonyl imide, both anions exhibiting a high anodic stability. Due to its intrinsic stability in reduction, the third salt, CaI2, has been selected despite its limited anodic stability (E0 = 0.54 V vs. SHE).

Microstructural analysis

A thorough characterization by XRD and DSC of POE-Ca(CF3SO3)2 salt complexes was previously reported by Mehta et al. [START_REF] Mehta | Phase Diagram of the Poly(ethylene oxide):Ca(CF3SO3)2 System[END_REF]. XRD was used to characterize crystallinity variations in the POE-Ca(CF3SO3)2 polymer electrolytes as related to the concentration of salt. XRD patterns of: (i) pristine, "salt-free" POE; (ii) samples with different O/Ca ratios; and (iii) Ca(CF3SO3)2 salt are reported in Figure S1 of Supplementary Information.

The homogeneous distribution of calcium in the polymer electrolytes was evaluated by X-ray mapping at room temperature. Three samples with the same salt concentration (O/Ca=30) were investigated, each including a different calcium salt. According to Figure 1, the X-ray mapping does not reveal any heterogeneity in the distribution of calcium, nor the presence of pores. This confirms that the proposed lyophilization/hot-pressing preparation procedure is able to yield highly homogeneous samples.

Differential scanning calorimetry (DSC)

DSC measurements were performed to elucidate the microstructural variations of the polymer electrolytes as related to the salt concentration and type. In general, the endothermic peaks shown in Figure 2, corresponding to melting temperature Tm, shift to lower temperatures as the concentration of salt raises. The shift of Tm to lower temperatures as the concentration of salt increases is associated to the more amorphous microstructure induced by the polymer/salt interactions. Table 2 summarizes Tm, melting enthalpy (∆Hm) and crystallinity (Xc) for all calcium polymer electrolytes at different O/Ca ratios. ∆Hm, decreases as the salt concentration raises. In agreement with XRD, this evidence is consistent with a reduction in the degree of crystallinity.

It can be noticed that Tm and Xc of POE-Ca(CF3SO3)2 (O/Ca=20) are lower than those reported for the analogue Na-based polymer electrolytes (i.e., POE-NaCF3SO3 with O/Na=20) [START_REF] Martinez-Cisneros | Development of sodium-conducting polymer electrolytes: Comparison between film-casting and films obtained via green processes[END_REF]. Such variation could be ascribed to the features of the salts. On one hand, the size of Ca 2+ and Na + cations (coordination number: 6) are comparable (1.14 vs 1.13 Å from fluorides; 1 vs 0.99 Å from oxides). On the other hand, Ca 2+ is divalent. Thus, with respect to Na + , Ca 2+ : (i) is more likely to undergo interchain cross-solvation; and (ii) is associated to two monovalent CF3SO3 -anions instead of only one. Indeed, CF3SO3 -are expected to provide an important contribution to modify the microstructure of the polymer electrolyte, facilitating the segmental mobility of the POE macromolecules.

Regarding the effect of the anions of calcium salts, the lowest crystallinity was obtained for POE-Ca(TFSI)2 polymer electrolytes. It is also highlighted that the difference in crystallinity between POE-Ca(TFSI)2 and POE-Ca(CF3SO3)2 is markedly lower than that observed between POE-LiTFSI and POE-LiCF3SO3 [START_REF] Vallée | Homme, Comparative study of poly(ethylene oxide) electrolytes made with LiN(CF3SO2)2, LiCF3SO3 and LiClO4: Thermal properties and conductivity behaviour[END_REF]. Moreover, Tm values are slightly higher for POE-Ca(TFSI)2 electrolytes. Hence, it is inferred that the main effects influencing the microstructure of POE arise from: (i) the interactions between Ca 2+ and the POE chains; and (ii) the hindering resulting from Ca 2+ bivalence (2 anions by cation).

Since the proposed POE-based calcium polymer electrolytes are semi-crystalline, DSC is unable to estimate accurately the glass transition temperature, Tg. Indeed, in these materials the crystalline phase constrains the amorphous phase, providing an "artificial"

Tg that is not accurate and is not reported in Table 2. Such a limitation could be addressed by supercooling the semi-crystalline polymer electrolyte, quenching the melted electrolyte at a very high speed would impede crystallization processes. However, this is usually not possible with most commercial DSC equipment. The DSC analyses carried out on the proposed POE-based polymer electrolytes from room temperature to 300°C reveal the presence of an endothermic peak with an onset at 270°C and a maximum at 287°C. In accordance with the results obtained by Metha et al. [START_REF] Mehta | Phase Diagram of the Poly(ethylene oxide):Ca(CF3SO3)2 System[END_REF], this peak is ascribed to the precipitation of calcium salts out of the liquid polymer electrolyte owing to the negative entropy of dissolution of calcium triflate in POE. This precipitation does not affect the applicability of the proposed calcium polymer electrolytes as it occurs at temperatures that are much higher than the typical operating temperatures of these systems (T < 100°C).

Thermogravimetric analysis (TGA)

Table 3 lists the onset temperatures of: (i) initial weight loss; (ii) residue at 450°C; and

(iii) percent (%) of non-volatile residues as compared to the wt% of salts in the various POE-based polymer electrolytes.

The POE host was completely removed as temperature raised above ca. 400°C. Hence, the residues detected at higher temperatures can be correlated to the other components included in the POE-based polymer electrolytes, namely the CaX2 salts. Thus, comparing the residues at 450ºC (roughly the onset of a thermal degradation plateau) with the nominal content of CaX2 in the polymer electrolytes, it can be deduced that both CaI2 and Ca(CF3SO3)2 are not significantly affected, while most of Ca(TFSI)2 undergoes degradation. The POE-CaI2 polymer electrolytes exhibit the lowest Tonset ~ 350°C. This evidence is ascribed to the reaction between the degradation byproducts of POE and CaI2, which releases I2. The latter is easily removed, as it already undergoes sublimation at room temperature and is characterized by a boiling point (Bp) equal to 183°C. Since POE-CaI2 polymer electrolytes do not lose weight below 350°C, I2 is not produced in the operating temperature range of solvent-free batteries. Accordingly, CaI2 is applicable in Ca polymer electrolytes.

With respect to the pristine POE host, the introduction of CaX2 salts raises the temperature of the weight loss by ca. 100°C. This does not mean that thermal degradation is delayed by the presence of the CaX2 salts, but rather that the volatile degradation byproducts interact with Ca salts, increasing their volatilization temperature [START_REF] Martinez-Cisneros | Development of sodium-conducting polymer electrolytes: Comparison between film-casting and films obtained via green processes[END_REF]. It is worth to highlight that TGA analyses discussed so far were carried out under an inert atmosphere.

These conditions reflect neither the real atmosphere in a battery, nor the conditions after its failure. Furthermore, scanning experiments such as those discussed so far do not allow achieving reliable information on how the weight loss at a given temperature depends on time. To address these issues, isothermal studies were carried out in the presence of oxygen. Figure 3 displays the weight losses of POE-Ca(CF3SO2)2 at 100°C and 170°C. It is shown that the onset of the thermal degradation occurs at much lower temperatures than those listed in Table 3. A negligible weight loss of less than 0.5% was noticed at 100°C. With this thermal stability, POE-Ca(CF3SO2)2 and most likely also the other POE-CaX2 polymer electrolytes can be used in a battery operating at temperatures at least as high as 100°C. On the other hand, Table 3 reveals that these polymer electrolytes are thermally unstable at 170°C since they exhibit an average weight loss of 2.8% per hour.

Indeed, in the case of an exothermal event, the temperature of the battery can reach and even exceed 170°C. It is emphasized that in the first hour at T = 170°C only 0.9% of volatile, thus easily flammable byproducts are released. This is not an absolute safety guarantee, but must be compared to the low Flash Point (Fp) of liquid electrolytes used in conventional lithium batteries. One example is dimethyl carbonate, DMC, whose Fp is approximately ~17ºC.

Thermomechanical behavior of POE-Ca(CF3SO3)2 electrolytes

The mechanical properties of POE-Ca(CF3SO3)2 electrolytes were studied by DMTA as a function of the temperature and of the concentration of dissolved Ca(CF3SO3)2. Figure 4 shows the storage modulus (E') as a function of the temperature for samples with different O/Ca ratios.

In the vitreous state, E' ranges between 4.4 and 5.1 GPa. In accordance with the concentration of Ca(CF3SO3)2, E' decreases as the salt concentration raises, since a decrease in crystallinity is produced, as previously stated through the DSC analysis.

The glass-rubber transition is marked by: (i) a clear drop of the storage modulus; and (ii) a peak in the tan δ signal, whose maximum is associated to the nominal glass transition temperature, Tα, reflecting the segmental mobility of the polymer electrolytes. Since Tg values measured from DSC are artificially increased by the constraining caused by the crystalline regions, they are investigated by DMTA on samples that had not undergone any thermal treatment and, accordingly, were in their pristine state. In general, Tα values are significantly higher than the Tg measured by DSC. A similar evidence, consisting of a gap of ca. 15°C between Tα and Tg, was recently observed on poly(oxyethylene) networks having much lower crystallinity and Tm [START_REF] Thiam | Optimizing ionic conduction of poly(oxyethylene) electrolytes through controlling the cross-link density[END_REF] than the POE homopolymer.

