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BACKGROUND Pelvic collections may occur after surgery or in medical diseases. EUS transmural (TM) treatment has been shown as highly effective and safe, becoming an alternative to surgery or radiology. We aimed to assess the results of EUS management of pelvic collections. METHODS Retrospective, single-center observational study conducted between 2004 and 2018. Patients with symptomatic collections treated by EUS-TM approach were enrolled. The procedures were performed with a therapeutic EUS-scope, following two possible options: puncture-aspiration-injection of antibiotics PAIA (group 1) or EUS-drainage by plastic double pigtail stents (DPS) with an ano-cavitary drain (ACD) or lumen-apposing metal Stent (LAMS) (group 2). The main objective was to assess the clinical effectiveness based on symptoms and collection resolution. RESULTS Seventy-three patients were included. Mean age was 42.5 years [12-87]. 30 patients in group 1 (41%) underwent PAIA and 43 in group 2 (59%) underwent DPS ± ACD in 41 patients (95%) and LAMS in 2. The collection was postoperative in 58%. The mean size was 48.9 mm [8-120], 33 +/- 17 mm in group 1, compared to 67 ± 21 mm in group 2 (p

Molecular classification in pathological anatomy is an important task as it is extremely convenient for the diagnosis of cancer and its subtypes for adequate therapeutic choice. With the development of computer vision, cancer classification has become an interdisciplinary subject in both medicine and computer vision.A multi-input convolutional neural network is designed for the molecular classification of cancer based on a collected dataset, which contains four tissues treated with four antibodies; each one of them is composed of 33 images. The proposed model achieves a satisfactory accuracy of 90.43% after data augmentation. Even though the data augmentation contributes to the model, the accuracy is still limited by the lack of sample diversity.

Background Identifying patients with metastatic colorectal cancer who will have an early disease progression during induction chemotherapy (IC) and identifying patients who may have a chemotherapy-free interval (CFI) after IC are two major challenges. Methods A logistic model was used to identify factors associated with early progression during IC and with short duration of the first CFI in 488 patients enrolled in the PRODIGE 9 trial. Independent factors were defined with a threshold 0.10. Results In multivariate analysis, baseline leukocytes >10 × 109/L (OR = 1.98 [1.02–3.8], p = 0.04), and stable or increasing CEA at 2 months (OR = 3.61 [1.68–7.75], p = 0.01) were independent factors associated with progression during IC. Male gender (OR = 1.725 [0.92–3.325], p = 0.09) and no tumour response at first evaluation (OR = 1.90 [0.96–3.76], p = 0.07) were significantly associated with a short CFI. The presence of BRAF V600E mutation was also associated with short CFI (OR = 4.59 [0.95; 22.3], p = 0.058). Conclusion High baseline leukocyte count and the lack of CEA decrease level at first evaluation were associated with early progression, and could be in favour of early chemotherapy intensification. Male gender, no tumour response at first evaluation and BRAF mutation are associated with a short CFI, and may be considered for maintenance chemotherapy after IC. Clinical trial number NCT00952029.

ObjectiveDiagnostic tests, such as Immunoscore, predict prognosis in patients with colon cancer. However, additional prognostic markers could be detected on pathological slides using artificial intelligence tools.DesignWe have developed a software to detect colon tumour, healthy mucosa, stroma and immune cells on CD3 and CD8 stained slides. The lymphocyte density and surface area were quantified automatically in the tumour core (TC) and invasive margin (IM). Using a LASSO algorithm, DGMate (DiGital tuMor pArameTErs), we detected digital parameters within the tumour cells related to patient outcomes.ResultsWithin the dataset of 1018 patients, we observed that a poorer relapse-free survival (RFS) was associated with high IM stromal area (HR 5.65; 95% CI 2.34 to 13.67; pConclusionThese findings suggest that artificial intelligence can potentially improve patient care by assisting pathologists in better defining stage III colon cancer patients’ prognosis.

