Nicole D. Bouvy

Cold-Activated Brown Adipose Tissue in Healthy Men

BACKGROUND Studies in animals indicate that brown adipose tissue is important in the regulation of body weight, and it is possible that individual variation in adaptive thermogenesis can be attributed to variations in the amount or activity of brown adipose tissue. Until recently, the presence of brown adipose tissue was thought to be relevant only in small mammals and infants, with negligible physiologic relevance in adult humans. We performed a systematic examination of the presence, distribution, and activity of brown adipose tissue in lean and obese men during exposure to cold temperature. Brown-adipose-tissue activity was studied in relation to body composition and energy metabolism. METHODS We studied 24 healthy men--10 who were lean (body-mass index [BMI] [the weight in kilograms divided by the square of the height in meters], < 25) and 14 who were overweight or obese (BMI, > or = 25)--under thermoneutral conditions (22 degrees C) and during mild cold exposure (16 degrees C). Putative brown-adipose-tissue activity was determined with the use of integrated (18)F-fluorodeoxyglucose positron-emission tomography and computed tomography. Body composition and energy expenditure were measured with the use of dual-energy x-ray absorptiometry and indirect calorimetry. RESULTS Brown-adipose-tissue activity was observed in 23 of the 24 subjects (96%) during cold exposure but not under thermoneutral conditions. The activity was significantly lower in the overweight or obese subjects than in the lean subjects (P=0.007). BMI and percentage of body fat both had significant negative correlations with brown adipose tissue, whereas resting metabolic rate had a significant positive correlation. CONCLUSIONS The percentage of young men with brown adipose tissue is high, but its activity is reduced in men who are overweight or obese. Brown adipose tissue may be metabolically important in men, and the fact that it is reduced yet present in most overweight or obese subjects may make it a target for the treatment of obesity.

Brown adipose tissue in morbidly obese subjects.

Background Cold-stimulated adaptive thermogenesis in brown adipose tissue (BAT) to increase energy expenditure is suggested as a possible therapeutic target for the treatment of obesity. We have recently shown high prevalence of BAT in adult humans, which was inversely related to body mass index (BMI) and body fat percentage (BF%), suggesting that obesity is associated with lower BAT activity. Here, we examined BAT activity in morbidly obese subjects and its role in cold-induced thermogenesis (CIT) after applying a personalized cooling protocol. We hypothesize that morbidly obese subjects show reduced BAT activity upon cold exposure. Methods and Findings After applying a personalized cooling protocol for maximal non-shivering conditions, BAT activity was determined using positron-emission tomography and computed tomography (PET-CT). Cold-induced BAT activity was detected in three out of 15 morbidly obese subjects. Combined with results from lean to morbidly obese subjects (n = 39) from previous study, the collective data show a highly significant correlation between BAT activity and body composition (P<0.001), respectively explaining 64% and 60% of the variance in BMI (r = 0.8; P<0.001) and BF% (r = 0.75; P<0.001). Obese individuals demonstrate a blunted CIT combined with low BAT activity. Only in BAT-positive subjects (n = 26) mean energy expenditure was increased significantly upon cold exposure (51.5±6.7 J/s versus 44.0±5.1 J/s, P = 0.001), and the increase was significantly higher compared to BAT-negative subjects (+15.5±8.9% versus +3.6±8.9%, P = 0.001), indicating a role for BAT in CIT in humans. Conclusions This study shows that in an extremely large range of body compositions, BAT activity is highly correlated with BMI and BF%. BAT-positive subjects showed higher CIT, indicating that BAT is also in humans involved in adaptive thermogenesis. Increasing BAT activity could be a therapeutic target in (morbid) obesity.

A multicenter, randomized efficacy study of the EndoBarrier Gastrointestinal Liner for presurgical weight loss prior to bariatric surgery.