For samples reported in Figure 4, Tα values slightly shift to higher temperatures (up to ~ 10°C), whereas the tan δ peak becomes gradually higher and broader as the salt concentration increases. In semi-crystalline polymers the behavior of tan δ illustrates only the segmental dynamics of the amorphous regions. Thus, it is generally observed that the amplitude of tan δ evolves, becoming sharper and more intense, as the crystallinity degree decreases. Thus, the tan δ behavior revealed by the POE-Ca(CF3SO3)2 polymer electrolytes may arise from the fact that the decrease of crystallinity, which normally facilitates the increase of the segmental mobility when the salt is less diluted, may be counterbalanced by stronger interactions between the salt and the polymeric macromolecular solvent. Since the mechanical strength is mainly dependent on the crystalline phase, the storage modulus drops dramatically above the melting temperature, leading to creeping phenomena as T ≥ 80°C. The evolution of E' was studied up to 100°C to reveal possible transient crosslinking triggered by the divalent nature of the cations and ascribable to Ca 2+ interchain solvation. For that purpose, POE-Ca(CF3SO3)2 and POE-Mg(CF3SO3)2 samples with different salt concentrations were compared. Although in the range of uncertainties, two trends can be highlighted. First, for both alkaline-earth based POE electrolytes, creeping decreases as the salt concentration lowers. For all salt concentrations, the resistance to creeping of POE-Mg(CF3SO3)2 is higher than that of POE-Ca(CF3SO3)2. This is in agreement with the higher hardness (HSAB theory) of Mg vs Ca and also with the mechanical strength improvement induced by stronger magnesium-oxygen bonds (Mg-O) [START_REF] Wu | Studies on the effect of nano-sized MgO in magnesium-ion conducting gel polymer electrolyte for rechargeable magnesium batteries[END_REF]. However, despite the divalent nature of Ca 2+ and Mg 2+ , this resistance to creeping is not as high as that previously observed for POE-NaCF3SO3 (O/Na = 20). Indeed, in that case, E' reached values up to 98 MPa at 80 °C [START_REF] Martinez-Cisneros | Development of sodium-conducting polymer electrolytes: Comparison between film-casting and films obtained via green processes[END_REF]. Even though the mechanical analyses only provide macroscopic descriptions of a given material, one can assume that if both Ca 2+ and Mg 2+ benefit from interchain and intrachain solvation, the latter is not predominant. Moreover, early studies [START_REF] Blumberg | A poly(ethylene oxide)-mercuric chloride complex[END_REF][36] dealt with a POE complex including HgCl2. In such systems, Hg 2+ was located in a POE helix, highlighting that solvation by POE of divalent cations may lead to a complex amorphous phase dynamic.

Ionic conductivity

The conductivity studies were carried out by Electrochemical Impedance Spectroscopy (EIS) in the frequency and temperature range of 1 Hz -10 MHz and 20 -90°C, respectively. The profile of the real component of the complex conductivity (σ') as a function of frequency and temperature, for three selected compositions based on Ca(CF3SO3)2 is shown in Figure 5.

The profile of the real component of conductivity presents a plateau, corresponding to the global ionic conductivity, which shifts to higher values as temperature increases and to higher frequency as the O/Ca ratio increases.

The trend of global ionic conductivity as a function of temperature and salt concentration during heating for samples based on Ca(CF3SO3)2 is reported in Figure 6.

At 20°C, all POE-Ca(CF3SO3)2 samples exhibit a very low conductivity, in agreement with the semi-crystalline nature of the polymer electrolyte. The ionic conductivity increases as the temperature raises for all O/Ca ratios. Conductivity maxima were reached at 90ºC and ranged from 0.23 mS•cm -1 (O/Ca=8) to 0.47 mS•cm -1 (O/Ca=30 very close to O/Ca =40). In this sense, it must be emphasized that, with respect to POE-LiCF3SO3 electrolytes, the ionic conductivity of POE-Ca(CF3SO3)2 electrolytes is significantly higher [START_REF] Caruso | Characterization of PEO-Lithium Triflate Polymer Electrolytes: Conductivity[END_REF]. In both liquid and polymer electrolytes, the conductivity depends on both the salt concentration and the mobility of the ions. As the concentration of salt in the electrolyte raises, the concentration of mobile ions is globally increased; at the same time, the ion pair dissociation and the mobility of the ions is decreased; consequently, the viscosity of liquid electrolytes raises and the segmental motion in solvent-free polymer electrolytes is inhibited. As a result of these opposite phenomena, in both liquid and polymer electrolytes, the ionic conductivity reaches a maximum at a specific concentration of salt. The highly concentrated sample characterized by an O/Ca ratio of 8 creeps at high temperature. On the other hand, from the conductivity plots it can be assumed that the other compositions do not creep in the explored temperature range.

Therefore, the highest conductivity (that reached 0.47 mS•cm -1 ), was obtained for the concentrations of Ca(CF3SO3)2 corresponding to O/Ca = 30, even though the gap with the lowest one i.e. O/Ca = 8 barely exceeds a factor 2. Nonetheless, as the Ca 2+ charge is twice that of Li + , these concentrations are comparable to those corresponding to a O/Li = 15 or 4, while the practical salt concentrations in Li-polymer batteries range between 20 and 30. As compared to the conductivities reported for the CAPEs based on poly(PEGdi-acrylate) network and calcium nitrate [START_REF] Genier | A novel calcium-ion solid polymer electrolyte based on crosslinked poly(ethylene glycol) diacrylate[END_REF], our CAPE of concentration O/Ca =30 leads, at 90°C, to conductivity values roughly ten times higher than those obtained for Li-PE with an equivalent O/Li ratio. This can be ascribed both to the higher dissociation of Ca triflate compared to Ca nitrate and to the high crosslink density of network. Regarding CAPE based on poly(oxytetramethylene) i.e. PTHF co-crosslinked with di-epoxy [START_REF] Wang | A Solid Polymer Electrolyte from Cross-Linked Polytetrahydrofuran for Calcium Ion Conduction[END_REF],

the less concentrated CAPE i.e. O/Ca=13.8 barely approaches 0.1 mS/cm at 90ºC. Due to a lesser solvating repeat unit than POE (lower DN), PTHF networks were found to provide with LiTFSI, conductivities one order of magnitude lower [START_REF] Alloin | Electrochemical comparison of several cross-linked polyethers[END_REF]. In ref. [START_REF] Wang | A Solid Polymer Electrolyte from Cross-Linked Polytetrahydrofuran for Calcium Ion Conduction[END_REF], the oligoTHF curing provides however, in average, through the di-epoxy ring opening 4 OH group per kg increasing the AN of the network, thus its solvating ability. Comparing our data with the few ones available reinforce our selection of a host polymer based on oxyethylene repeat unit.

Data presented in Figure 6 were fitted by using the Vogel-Tamman-Fuelcher (VTF) equation as elsewhere described [START_REF] Di Noto | Broadband Dielectric Spectroscopy: A Powerful Tool for the Determination of Charge Transfer Mechanisms in Ion Conductors[END_REF]:

( ) = / ( ) (eq. 2)
where A0,i is proportional to the number of charge carriers, Ea,i is the pseudo-activation energy for conduction and T0,i is the ideal thermodynamic glass transition temperature.

The pseudo-activation energy of conductivity is similar for all the Ca/O ratios (ca. 14.3 kJ/mol) with the exception of Ca/O = 16 (19.2 kJ/mol). These values are in accordance with other studies for systems based on POE and LiClO4 [START_REF] Vezzù | Effect of subcritical CO2 on ionic conductivity of {Al[O(CH2CH2O)8.7]ρ (LiClO4)z}n hybrid inorganicorganic networks[END_REF].

We extended this study to both POE-CaI2 and POE-Ca(TFSI)2 electrolytes, where O/Ca = 30 and 40, corresponding to a Li polymer electrolyte of 15 and 20 respectively. In addition to its intrinsic stability in reduction, CaI2 has two main advantages, namely its molar weight 294 g as compared to 338 g for Ca(CF3SO3)2 and 600 g for Ca(TFSI)2 and its low cost. Regarding Ca(TFSI)2, it was chosen to achieve a good comparison with LiTFSI considered, since early work [START_REF] Sylla | Electrochemical study of linear and crosslinked POE-based polymer electrolytes[END_REF], as the reference salt in Li-POE electrolytes. Unfortunately, POE-CaI2 exhibits poor conductivities, slightly exceeding 0.01 mS at 85ºC

for the ratio O/Ca = 40. On the other hand, POE-Ca(TFSI)2 polymer electrolytes revealed ionic conductivities higher than those obtained with POE-Ca(CF3SO3)2. Indeed, at 90°C, the maxima ranged from 0.82 mS•cm -1 (O/Ca = 30) to 0.48 mS•cm -1 (O/Ca = 40).

However, these values are questionable as creeping occurs from 80 to 85ºC for O/Ca 30 and 40, respectively. From these preliminary data, it can be inferred that Ca(CF3SO3)2 is the most suitable among the investigated Ca salts, in terms of conductivity, molar weight and electrochemical window. Moreover, based on data obtained in Li-polymer electrolytes, where the cationic transference number (T + ) of LiCF3SO3 is roughly 3 times higher than that of LiTFSI [START_REF] Alloin | Comparative ion transport in several polymer electrolytes[END_REF], higher T + and, consequently, higher cationic conductivity, σ + , can be expected for POE-Ca(CF3SO3)2 electrolytes.

