A Prospective Study of the Conservative Management of Asymptomatic Preoperative and Postoperative Gallbladder Disease in Bariatric Surgery

Pineda, Omar; Maydón, Hernán; Amado, Mónica; Sepúlveda, Elisa; Guilbert, Laure; Espinosa, Omar; Zerrweck, Carlos

doi:10.1007/s11695-016-2264-3

Cited by 45 publications

(24 citation statements)

References 34 publications

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“…Plasma levels of GLP-2 and BA are increased in obese subjects following bariatric surgery, a population at significantly increased risk for gallstones and acute GB disease [35], [36]. Although the association of bariatric surgery and biliary disease has been generally ascribed to weight loss, it is notable that elevated levels of BA may promote i) FXR-dependent secretion of FGF15/19 and ii) Tgr5 activation, leading to indirect and direct mechanisms that attenuate GB emptying.…”

Section: Discussionmentioning

confidence: 99%

Glucagon-like peptide-2 promotes gallbladder refilling via a TGR5-independent, GLP-2R-dependent pathway

Yusta

Matthews

Flock

et al. 2017

Molecular Metabolism

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ObjectiveGlucagon-like peptides (GLPs) are secreted from enteroendocrine cells in response to nutrients and bile acids and control metabolism via actions on structurally-related yet distinct G protein coupled receptors. GLP-1 regulates gut motility, appetite, islet function, and glucose homeostasis, whereas GLP-2 enhances intestinal nutrient absorption. GLP-1R agonists are used to treat diabetes and obesity, and a GLP-2R agonist is approved to treat short bowel syndrome. Unexpectedly, reports of gallbladder disease have been associated with the use of both GLP-1R and GLP-2R agonists and after bariatric surgery, although the mechanisms remain unknown.MethodsWe investigated whether GLP-1 or GLP-2 acutely controls gallbladder (GB) volume and whether GLP-2 regulates GB muscle activity in mice. The expression of Tgr5, Glp2r, and Glp1r was assessed in mouse GB, and the effects of GLP-2 on hepatic bile acid (BA) flow, intestinal and liver BA uptake, and GB gene expression were determined. GLP-2 regulation of GB volume was assessed in wildtype, Glp2r−/− and Tgr5−/− mice. The effect of GLP-2 on GB smooth muscle (GBSM) calcium transients was characterized ex vivo.ResultsAcute administration of the GLP-1R agonist exendin-4 lowered glucose but had no effect on GB volume in mice. In contrast, GLP-2 rapidly enhanced GB filling in a dose-dependent manner, actions maintained in the presence of cholecystokinin, and mediated through the canonical GLP-2R. GLP-2 also rapidly induced immediate early gene expression in GB, consistent with detection of the endogenous Glp2r in GB RNA. The ability of GLP-2 to increase GB volume was not abrogated by systemic administration of hexamethonium, propranolol, a vasoactive peptide receptor antagonist or N-Nitroarginine methyl ester, and was maintained in Tgr5−/− mice. In contrast, lithocholic acid, a Tgr5 agonist, increased GB filling in Glp2r−/− but not in Tgr5−/− mice. GLP-2 had no effect on ileal uptake or hepatic clearance of taurocholic acid or on hepatic bile flow, yet reduced the frequency of spontaneous calcium transients in murine GBSM ex vivo, in a tetrodotoxin-sensitive manner.ConclusionsOur data extend endocrine concepts of regulation of GB filling beyond FXR-FGF15/19 and the direct effects of BA via Tgr5, to encompass a novel BA-Tgr5-L cell GLP-2 axis providing nutrient-mediated feedback from BA to terminate meal-related GB contraction. These findings have implications for conditions characterized by elevated circulating levels of GLP-2 such as after bariatric surgery and the development and use of agents that promote Tgr5 activation, L cell secretion, or GLP-2R agonism for the treatment of metabolic disease.

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Section: Discussionmentioning

confidence: 99%

Glucagon-like peptide-2 promotes gallbladder refilling via a TGR5-independent, GLP-2R-dependent pathway

Yusta

Matthews

Flock

et al. 2017

Molecular Metabolism

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“…21 Although controversial due to a reported incidence of postoperative cholelithiasis in up to 38% of patients, we currently follow a conservative approach to asymptomatic gallstone disease. [22][23][24] In patients with symptomatic gallstones a staged approach is followed due to the increased risk of perioperative complications associated with concomitant cholecystectomy. 25 Should patients develop postoperative choledocholithiasis, laparoscopic assisted endoscopic retrograde cholangiography (ERCP) is considered.…”

Section: Discussionmentioning

confidence: 99%

Metabolic surgery in South Africa: an initial academic hospital experience

et al. 2019

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Background: In South Africa, 42.0% of adult females and 13.5% of adult males are classified as obese, the highest recorded numbers in Sub-Saharan Africa. Metabolic surgery has been proven to be a safe and effective treatment, yet due to demand on government resources has only been performed to a limited extent in public hospitals. The aim of this study was to describe the safety and efficacy of performing metabolic surgery at a single academic hospital in South Africa. Methods: This was a single centre retrospective review of 57 metabolic surgery procedures performed from October 2011 to September 2017 at Tygerberg Hospital, Cape Town, South Africa. The primary outcome was safety including mortality and adverse events. Secondary outcomes included effect of surgery on weight and diabetes resolution. Results: A total of 57 patients underwent laparoscopic metabolic surgery, of which 44 (83.0%) were female with a mean age (standard deviation) of 42.8 (8.0) years. Fifty-six patients (98%) underwent Roux-and-Y gastric bypass and one (2%) had a sleeve gastrectomy performed. There were no mortalities and overall morbidity was 14.0%, with 3 (5.3%) classified as major and 5 (8.8%) as minor. The follow-up rate at 1 year was 100%. Mean preoperative body mass index (BMI) was 58.8 kg/m2, and comorbidities included hypertension (59.6%), Type 2 Diabetes (42.1%), and dyslipidaemia (36.8%). There were no conversions to open surgery and at one year the mean (95% confidence interval) percentage excess body mass index loss was 50.4% (44.0-56.8%). Conclusions: Metabolic surgery can be performed safely in the public sector in South Africa, with short-term safety and efficacy outcomes comparable to international reports. Larger scale studies are needed to determine long-term outcomes and cost-effectiveness.

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“…RYGB made up 17.8% of bariatric procedures in 2017 and BPD-DS only 0.7%. Because a low percentage of patients require cholecystectomy after 12 [51] or 24 [21] months and preexisting asymptomatic gallstones do not necessarily progress to symptomatic gallstones after bariatric surgery [52], conservative management in asymptomatic patients is safer than performing a concomitant prophylactic cholecystectomy in LRYGB [53].…”

Section: Asymptomatic Patients Undergoing Lrygbmentioning

confidence: 99%

Systematic review of management of gallbladder disease in patients undergoing minimally invasive bariatric surgery

Leyva‐Alvizo

Arredondo-Saldaña

Leal-Isla-Flores

et al. 2020

Surgery for Obesity and Related Diseases

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A Prospective Study of the Conservative Management of Asymptomatic Preoperative and Postoperative Gallbladder Disease in Bariatric Surgery

Cited by 45 publications

References 34 publications

Glucagon-like peptide-2 promotes gallbladder refilling via a TGR5-independent, GLP-2R-dependent pathway

Glucagon-like peptide-2 promotes gallbladder refilling via a TGR5-independent, GLP-2R-dependent pathway

Metabolic surgery in South Africa: an initial academic hospital experience

Systematic review of management of gallbladder disease in patients undergoing minimally invasive bariatric surgery

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