Recent studies have offered ample insight into genome-wide expression patterns to define pancreatic ductal adenocarcinoma (PDAC) subtypes, although there remains a lack of knowledge regarding the underlying epigenomics of PDAC. Here we perform multi-parametric integrative analyses of chromatin immunoprecipitation-sequencing (ChIP-seq) on multiple histone modifications, RNA-sequencing (RNA-seq), and DNA methylation to define epigenomic landscapes for PDAC subtypes, which can predict their relative aggressiveness and survival. Moreover, we describe the state of promoters, enhancers, super-enhancers, euchromatic, and heterochromatic regions for each subtype. Further analyses indicate that the distinct epigenomic landscapes are regulated by different membrane-to-nucleus pathways. Inactivation of a basal-specific super-enhancer associated pathway reveals the existence of plasticity between subtypes. Thus, our study provides new insight into the epigenetic landscapes associated with the heterogeneity of PDAC, thereby increasing our mechanistic understanding of this disease, as well as offering potential new markers and therapeutic targets., Pancreatic ductal adenocarcinoma (PDAC) is a complex disease and its underlying epigenomic heterogeneity is not fully understood. Here, the authors utilize patient-derived PDAC xenografts to define the epigenomic landscape of PDAC, highlighting chromatin states linked to differing disease aggressiveness and survival.

The Nefza-Bizerte region, eastern part of the Tunisian Alpine chain, covers the thrust sheets domain called the Tell and its Atlassic foreland. The deep structures under the Tellian thrust sheets are not enough explored. The structural interpretation of magmatic rocks, Triassic outcrops and the depressions are still a subject of discussion. In this work, we intend to investigate deep faults and their eventual role in magmatism and Triassic salt setting up and to explain the depression genesis. Analysis of the Bouguer anomaly map and its derivatives reveals the main gravity lineaments, organized in major NE- and NW-trending systems. The NE-trending system, dipping towards the NW, is the main component of the structural scheme and has controlled the tectonic evolution of this area. After the immobilization of the Tellian thrust sheets during the uppermost Langhian, the Tell and its Atlassic foreland were affected by the Tortonian compressive event with a NW-trending maximum horizontal stress. The reverse kinematics of the NE-trending deep-seated faults created at their front continental environments filled later by post-nappes Neogene deposits. After the early Pleistocene, a NNW-directed compressional stress regime deformed the post-nappes Neogene series and generated NW-trending grabens. This coexistence of compression-extension continues until present day.

International audience; Despite rectal cancer being unusual before 40, fertility preservation (FP) remains a major concern for these reproductive-age women. Treatment usually involves pelvic radiotherapy, neoadjuvant chemotherapy, and surgery of rectum and mesorectum resection, at high risk of impairing fertility in women with risks of premature ovarian failure and radio-induced uterus damage. To date, there is no consensus on FP strategy for rectal cancer. We shared experiences between oncofertility experts from a French research network Groupe de Recherche et d'Etude en Cryoconservation Ovarienne et Testiculaire about a case of rectal cancer in a young woman. Indications, advantages and disadvantages of different FP strategies were discussed: ovarian transposition, cryopreservation of ovarian cortex and oocyte vitrification. This case was the starting point that led to the development of a French multidisciplinary e-meeting for sharing experiences and for suggesting the best strategy when faced with a complex oncofertility case.