Discussion

Decreasing the flammability of high-capacity batteries is an important and current challenge for their application in the automotive field and grid implementations. Whereas in Li and Na batteries solid inorganic electrolytes can be a solution to improve safety, as of today no ceramic or glassy electrolyte allows multivalent cations to move at least, in the explored temperature range. This preliminary study validates the possibility to dissolve, up to fairly high salt concentrations, three calcium salts in the reference host polymer, POE. The choice of POE is dictated by the state of the art in lithium polymer electrolytes. Indeed, it is assumed that if POE has demonstrated sufficient electrochemical stability vs Li metal, it could be advantageously used with Ca metal. Additionally, POE homo-and copolymers have an anodic stability close to 3.9 V vs Li/Li + thus 3.72 V vs Ca/Ca 2+ . Hence, they could be electrochemically stable with several cathodes previously proposed. Thus, Ca 2+ was reversibly inserted in nanocrystallized V2O5 [START_REF] Amatucci | Investigation of Yttrium and Polyvalent Ion Intercalation into Nanocrystalline Vanadium Oxide[END_REF] while enhanced insertion in V2O5 nanocomposites compared to Li [START_REF] Bervas | Vanadium oxide-propylene carbonate composite as a host for the intercalation of polyvalent cations[END_REF] was reported, validating the capability of CaB to benefit from high-performing positive electrode materials. Even though these validations were performed using liquid electrolytes, Gauthier et al. [START_REF] Gauthier | Large lithium polymer battery development The immobile solvent concept[END_REF] built and successfully tested Li/VOx prototypes based on solvent-free polymer salt complexes used both as polymer electrolytes and as binders of LiVOx composite cathodes, paving the way for the use of CAPE as binders for V2O5 cathode materials.

Whether the present work illustrates the feasibility in terms of salt solubility and conductivity of POE electrolytes, it however also emphasizes their limitations in terms of (i) crystallinity and Tm and (ii) mechanical properties (creeping from 80 to 85°C). These limitations could be overcome by using amorphous polyether networks, which demonstrated high conductivities as Li polymer electrolytes, while avoiding creeping [START_REF] Thiam | Optimizing ionic conduction of poly(oxyethylene) electrolytes through controlling the cross-link density[END_REF]. Nonetheless, information about cationic transference numbers, T + is missing in this paper as their determination currently faces two issues: (i) Ca 2+ does not deposit onto Ca 0 ; this hinders the electrochemical determination from symmetric Ca 0 /Ca-electrolyte/ Ca 0 cells [46[47]; and (ii) the inadequacy of Pulse Field Gradient NMR as a characterization technique, as the main Ca isotope is not detected by NMR. Nonetheless, a cationic transference number has recently been measured [START_REF] Wang | A Solid Polymer Electrolyte from Cross-Linked Polytetrahydrofuran for Calcium Ion Conduction[END_REF] using the impedance technique [START_REF] Evans | Electrochemical measurement of transference numbers in polymer electrolytes[END_REF]. This measurement at least exists even though we are fully convinced neither by the shape of the polarization curve [START_REF] Wang | A Solid Polymer Electrolyte from Cross-Linked Polytetrahydrofuran for Calcium Ion Conduction[END_REF]

Conclusions

The experimental data presented in this work validate the use of liquid-free CAPE based on the reference and commercially available poly(oxyethylene) (POE). All the calcium salts tested in this work were found to be homogeneously dissolved in the POE host polymer and we did not detect any microphase separation. The thermal stability of Ca polymer electrolytes points to a very high level of safety; the conductivity levels beyond the melting temperature, though not outstanding, are satisfactory for the intended application. However, the proposed CAPE suffer from two main drawbacks: (i) low conductivities from ambient temperature to Tm; and (ii) an insufficient mechanical strength, that prevents their processing into thin films. After validating the suitability of POE chains as a macromolecular solvent, from now on we are aiming at improving room temperature conductivities by using amorphous polyether networks prepared either from polycondensates [START_REF] Thiam | Optimizing ionic conduction of poly(oxyethylene) electrolytes through controlling the cross-link density[END_REF] or from POE copolymers [50][51]. Although these networks, due to their three-dimensional nature, would allow the polymer electrolyte creeping to be avoided, their processing into films 10 to 20 µm thick is challenging as it requires a high density of crosslinks, that is detrimental to ionic conductivity [23][24]. Nevertheless, nanocomposite strategies [START_REF] Azizi Samir | Cross-Linked Nanocomposite Polymer Electrolytes Reinforced with Cellulose Whiskers[END_REF] based on the use of moderate wt% amounts of Crystalline Nano Cellulose (CNC) should reconcile a high mechanical strength and high conductivities, allowing the ohmic drop in the electrolyte to be decreased. Contrarily to Li and even Na polymer electrolytes, the development of CAPEs still remains a pioneering topic that requires intensive research efforts, e.g. exploration of new salts benefiting from extended delocalization of the anionic charge [START_REF] Thiam | Lithium salts based on a series of new anilinyl-perfluorosulfonamide salts and their polymer electrolytes[END_REF], accurate determination of cationic transference numbers, studies to elucidate the evolution of the interface between Ca 0 and CAPEs based on various Ca salts, etc. This physicochemical work paves the way for the development of improved polymer electrolytes able to conduct Ca species.

Figure 7

 7 Figure 7 compares the Arrhenius plots of POE electrolytes based on CaI2 and Ca(TFSI)2.

Figure 1 .

 1 Figure 1. Distribution of calcium obtained by X-ray mapping in the proposed electrolytes. Top panel: POE-Ca(CF3SO3)2; middle panel; POE-Ca(TFSI)2; bottom panel: POE-CaI2. All the samples exhibit an O/Ca molar ratio equal to 30.

Figure 3 .

 3 Figure 3. Isothermal TGA analyses of POE-Ca(CF3SO3)2 carried out at 100 and 170°C in a mixture of air and nitrogen.

Figure 4 .

 4 Figure 4. Storage moduli (E') obtained by DMTA for POE-Ca(CF3SO3)2 electrolytes at different O/Ca ratios. The inset shows peaks corresponding to the tan δ of the electrolytes as temperature is raised.

Figure 5 .

 5 Figure 5. Real component of the complex conductivity (σ') vs frequency and temperature for POE-Ca(CF3SO3)2 samples (O/Ca = 8, 20, 40).

Figure 6 .

 6 Figure 6. Ionic conductivity as a function of temperature and O/Ca ratio for POE-Ca(CF3SO3)2 samples.

Figure 7 .

 7 Figure 7. Ionic conductivity as a function of temperature and O/Ca ratio for POE-CaI2 and POE-Ca(TFSI)2 electrolytes. Dotted lines correspond to VTF fitting.

  is applied to obtain electrolyte films.

	Briefly, each electrolyte film is obtained by dissolving in deionized water specific
	amounts of POE and the corresponding calcium salt according to the O/Ca ratios. For
	instance, in case of the POE-Ca(CF3SO3)2 electrolyte (O/Ca=40), 0.19 g of Ca(CF3SO3)2
	were dissolved in 1g of POE and 10 ml of deionized water. Solutions are stirred for five
	hours, frozen at -20°C and then lyophilized over the course of 48 hours by means of a
	FreeZone instrument (LABCONCO, USA). The resulting powders are then deposited on
	a stainless steel plate and brought to 100°C for 20 minutes; this process: (1) eliminates
	the residual moisture; and (ii) melts the powders. The melted polymer undergoes hot-
	pressing at 50 kN and 100°C, resulting in films that exhibit a thickness of 100-150 μm.

  (see supplementary information) nor by the establishment of a steady-state current. Moreover the fairly high T + reported, 0.352, was obtained for the concentration O/Ca = 1.9 (similar to O/Li #1) far from the usual salt concentrations in polymer electrolyte-based batteries, falling more within the salt in polymer concept. Regarding the mobility of alkaline-earth cations, Vincent reported that Mg 2+ moves together with oligoether chains having molecular weights below the entanglement threshold (~3,200 g•mole -1 )[START_REF] Shi | The effect of molecular weight on cation mobility in polymer electrolytes[END_REF]. He also compared, by d.c. polarization[START_REF] Vincent | Ion transport in polymer electrolytes[END_REF], the mobility of Mg 2+ and Ca 2+ hosted in oligomers (Mn >> 3,200 g) and linear polymers (commercial POE and polycondensates), using mercury amalgams (Mg/Hg and Ca/Hg) electrodes. Surprisingly, Vincent did not use the impedance technique that he previously co-authored[START_REF] Evans | Electrochemical measurement of transference numbers in polymer electrolytes[END_REF] to access T + . In both host polymers, Mg 2+ was found to be immobile. Conversely, an important current passed for more than 20 hours in the calcium symmetric cell. Indeed, if alkaline cations, from Li + to K + , and alkaline-earth cations, from Mg 2+ to Ba 2+ are both considered as Hard Acids (HSAB theory), one can infer that Li + should have roughly the same hardness as Mg 2+ when Ca 2+ hardness should be close to K + one. Since the ether function of ethylene oxide repeat unit is a Hard Base, a high Acid Hardness should be more detrimental to the mobility of alkaline-earth cations compared to alkaline cations, especially as the former have a double positive charge.Besides Vincent, on the basis of water molecules exchanges, assumed a higher hardness of Mg 2+ vs Ca 2+ , assumption in accordance with the reinforcement of thermoplastics, elastomers and gels induced by MgO fillers[START_REF] Wu | Studies on the effect of nano-sized MgO in magnesium-ion conducting gel polymer electrolyte for rechargeable magnesium batteries[END_REF]. A significant reinforcement above Tm, with regard to POE host, should be therefore induced by the dissolution of Ca and, above all, of Mg salts. Nonetheless, even though both Ca 2+ and Mg 2+ triflate delay the creeping of their related polymer electrolytes with regard to the POE host, this reinforcement, even in the case of Mg triflate, is not noticeable with regard to POE/Na triflate[START_REF] Martinez-Cisneros | Development of sodium-conducting polymer electrolytes: Comparison between film-casting and films obtained via green processes[END_REF] (vide

	supra). As a tentative explanation, one can infer that both divalent cations are mainly
	located inside POE (intra-chain solvation) minimizing inter-chain solvation and,
	therefore, transient crosslinks. Based on macroscopic, therefore questionable, DMTA
	data, this assumption is however supported by the crystallographic structure of
	POE/HgCl2 complexes [35][36].

