Résultat d'une prise en charge monocentrique et pluridisciplinaire des cancers colorectaux avec métastases hépatiques synchrones non résécables (analyse en intention de traiter)

PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF

One-Anastomosis Gastric Bypass and Hiatal Hernia: Nissen Fundoplication with the Excluded Stomach to Decrease the Risk of Postoperative Gastroesophageal Reflux

Introduction: The realization of an antireflux valve according to the Nissen technique during the operation of one-anastomosis gastric bypass (OAGB) may theoretically decrease the incidence of postoperative reflux in patients with hiatal hernia (HH). Material and Methods: In this retrospective study, we included all patients operated on between January 2015 and January 2019 for an OAGB associated with the creation of an antireflux Nissen valve (360-degree wrap). The patients included had type II or type III HH that had been diagnosed preoperatively or discovered intraoperatively. Results: Twenty-two patients were operated on during the period considered. The mean preoperative BMI was 40 ± 14 kg/m2. Five patients (22.7%) had a history of bariatric surgery. Typical symptoms of gastroesophageal reflux disease (GERD) were preoperatively present in four patients (18%), and HH was revealed preoperatively only in four patients; for all the other patients, the diagnosis of HH was made intraoperatively. The rate of early and/or late postoperative complications was 0%. The mean duration of follow-up was 23 ± 15 months. No dysphagia was reported during follow-up. Three patients presented with symptomatic GERD postoperatively, including one de novo. Mean BMI at the end of follow-up was 24 ± 3 kg/m2, and the % of total weight loss was 108 ± 30%. Conclusions: OAGB with a Nissen antireflux valve seems to be a safe and effective surgical technique and it could be an extra arrow in the surgeon’s quiver in the presence of HH in a patient scheduled for OAGB

Loss of Human Beta Cell Identity in a Reconstructed Omental Stromal Cell Environment

In human type 2 diabetes, adipose tissue plays an important role in disturbing glucose homeostasis by secreting factors that affect the function of cells and tissues throughout the body, including insulin-producing pancreatic beta cells. We aimed here at studying the paracrine effect of stromal cells isolated from subcutaneous and omental adipose tissue on human beta cells. We developed an in vitro model wherein the functional human beta cell line EndoC-βH1 was treated with conditioned media from human adipose tissues. By using RNA-sequencing and western blotting, we determined that a conditioned medium derived from omental stromal cells stimulates several pathways, such as STAT, SMAD and RELA, in EndoC-βH1 cells. We also observed that upon treatment, the expression of beta cell markers decreased while dedifferentiation markers increased. Loss-of-function experiments that efficiently blocked specific signaling pathways did not reverse dedifferentiation, suggesting the implication of more than one pathway in this regulatory process. Taken together, we demonstrate that soluble factors derived from stromal cells isolated from human omental adipose tissue signal human beta cells and modulate their identity

Loss of G protein pathway suppressor 2 in human adipocytes triggers lipid remodeling by upregulating ATP binding cassette subfamily G member 1

International audienceObjective: Adipogenesis is critical for adipose tissue remodeling during the development of obesity. While the role of transcription factors in the orchestration of adipogenic pathways is already established, the involvement of coregulators that transduce regulatory signals into epigenome alterations and transcriptional responses remains poorly understood. The aim of our study was to investigate which pathways are controlled by G protein pathway suppressor 2 (GPS2) during the differentiation of human adipocytes.Methods: We generated a unique loss-of-function model by RNAi depletion of GPS2 in human multipotent adipose-derived stem (hMADS) cells. We thoroughly characterized the coregulator depletion-dependent pathway alterations during adipocyte differentiation at the level of transcriptome (RNA-seq), epigenome (ChIP-seq H3K27ac), cistrome (ChIP-seq GPS2), and lipidome. We validated the in vivo relevance of the identified pathways in non-diabetic and diabetic obese patients.Results: The loss of GPS2 triggers the reprogramming of cellular processes related to adipocyte differentiation by increasing the responses to the adipogenic cocktail. In particular, GPS2 depletion increases the expression of BMP4, an important trigger for the commitment of fibroblast-like progenitors toward the adipogenic lineage and increases the expression of inflammatory and metabolic genes. GPS2-depleted human adipocytes are characterized by hypertrophy, triglyceride and phospholipid accumulation, and sphingomyelin depletion. These changes are likely a consequence of the increased expression of ATP-binding cassette subfamily G member 1 (ABCG1) that mediates sphingomyelin efflux from adipocytes and modulates lipoprotein lipase (LPL) activity. We identify ABCG1 as a direct transcriptional target, as GPS2 depletion leads to coordinated changes of transcription and H3K27 acetylation at promoters and enhancers that are occupied by GPS2 in wild-type adipocytes. We find that in omental adipose tissue of obese humans, GPS2 levels correlate with ABCG1 levels, type 2 diabetic status, and lipid metabolic status, supporting the in vivo relevance of the hMADS cell-derived in vitro data.Conclusion: Our study reveals a dual regulatory role of GPS2 in epigenetically modulating the chromatin landscape and gene expression during human adipocyte differentiation and identifies a hitherto unknown GPS2-ABCG1 pathway potentially linked to adipocyte hypertrophy in humans