Background:The endoscopically placed duodenal-jejunal bypass sleeve or EndoBarrier Gastrointestinal Liner has been designed to achieve weight loss in morbidly obese patients. We report on the first European experience with this device. Methods:A multicenter, randomized clinical trial was performed. Forty-one patients were included and 30 underwent sleeve implantation. Eleven patients served as a diet control group. All patients followed the same low-calorie diet during the study period. The purpose of the study was to determine the safety and efficacy of the device. Results:Twenty-six devices were successfully implanted. In 4 patients, implantation could not be achieved. Four devices were explanted prior to the initial protocol end point because of migration (1), dislocation of the anchor (1), sleeve obstruction (1), and continuous epigastric pain (1). The remaining patients all completed the study. Mean procedure time was 35 minutes (range: 12–102 minutes) for a successful implantation and 17 minutes (range: 5–99 minutes) for explantation. There were no procedure related adverse events. During the study period the 26 duodenal-jejunal bypass sleeve patients (100%) had at least one adverse event, mainly abdominal pain and nausea during the first week after implantation. Initial mean body mass index (BMI, kg/m2) was 48.9 and 47.4 kg/m2 for the device and control patients, respectively. Mean excess weight loss after 3 months was 19.0% for device patients versus 6.9% for control patients (P < 0.002). Absolute change in BMI at 3 months was 5.5 and 1.9 kg/m2, respectively. Type 2 diabetes mellitus was present at baseline in 8 patients of the device group and improved in 7 patients during the study period (lower glucose levels, HbA1c, and medication requirements). Conclusion:The EndoBarrier Gastrointestinal Liner is a feasible and safe noninvasive device with excellent short-term weight loss results. The device also has a significant positive effect on type 2 diabetes mellitus. Long-term randomized and sham studies for weight loss and treatment of diabetes are necessary to determine the role of the device in the treatment of morbid obesity.This study was registered at www.clinicaltrials.gov (registration number: NCT00830440).

Burden of adhesions in abdominal and pelvic surgery: systematic review and met-analysis

Objective To estimate the disease burden of the most important complications of postoperative abdominal adhesions: small bowel obstruction, difficulties at reoperation, infertility, and chronic pain. Design Systematic review and meta-analyses. Data sources Searches of PubMed, Embase, and Central, from January 1990 to December 2012, without restrictions to publication status or language. Study selection All types of studies reporting on the incidence of adhesion related complications were considered. Data extraction and analysis The primary outcome was the incidence of adhesive small bowel obstruction in patients with a history of abdominal surgery. Secondary outcomes were the incidence of small bowel obstruction by any cause, difference in operative time, enterotomy during adhesiolysis, and pregnancy rate after abdominal surgery. Subgroup and sensitivity analyses were done to study the robustness of the results. A random effects model was used to account for heterogeneity between studies. Results We identified 196 eligible papers. Heterogeneity was considerable for almost all meta-analyses. The origin of heterogeneity could not be explained by study design, study quality, publication date, anatomical site of operation, or operative technique. The incidence of small bowel obstruction by any cause after abdominal surgery was 9% (95% confidence interval 7% to 10%; I2=99%). the incidence of adhesive small bowel obstruction was 2% (2% to 3%; I2=93%); presence of adhesions was generally confirmed by emergent reoperation. In patients with a known cause of small bowel obstruction, adhesions were the single most common cause (56%, 49% to 64%; I2=96%). Operative time was prolonged by 15 minutes (95% confidence interval 9.3 to 21.1 minutes; I2=85%) in patients with previous surgery. Use of adhesiolysis resulted in a 6% (4% to 8%; I2=89%) incidence of iatrogenic bowel injury. The pregnancy rate after colorectal surgery in patients with inflammatory bowel disease was 50% (37% to 63%; I2=94%), which was significantly lower than the pregnancy rate in medically treated patients (82%, 70% to 94%; I2=97%). Conclusions This review provides detailed and systematically analysed knowledge of the disease burden of adhesions. Complications of postoperative adhesion formation are frequent, have a large negative effect on patients’ health, and increase workload in clinical practice. The quantitative effects should be interpreted with caution owing to large heterogeneity. Registration The review protocol was registered through PROSPERO (CRD42012003180).

Increase in Brown Adipose Tissue Activity after Weight Loss in Morbidly Obese Subjects

CONTEXT Stimulation of thermogenesis in brown adipose tissue (BAT) is a potential target to treat obesity. We earlier demonstrated that BAT activity is relatively low in obese subjects. It is unknown whether BAT can be recruited in adult humans. OBJECTIVE To study the dynamics of BAT, we observed BAT activity in morbidly obese subjects before and after weight loss induced by bariatric surgery. DESIGN This was an observational prospective cohort study. SETTING The study was conducted at a referral center. PATIENTS Ten morbidly obese subjects eligible for laparoscopic adjustable gastric banding surgery were studied before and 1 yr after bariatric surgery. MAIN OUTCOME MEASURE The main outcome measure was BAT activity, as determined after acute cold stimulation using (18)F-fluorodeoxyglucose positron emission tomography and computed tomography. RESULTS Before surgery, only two of 10 subjects showed active BAT. One year after surgery, the number of subjects with active BAT was increased to five. After weight loss, BAT-positive subjects had significantly higher nonshivering thermogenesis compared with BAT-negative subjects (P < 0.05). CONCLUSIONS The results show that in humans BAT can be recruited in the regions in which it was also reported in lean subjects before. These results for the first time show recruitment of BAT in humans and may open the door for BAT-targeted treatments of obesity.