Acknowledgements

This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 829145 (FETOPEN-VIDICAT).

V. Di Noto thanks the University Carlos III of Madrid for the "Cátedras de Excelencia UC3M-Santander" (Chair of Excellence UC3M-Santander).

TABLES

Table 1. Relevant properties of Li, Na, K, Mg and Ca for battery applications [START_REF] Park | Stable and high-power calcium-ion batteries enabled by calcium intercalation into Graphite[END_REF].


Clémentine Owen
email: clementine.owen@aphp.frlecontenudece

Keywords: Cancer de l'endomètre, ganglion sentinelle, lymphade ́nectomie, pronostique endometrial cancer, sentinel lymph node, lymphadenectomy, prognosis

En 2018, dans le monde, près de 382 100 nouveaux cas de cancer de l'endomètre ont été recensés, ce qui représente environ 4,4 % des nouveaux cas de cancer chez la femme. En France, en 2018, le cancer de l'endomètre est le premier cancer gynécologique en incidence et le quatrième cancer chez la femme. Le rationnel de la prise en charge thérapeutique du cancer de l'endomètre repose sur l'estimation d'un risque théorique de récidive et de métastase ganglionnaire sur des critères IRM et biopsique préopératoire. Cependant le statut ganglionnaire reste l'élément déterminant du traitement adjuvant. Afin de diminuer la morbidité de la lymphade ́nectomie, le concept du ganglion sentinelle a été développé. La technique du ganglion sentinelle a évolué ces dernières années grâce à l'avènement de la robotique et la création de caméra à détection de fluorescence. Il a été montré que la détection du ganglion sentinelle au Vert d'Indocyanine (ICG) permettait une migration bilatérale plus fréquente de 88 à 100 % et une meilleure détection des ganglions sentinelles pelviens dans 97 % des cas avec une baisse de la morbidité. Récemment, devant l'absence de rôle thérapeutique de la stadification ganglionnaire, les risques opératoires et le décalage des traitements adjuvants, en cas de métastase ganglionnaire pelvienne à l'examen histologique définitif, la question de réaliser secondairement la lymphade ́nectomie lomboaortique se pose. La procédure du ganglion sentinelle élargie à l'ensemble des cancers de l'endomètre de stade précoce devrait aboutir à une réduction majeure du recours à une stadification secondaire et une meilleure adaptation de la thérapeutique adjuvante.

Introduction

En 2018, dans le monde, près de 382 100 nouveaux cas de cancer de l'endomètre ont été́ recensés, ce qui représente environ 4,4 % des nouveaux cas de cancer chez la femme [START_REF] Ferlay | Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods[END_REF]. Ce taux le situe au septième rang en termes d'incidence, après le cancer du sein, du côlon-rectum, du poumon, du col de l'utérus, de la thyroïde et des carcinomes cutanés [START_REF] Ferlay | Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods[END_REF]. Le nombre de décès liés au cancer de l'endomètre dans le monde est estimé à 89 900 décès [START_REF] Ferlay | Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods[END_REF].

En France, en 2018, le cancer de l'endomètre est le premier cancer gynécologique en incidence et le quatrième cancer chez la femme [START_REF] Defossez | Estimations nationales de l'incidence et de la mortalité par cancer en France métropolitaine entre 1990 et 2018. Étude à partir des registres des cancers du réseau Francim[END_REF]. Environ 8 224 nouveaux cas et près de 2 415 décès ont été rapportés [START_REF] Defossez | Estimations nationales de l'incidence et de la mortalité par cancer en France métropolitaine entre 1990 et 2018. Étude à partir des registres des cancers du réseau Francim[END_REF]. Le cancer de l'endomètre affecte les femmes entre 55 et 65 ans en période post-ménopausique, mais peut être diagnostiqué en période préménopausique dans 14 % des cas et avant 40 ans dans 5 % des cas posant le problème de la préservation de la fertilité [START_REF] Ballester | Nouvelles recommandations EMSO, ESGO, ESTRO sur la prise en charge des cancers de l'endomètre[END_REF][START_REF] Wei | Comparison of fertility-sparing treatments in patients with early endometrial cancer and atypical complex hyperplasia: A meta-analysis and systematic review[END_REF].

Le rationnel de la prise en charge thérapeutique du cancer de l'endomètre (chirurgie, radiothérapie externe, curiethérapie, chimiothérapie, traitement anti-hormonal et thérapies ciblées) repose sur l'estimation d'un risque théorique de récidive et de métastase ganglionnaire [START_REF] Bendifallah | Cancer de l'endomètre de stade précoce : implication clinique des modèles prédictifs[END_REF][START_REF] Querleu | Prise en charge primaire des cancers de l'endomètre : recommandations SFOG-CNGOF[END_REF]. Ce risque repose sur la caractérisation de facteurs pronostiques (cliniques, histologiques, classification moléculaire et imagerie) isolés ou regroupés sous la forme de classification comme celle proposée par l'ESMO-ESGO-ESTRO [START_REF] Bendifallah | Cancer de l'endomètre de stade précoce : implication clinique des modèles prédictifs[END_REF][START_REF] Colombo | ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: Diagnosis, Treatment and Follow-up[END_REF][START_REF] Koh | Uterine Neoplasms, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology[END_REF].

Si la question de la prise en charge chirurgicale et adjuvante des cancers de l'endomètre de stade avancé et/ou à haut risque de récidive est assez codifié [START_REF] Querleu | Prise en charge primaire des cancers de l'endomètre : recommandations SFOG-CNGOF[END_REF][START_REF] Colombo | ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: Diagnosis, Treatment and Follow-up[END_REF][START_REF] Koh | Uterine Neoplasms, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology[END_REF], le cancer de l'endomètre de stade précoce (stade FIGO I) qui représente près de 80 % des formes au diagnostic est soumis a ̀ de nombreuses variations de prise en charge a ̀ travers le monde [START_REF] Ballester | Nouvelles recommandations EMSO, ESGO, ESTRO sur la prise en charge des cancers de l'endomètre[END_REF][START_REF] Koh | Uterine Neoplasms, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology[END_REF]. Ces disparités concernent (i) la question de la stadification ganglionnaire et les indications systématiques d'une lymphade ́nectomie pelvienne et lombo-aortique, (ii) l'intérêt de la procédure du ganglion sentinelle, (iii) la problématique du traitement en l'absence d'information du statut ganglionnaire mais aussi les indications du traitement adjuvant après chirurgie [START_REF] Querleu | Prise en charge primaire des cancers de l'endomètre : recommandations SFOG-CNGOF[END_REF][START_REF] Colombo | ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: Diagnosis, Treatment and Follow-up[END_REF][START_REF] Koh | Uterine Neoplasms, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology[END_REF][START_REF] Creutzberg | Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. PORTEC Study Group. Post Operative Radiation Therapy in Endometrial Carcinoma[END_REF][START_REF] Nout | Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, noninferiority, randomised trial[END_REF][START_REF] De Boer | Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial[END_REF]. En conséquence, un certain nombre de patientes se voit attribuer des traitements qui peuvent se révéler inadaptés, inutiles ou inefficaces, et potentiellement délétères [START_REF] Bendifallah | Cancer de l'endomètre de stade précoce : implication clinique des modèles prédictifs[END_REF][START_REF] Creutzberg | Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. PORTEC Study Group. Post Operative Radiation Therapy in Endometrial Carcinoma[END_REF][START_REF] Nout | Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, noninferiority, randomised trial[END_REF][START_REF] De Boer | Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial[END_REF][START_REF] May | Lymphadenectomy for the management of endometrial cancer[END_REF].

Dans le présent manuscrit nous proposons (i) une synthèse de la problématique clinique du statut ganglionnaire dans le cancer de l'endomètre de stade précoce, (ii) une revue récente des techniques de procédure de ganglion sentinelle et une synthèse des indications chirurgicales actuelles en prenant en compte l'évaluation du statut ganglionnaire.

Place de l'évaluation ganglionnaire dans le cancer de l'endomètre La stratégie actuelle de prise en charge du cancer de l'endomètre est basée sur l'identification et la combinaison de facteurs pronostiques. Deux principales questions font l'objet de discussions dans la littérature internationale :

(i)
La première concerne l'évaluation du statut ganglionnaire. Cette question renvoie à la problématique de l'intérêt pronostique et thérapeutique de la lymphade ́nectomie pelvienne et lombo-aortique mais aussi du ganglion sentinelle. (ii) La seconde concerne l'estimation du risque de récidive et l'optimisation des thérapeutiques adjuvantes.

Ces deux problématiques sous-tendent une question plus globale, qui est celle de l'optimisation de la prise en charge thérapeutique (chirurgicale et adjuvante). En pratique, l'enjeu est de ne pas surtraiter les patientes à risque faible de récidive et, a contrario, de ne pas sous-estimer le risque réel de récidive [START_REF] Ballester | Nouvelles recommandations EMSO, ESGO, ESTRO sur la prise en charge des cancers de l'endomètre[END_REF][START_REF] Querleu | Prise en charge primaire des cancers de l'endomètre : recommandations SFOG-CNGOF[END_REF][START_REF] Colombo | ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: Diagnosis, Treatment and Follow-up[END_REF][START_REF] Ballester | Detection rate and diagnostic accuracy of sentinel-node biopsy in early stage endometrial cancer: a prospective multicentre study (SENTI-ENDO)[END_REF][START_REF] Morice | Endometrial cancer[END_REF].

