Lara Ribeiro-Parenti

Enhanced Ghrelin Levels and Hypothalamic Orexigenic AgRP and NPY Neuropeptide Expression in Models of Jejuno-Colonic Short Bowel Syndrome

Short bowel syndrome (SBS) patients developing hyperphagia have a better outcome. Gastrointestinal endocrine adaptations help to improve intestinal functions and food behaviour. We investigated neuroendocrine adaptations in SBS patients and rat models with jejuno-ileal (IR-JI) or jejuno-colonic (IR-JC) anastomosis with and without parenteral nutrition. Circulating levels of ghrelin, PYY, GLP-1, and GLP-2 were determined in SBS rat models and patients. Levels of mRNA for proglucagon, PYY and for hypothalamic neuropeptides were quantified by qRT-PCR in SBS rat models. Histology and immunostaining for Ki67, GLP-1 and PYY were performed in SBS rats. IR-JC rats, but not IR-JI, exhibited significantly higher crypt depths and number of Ki67-positive cells than sham. Fasting and/or postprandial plasma ghrelin and PYY concentrations were higher, or tend to be higher, in IR-JC rats and SBS-JC patients than in controls. Proglucagon and Pyy mRNA levels were significantly enhanced in IR-JC rats. Levels of mRNA coding hypothalamic orexigenic NPY and AgRP peptides were significantly higher in IR-JC than in sham rats. We demonstrate an increase of plasma ghrelin concentrations, major changes in hypothalamic neuropeptides levels and greater induction of PYY in SBS-JC rats and patients suggesting that jejuno-colonic continuity creates a peculiar environment promoting further gut-brain adaptations.

Gastrojejunostomy stricture rate: comparison between antecolic and retrocolic laparoscopic Roux-en-Y gastric bypass

BACKGROUND Roux-en-Y gastric bypass procedure is an effective treatment for morbid obesity. One of the most frequent complications after this operation is the appearance of a gastrojejunal anastomotic stricture. Mechanisms underlying the development of such complication are unclear. OBJECTIVE The aim of the present retrospective study was to compare the rates of gastrojejunostomy stricture between the antecolic and retrocolic technique in a large cohort of patients undergoing Roux-en-Y gastric bypass for morbid obesity, with the same gastrojejunal anastomotic technique. SETTING University Hospital, France. METHODS From November 2000 to March 2012, 1500 patients underwent laparoscopic Roux-en-Y gastric bypass. The antecolic and the retrocolic technique were used in respectively 572 and 928 consecutive patients. All procedures were performed using a circular stapled gastrojejunostomy and absorbable sutures. RESULTS There was no significant difference with respect to gender, age, body mass index, and obesity related co-morbidities between both groups. Patients were followed for 24-146 months (mean 67.5 mo). Fifty-one patients developed a gastrojejunal stricture (3.4%), 37 in the antecolic group (6.5%) and 14 in the retrocolic group (1.5%). The difference was significant (P< .0001). The mean time to onset of gastrojejunal stricture symptoms after surgery was 1 month, ranging from 1 to 3 months. All patients were successfully treated using Savary-Gilliard dilatators. All patients with a gastrojejunal stricture were followed up for a minimum of 36 months. No recurrence was observed and no revisional surgery was needed. Weight loss was similar in patients who developed an anastomotic stricture compared with those without stricture. In the antecolic group internal hernia occurred in 12 of the 110 with no closure of mesenteric defects and in 8 of the 462 (1.7%) with defects closed. In the retrocolic group, 11 patients (1.2%) developed an internal hernia. CONCLUSIONS A significant lower gastrojejunal stricture rate was observed in the retrocolic group, with no increased risk of internal hernia, when mesenteric defects were closed. The antecolic technique seems to be a risk factor for gastrojejunal stricture development after laparoscopic gastric bypass.

Classification, surgical management and outcomes of patients with gastrogastric fistula after Roux-En-Y gastric bypass

BACKGROUND Gastrogastric fistula (GGF) is a known complication after Roux-en-Y gastric bypass that can lead to marginal ulceration (MU) and failure of weight loss. OBJECTIVES To describe our experience with GGF management and propose a classification of GGF based on its anatomic location. SETTING University hospital, France. METHODS After internal review board approval, data from all patients with a GGF were reviewed. GGF was classified as type 1 when located in the proximal part of the gastric pouch and type 2 when located near the gastrojejunostomy. RESULTS Nine patients developed a GGF (.5%). GGF symptoms included epigastric pain (78%), vomiting (11%), gastrointestinal bleeding (11%), and weight regain (44%). Upper contrast study identified GGF in all patients. Upper endoscopy confirmed GGF in 6 patients, all with type 2. Eight patients required revisional surgery. Patients with type 1 GGF (n = 3) had excision of the fistulous tract. Patients with type 2 GGF (n = 5) had associated revision of the gastrojejunostomy. Mean operative time was significantly longer for type 2 GGF. The mean follow-up was 43 months, with no patient lost. One patient developed a recurrent MU requiring iterative revision. After that, all revisional patients were symptom free and the mean body mass index was 35.3±9.5 kg/m². CONCLUSION Weight regain and epigastric pain with or without associated MU are the most common signs of GGF. Combining upper gastrointestinal endoscopy and contrast study is the best method to confirm the diagnosis. Surgical treatment should be tailored to both GGF location and status of the gastrojejunostomy. Based on its anatomic location, GGF classification could serve as a working basis to compare different surgical approaches.