Degradation of mesh coatings and intraperitoneal adhesion formation in an experimental model

In laparoscopic ventral hernia repair a mesh is placed in direct contact with the viscera, often leading to substantial adhesions. In this experimental study the ability of different coated and uncoated meshes to attenuate adhesion formation was examined.

The Bile Acid Chenodeoxycholic Acid Increases Human Brown Adipose Tissue Activity

The interest in brown adipose tissue (BAT) as a target to combat metabolic disease has recently been renewed with the discovery of functional BAT in humans. In rodents, BAT can be activated by bile acids, which activate type 2 iodothyronine deiodinase (D2) in BAT via the G-coupled protein receptor TGR5, resulting in increased oxygen consumption and energy expenditure. Here we examined the effects of oral supplementation of the bile acid chenodeoxycholic acid (CDCA) on human BAT activity. Treatment of 12 healthy female subjects with CDCA for 2 days resulted in increased BAT activity. Whole-body energy expenditure was also increased upon CDCA treatment. In vitro treatment of primary human brown adipocytes derived with CDCA or specific TGR5 agonists increased mitochondrial uncoupling and D2 expression, an effect that was absent in human primary white adipocytes. These findings identify bile acids as a target to activate BAT in humans.

Laparoscopic surgery in the rat. Beneficial effect on body weight and tumor take.

AbstractBackground: The ability of laparoscopic techniques to treat malignant disease is controversial. We developed a rat model to assess metabolic and oncological effects of laparoscopic surgery. Methods: Experiment I. The postoperative body weight in 10 rats having laparoscopic bowel resection (group I), 10 rats having open bowel resection (group II) and 5 rats having anesthesia only (group III) was determined. Experiment II. Tumor take was scored in 11 rats having laparoscopic bowel resection (group IV), 11 rats having open bowel resection (group V), 6 rats having CO2 pneumoperitoneum without bowel resection (group VI) and 6 rats having anesthesia only (group VII). All rats had CC531 cancer cells injected intraperitoneally postoperatively. Results: Experiment I. Body weight loss in group I compared to group II (p<0.036). Rats of group III lost no weight postoperatively. Experiment II. Tumor take was less in the subcutis (p=0.005), parietal peritoenum (p<0.001) and bowel anastomosis (p=0.021) in group IV compared to group V. Tumor take was significantly greater at all sites except for subcutis in group VI compared to VII (all p<0.022). Conclusions: Laparoscopic surgery is associated with less postoperative weight loss and less tumor take compared to open surgery. CO2 insufflation appears to increase tumor take.

Robot-Assisted vs. Conventional Laparoscopic Rectopexy for Rectal Prolapse : A Comparative Study on Costs and Time

PurposeLaparoscopic rectopexy has become one of the most advocated treatments for full-thickness rectal prolapse, offering good functional results compared with open surgery and resulting in less postoperative pain and faster convalescence. However, laparoscopic rectopexy can be technically demanding. Once having mastered dexterity, with robotic assistance, laparoscopic rectopexy can be performed faster. Moreover, it shortens the learning curve in simple laparoscopic tasks. This may lead to faster and safer laparoscopic surgery. Robot-assisted rectopexy has been proven safe and feasible; however, until now, no study has been performed comparing costs and time consumption in conventional laparoscopic rectopexy vs. robot-assisted rectopexy.MethodsOur first 14 cases of robot-assisted laparoscopic rectopexy were reviewed and compared with 19 patients who underwent conventional laparoscopic rectopexy in the same period.ResultsRobot-assisted laparoscopic rectopexy did not show more complications. However, the average operating time was 39 minutes longer, and costs were -57.29 (or:

Learning Curves of Robot-assisted Laparoscopic Surgery Compared With Conventional Laparoscopic Surgery: An Experimental Study Evaluating Skill Acquisition of Robot-assisted Laparoscopic Tasks Compared With Conventional Laparoscopic Tasks in Inexperienced Users. .

745.09) higher.ConclusionRobot-assisted laparoscopic rectopexy is a safe and feasible procedure but results in increased time and higher costs than conventional laparoscopy.