ObjectivesRoux-en-Y gastric bypass (RYGB) has greater efficacy for weight loss in obese patients than gastric banding (BAND) surgery. We hypothesise that this may result from different effects on food hedonics via physiological changes secondary to distinct gut anatomy manipulations.DesignWe used functional MRI, eating behaviour and hormonal phenotyping to compare body mass index (BMI)-matched unoperated controls and patients after RYGB and BAND surgery for obesity.ResultsObese patients after RYGB had lower brain-hedonic responses to food than patients after BAND surgery. RYGB patients had lower activation than BAND patients in brain reward systems, particularly to high-calorie foods, including the orbitofrontal cortex, amygdala, caudate nucleus, nucleus accumbens and hippocampus. This was associated with lower palatability and appeal of high-calorie foods and healthier eating behaviour, including less fat intake, in RYGB compared with BAND patients and/or BMI-matched unoperated controls. These differences were not explicable by differences in hunger or psychological traits between the surgical groups, but anorexigenic plasma gut hormones (GLP-1 and PYY), plasma bile acids and symptoms of dumping syndrome were increased in RYGB patients.ConclusionsThe identification of these differences in food hedonic responses as a result of altered gut anatomy/physiology provides a novel explanation for the more favourable long-term weight loss seen after RYGB than after BAND surgery, highlighting the importance of the gut–brain axis in the control of reward-based eating behaviour.

BackgroundThe objective of the present study was to evaluate the cost-utility of bariatric surgery in a lifetime horizon from a Swedish health care payer perspective.MethodsA decision analytic model using the Markov process was developed covering cardiovascular diseases, type 2 diabetes, and surgical complications. Clinical effectiveness and safety were based on the literature and data from the Scandinavian Obesity Surgery Registry. Gastric bypass, sleeve gastrectomy, and gastric banding were included in the analysis. Cost data were obtained from Swedish sources.ResultsBariatric surgery was cost saving in comparison with conservative management. It also led to a substantial reduction in lifetime risk of events: from a 16 % reduction in the risk of transient ischaemic attacks to a 62 % reduction in the incidence of type 2 diabetes. Over a lifetime, surgery led to savings of €8408 and generated an additional 0.8 years of life and 4.1 quality-adjusted life years (QALYs) per patient, which translates into gains of 32,390 quality-adjusted person-years and savings of €66 million for the cohort, operated in 2012. Analysis of the consequences of a 3-year delay in surgery provision showed that the overall lifetime cost of treatment may be increased in patients with diabetes or a body mass index >40 kg/m2. Delays in surgery may also lead to a loss of clinical benefits: up to 0.6 life years and 1.2 QALYs per patient over a lifetime.ConclusionBariatric surgery, over a lifetime horizon, may lead to significant cost savings to health care systems in addition to the known clinical benefits.Electronic supplementary materialThe online version of this article (doi:10.1007/s11695-014-1567-5) contains supplementary material, which is available to authorized users.

The trefoil protein TFF3 stimulates invasion and angiogenesis in vitro. To determine whether it has a role in breast tumor metastasis and angiogenesis, its levels were measured by immunohistochemistry in breast tissue with a specific monoclonal antibody raised against human TFF3. TFF3 is expressed in normal breast lobules and ducts, at higher levels in areas of fibrocystic change and papillomas, in all benign breast disease lesions, and in 89% of in situ and in 83% of invasive carcinomas. In well-differentiated tumor cells, TFF3 is concentrated at the luminal edge, whereas in poorly differentiated cells polarity is inverted and expression is directed toward the stroma. Expression was high in well-differentiated tumors and was associated significantly with low histological grade and with estrogen and progesterone receptor expression, accordant with induction of TFF3 mRNA by estrogen in breast cancer cells. Paradoxically, TFF3 expression was associated with muscle, neural, and lymphovascular invasion and the presence and number of involved lymph nodes, and it was an independent predictive marker of lymphovascular invasion and lymph node involvement. Consistent with an angiogenic function, TFF3 expression correlated strongly with microvessel density evaluated with CD31 and CD34. In conclusion, TFF3 is expressed in both the normal and diseased breast. Although associated with features of good prognosis, its profile of expression in invasive cancer is consistent with a role in breast tumor progression and tumor cell dissemination.

Background: Obesity surgery is effective for obesity and type 2 diabetes (T2DM). However, many patients do not achieve sustained diabetes remission following surgery. Liraglutide, a GLP-1 analogue, improves glycaemia and reduces body weight. Our aim was to evaluate the safety and effectiveness of Liraglutide 1•8 mg in patients with persistent or recurrent T2DM after surgery. Methods: In this double-blind, placebo-controlled trial, adults with HbA1c >48 mmol/mol (>6•5%) at least one year after surgery were randomised 2:1 to once-daily subcutaneous Liraglutide 1•8 mg or Placebo, together with a reduced-calorie diet and increased physical activity. The primary outcome was the change in HbA1c from baseline to 26 weeks. EudraCT 2014-003923-23 and ISRCTN 13643081. Findings: Between February 2016 and November 2018, we assigned 80 patients to receive Liraglutide (n=53) or Placebo (n=27). Seventy-one (89%) participants completed the study up to week 26 (complete-cases population). A multivariable linear regression analysis taking baseline HbA1c and type of surgery into account as covariates showed that Liraglutide was associated with a difference in HbA1c change of-13•3 mmol/mol or-1•22%, 95% CI-19•7 to-7•0, p<0•001) vs Placebo at 26 weeks. Liraglutide was associated with a difference in the change of weight of-4•23 kg [95% CI-6•81 to-1•64, p<0•001) vs Placebo. No significant influence of type of surgery was noted. Interpretation: This is the first randomised controlled trial of adjunctive Liraglutide treatment in patients with diabetes mellitus after metabolic surgery. The results support the use of Liraglutide therapy in this clinical context. Funding: JP Moulton Charitable Foundation 3 surgery. We have previously shown that the acute peripheral administration of the GLP-1 RA Exendin-4 in rodent models of RYGB has additive effects to the already enhanced endogenous GLP-1 secretion as demonstrated by an additional reduction in food intake 11. Indeed, data from retrospective non-randomised studies in humans support this hypothesis: the administration of GLP-1 RAs in patients with and without T2DM and a suboptimal response to metabolic surgery was associated with weight loss and glycaemic improvements 12-15. This RCT was therefore designed to investigate the safety and efficacy of pharmacological administration of the GLP-1 RA Liraglutide on glycaemic control in patients with persistent or recurrent T2DM after RYGB or VSG surgery. Methods Study population This was a prospective randomised double-blinded placebo-controlled clinical trial. Eighty patients with obesity and persistent or recurrent T2DM that had undergone RYGB or VSG surgery at least 12 months before randomisation were recruited from the