Roux-en-Y Gastric-Bypass and sleeve gastrectomy induces specific shifts of the gut microbiota without altering the metabolism of bile acids in the intestinal lumen

Some shifts in the gut microbiota composition and its metabolic fingerprints have been associated to Sleeve gastrectomy (SG) and Roux-en-Y Gastric Bypass (RYGB). So far, plasma bile acids have been associated with post-operative glucose improvement and weight loss, but nothing is known about their metabolism in the gut lumen. As bile acids are physiologically transformed by the microbiota into various species, the aim of this work was to study how SG and RYGB-associated dysbiosis impact the bioconversion of bile acids in the intestinal lumen. Comparing SHAM (n = 9) with our validated rat models of SG (n = 5) and RYGB (n = 6), we quantified luminal bile acids along the gut and found that the metabolic transformation of bile acids (deconjugation, dehydroxylation, and epimerization) is not different from the duodenum to the colon. However, in the cecum where the biotransformation mainly takes place, we observed deep alterations of the microbiota composition, which were specific of each type of surgery. In conclusion, despite specific dysbiosis after surgery, the bile acids metabolism in the gut lumen is highly preserved, suggesting that a resilience of the gut microbiota occurs after these procedures.

A Simple Trick to Prevent VOMIT After Sleeve Gastrectomy

Victim of medical imaging technologies (VOMIT) is a term coined by a pediatric neurosurgeon to describe anxiety-inducing false-positive results on radiologic imaging [1]. Morbidly obese patients have a low functional physiological reserve that constrains to a fast diagnostic work-up, and an aggressive and early treatment of potential complications [2]. Upper gastrointestinal contrast study (UGI) is a useful modality to detect functional and surgical complications after sleeve gastrectomy (SG) [3]. However, in some cases, the residual gastric tube is floppy, and the findings are hard to interpret. In this paper, we present a simple trick which aims to prevent SG patients from suffering physically as well as mentally and from undergoing unnecessary further diagnostic interventions due to a false-positive UGI finding. Discussion

Inhibition of monoacylglycerol lipase, an anti-inflammatory and antifibrogenic strategy in the liver

Objective Sustained inflammation originating from macrophages is a driving force of fibrosis progression and resolution. Monoacylglycerol lipase (MAGL) is the rate-limiting enzyme in the degradation of monoacylglycerols. It is a proinflammatory enzyme that metabolises 2-arachidonoylglycerol, an endocannabinoid receptor ligand, into arachidonic acid. Here, we investigated the impact of MAGL on inflammation and fibrosis during chronic liver injury. Design C57BL/6J mice and mice with global invalidation of MAGL (MAGL -/- ), or myeloid-specific deletion of either MAGL (MAGLMye-/-), ATG5 (ATGMye-/-) or CB2 (CB2Mye-/-), were used. Fibrosis was induced by repeated carbon tetrachloride (CCl4) injections or bile duct ligation (BDL). Studies were performed on peritoneal or bone marrow-derived macrophages and Kupffer cells. Results MAGL -/- or MAGLMye-/- mice exposed to CCl4 or subjected to BDL were more resistant to inflammation and fibrosis than wild-type counterparts. Therapeutic intervention with MJN110, an MAGL inhibitor, reduced hepatic macrophage number and inflammatory gene expression and slowed down fibrosis progression. MAGL inhibitors also accelerated fibrosis regression and increased Ly-6Clow macrophage number. Antifibrogenic effects exclusively relied on MAGL inhibition in macrophages, since MJN110 treatment of MAGLMye-/- BDL mice did not further decrease liver fibrosis. Cultured macrophages exposed to MJN110 or from MAGLMye-/- mice displayed reduced cytokine secretion. These effects were independent of the cannabinoid receptor 2, as they were preserved in CB2Mye-/- mice. They relied on macrophage autophagy, since anti-inflammatory and antifibrogenic effects of MJN110 were lost in ATG5Mye-/- BDL mice, and were associated with increased autophagic flux and autophagosome biosynthesis in macrophages when MAGL was pharmacologically or genetically inhibited. Conclusion MAGL is an immunometabolic target in the liver. MAGL inhibitors may show promising antifibrogenic effects during chronic liver injury.