Les différentes imageries préopératoires (échographie pelvienne, IRM pelvienne, TDM, PET-TDM) ne permettent pas de Connaître avec certitude le groupe à risque ou le statut ganglionnaire (mauvaise sensibilité mais haute spécificité) mais peuvent être une alternative à la stadification ganglionnaire lombo-aortique en cas de risque chirurgical [START_REF] Morice | Endometrial cancer[END_REF][START_REF] Querleu | Lymph node dissection in the surgical management of stage I endometrial carcinomas[END_REF][START_REF] Bollineni | High Diagnostic Value of 18F-FDG PET/CT in Endometrial Cancer: Systematic Review and Meta-Analysis of the Literature[END_REF][START_REF] Lavaud | Preoperative MR imaging for ESMO-ESGO-ESTRO classification of endometrial cancer[END_REF][START_REF] Tanaka | The diagnostic accuracy of fluorodeoxyglucose-positron emission tomography/computed tomography and sentinel node biopsy in the prediction of pelvic lymph node metastasis in patients with endometrial cancer: A retrospective observational study[END_REF][START_REF] Fares | Preoperative Prediction of Lymph Nodal Metastases in Endometrial Carcinoma: Is it Possible?: A Literature Review[END_REF]. Avec une mesure à cinq millimètres de l'endomètre chez les patientes ménopausées, l'échographie a une sensibilité de 90 % et une spécificité de 54 % pour le diagnostic de néoplasie endométriale sans pouvoir donner une information ganglionnaire [START_REF] Morice | Endometrial cancer[END_REF] Techniques chirurgicales de l'évaluation du statut ganglionnaire dans le cancer de l'endomètre

La stadification ganglionnaire fait partie de la prise en charge du cancer de l'endomètre depuis la mise à jour de la classification FIGO en 1988 [START_REF] Shepherd | Revised FIGO staging for gynaecological cancer[END_REF]. La lymphade ́nectomie pelvienne et lombo-aortique ont été longtemps recommandées pour tous les cancers de l'endomètre sans pour autant être réalisées de façon uniforme dans tous les pays, avec certaines séries observationnelles rétrospectives qui rapportaient un bénéfice sur la survie globale et sans récidive à 5 ans dans les groupes à risques élevés et intermédiaires [START_REF] Chan | Therapeutic role of lymph node resection in endometrioid corpus cancer: a study of 12,333 patients[END_REF]. Les études récentes ont montré l'absence de bénéfice des curages et notamment du curage pelvien sur la survie sans récidive et la survie globale dans les stades précoces tout en augmentant les risques de complications à court et à moyen terme [START_REF] May | Lymphadenectomy for the management of endometrial cancer[END_REF][START_REF] Kitchener | Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study[END_REF][START_REF] Benedetti Panici | Systematic pelvic lymphadenectomy vs. no lymphadenectomy in early-stage endometrial carcinoma: randomized clinical trial[END_REF][START_REF] Frost | Lymphadenectomy for the management of endometrial cancer. Cochrane Gynaecological, Neuro-oncology and Orphan Cancer Group[END_REF]. [START_REF] Barranger | Laparoscopic sentinel node procedure using a combination of patent blue and radiocolloid in women with endometrial cancer[END_REF][START_REF] Delpech | The sentinel node concept in endometrial cancer: histopathologic validation by serial section and immunohistochemistry[END_REF][START_REF] Vermersch | Place of indocyanine green coupled with fluorescence imaging in research of breast cancer sentinel node[END_REF][START_REF] Daraï | Sentinel node biopsy for the management of early stage endometrial cancer: long-term results of the SENTI-ENDO study[END_REF].

La technique du ganglion sentinelle augmente par ailleurs la détection des métastases du fait de l'ultrastadification qui permet de détecter 4,5 % de ganglions métastatiques considérés négatifs en analyse histologique standard [START_REF] Kim | Pathologic ultrastaging improves micrometastasis detection in sentinel lymph nodes during endometrial cancer staging[END_REF][START_REF] Gasparri | Surgical staging in endometrial cancer[END_REF]. Cependant, il convient de souligner que la plupart de ces métastases correspondent soit à des cellules isolées soit à des micro-métastases dont la valeur pronostique reste discutée [START_REF] Plante | Isolated tumor cells identified by sentinel lymph node mapping in endometrial cancer: Does adjuvant treatment matter?[END_REF][START_REF] Bogani | Low-volume disease in endometrial cancer: The role of micrometastasis and isolated tumor cells[END_REF].

L'objectif est d'obtenir moins de 5 % de faux négatif (FN) [START_REF] Rocha | Indocyanine green and infrared fluorescence in detection of sentinel lymph nodes in endometrial and cervical cancer staginga systematic review[END_REF]. Il existe 5 à 10 % d'échec de ganglion sentinelle en per-opératoire [START_REF] Ballester | Detection rate and diagnostic accuracy of sentinel-node biopsy in early stage endometrial cancer: a prospective multicentre study (SENTI-ENDO)[END_REF][START_REF] Gasparri | Surgical staging in endometrial cancer[END_REF]. Concernant la réalisation du ganglion sentinelle, une analyse extemporanée peropératoire permet de Connaître le statut ganglionnaire pelvien. En cas de positivité du ganglion sentinelle en per-opératoire, il convient de compléter l'exploration ganglionnaire [START_REF] Querleu | Prise en charge primaire des cancers de l'endomètre : recommandations SFOG-CNGOF[END_REF].

Il n'y a pas de consensus concernant le complément du curage pelvien [START_REF] Querleu | Prise en charge primaire des cancers de l'endomètre : recommandations SFOG-CNGOF[END_REF][START_REF] Colombo | ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: Diagnosis, Treatment and Follow-up[END_REF][START_REF] Koh | Uterine Neoplasms, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology[END_REF]. En effet, par analogie avec le cancer du col de l'utérus, la morbidité du curage pelvien associé à la radiothérapie externe augmente sans apporter d'information supplémentaire diagnostique ou thérapeutique [START_REF] Vercellino | AÀ GCIG international survey: clinical practice patterns of sentinel lymph node biopsies in cervical cancer[END_REF]. La lymphade ́nectomie lombo-aortique réalisée dans le même temps opératoire permet une stadification chirurgicale complète en un temps, et donc de débuter plus rapidement les traitements adjuvants (chimiothérapie et radiothérapie) [START_REF] Querleu | Prise en charge primaire des cancers de l'endomètre : recommandations SFOG-CNGOF[END_REF][START_REF] Colombo | ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: Diagnosis, Treatment and Follow-up[END_REF][START_REF] Koh | Uterine Neoplasms, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology[END_REF]. En cas de ganglion sentinelle positif à l'examen histologique définitif après ganglion sentinelle négatif en extemporané (situation intéressant moins de 10 % des patientes) [START_REF] Querleu | Prise en charge primaire des cancers de l'endomètre : recommandations SFOG-CNGOF[END_REF][START_REF] Ouldamer | Call for Surgical Nodal Staging in Women with ESMO/ESGO/ESTRO High-Intermediate Risk Endometrial Cancer: A Multicentre Cohort Analysis from the FRANCOGYN Study Group[END_REF], il convient de réaliser une lymphade ́nectomie lombo-aortique. Dans ce cas non plus, il n'existe pas de consensus concernant la réalisation des curages pelviens [START_REF] Querleu | Prise en charge primaire des cancers de l'endomètre : recommandations SFOG-CNGOF[END_REF][START_REF] Colombo | ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: Diagnosis, Treatment and Follow-up[END_REF][START_REF] Koh | Uterine Neoplasms, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology[END_REF][START_REF] Vercellino | AÀ GCIG international survey: clinical practice patterns of sentinel lymph node biopsies in cervical cancer[END_REF].

Récemment, devant l'absence de rôle thérapeutique de la stadification ganglionnaire, Contributions de la procédure du ganglion sentinelle dans la prise en charge des cancers de l'endomètre

Il existe une importante disparité de prise en charge chirurgicale dans les cancers de l'endomètre à haut risque de récidive notamment l'absence fréquente de lymphade ́nectomie pelvienne et/ou lombo-aortique [START_REF] Morice | Endometrial cancer[END_REF][START_REF] Racin | Lymphadenectomy in elderly patients with high-intermediate-risk, high-risk or advanced endometrial cancer: Time to move from personalized cancer medicine to personalized patient medicine![END_REF]. La morbidité per-opératoire et postopératoire de la lymphade ́nectomie lombo-aortique n'est pas en faveur de sa réalisation systématique malgré les recommandations [START_REF] Querleu | Prise en charge primaire des cancers de l'endomètre : recommandations SFOG-CNGOF[END_REF][START_REF] Colombo | ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: Diagnosis, Treatment and Follow-up[END_REF][START_REF] Koh | Uterine Neoplasms, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology[END_REF][START_REF] Wang | Meta-analysis of laparoscopy sentinel lymph node mapping in endometrial cancer[END_REF][START_REF] Naoura | Relevance of sentinel lymph node procedure for patients with high-risk endometrial cancer[END_REF][START_REF] Sullivan | Sentinel Lymph Node Biopsy in Endometrial Cancer: a New Standard of Care?[END_REF]. Même si certaines études rétrospectives ont montré un bénéfice d'une lymphade ́nectomie complète sur la survie à cinq ans, ce résultat n'a pas été prouvé dans les études prospectives [START_REF] Racin | Lymphadenectomy in elderly patients with high-intermediate-risk, high-risk or advanced endometrial cancer: Time to move from personalized cancer medicine to personalized patient medicine![END_REF][START_REF] Ducie | Comparison of a sentinel lymph node mapping algorithm and comprehensive lymphadenectomy in the detection of stage IIIC endometrial carcinoma at higher risk for nodal disease[END_REF]. Sans pour autant pouvoir se passer d'une stadification ganglionnaire, cette stadification n'est pas considérée comme thérapeutique [START_REF] Querleu | Lymph node dissection in the surgical management of stage I endometrial carcinomas[END_REF][START_REF] Kitchener | Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study[END_REF]. De plus, il a été montré le taux de deux pour cent de métastases lombo-aortiques en l'absence de métastase pelvienne tous stades confondus [START_REF] Abu-Rustum | The incidence of isolated paraaortic nodal metastasis in surgically staged endometrial cancer patients with negative pelvic lymph nodes[END_REF].