International audience; Background & aims: Pancreatic ductal adenocarcinoma (PDAC) is associated with the highest incidence of venous thromboembolism (VTE) of any cancer type. However, little is known about risk factors for VTE or its outcomes in patients with PDAC.Methods: We collected data from a prospective, observational study performed at multiple centers in France from May 2014 through November 2018 (the Base Clinico-Biologique de l'Adénocarcinome Pancréatique [BACAP] study) linked to a database of patients with a new diagnosis of PDAC of any stage. Data were collected from 731 patients at baseline and during clinical follow-up or in the event of symptoms. The primary endpoint was the onset of VTE during follow-up. The secondary endpoints were progression-free survival (PFS) and overall survival (OS) times.Results: During a median follow-up of 19.3 months, 152 patients (20.79%) developed a VTE. The median time from PDAC diagnosis to the onset of VTE was 4.49 months. Cumulative incidence values of VTE were 8.07% (95% confidence interval [CI], 6.31-10.29) at 3 months and 19.21% (95% CI, 16.27-22.62) at 12 months. In multivariate analysis, PDAC primary tumor location (isthmus vs head: hazard ratio [HR], 2.06; 95% CI, 1.09-3.91; P = .027) and stage (locally advanced vs resectable or borderline: HR, 1.66; 95% CI, 1.10-2.51, P = .016; metastatic vs resectable or borderline: HR, 2.50; 95% CI, 1.64-3.79; P < .001) were independent risk factors for the onset of VTE. Patients who developed VTE during follow-up had shorter times of PFS (HR, 1.74; 95% CI, 1.19-2.54; P = .004) and OS (HR, 2.02; 95% CI, 1.57-2.60; P < .001).Conclusion: In an analysis of data from the BACAP study, we found that frequent and early onsets of VTE after diagnoses of PDAC are associated with significant decreases in times of PFS and OS. Studies are needed to determine whether primary prophylaxis of VTE in patients with PDAC will improve morbidity and mortality related to VTE. (ClinicalTrials.gov, Number: clinicaltrials.gov as number NCT02818829).

The North Gabes-El Hamma region is located in the south of Tunisia at the northern limit of the Saharan platform. It has been the subject of several geological, mining and especially hydrogeological studies. These studies aim to evaluate the underground water potentialities of this region in order to exploit them in a rational way. It is within this framework that the present study is carried out, and it concerns the reinterpretation of 124 Vertical Electrical Soundings (VES) covering the study area. This study aims first to highlight aquifers and then to characterize them geometrically (thickness, depth and lateral extensions). To achieve this, the interpretation of the VES was carried out first in a qualitative way (establishment of apparent iso-resistivity maps and pseudosections) and then in a quantitative way (calibration of the VES on water boreholes, establishment of geoelectric sections and the roofs isobath and isopach maps of aquifer levels). From the hydrostratigraphic point of view, the results show that the North Gabes-El Hamma region is characterized by the presence of two aquifers. The first one is superficial, with limited potentialities and would be constituted by heterogeneous silico-clastic series of mio-plio-quaternary age (MPQ) characterized by geoelectric levels of quite variable resistivities. The second aquifer is deeper, with higher potentialities and would be constituted by Lower Senonian carbonate series (SIC) characterized by resistivities between 15 and 28 Ω m. From the structural point of view, the region is affected by intense fracturing in two main directions: NE-SW and NW-SE. The role of these faults, some of which are already known, is very important since they have subdivided the region into high zones (horsts) where the SIC would be eroded (with variable intensities) and low zones (grabens) where the SIC would be preserved under a thick MPQ cover. Moreover, these faults facilitate the lateral and especially vertical flow of groundwater and contribute to intercommunication between aquifers. In order to orient and rationalize the exploitation of the different aquifers of the North Gabes-El Hamma region, a synthetic map presenting their characteristics (geographical distribution and depths) has been established.

Treating pancreatic cancer is extremely challenging due to multiple factors, including chemoresistance and poor disease prognosis. Chemoresistance can be explained by: the presence of a dense stromal barrier leading to a lower vascularized condition, therefore limiting drug delivery; the huge intra-tumoral heterogeneity; and the status of epithelial-to-mesenchymal transition. These factors are highly variable between patients making it difficult to predict responses to chemotherapy. Nicotinamide phosphoribosyl transferase (NAMPT) is the main enzyme responsible for recycling cytosolic NAD+ in hypoxic conditions. FK866 is a noncompetitive specific inhibitor of NAMPT, which has proven anti-tumoral effects, although a clinical advantage has still not been demonstrated. Here, we tested the effect of FK866 on pancreatic cancer-derived primary cell cultures (PCCs), both alone and in combination with three different drugs typically used against this cancer: gemcitabine, 5-Fluorouracil (5FU) and oxaliplatin. The aims of this study were to evaluate the benefit of drug combinations, define groups of sensitivity, and identify a potential biomarker for predicting treatment sensitivity. We performed cell viability tests in the presence of either FK866 alone or in combination with the drugs above-mentioned. We confirmed both inter- and intra-tumoral heterogeneity. Interestingly, only the in vitro effect of gemcitabine was influenced by the addition of FK866. We also found that NAMPT mRNA expression levels can predict the sensitivity of cells to FK866. Overall, our results suggest that patients with tumors sensitive to FK866 can be identified using NAMPT mRNA levels as a biomarker and could therefore benefit from a co-treatment of gemcitabine plus FK866.