Rab4b Deficiency in T Cells Promotes Adipose Treg/Th17 Imbalance, Adipose Tissue Dysfunction, and Insulin Resistance

International audienceObesity modifies T cell populations in adipose tissue, thereby contributing to adipose tissue inflammation and insulin resistance. Here, we show that Rab4b, a small GTPase governing endocytic trafficking, is pivotal in T cells for the development of these pathological events. Rab4b expression is decreased in adipose T cells from mice and patients with obesity. The specific depletion of Rab4b in T cells causes adipocyte hypertrophy and insulin resistance in chow-fed mice and worsens insulin resistance in obese mice. This phenotype is driven by an increase in adipose Th17 and a decrease in adipose Treg due to a cell-autonomous skew of differentiation toward Th17. The Th17/Treg imbalance initiates adipose tissue inflammation and reduces adipogenesis, leading to lipid deposition in liver and muscles. Therefore, we propose that the obesity-induced loss of Rab4b in adipose T cells may contribute to maladaptive white adipose tissue remodeling and insulin resistance by altering adipose T cell fate

Endoscopic Management of Bariatric Surgery Complications According to a Standardized Algorithm

International audienceBackground and Aims Endoscopy is effective in management of bariatric surgery (BS) adverse events (AEs) but a comprehensive evaluation of long-term results is lacking. Our aim is to assess the effectiveness of a standardized algorithm for the treatment of BS-AE. Patients and Methods We retrospectively analyzed 1020 consecutive patients treated in our center from 2012 to 2020, collecting data on demographics, type of BS, complications, and endoscopic treatment. Clinical success (CS) was evaluated considering referral delay, healing time, surgery, and complications type. Logistic regression was performed to identify variables of CS. Results In the study period, we treated 339 fistulae (33.2%), 324 leaks (31.8%), 198 post-sleeve gastrectomy twist/stenosis (19.4%), 95 post-RYGB stenosis (9.3 %), 37 collections (3.6%), 15 LAGB migrations (1.5%), 7 weight regains (0.7%), and 2 hemorrhages (0.2%). Main endoscopic treatments were as follows: pigtail-stent positioning under endoscopic view for both leaks (CS 86.1%) and fistulas (CS 77.2%), or tinder EUS-guidance for collections (CS 88.2%); dilations and/or stent positioning for sleeve twist/stenosis (CS 80.6%) and bypass stenosis (CS 81.5%). After a median (IQR) follow-up of 18.5 months (4.29-38.68), complications rate was 1.9%. We found a 1% increased risk of redo-surgery every 10 days of delay to the first endoscopic treatment. Endoscopically treated patients had a more frequent regular diet compared to re-operated patients. Conclusions Endoscopic treatment of BS-AEs following a standardized algorithm is safe and effective. Early endoscopic treatment is associated with an increased CS rate

Endoscopic internal drainage for the management of leak, fistula, and collection after sleeve gastrectomy: our experience in 617 consecutive patients

International audienceBackground: Endoscopy plays a pivotal role in the management of adverse events (AE) following bariatric surgery. Leaks, fistulae, and post-operative collection after sleeve gastrectomy (SG) may occur in up to 10% of cases. Objectives: To evaluate the efficacy and safety of endoscopic internal drainage (EID) for the management of leak, fistula, and collection following SG. Setting: Retrospective, observational, single center study on patients referred from several bariatric surgery departments to an endoscopic referral center. Methods: EID was used as first-line treatment for the management of leaks, fistulae, and collections. Leaks and fistulae were treated with double pigtail stent (DPS) deployment in order to guarantee internal drainage and second intention cavity obliteration. Collections were treated with endoscropic ultrasound (EUS)-guided deployment of DPS or lumen apposing metal stents. Results: A total of 617 patients (83.3% female; mean age, 43.1 yr) were enrolled in the study for leak (n = 300, 48.6%), fistula (n = 285, 46.2%), and collection (n = 32, 5.2%). Median follow-up was 19.5 months. Overall clinical success was 84.7% whereas 15.3% of cases required revisional surgery after EID failure. Clinical success according to type of AE was 89.5%, 78.5%, and 90% for leak, fistula, and collection, respectively. A total of 10 of 547 (1.8%) presented a recurrence during follow-up. A total of 28 (4.5%) AE related to the endoscopic treatment occurred. At univariate logistic regression predictors of failure were: fistula (OR 2.012), combined endoscopic approach (OR 2.319), need for emergency surgery (OR 1.755), and previous endoscopic treatment (OR 4.818). Conclusion: Early EID for the management of leak, fistula, and post-operative collection after SG seems a safe and effective first-line approach with good long-term results. (C) 2021 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved