The short-term and long-term effects of bariatric/metabolic surgery on subcutaneous adipose tissue inflammation in humans.

CONTEXT: The mechanisms mediating the short- and long-term improvements in glucose homeostasis following bariatric/metabolic surgery remain incompletely understood. OBJECTIVE: To investigate whether a reduction in adipose tissue inflammation plays a role in the metabolic improvements seen after bariatric/metabolic surgery, both in the short-term and longer-term. DESIGN: Fasting blood and subcutaneous abdominal adipose tissue were obtained before (n=14), at one month (n=9), and 6-12months (n=14) after bariatric/metabolic surgery from individuals with obesity who were not on insulin or anti-diabetes medication. Adipose tissue inflammation was assessed by a combination of whole-tissue gene expression and flow cytometry-based quantification of tissue leukocytes. RESULTS: One month after surgery, body weight was reduced by 13.5±4.4kg (p<0.001), with improvements in glucose tolerance reflected by a decrease in area-under-the-curve (AUC) glucose in 3-h oral glucose tolerance tests (-105±98mmol/L * min; p=0.009) and enhanced pancreatic ß-cell function (insulinogenic index: +0.8±0.9pmol/mmol; p=0.032), but no change in estimated insulin sensitivity (Matsuda insulin sensitivity index [ISI]; p=0.720). Furthermore, although biomarkers of systemic inflammation and pro-inflammatory gene expression in adipose tissue remained unchanged, the number of neutrophils increased in adipose tissue 15-20 fold (p<0.001), with less substantial increases in other leukocyte populations. By the 6-12month follow-up visit, body weight was reduced by 34.8±10.8kg (p<0.001) relative to baseline, and glucose tolerance was further improved (AUC glucose -276±229; p<0.001) along with estimated insulin sensitivity (Matsuda ISI: +4.6±3.2; p<0.001). In addition, improvements in systemic inflammation were reflected by reductions in circulating C-reactive protein (CRP; -2.0±5.3mg/dL; p=0.002), and increased serum adiponectin (+1358±1406pg/mL; p=0.003). However, leukocyte infiltration of adipose tissue remained elevated relative to baseline, with pro-inflammatory cytokine mRNA expression unchanged, while adiponectin mRNA expression trended downward (p=0.069). CONCLUSION: Both the short- and longer-term metabolic improvements following bariatric/metabolic surgery occur without significant reductions in measures of adipose tissue inflammation, as assessed by measuring the expression of genes encoding key mediators of inflammation and by flow cytometric immunophenotyping and quantification of adipose tissue leukocytes.

Incidental gastric mesenchymal tumors identified during laparoscopic sleeve gastrectomy.

BACKGROUND: Laparoscopic sleeve gastrectomy (SG) is a well-tolerated and effective procedure for sustained weight loss and amelioration of weight-related co-morbidities. Rarely, unexpected pathology may be identified intraoperatively, which may alter the surgical plan. Gastrointestinal stromal tumors (GISTs) are among the more frequently encountered tumors and pose a particular concern because of their malignant potential. We review our findings of incidental tumors encountered during 1415 consecutive SGs. METHODS: Abnormal pathology records from all patients who underwent SG at our institution between 2009 and 2014 were reviewed. Patient demographic characteristics and clinical characteristics, tumor characteristics, including immunohistochemistry, operative course, and patient follow-up were reviewed. RESULTS: There were 17 incidental gastric mesenchymal tumors identified (1.2%) in 1415 SG procedures. This included 12 GISTs (.8%), 2 schwannomas (.1%), and 3 leiomyomas (.3%). In the majority of cases (1210/1415), the gastric specimens were not reviewed by a pathologist because there were no gross abnormalities appreciated by the surgeon. The GISTs were between .3 and 2.9 cm, and all were low grade with negative margins. Patients with GISTs tended to be older (mean age 55±9.3 y) than the rest of the patients. There was no evidence of recurrence on follow-up. CONCLUSION: Incidental gastric mesenchymal tumors are rarely encountered during SG. The vast majority were GISTs with an incidence of .8% in this population. Concomitant SG and tumor resection were feasible, without compromising the objectives of each. Complete tumor excision is necessary for tumors>2 cm.

Metabolic dysfunction drives a mechanistically distinct proinflammatory phenotype in adipose tissue macrophages.

Adipose tissue macrophage (ATM)-driven inflammation plays a key role in insulin resistance; however, factors activating ATMs are poorly understood. Using a proteomics approach, we show that markers of classical activation are absent on ATMs from obese humans but are readily detectable on airway macrophages of patients with cystic fibrosis, a disease associated with chronic bacterial infection. Moreover, treating macrophages with glucose, insulin, and palmitate-conditions characteristic of the metabolic syndrome-produces a "metabolically activated" phenotype distinct from classical activation. Markers of metabolic activation are expressed by proinflammatory ATMs in obese humans/mice and are positively correlated with adiposity. Metabolic activation is driven by independent proinflammatory and anti-inflammatory pathways, which regulate balance between cytokine production and lipid metabolism. We identify PPARγ and p62/SQSTM1 as two key proteins that promote lipid metabolism and limit inflammation in metabolically activated macrophages. Collectively, our data provide important mechanistic insights into pathways that drive the metabolic-disease-specific phenotype of macrophages.

Outpatient laparoscopic sleeve gastrectomy in a free-standing ambulatory surgery center: first 250 cases.

BACKGROUND: A growing body of evidence supports the laparoscopic sleeve gastrectomy (LSG) as a safe and effective procedure for sustained weight loss and amelioration of weight-related co-morbidities. Procedures performed in ambulatory surgery centers (ASC) can provide several advantages over hospital-based surgery. We present our results of 250 consecutive patients undergoing LSG in an ASC. The objective of this study was to assess the safety and efficacy of outpatient LSG in a freestanding ASC. METHODS: Data was collected prospectively from 250 consecutive patients who underwent LSG at a freestanding ASC. Patients were excluded from the ASC if they weighed>450 pounds, if anticipated operative time was>2 hours, if the patient had impaired mobility limiting early ambulation, or if there were medical problems requiring postoperative monitoring beyond 23 hours. Revisions were not included in this study. RESULTS: Mean age was 47 years (range, 23-74 yr). Mean preoperative body mass index (BMI) was 43 kg/m² (29-71 kg/m²). Mean operative time was 60 minutes (31-161 min). Mean recovery room time was 131 minutes (30-385 min). Mean percent excess weight loss (%EWL) was 60% at 1 year and 63% at 2 years. Nine patients (3.6%) were readmitted within 30 days. Two patients (.8%) were transferred from the ASC to a hospital. There was 1 staple line leak (.4%). There were no open conversions and no deaths. CONCLUSIONS: LSG can be performed safely in a freestanding ASC in select patients with outcomes comparable to the inpatient standard. Additional studies are needed to formulate selection criteria and guidelines to maximize patient safety and outcomes.