International audience; Anastomotic leakages are severe and often lethal adverse events of surgery for esophageal cancer. The endoscopic treatment is growing up in such indications. The aim was to evaluate the efficacy and describe the strategy of the endoscopic management of anastomotic leakages/fistulas after esophageal oncologic surgery. Single-center retrospective study on 126 patients operated for esophageal carcinomas between 2010 and 2014. Thirty-five patients with postoperative fistulas/leakages (27 %) were endoscopically managed and included. The primary endpoint was the efficacy of the endoscopic treatment. The secondary endpoints were: delays between surgery, diagnosis, endoscopy and recovery; number of procedures; material used; and adverse events rate. Uni- and multivariate analyses were carried out to determine predictive factors of success. There were mostly men, with a median age of 61.7 years +/- 8.9 [43-85]. 48.6 % underwent Lewis-Santy surgery and 45.7 % Akiyama's. 71.4 % patients received neo-adjuvant chemo-radiation therapy. The primary and secondary efficacy was 48.6 and 68.6 %, respectively. The delay between surgery and endoscopy was 8.5 days [6.00-18.25]. Eighty-eight percentages of the patients were treated using double-type metallic stents, with removability and migration rates of 100 and 18 %, respectively. In the other cases, we used over-the-scope clips, naso-cystic drain or combined approach. The mean number of endoscopy was 2.6 +/- 1.57 [1-10]. The mortality rate was 17 %, none being related to procedures. No predictive factor of efficacy could be identified. The endoscopic management of leakages or fistulas after esophageal surgery reached an efficacy rate of 68.8 %, mostly using stents, without significant adverse events. The mortality rate could be decreased from 40-100 to 17 %.

The Oued Gueniche plain is located in the northeastern Tunisia. It is a part of the Bizerte Neogene molassic basin, developed at the front of the Alpine chain (The Maghrebides). The subsurface structure of this area is not enough explored and was subject of controversial interpretations. Gravity and seismic data acquired in the northeast of Tunisia were used to specify the subsurface structural configuration and the formation mechanism of the Oued Gueniche plain, as well as, its relationship with the surrounding folds. A total number of 664 gravity measurements were used to define the density distributions below the surface in the study area. The complete Bouguer gravity anomaly was performed with a reduction density of 2.4 g/cm3. Bouguer anomalies range from 9.5 to 34.8 mGal, high anomalies coincide with the Oued Gueniche plain in the northwest while weak anomalies are located on the southern part of the study area. The main NE-SW anomalies are superposed to the geological structures. The power spectrum of gravity data shows that the calculated average depth to the top of regional gravity sources is approximately 4 km while that of local (or residual) sources is approximately 0.6 km. The techniques for locating the limits of anomalous structures and estimating their depths (tilt derivative (TDR), Euler deconvolution (ED) and analytical signal (AS)) were applied to the Bouguer anomaly map to further specify the underground geological characteristics. The maxima of the horizontal gradient magnitudes (MGH) of Bouguer anomalies, upward continuated at different altitudes, revealed several NE-SW and E-W trending lineaments. A three-dimensional (3D) inversion model of gravity data has been developed for the Oued Gueniche plain in order to follow the distribution of densities. In addition, the interpretation of seismic profiles indicates that the central part of this plain is marked by the diapirism of Triassic rocks. The combination of these results with those of the surface (geological map and shallow hydrogeological boreholes) has led us to propose a kinematic model of the Bizerte region since the Middle Miocene and to update the structural scheme. Then, the NE-SW major faults (e.g. the newly defined Sfaia-Metline fault) and the NW-SE secondary ones have controlled the paleogeography and the structuration of the study area.