Depuis plusieurs années, de nombreuses équipes comparent les résultats du ganglion sentinelle pelvien et de la lymphade ́nectomie complète pour montrer la faisabilité et la validité du ganglion sentinelle pelvien dans les cancers de l'endomètre à haut risque préopératoire [START_REF] Querleu | Prise en charge primaire des cancers de l'endomètre : recommandations SFOG-CNGOF[END_REF][START_REF] Racin | Lymphadenectomy in elderly patients with high-intermediate-risk, high-risk or advanced endometrial cancer: Time to move from personalized cancer medicine to personalized patient medicine![END_REF][START_REF] Ducie | Comparison of a sentinel lymph node mapping algorithm and comprehensive lymphadenectomy in the detection of stage IIIC endometrial carcinoma at higher risk for nodal disease[END_REF][START_REF] Gasparri | Surgical staging in endometrial cancer[END_REF][START_REF] Ouldamer | Call for Surgical Nodal Staging in Women with ESMO/ESGO/ESTRO High-Intermediate Risk Endometrial Cancer: A Multicentre Cohort Analysis from the FRANCOGYN Study Group[END_REF][START_REF] Naoura | Relevance of sentinel lymph node procedure for patients with high-risk endometrial cancer[END_REF]. Dans les dernières recommandations des USA (NCCN), le ganglion sentinelle pelvien est recommandé en préopératoire dans les bas risques et les risques intermédiaires, ainsi que les hauts risques tout en restant associé à une lymphade ́nectomie lombo-aortique dans l'attente de données complémentaires [START_REF] Koh | Uterine Neoplasms, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology[END_REF][START_REF] Holloway | Sentinel lymph node mapping and staging in endometrial cancer: A Society of Gynecologic Oncology literature review with consensus recommendations[END_REF][START_REF] Sullivan | Sentinel Lymph Node Biopsy in Endometrial Cancer: a New Standard of Care?[END_REF][START_REF] Touhami | Performance of sentinel lymph node (SLN) mapping in high-risk endometrial cancer[END_REF].

En 2016, la méta analyse de Ruscito et coll. a montré qu'il n'y avait pas de différence significative entre l'ICG seul comparé aux autres combinaisons de détection et jusqu'à 100 % de migration bilatérale [START_REF] Ruscito | Sentinel Node Mapping in Cervical and Endometrial Cancer: Indocyanine Green Versus Other Conventional Dyes-A Meta-Analysis[END_REF]. En 2016, la méta-analyse de Rocha et coll. a montré une détection du ganglion sentinelle de 78 à 100 % [START_REF] Rocha | Indocyanine green and infrared fluorescence in detection of sentinel lymph nodes in endometrial and cervical cancer staginga systematic review[END_REF]. En 2015, la revue de la littérature de

  les risques opératoires et le décalage des traitements adjuvants, en cas de métastase ganglionnaire pelvienne à l'examen histologique définitif, la question de réaliser secondairement la lymphade ́nectomie lombo-aortique se pose. La stadification lomboaortique se justifiait du fait de 10 à 15 % de FN à la TEP-TDM et sur la théorie curative des curages. Devant les améliorations et les innovations en termes d'imagerie, notamment avec l'amélioration de la TEP-TDM et l'apparition de la TEP-IRM, il apparaît que ces imageries ont toute leur place pour évaluer l'atteinte ganglionnaire lombo-aortique en évitant une ré-intervention avec des risques opératoires non négligeables. En 2012, dans une métaanalyse sur la TEP-TDM, Chang et coll. ont montré une sensibilité de 63 % [IC 95 % : 48,7-75,7 %], une spécificité de 94,7 % [IC 95 % : 90,4-97,4 %] dans la détection des métastases ganglionnaires. La valeur prédictive positive était de 10,4 [IC 95 % : 5,6-19,3] et la valeur prédictive négative 0,39 [IC 95 % : 0,28-0,56]. Ces résultats confirment que les imageries peuvent permettre d'éviter une ré-intervention[START_REF] Morice | Endometrial cancer[END_REF][START_REF] Bollineni | High Diagnostic Value of 18F-FDG PET/CT in Endometrial Cancer: Systematic Review and Meta-Analysis of the Literature[END_REF][START_REF] Chang | 18F-FDG PET or PET/CT for detection of metastatic lymph nodes in patients with endometrial cancer: a systematic review and meta-analysis[END_REF][START_REF] Legros | Paraaortic Lymph Node Invasion in High-risk Endometrial Cancer: Performance of 18FDG PET-CT[END_REF][START_REF] Atri | Utility of PET/CT to Evaluate Retroperitoneal Lymph Node Metastasis in High-Risk Endometrial Cancer: Results of ACRIN 6671/GOG 0233 Trial[END_REF][START_REF] Wetter | PET/MR imaging of pelvic malignancies[END_REF][START_REF] Fraum | Measurement Repeatability of 18F-FDG-PET/CT versus 18F-FDG-PET/MRI in Solid Tumors of the Pelvis[END_REF].

  . Pour l'évaluation ganglionnaire préopératoire, l'IRM a une sensibilité de 58,8 % et une spécificité de 92,8 %[START_REF] Fares | Preoperative Prediction of Lymph Nodal Metastases in Endometrial Carcinoma: Is it Possible?: A Literature Review[END_REF]. Le PET scanner a quant à lui une sensibilité de 74,2 % et une spécificité de

	92,8 % (19). Tableau 1 : Classification FIGO et TNM (6).
	La prise en charge chirurgicale minimale du cancer de l'endomètre des stades
	précoces associe une hystérectomie totale avec annexectomie bilatérale (6). La cytologie
	péritonéale n'est plus nécessaire pour la stadification mais reste recommandée (6-8). Ce
	paradoxe repose sur la valeur discutable de la cytologie péritonéale comme facteur
	pronostique. En effet, si la valeur de la cytologie ne modifie pas le stade FIGO, sa positivité,
	quels que soient le type et le stade du cancer de l'endomètre, peut influencer les traitements
	adjuvants avec un risque de diminution de la survie sans récidive (20,21). L'omentectomie
	est réalisée exclusivement pour le type histologique séreux selon les recommandations
	françaises et européennes (3,6,7). À noter que les recommandations des USA préconisent la
	réalisation de l'omentectomie pour tous les types 2 (carcinomes séreux, carcino-sarcomes,
	carcinomes à cellules claires et indifférenciées) (8).
	En fonction des données du bilan préopératoire permettant de définir des groupes
	présumés à risque de récidive, une stratégie thérapeutique chirurgicale incluant la place de
	l'évaluation ganglionnaire est proposée. Tableau 2 : Définition de groupes de risque basée
	sur le bilan pré opératoire (6). La difficulté d'évaluation des emboles en préopératoire reste
	entière (6). Cependant, le taux de discordance entre les données préopératoires basées sur
	l'IRM et la biopsie et l'histologie définitive contribuent à un risque d'indication de stadification
	ganglionnaire seconde. Phelippeau et coll. ont souligné le taux important de patientes
	pouvant nécessiter une restadification ganglionnaire pour adapter les thérapeutiques
	complémentaires du fait du taux élevé de discordance (22). En effet, de 21 à 33 % des
	cancers de l'endomètre présumés à bas risque sont reclassés à risque intermédiaire élevé
	ou risque élevé en postopératoire (14,23). Le taux de discordance est estimé de 10 à 20 %
	entre le groupe à risque pré et postopératoire pour les cancers de l'endomètre (6,14).
	Tableau 3 : Définition de groupes de risque basée sur la pathologie définitive (6). L'ensemble
	de ces données contribue à un paradoxe thérapeutique consistant à poser des indications

thérapeutiques adjuvantes en l'absence d'information sur le statut ganglionnaire (Tableau 4 : Nouveaux groupes à risque selon l'ESMO-ESGO-ESTRO ; Annexe 1 : Traitement adjuvant en fonction du statut ganglionnaire)

[START_REF] Querleu | Prise en charge primaire des cancers de l'endomètre : recommandations SFOG-CNGOF[END_REF][START_REF] Colombo | ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: Diagnosis, Treatment and Follow-up[END_REF][START_REF] Koh | Uterine Neoplasms, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology[END_REF][START_REF] Ballester | Detection rate and diagnostic accuracy of sentinel-node biopsy in early stage endometrial cancer: a prospective multicentre study (SENTI-ENDO)[END_REF][START_REF] Morice | Endometrial cancer[END_REF][START_REF] Querleu | Lymph node dissection in the surgical management of stage I endometrial carcinomas[END_REF][START_REF] Racin | Lymphadenectomy in elderly patients with high-intermediate-risk, high-risk or advanced endometrial cancer: Time to move from personalized cancer medicine to personalized patient medicine![END_REF]

. Depuis 2017, pour les groupes à risque présumés en préopératoire, les recommandations françaises indiquent que les patientes à risque bas pourraient bénéficier d'une procédure du ganglion sentinelle alors que pour le risque intermédiaire la procédure est recommandée. Pour les patientes à risque élevé une lymphade ́nectomie pelvienne et lombo-aortique est indiquée

[START_REF] Querleu | Prise en charge primaire des cancers de l'endomètre : recommandations SFOG-CNGOF[END_REF]

. Cependant, on peut discuter l'intérêt de la stadification ganglionnaire chirurgicale en fonction de la balance bénéfice-risque de la chirurgie

[START_REF] Morice | Endometrial cancer[END_REF]

. En effet, le geste chirurgical est potentiellement réalisé chez des patientes âgées pouvant présenter de nombreuses comorbidités médicales (diabète, obésité, pathologies cardiovasculaires) et de plus le taux d'envahissement ganglionnaire est relativement faible

[START_REF] Querleu | Prise en charge primaire des cancers de l'endomètre : recommandations SFOG-CNGOF[END_REF][START_REF] May | Lymphadenectomy for the management of endometrial cancer[END_REF][START_REF] Ballester | Detection rate and diagnostic accuracy of sentinel-node biopsy in early stage endometrial cancer: a prospective multicentre study (SENTI-ENDO)[END_REF][START_REF] Morice | Endometrial cancer[END_REF][START_REF] Baubil | Prise en charge chirurgicale des ganglions dans le cancer de l'endomètre au stade I[END_REF][START_REF] Holloway | Sentinel lymph node mapping and staging in endometrial cancer: A Society of Gynecologic Oncology literature review with consensus recommendations[END_REF][START_REF] Wang | Meta-analysis of laparoscopy sentinel lymph node mapping in endometrial cancer[END_REF]

.

