BackgroundThe development of insulin resistance (IR) in mouse models of obesity and type 2 diabetes mellitus (DM) is characterized by progressive accumulation of inflammatory macrophages and subpopulations of T cells in the visceral adipose. Regulatory T cells (Tregs) may play a critical role in modulating tissue inflammation via their interactions with both adaptive and innate immune mechanisms. We hypothesized that an imbalance in Tregs is a critical determinant of adipose inflammation and investigated the role of Tregs in IR/obesity through coordinated studies in mice and humans.Methods and Findings Foxp3-green fluorescent protein (GFP) “knock-in” mice were randomized to a high-fat diet intervention for a duration of 12 weeks to induce DIO/IR. Morbidly obese humans without overt type 2 DM (n = 13) and lean controls (n = 7) were recruited prospectively for assessment of visceral adipose inflammation. DIO resulted in increased CD3+CD4+, and CD3+CD8+ cells in visceral adipose with a striking decrease in visceral adipose Tregs. Treg numbers in visceral adipose inversely correlated with CD11b+CD11c+ adipose tissue macrophages (ATMs). Splenic Treg numbers were increased with up-regulation of homing receptors CXCR3 and CCR7 and marker of activation CD44. In-vitro differentiation assays showed an inhibition of Treg differentiation in response to conditioned media from inflammatory macrophages. Human visceral adipose in morbid obesity was characterized by an increase in CD11c+ ATMs and a decrease in foxp3 expression.ConclusionsOur experiments indicate that obesity in mice and humans results in adipose Treg depletion. These changes appear to occur via reduced local differentiation rather than impaired homing. Our findings implicate a role for Tregs as determinants of adipose inflammation.

Dipeptidyl peptidase-4 (DDP4) inhibitors target the enzymatic degradation of incretin peptides and represent a major advance in the treatment of type 2 diabetes. DPP4 has a number of nonenzymatic functions that involve its interaction with adenosine deaminase (ADA) and other extracellular matrix proteins. Here, we assessed the nonenzymatic role of DPP4 in regulating dendritic cell (DC)/macrophage–mediated adipose inflammation in obesity. Both obese humans and rodents demonstrated increased levels of DPP4 expression in DC/macrophage cell populations from visceral adipose tissue (VAT). The DPP4 expression increased during monocyte differentiation to DC/macrophages and with lipopolysaccharide (LPS)-induced activation of DC/macrophages. The DPP4 colocalized with membrane-bound ADA on human DCs and enhanced the ability of the latter to stimulate T-cell proliferation. The DPP4 interaction with ADA in human DC/macrophages was competitively inhibited by the addition of exogenous soluble DPP4. Knockdown of DPP4 in human DCs, but not pharmacologic inhibition of their enzymatic function, significantly attenuated the ability to activate T cells without influencing its capacity to secrete proinflammatory cytokines. The nonenzymatic function of DPP4 on DC may play a role in potentiation of inflammation in obesity by interacting with ADA. These findings suggest a novel role for the paracrine regulation of inflammation in adipose tissue by DPP4.

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BACKGROUND Intraoperative cholangiography (IOC) is the current gold standard for biliary imaging during laparoscopic cholecystectomy (LC). However, utilization of IOC remains low. Near Infrared Fluorescence Cholangiography (NIRF-C) is a novel, noninvasive method for real-time, intraoperative biliary mapping. Our aims were to assess the safety and efficacy of NIRF-C for identification of biliary anatomy during LC. METHODS Patients were administered indocyanine green (ICG) prior to surgery. NIRF-C was used to identify extrahepatic biliary structures before, and after partial and complete dissection of Calot's triangle. Routine IOC was performed in each case. Identification of biliary structures using NIRF-C and IOC, and time required to complete each procedure were collected. RESULTS Eighty-two patients underwent elective LC with NIRF-C and IOC. Mean age and BMI were 42.6±13.7 years and 31.5±8.2 kg/m2, respectively. ICG was administered 73.8±26.4 minutes prior to incision. NIRF-C was significantly faster than IOC (1.9±1.7 vs. 11.8±5.3 minutes, p<0.001). IOC was unobtainable in 20 (24.4%) patients while NIRF-C did not visualize biliary structures in 4 (4.9%) patients. After complete dissection, the rates of visualization of the cystic duct, common bile duct, and common hepatic duct using NIRF-C were 95.1%, 76.8%, and 69.5%, respectively, compared to 72.0%, 75.6%, and 74.3% for IOC. In 20 patients where IOC could not be obtained, NIRF-C successfully identified biliary structures in 80% of the cases. Higher BMI was not a deterrent to visualization of anatomy with NIRF-C. No adverse events were observed with NIRF-C. CONCLUSIONS NIRF-C is a safe and effective alternative to IOC for imaging extrahepatic biliary structures during LC. This technique should be evaluated further under a variety of acute and chronic gallbladder inflammatory conditions to determine its usefulness in biliary ductal identification.

ABSTRACT

Computer-assisted surgical devices, or "surgical robots," have recently been approved for general surgical use. The device allows the surgeon remote control of multi-articulated instrument arms with a three-dimensional view. Here we report the first known case of pancreatic resection with use of a computer-assisted, or robotic, surgical device. A 46-year old woman presented with back pain and a complex cystic mass in the tail of the pancreas. The daVinci surgical robot was used to remove the lesion en bloc with the tail of the pancreas and spleen. The patient did well and returned to full activity promptly. In summary, robotic technology may enhance advanced laparoscopic procedures. Pancreatic resection is feasible, and future experience will determine the true benefits of this technique.

The presence of dumping syndrome after gastric bypass does not influence weight loss, though eating behaviors may directly influence it.

Transgastric instrumentation does contaminate the abdominal cavity but pathogens are clinically insignificant due to species or bacterial load. Patients on PPIs do have an increased bacterial load in the gastric aspirate, with no clinical significant infection.