Le Tableau 5 propose une synthèse des indications de la stadification ganglionnaire selon les recommandations françaises, européennes et des USA

[START_REF] Querleu | Prise en charge primaire des cancers de l'endomètre : recommandations SFOG-CNGOF[END_REF][START_REF] Colombo | ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: Diagnosis, Treatment and Follow-up[END_REF][START_REF] Koh | Uterine Neoplasms, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology[END_REF]

.

  Pour les cancers de l'endomètre à haut risque de récidive (risque intermédiaire élevé et hauts risques post-opératoires), une stadification ganglionnaire complète reste recommandée du fait d'une atteinte ganglionnaire de 22 à 50 %[START_REF] Querleu | Prise en charge primaire des cancers de l'endomètre : recommandations SFOG-CNGOF[END_REF][START_REF] Racin | Lymphadenectomy in elderly patients with high-intermediate-risk, high-risk or advanced endometrial cancer: Time to move from personalized cancer medicine to personalized patient medicine![END_REF]. Il a été montré dans certaines études un bénéfice d'une lymphade ́nectomie complète sur la survie à cinq ans[START_REF] Querleu | Lymph node dissection in the surgical management of stage I endometrial carcinomas[END_REF][START_REF] Ducie | Comparison of a sentinel lymph node mapping algorithm and comprehensive lymphadenectomy in the detection of stage IIIC endometrial carcinoma at higher risk for nodal disease[END_REF].La technique de la lymphade ́nectomie pelvienne consiste en un évidement complet de la loge graisseuse sous les vaisseaux iliaques externes, au-dessus du nerf obturateur, en interne de l'artère ombilicale et de l'artère iliaque interne. La lymphade ́nectomie lomboaortique ne pourra jamais être exhaustive mais doit y tendre tout en privilégiant la zone

supra mésentérique qui concentre 35 % des métastases ganglionnaires lombo-aortiques dans les cancers de l'endomètre à haut risque de récidive. Les limites de la lymphade ́nectomie lombo-aortique se situent entre les deux uretères, au contact des gros vaisseaux, sous la veine rénale gauche avec une séparation en sous et sus-mésentérique inférieure. Les zones iliaques communes et pré-sacrée doivent être incluses

[START_REF] Querleu | Prise en charge primaire des cancers de l'endomètre : recommandations SFOG-CNGOF[END_REF][START_REF] Querleu | Lymph node dissection in the surgical management of stage I endometrial carcinomas[END_REF]

. L'avènement du ganglion sentinelle dans le cancer de l'endomètre a permis un changement de paradigme avec à la fois la baisse de la morbidité et une information ganglionnaire plus précise du fait de l'ultrastadification qui permet une adaptation des traitements adjuvants

[START_REF] Barranger | Laparoscopic sentinel node procedure using a combination of patent blue and radiocolloid in women with endometrial cancer[END_REF][START_REF] Delpech | The sentinel node concept in endometrial cancer: histopathologic validation by serial section and immunohistochemistry[END_REF]

. Le ganglion sentinelle, premier relais ganglionnaire de drainage a montré sa validité et la moindre morbidité dans d'autres cancers

[START_REF] Gipponi | Sentinel lymph node as a new marker for therapeutic planning in breast cancer patients[END_REF]

. La validation histologique de la procédure du ganglion sentinelle a été démontrée par Barranger et coll. mais en imposant une technique lourde et coûteuse avec d'une part une lymphoscintigraphie préopératoire avec injection de Technétium 99Tc le plus souvent péricervicale nécessitant un service de médecine nucléaire et d'autre part l'utilisation d'un colorant au bleu patenté avec un risque d'allergie

  En 2016, Bodurtha Smith et coll. ont rapporté dans leur méta-analyse une sensibilité du ganglion sentinelle pelvien à détecter les métastases de 96 %. Le taux de détection du ganglion sentinelle était de 81 % [IC 95 % : 77-84 %] avec 50 % de détection bilatérale [IC 95 % : 44-56 %]. Cette revue de la littérature a montré qu'il existait 17 % [IC 95 % : 11-23 %] de ganglion sentinelle lombo-aortiques (44). En 2019, la revue de la littérature de Bogani et coll. a montré que le ganglion sentinelle augmentait le taux de détection de métastases avec 14,7 % de ganglions positifs dans les ganglions sentinelles et 9,9 % dans la lymphade ́nectomie (OR 2,03 [IC 95 % : 1,30-3,18], Cet essai comprenait 132 patientes dont 46 patientes opérées par chirurgie robotique et 86 par coelioscopie. La détection du ganglion sentinelle était positive dans 90,9 % des cas avec l'ICG versus 64,4 % avec le colorant bleu (p < 0,0001). Il n'a pas été observé de différence

	La technique du ganglion sentinelle a évolué ces dernières années grâce à
	l'avènement de la robotique et la création de caméra à détection de fluorescence. L'ICG est
	un colorant utilisé depuis de nombreuses années dans d'autres disciplines médicales
	(37,50). Il permet à l'aide d'une caméra multi-spectrale d'améliorer la visualisation des dans la durée de l'intervention (médiane de dix minutes par hémi pelvis) ni le nombre de
	lymphatiques mais aussi de la vascularisation en vue d'optimiser la qualité du geste ganglion détecté par hémi pelvis (moyenne 1,2). Les taux de détection pour l'un ou l'autre
	chirurgical (44). De nombreuses études ont montré la faisabilité et la supériorité de l'ICG des colorants étaient très semblables, que l'approche chirurgicale soit robotique (IMC moyen
	injecté à un millilitre à trois heures et neuf heures dix minutes avant le début de l'intervention. 45) ou coelioscopique (IMC moyen 29).
	Ces études récentes et les méta-analyses de 2016 ont montré une migration bilatérale plus
	fréquente de 88 à 100 % et une meilleure détection des ganglions sentinelles pelviens dans
	97 % des cas (43,44,49-52). Il a été par ailleurs montré une baisse de la morbidité avec
	l'ICG (37,53).
	La technique initiale a été décrite avec l'utilisation de 0,2 ml de Technétium 99Tc
	injecté à trois, six, neuf et douze heures au niveau du col la veille ou le matin de
	l'intervention avec réalisation d'une lymphoscintigraphie permettant de contrôler la migration Les principaux écueils sont le risque de pollution du champ opératoire par le vert ce qui
	isotopique, associée à une injection d'un millilitre de bleu patenté à trois et neuf heures au peut rendre alors la procédure plus longue et fastidieuse. Enfin, il n'existe aucun consensus
	niveau du col. Cette technique a été utilisée pour la validation histologique de la procédure concernant la dose et la concentration à injecter (50,52,53).
	du ganglion sentinelle (7,13,35).

p=0,002) sans différence en taux de récidive. Cette revue de la littérature a prouvé la noninfériorité du ganglion sentinelle par rapport à la lymphade ́nectomie voire une meilleure performance du ganglion sentinelle

[START_REF] Bogani | Sentinel node mapping vs. lymphadenectomy in endometrial cancer: A systematic review and meta-analysis[END_REF]

. À l'heure actuelle, coexistent différentes méthodes pour la recherche du ganglion sentinelle dans le cancer de l'endomètre : la méthode isotopique, la méthode colorimétrique (bleu patenté), la méthode dite combinée : isotopique et colorimétrique, et plus récemment la fluorescence au Vert d'Indocyanine (ICG)

[START_REF] Vermersch | Place of indocyanine green coupled with fluorescence imaging in research of breast cancer sentinel node[END_REF]

. De plus, le site d'injection varie en fonction des études ; principalement péri-cervical mais pour certains intra-myométrial sous contrôle hystéroscopique ou per-coelioscopique par injection fundique

[START_REF] Morice | Endometrial cancer[END_REF][START_REF] Barranger | Laparoscopic sentinel node procedure using a combination of patent blue and radiocolloid in women with endometrial cancer[END_REF][START_REF] Delpech | The sentinel node concept in endometrial cancer: histopathologic validation by serial section and immunohistochemistry[END_REF][START_REF] Buda | Sentinel lymph node detection in endometrial cancer: hysteroscopic peritumoral versus cervical injection[END_REF][START_REF] Bogani | Sentinel lymph node detection in endometrial cancer: does injection site make a difference?[END_REF][START_REF] Selman | AÀ systematic review of tests for lymph node status in primary endometrial cancer[END_REF]

.

Dans les cancers de l'endomètre de bas risque et de risque intermédiaire préopératoire, le taux de ganglion sentinelle positif est de 1 à 18 %

[START_REF] Ballester | Detection rate and diagnostic accuracy of sentinel-node biopsy in early stage endometrial cancer: a prospective multicentre study (SENTI-ENDO)[END_REF][START_REF] Benedetti Panici | Systematic pelvic lymphadenectomy vs. no lymphadenectomy in early-stage endometrial carcinoma: randomized clinical trial[END_REF][START_REF] Frost | Lymphadenectomy for the management of endometrial cancer. Cochrane Gynaecological, Neuro-oncology and Orphan Cancer Group[END_REF][START_REF] Rossi | A comparison of sentinel lymph node biopsy to lymphadenectomy for endometrial cancer staging (FIRES trial): a multicentre, prospective, cohort study[END_REF]

. En 2016, la méta-analyse de Ruscito et coll. (50) proposait d'évaluer la pertinence de la fluorescence à l'ICG dans les cancers pelviens. Une analyse comparative aux autres traceurs conventionnels (la méthode isotopique au Technétium 99Tc, la méthode colorimétrique (bleu patenté) et la méthode dite combinée) a été réalisée sur la base de six études incluant 538 patientes (54) :

-Comparativement aux colorants bleus, l'ICG présentait un taux de détection global supérieur (OR 0,27 [IC 95 % : 0,15-0,50], p < 0,0001) et un taux de détection bilatérale significativement amélioré (OR 0,27 [IC 95 % : 0,19-0,40], p < 0,00001).

-Comparativement à la méthode isotopique au Technétium 99Tc et la méthode dite combinée aucune différence significative dans les taux de détection et le taux de FN n'a été rapportée confirmant au minimum sa non-infériorité

[START_REF] Frumovitz | Near-infrared fluorescence for detection of sentinel lymph nodes in women with cervical and uterine cancers (FILM): a randomised, phase 3, multicentre, non-inferiority trial[END_REF]

.

En 2019, Rozenholc et coll.

[START_REF] Rozenholc | Green versus blue: Randomized controlled trial comparing indocyanine green with methylene blue for sentinel lymph node detection in endometrial cancer[END_REF]

sur la base d'un essai randomisé, proposaient une évaluation du taux de détection des ganglions sentinelles en comparant l'utilisation de l'ICG au colorant bleu de méthylène seul chez les femmes présentant un cancer de l'endomètre.

Définition de groupes de risque basée sur le bilan pré opératoire (6) Risque bas

  Les résultats de la cytologie péritonéale doivent être rapportés séparément et ne modifient pas la classification. -Endométrioïde stade IA grade 1 -Endométrioïde stade IA grade 2

	Plante et coll. a montré 96 % de détection du ganglion sentinelle et 88 % de détection bilatérale (51). En 2018, l'étude multicentrique de Frumovitz et coll. a montré une supériorité de l'ICG seul avec 97 % de détection du ganglion sentinelle contre 72 % pour le bleu patenté (53). L'ICG peut donc être utilisé seul pour la détection des ganglions sentinelles traitement adjuvant permettant de simplifier les options thérapeutiques (Annexe 2). Cette révision nécessite un accord des sociétés savantes françaises impliquées dans le traitement du cancer de l'endomètre. Depuis quelques années, l'utilisation des micros-ARN a permis d'identifier un groupe à risque d'envahissement ganglionnaire et de récidive (66). Cette piste pourra à l'avenir probablement permettre en préopératoire d'identifier les patientes ayant un bénéfice à Tableau 1 : Classification FIGO 2009 et correspondance TNM (6) FIGO (2009) Description TNM 2009 Stade I a IA IB Tumeur limité au corps utérin Tumeur envahissant moins de 50% du myomètre Tumeur envahissant 50% ou plus du myomètre T1 T1a T1b Invasion du stroma cervical sans dépasser l'utérus T2 IIIA IIIB IIIC Extension locale et/ou régionale Séreuse et/ou annexes b Envahissement vaginal et/ou paramétrial b Atteintes des ganglions lymphatiques b T3 et/ou N1 T3a N1 -Type 2 T3b -Endométrioïde Stade II et plus Risque élevé -Endométrioïde stade IB grade 3 Stade III a -Endométrioïde stade IB grade 2 Stade II a -Endométrioïde stade IA grade 3 -Endométrioïde stade IB grade 1 Tableau 2 : Risque intermédiaire Tableau 3 :
	(40,43,44,49-53). Plusieurs avantages sont associés à la fluorescence au Vert IIIC1 Ganglions pelviens l'évaluation du statut ganglionnaire (14,66-68). IIIC2 Ganglions para aortiques +/-ganglions pelviens
	Stade IV a d'Indocyanine : (i) le faible coût de la procédure qui requiert une ampoule (45 euros) et une Extension aux organes locorégionaux ou métastase T4 et/ou M1 IVA Extension à la muqueuse vésicale et/ou intestinale T4
	inguinaux) caméra qui peut être utilisée dans de nombreuses autres disciplines chirurgicales, (ii) un IVB Métastases à distance (intra-abdominales, ganglions M1
	faible risque de survenue de réactions allergiques (estimé à moins de 1/10 000 cas), (iii) une
	visualisation des lymphatiques en cours d'intervention qui permet une incision précise, une
	dissection contrôlée et une courbe d'apprentissage plus courte de la technique, (iv) une
	diminution globale du coût par l'absence de lymphoscintigraphie (26,37,50,52,53).
	Enfin, face à l'apport du ganglion sentinelle dans l'évaluation du statut ganglionnaire,
	se pose la problématique d'une simplification de l'algorithme thérapeutique adjuvant dans le
	cancer de l'endomètre. Ceci impose un préalable notamment l'utilisation de l'examen en
	extemporané pour l'évaluation du ganglion sentinelle ce qui permet dans le même temps
	opératoire de réaliser une lymphade ́nectomie complémentaire. En cas, de stade présumé IA
	et de non identification des ganglions sentinelles en pelvien, le statut des emboles garde sa
	valeur pour opter pour un traitement adjuvant. Pour le groupe présumé à risque
	intermédiaire, en cas de non identification des ganglions sentinelles en pelvien, une
	lymphade ́nectomie est recommandée uni ou bilatérale en fonction de la détection uni ou
	bilatérale. Pour ce groupe, la valeur des emboles est limitée puisque le statut ganglionnaire
	est connu. Reste le problème des ganglions sentinelles négatifs en per-opératoire retrouvés
	positifs en histologie définitive qui reste une situation rare (6,56). Dans ce contexte, le statut

des emboles et les comorbidités des patientes doivent conduire à une décision au cas par cas en comité multidisciplinaire. Compte tenu des avantages du ganglion sentinelle systématiquement utilisé, ceci nous conduit à proposer une révision de l'algorithme du Conclusion Au vu des dernières avancées, il paraît licite de recommander l'utilisation exclusive du Vert d'Indocyanine du fait d'une diminution des effets secondaires et de la morbidité en augmentant la détection des ganglions sentinelles. La procédure du ganglion sentinelle élargie à l'ensemble des cancers de l'endomètre de stade précoce devrait aboutir à une réduction majeure du recours à une stadification secondaire. a Grade 1,2 ou 3. b

Définition de groupes de risque basée sur la pathologie définitive (6)

	Risque bas	-Endométrioïde stade IA grade 1 -Endométrioïde stade IA grade 2 Absence d'emboles
	Risque intermédiaire	-Endométrioïde stade IB grade 1 -Endométrioïde stade IB grade 2 Absence d'emboles
		-Endométrioïde stade IA grade 3 +/-emboles
	Risque intermédiaire haut	-Endométrioïde stade IA grade 1 -Endométrioïde stade IA grade 2
		-Endométrioïde stade IB grade 1
		-Endométrioïde stade IB grade 2 + emboles
	Risque élevé	-Endométrioïde stade IB grade 3 +/-emboles
		-Stade II ou plus
		-Type 2

Tableau 4 : Nouveaux groupes à risque selon l'ESMO-ESGO-ESTRO (7)

	Tableau 5 :
	Risque bas	-Endométrioïde stade IA grade 1 -Endométrioïde stade IA grade 2 Absence d'emboles
	Risque intermédiaire	-Endométrioïde stade IB grade 1 -Endométrioïde stade IB grade 2 Absence d'emboles
		-Endométrioïde stade IA grade 3 +/-emboles
	Risque intermédiaire haut	-Endométrioïde stade IA grade 1
		-Endométrioïde stade IA grade 2
		-Endométrioïde stade IB grade 1
		-Endométrioïde stade IB grade 2 + emboles
		-Endométrioïde stade IB grade 3 +/-emboles
	Risque élevé	-Stade II
		-Stade III, endométrioïde, sans
		maladie résiduelle
		-Type 2
	Avancé	-Stade III, avec maladie résiduelle
		-Stade IVA
	Métastatique	-Stade IVB

Synthèse des recommandations Françaises, Européennes et USA en fonction du bilan préopératoire

  [START_REF] Querleu | Prise en charge primaire des cancers de l'endomètre : recommandations SFOG-CNGOF[END_REF][START_REF] Colombo | ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: Diagnosis, Treatment and Follow-up[END_REF][START_REF] Koh | Uterine Neoplasms, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology[END_REF]

		SFOG/CNGOF	ESMO (Europe) (7)	NCCN (USA) (8)
		(France) (6)
	Risque faible	GS pelvien possible	Pas d'exploration	GS pelvien
			ganglionnaire
	Risque intermédiaire	GS pelvien	pelvienne et lombo-Lymphade ́nectomie	GS pelvien
			aortique
	Risque élevé	Lymphadénectomie	Lymphade ́nectomie	GS pelvien
		pelvienne et lombo-	pelvienne et lombo-	Lymphade ́nectomie
		aortique	aortique	pelvienne et lombo-
				aortique